What is love? |

Introduction

According to psychologist Robert Sternberg, love can be considered to have three main components: passion, intimacy, and commitment. Passion is sexual arousal and an intense desire to be with another person; it is expressed through hugging, kissing, and sexual intimacy. Intimacy is a feeling of closeness and connectedness and is expressed through communication and doing things to support the other person. Commitment is a decision that one loves the other person and wants to maintain that love over time. Commitment is often expressed through fidelity, and the institution of marriage makes one’s commitment legally binding.

The amount of love that one feels depends on the strength of these three components. The kind of love one feels depends on the mixture of these components. One might have a commitment to a partner but feel little passion; or one might be passionately in love but not be able to communicate the deep feelings that go with intimacy. The amount or kind of love one partner experiences in a relationship might not be the same as the other partner’s experience. Misunderstandings often result, for example, when one partner thinks the relationship contains commitment and the other partner sees the relationship as only a passionate one. Finally, a loving relationship can change over time. In marriage, the passion may fade over the years, while intimacy and commitment bloom.

Passionate Love

Passionate love is the kind of love sometimes described as “love at first sight.” It occurs suddenly, and one feels as if one has fallen into love. Passionate love is a state of sexual arousal without the intimacy and commitment components. One knows that one is passionately in love when one is always daydreaming about the other person, longs to be constantly with the other person, and feels ecstatic when with the other person. Passionate love thrives on unavailability. As in unrequited love, either the loved one does not reciprocate the intensity of the lover’s affections or the lovers cannot get together as often as they wish. Being loved is reinforcing, and some psychologists say that passionate love may survive only under conditions of intermittent reinforcement, where uncertainty about when one will be reinforced plays a major role. Romeo and Juliet’s passionate love, for example, was inflamed by the prohibitions of their feuding families.

In passionate love, partners idealize each other. They engage in perceptual accentuation, or seeing what they want to see. Only the good features of each other are noticed and enhanced. The more the partners live in the illusion of their ideals, the more intense is the passionate love. Passionate love really is “blind.”

Most people think of passionate love as being true love, and many people think that passionate love is the only kind of love; they expect passionate love to last forever. Despite their expectations (and wishes), passionate love does not last. Indeed, passionate love appears to last a maximum of two and a half years. After that time, according to Charles Hill, Zick Rubin, and Letitia Paplau, almost one-half of dating couples report having broken up. As partners become more familiar with each other, illusions are shattered and the passion wanes. Unfortunately, some people believe that this is the end of love.

Romantic Love

For many people, however, love does persist—in the form of romantic love. Romantic love is passionate love with the added component of intimacy. The romantic ideal, which has existed since the medieval time of courtly love, looks much like passionate love. It contains the belief that love is fated and uncontrollable, strikes at first sight, transcends all social boundaries, and mixes agony and ecstasy. This ideal is very much alive today; it is reflected in romance novels, motion pictures, and advertisements. Psychologists have found that this type of love is a poor basis for marriage, which requires steady companionship and objectivity. If a relationship is to survive, romantic passion is not enough.

Rubin has shown that there is a type of romantic love that contains intimate communication and caring. In his study, loving feelings of dependency, exclusivity, and caring were contrasted with the type of liking that exists in friendship. Men, more than women, tended to blur the distinction between liking and loving. Both sexes, though, often experience liking the person they are in love with. Rubin also noticed that one can tell if two people are “in love” simply by observing them: Partners who are strongly in love exhibit more mutual eye contact than partners who are weakly in love.

Intimacy without passion or a long-term commitment is experienced as liking. One feels closeness, bondedness, and warmth toward the other—as one does in friendship. There is a willingness to let the other person see even the disliked parts of oneself and a feeling of being accepted when these parts are disclosed. Intimacy includes open communication, acceptance, and the sharing of oneself and one’s resources. There is a high degree of trust in intimate relationships.

Companionate Love

When commitment is added to intimacy, one experiences what psychologists Ellen Berscheid and Elaine Walster call companionate love. There is a deep attachment that is based on extensive familiarity with the loved one. Companionate love often encompasses a tolerance for the partner’s shortcomings, along with a desire to overcome difficulties and conflicts in a relationship. There is a commitment to the ongoing nurturing of the relationship and to an active caring for the partner, even during rough times. Marriages in which the physical attraction has waned but intimate caring and commitment have increased are characterized by this type of love. When researchers asked couples who had been married for at least fifteen years what kept their relationships alive, they put long-term commitment at the top of the list. The romantic passion that brings a couple together is not the force that keeps them together. Each partner must trust that the other is committed to nurturing support, acceptance, and communication in the relationship.

Attraction

Psychologists have used theories and laboratory studies to answer the basic question, “Why do some people have a happy love life while others have unhappy relationships?” Part of the answer comes from the partner one chooses.

One may think that opposites attract, but psychologist Donn Byrne has shown that people are attracted to those who are similar to them in attractiveness, interests, intelligence, education, age, family background, religion, and attitudes. Researchers have noted what is called a “matching phenomenon” when choosing romantic partners. This phenomenon is described as a tendency to choose partners who are a good match to ourselves in attractiveness and other traits. Studies have shown that those who were a good match in physical attractiveness were more likely to be dating longer than couples who were not well matched, and that married couples are more closely matched in attractiveness than couples who are casually dating. Furthermore, Rubin and his associates have found that dating couples who eventually broke up were less well matched in age, educational ambitions, intelligence, and physical attractiveness than those who stayed together.

Another factor that is extremely important in predicting attraction is proximity. Studies have shown that most people marry someone who lives in the same neighborhood or works at the same job; and it is not simply a matter of physical proximity, but a matter of how often one crosses paths with the potential mate that determines the likelihood of romantic involvement. Overall, people tend to like and be attracted to those who have the potential to reward them. People tend to be attracted to those who are similarly attractive, who share their opinions and attitudes, whom they have grown accustomed to meeting, and with whom they have shared positive experiences.

Love in Relationships

After one finds a partner, whether one is happy or unhappy in love depends on the relationship one creates. According to Cindy Hazan and PhilipShaver, both adults and teenagers recreate the same type of relationship they experienced with their parents during childhood. Secure lovers create an intimate relationship that is neither excessively dependent nor independent. They bring a secure sense of self and an interest in developing the independence of their partner into the relationship. Avoidant lovers are overly independent. They get nervous when their partner gets too close because they do not trust the other person completely. Anxious-ambivalent lovers are too dependent; they often worry that their partner does not really love them or will not want to stay with them. Thus, many lovers end up playing out the script that they were taught as children.

Men often follow a different script from that followed by women when they are in love. Men tend to choose a partner on the basis of physical attractiveness, while women emphasize interpersonal warmth and occupational status. Romance involves both passion and affection; men, however, tend to get hooked into the passion first, while women tend to want the affection as a prerequisite to sex. As the relationship matures, men want the affection as much as the sex, and women get equally excited by sexual stimuli as do men. Who, then, one might ask, are the real romantics? Men agree with more of the statements about romantic love; they fall in love more quickly; and they hold on to a waning affair more so than do women. After the breakup of a relationship, a man feels more lonely, obsessed with what went wrong, and depressed than does a woman.

Indeed, men and women may inhabit different emotional worlds. Men and women both want intimacy, but they express themselves differently. Men are more likely to be doers and women to be talkers. For example, a man will wash a woman’s car or bring her flowers to show he loves her, while a woman will tell a man how much she loves him. When asked what causes an emotion such as love, men will say it is something in the world outside themselves, such as seeing an attractive woman. Women, on the other hand, will attribute being in love to positive interactions with others or to internal factors such as moods. These socially learned differences between men and women in their styles of intimacy are often a source of tension between them. Women sometimes want men to talk more, while men will want women to stop talking. Finally, some men will sacrifice intimacy because they fear loss of independence, while some women sacrifice independence because they fear a loss of intimacy.

History of Research on Love

Psychologists have approached the topic of love from a variety of perspectives. In the early 1900s, clinical psychologists looked at love mainly in terms of its sexual component. For example, Sigmund Freud defined love as sublimated sexuality. By the middle of the twentieth century, humanistic psychologists such as Abraham Maslow, Erich Fromm, and Carl R. Rogers saw love as including the empathy, responsibility, and respect that is characteristic of friendship. Next, there was an attempt to measure love as distinct from friendship, with Rubin creating his liking and loving scales.

Since love involves emotions, motivations, and cognitions, Walster and Berscheid drew on the earlier work of Stanley Schachter and Jerome Singer to devise a multifactor explanation of love called thetwo-factor theory. They theorize that love arises when a person is physiologically aroused and labels that arousal as love. For example, being in a dangerous situation creates physiological arousal, and, if one is with an attractive partner, one could feel that the sweating palms and pounding heart mean that one is falling in love. Researchers have found that men approached by an unknown, attractive woman as they crossed a dangerous bridge were more likely to ask her out and indicate attraction than men approached by the woman while crossing a sturdy, safe bridge. Studies show that watching scary movies, riding on roller coasters, and exercising are all arousing activities that increase the likelihood that people will be attracted to one another.

Social psychologist Byrne tried to explain both the passionate feeling and the friendship feeling as arising from the reinforcement one gets from one’s lover. People like, and love, people who give them rewards, whether the reward is sexual gratification or a feeling of being needed.

Although many social psychologists have focused on separate concepts, such as interpersonal attraction, social exchange, and cognitive consistency, to explain love, Sternberg combined all these concepts in his triangular theory of love. Sternberg contends that liking and loving are interrelated phenomena and that there are different types of love that develop from different combinations of liking and loving. Sternberg’s theory explains the difference between a partner’s love for his or her child and lovers’ love for each other.

Historically, conceptions of love have been tied to economic conditions and to social role definitions. One example of these economic conditions is the Industrial Revolution, which moved men out of the fields and into the factories. Women also moved—from the fields into the home. Men’s social role was to produce; women’s was to love (provide nurturance and intimacy). These roles created societal expectations for the nature of love. Thus, one’s expectations determine whether one will be satisfied or disappointed with love. For example, Western society often expects a woman to define herself in terms of her relationship with a man; love is closely linked to sex and marriage. Yet women live longer than men, which often means that a woman will be living without a man in her later years. Women can retain society’s expectations or can change their expectations so that they can connect with others on a basis other than traditional concepts of love. Psychologists will continue to investigate changing expectations about loving relationships.

Bibliography

Buss, David M. The Dangerous Passion. New York: Free Press, 2000. Print.

Fisher, Helen. Why We Love: The Nature and Chemistry of Romantic Love. New York: Holt, 2005. Print.

Fromm, Erich. The Art of Loving. New York: Harper, 1956. Print.

Horstman, Judith. The Scientific American Book of Love, Sex, and the Brain: The Neuroscience of How, When, Why, and Who We Love. San Francisco: Jossey-Bass, 2012. Print.

Jolly, Alison. Lucy’s Legacy: Sex and Intelligence in Human Evolution. Cambridge: Harvard UP, 2001. Print.

Paludi, Michele Antoinette. The Psychology of Love. Santa Barbara: Praeger, 2012. Print.

Person, Ethel S. Dreams of Love and Fateful Encounters. Washington: American Psychiatric, 2007. Print.

Rubin, Zick. Liking and Loving. New York: Holt, 1973. Print.

Shaver, P., C. Hazan, and D. Bradshaw. “Love as Attachment: The Integration of Three Behavioral Systems.” The Psychology of Love. Ed. Robert J. Sternberg and Michael L. Barnes. New Haven: Yale UP, 1988. Print.

Sternberg, Robert J. Love Is a Story: A New Theory of Relationships. New York: Oxford UP, 1999. Print.

Wright, Robert. The Moral Animal: The New Science of Evolutionary Psychology. London: Abacus, 2005. Print.

Young, Larry, and Brian Alexander. The Chemistry Between Us: Love, Sex, and the Science of Attraction. New York: Current, 2012. Print.

What are the similarities between plant and animal cells, other than similar organelles or that they are both eukaryotic cells?

It's difficult to discuss similarities between the two cell types without mentioning their eukaryotic nature or their shared organelles, because these elements are so fundamental to their identity. However, we can generally talk about and compare their metabolisms, organization and lifestyles without turning it into a list of organelles.

Plants and animals both came from the same common ancestor, although we don't know exactly what that common ancestor was or when it lived. This is...

It's difficult to discuss similarities between the two cell types without mentioning their eukaryotic nature or their shared organelles, because these elements are so fundamental to their identity. However, we can generally talk about and compare their metabolisms, organization and lifestyles without turning it into a list of organelles.

Plants and animals both came from the same common ancestor, although we don't know exactly what that common ancestor was or when it lived. This is evidenced not only by our shared organelles, but by our similar metabolisms, DNA and appearance in the fossil record. We know that the fundamental structures of cells, such as phospholipid membranes and the structure and usage of DNA must have been a very ancient trait, because they're virtually identical in plants and animals, in addition to various reactions such as respiration. Basically, plants and animals were latecomers to the game of life, and took the foundations laid by billions of years of evolution and made themselves exponentially more complex, but the basic elements are clearly inherited from something much older.

Plants and animals are also basically the only things that can be confidently said to practice sexual reproduction, which is part of why they have the diversity and complexity that we have come to associate with them. Likewise, they are generally unable to alter their DNA during their lifetimes, as bacteria are. 

Finally, plants and animals tend to be highly organized, and in multicellular forms, they tend to have specialized sub-categories of cells that perform a particular function within the organism. Unlike bacteria or other single-celled organisms, the DNA contained in any given multicellular plant cell may not represent the entire genetic content expressed in that particular cell.

How does Ars Poetica/On the Art of Poetry by Horace contribute to our knowledge of the drama and dramatical conventions of his age?

Horace’s Ars Poetica, composed around 15 B.C.E., guides potential poets in developing their art, and thereby reveals several conventions of favorable Roman poetry. It’s important to note that “poetry” here includes Roman drama.

First, he states that the aim of poetry should be to simultaneously delight and instruct its audience: “He who joins the instructive with the agreeable, carries off every vote, by delighting and at the same time admonishing the reader.” Here, Horace reveals...

Horace’s Ars Poetica, composed around 15 B.C.E., guides potential poets in developing their art, and thereby reveals several conventions of favorable Roman poetry. It’s important to note that “poetry” here includes Roman drama.

First, he states that the aim of poetry should be to simultaneously delight and instruct its audience: “He who joins the instructive with the agreeable, carries off every vote, by delighting and at the same time admonishing the reader.” Here, Horace reveals that Roman poetry was valued by how well it merged aesthetic qualities with useful or practical insights. In Latin, these aims are dolce, or delight, and utile, or utility.

Next, Horace advises that poetry shouldn’t be protracted, but instead, concise. He reasons, “All superfluous instructions flow from the too full memory.” Whatever can’t be remembered isn’t useful; a poem or dramatic work should then be easy to recollect, and not be too excessive in length.

Finally, Horace insists that poetry should be harmonious, or possess a certain musical quality. At several points he instructs the reader in the use of stressed and unstressed syllables, and claims that one can always look to Homer for perfect examples of harmonious verse.

What is prenatal physical development?

Introduction

Pregnancy encompasses the development of a single-celled fertilized egg into a trillion-celled baby. The many changes that transform the fertilized egg into a newborn infant over nine months of human pregnancy constitute prenatal development. Prenatal development comprises three stages (zygote, embryo, and fetus) and is also commonly categorized into three trimesters, each lasting three months. Although prenatal development typically follows a predictable course, development can be disrupted by both genetic and environmental factors. This disruption may result in a range of outcomes, from fetal death and severe abnormalities such as deformed or missing limbs, to minor abnormalities such as low birth weight and neurological dysfunction such as learning disabilities or attention-deficit hyperactivity disorder (ADHD).

The fourth century b.c.e. Greek philosopher Aristotle is regarded as the first in Western civilization to study prenatal development. In the years that followed, others superficially investigated the topic. However, it was not until the beginning of the twentieth century that researchers intensified their study of prenatal development. In the early 1900s, researchers were significantly influenced by the evolutionary theories of Charles Darwin and believed that all aspects of prenatal development were genetically determined.

Josef Warkany, a pioneering American scientist, engendered a shift in the thinking of the scientific community during the 1940s. Warkany documented that environmental factors, called teratogens, could adversely affect prenatal development and cause malformations at birth. About a decade later, the notion that environmental factors could harm prenatal development became mainstream after the 1950s thalidomide tragedy. Thalidomide was a drug given to pregnant women to combat symptoms of nausea. When taken in the first trimester of pregnancy, the drug produced severe physical deformities in infants, including missing arms and stunted limbs, and its use was subsequently banned. Following this tragedy and the resulting acceleration in understanding of the importance of intrauterine life, diagnostic tests have become routinely used to monitor the course of prenatal development.

Stages of Prenatal Development

Prenatal development begins when a sperm successfully fertilizes an egg (ovum) and usually lasts an average of thirty-eight weeks (nine months). The American College of Obstetrics and Gynecology has standardized the terminology used to describe the three stages of prenatal development. The first stage, the zygote (or germinal) stage, begins at fertilization and ends two weeks later, shortly after implantation of the zygote in the uterine wall. The second stage, the embryo stage (weeks three to eight), is the most vulnerable to teratogenic (environmental) insult. The fetal stage (weeks nine to thirty-eight) represents the final and longest stage of prenatal development.

The Zygote Stage

Fertilization of an egg by a sperm creates a zygote. The two-week period of the zygote after conception ends with its implantation into the uterine wall. During these two weeks, the zygote grows rapidly and is carried by currents in one of the Fallopian tubes toward the uterus. The movement through the Fallopian tube usually takes five days. The zygote divides from a single cell into a mass of approximately one hundred cells. Approximately one week after fertilization, the zygote is ready to attach itself to the uterine wall. Many potential pregnancies terminate at this point as a result of implantation failure. Implantation takes approximately one week to complete, connects the zygote with the woman’s blood supply, and triggers hormonal changes that prevent menstruation. At this stage, the implanted zygote is less than a millimeter in diameter but is beginning to differentiate into two structures: the germinal disc and the placenta. The germinal disc eventually develops into the baby, while the remaining cells transform into the placenta. The placenta is the structure through which nutrients and waste are exchanged between the mother and the developing child. Successful implantation and differentiation into the placenta and germinal disc mark the end of the period of the zygote.

The Embryo Stage

On successful implantation in the uterine wall, the zygote is called an embryo and pregnancy enters its second stage. The embryo stage typically begins three weeks after conception (fertilization) and lasts through the eighth week of pregnancy. At the beginning of the embryo stage, the embryo is only two millimeters long and less than an ounce in weight. The embryo is enclosed in a protective sac called the amnion, which is filled with amniotic fluid that cushions and maintains a constant temperature for the embryo. The embryo’s cells form into three layers: The outer layer (ectoderm) becomes the hair, the outer layer of skin, and the nervous system; the middle layer (mesoderm) forms muscles, bones, and the circulatory system; and the inner layer (endoderm) forms the digestive system and lungs. At the beginning of this stage, the embryo looks more like a lizard than a human being, as a result of the shape of its body and head. By the end of the eighth week of pregnancy, the embryo manifests distinguishable human characteristics (eyes, arms, legs) and contains in rudimentary form all of its organs and body structures. Despite these significant changes, the embryo remains too small to be detected by the mother.

The Fetal Period

The longest and final phase of prenatal development is known as the fetal period. The fetal period represents a time when the finishing touches are put on the structures of the fetus. This period begins at nine weeks and ends with the birth of the baby. During this stage of pregnancy, the growth and development of the fetus is astounding. The fetus will increase in mass from less than one ounce at week nine, to eight ounces at four months, and to nearly eight pounds at birth. Around the start of the fetal period, the fetus begins to differentiate sex characteristics. At twelve weeks, the circulatory system becomes functional. At sixteen weeks, the mother can detect fetal movements known as quickening. By twenty weeks, a fine layer of hair (called lanugo) begins to grow over most of the fetus’s body. Sucking and swallowing reflexes are present by twenty-four weeks of gestation. Brain specialization becomes particularly acute by about twenty-eight weeks. At thirty-two weeks of gestation (seven months), the fetus is viable outside the mother’s womb. By this time, most systems function well enough that a fetus born at this age has a chance to survive. Despite the potential to survive, premature birth predisposes a baby to myriad additional developmental problems (health problems, learning disabilities, and cognitive deficits). By thirty-two weeks of prenatal development, the fetus has regular periods of physical activity, and the eyes and ears begin to function. By thirty-six weeks of gestation, the fetus experiences rapid weight gain, and development consists largely of an increase in weight and length. At approximately thirty-eight weeks of gestation, birth will occur. The average newborn baby weighs between seven and eight pounds.

Disruptions in Prenatal Development

Although most of prenatal development progresses in a healthy and predictable fashion, numerous factors can disrupt the course of prenatal development. It is customary to divide the possible cause of these malformations into genetic factors (chromosomal abnormalities) and environmental factors (such as drugs or viral infections). There is often an interaction between environmental conditions and genetic factors such that the environment can either exacerbate or mitigate any potential adverse outcomes. The impact of both genetic and environmental factors may result in abnormalities that range from fetal death and severe structural defects to subtle neurological malformations that may not manifest themselves until several years after birth (as with learning disabilities or ADHD).

General Risk Factors

Parental age can have an impact on prenatal development. Women over the age of thirty-five are at greater risk of giving birth to children with birth defects such as Down syndrome and other chromosomal abnormalities. Recent research suggests that older men also have an increased risk of fathering children with birth defects as a result of the presence of damaged sperm that may fertilize the egg. Teenage girls are also at greater risk for giving birth to children with birth defects as a result of poor maternal health and inadequate prenatal care. When prenatal nourishment and care are lacking, the baby is more likely to be born prematurely, have a lower birth weight, and be at greater risk for learning difficulties and a host of behavioral and emotional problems. Recent research has also implicated other factors during pregnancy as a general risk factor for psychological, behavioral, and educational outcomes.

Genetic and Chromosomal Risk Factors

Thousands of genetic and chromosomal anomalies can potentially disturb normal prenatal development. Although many of the causes of genetic and chromosomal abnormalities are unknown, some may be attributable to exposure to teratogens that damage the chromosomes during prenatal development. Research emerging out of the Human Genome Project is continuously documenting additional chromosomal abnormalities that may have an impact on prenatal development. A chromosome is a microscopic component of a cell that carries its genetic makeup. One of the most common chromosomal disorders is Down syndrome. Individuals with Down syndrome have slanted eyes; thick, fissured tongues; and a flat, broad face. They are often mentally disabled and have significant language impairments. Other chromosomal and genetic disorders include Turner syndrome, Klinefelter syndrome, fragile X syndrome, muscular dystrophy, and neural tube defects that result in spina bifida. Many of these conditions produce intellectual disability and physical anomalies such as brain damage, unusual appearance, and malformed limbs.

Prenatal Diagnostic Tests

Prenatal diagnosis of potential problems is possible using tests, such as amniocentesis, that can detect the presence of many chromosomal and genetic abnormalities. Amniocentesis involves the insertion of a hollow needle through the mother’s abdomen into the amniotic sac and the withdrawal of fluid containing fetal cells. Amniocentesis can detect chromosomal abnormalities such as Down syndrome, but it is not usually performed until the fifteenth week of pregnancy. Chorionic villus sampling (CVS) provides the same information as amniocentesis, but at a much earlier gestational period (seven weeks). In CVS, fetal cells are obtained from the placenta by means of a tube inserted through the vagina. There is greater risk of infection and miscarriage with CVS. Fetoscopy is a surgical procedure involving the insertion of an instrument that permits actual viewing of the fetus and the obtaining of fetal tissue. This procedure is more precise than CVS and amniocentesis but carries a highter risk of miscarriage.

Ultrasound involves the use of sound waves that provide a computer-enhanced image of the fetus. It is a noninvasive, painless, and low-risk procedure that provides an actual image of fetal shape and movement. It is useful for detecting normal and abnormal fetal development and for determining fetal position and age. Preimplantation diagnosis is an experimental, highly technical genetic examination of cells before their implantation in the uterine wall. It typically follows in vitro fertilization and permits the detection of specific genetic disorders. In the future, it may be useful for correcting genetic disorders as well.

Through prenatal diagnostic tests, researchers are able to detect genetic weaknesses (and strengths) from the earliest moments of life. Researchers have also begun to experiment with ways of altering genetic messages, the results of which may lead to corrections of genetic abnormalities in the future.

Environmental Risk Factors

A teratogen is an environmental agent such as alcohol, cocaine, or infectious organism that has an adverse impact on prenatal development following maternal exposure. The word has Greek origins and literally means “monster-forming.” Certain stages of prenatal development are more vulnerable to teratogens than others. Exposure during the period of the zygote usually results in spontaneous abortion of the fertilized egg, while exposure during the embryo stage can lead to major defects in bodily structure and quite possibly death. Exposure during the fetal period usually produces minor structural defects, such as wide-set eyes, and neurological impairment, such as intellectual disability or learning problems. Some of the more commonly implicated teratogens include infectious agents such as cytomegalovirus, varicella virus, and human parvovirus B19, and drugs such as alcohol, cocaine, and nicotine.

The fetus is most vulnerable to the effects of teratogens during the first trimester. These effects are severe and may result in structural deformities and death.

Sarnoff Mednick and others at the University of Southern California reported on a more subtle form of prenatal disturbance following second trimester exposure. Mednick reported preliminary data that linked second trimester viral infections to later psychological outcomes such as depression and schizophrenia. Jose Cordero, former U.S. assistant surgeon general and director of the CDC’s Center for Birth Defects and Disabilities, indicated greater need for awareness of a broader range of teratogens such as fever and infectious agents in relation to outcomes such as learning disabilities, mood disorders, and attention deficits. Stefan Dombrowski, a professor at Rider University in New Jersey, and Roy Martin, a professor at the University of Georgia, compiled the first book on the topic of prenatal exposures in relation to psychological, behavioral, and educational outcomes in children. These two researchers indicate that certain prenatal exposures including fever, influenza, stress, and air pollution may be associated with adverse psychological, behavioral, and educational outcomes. The hypothesis guiding this research is that a prenatal exposure disrupts the neurological development of the fetus and produces abnormal behavioral and psychological outcomes in offspring.

There are additional environmental agents that can potentially disrupt the normal course of prenatal development. Studies have investigated the impact of caffeine. Although the results are equivocal, exposure to moderate amounts of caffeine may result in lower birth weight and decreased fetal muscle tone. Excessive caffeine use during pregnancy should, therefore, be avoided. The impact of alcohol during pregnancy is well documented. Chronic alcohol use produces fetal alcohol syndrome and associated cognitive deficits and physical deficits such as heart problems, retarded growth, and misshapen faces. Maternal alcohol use during prenatal development is the most common cause of intellectual disability. Because even moderate daily alcohol use (two ounces of alcohol) has been associated with some of these outcomes, it is recommended that alcohol use during pregnancy be avoided. Nicotine exposure from cigarette smoking is another well-established teratogen. Research indicates that prenatal cigarette exposure increases the risk for low birth weight, cognitive deficits, learning problems, behavior problems, and even fetal death as a result of nicotine-induced placental and neurological defects.

Overall, the critical prenatal period for exposure to teratogens is during the first trimester of pregnancy. Within the first trimester, certain periods are even more sensitive to teratogens than others. For example, the first six weeks of pregnancy is a particularly sensitive period in the development of the central nervous system, while the eyes are vulnerable during weeks five through eight. It is commonly accepted that exposure to teratogens during the first eight weeks of pregnancy may induce major structural abnormalities. Exposure during the remainder of prenatal development, depending on the type of teratogen and intensity and duration of exposure, may lead to minor structural abnormalities (wide eyes, webbed hands) as well as cognitive, behavioral, and psychological difficulties. Although central nervous system development and brain growth are most vulnerable to disruptions during the first trimester of pregnancy, these structures continue to develop throughout the prenatal period. Thus, exposure to any environmental risk factor should be minimized if at all possible.

Bibliography

Berk, Laura E. Infants and Children: Prenatal through Middle Childhood. 7th ed. Boston: Pearson, 2011. Print.

Cordero, J. F. “A New Look at Teratogens and Behavioral Outcomes: A Commentary.” Birth Defects Research Part A: Clinical and Molecular Teratology 67 (2003): 900–902. Print.

Dombrowski, S. C., R. P. Martin, and M. O. Huttunen. “Association between Maternal Fever and Psychological/Behavioral Outcomes: A Hypothesis.” Birth Defects Research Part A: Clinical and Molecular Teratology 67 (2003): 905–10. Print.

Marin-Padilla, Miguel. The Human Brain: Prenatal Development and Structure. New York: Springer, 2011. Print.

Martin, R. P., and S. C. Dombrowski. Prenatal Exposures: Psychological and Educational Consequences for Children. New York:. Springer, 2008. Print.

Moore, Keith L., T. V. N. Persaud, and Mark G. Torchia. Before We Are Born: Essentials of Embryology and Birth Defects. 8th ed. Philadelphia: Saunders/Elsevier, 2013. Print.

Paul, Annie Murphy. Origins: How the Nine Months before Birth Shape the Rest of Our Lives. New York: Free, 2011. Print.

Shepard, Thomas H., et al. “Update on New Developments in the Study of Human Teratogens.” Teratology 65.4 (2002): 153–61. Print.

Warkany, Josef. Congenital Malformations. Chicago: Year Book, 1971. Print.

Watson, Jennifer B., Sarnoff A. Mednick, Matti O. Huttunen, and Xueyi Wang. “Prenatal Teratogens and the Development of Adult Mental Illness.” Development and Psychopathology 11.3 (1999): 457–66. Print.

What is the RNA world?

The Central Dogma and the Modern Genetic World

Soon after the discovery of the double-helical structure of DNA in 1953 by James Watson
and Francis Crick, Crick proposed an idea regarding information flow in cells that he called the “central dogma of molecular biology.” Crick correctly predicted that in all cells, information flows from DNA to RNA to protein. DNA was known to be the genetic material, the “library” of genetic information, and it had been clear for some time that the enzymes that actually did the work of facilitating chemical reactions were invariably protein molecules. The discovery of three classes of RNA during the 1960s seemed to provide the link between the DNA instructions and the protein products.

In the modern genetic world, cells contain three classes of RNA that act as helpers in the synthesis of proteins from information stored in DNA, a process called translation. A messenger RNA (mRNA) is transcribed from a segment of DNA (a gene) that contains information about how to build a particular protein and carries that information to the cellular site of protein synthesis, the ribosome. Ribosomal RNA (rRNA) interacting with many proteins make up the ribosome, whose major job is to coordinate and facilitate the protein-building procedure. Transfer RNA (tRNA) acts as decoding molecules, reading the mRNA information and correlating it with a specific amino acid. As the ribosome integrates the functions of all three types of RNA, polypeptides are built one amino acid at a time. These polypeptides, either singly or in aggregations, can then function as enzymes, ultimately determining the capabilities and properties of the cell in which they act.

While universally accepted, the central dogma led many scientists to question how this complex, integrated system came about. It seemed to be a classic “chicken and egg” dilemma: proteins could not be built without instructions from DNA, but DNA could not replicate and maintain itself without help from protein enzymes. The two seemed inextricably mutually dependent on each other. An understanding of the origins of the modern genetic system seemed far away.

The Discovery of Ribozymes

In 1983, a discovery was made that seemed so radical it was initially rejected by most of the scientific community. Molecular biologists Thomas Cech and Sidney Altman, working independently and in different systems, announced the discovery of RNA molecules that possessed catalytic activity. This meant that RNA itself could function as an enzyme, obliterating the idea that only proteins could function catalytically.

Cech had been working with the protozoan Tetrahymena. In most organisms except bacteria, the coding portions of DNA genes (exons) are interrupted by noncoding sequences (introns), which are transcribed into mRNA but must be removed before translation. Protein enzymes called nucleases are usually responsible for cutting out the introns and joining together the exons in a process called splicing. The molecule with which Cech was working was an rRNA molecule that contained introns but could apparently remove them and rejoin the coding regions without any help. It was a self-splicing RNA molecule, which clearly indicated its enzymatic capability. Altman was working with the enzyme ribonuclease (RNase) P in bacteria, which is responsible for cutting mature tRNA molecules out of an immature RNA segment. RNase P thus also acts as a nuclease. It was known for some time that RNase P contains both a protein and an RNA constituent, but Altman was ultimately able to show that it was the RNA rather than the protein that actually catalyzed the reaction.

The importance of these findings cannot be overstated, and Cech and Altman ultimately shared the 1989 Nobel Prize in Chemistry for the discovery of these RNA enzymes, or ribozymes (joining the terms “ribonucleic acid” and “enzymes”). Subsequently, many ribozymes have been found in various organisms, from bacteria to humans. Some of them are able to catalyze different types of reactions, and new ones are periodically reported. Ribozymes have thus proven to be more than a mere curiosity, playing an integral role in the molecular machinery of many organisms.

At around the same time as these important discoveries, still other functions of RNA were being identified. While perhaps not as dramatic as the ribozymes, antisense RNAs, small nuclear RNAs, and a variety of others further proved the versatility of RNA. While understanding the roles of ribozymes and other unconventional RNAs is important to the understanding of genetic functioning in present-day organisms, these discoveries were more intriguing to many scientists interested in the origin and evolution of life. In a sense, the existence of ribozymes was a violation of the central dogma, which implied that information was ultimately utilized solely in the form of proteins. While the central dogma was not in danger of becoming obsolete, a clue had been found that might possibly allow a resolution, at least in theory, to questions about whether the DNA or the protein came first. The exciting answer: perhaps neither.

The RNA World Theory and the Origin of Life

Given that RNA is able to store genetic information (as it certainly does when it functions as mRNA) and the new discovery that it could function as an enzyme, there was no longer any need to invoke the presence of either DNA or protein as necessities in the first living system. The first living molecule would have to be able to replicate itself without any help, and just such an “RNA replicase” has been proposed as the molecule that eventually led to life as it is now known. Like the self-splicing intron of Tetrahymena, this theoretical ribozyme could have worked on itself, catalyzing its own replication. This RNA would therefore have functioned as both the genetic material and the replication enzyme, allowing it to make copies of itself without the need for DNA or proteins. Biologist Walter Gilbert
coined the term “RNA world” for this interesting theoretical period dominated by RNA. Modern catalytic RNAs can be thought of as molecular fossils that remain from this period and provide clues about its nature.

How might this initial RNA have come into being in the first place? Biologist Aleksandr Oparin
predicted in the late 1930s that if simple gases thought to be present in Earth’s early atmosphere were subjected to the right conditions (energy in the form of lightning, for example), more complex organic molecules would be formed. His theory was first tested in 1953 and was resoundingly confirmed. A mixture of methane, ammonia, water vapor, and hydrogen gas was energized with high-voltage electricity, and the products were impressive: several amino acids and aldehydes, among other organic molecules. Subsequent experiments have been able to produce ribonucleotide bases. It seems reasonable, then, that nucleotides could have been present on the early Earth and that their random linkage could lead to the formation of an RNA chain.

After a while, RNA molecules would have found a way to synthesize proteins, which by their very nature are able to act as more efficient and diverse enzymes than ribozymes. Why are proteins better enzymes than ribozymes? Since RNA contains only four bases, which are fundamentally similar in their chemical properties, the range of different configurations and functional capabilities is somewhat limited. Proteins, on the other hand, can be constructed from a pool of at least twenty different amino acids, whose functional groups differ widely in terms of their chemical makeup and potential reactivity. It is logical to suppose, therefore, that proteins eventually took over most of the roles of RNA enzymes because they were simply better suited to doing so. Several of the original, efficient ribozymes would have been retained, and those are the ones that still can be observed.

How could a world composed strictly of RNAs, however, be able to begin protein synthesis? While it seems like a tall order, scientists have envisioned an early version of the ribosome that was composed exclusively of RNA. Biologist Harry Noller reported in the early 1990s that the activity of the modern ribosome that is responsible for catalyzing the formation of peptide bonds between amino acids is in fact carried out by rRNA. This so-called peptidyl-transferase activity had always been attributed to one of the ribosomal proteins, and rRNA had been envisioned as playing a primarily structural role. Noller’s discovery that the large ribosomal RNA is actually a ribozyme allows scientists to picture a ribosome working in roughly the same way that modern ones do, without containing any proteins. As proteins began to be synthesized from the information in the template RNAs, they slowly began to assume some of the RNA roles and probably incorporated themselves into the ribosome to allow it to function more efficiently.

The transition to the modern world would not be complete without the introduction of DNA as the major form of the genetic material. RNA, while well suited to diverse roles, is actually a much less suitable genetic material than DNA for a complex organism, even one only as complex as a bacterium. This is because the slight chemical differences between the sugars contained in the nucleotides of RNA and DNA cause the RNA to be more reactive and much less chemically stable, which is good for a ribozyme but bad if the genetic material is to last for any reasonable amount of time. Once DNA came into existence, therefore, it is likely that the relatively complex organisms of the time quickly adopted it as their genetic material; shortly thereafter, it became double-stranded, which facilitated its replication immensely. This left RNA, the originator of it all, relegated to the status it now enjoys; molecular fossils exist that uncover its former glory, but it functions mainly as a helper in protein synthesis.

This still leaves the question of how DNA evolved from RNA. At least two protein enzymes were probably necessary to allow this process to begin. The first, ribonucleoside diphosphate reductase, converts RNA nucleotides to DNA nucleotides by reducing the hydroxyl group located on the 2′ carbon of ribose. Perhaps more important, the enzyme reverse transcriptase would have been necessary to transcribe RNA genomes into corresponding DNA versions. Examples of both of these enzymes exist in the modern world.

Some concluding observations are in order to summarize the evidence that RNA, and not DNA, was very likely the first living molecule. No enzymatic activity has ever been attributed to DNA; in fact, the 2′ hydroxyl group that RNA possesses and DNA lacks is vital to RNA’s ability to function as a ribozyme. Furthermore, ribose is synthesized much more easily than deoxyribose under laboratory conditions. All modern cells synthesize DNA nucleotides from RNA precursors, and many other players in the cellular machinery are RNA-related. Important examples include adenosine triphosphate (ATP), the universal cellular energy carrier, and a host of coenzymes such as nicotinamide adenine dinucleotide (NAD), derived from B vitamins and vital for energy metabolism.

Impact and Applications

The discovery of ribozymes and the other interesting classes of RNA has dramatically altered the understanding of genetic processes at the molecular level and has provided compelling evidence in support of exciting new theories regarding the origin of life and cellular evolution. The RNA world theory, first advanced as a radical and unsupported hypothesis in the early 1970s, has gained widespread acceptance by scientists. It is the solution to the evolutionary paradox that has plagued scientists since the discovery and understanding of the central dogma: Which came first, DNA or proteins? Since they are inextricably dependent on each other in the modern world, the idea of the RNA world proposes that, rather than one giving rise to the other, they are both descended from RNA, that most ancient of genetic and catalytic molecules.

Unfortunately, the RNA world model is not without its problems. In the mid- to late 1990s, several studies on the stability of ribose, the sugar portion of ribonucleotides, showed that it breaks down relatively easily, even in neutral solutions. A study of the decay rate of ribonucleotides at different temperatures also caused some concern for the RNA world theory. Most current scenarios see life arising in relatively hot conditions, at least near boiling, and the instability of ribonucleotides at these temperatures would not allow for the development of any significant RNA molecules. Ribonucleotides are much more stable at 0 degrees Celsius (32 degrees Fahrenheit), but evidence for a low-temperature environment for the origin of life is limited. Consequently, some evolutionists are suggesting that the first biological entities might have relied on something other than RNA, and that the RNA world was a later development. Therefore, although the RNA world seems like a plausible model, another model is now needed to establish the precursor to the RNA world.

Apart from origin-of-life concerns, the discoveries that led to the RNA world theory are beginning to have a more practical impact in the fields of industrial genetic engineering and medical gene therapy. The unique ability of ribozymes to find particular sequences and initiate cutting and pasting at desired locations makes them powerful tools. Impressive uses have already been found for these tools in theoretical molecular biology and in the genetic engineering of plants and bacteria. Most important to humans, however, are the implications for curing or treating genetically related disease using this powerful RNA-based technology.

Gene therapy, in general, is based on the idea that any faulty, disease-causing gene can be replaced by a genetically engineered working replacement. While theoretically a somewhat simple idea, in practice it is technically very challenging. Retroviruses
may be used to insert DNA into particular target cells, but the results are often not as expected; the new genes are difficult to control or may have adverse side effects. Molecular biologist Bruce Sullenger pioneered a new approach to gene therapy that seeks to correct the genetic defect at the RNA level. A ribozyme can be engineered to seek out and replace damaged sequences before they are translated into defective proteins. Sullenger has shown that this so-called trans-splicing technique can work in nonhuman systems, and in 1996 he began trials to test his procedure in humans.

Many human diseases could be corrected using gene-therapy technology of this kind, from inherited defects such as sickle-cell disease to degenerative genetic problems such as cancer. Even pathogen-induced conditions such as acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), could be amenable to this approach. It is ironic and gratifying that an understanding of the ancient RNA world holds promise for helping scientists to solve some of the major problems in the modern world of DNA-based life.

Key Terms




ribosomal RNA (rRNA)


:

a type of RNA that forms a major part of the structure of the ribosome





ribosome


:

an organelle that functions in protein synthesis, containing a large and a small subunit composed of proteins and ribosomal RNA molecules




ribozyme

:

an RNA molecule that can function catalytically as an enzyme





Bibliography

Atkins, John F., Raymond F. Gesteland, and Thomas R. Cech, eds. RNA Worlds: From Life's Origins to Diversity in Gene Regulation. Cold Spring Harbor: Cold Spring Harbor, 2011. Print.

Bernhardt, Harold S. "The RNA World Hypothesis: The Worst Theory of the Early Evolution of Life (except for All the Others)." Biology Direct 7.23 (2012):1–10. Web. 14 Aug. 2014.

de Duve, Christian. “The Beginnings of Life on Earth.” American Scientist Sept./Oct. 1995: 428–37. Print.

Elliott, David, and Michael Ladomery. Molecular Biology of RNA. New York: Oxford UP, 2011. Print.

Hart, Stephen. “RNA’s Revising Machinery.” BioScience 46.5 (1996): 318–21. Print.

Hazen, Robert M. Genesis: The Scientific Quest for Life’s Origin. Washington: Henry, 2005. Print.

Horgan, John. “The World according to RNA.” Scientific American Jan. 1996: 27–30. Print.

Luisi, Pier Luigi. The Emergence of Life: From Chemical Origins to Synthetic Biology. New York: Cambridge UP, 2006. Print.

Miller, Stanley L. From the Primitive Atmosphere to the Prebiotic Soup to the Pre-RNA World. Washington: Natl. Aeronautics and Space Administration, 1996. Print.

Rauchfuss, Horst. Chemical Evolution and the Origin of Life. Trans. Terence N. Mitchell. Berlin: Springer, 2008. Print.

Szostak, Jack W. "The Eightfold Path to Non-Enzymatic RNA Replication." Journal of Systems Chemistry 3.2 (2012): 1–14. Web. 14 Aug. 2014.

Watson, James D., et al. Molecular Biology of the Gene. 7th ed. San Francisco: Benjamin, 2014. Print.

Yang, Lin, John E. Froberg, and Jeannie T. Lee. "Long Noncoding RNAs: Fresh Perspectives into the RNA World." Trends in Biochemical Sciences 39.1 (2014): 35–43. Print.

What is idiopathic thrombocytopenic purpura?

Definition

Idiopathic thrombocytopenic purpura (ITP) is a treatable blood disorder.
Antibodies that are produced in the spleen attack and
destroy the body’s own blood-clotting cells (platelets), which help stop bleeding.
Normally, platelets move to damaged areas of the body and stick together, forming
a sort of barrier against germs. If there are not enough platelets in the body,
bleeding injuries are difficult to stop. Although people with ITP have a lower
than normal number of platelets in their blood, all other blood cell counts are normal.

There are two types of ITP. Acute ITP, which lasts less than six months and usually occurs in children, is the most common. Chronic ITP lasts more than six months and usually occurs in adults.

Causes

The cause of most cases of ITP is unknown. In children, the disorder has been
linked to viral
infections. It is believed that in these cases the immune
system becomes confused and begins attacking healthy platelet cells. When too many
platelets are destroyed, ITP can result. The disorder in adults has not been
linked to viral infections. Some cases of ITP are thought to be caused by drugs,
infection, or other immune disorders. Pregnant women too sometimes develop the
disorder.

Risk Factors

Persons with an increased chance of developing ITP include children who have had a recent viral infection or have had a live-virus vaccination (which may sometimes put a child at a higher risk); women, usually younger than age forty years; and women in general, who are two to three times more likely to get ITP than are men.

Symptoms

Both adults and children may notice the following symptoms of ITP: easy
bruising, dark urine or stools, bleeding for longer than normal following an
injury, unexplained nosebleeds, bleeding from the gums, heavier-than-normal
menstrual periods (in adult women), red dots called petechiae on the skin
(petechiae may occur in groups and resemble a rash), and, in rare cases, bleeding
within the intestinal tract or brain.

Screening and Diagnosis

A doctor will ask about symptoms and medical history and will perform a
physical exam. Tests may include a complete blood count (CBC), in which a
blood sample is tested to see if the numbers of different blood cells are normal;
and a bone marrow test, in which a needle is inserted into the skin and into the
bone and a small amount of bone marrow is removed. The sample is tested to ensure
the marrow contains normal numbers of platelet-producing cells. This test is done
to rule out other disorders. Another test is a computed tomography (CT)
scan (in rare cases). The CT scan is done if there is a
concern about bleeding in the brain.

Treatment and Therapy

Treatment for ITP is different for children and for adults. Most children
recover from ITP without any treatment. However, a doctor may recommend the
following: medications to increase platelet counts in the blood, such as
steroids (for example, prednisone), which lowers the
activity of the immune system and keeps it from destroying platelets; and gamma
globulin infusions (an antibody-containing protein that slows down platelet
destruction). An infusion means that the injection is given by IV (intravenously)
or through a shot. It usually works more quickly than steroids. Both of these
treatments work but both can have side effects. Eighty-five percent of children
who have ITP recover within a year and do not experience the problem again.

Two newer drugs stimulate platelet production: eltrombopag (Promacta) and
romiplostim (Nplate). Using these drugs and also using the targeted monoclonal
antibody rituximab (Rituxan) may prevent the need for a splenectomy. A
splenectomy is the surgical removal of the spleen. This
procedure stops the destruction of platelets because the antibodies are made in
the spleen. In adults, if drug intervention does not do enough to raise platelet
counts, the doctor may recommend a splenectomy.

A splenectomy leaves the body more vulnerable to infection from other sources. This surgery is usually not performed until medications have proven ineffective. Doctors also sometimes recommend lifestyle changes when platelet counts are low, including avoiding contact sports; patients also are recommended to wear a helmet during sports activities.

Prevention and Outcomes

Because the cause of ITP is unknown, there are no specific ways to prevent the disease. However, because bleeding and injury can be serious for people with ITP, one should take precautions to avoid injury, such as using padding on an infant’s crib or around a play area and ensuring that older children wear helmets and protective gear when playing sports (to help reduce bruising injuries). Persons with low platelet counts should stop playing contact sports.

People who have ITP should also avoid medications that contain aspirin or
ibuprofen. These medicines can reduce platelet function. To help stay healthy, one
should eat a healthful diet, low in saturated fat and rich in whole grains,
fruits, and vegetables; get regular exercise; lose weight if overweight; stop
smoking; and drink alcohol, if desired, only in moderation (two drinks per day for
men and onedrink per day for women).

Bibliography

Bick, Roger L. Disorders of Thrombosis and Hemostasis: Clinical and Laboratory Practice. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2002.

Bussel, J. B., et al. “Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura.” New England Journal of Medicine 357, no. 22 (November 29, 2007): 2237-2247.

George, J. N. “Platelets.” The Lancet 355 (April 29, 2000): 1531-1539.

George, J. N., et al. “Update on Idiopathic Thrombocytopenic Purpura.” Available at http://www.hematology.org/publications/hematologist/ 2010/4965.aspx.

Karpatkin, S. “Autoimmune (Idiopathic) Thrombocytopenic Purpura.” The Lancet 349 (1997): 1531-1536.

Lichtman, Marshall A., et al., eds. Williams Hematology. 7th ed. New York: McGraw-Hill, 2006.

McCrae, Keith R., ed. Thrombocytopenia. New York: Taylor & Francis, 2006.

Newland, A., et al. “An Open-Label, Unit Dose-Finding Study of AMG 531, a Novel Thrombopoiesis-Stimulating Peptibody, in Patients with Immune Thrombocytopenic Purpura.” British Journal of Haematology 135, no. 4 (2006): 547-553.

What are lymphadenopathy and lymphoma?

Causes and Symptoms

The lymphatic system consists of a large complex of lymph vessels and groups of lymph nodes (“lymph glands”). The lymph vessels include a vast number of capillaries that collect fluid and dissolved proteins, carbohydrates, and fats from tissue fluids. The lacteals of the intestinal villi are lymph vessels that serve to absorb fats from the intestine and transport them to the bloodstream.

Lymph nodes are found throughout the body but are concentrated most heavily in regions of the head, neck, armpits, abdomen, and groin. Nodes function to filter out foreign materials, such as bacteria or viruses, which make their way into lymphatic vessels.

The sizes of lymph nodes vary: some are as small as a pinhead, some as large as a bean. In general, they are shaped much like kidney beans, with an outer covering. Internally, they consist of a compartmentalized mass of tissue that contains large numbers of B and T lymphocytes as well as antigen-presenting cells (APC). The lymphatic circulation into the lymph nodes consists of a series of entering, or afferent, vessels, which empty into internal spaces, or sinuses. A network of connective tissue, the reticulum, regulates the lymph flow and serves as a site of attachment for lymphocytes and macrophages. The lymphatic circulation leaves the node through efferent, or exiting, vessels in the lower portion of the organ, the hilum.

Among the functions of lymph nodes are those of the immune response. B and
T lymphocytes tend to congregate in specialized areas of the lymph nodes: B cells in the outer region, or cortex, and T cells in the underlying paracortex. When antigen is presented by an APC, T- and B-cell interaction triggers B-cell maturation and proliferation within the germinal centers of the cortex. The result may be a significant enlargement of the germinal centers and subsequently of the lymph node itself.

Lymphadenopathy, or enlarged lymph nodes, may signify a lymphoma, or cancer of the lymphatic system. More commonly, however, the enlarged node is secondary to other phenomena, usually local infections. For example, an ear infection may result in the entrance of bacteria into local lymphatic vessels. These vessels drain into regional nodes of the neck. The result is an enlargement of the nodes in this area, as an immune response is carried out.

Enlarged nodes caused by infections can, in general, be easily differentiated from those caused by malignancies. Infectious nodes are generally smaller than 2 centimeters in diameter, soft, and tender. They usually occur in areas where common infections occur, such as the ears or the throat. Malignant lymph nodes are often large and occur in groups. They are generally firm and hard, and they often appear in unusual areas of the body (for example, along the diaphragm). To confirm a malignancy, a biopsy of material may be necessary.

Infectious nodes can also be caused by diseases such as infectious mononucleosis, tuberculosis, and
Acquired immunodeficiency syndrome (AIDS). Lymphadenopathy syndrome (LAS), a generalized enlargement of the lymph nodes, is a common feature of the prodromal
AIDS-related complex (ARC).

Since lymphadenopathy can be caused by any immune proliferation in the germinal centers, allergy-related illnesses may also cause enlargement of the lymph nodes. Consequently, immune disorders such as rheumatoid arthritis, systemic
lupus erythematosus, and even hay fever
allergies may show enlarged nodes as part of their syndromes.

As is the case for any cell in the body, cells constituting the lymphatic system may undergo a malignant transformation. The broadest definition of these lymphoproliferative diseases, or lymphomas, can include both
Hodgkin disease and Hodgkin lymphomas, in addition to acute and chronic lymphocytic leukemias (ALL and CLL). With the understanding of, and ability to detect, specific cell markers, it is possible to classify many of these lymphomas on the basis of their cellular origin. Such is the case for ALL, CLL, Burkitt lymphoma, and many other forms of non-Hodgkin lymphomas. The cell type that ultimately forms the basis for Hodgkin disease remains uncertain.

Hodgkin disease is a malignant lymphoma that first manifests itself as a painless enlargement of lymphoid tissue. Often, this is initially observed in the form of swollen lymph nodes in the neck or cervical region. Occasionally, the victim may exhibit a mild fever, night sweats, and weight loss. Untreated, the disease spreads from one lymphatic region to another, resulting in diffuse adenopathy. An enlarged spleen (splenomegaly) is a common result. As the disease spreads, other organs such as the liver, lungs, and bone marrow may be involved.

The disease is characterized by the presence of a characteristic cell type—the Reed-Sternberg cell.Reed-Sternberg cells appear to be of macrophage origin, with multilobed nuclei or multiple nuclei. They may also be present in other lymphatic disorders, but their presence is considered to be indicative of all cases of Hodgkin disease. The precise relationship of the cell to the lymphoma is unclear, but some researchers in the field believe that the Reed-Sternberg cell is the actual malignant cell of the disease. The other infiltrative cells present in the node, including many B and T lymphocytes, may simply represent the reaction to the neoplasm. This interpretation, however, has been disputed.

Lymphoma
staging is a system of classifying lymphomas according to the stage of development of the disease. Staging is important in that the prognosis and basis for treatment are in part determined by the stage of disease. Characterizing the form of Hodgkin disease, therefore, involves two forms of classification. The first is a four-part classification based on the histology or cell type (Rye Conference classification). This scheme is based upon the proportion of Reed-Sternberg cells, ranging from their being “hard to find” to their being the predominant type. The prognosis becomes less favorable as the proportion of these cells increases.

Clinical staging, like that based on histology, is a four-part classification scheme (it is actually six parts, since stage III can be divided into subclasses). In this system, classification is based upon the extent of spread or extralymphatic involvement. For example, stage I features the involvement of a single lymph node region or a single extralymphatic site. Stage IV involves multiple disseminated foci. Early-stage disease is more easily treated and has a better prognosis than late-stage disease.

Non-Hodgkin lymphomas (NHLs) represent a multitude of malignant disorders. Unlike Hodgkin disease, they frequently arise in lymphatic tissue that is not easily observed; for example, in the gastrointestinal tract, tonsils, bone, and central nervous system. They have a tendency to spread rapidly, with malignant cells being released into the bloodstream early in the disease. Consequently, by the time diagnosis of NHL is made, the disease has often spread and the prognosis may be poor.

Though the etiology of most forms of NHL remains unknown, certain characteristics are evident in some forms of these diseases. For example, a portion of chromosome 14 is elongated in about 60 percent of NHL patients. Nearly one-third of patients with NHLs of B-cell origin demonstrate a chromosomal translocation, often involving a piece of chromosome 14 being translocated to chromosome 18. Though the relationship of these changes to disease is unclear, one can surmise that chromosomal defects play at least some role in the development of some forms of these disorders.

At least two forms of NHL are either caused by viruses or related to their presence:
Burkitt lymphoma and adult T-cell lymphoma/leukemia. Burkitt lymphoma, which was first described by Denis Burkitt in central Africa, is a B-cell tumor that occurs primarily in children. It is generally manifested as a large tumor of the jaw. This type of lymphoma is associated with early infection by the Epstein-Barr virus, or EBV (also the etiological agent of infectious mononucleosis). The relationship of the disorder to the virus remains unclear, and EBV may be either a specific cause or a necessary cofactor.

Specific chromosomal abnormalities are also associated with Burkitt lymphoma. In 75 percent of cases, a translocation from chromosome 8 to chromosome 14 is evident, while in most other cases, a portion of chromosome 8 is translocated to either chromosome 2 or chromosome 22. Each of these translocations involves the transfer of the same gene from chromosome 8, the c-myc gene. The site to which the c-myc is translocated is in each instance a region that encodes protein chains for antibody production, proteins that are produced in large quantities. The c-myc gene product normally plays a role in committing a cell to divide. By being translocated into these specific regions, the c-myc gene product is overproduced, and the B cell undergoes continual replication.

Approximately 80 percent of NHL tumors are of B-cell origin; the remainder are primarily of T-cell origin. Those lymphomas that arise within the thymus, the organ of T-cell maturation, are called lymphoblastic lymphomas. Those that originate as more differentiated and mature T cells outside the thymus include a heterogeneous group of diseases (for example, peripheral T-cell lymphomas and Sézary syndrome). Often, by the time of diagnosis, these disorders have spread beyond the early stage of classification and have become difficult to treat.

Treatment and Therapy

Treatment and other means of dealing with lymphadenopathy depend on the specific cause. In the case of lymph node enlargement that is secondary to infections, treatment of the primary cause is sufficient to restore the normal appearance of the node. For example, in a situation in which nodes in the neck region are enlarged as the result of a throat infection, antibiotic treatment of the primary cause—that is, the bacterial infection—is sufficient. The nodes will resume their normal size after a short time.

Dealing with lymph node enlargement caused by lymphoma requires a much more aggressive form of treatment. There are many kinds of lymphomas, which differ in type of cell involvement and stage of differentiation of the involved cells. The manifestations of most lymphomas, however, are similar. In general, these disorders first present themselves as painless, enlarged nodes. Often, this occurs in the neck region, but in many forms of NHL, the lymphadenopathy may manifest itself elsewhere in the lymphatic system. As the disease progresses, splenomegaly (enlarged spleen) and hepatomegaly (enlarged liver) may manifest themselves. Frequently, the bone marrow becomes involved. If the enlarged node compresses a vital organ or vessel in the body, immediate surgery may be necessary. For example, if one of the veins of the heart is compressed, the patient may be in immediate, life-threatening danger. Treatment generally includes radiation therapy and/or chemotherapy.

As is true for lymphomas in general, Hodgkin disease is found more commonly in males than in females. In the United States, it occurs at a rate of 3.2 per 100,000 population per year for men and 2.4 per 100,000 for women, with more than nine thousand cases expected to be diagnosed in 2013. More than one thousand persons die of the disease each year. The cause of the disease is unknown, though attempts have been made to assign the Epstein-Barr virus to this role.

Hodgkin disease has an unusual age incidence. The age-specific incidence exhibits a bimodal curve. The disease shows an initial peak among young adults between fifteen and thirty years of age. The incidence drops after age thirty, only to show an additional increase in frequency after age fifty. This is in contrast to NHL, which shows a sharp increase in incidence only after age forty-five. The reasons are unknown.

As noted earlier, the staging of Hodgkin disease is important in determining methods of treatment; the earlier the stage, the better the prognosis. Patients in stage I (single node or site of involvement) or stage II (two or more nodes on the same side of the diaphragm involved, or limited extralymphatic involvement) have a much better prognosis than patients in stages III and IV (splenic or disseminated disease). Prior to the mid-1960s, a diagnosis of Hodgkin disease was almost a death sentence. The development of radiation therapy and chemotherapy has dramatically increased the chances for survival; long-term remission can be achieved in nearly 70 percent of patients, and the “cure” rate may be higher than 90 percent with early detection. In part, this has been the result of understanding the progression of the disease (reflected in the process of staging) and utilizing a therapeutic approach to eradicate the disease both at its current site and at likely sites of spreading.

Radiation therapy
is the treatment of choice for patients in stages I and II; spreading beyond local nodes is still unlikely in these stages. The body is divided into three regions to which radiation may be delivered: The mantle field covers the upper chest and armpits; the para-aortic field is the region of the diaphragm and spleen; and the third field is the pelvic area. For example, a patient manifesting lymphadenopathy in a single node in the neck region may undergo only “mantle” irradiation. As noted above, with early detection, such treatment is effective 90 percent of the time (based on five-year disease-free survival).

Beyond stage II, a combination of radiation therapy and chemotherapy treatment is warranted. A variety of chemotherapy programs have been developed, the most common of which is known by the acronym MOPP (nitrogen mustard/Oncovin/procarbazine/prednisone). With combined radiation therapy and chemotherapy, even stage III disease may go into remission 60 to 70 percent of the time, while 40 to 50 percent of stage IV patients may enter remission. In general, therapy takes six to twelve months.

Non-Hodgkin lymphomas represent a heterogeneous group of malignancies. Eighty percent are of B-lymphocyte origin. The wide variety of types has made classification difficult. The most useful method of classification for clinical purposes is based on the relative aggressiveness of the disease, low-grade being the slowest growing, followed by intermediate-grade and high-grade, which is the most aggressive.

NHLs often arise in lymphoid areas outside the mainstream. For example, the first sign of disease may be an abdominal mass or pain. Fever and night sweats are uncommon, at least in the early stages. Consequently, once the disease is manifested, it is often deep and widespread. Because the disorder is no longer localized by this stage, radiation therapy by itself is of limited use. For comparison, nearly half of Hodgkin disease patients are in stage I at presentation; not quite 15 percent of NHL patients are in stages I and II. Consequently, treatment almost always involves extensive chemotherapy.

A variety of aggressive forms of chemotherapy may be applied. These may include either single drugs such as alkaloids (vincristine sulfate) and alkylating agents (chlorambucil) or combination programs such as that of MOPP. Low-grade types of NHL are frequently slow growing and respond well to less aggressive forms of therapy. Low-grade NHL patients often enter remission for years. Unfortunately, the disorder often recurs with time and may become resistant to treatment; remission may occur in 50 percent of the patients, but only about 10 percent survive disease-free after ten years. High-grade lymphomas are rapidly growing, and the prognosis for most patients in the short term is not good. Those patients who do achieve remission with aggressive therapy, however, often show no recurrence of disease. As many as 50 percent of these persons may be “cured.” The difference in prognosis between low-grade and high-grade disease may relate to the characteristics of the malignant cell. A rapidly growing cancer cell may be more susceptible to aggressive therapy than a slow-growing cancer and more likely to die as a result. Thus, if a patient enters remission following therapy, there is greater likelihood that the cancer has been eradicated.

Perspective and Prospects

What was likely Hodgkin disease was first described in 1666 as an illness in which lymphoid tissues and the spleen had the appearance of a “cluster of grapes.” The disorder was invariably fatal. In 1832, Thomas Hodgkin published a thorough description of the disease, including its progression from the cervical region of the body to other lymphatic regions and organs. The unusual histological appearance of the cellular mixture characteristic of Hodgkin disease was noted during the nineteenth century. It was early in the twentieth century, however, that Dorothy Reed and Karl Sternberg described the cell that is characteristic of the disorder: the Reed-Sternberg cell. As noted earlier, the number and proportion of such cells are the bases for the classification of the disease.

Two forms of non-Hodgkin lymphoma are known to be associated with specific viruses: Burkitt lymphoma (BL) and adult T-cell leukemia (ATL). BL was described by Denis Burkitt, who studied the pattern of certain forms of lymphomas among Ugandan children during the late 1950s. He noted that nearly all cases were found in children between the ages of two and fourteen, and noted that most cases in Africa were found in the malarial belt. Burkitt suspected that a mosquito might be involved in the transmissions of BL. Though no link has been found with arthropod transmission, the idea that BL might be associated with a viral agent bore fruit. In 1964, Michael Epstein and Yvonne Barr reported the presence of a particle in BL tissue that resembled the herpes virus. The Epstein-Barr virus was eventually linked to BL, though the specific role played by the virus remains elusive.

Adult T-cell leukemia was first noted in Japan during the 1970s. Japanese scientists observed that the majority of NHLs there were of T-cell origin and exhibited a similar clinical spectrum. The disease was later observed in the Caribbean basin, the southeastern United States, South America, and central Africa. In 1980, Robert Gallo isolated the etiological agent, the human T-cell lymphotrophic type I virus (HTLV-I).

The treatment of Hodgkin disease represents one of the few success stories in dealing with cancers. In addition, some forms of NHL—notably, Burkitt lymphoma—respond well to treatment. The prognosis for most patients with NHL, however, is less than optimal. In addition, the specific causes of most NHL syndromes are not known. Those with which a virus is linked may, in theory, be prevented by means of vaccination. The etiological agents or factors associated with the development of other forms of lymphomas remain elusive.

Bibliography

Cerroni, Lorenzo, Kevin Gatter, and Helmut Kerl. Skin Lymphoma: The Illustrated Guide. 3d ed. Hoboken, N.J.: Wiley-Blackwell, 2009.

Delves, Peter J., et al. Roitt’s Essential Immunology. 12th ed. Malden, Mass.: Blackwell, 2011.

Greer, John, et al., eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health, 2009.

Holman, Peter, and Jodi Garrett. One Hundred Questions and Answers About Lymphoma. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2011.

Jacobs, Charlotte. Henry Kaplan and the Story of Hodgkin's Disease. Stanford, Calif.: Stanford University Press, 2010.

Jandl, James H. Blood: Textbook of Hematology. 2d ed. Boston: Little, Brown, 1996.

Knowles, Margaret A., and Peter J. Selby. Introduction to the Cellular and Molecular Biology of Cancer. 4th ed. New York: Oxford University Press, 2006.
Leukemia and Lymphoma Society. http://www.leuke mia.org.

Lymphoma Information Network. http://www.lym phomainfo.net.

National Cancer Institute. What You Need to Know About Non-Hodgkin’s Lymphoma. Rev. ed. Bethesda, Md.: Department of Health and Human Services, Public Health Service, National Institutes of Health, 2007.

Schwab, M. Encyclopedia of Cancer. 3d ed. Philadelphia: Springer, 2012.

Specht, Lena, and Joachim Yahalom. Radiotherapy for Hodgkin Lymphoma. New York: Springer, 2011.

What is H1N1 influenza? |

Causes and Symptoms

In April 2009, the US Centers for Disease Control and Prevention (CDC) reported two cases of swine influenza A (H1N1) in children residing in Southern California. Neither child had any exposure to pigs or had traveled abroad in the weeks prior to illness. This strain was found to have a unique genetic code that had not previously been identified in either swine or human cases. Specimens collected from an outbreak of influenza in Mexico, beginning in early 2009, proved to be identical to the strains found in California. By May 5, there were 642 confirmed cases of human swine-origin influenza in forty-one states. By May 25, the virus had spread to forty-three countries with 12,515 reported cases and 95 deaths. On June 11, 2009, the World Health Organization (WHO) declared the start of a global pandemic, which lasted until August 2010. Overall, the 2009–2010 H1N1 pandemic caused nearly 15,000 confirmed deaths worldwide. The virus continues to circulate but has not caused widespread infections as it did from 2009 to 2010.

The genetic code of influenza A is sequenced on eight separate segments of single-stranded RNA. When multiple strains of influenza virus infect the same host, such as a pig, these segments of RNA can be exchanged between strains during viral replication, and new strains emerge. Genetic sequence analysis of the H1N1 swine influenza strain which emerged early in 2009 has multiple genetic precursors. Genes from swine H1N2 influenza virus circulating among the North America swine population in the 1990s, genes from H3N2 North American swine influenza, and genes from H1N1 Eurasian swine influenza all have similarity to portions of the 2009 pandemic H1N1 virus genome. The final reassortment of swine (Eurasian and North American), avian, and human influenza A genes may have occurred at a Mexican pig farm with spread of the new quadruple reassortment virus into the human population.

Shifts in the hemagglutinin and neuraminidase surface antigens yielding a novel influenza virus occur every ten to thirty years. In the intervening periods, smaller changes in the hemagglutinin (antigen drift) allow the virus to circulate in the human population, but it does not infect sufficient numbers to cause large epidemics or pandemics. These viruses cause severe disease in the very young and elderly individuals who become infected. However, when novel strains emerge after an antigenic shift, children and young adults join those at the extremes of age in having severe disease. This situation is the result of children and young adults having not been exposed to an influenza A subtype similar to the new strain, leaving them without an effective immune response. The 2009 H1N1 swine influenza A followed this pattern, with severe cases and deaths occurring in children and young adults. Infections are worse when there is an underlying illness, such as asthma or diabetes, but nearly half of the severe cases have no underlying medical illness. Obesity emerged as a risk factor for severe and fatal H1N1 disease.

Pregnant women are at high risk for severe influenza caused by any subtype, but the novel H1N1 swine influenza A seems to have struck this group of patients especially hard. Early data from the United States show that pregnant women infected with the H1N1 strain are significantly more likely to be admitted to the hospital or die as a result of their infection than the general population. Pregnancy ratchets down the immune response to allow the developing infant not to be rejected. Further into pregnancy, the enlarging uterus and fetus restrict movement of the diaphragm and facilitate the development of pneumonia. Additionally, these pregnant young adults join their nonpregnant peers in lacking immunity by virtue of having no prior exposure to the H1N1 influenza subtype.

The H1N1 virus's manner of spreading is similar to other strains of influenza. Large droplets from coughing and sneezing by an infected patient are spread to the mucosal surfaces (nose, mouth, and eyes) of uninfected individuals. This droplet spread is most intense when the distances are short, a few feet, but may occur up to ten feet. Direct contact with infected respiratory secretions is also important in the spread of infections and the virus can survive on surfaces and objects for a few hours. Small droplet aerosols may also have a role, but there is less evidence that this is a significant method of transfer. Infected persons can shed the virus and spread disease beginning one day before becoming ill and up to five to seven days after symptoms appear. Infection can result from contact with infected pigs, as probably occurred in the original cases in Mexico, but pork and pork products are not infective.

The incubation period (time between infection and illness) is two to seven days. The most common symptoms have been fever, cough, and sore throat, but 25 percent of patients have had diarrhea or vomiting, which are unusual symptoms for influenza. Headache, aching muscles, burning eyes, and other symptoms accompanying influenza infection may occur. While fever was reported to occur in 94 percent of the first 642 confirmed cases in April and May 2009, subsequent series of cases have reported the absence of fever in 10 to 50 percent of those infected. The severity of illness can vary widely from that of a self-limited mild illness to severe disease requiring admission to a hospital intensive care unit. Individuals that develop severe illness usually show rapid deterioration between day three and five. Respiratory failure from pneumonia, shock, and failure of other organs may follow.

Early diagnosis of H1N1 influenza is important as therapeutic intervention can reduce severity, shorten the course of the illness, and prevent further spread of the infection. A number of rapid influenza diagnostic tests (RIDTs) are available and provide results in thirty minutes or less. A molecular technique called reverse transcriptase
polymerase chain reaction (RT-PCR) is able to detect specific influenza RNA in respiratory secretions. This test is highly sensitive and specific and can accurately diagnose infection with H1N1 influenza, but it is performed only in special laboratories and results can take days making them of little use for immediate diagnosis and therapeutic decision making.

Primary viral pneumonia is the most common type of pneumonia in severe cases, but secondary bacteria pneumonia has been found in 30 percent of fatal cases. The most common bacteria are Streptococcus pneumoniae and Staphylococcus aureus. Overall, it appears that 10 to 20 percent of patients with disease severe enough to require admission to a hospital intensive care unit will die.

Treatment and Therapy

The H1N1 influenza is treated with neuraminidase inhibitors. Oseltamivir, which is available as a capsule and an oral suspension, and zanamivir, which is supplied as an inhaled powder, are oral neuraminidase inhibitors that can be used for both treatment and prophylaxis. A new intravenous neuraminidase inhibitor, peramivir, was approved by the FDA for emergency treatment of H1N1 during the pandemic; however, the emergency-use authorization for peramivir expired in June 2010. Zanamivir is also available for oral use to treat H1N1. Antiviral therapy is most effective when started early in the course of the illness, but viral RNA has been detected in the lower respiratory tract for as long as two weeks, suggesting that antiviral therapy may be beneficial even in the later stages of the illness. Consequently, it is recommended by the CDC that any patient who is not improving receive antiviral therapy even if it is more than forty-eight hours after symptoms have begun.

Complex care in an intensive care unit is necessary for severely ill patients. Respiratory failure must be managed by intubation and mechanical ventilation often involving sophisticated equipment and techniques.

Secondary bacterial pneumonia occurs in some patients and staphylococci and streptococci have been found to be the most common invading pathogens. Antibacterial agents effective against these bacteria must be given in addition to the antiviral to successfully treat this complicated pneumonia.

Prevention of H1N1 disease can be accomplished by administration of the seasonal flu vaccine, which is available by shot or nasal spray. Vaccines against H1N1 are made from influenza virus that has been grown in chicken eggs and are not recommended for persons allergic to eggs. The nasal mist can be given to healthy individuals between the ages of two and forty-nine, except pregnant women. All others must receive the injectable killed vaccine, including high-risk patients, such as pregnant women and HIV patients who have decreased immunity. Since the protective immune response to H1N1 following vaccination takes two weeks to develop, oral antiviral therapy may be administered during this period to afford protection. In some cases, such as patients allergic to eggs, longer prophylaxis may be warranted and has been shown to be safe and effective for extended duration.

Perspective and Prospects

In 1936, Richard E. Shope first reported antibodies to swine influenza in humans, and shortly thereafter viruses isolated from swine and from humans were linked to the 1918 influenza virus. These viruses are now known to be H1N1 influenza A, and direct descendants of the 1918 virus still persist in pigs and humans. The human H1N1 virus undergoes continual and gradual antigenic drift, causing annual disease and even epidemics. The porcine enzootic H1N1 strain only rarely infects humans. An outbreak of swine H1N1 influenza at Fort Dix, New Jersey, in 1976 caused concern and led to a vaccination campaign, but further spread never occurred. In recent years, analysis of material preserved from fatal cases of 1918 influenza have resulted in complete sequencing of the viral genome. These data have demonstrated that all subsequent pandemic viruses are descendants of the 1918 virus, as are nearly all human influenza A viruses worldwide. Descendants of the 1918 virus resulting from antigenic shifts caused pandemics in 1957 (H2N2) and 1968 (H3N2). Intrasubtype reassortment caused pandemics in 1947 (H1N1), 1957 (H1N1), 1997 (H3N2), and 2003 (H3N2). The origin of the 1918 virus remains unclear, but it is thought to be derived from avian strains with simultaneous adaptation to both humans and swine with possible genetic contributions from an as-yet-to-be-identified different animal host.

Another interesting aspect of the 1918 pandemic is the occurrence of three waves in the Northern Hemisphere. The first wave, beginning in March, lasted six months and had high attack rates, but death rates remained at expected levels. The second wave, from September to November, and a third wave in early 1919 were both characterized by high mortality. Since the autopsy material used for genetic sequencing was from second-wave cases, it has not been possible to determine if any changes in the virus occurred from the less-fatal, first-wave virus.

The 2009 H1N1 virus had a number of similar features to the 1918 virus. The pandemic began in March and spread around the world with continuous activity throughout the summer in the Northern Hemisphere. In September, activity increased and continued to progress. However, there was no increased activity in the winter and into spring 2010, which is unlike the third wave of the 1918 pandemic that occurred in early 1919. While the fatality rate of the 2009 virus was much lower than the 1918 virus, many deaths occurred across all age groups. Vaccines, antivirals, and modern intensive care therapies provided measures to combat influenza that were unavailable in 1918. Demand for vaccines, antivirals, intensive care unit beds, ventilators, and health care providers was high, but resources kept pace. Some H1N1 activity continues worldwide, but the virus has not caused widespread infections since the 2009–2010 pandemic. Successful vaccination, along with handwashing and the use of respirators and masks in health care facilities, significantly slowed the spread of the virus.

Bibliography

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Morens, David M., Jeffrey K. Taubenberger, and Anthony S. Fauci. “The Persistent Legacy of the 1918 Influenza Virus.” New England Journal of Medicine 361 (2009): 225–229.

Myers, Kendall P., Christopher W. Olsen, and Gregory C. Gray. “Cases of Swine Influenza in Humans: A Review of the Literature.” Clinical Infectious Diseases 44 (2007): 1084–1088.

"Seasonal Influenza (Flu)." Centers for Disease Control and Prevention, May 17, 2013.

Stahl, Rebecca J., and Brian S. Alper. "Pandemic (H1N1) Influenza." Health Library, October 31, 2012.

Trifonov, Vladimir, Hossein Khiabanian, and Raul Rabadan. “Geographic Dependence, Surveillance, and Origins of the 2009 Influenza A (H1N1) Virus.” New England Journal of Medicine 361 (2009): 115–119.