Reading

Tests,Procedures, an~Te_chniques

• DNA Fingerprinting A technique called DNA fingerprinting is used in research and in courts of law to ascertain whether a person's DNA matches the DNA obtained from samples or pieces of legal evidence such as blood stains or hairs. In each person, certain DNA segments contain base sequences that are repeated several times. Both the number of repeat copies in one region and the number of regions subject to repeat are different from one person to another. DNA fingerprinting can be . done with minute quantities of DNA-for example, from a single strand of hair, a drop of semen, or a spot of blood. It also can be .used to identify a crime victim or a child's bio­ logical parents and even to detennine whether two people have a common ancestor.

~n Liposuction A surgical procedure called liposuctio.n (Jip- = fat) or suction lipectomy (-ectomy = to cut out) involves suctioning small

Abdominal Liposuction

Papanlcolaou Test

amounts of adipose tissue from various areas of the body. After an incision is made .in the skin, the fat is removed through a hollow tube, called a cannula, with the assistance of a powerful vacuum pressure unit that suctions out the fat. The technique can be used as a body-contouring procedure in regions such as the thighs, buttocks, arms, breasts, and

1 abdomen, and to transfer fat to another area of the body. Postsurgical complications

Speculum -

Tests, Procedures, and Techniques 7

that may develop include fat that may enter blood vessels broken during the procedure and obstruct blood flow, infec­ tion, loss of feeling in the area, fluid depletion, injmy to internal structures, and severe postoperative pain.

LJ Medical Uses of Isotonic, Hypertonic, and Hypotonic Solutions

RBCs and other body cells may be damaged or destroye~ if exposed to hypertonic or hypotonic solutions. For this reason, most intravenous (IV) solutions, liquids infused into the blood of a vein, are isotonic. Exan1ples are iso­ tonic saline (0.9% NaCl) and D5W, which stands for dextrose 5% in water. Sometimes infusion of a hypertonic solution such as mannitol is useful to treat patients who have cerebral edema, excess interstitial fluid in the brain. Infusion of such a solution relieves fluid overload by caus- \ ing osmosis of water from interstitial fluid into the blood. The kidneys then excrete the excess water from the blood into the urine. Hypotonic solutions, given either orally or through an IV, can be used to treat people who are dehy­ drated. The water in the hypotonic solution moves from the blood into interstitial fluid and then into body cells to rehydrate. them. Water and most sports drinks that you consume to "rehydrate" after a workout are hypotonic relative to your body cells.

Gl Papanicolaou Test A Papanicolaou test (pa-pa-NI-ko-16), also called a Pap test or Pap smear, involves collection and microscopic examination of epithelial cells that have been scraped off the apical layer of a tissue. A very common type of Pap test involves examining the cells from the nonkeratinized stratified squamous epithelium of the vagina and cervix (inferior portion) of the uterus. This type of Pap test is performed mainly to detect early changes in the cells of the female reproductive system that may indicate a /

/

8 2 Chemistry, Cells, and Tissues

precancerous condition or cancer. In performing a Pap smear, a physician collects cells, which are then smeared on a microscope slide. The slides are then sent to a labo­ rato1y for analysis. Pat tests should be started within three years of the onset of sexual activity, or age 21, whichever comes first. Annual screening is recommended for females ages 21-30 and every 2-3 years for females age 30 or older following three consecutive negative Pap tests.

1ii Recombinant DNA Scientists have developed techniques for inserting gen~s · from other organisms into a variety of host cells. Manipulating the cell in this way can cause the host organ­ ism to produce proteins it normally does not synthesize. Organisms so altered are called recombinants, and their DNA-a combination of DNA from different sources-is called recombinant DNA'. When recombinant DNA functions properly, the host will synthesize the protein specified by the new gene it has ·acqnired. The technology that has arisen from the manipnlation of genetic material

· is referred to as genetic engineering. The practical applications of recoml:iinant DNA

teclihology are enormous. Strains of recombinant bac­ teria now produce large quantities of many important

. therapeutic substances, including human growth hormone (hGH), required for normal growth and metabolism; insulin, a hormone that helps regulate blood glucose level and is used by diabetics; inte,feron (JPN), an anti­ viral (and possibly anticancer) substance; and erythropoi- . etin (EPO), a hormone that stimulates production of red blood cells.

1111 Stem Cell Research and Therapeutic Cloning Stem cells are unspecialized cells that have the ability to divide for indefinite periods and give rise to specialized cells. In the context of human development, a zygote (fertilized ovum) is a stem cell. Because it has the poten­ tial to form an entire organism, a zygote is known as a totipotent stem cell (to-TIP-6-tent;'totus- = whole; -poten­ tia = power). Inner cell mass cells, called pluripotent ste,n cells (ploo-RIP-6-tent; plur- = several), can give rise to many (but not all) different types of cells. Later, pluripo­ tent stem cells can undergo further specialization into multipotent stem cells (mul-TIP-6-tent), stem cells with a specific function. Examples include keratinocytes that produce new skin cells, myeloid and lymphoid stem cells that develop into blood cells, and spermatogonia that give rise to sperm. Pluripotent stem cells currently used in research are . derived from (1) the embryoblast of embryos in the blastocyst stage that were destined to be used for infertility treatments but were not needed. and from (2) nonliving fetuses terminated during the first three months of pregnancy. . ... -- -..

On Octob.er 13, 2001, researchers reported cloning of the first human embryo to grow cells to treat human' dis­ eases. Therapeutic cloning is envisioned as a procedure in which the genetic material of a patient with a particu-

lar disease is used to create pluripotent stem cells to treat the disease. Using the principles of therapeutic cloning, scientists hope to make an embryo clone of a patient, remove tl1e pluripotent stem cells from the embryo, and then use them to grow tissues to treat particular diseases and disorders, such as cancer, Parkinson disease, Alzheimer disease, spinal cord injury, diabetes, heart dis­ ease, stroke, burns, birth defects, osteoarthritis, and rheumatoid arthritis. Presumably, the tissues would not be rejected since they would contain the patient's own genetic material.

Scientists are also investigating the potential clinical applications of adult stem cells-stem cells that remain in the body throughout adulthood. Recent experiments sug~ gest that the ovaries of adult mice contain stem cells that'1 can develop into new ova (eggs). If these same types of stem cells are found in the ovaries of adult women, scien­ tists could potentially harvest some of them from a woman about to undergo a sterilizing medical treatment (such as chemotherapy), store them, and then return the stem cells to her ovaries after the medical treatment is completed in order to restore fertility. Studies have also suggested that stem cells in human adult red bone mar­ row have the ability to differentiate into cells of the liver, kidney, heart, lung, skeletal muscle, skin, and organs of the gastrointestinal tract. In theory, adult stem cells from red bone marrow could be harvested from a patient and then used to repair other tissues and organs in that patient's body without having to use stem cells from embryos.

iii Tissue Engineering The technology of tissue engineering has allowed sci­ entists to grow new tissues in the laboratory to replace_. damaged tissues in the body. Tissue engineers haye already developed laboratory-grown versions of skin .and cartilage using scaffolding beds of biodegradable/syn­ thetic materials or collagen as substrates that permit body cells to be cultured. As the cells divide and assemble, the scaffolding degrades; the new, permanent tissue is then implanted in the patient. Other structures currently under development inc.Jude bones, tendons, heart valves, bone marrow, and intestines. Work is also under way to develop insulin-producing cells for diabetics, dopamine­ producing cells for Parkinson disease patients, and even entire livers and kidneys. II

Disorders Affecting Chemistry, Cells, and Tissues

• Basement Membranes and Disease Under certain conditions, basement membranes become markedly thickened, due to increased production of colla­ gen and laminin. In untreated cases of diabetes mellitus, the basement membrane of small blood vessels (capillaries)

thickens, especially in the eyes and kidneys. Because of this the blood vessels cannot function properly and blindness and kidney failure may result.

lJ Cancer Cancer is a group of diseases characterized by uncon­ trolled or abnormal cell proliferation. When cells in a part of the body divide without control, the excess tissue that develops is called a tumor or neoplasm (NE-6-plazm; neo- = new). The study of tumors is called oncology (on­ KOL-6-je; onco- = swelling or mass). Tumors may be cancerous and often fatal, or they may be harmless. A can­ cerous neoplasm is called a malignant tumor or malig­ nancy. One property of most malignant tumors is their ability to undergo metastasis (me-TAS-ta-sis), the spread of cancerous cells to other parts of the body. A benign tumor is a neoplasm that does not metastasize. An exam­ ple is a wart. Most benign tumors may be removed surgi­ cally if they interfere with normal body function or become disfiguring. Some benign tumors can be inopera­ ble and perhaps fatal.

~ Types of Cancer The name of a cancer is derived from the type of tissue in which it develops. Most human cancers are carcinomas (kar-si-NO -maz; carcin = cancer; -omas = tumors), malignant tumors that arise from epithelial cells. Melanomas (mel-a-NO-maz; melan- = black), for exam­ ple, are cancerous growths of melanocytes, skin epithelial cells that produce the pigment melanin. Sarcoma (sar­ KO-ma; sarc- = flesh) is a general term for any cancer arising from n1uscle cells or connective tissues. For example, osteogenic sarcoma (osteo- = bone; -genie = origin), the most frequent type of childhood cancer, destroys normal bone tissue. Leukemia (loo-KE-me -a; leuk- = white; -emia = blood) is a cancer of blood-form­ ing organs characterized by rapid growth of abnormal leukocytes (white blood cells). Lymphoma (lim-FO-ma) is a malignant disease of lymphatic tissue-for example, of lymph nodes.

1111 Growth and Spread of Cancer Cells of malignant tumors duplicate rapidly and continu­ ously. As malignant cells invade surrounding tissues, they often trigger angiogenesis, the growth of new net­ works of blood vessels. Proteins that stimulate angiogen­ esis in tumors are called tumor angiogenesis factors (TAFs). The formation of new blood vessels can occur either by overproduction of T AFs or by the lack of natu­ rally occurring angiogenesis inhibitors. As the cancer grows,it begins to compete with normal tissues for space and nutrients. Eventually, the normal tissue decreases in size and dies. Some malignant cells may detach from the initial (primary) tumor and invade a body cavity or enter the blood or lymph, then circulate to and invade other body tissues, establishing secondary tumors. Malignant cells resist the antitumor defenses of the body. The pain

Disorders Affecting Chemistry, Cells, and Tissues 9

associated with cancer develops when the tumor presses on nerves or blocks a passageway in an organ so that secretions build up pressure, or as a result of dying tissue or organs.

CJ Causes of Cancer Several factors may trigger a normal cell to lose control and become cancerous. One cause is environmental agents: substances in the air we breathe, the water we drink, and the food we eat. A chemical agent or radia­ tion that produces cancer is called a carcinogen ( car­ SIN-6-jen). Carcinogens induce mutations, permanent changes in the DNA base sequence of a gene. The World Health Organization estimates that carcinogens are associated with 60-90% of all human cancers. Examples of carcinogens are hydrocarbons found in cigarette tar, radon gas from the earth, and ultraviolet (UV) radiation in sunlight.

Intensive research efforts are now directed toward studying cancer-causing genes, or oncogenes (ON-ko-jenz). When inappropriately activated, these genes have the ability to transform a normal cell into a cancerous cell. Most oncogenes derive from normal genes called proto­ oncogenes that regulate growth and development. The proto-oncogene undergoes some change that causes it either to be expressed inappropriately or to make its products in excessive ainounts or at the wrong time. Some oncogenes cause excessive production of growth factors, chemicals that stimulate cell growth. Others may trigger changes in a cell-surface receptor, causing it to send signals as though it were being activated by a growth factor. As a result, the growth pattern of the cell becomes abnormal.

Proto-oncogenes in every cell carry out normal cellu­ lar functions until a malignant change occurs. It appears that some proto-oncogenes are activated to oncogenes by mutations in which the DNA of the proto-oncogene is altered. Other proto-oncogenes are activated by a rear­ rangement of the chromosomes so that segments of DNA are exchanged. Rearrangement activates proto­ oncogenes by placing them near genes that enhance their activity.

Some cancers have a viral origin. Viruses are tiny pack­ ages of nucleic acids, either RNA or DNA, that can repro­ duce only while inside the cells they infect. Some viruses, termed oncogenic viruses, cause cancer by stimulating abnormal proliferation of cells. For instance, the human papillomavirus (HPV) causes virtually all cervical cancers in women. The virus produces a protein that causes protea­ sames to destroy p53, a protein that normally suppresses unregulated cell division. In the absence of this suppressor protein, cells proliferate without control.

Recent studies suggest that certain cancers may be linked to a cell having abnormal numbers of chromosomes. As a result, the cell could potentially have extra copies of oncogenes or too few copies of tumor-suppressor genes, which in either case could lead to uncontrolled cell

10 2 Chemistry, Cells, and Tissues

proliferation. There is also some evidence suggesting that cancer may be caused by normal stem cells that develop into cancerous stem cells capable of forming malignant tumors.

Inflammation is a defensive response to tissue damage. It appears that inflammation conn·ibutes to various steps in the development of cancer. Some evidence suggests that chronic inflammsdnn stimulates the proliferation of mutated cells and enhances their survival, promotes angio­ genesis, and contributes to invasion and metastasis of cancer cells. There is a clear relationship between certain chronic inflammatory conditions and the transformation of inflamed tissue into a malignant tissue. For example, chronic gastritis (inflammation of the stomach lining) and peptic ulcers may be a causative factor in 60-90% of stom­ ach cancers. Chronic hepatitis (inflammation of the liver) and cirrhosis of the liver are believed to be responsible for about 80% of liver cancers. Colorectal cancer is ten time more likely to occur in patients with chronic inflammatory diseases of the colon, such as ulcerative colitis and Crohn's disease. And the relationship between asbestosis and silico­ sis, two chronic lung inflammatory conditions, and lung cancer has long been recognized. Chronic inflammation is also an underlying contributor to rheumatoid arthritis, Alzheimer disease, depression, schizophrenia, cardiovascu­ lar disease, and diabetes.

l!tl Carcinogenesis: A Multistep Process Carcinogenesis (kar' -si-n6-JEN-e-sis), the process by which cancer develops, is a multistep process in which as many as IO distinct mutations may have to accumulate in a cell before it becomes cane erous. The progression of genetic changes leading to cancer is best understood for colon (colorectal) cancer. Such cancers, as well as lung and breast cancer, take years or decades to develop. In colon cancer, the tumor begins as an area of increased cell pro­ liferation that results from one mutation. This growth then progresses to abnormal, but noncancerous, growths called adenomas. After two or three additional mutations, a mutation of the tumor-suppressor gene p53 occurs and a carcinoma develops. The fact that so many mutations are needed for a cancer to develop indicates that cell growth is normally controlled with many sets of checks and balances. A compromised immune system is also a significant com­ ponent in carcinogenesis.

• Treatment of Cancer Many cancers are removed surgically. However, when cancer is widely distributed throughout the body or exists in organs such as the brain whose functioning would be greatly harmed by surgery, chemotherapy and radiation therapy may be used instead. Sometimes sur­ gery, chemotherapy, and radiation therapy are used in combination. Chemotherapy involves administering drugs that cause death of cancerous cells. Radiation therapy breaks chromosomes, thus blocking cell division. Because cancerous cells divide rapidly, they are more

vulnerable to the destructive effects of chemotherapy and radiation therapy than are normal cells. Unfortunately for the patients, hair follicle cells, red bone marrow cells, and cells lining the gastrointestinal tract also are rapidly dividing. Hence, the side effects of chemotherapy and radiation therapy include hair loss due to death of hair follicle cells, vomiting and nausea due to deatl1 of cells lining the stomach and intestines, and susceptibility to infection due to slowed production of white blood cells in red bone marrow.

Treating cancer is difficult because it is not a single disease and because the cells in a single tumor population rarely behave all in the same way. Although most cancers are thought to derive from a single abnormal cell, by the time a tumor reaches a clinically detectable size, it may contain a diverse population of abnormal cells. For example, some cancerous cells metastasize readily, and otl1ers do not. Some are sensitive to chemotherapy drugs and some are drug-resistant. Because of differences in drug resistance, a single chemotherapeutic agent may destroy susceptible cells but permit resistant cells to proliferate.

Another potential treatment for cancer that is currently under development is virotherapy, the use of viruses to kill cancer cells. The viruses employed in this strategy are designed so tl1at they specifically target cancer cells witl1- out affecting the healthy cells of the body. For example, proteins (such as antibodies) that specifically bind to receptors found only in cancer cells are attached to viruses. Once inside the body, tl1e viruses bind to cancer cells and then infect them. The cancer cells are eventually killed once the viruses cause cellular lysis.

Researchers are also investigating the role of metastasis regulatory genes that control the ability of cancer cells to undergo metastasis. Scientists hope to develop therapeutic drugs that can manipulate these genes and, therefore, block metastasis of cancer cells.

111 Marfan Syndrome Marfan syndrome (MAR-fan) is an inherited disorder caused by a defective fibrillin gene. The result is abnormal development of elastic fibers. Tissues rich in elastic fibers are malformed or weakened. Structures affected most seri­ ously are the covering layer of bones (periosteum), the liga­ ment that suspends the lens of the eye, and the walls of the large arteries. People with Marfan syndrome tend to be tali and have disproportionately long arms, legs, fingers, and toes. A common symptom is blurred vision caused by dis­ placement of the lens of the eye. The most life-threatening complication of Marfan syndrome is weakening of the aorta (the main artery that emerges from ilie heart), which can suddenly burst.

• Progeria and Werner Syndrome Progeria (prii-JER-e -a) is a disease characterized by nor­ mal development in the first year of life followed by rapid aging. It is caused by a genetic defect in which telomeres

,,

are considerably shorter than normal. Symptoms include dry and wrinkled skin, total baldness, and birdlike facial features. Death usually occurs around age 13.

Werner syndrome is a rare, inherited disease that causes a rapid acceleration of aging, usually while the per­ son is only in his or her twenties. It is characterized by wrinkling of the skin, graying of the hair and baldness, cataracts, muscular atrophy, and a tendency to develop diabetes mellitus, cancer, and cardiovascular disease. Most afflicted individuals die before age 50. Recently, the gene that causes Werner syndrome has been identified. Researchers hope to use the information to gain insight into the mechanisms of aging, as well as to help those suf­ fering from the disorder.

fl'li Sj1igren's Syndrome Sjiigren's syndrome (SHO -grenz) is a common auto­ immune disorder that causes inflammation and destruc­ tion of exocrine glands, especially the lacrimal (tear) glands and saliva1y glands. Signs include dryness of the eyes, mouth, nose, ears, skin, and vagina, and salivary gland enlargement. Systemic effects include fatigue, arthritis, difficulty in swallowing, pancreatitis (inflam­ mation of the pancreas), pleuritis (inflammation of the pleurae of the lungs), and muscle and joint pain. The disorder affects females more than males by a ratio of 9 to 1. About 20% of older adults experience some signs of Sji:igren's. Treatment is supportive, including using artificial tears to moisten the eyes, sipping fluids, chew­ ing sugarless gum, using a saliva substitute to moisten the mouth, and using moisturizing creams for the skin. If symptoms or complications are sever, medications may be used. These include cyclosporine eyedrops, polocarpine to increase saliva production, immunosup­ pressants, nonsteroidal anti-inflammatory drngs, and corticosteroids.

ll!I Systemic Lupus Erythematosus Systemic lupus erythematosus (er-i-the -ma-TO -sus), SLE, or simply lupus, is a chronic inflammatory disease of connective tissue occurring mostly in nonwhite women during their childbearing years. It is an autoimmune dis­ ease that can cause tissue damage in every body system. The disease, which can range from a mild condition in most patients to a rapidly fatal disease, is marked by periods of exacerbation and remission. The prevalence of SLE is about 1 in 2000, with females more likely to be afflicted than males by a ratio of 8 or 9 to 1.

Although the cause of SLE is unknown, genetic, envi­ ronmental, and hormonal factors all have been implicated. The genetic component is suggested by studies of twins and family history .. Environmental factors include virnses, bacteria, chemicals, drugs, exposure to excessive sunlight, and emotional stress. Sex hormones, such as estrogens, may also trigger SLE.

Signs and symptoms of SLE include painful joints, low­ grade fever, fatigue, mouth ulcers, weight loss, enlarged

Additional Clinical Considerations 11

lymph nodes and spleen, sensitivity to sunlight, rapid loss oflarge amounts of scalp hair, and anorexia. A distinguish­ ing feature of lupus is an eruption across tl1e bridge of the nose and cheeks called a "butterfly rash." Otl1er skin lesions may occur, including blistering and ulceration. The erosive nature of some SLE skin lesions was thought to resemble the damage inflicted by the bite of a wolf-thus, the name lupus ( = wall). The most serious complications of the disease involve inflamniat:ion of the kidneys, liver, spleen, lungs, heart, brain, and gastrointestinal tract. Because there is no cure for SLE, treatment is supportive, including anti-inflammatory drugs, such as aspirin, and immunosuppressive drugs.

""Tay-Sachs Disease Some disorders are caused by faulty or absent lysosomal enzymes. For instance, Tay-Sachs disease, which most often affects children of Ashkenazi (eastern European Jewish) descent, is an inherited condition characterized by the absence of a single lysosomal enzyme called Hex A. This enzyme normally breaks down a membrane glyco­ lipid called ganglioside GM2 that is especially prevalent in nerve cells. As the excess ganglioside GM2 accumulates, the nerve cells function less efficiently. Children witl1 Tay­ Sachs disease typically experience seizures and muscle rigidity. They gradually become blind, demented, and uncoordinated and usually die before the age of 5. Tests can now reveal whether an adult is a carrier of tl1e defec­ tive gene. Iii

Additional Clinical Considerations

111 Adhesions Scar tissue can form adhesions, abnormal joining of tissues. Adhesions commonly form in the abdomen around a site of previous inflammation such as an inflamed appendix, and they can develop after surgery. Although adhesions do not always cause problems, they can decrease tissue flexibility, cause obstruction {such as in the intes­ tine), and make a subsequent operation more difficult. An adhesiotomy, the surgical release of adhesions, may be required.

• Chondroitin Sulfate, Glucosamine, and Joint Disease

In recent years, chondroitin sulfate and glucosamine (a proteoglycan) have been used as nutritional supplements either alone or in a combination to promote and maintain the structure and function of joint cartilage, to provide pain relief from osteoarthritis, and to reduce joint inflam­ mation. Although these supplements have benefited some individuals with moderate to severe osteoarthritis, the benefit is minimal in lesser cases. More research is needed to determine how they act and why they help some people and not others.

12 2 Chemistry, Cells, and Tissues

• Digitalis increases ca>+ in Heart Muscle Cells Digitalis often is given to patients with hea,-r failure, a condition of weakened pumping action by the heart. Digitalis exerts its effect by slowing the action of the sodium-potassium pumps, which lets more Na+ accumu­ late inside heart muscle cells. The result is a decreased Na+ concentration gradient across the plasma membrane, which causes the Na+ /Caz+ antiporters to slow down. As a result, 1nore Ca2+ remains inside heart muscle cells. The slight increase in the level of Caz+ in the cytosol of heart muscle cells increases the force of their contractions and thus strengthens the force of the heartbeat.

cJ Fatty Acids in Health and Disease As its name implies, a group of fatty acids called essential fatty acids (EFAs) is essential to human health. However, they cannot be made by the human body and must be obtained from foods or supplements. Among the more important EFAs are o,nega-3 fatty acids, omega-6 fatty acids, and cis-fatty acids.

Omega-3 and omega-6 fatty acids are polyunsatu­ rated fatty acids that are believed to work together to promote health. They may have a protective effect against heart disease and stroke by lowering total cho­ lesterol, raising HDL (high-density lipoproteins or "good cholesterol") and lowering LDL (low-density lipoproteins or "bad cholesterol"). In addition, omega-3 and omega-6 fatty acids decrease bone loss by increas­ ing calcium utilization by the body; reduce symptoms of arthritis due to inflammation; promote wound healing; improve certain skin disorders (psoriasis, eczema, and acne); and improve mental functions. Primary sources of omega-3 fatty acids include flaxseed, fatty fish, oils that have large amounts of polyunsaturated fatty acids, fish oils, and walnuts. Primary sources of omega-6 fatty acids include most processed foods (cereals, breads, white rice), eggs, baked goods, oils with large amounts of polyunsaturated fatty acids, and meats (especially organ meats, such as liver).

The hydrogen atoms on either side of the double bond in oleic acid are on the same side of the unsaturated fatty acid. Such an unsaturated fatty acid is called a cis-fatty acid. Cis-fatty acids are nutritionally beneficial unsaturated fatty acids that are used by the body to produce hormone-like regulators and cell membranes. However, when cis-fatty acids are heated, pressurized, and combined with a catalyst (usually nickel) in a process called hydrogenation, they are changed to unhealthy trans-fatty acids. In trans-fatty acids the hydrogen atoms are on opposite sides of the double bond of an unsaturated fatty acid. Hydrogenation is used by manufacturers to make vegetable oils solid at room temperature and less likely to turn rancid. Hydrogenated or trans-fatty acids are common in commercially baked goods (crackers, cakes, and cookies), salty snack foods, some margarines, and fried foods (donuts and french fries). When oil is used for frying and if the oil is reused (like in fast food French fry machines) cis-fatty acids are converted

to trans-fatty acids. If a product label contains the words hydrogenated or partially hydrogenated, then the product contains trans-fatty acids. Among the adverse effects of trans-fatty acids are an increase in total cholesterol, a decrease in I-:IDL, an increase in LDL, and an increase in triglycerides. These effects, which can increase the risk of heart disease and other cardiovascular diseases, are similar to those caused by saturated fats.

' : Free Radicals and Their Effects on Health In our bodies, several processes can generate free radicals, including exposure to ultraviolet radiation in sunlight, exposure to x-rays, and some reactions that occur during normal metabolic processes. Certain harmful substances, such as carbon tetrachloride ( a solvent used in dry clean­ ing), also give rise to free radicals when they participate in metabolic reactions in the body. Among the many disor­ ders, diseases, and conditions linked to oxygen-derived free radicals are cancer, atherosclerosis, Alzheimer disease, emphysema, diabetes mellitus, cataracts, macular degen­ eration, rheumatoid arthritis, and deterioration associated with aging. Consuming 1nore antioxidantl'-substances that inactivate oxygen-derived free radicals-is thought to slow the pace of damage caused by free radicals. Important dietary antioxidants include selenium, zinc, beta-carotene, and vitamins C and E.

u Genomics In the last decade of the twentieth century, the genomes of humans, mice, fruit flies, and more than 50 microbes were sequenced. As a result, research in the field of genomics, the study of the relationships between the genome and the biological functions of an organism, has flourished. The Human Genome Project began in June 1 990 as an effort to sequence all of the nearly 3 .2 billion nucleotides of our genome, and was completed in April 2003. More than 99.9% of the nucleotide bases are identi­ cal in everyone. Less than 0.1 % of our DNA (1 in each 1000 bases) accounts for inherited differences among humans. Surprisingly, at least half of the human genome consists of repeated sequences that do not code for proteins, so-called "junk" DNA. The average gene consists of 3 000 nucleotides, but sizes vary greatly. The larg­ est known human gene, with 2 .4 million nucleotides, codes for the· protein dystrophin. Scientists now know that the total number of genes in the

Human "Genome Project: human genome is about 30,000, logo with DNA chromosome

far fewer than the I 00,000 previously predicted to exist. Information regarding the human genome and how it is affected by the environment seeks to identify and dis­ cover the functions of the specific genes that play a role in genetic diseases. Genomic medicine also aims to design new drugs and to provide screening tests to enable physicians to provide more effective counseling and treatment for disorde-r_s ,vi.th significant genetic components such as hypertenslon (high blood pressure), obesity, diabetes, and cancer.

Harmful and Beneficial Effects of Radiation Radioactive isotopes may have either harmful or helpful effects. Their radiations can break apart molecules, posing· a serious threat to the human body by producing tissue dam­ age and/or causing various types of cancer. Although the decay of naturally occurring radioactive isotopes typically releases just a small ainount of radiation into the environ­ ment, localized accumulations can occur. Radon-222, a colorless and odorless gas that is a naturally occurring radio­ active breakdm.vn product of uranium, may seep out of the soil and accumulate in buildings. It is not only associated with many cases oflung cancer in smokers but has also been implicated in many cases o'f lung cancer in nonsmokers. Beneficial effects of certain radioisotopes include their use in 1nedical imaging procedures to diagnose and treat certain disorders. Some radioisotopes can be used as tracers to fol­ low the movement of certain substances through the body. Thallium-201 is used to monitor blood flow through the heart during an exercise stress test. Iodine-131 is used to detect cancer of the thyroid gland and to assess its size and activity, and may also be used to destroy.part of an overactive thyroid gland. Cesium-137 is used to treat advanced cervical cancer, and iridium is used to treat prostate cancer.

!ill Smooth ER.and Drug Tolerance One of the functions of smooth ER, as noted earlier, is to detoxify certain drugs. Individuals who repeatedly take such drugs, such as the sedative phenobarbital, develop changes in the smooth ER in their liver cells. Prolonged administration of phenobarbital results in increased tolerance to the drug; the same dose no longer produces the same degree of sedation. With repeated exposure to the drug, the amount of smooth ER and its enzymes increases to protect the cell from its toxic effects. As the amount of smooth ER increases, higher and higher dosages of the drug are needed to achieve the original effect.

fill Tumor-Suppressor Genes Abnormalities in gene.s that regulate the cell cycle or apop­ tosis are associated with many diseases. For example, dam­ age to genes called tumor-suppressor genes, which produce proteins that normally inhibit cell division, causes some types of cancer. Loss or alteration of a tumor-sup­ pressor gene called p53 on chromosome I 7 is the most

Medical Terminology 13

common genetic change leading to a wide variety of tumors, including breast and colon cancers. The normal p5 3 protein arrests cells in the G 1 phase, which prevents cell division. Normal p53 protein also assists in repair of damaged DNA and induces apoptosis in the cells where DNA repair was not successful. For this reason, the p53 gene is nicknamed "the guardian angel of the genome."

; Viruses and Receptor-Mediated Endocytosis Although receptor-mediated endocytosis normally imports needed materials, some viruses are able to use this mecha­ nism to enter and infect body cells. For example, the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), can attach to a receptor called CD4. This receptor is present in the plasma membrane of white blood cells called helper T cells. After binding to CD4, HIV enters the helper T cell via receptor-mediated endocytosis.

Medical Terminology

Anaplasia (an' -a-PLA-ze -a; an- = not; -plasia = to shape) The loss of tissue differentiation and function that is characteristic of n1ost malignancies.

Atrophy (AT-ro -fe ; a- = without; -trophy = nourish­ ment) A decrease in the size of cells, with a subsequent decrease in the size of the affected tissue or organ; wast­ ing away.

Biopsy (BI-op-se; bio-=life; -opsy=to view) The removal of a san1ple of living tissue for microscopic examination to help diagnose disease.

Dysplasia (dis-PLA-ze -a; dys- = abnormal) Alteration in the size, shape, and organization of cells due to chronic irritation or inflammation; may progress to neoplasia (tumor formation, usually malignant) or revert to nor­ mal if the irritation is removed.

Hyperplasia (hi -per-PLA-ze-a; hyper- = over) Increase in the number of cells of a tissue due to an increase in the frequency of cell division.

Hypertrophy (hi -PER-tro -fe) Increase in the size of a tissue because its cells enlarge without undergoing cell division.

Metaplasia (met'-a-PLA-ze-a; meta- = change) The transformation of one type of cell into another.

Progeny (PROJ-e-ne;pro- = forward; -geny = production) Offspring or descendants.

Proteomics (pro' -te-O-miks; protea- = protein) The study of the proteome (all of an organism's proteins) in order to identify all the proteins produced; it involves determining the three-dimensional structure of proteins so that drugs can be designed to alter protein activity to help in the treatment and diagnosis of disease.

Tissue rejection An immune response of the body directed at foreign proteins in a transplanted tissue or organ;

14 2 Chemistry, Cells, and Tissues

immunosuppressive drugs, such as cyclosporine, have largely over-come tissue rejection in heart-, kidney-, and liver-transplant patients.

Tissue transplantation The replacement of a diseased or injured tissue or organ. The most successful transplants involve use of a person's own tissues or those from an identical twin.

Tuntor marker A substance introduced into circulation by tumor cells that indicates the presence of a tumor, as

well as the specific type. Tumor markers may be used to screen, diagnose, make a prognosis, evaluate a response to treatment, and monitor for recurrence of cancer.

Xenotransplantation (zen' -6-trans-plan-TA-shun; xeno-= strange, foreign) The replacement of a diseased or injured tissue or organ with cells or tissues from an animal. Porcine (from pigs) and bovine (from cows) heart valves are used for some heart-valve replacement surgenes.