What are molecular genetics? |

Identity and Structure of Genetic Material

Molecular genetics is the branch of genetics that deals with the identity of the molecules of heredity, their structure and organization, how these molecules are copied and transmitted, how the information encrypted in them is decoded, and how the information can change from generation to generation. In the late 1940s and early 1950s, scientists realized that the materials of heredity were nucleic acids. DNA was implicated as the substance extracted from a deadly strain of pneumococcal bacteria that could transform a mild strain into a lethal one and as the substance injected into bacteria by viruses as they start an infection. RNA was shown to be the component of a virus that determined what kind of symptoms of infection appeared on tobacco leaves.

The nucleic acids are made up of nucleotides
linked end to end to produce very long molecules. Each nucleotide has sugar and phosphate parts and a nitrogen-rich part called a base. Four bases are commonly found in each DNA and RNA. Three—adenine (A), guanine (G), and cytosine (C)—are found in both DNA and RNA, while thymine (T) is normally found only in DNA and uracil (U) only in RNA. In the double-helical DNA molecule, two strands are helically intertwined in opposite directions. The nucleotide strands are held together in part by interactions specific to the bases, which “pair” perpendicularly to the sugar-phosphate strands. The structure can be envisioned as a ladder. The A and T bases pair with each other, and G and C bases pair with each other, forming “rungs”; the sugar-phosphates, joined end to end, form the “sides” of the ladder. The entire molecule twists and bends in on itself to form a compact whole. An RNA molecule is essentially “half” of this ladder, split down the middle. RNA molecules generally adopt less regular structures but may also require pairing between bases.

DNA and RNA, in various forms, serve as the molecules of heredity. RNA is the genetic material that some viruses package in viral particles. One or several molecules of RNA may make up the viral information. The genetic material of most bacteria is a single circle of double-helical DNA, the circle consisting of from slightly more than 500,000 to about 5 million nucleotide pairs. In eukaryotes such as humans, the DNA genetic material is organized into multiple linear DNA molecules, each one the essence of a morphologically recognizable and genetically identifiable structure called a chromosome.

In each organism, the DNA is closely associated with proteins. Proteins are made of one or more polypeptides. Polypeptides are linear polymers, like nucleic acids, but the units linked end to end are amino acids rather than nucleotides. More than twenty kinds of amino acids make up polypeptides. Proteins are generally smaller than DNA molecules and assume a variety of shapes. Proteins contribute to the biological characteristics of an organism in many ways: They are major components of structures both inside (membranes and fibers) and outside(hair and nails) the cell; as enzymes, they initiate the thousands of chemical reactions that cells use to get energy and build new cells; and they regulate the activities of cells. Histone proteins pack eukaryotic nuclear DNA into tight bundles called nucleosomes. Further coiling and looping of nucleosomes results in the compact structure of chromosomes. These can be seen with help of a microscope. The complex of DNA and protein is called chromatin.

The term “genome” d the roster of genes and other DNA of an organism. Most eukaryotes have more than one genome. The principal genome is the genome of the nucleus that controls most of the activities of cells. Two organelles, the mitochondria (which produce energy by oxidizing chemicals) and the plastids (such as chloroplasts, which convert light to chemical energy in photosynthesis) have their own genomes. The organelle genomes have only some of the genes needed for their functioning. The others are present in the nuclear genome. Nuclear genomes have many copies of some genes. Some repeated sequences are organized tandemly, one after the other, while others are interspersed with unique sequences. Some repeated sequences are genes present in many copies, while others are DNAs of unknown function.

Copying and Transmission of Genetic Nucleic Acids

James Watson and Francis Crick’s double-helical structure for DNA suggested to them how a faithful copy of a DNA could be made. The strands would pull apart. One by one, the new nucleotide units would then arrange themselves by pairing with the correct base on the exposed strands. When zipped together, the new units make a new strand of DNA. The process, called DNA replication, makes two double-helical DNAs from one original one. Each daughter double-helical DNA has one old and one new strand. This kind of replication, called semiconservative replication, was confirmed by an experiment by Matthew Meselson and Franklin Stahl.

Enzymes cannot copy DNA of eukaryotic chromosomes completely to each end of the DNA strands. This is not a problem for bacteria, whose circular genomes do not have ends. To keep the ends from getting shorter with each cycle of replication, eukaryotic chromosomes have special structures called telomeres at their ends that are targets of a special DNA synthesis enzyme.

When a cell divides, each daughter cell must get one and only one complete copy of the mother cell’s DNA. In most bacterial chromosomes, this DNA synthesis starts at only one place, and that starting point is controlled so that the number of starts equals the number of cell fissions. In eukaryotes, DNA synthesis begins at multiple sites, and each site, once it has begun synthesis, does not begin another round until after cell division. When DNA has been completely copied, the chromosomes line up for distribution to the daughter cells. Protein complexes called kinetochores bind to a special region of each chromosome’s DNA called the “centromere.” Kinetochores attach to microtubules, fibers that provide the tracks along which the chromosomes move during their segregation into daughter cells.

Gene Expression, Transcription, and Translation

DNA is often dubbed the blueprint of life. It is more accurate to describe DNA as the computer tape of life’s instructions because the DNA information is a linear, one-dimensional series of units rather than a two-dimensional diagram. In the flow of information from the DNA tape to what is recognized as life, two steps require the decoding of nucleotide sequence information. The first step, the copying of the DNA information into RNA, is called transcription, an analogy to medieval monks sitting in their cells copying, letter by letter, old Latin manuscripts. The letters and words in the new version are the same as in the old but are written with a different hand and thus have a slightly different appearance. The second step, in which amino acids are polymerized in response to the RNA information, is called translation. Here, the monks take the Latin words and find English, German, or French equivalents. The product is not in the nucleotide language but in the language of polypeptide sequences. The RNAs that direct the order of
amino acids are called messenger RNAs (mRNAs) because they bring instructions from the DNA to the ribosome, the site of translation.

Multicellular organisms consist of a variety of cells, each with a particular function. Cells also respond to changes in their environment. The differences among cell types and among cells in different environmental conditions are caused by the synthesis of different proteins. For the most part, regulation of which proteins are synthesized and which are not occurs by controlling the synthesis of the mRNAs for these proteins. Genes can have their transcription switched on or switched off by the binding of protein factors to a segment of the gene that determines whether transcription will start or not. An important part of this gene segment is the promoter. It tells the transcription apparatus to start RNA synthesis only at a particular point in the gene.

Not all RNAs are ready to function the moment their synthesis is over. Many RNA transcripts have alternating exon and intron segments. The intron segments are taken out with splicing of the end of one exon to the beginning of the next. Other transcripts are cut at several specific places so that several functional RNAs arise from one transcript. Eukaryotic mRNAs get poly-A tails (about two hundred nucleotide units in which every base is an A) added after transcription. A few RNAs are edited after transcription, some extensively by adding or removing U nucleotides in the middle of the RNA, others by changing specific bases.

Translation occurs on particles called ribosomes and converts the sequence of nucleotide residues in mRNA into the sequence of amino acid residues in a polypeptide. Since protein is created as a consequence of translation, the process is also called protein synthesis. The mRNA carries the code for the order of insertion of amino acids in three-nucleotide units called codons. Failure of the ribosome to read nucleotides three at a time leads to shifts in the frame of reading the mRNA message. The frame of reading mRNA is set by starting translation only at a special codon.

Transfer RNA (tRNA) molecules actually do the translating. There is at least one tRNA for each of the twenty common amino acids. Anticodon regions of the tRNAs each specifically pair with only a specific subset of mRNA codons. For each amino acid there is at least one enzyme that attaches the amino acid to the correct tRNA. These enzymes are thus at the center of translation, recognizing both amino acid and nucleotide residues.

The ribosomes have sites for binding of mRNA, tRNA, and a variety of protein factors. Ribosomes also catalyze the joining of amino acids to the growing polypeptide chain. The protein factors, usually loosely bound to ribosomes, assist in the proper initiation of polypeptide chains, in the binding of amino acid-bearing tRNA to the ribosome, and in moving the ribosome relative to the mRNA after each additional step. Three steps in translation use biochemical energy: attaching the amino acid to the tRNA, binding the amino acyl tRNA to the ribosome-mRNA complex, and moving the ribosome relative to the mRNA.

Small RNAs

An additional level of control of gene expression is achieved via the presence of two classes of small RNAs, the microRNAs (miRNAs) and the small interfering RNAs (siRNAs). In 1993, Victor Ambrose and his coworkers discovered that in
Caenorhabditis elegans
, lin-4, a small 22-nucleotide noncoding RNA, was able to negatively regulate the translation of lin-14, which is involved in C. elegans larval development. Since then, these small RNAs have been found in plants, green algae, viruses, and animals. These small RNAs function as gene-silencers by binding to target mRNA sequences and preventing their translation or targeting the mRNAs for degradation in a process known as RNA interference (RNAi).

The pathway by which the small RNAs’ are processed has been intensively studied. After transcription and processing in the nucleus, small RNAs’ precursors are exported into the cytoplasm, where they undergo further processing by an enzyme called Dicer, which produces a single-stranded 21-23-nucleotide RNA. This small RNA attaches to an RNA-induced silencing complex (RISC) and is directed to a specific mRNA to which it shares base pair complementarity. In the case of miRNA, slight imperfections in the match between the miRNA and its target lead to a bulge in the duplex, which blocks translation. In contrast, the perfect binding of the siRNA with its target mRNA forms a duplex, which is targeted for degradation by endonucleases.

The discovery of miRNAs and siRNAs has had important scientific and clinical implications. miRNAs have been demonstrated to play a role in several human cancers and infectious diseases. In addition, researchers have been using RNAi both as a possible therapeutic and as a tool in research to manipulate gene expression.

Protein Processing and DNA Mutation

The completed polypeptide chain is processed in one or more ways before it assumes its role as a mature protein. The linear string of amino acid units folds into a complex, three-dimensional structure, sometimes with the help of other proteins. Signals in some proteins’ amino acid sequences direct them to their proper destinations after they leave the ribosomes. Some signals are removable, while others remain part of the protein. Some newly synthesized proteins are called polyproteins because they are snipped at specific sites, giving several proteins from one translation product. Finally, individual amino acid units may get other groups attached to them or be modified in other ways.

The DNA information can be corrupted by reaction with certain chemicals, some of which are naturally occurring while others are present in the environment. Ultraviolet and ionizing radiation can also damage DNA. In addition, the apparatus that replicates DNA will make a mistake at low frequency and insert the wrong nucleotide.

Collectively, these changes in DNA are called DNA damage. When DNA damage goes unrepaired before the next round of copying of the DNA, mutations (inherited changes in nucleotide sequence) result. Mutations may be substitutions, in which one base replaces another. They may also be insertions or deletions of one or more nucleotides. Mutations may be beneficial, neutral, or harmful. They are the targets of the natural selection that drives evolution. Since some mutations are harmful, survival of the species requires that they be kept to a low level.

Systems that repair DNA are thus very important for the accurate transmission of the DNA information tape. Several kinds of systems have evolved to repair damaged DNA before it can be copied. In one, enzymes directly reverse the damage to DNA. In a second, the damaged base is removed, and the nucleotide chain is split to allow its repair by a limited resynthesis. In a third, a protein complex recognizes the DNA damage, which results in incisions in the DNA backbone on both sides of the damage. The segment containing the damage is removed, and the gap is filled by a limited resynthesis. In still another, mismatched base pairs, such as those that result from errors in replication, are recognized, and an incision is made some distance away from the mismatch. The entire stretch from the incision point to past the mismatch is then resynthesized. Finally, the molecular machinery that exchanges DNA segments, the recombination machinery, may be mobilized to repair damage that cannot be handled by the other
systems.

Invasion and Amplification of Genes

Mutation is only one way that genomes change from generation to generation. Another way is via the invasion of an organism’s genome by other genomes or genome segments. Bacteria have evolved restriction
modification systems to protect themselves from such invasions. The gene for restriction encodes an enzyme that cleaves DNA whenever a particular short sequence of nucleotides is present. It does not recognize that sequence when it has been modified with a methyl group on one of its bases. The gene for modification encodes the enzyme that adds the methyl group. Thus the bacterium’s own DNA is protected. However, DNA that enters the cell from outside, such as by phage infection or by direct DNA uptake, is not so protected and will be targeted for degradation by the restriction enzyme. Despite restriction, transfer of genes from one species to another (horizontal, or lateral, gene transfer) has occurred.

As far as is known, restriction modification systems are unique to bacteria. Gene transfer from bacteria to plants occurs naturally in diseases caused by bacteria of the Agrobacterium
genus. As part of the infection process, these bacteria transfer a part of their DNA containing genes, active only in plants, into the plant genome. Studies with fungi and higher plants suggest that eukaryotes cope with gene invasion by inactivating the genes (gene silencing) or their transcripts (cosuppression).

Another way that genomes change is by duplications of gene-sized DNA segments. When the environment is such that the extra copy is advantageous, the cell with the duplication survives better than one without the duplication. Thus genes can be amplified under selective pressure. In some tissues, such as salivary glands of dipteran insects and parts of higher plant embryos, there is replication of large segments of chromosomes without cell division. Monster chromosomes result.

Genomes also change because of movable genetic elements. Inversions of genome segments occur in bacteria and eukaryotes. Other segments can move from one location in the genome to another. Some of these movements appear to be rare, random events. Others serve particular functions and are programmed to occur under certain conditions. One kind of mobile element, the retrotransposon, moves into new locations via an RNA intermediate. The element encodes an enzyme that makes a DNA copy of the element’s RNA transcript. That copy inserts itself into other genome locations. The process is similar to that used by retroviruses to establish infection in cells. Other mobile elements, called transposons or transposable elements, encode a transposase enzyme that inserts the element sequence, or a copy of it, into a new location. When that new location is in or near a gene, normal functioning of that gene is disturbed.

The production of genes for antibodies (an important part of a human’s immune defense system) is a biological function that requires gene rearrangements. Antibody molecules consist of two polypeptides called light and heavy chains. In most cells in the body, the genes for light chains are in two separated segments, and those for heavy chains are in three. During the maturation of cells that make antibodies, the genes are rearranged, bringing these segments together. The joining of segments is not precise. The imprecision contributes to the diversity of possible antibody molecules.

Cells of baker’s or brewer’s yeast (Saccharomyces cerevisiae) have genes specifying their sex, or mating type, in three locations. The information at one location, the expression locus, is the one that determines the mating type of the cell. A copy of this information is in one of the other two sites, while the third has the information specifying the opposite mating type. Yeast cells switch mating types by replacing the information at the expression locus with information from a storage locus. Mating-type switching and antibody gene maturation are only two examples of programmed gene rearrangements known to occur in a variety of organisms.

Genetic Recombination

Recombination occurs when DNA information from one chromosome becomes attached to the DNA of another. When participating chromosomes are equivalent, the recombination is called homologous. Homologous recombination in bacteria mainly serves a repair function for extreme DNA damage. In many eukaryotes, recombination is essential for the segregation of chromosomes into gamete cells during meiosis. Nevertheless, aspects of the process are common between bacteria and eukaryotes. Starting recombination requires a break in at least one strand of the double-helical DNA. In the well-studied yeast cells, a double-strand break is required. Free DNA ends generated by breaks invade the double-helical DNA of the homologous chromosome. Further invasion and DNA synthesis result in a structure in which the chromosomes are linked to one another. This structure, called a half-chiasma, is
recognized and resolved by an enzyme system. Resolution can result in exchange so that one end of one chromosome is linked to the other end of the other chromosome and vice versa. Resolution can also result in restoration of the original linkage. In the latter case, the DNA around the exchange point may be that of the other DNA. This is known as gene conversion.

Impact and Applications

Molecular genetics is at the heart of biotechnology, or genetic engineering. Its fundamental investigation of biological processes has provided tools for biotechnologists. Molecular cloning and gene manipulation in the test tube rely heavily on restriction enzymes, other nucleic-acid-modifying enzymes, and extrachromosomal DNA, all discovered during molecular genetic investigation. The development of nucleic acid hybridization, which allows the identification of specific molecular clones in a pool of others, required an understanding of DNA structure and dynamics. The widely used polymerase chain reaction (PCR), which can amplify minute quantities of DNA, would not have been possible without discoveries in DNA replication. Genetic mapping, a prelude to the isolation of many genes, was sped along by molecular markers detectable with restriction enzymes or the PCR. Transposable elements and the transferred DNA of Agrobacterium, because they often inactivate genes when they insert in them, were used to isolate the genes they inactivate. The inserted elements served as tags or handles by which the modified genes were pulled out of a collection of genes.

The knowledge of the molecular workings of genes gained by curious scientists has allowed other scientists to intervene in many disease situations, provide effective therapies, and improve biological production. Late twentieth century scientists rapidly developed an understanding of the infection process of the acquired immunodeficiency syndrome (AIDS) virus. The understanding, built on the skeleton of existing knowledge, has helped combat this debilitating disease. Molecular genetics has also led to the safe and less expensive production of proteins of industrial, agricultural, and pharmacological importance. The transfer of DNA from Agrobacterium to plants has been exploited in the creation of transgenic plants. These plants offer a new form of pest protection that provides an alternative to objectionable pesticidal sprays and protects against pathogens for which no other protection is available. Recombinant insulin and recombinant growth hormone are routinely given to those whose conditions demand them. Through molecular genetics, doctors have diagnostic kits that can, with greater rapidity, greater specificity, and lower cost,
determine whether a pathogen is present. Finally, molecular genetics has been used to identify genes responsible for many inherited diseases of humankind. Someday medicine may correct some of these diseases by providing a good copy of the gene, a strategy called gene therapy.

Key terms



DNA

:

deoxyribonucleic acid, a long-chain macromolecule, made of units called nucleotides and structured as a double helix joined by weak hydrogen bonds, which forms genetic material for most organisms




genome

:

the assemblage of the genetic information of an organism or of one of its organelles




replication

:

the process by which one DNA molecule is converted to two DNA molecules identical to the first




RNA

:

ribonucleic acid, the macromolecule in the cell that acts as an intermediary between the genetic information stored as DNA and the manifestation of that genetic information as proteins




transcription

:

the process of forming an RNA molecule according to instructions contained in DNA




translation

:

the process of forming proteins according to instructions contained in an RNA molecule





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What is pharmacology? |

Science and Profession

The science of pharmacology includes the history, source, physical and chemical
properties, and biochemical and physiological effects of drugs (therapeutic
chemicals, diagnostic chemicals, toxins, and related substances).

“Drug” is a noun in common usage, but it has complex meanings. “Drug” or
“medicine” is often used today to indicate a therapeutic substance usually
obtained from a pharmacy or drugstore. “Drug” also is used to indicate an illegal
substance used for mood-altering effects. Historically, people made their own
drugs from materials found naturally in plants, animals, and minerals; some people
continue to do so. The term “drug” in this article will focus on the meaning as it
is understood by scientists called pharmacologists. Any chemical can be thought of
as a drug by a pharmacologist: A drug is simply a chemical that produces a change
in a biological process.

Water and oxygen can be thought of as drugs, as can foods and poisons. “Drug,”
therefore, is a word to indicate an idea, concept, or perception about a chemical.
When the chemical, such as oxygen, is causing a change in a biological process,
then the chemical is acting as a drug. If the same chemical is causing a change in
some other kind of system—for example, causing an iron rod to rust—then the
chemical is not acting as a drug. Drugs may be found in nature or made by humans.
Most of the chemicals used today as drugs are made by humans.

The biological process that is being changed by a drug may be one occurring in a sick person. Many drugs are used therapeutically—that is, to treat diseases—but pharmacologists do not limit drugs to therapeutic chemicals. They are interested in drug effects on any biological process, even healthy ones occurring in plants and microorganisms, as well as those in animals and humans.

All drugs, even therapeutic drugs, have several effects on biological processes.
Some of these effects are seen only at high concentrations. Unwanted effects,
especially if they are injurious, are called adverse effects. A serious adverse
effect, especially if it requires special medical treatment, may be considered a
toxic reaction, or poisoning. Any chemical that produces
an injurious effect, one that is detrimental to a biological process, is called a
toxin. The severity of the toxic effect is based on the
concentration of the toxic substance. Toxic substances in the environment are
called pollutants.

The idea of drug concentration is very important. “Concentration” refers to the
number of chemical molecules in a specified volume (such as a teaspoonful, an
ounce, or a milliliter) of liquid or gas. Concentration is related to dosage and
to the intensity of a drug’s effect on a biological process. It is important to
remember, however, that the effect of a drug on the body may vary considerably
depending on the route of administration. For instance, if one were to eat a drug,
then metabolism of the drug is usually very slow, whereas if one were to inject a
drug into the bloodstream, then the effects of the drug are observed quite
rapidly. Therefore, when pharmacologists discuss drugs and their effects,
particularly on humans, they will also frequently discuss the route of
administration to make the context of the effect clear.

Concentration and the related concept of dilution are easy to understand. Two
spoonfuls of sugar in a glass of water form a more concentrated solution of
sugar-water than one spoonful of sugar. The more concentrated sugar-water will
taste sweeter. Since taste is a biological process caused by a chemical, the
chemical (sugar) can be thought of as a drug. The concentration of the chemical
affects the biological process. There is a limit, however, to the sweetness of a
solution. At some point, more sugar added to the solution will not increase the
sensation of sweetness. Adding more sugar may result in a “toxic” reaction of
nausea and even vomiting.

There are also different kinds of sugars. When one says that some are sweeter than
others, one means that sweeter sugars will be just as sweet at very dilute
concentrations as less-sweet sugars at very high concentrations. Thus the first
kind of sugar is said to be more potent than the second, even though the second
can be just as sweet at high concentrations. Some sugars, however, will not taste
very sweet regardless of the concentration. This example illustrates principles
that are shared by many drugs. It is important to understand that taking a double
dose of a drug will not necessarily produce a double effect. It is also important
to understand that a tiny dose of one drug can have the same, or even stronger,
biological effect than a large dose of a similar drug.

Most therapeutic drugs act directly on special parts of cells within the body
called receptors. A receptor is part of the cell structure. A
receptor for a specific drug is always located at the same place within a cell.
Yet there are different kinds of receptors found at various locations in cells.
Many receptors are found on the cell surface; others are found inside cells. Some
receptors are found only on certain types of cells.

Each type of receptor has a specific function. When a drug “fits” a receptor, like
how a key fits a lock, the receptor starts the biological process for which the
drug is known. Different kinds of drugs can fit a single type of receptor, which
explains why different drugs (for example, aspirin and acetaminophen) can have
similar effects (relieve pain). Furthermore, one drug may be able to act on
several different types of receptors. A receptor, however, can have only one
biological response to all the drugs that act on it.

A drug acting on receptors in cells of one organ can affect distant organs. For
example, a drug acting on brain cells may cause the nerves acting on blood vessels
to increase blood pressure, which can change the heartbeat. The effect of a drug
on receptors is usually temporary and should be reversible. In most cases in which
a drug works through a receptor, the receptor releases the drug after the two have
come together. If this release does not occur, the receptor is said to be blocked.
The blockage of a receptor can be therapeutically beneficial, but it may sometimes
lead to an adverse reaction.

In humans and animals, most drugs travel in the bloodstream to reach cell receptors. The drug enters the bloodstream after being applied to a body surface or after being swallowed, inhaled, or injected. The effect of the drug is eventually diminished because the body dilutes the drug, chemically alters it (so that it no longer has a pharmacological effect), and eliminates it. Chemical alteration of drugs usually occurs in the liver by a process called biotransformation. Elimination of most drugs, or their biotransformed relatives, usually occurs through the urine but may sometimes occur through secretions (sweat, tears, or breast milk), feces, or even exhaled gases.

Diagnostic and Treatment Techniques

Three examples of the use of therapeutic chemicals in the field of pharmacology are anesthesia, cardiac-enhancing drugs, and drugs that fight infections. These examples demonstrate the use of various classes of drugs and provide insight to the variety of drug action.

Anesthetics are chemical painkillers. They are very
important drugs, because most diseases are accompanied by pain. Often,
the first objective of a patient is to get relief from the pain, even though the
anesthetic may do nothing to cure the disease. Pain is a sensation felt in the
brain, not at the site of injury. Special nerves at the site of injury send a
signal (nerve impulse) to the brain, where it is interpreted as pain occurring at
a specific location in the body. Mild pain and severe pain are detected by
different kinds of nociceptive (pain-sensing) nerves. As pain increases in
severity, the brain not only perceives and interprets the pain but also sends out
special autonomic signals.

Autonomic signals from the brain serve an extremely important function: They
control body functions that do not require conscious thought, such as sweating,
heart rate, blood pressure, digestion, and eye focus. Autonomic signals coordinate
these functions and change them in response to conditions outside the body. When
the body is threatened, such as when a person is frightened, autonomic signals
prepare the body to fight or to flee the threatening situation. The pain of
surgery causes the brain to send autonomic signals to put the body in a defensive
state, resulting in sweating and increases in heart rate, breathing, and blood
pressure. Additionally, all the muscles of the body will become tense. This
defensive state is undesirable during surgery.

Drugs used to relieve pain without causing unconsciousness are called analgesics.
Mild pain can usually be controlled with an analgesic such as aspirin. More
severe pain may require an opioid analgesic such as morphine.
Sometimes, the term “narcotic” is used as a synonym for opioid analgesics, but
that term is often used in a legal context to indicate any chemical that can cause
dependence (addiction). An analgesic changes the way in
which the brain interprets a nociceptive stimulus. The most severe pain, such as
that during surgery, is controlled by an anesthetic. An anesthetic may act at a
specific site, such as on the nerves of a tooth; a local
anesthetic such as novocaine blocks the transmission of the
nociceptive stimulus to the brain. Other anesthetics, required for major surgery,
cause a loss of consciousness; these are called general anesthetics. As with all
therapeutic drugs, the action of an anesthetic is reversible.

A general anesthetic should perform several functions: It should alter the brain’s
interpretation of pain, cause a temporary amnesia that prevents remembrance of the
nociceptive sensation, produce autonomic stability, and cause muscle relaxation.
This is much to ask of a single drug. Therefore, general anesthesia is achieved by
using several drugs, each capable of accomplishing one or more of the goals.

A general anesthetic agent usually works on nerve cells to provide pain relief and amnesia. These general functions are provided by both kinds of general anesthetics, those that are inhaled and those that are injected. Other drugs are used to control autonomic signals and to provide for muscle relaxation. When the surgery is completed, the patient returns to consciousness as the anesthetic agents are removed from the nerves. This is done by biotransformation and by excretion. Pain immediately after surgery will be controlled by an opioid analgesic. When the pain diminishes as healing progresses, it becomes milder and can be controlled with a nonopioid analgesic.

Drugs are also important in helping people recover from a myocardial infarction
(heart
attack). The heart is a pump that supplies blood to all cells
of the body. Blood carries oxygen and nutrients to the cells and removes waste
materials from them. The heart is a living muscle composed of cells, and blood
vessels must supply each cell of the muscle. If a blood vessel in the heart
becomes suddenly blocked, then the cells served by that blood vessel become
starved and die. This is a heart attack. If only a small portion of the heart is
injured, the person can survive the attack, especially if drugs are given that
strengthen the heart.

An important class of drugs used to strengthen the heart is composed of the
cardiac glycosides, such as digitalis. These drugs act to improve the ability of
the heart cells to use calcium efficiently. Calcium is essential to maintaining a
normal heartbeat. Because a heart attack is painful, it causes a defensive
autonomic response from the brain. It is important to use analgesics to relieve
the pain and other drugs to control the autonomic response. Another important
therapy is to provide more oxygen to the heart. This is done directly, by
administering oxygen, but it is also done by using drugs that can remove the
blockage from the blood vessel. Since the blockage usually occurs when a blood
clot forms in a damaged blood vessel, drugs that dissolve clots can sometimes open
the blocked vessel and restore the flow of oxygen-rich blood to the starved cells.
A person recovering from a heart attack will sometimes be given drugs to prevent
another blockage. Some drugs prevent fatty deposits from forming in the vessels,
while others act to slow down clot formation.

Drugs used to treat infection are designed to kill cells. Infection is
caused by foreign microbes attacking the body. The microbes may be viruses,
bacteria, fungi, or even parasitic worms. Antimicrobial drugs (antibiotics) are
given to the infected person to destroy the foreign cells without damaging the
patient’s own cells. Therefore, the drug must be selectively toxic to the foreign
cells. Few drugs are perfectly selective, however, and most have some toxic
effects on the patient as well.

There are many ways to develop a selectively toxic drug, but selectivity usually
depends on a unique feature of the invading foreign cells, such as the cell walls
of bacteria. Human cells are surrounded by cell membranes. Bacteria have cell
membranes as well, but they also have cell walls outside these membranes. If the
bacterial cell
wall is damaged, then the bacterium becomes weakened and can
be killed by the body’s defense mechanisms. Penicillin is
an antibiotic drug that damages the cell walls of many bacteria. Penicillin has
few adverse effects on the infected person, because human cells do not have cell
walls. (Unfortunately, however, some people develop an allergic reaction to
penicillin.)

Perspective and Prospects

In the prehistoric world, priests were called upon to intercede for persons suffering from disease and pain. As humans gained experience and developed a means of sharing that experience, especially through written records, it was noticed that certain components of the diet could reliably inflict or relieve pain; these were the first drugs. Similar effects could be obtained by inhaling natural materials or applying them to the skin through rubbing or injection. Such activities were thought to involve supernatural powers, however, and authority to use these drugs was still restricted to members of the priesthood, namely, medicine men or shamans.

Writings about the medicinal properties of natural materials can be found in
Chinese, Egyptian, Greek, Indian, and Sumerian manuscripts, some of which are
thought to be as much as six thousand years old. The Ebers Papyrus of Egypt (1550
BCE) contains more than eight hundred prescriptions using seven hundred drugs. It
was known that some drugs were cathartics, some were diuretics, and others were
purgatives, soporifics, or poisons. Yet factual knowledge about why these actions
occurred was lacking, in large measure because knowledge of body function and
chemistry was lacking. In this absence, people speculated that drug action was due
to “essential properties” of the drug, such as warmth or wetness.

Only with the European Renaissance in the early sixteenth century was the
scientific
method applied to questions about the natural world, both
physical and living. In 1543, Andreas Vesalius published the first
complete description of human anatomy. In the early seventeenth century,
William
Harvey discovered the circulation of blood, and
Antoni van
Leeuwenhoek discovered living cells with his microscope. In
the eighteenth century, the chemistry of oxygen was established by
Carl
Scheele, Joseph Priestley, and Antoine
Lavoisier, and by the end of the century, chemical methods
were becoming available to separate pure drugs from crude natural concoctions. In
1806, Friedrich W. Serturner purified morphine from the opium poppy, and in 1856,
Friedrich
Wöhler isolated cocaine from coca. Also of great intellectual
and economic significance was the 1828 synthesis by Wöhler of urea, the first of
many chemicals which heretofore had been available only from living organisms.
Hormones, general anesthetics, and the bacterial cause of infectious diseases were
discovered.

Until the twentieth century, drugs were discovered empirically; they existed in
nature and needed to be “found.” The knowledge gained during the nineteenth
century about how drugs worked enabled pharmacologists of the twentieth century to
“design” drugs not found in nature. For example, Paul Ehrlich,
a German scientist, announced in 1910 that he had successfully combined a dye that
stains bacteria with the poison arsenic to create an antibacterial drug,
arsphenamine (Salvarsan), that is highly effective in treating syphilis. In a
similar way, the antibacterial sulfonamide chemicals were developed in the
1930s.

It was soon recognized that the powerful effect of pure drugs (in contrast to
potions made from natural materials) had the potential to harm as well as to help,
to kill or to cure. The safe use of these drugs required special knowledge, so
government agencies were established in the twentieth century to regulate drug
manufacture and distribution. The original Pure Food and Drug Act, passed by the
United States Congress in 1906, imposed quality controls on drug manufacturers. In
1927, Congress created the Food, Drug, and Insecticide Administration (FDIA), to
enforce the 1906 law. Until 1914, any drug could be obtained without a
prescription; this was changed by the Harrison Narcotic Act. Further limitations
on the sale of drugs to the general public came with the Food, Drug, and Cosmetic Act of
1938 and the Durham-Humphrey Amendment of 1951. The
Controlled
Substances Act of 1970 superseded the Harrison Narcotic
Act.

With the passage of time, enforcement responsibilities were changed. The FDIA
became the Food
and Drug Administration (FDA) in 1931 and was transferred
from the Department of Agriculture to what is now the Department of Health and Human
Services. The Drug Enforcement Administration for
controlled substances was established within the Justice Department.

At the beginning of the twenty-first century, drugs were available to alter
personality, to cure some types of cancer, to influence the reproductive system,
and to control the body’s response to foreign materials such as transplanted
organs. Many of these drugs were designed using powerful computers. Drugs were
even being developed to alter cellular genetics.

Bibliography

American
Pharmaceutical Association. Handbook of Nonprescription
Drugs. 18th ed. Washington, DC: Author, 2014. Print.

Brunton, Laurence L.,
et al., eds. Goodman and Gilman’s The Pharmacological Basis of
Therapeutics. 12th ed. New York: McGraw-Hill, 2011.
Print.

Griffith, H. Winter.
Complete Guide to Prescription and Nonprescription
Drugs. Rev. ed. New York: Penguin Group, 2013. Print.

Liska, Ken.
Drugs and the Human Body, with Implications for Society.
8th ed. Upper Saddle River: Pearson/Prentice Hall, 2009. Print.

Parrish, Richard.
Defining Drugs: How Government Became the Arbiter of
Pharmaceutical Fact. Somerset: Transaction, 2003.
Print.

PDR for
Nonprescription Drugs, Dietary Supplements, and Herbs. 33rd ed.
Montvale: PDR Network, 2012. Print.

What is measurement of religiosity?

Introduction

During the twentieth century, academic psychologists were concerned with developing an empirical science that would compare favorably with other natural sciences. Hence, the constructs in models of human behavior were operationalized with the goal of yielding numeric data that could be analyzed statistically. Quantitative methods (experiments, quasi-experiments, surveys, correlational studies) superseded the earlier descriptive, qualitative methods (Oedipal interpretations, clinical and literary case studies, introspective reports) and required relatively objective measurement of psychological attributes or traits. A fundamental notion in psychometric theory is that measurements taken on people should at the very least allow ordering along some continuum or dimension, such as intelligence or anxiety. However, measurement also may connote appraisal or understanding. Thus, the early explorations of religious experience (such as those of Sigmund Freud, Carl Jung, or William James) may be very broadly considered as involving, in some sense, the “measure” of religious experience.

The development of models and methods in the study of religiosity (religious feelings, beliefs, and behaviors) parallels this general timeline, although the emphasis on empiricism occurred in the latter half of the twentieth century. Since then, most psychologists of religion have been academic social psychologists who relied heavily on psychometric measures of religiosity, such as self-report questionnaires. However, since the 1980s, a resurgent interest in narrative or interpretive methods has competed with the psychometric tradition. Additionally, psychology of religion has become an international enterprise more open to qualitative methods. For example, Europeans are not averse to phenomenological interpretations of religious experience. The result of these diverging views is a broadening of the methodological base for testing models and theories of religion and an increasing sophistication with respect to measurement of religiosity. Many psychologists welcome this development, as they feel that more meaningful research is possible. For example, Kenneth I. Pargament, a renowned psychologist who studies coping behavior and religious beliefs, maintains that empirical methods must be balanced with phenomenological or interpretive methods, since religious experience is often private and symbolic and, therefore, not observable.

Social Psychology, Attitudes, and Surveys

Mainstream social psychologists regard attitudes as learned habits for responding to social stimuli and attempt to identify the cognitive, affective (emotional), and behavioral components of the attitude. Religiosity (also known as religiousness) is generally understood as a person’s essential attitude toward religion. The word “religion” has a Latin root that implies binding and restraining. Religion is therefore a personal and social force that serves to bind people together in a community of worshipers, unite them in reverence with a spiritual dimension of existence, and restrain their inappropriate impulses via moral commandments.

The form of attitude surveying with which the average American would be most familiar is the national opinion poll as conducted by George Gallup, Louis Harris, a major newspaper or magazine, or a marketing research firm. For example, the Gallup Poll measures a person’s overall religiosity by asking, “How important would you say religion is in your own life?” Nationally, more than half of the adults surveyed in 2012 respond “very important,” where importance tends to increase with age. In addition, there are gender, ethnic, and church affiliation differences; for example, the subgroups comprising women, African Americans, or Protestants are most likely to say that religion is very important.

Pollsters usually break down religion into specific behavioral, cognitive, and affective components. An important behavioral component is affiliation with a particular denomination (a religious organization within the host culture usually referred to as a church). In 2013, according to Gallup, about 83 percent of all adults in the United States claimed a religious affiliation (such as Protestant, Catholic, or Jewish), but only about 69 percent said they were actually members of a specific denomination. The largest single denomination in the United States in 2013 was Roman Catholic (27 percent), followed by Baptists (12 percent), then Methodists (5 percent). However, taken in the aggregate, 41 percent of the adults surveyed were Protestant.

Attending worship services is another behavior that may be measured. In 2013, 39 percent of US adults attended a service during the last seven days. Since 1939, this figure has been very stable. Other measurable religious activities include reading the Bible and praying: 47 percent of U.S. adults have read the Bible in the last week and 75 percent pray daily.

Another approach would be to measure people’s level of acceptance or endorsement of specific church policies (or of government laws relating to religion). For example, 59 percent of American Catholics disagree with the official teachings of their church of not allowing divorced people to remarry in the church and 79 percent disagree with not permitting people to use artificial means of birth control, according to 2014 poll conducted by Univision. Polls have also discovered that about three-quarters of all Americans would accept teaching about world religions and the Bible (as literature and history) in the public schools.

Cognitive dimensions of religiousness include beliefs about God or a spiritual reality, as well as what people believe about religion. According to a 2014 Gallup poll, 86 percent of US adults believe in God or in a higher power. As of 2011, 85 percent believe in heaven and 75 percent believe in hell. In 2013, 56 percent believed that religion, rather than being out of date, could answer most of the day's problems; 21 percent believed that religion is increasing its influence on American life, while 76 percent believed it is losing influence. According to Gallup, in 2014, about 45 percent of adults surveyed had a "Great deal" or "Quite a lot" of confidence in the church and organized religion.

The affective components of religiosity deal with emotions, priorities, values, and evaluations. For example, in evaluating the overall priority they give to religion in their lives, 56 percent of Americans state that religion is “very important,” while only 22 percent say it is “not very important.”

Religious Orientation Scales

In the 1960s, a dominant theme in research on religiosity emerged in response to the work of Gordon Allport, who had developed a model of religious orientation characterized by intrinsic and extrinsic dimensions. The former type of religiosity is interiorized, private, devotional, and based on individual commitment. Some items purporting to measure intrinsic religiosity have dealt with personal piety, church attendance, and the importance of religion. Extrinsic religiosity is more institutional, public, and pragmatic. Some of the items on scales designed to measure the extrinsic dimension include seeing religion as a vehicle for social relationships, consolation of grief, maintenance of order, and adherence to tradition. Many psychometric scales have been developed to assess orientation, an aspect of religiosity. Some measure orientation with a single intrinsic/extrinsic, bipolar scale, others with two distinct subscales. In contrast, in 1991, C. Daniel Batson and P. Schoenrade developed the Quest Scale to measure a third type. A quest orientation recognizes the positive value of doubt in the face of complex, existential questions regarding the meaning of life. What is particularly interesting is that Quest Scale scores tend to correlate negatively with prejudice measures.

Other Measures of Religiosity

Peter C. Hill and Ralph W. Hood, Jr., edited a much-needed compendium of scales titled Measures of Religiosity (1999). There are 126 scales grouped in seventeen chapters, thematically arranged. For example, there are measures of beliefs, attitudes, orientation, development, commitment, experience, values, and coping. Scales are presented along with information about the measured variable or dimension; scoring; psychometric properties, including evidence for reliability and validity; characteristics of people studied during the test development phase (norming samples); documentation regarding where the measure appeared in the research literature; and references for follow-up study. By identifying measures of similar constructs with different names or, conversely, measures of dissimilar constructs with the same name, Hill and Hood hope to promote a better understanding of the constructs measured. Richard Gorsuch also has suggested that construct and convergent validity could be improved if different researchers would use the same measures in well-developed, theoretically driven programs of research.

It is rare for scales used in the measurement of religiosity to meet well-known criteria for psychological tests. For example, few researchers publish standardized norms or even basic descriptive statistics for the samples used, such as measures of central tendency (means or medians) and variability ( standard deviations or ranges). While reliability may be good, information regarding validity is often inadequate. Validity is further compromised by the inherent sampling bias of many American religiosity scales, since most were developed using samples of convenience comprising US Protestants. Therefore, scales may be invalid for groups other than US Protestants. Traditional criteria and standards for scales may be found in texts such as Psychological Testing (1997) by Anne Anastasi and Susana Urbina or in the Standards for Educational and Psychological Testing (1999).

Religiosity measures may be classified as substantive scales or functional scales. If the former, the focus is on content; and if the latter, the focus is on process. For example, measures of religious beliefs tend to be substantive and are about what is believed, whereas measures of religious orientation tend to be functional and are variants or departures from Allport and Ross’s Religious Orientation Scale (1967).

Although social psychologists still dominate the field, developmental, cognitive, and evolutionary psychologists are contributing measures that correspond to their models of religious experience. While measures across these domains are primarily paper-and-pencil questionnaires, some are structured or semistructured interviews and some, as in the evolutionary approach, measure neurophysiological variables as indicators of religious or spiritual states.

How Religiosity Measures Are Used

Numerous applications of the various measures of religiosity are possible. Researchers can correlate any of these to other attitudes, personality traits, or demographic variables. Questions such as whether religious people are more superstitious, how religiosity differs between Democrats and Republicans, and whether religion helps people cope with marital problems can be addressed. For example, depending on how one decides to measure religion (and how one measures superstition), there is a slight tendency for more religious people to be a little less superstitious, but there are many people who are neither very religious nor very superstitious, and there are some who are both.

Using data from political polls, it can be verified that Jews, Catholics, and black Baptists tend to vote for Democrats, while most mainline white Protestant groups tend to vote for Republicans. Much of this correlation can be explained by historical and social-class features, however, in addition to the religious positions of the denominations.

Whether (and how) religion helps people cope with marital or other real-life problems is a difficult question to resolve. True experimentation, with random assignment of people to experimental and control conditions, would be necessary to confirm a cause-and-effect relationship. What seems to be apparent, however, is that religious people have a lower incidence of divorce and report slightly higher levels of marital satisfaction. This could be attributable to the fact that religious people feel more obligated to report that they have better marital relations, or it could be attributable to the fact that people who have problems in staying with a spouse also have problems in staying with their religion. When parents are asked whether religion has helped strengthen their family relationships, nearly four in five report that it has.

Clinical applications of the measurement of religiosity are also numerous. Very religiously committed individuals may have a problem with entering purely secular psychotherapy. The therapist may be seen as a nonbeliever who will challenge the patient’s worldview. Depending on the denomination, patients’ motivation for change may be tempered by the belief that their sufferings are a punishment inflicted by God.

From a more positive perspective, a patient’s religion can both serve as a source of impulse control (for example, as a check on suicidal tendencies) and provide a wide range of formal and informal social supports. For all these reasons, it is necessary for clinicians to assess the religiosity of their patients. Tolerant therapists can then use the patient’s worldview as a reference point. Therapists who cannot tolerate a given patient’s religiosity can make an appropriate referral (to another therapist who can) before the therapist is frustrated and the psychotherapeutic relationship has been damaged.

Other applications are possible in social and applied psychology. By understanding the religiosity of their “target segment,” for example, advertisers can tailor commercial and political messages to synchronize them with the values and worldviews of potential customers or voters.

Historical Background

In the late nineteenth century, psychologists turned to the field of religion and speculated about its origins and importance. William James was one of the foremost scholars of this period. His approach was chiefly that of the case study. The strength of his qualitative and narrative approach was that religion was embedded within the broader context of human life. The weakness was that two different investigators could look at the same religious person or phenomenon and come to very different conclusions, for there were no quantitative data.

The psychoanalyst Erik H. Erikson also employed the case study approach. For example, he wrote about the lives of Martin Luther and Mahatma Gandhi in terms of his eight-stage, epigenetic theory. Other theorists with a positive view of religion included neo-Freudians such as Carl Jung and Erich Fromm, and humanistic “third force” representatives such as Abraham Maslow. However, for these theorists, religion was secondary to their studies of personality, and their work was, therefore, seen by academic psychologists of religion as more philosophical than scientific.

For these reasons, the quantitative approach of the pollsters and psychologists dominates academic psychology. Yet doubt may be cast on the scientific status of this approach as well. A serious problem has to do with social desirability—people often respond in a way they think they should respond. Even though responses may be anonymous, people may (unconsciously or not) seek to portray themselves in a favorable light (in other words, as more religious than they really are). Another concern is the use of ambiguous terms in questions. Each denomination tends to define terms in its own way. What one denomination calls “services” might be called “worship” or “mass” by another. The Lord’s Supper is also known as Holy Communion and the Eucharist. Terms such as “God” and “personal commitment” may be so vague as to preclude construct validity.

The same item may have a different meaning for different people. For example, a person answering “rarely or never” to the question “How often do you ask God to forgive your sins?” may be an atheist who sees no purpose to the confession or a pious individual who rarely sins. Someone who disagrees with the statement “The word of God is revealed only in the Scriptures” may be an atheist or someone who believes in the possibility of present-day revelation. Certainly, national polls and measures of religiosity have ignored the importance of the context of the respondent’s denomination. Religiosity, as measured by the same scale, may mean one thing for an Orthodox Jew and another for a Jehovah’s Witness.

Many social scientists predicted the demise of religion during the twentieth century. Karl Marx believed that religion was the “opiate” of the people: a social institution used by the ruling classes to control and placate the exploited masses. After a proletarian revolution and the establishment of a just (Communist) social order, reasoned Marx, there would be no need for religion or, for that matter, the other instruments of state repression. Freud contended that, as psychoanalysis became more prevalent, people would turn away from religion; society would be composed of self-restrained individuals in control of their sexual and aggressive drives. The behaviorist B. F. Skinner regarded religious behavior as the result of accidental reinforcement, a superstitious approach to life that would diminish as humanity developed better technology for controlling the contingencies of its own reinforcement.

Instead, religion remains in myriad forms. For example, many intellectuals have moved away from institutionalized religion toward secular humanism. This requires those who study religion to rethink certain definitions, such as whether secular humanism can be defined as a religion and whether its religiosity can be measured. A more relevant question is not whether religion will continue to exist, but whether qualitative methods can attain the precision that science demands and whether quantitative methods can ever adequately measure the richness of human religious experience.

Bibliography

Allport, Gordon W. The Individual and His Religion: A Psychological Interpretation. 1950. Reprint. New York: Macmillan, 1970. Print.

American Educational Research Association, American Psychological Association, and National Council on Measurement in Education. Standards for Educational and Psychological Testing. Washington: American Psychological Association, 1999. Print.

Anastasi, Anne, and Susan Urbina. Psychological Testing. 7th ed. Upper Saddle River: Prentice Hall, 1997. Print.

Cook, Kaye V., et al. "The Complexity of Quest in Emerging Adults' Religiosity, Well-Being, and Identity." Journ. of the Scientific Study of Religion 53.1 (2014): 73–89. Print.

DeBono, Kenneth, and Anja Kuschpel. "Gender Differences in Religiosity: The Role of Self-Monitoring." North American Journ. of Psychology 16.2 (2014): 415–26. Print.

Erikson, Erik H. Gandhi’s Truth: On the Origin of Militant Nonviolence. New York: Norton, 1993. Print.

Erikson, Erik H. Young Man Luther: A Study in Psychoanalysis and History. New York: Norton, 1993. Print.

Gallup, George, Jr., and D. Michael Lindsay. Surveying the Religious Landscape: Trends in U.S. Beliefs. Harrisburg: Morehouse, 1999. Print.

Hill, Peter C., and Ralph W. Hood, Jr., eds. Measures of Religiosity. Birmingham,: Religious Education, 1999. Print.

Hood, Ralph W., Jr., Bernard Spilka, Bruce Hunsberger, and Richard Gorsuch. The Psychology of Religion: An Empirical Approach. 4th ed. New York: Guilford, 2009. Print.

Meadow, Mary Jo, and R. D. Kahoe. Psychology of Religion: Religion in Individual Lives. New York: Harper, 1984. Print.

Van Slyke, James A. The Cognitive Science of Religion. Burlington: Ashgate, 2011. Print.

Whitehouse, Harvey. Modes of Religiosity: A Cognitive Theory of Religious Transmission. Walnut Creek, Calif.: AltaMira, 2004. Print.

Wulff, David M. The Psychology of Religion: Classic and Contemporary. 2d ed. New York: Wiley, 1997. Print.

In the Giver, what happens in the release ceremony?

During chapter four, Jonas is giving a bath to an elderly woman named Larissa.  At one point during their conversation, she tells Jonas that they celebrated the release of an old person earlier that day.  Jonas asks her what the celebratory ceremony is like.  In a lot of ways it is similar to a funeral, except that the person is still alive . . . and will be killed a little bit later.  

Larissa...

During chapter four, Jonas is giving a bath to an elderly woman named Larissa.  At one point during their conversation, she tells Jonas that they celebrated the release of an old person earlier that day.  Jonas asks her what the celebratory ceremony is like.  In a lot of ways it is similar to a funeral, except that the person is still alive . . . and will be killed a little bit later.  

Larissa tells Jonas that every release ceremony has a "telling."  Somebody gets up and narrates important parts of the person's life that is about to be released.  Other people are allowed to get up and speak as well about things they remember about that person.  The person being released is allowed to speak as well.  That's basically a goodbye speech.  

"Well there was the telling of his life … is always first. Then the toast. We all raised our glasses and cheered. We chanted the anthem. He made a lovely good-bye speech. And several of us made little speeches wishing him well."

After all of the speeches are made, the person is taken away to another room in order to be released.  Only members of the release committee are allowed to see and know what happens next.  That's why everybody assumes being released is happy and wonderful instead of murder.  

What are carotenoids as a dietary supplement?

Overview

Carotenoids are red, orange, and yellow pigments found in fruits and
vegetables. About six hundred carotenoids have been identified, and all of them
have antioxidant properties. Some carotenoids can be converted in the body to
vitamin
A, and these are called provitamin A carotenoids. The
best-known carotenoids include beta-carotene, lutein,
lycopene, astaxanthin, and zeaxanthin.

The results of some observational studies suggest that a diet high in these carotenoids can reduce the risk of developing various illnesses, including cardiovascular disease, age-related vision loss, and various types of cancer. These findings led to large-scale studies of synthetic beta-carotene for preventing cancer (especially lung cancer), heart disease, cataracts, strokes, and macular degeneration. The results showed, at best, no benefit and, at worst, a possible increase in disease risk.

Many proponents of alternative medicine considered this outcome paradoxical and attempted to explain the outcome in various ways, such as beta-carotene alone may not be as useful as mixed carotenoids (and other healthful substances) found in fruits and vegetables, and synthetic beta-carotene may be less effective than natural beta-carotene. Also, the participants in these studies were inappropriate for the trials (generally, they were smokers).

However, while any of these explanations may be correct, it is also quite possible that carotenoids simply do not provide any of the healthful effects attributed to them. Observational studies are notoriously unreliable for proving a treatment effective. Such studies only find associations between events, rather than cause and effect. It is quite possible, for example, that people who tend to eat more fruits and vegetables may be healthier in various other ways than those who do not, and that these other factors account for the apparent improvements.

Consider the history of medical beliefs about hormone replacement therapy
(HRT) for menopausal women. Observational studies had found
evidence that women who used HRT had less heart
disease, and on this basis millions of women were prescribed
HRT. However, when proper double-blind studies were done, the results indicated
that HRT actually caused heart disease.

Similarly, nothing more reliable than observational studies underlies the
widespread belief that lycopene can prevent prostate
cancer and that lutein can do the same for cataracts.
One double-blind study does hint that mixed carotenoid supplementation is
beneficial for people with human immunodeficiency virus infection,
but the results were statistically weak. Thus, while it is a good idea to eat
fruits and vegetables, it is not clear that taking concentrated extracts of
various substances found in fruits and vegetables provides any health
benefits.

Age-Related Eye Disease Study Research Group. “A Randomized, Placebo-Controlled Clinical Trial of High-Dose Supplementation with Vitamins C and E and Beta Carotene for Age-Related Cataract and Vision Loss.” Archives of Ophthalmology 119 (2001): 1439-1452.

Austin, J., et al. “A Community Randomized Controlled Clinical Trial of Mixed Carotenoids and Micronutrient Supplementation of Patients with Acquired Immunodeficiency Syndrome.” European Journal of Clinical Nutrition 60 (2006): 1266-1276.

Epstein, K. R. “The Role of Carotenoids on the Risk of Lung Cancer.” Seminars in Oncology 30 (2003): 86-93.

Hak, A. E., et al. “Plasma Carotenoids and Tocopherols and Risk of Myocardial Infarction in a Low-Risk Population of US Male Physicians.” Circulation 108 (2003): 802-807.

Peterson, C. E., et al. “Combined Antioxidant Carotenoids and the Risk of Persistent Human Papillomavirus Infection.” Nutrition and Cancer 62 (2010): 728-733.

In Tuck Everlasting, from chapters 23-25, how is the wheel turning again?

The line of text that your question is referring to is found in chapter 25.  

The first week of August was long over. And now, though autumn was still some weeks away, there was a feeling that the year had begun its downward arc, that the wheel was turning again, slowly now, but soon to go faster, turning once more in its changeless sweep of change.

But the wheel that the text is speaking...

The line of text that your question is referring to is found in chapter 25.  

The first week of August was long over. And now, though autumn was still some weeks away, there was a feeling that the year had begun its downward arc, that the wheel was turning again, slowly now, but soon to go faster, turning once more in its changeless sweep of change.

But the wheel that the text is speaking of was first introduced in the opening prologue of Tuck Everlasting.  

The first week of August hangs at the very top of summer, the top of the live-long year, like the highest seat of a Ferris wheel when it pauses in its turning.

The "wheel" is referring to a passage of time.  Specifically the passage of time from season to season.  In the book Tuck Everlasting, author Natalie Babbitt  tells readers that the first week of August is like that momentary pause at the top of a Ferris wheel.  At that point, the rider isn't moving up or down.  He/she is stuck in place for a fraction of an instant.  The reason August is like that is because summer is hanging on for a bit longer before the weather turns and fall begins to creep in.  

Most of Tuck Everlasting takes place during that first week of August.  The text tells readers that it was uncomfortably hot during that week.  Most people, when confronted with hot and humid weather don't feel like doing anything.  Motion makes it worse.  So staying as still as possible is key.  That coincides with August being like the momentarily frozen Ferris wheel.  The weather is stagnant.  The people are stagnant.  Chapter 23 really drives home those feelings.  Time seems to stand still for Winnie, because she is anxious to help Mae escape and the weather makes it even worse.  

It was the longest day: mindlessly hot, unspeakably hot, too hot to move or even think. The countryside, the village of Treegap, the wood—all lay defeated. Nothing stirred.

By chapter 25, several weeks have passed since the night of the rescue.  The hot weather has broken, fall is beginning to creep in, the seasonal wheel is beginning to move again, and Winnie is being forced to move on from the Tuck family as well.  The chapter ends with Winnie making a very physical move away from remembering the immortality that the Tuck family offered her.  She pours out the bottle of spring water and her own wheel of time keeps turning.  

Who is the protagonist in In the Castle of My Skin by George Lamming?

Because George Lamming's novel In the Castle of My Skin is autobiographical in nature, the protagonist is G., a boy very similar to the author himself as a child. We should be careful to consider G. as at least a partially fictional creation, though, and not necessarily a faithful representation of George Lamming himself, since the novel is not considered a true autobiography.

As you read Chapter 1, you don't yet know the protagonist's...

Because George Lamming's novel In the Castle of My Skin is autobiographical in nature, the protagonist is G., a boy very similar to the author himself as a child. We should be careful to consider G. as at least a partially fictional creation, though, and not necessarily a faithful representation of George Lamming himself, since the novel is not considered a true autobiography.

As you read Chapter 1, you don't yet know the protagonist's name, but you know that he's narrating the story and that he's just turned nine years old. By Chapter 2, as G. is talking with his mother and his neighbors, you realize they call him "G." This name will stick with him all throughout the novel. (You might be tempted to call him George, but again, we need to acknowledge that the author and the protagonist have separate identities.)

Although the narration makes dramatic shifts to focus on other characters and images, veering away from the first-person point of view provided by G., he remains the novel's most important character and the vehicle through which the larger story of the changing community of the Caribbean village is told.

Some readers might even argue that the entire village itself is the real protagonist. You can certainly make a case for that by citing how often the narration focuses on other members of the community.

What is benign prostatic hyperplasia (BPH)?

Related conditions:

Prostate cancer, urinary retention

Definition:

Benign prostatic hyperplasia (BPH) refers to an enlarged prostate gland. The prostate is a reproductive gland in men that produces semen, the fluid that nourishes and transports sperm. It is about the size and shape of a walnut and is located below the bladder. The gland surrounds the urethra, the tube that carries urine outside the body. The prostate grows in size in most men as they age.

Risk factors: Increasing age and a family history of BPH contribute to the risk of developing this condition.

Etiology and the disease process: The exact cause of BPH is unknown. It is not cancerous, nor does it increase the risk of developing prostate cancer.

Incidence: Approximately 50 percent of men between the ages of fifty-one and sixty and 90 percent over age eighty develop BPH. About half of all men diagnosed with BPH have moderate to severe symptoms.

Symptoms: The enlarged prostate presses down on the urethra and irritates or obstructs the bladder. Common symptoms include frequent urination two or more times per night, a sudden urge to urinate, a weak urine stream, dribbling after urinating, straining to urinate, the inability to prevent urine leakage, or the sensation that the bladder is not empty even after urinating. In extreme cases, urinary retention, the complete inability to urinate, is a problem.

Screening and diagnosis: The evaluation typically consists of a complete medical history, a digital rectal exam to feel the size of the prostate, a urinalysis to check for blood or infection in the urine, a prostate-specific antigen (PSA) blood test to screen for prostate cancer, and questions to assess the severity of symptoms. Additionally, urine flow rate, a post-void residual urine test, a pressure-flow study, an x-ray of the urinary tract, or cystoscopy (a test using a scope inserted into the urethra and bladder) may be recommended.

Treatment and therapy: Depending on the severity of symptoms, treatment can include lifestyle modifications, such as decreasing the intake of fluid before bedtime and limiting the consumption of alcohol and caffeine, or medication to increase urine flow. In extreme cases, surgery to remove part of the prostate may be recommended.

Prognosis, prevention, and outcomes: Many men with BPH have only minor symptoms and are able to manage their discomfort with lifestyle modifications. A yearly exam is recommended to monitor symptoms and the impact of BPH on daily life.

Alan, R., and A. Carmack. “Benign Prostatic Hyperplasia.” Health Library. EBSCO Publishing, 1 Aug. 2014. Web. 12 Sept. 2014.

Bachmann, Alexander, and Jean J. M. C. H. de la Rosette. Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms in Men. New York: Oxford UP, 2012. Print.

Chapple, Christopher R., John D. McConnell, and Andrea Tubaro. Benign Prostatic Hyperplasia: Current Therapy. Malden: Blackwell, 2000. Print.

Kirby, R. S., and Peter J. Gilling. Fast Facts: Benign Prostatic Hyperplasia. Abingdon: Health, 2011. Digital file.

Rosario, Derek J. P., Scott A. MacDiarmid, and John E. T. Pillinger. Benign Prostatic Hyperplasia. Philadelphia: Elsevier, 2005. Print.

What are seizures? |

Causes and Symptoms

Seizures can be divided into two fundamental groups—partial and generalized. In partial seizures, the abnormal discharge of neurons usually arises in a portion of one hemisphere and may spread to other parts of the brain during a seizure. Generalized seizures, however, have no evidence of localized onset; the clinical manifestations and abnormal electrical discharge give no indication of the locus of onset of the abnormality, if such a locus exists.

Partial seizures are divided into three groups: simple partial seizures, complex partial seizures, and partial seizures secondarily generalized. Simple partial seizures are associated with the preservation of consciousness and unilateral hemispheric involvement. The area of seizure may spread until the entire side is involved. This type of seizure, with motor, sensory, or autonomic signs, was originally called Jacksonian epilepsy. Complex partial seizures are associated with alteration or loss of consciousness and bilateral hemispheric involvement. A partial seizure secondarily generalized is a generalized tonic-clonic seizure that proceeds directly from either a simple partial seizure or a complex partial seizure. The distinction between simple partial seizures and complex partial seizures is clarified by the observation that neurologic problems that are confined to one hemisphere, such as a unilateral cerebral stroke, generally spare consciousness, whereas bilateral cerebral (or brain stem) involvement causes alteration of consciousness.

If there is no evidence of localized onset, then the attack is a generalized seizure. Generalized seizures are more heterogeneous than partial seizures. The generalized seizures include generalized tonic-clonic (grand mal), absence (petit mal), atonic, myoclonic, clonic, and tonic seizures.

Tonic-clonic seizure is a common seizure pattern with sudden loss of consciousness, tonic contraction of muscles, loss of postural control, and a cry caused by contraction of respiratory muscles forcing exhalation. This is followed by a generalized contraction of the muscles of the four extremities. After two to five minutes of unconsciousness and the cessation of clonic contractions, the individual gradually regains consciousness. Fecal and urinary incontinence, as well as biting of the tongue, may occur. The individual does not remember the event and may not be completely functional for several days.

The absence seizure usually begins in childhood or early adolescence, and in many cases individuals outgrow the condition. Although unresponsiveness is the rule, motionlessness occurs in less than 10 percent of absence attacks; in fact, phenomena such as mild clonic motion and increased or decreased postural tone may accompany such attacks. Absence seizures are generally brief, usually lasting less than ten seconds and very rarely longer than forty-five seconds. The attacks are not associated with auras, hallucinations, or other symptoms characteristic of partial seizures, generalized tonic-clonic seizures, or infantile spasms. Individuals exhibiting these seizures are normal except for the seizures, but the seizures may occur as frequently as one hundred times a day.

Atonic seizures are characterized by a sudden loss of muscle tone. Myoclonic seizures are sudden and brief contractions of a single group of muscles or of the entire body. The patients fall but do not lose consciousness. Clonic and tonic seizures are characterized by alternation of contraction and relaxation and by contraction, respectively.

Infantile spasms are generalized seizures occurring in the first year of life. These are synchronous contractions of the muscles of the neck, trunk, and arms. About 90 percent of infants experiencing these attacks are intellectually disabled.

Seizures may be further subdivided into epileptic (those involving recurrent seizures) and nonepileptic. The term “nonepileptic seizure,” however, is somewhat problematic. For example, a seizure caused by
hypoglycemia (low blood sugar) may not be considered an epileptic attack by some because it is a transient event easily corrected by metabolic manipulation. Of the organic nonepileptic seizures, the most common are of cardiovascular origin; others are caused by transient cerebral ischemia, movement disorders, toxic or metabolic problems, sleep disorders, and even headaches. Nonepileptic attacks may also be of nonorganic or psychiatric origin, such as with hysteria and schizophrenia, in which case they are called psychogenic seizures or pseudoseizures.

Attempts to find a cause for the sudden abnormal discharge of cerebral neurons has not been possible in all types of seizure activity. In some cases, a brain tumor, scar tissue remaining from trauma to the brain, or a progressive neurological disease may be responsible. In the great majority of cases, however, no pathologic basis for the seizures is evident, either during life or at autopsy. The latter type of seizure has been classified as “idiopathic.” In certain circumstances, for example, fever, infection, or hyperglycemia, the response may include seizure. In many instances, these events are isolated and do not recur, and for this reason they are not categorized as epilepsy.

The cause of a seizure is related to the age of onset of the first attack. When seizures begin in the neonatal and infant period, the most likely causes are perinatal
anoxia (a deficiency of oxygen), congenital brain defects, meningitis, birth injuries, or other metabolic problems, such as hypoglycemia or hypercalcemia (excessive calcium). Less common causes of seizures in young children include toxins such as
lead poisoning, as well as rare degenerative diseases. In older children or adults, although metabolic or degenerative processes must be considered, other causes become more probable.

Head trauma accounts for the origin of many partial epileptic seizures in young adults, whereas brain tumors and vascular diseases are the major cause of such seizures in later life. Brain tumor is not a common cause of epilepsy in children, since 60 to 70 percent of brain tumors in children are located in the posterior fossa. Arteriosclerotic cerebrovascular disease is the most common cause of seizures in patients over the age of fifty. In about 4 percent of patients with brain infarction and 10 percent of those with intracerebral hemorrhage, seizures accompany the stroke; an additional 3 percent of patients who experience a stroke have recurrent seizures in later life, presumably generated by the cerebral
scar.

Most idiopathic seizure activity appears to have its origin in an inherited propensity to cerebral dysrhythmia. Although there is a high incidence of electroencephalographic (EEG) abnormalities in close relatives of persons with recurrent seizures, not all family members have clinical seizures. In general, genetic factors are particularly important when recurrent seizures begin in childhood and decrease in importance with age.

In most studies of early seizures predicting future epilepsy, the conditions that are associated with high risk include a depressed skull fracture, an acute intracerebral hematoma, post-traumatic amnesia lasting more than twenty-four hours, and the presence of tears in the dura mater of the brain or focal neurologic signs.

Generalized tonic-clonic seizures sometimes develop during the course of chronic
intoxication with
alcohol or barbiturates, almost always in association with withdrawal or reduction of the drugs. How long a period of chronic drug intoxication or abuse must last to produce seizures upon withdrawal is uncertain, but such patients often give a history of many years (sometimes decades) of drug dependence. Usually, the patients experience one or more seizures or short bursts of two to six seizures over a period of hours. An episode of alcohol withdrawal rarely precipitates more than a single burst of convulsions, while convulsions may recur for several days after barbiturate withdrawal. Studies have shown that among those who have had withdrawal seizures without other evidence of neurological damage, seizures almost always occurred during the seven-hour to forty-eight-hour period following the cessation of drinking. With alcohol withdrawal seizures, tremor, anorexia, and insomnia follow the seizure in perhaps 20 to 30 percent of cases. Delirium tremens is a less frequent event.

Treatment and Therapy

Prior to treatment, it is necessary for the physician to conduct a thorough investigation of the patient to identify any remediable cause of the seizures. This investigation would include metabolic diseases, endocrine system disturbances, cerebral tumors, abscess of the brain, or meningitis.

Persons who have recurrent convulsions controlled by medications can participate in sports and lead a relatively normal life; most countries will permit a person to drive an automobile if he or she has experienced no seizures for six months to one year. If seizures are uncontrolled, however, then automobile driving, swimming, the operation of unguarded machinery, and ladder climbing are not advised.

Drug therapy varies with the type of seizure presented. In the case of recurrent seizures, it generally consists of at least two to four years of daily medication. Careful neurologic examinations every four to six months, monitoring of seizure frequency correlated with drug blood level, and serial EEGs about once a year are also required. If there is a change in seizure frequency despite adequate drug blood levels, if there are focal neurologic signs or signs of increased intracranial pressure, or if evidence of focal changes on EEGs develop, further evaluation, including a computed tomography (CT) scan, is necessary. A small brain tumor may not be apparent even on a CT scan at the time of the initial evaluation, particularly in a patient with adult-onset epilepsy or in an older child or adolescent with partial seizures without a documented specific cause.

Absence seizures present less urgency. The patient rarely seeks medical advice until repeated episodes have occurred. Early treatment and prevention or reduction of repeated seizures can be beneficial. The drugs of choice for absence epilepsy are ethosuximide or valproate sodium. Medication is generally discontinued after two to four seizure-free years, depending on the presence or absence of generalized tonic-clonic seizures and the results of the EEGs. After the medication is discontinued, and after follow-up for fifteen to twenty-three years, there is about a 12 percent incidence of recurrence.

If the seizure process is strong enough to require more than one drug, multiple drug administration needs to be maintained. The aim of the treatment is to achieve the best possible seizure control with the least amount of side effects. This goal may necessitate a compromise in patients with resistant seizures; such patients may prefer having an occasional seizure to being continuously sedated or unsteady. This is particularly true with patients who experience partial seizures that are not excessively disruptive.

The side effects of drugs may cause impairment of liver function in susceptible individuals. Thus, periodic monitoring of the patient’s complete blood count and platelet count is necessary, as are liver function tests. This monitoring is done more frequently at the onset of therapy or after an upward adjustment of dosage.

The selection of specific drugs to be used for the prevention and control of seizures depends on the type of seizure. The most commonly used drugs include phenytoin, carbamazepine, phenobarbital, primidone, ethosuximide, methsuximide, clonazepam, valproate sodium, and trimethadione.

The pharmacokinetics and side effects of these drugs in infants and children differ somewhat from those observed in older children and adults. Absorption, plasma-protein binding, and metabolism are subject to age-specific variations. Younger children usually require a higher dose per kilogram to maintain a therapeutic blood level than do adults. Some of the classic signs of toxicity to the medications that are seen in adults may not be obvious in children.

If the seizures are related to a lesion in the brain, neurosurgical treatment is indicated. Surgery is the obvious form of treatment for demonstrable structural lesions such as cysts lying in accessible areas of the cerebral hemispheres. In a more restricted sense, surgical therapy is considered in patients without a mass lesion when the seizures are unresponsive to drug treatment and the patient has a consistent, electrophysiologically demonstrable focus emanating from, for example, a scar. Specific surgical treatments vary from case to case.

Up to 80 percent of properly selected patients have been found to benefit to some extent from surgical removal of the focal lesion. In some cases of intractable seizures associated with behavior disorders and hemiplegia of childhood, removal of a damaged cerebral hemisphere has been found to control the intractable seizures and to improve the behavior disorder without causing further neurological deficit.

Perspective and Prospects

In the twentieth century, major developments were made in diagnosis and therapy. In 1929, Hans Berger recorded the first human electroencephalogram. Descriptions of EEG patterns and their correlation with clinical absences, partial seizures, and generalized tonic-clonic seizures led to important developments in classification and treatment. Special EEG recordings with activation techniques, depth recordings, and long-term recordings for patients with intractable seizures became available to aid in the diagnosis and medical management of patients and in the selection of candidates for possible neurosurgical treatment.

Prolonged EEG recording by telemetry (the transmission of data electronically to a distant location) and ambulatory monitoring became helpful in making a diagnosis in patients who have brief spells of uncertain type. Electrical activity at the time of the attack can be documented. Videotaping with split-screen EEG recording and patient observation allows excellent correlation between the clinical and EEG manifestations, which aids in the classification and determination of appropriate therapy in difficult clinical problems. In those patients with intractable epilepsy, prolonged recording can document the frequency of seizures and correlation with anticonvulsive drug blood levels.

Radiological advances and CT scans in the 1970s, and later positron emission tomography (PET) scans, improved diagnostic skill in delineating potentially remediable lesions in patients with seizures.

During the twentieth century, many other medications became available for patients with seizures. The use of the operating microscope and technical advances in microsurgical techniques refined surgical treatments and improved the outlook for patients with structural lesions such as brain tumors, vascular malformations, and scars.

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