Biophysical

MACROPHAGE INFLAMMATORY PROTEIN 1 ALPHA(MIP-1 ALPHA)

Macrophage inflammatory proteins are produced by white blood cells called macrophages after stimulation from bacteria. These proteins stimulate the activity of other white blood cells (called neutrophils, eosinophils, and basophils) in response to infection or inflammation. The two macrophage inflammatory proteins (MIP-1 alpha and MIP-1 beta) are the major factors produced by macrophages stimulated with bacterial endotoxins. Both are involved in the activation of granulocytes and appear to be involved in acute neutrophilic inflammation. Both also stimulate the production of reactive oxygen species in neutrophils, stimulate the release of lysosomal enzymes, and induce the synthesis of other pro-inflammatory cytokines in fibroblasts and macrophages. MIP-1 alpha is a potent basophil agonist, inducing a rapid change of cytosolic free calcium and the release of histamine and sulfidoleukotrienes.

MACROPHAGE INFLAMMATORY PROTEIN 1 BETA(MIP-1 BETA)

Macrophage inflammatory proteins are produced by white blood cells called macrophages after stimulation from bacteria. These proteins stimulate the activity of other white blood cells (called neutrophils, eosinophils, and basophils) in response to infection or inflammation. The two macrophage inflammatory proteins (MIP-1 alpha and MIP-1 beta) are the major factors produced by macrophages stimulated with bacterial endotoxins. Both are involved in the activation of granulocytes and appear to be involved in acute neutrophilic inflammation. Both also stimulate the production of reactive oxygen species in neutrophils, stimulate the release of lysosomal enzymes, and induce the synthesis of other pro-inflammatory cytokines in fibroblasts and macrophages.

MAGNESIUM(Mg)

Magnesium (Mg) is a mineral involved in many bodily processes, including nerve signaling, the building of healthy bones, and muscle contraction. It is important in the normal functioning of more than 300 enzymes in the body. Low blood levels of magnesium may result from a number of conditions including chronic diarrhea, chronic vomiting, hyperaldosteronism, celiac disease, and others. Magnesium is a cofactor for more than 300 human enzymes. It is an activator of many enzyme systems and is important in oxidative phosphorylation, glycolysis, cell replication, nucleotide metabolism, and protein biosynthesis. Because magnesium inhibits the entry of calcium into neurons, low magnesium levels result in increased neuromuscular excitability. Hypermagnesemia may result from renal failure, adrenal insufficiency, hypothyroidism, tissue breakdown, or the overuse of antacids or laxatives. Hypomagnesemia may result from malabsorption, starvation, severe diarrhea, chronic vomiting, celiac sprue, chronic renal failure with wasting, renal tubular acidosis, acute pancreatitis, hyperthyroidism, hyperparathyroidism, diabetes mellitus, hyperaldosteronism, and the use of certain medications.

MATRIX METALLOPROTEINASE 2(MMP-2)

Matrix metalloproteinases, such as MMP-2 (also called gelatinase A), are enzymes that break down the structural proteins that hold tissues together. The blood levels of several of these enzymes may be elevated during normal wound healing, pregnancy, and the creation of new blood vessels, but these levels may also be elevated in various diseases involving tissue destruction and/or inflammation, including various cancers, periodontitis, rheumatoid arthritis, osteoarthritis, ulcerated wounds, and certain autoimmune diseases. Under physiologic conditions, MMPs are involved in extracellular degradation and breakdown of matrix proteins during normal tissue remodeling processes such as wound healing, pregnancy, and angiogenesis. However, the release of these enzymes by various cell types has also been implicated in the pathogenesis of many diseases, including periodontitis, rheumatoid arthritis, osteoarthritis, glomerulonephritis, chronic ulcerations, uterine involution, autoimmune disorders of skin and dermal photoaging, and tumor progression and metastasis. It has been suggested that tissue destruction in disease processes often correlates with an imbalance of MMPs over their protein inhibitors, tissue inhibitors of MMPs (TIMPs).

MATRIX METALLOPROTEINASE 3(MMP-3)

Matrix metalloproteinases (MMPs) are enzymes that break down the structural proteins that hold tissues together. The blood levels of several of these enzymes may be elevated during normal wound healing, pregnancy, and the creation of new blood vessels, but these levels may also be elevated in various diseases involving tissue destruction and/or inflammation, including various cancers, periodontitis, rheumatoid arthritis, osteoarthritis, ulcerated wounds, and certain autoimmune diseases. Under physiologic conditions, MMPs are involved in extracellular degradation and breakdown of matrix proteins during normal tissue remodeling processes such as wound healing, pregnancy, and angiogenesis. However, the release of these enzymes by various cell types has also been implicated in the pathogenesis of many diseases, including periodontitis, rheumatoid arthritis, osteoarthritis, glomerulonephritis, chronic ulcerations, uterine involution, autoimmune disorders of skin and dermal photoaging, and tumor progression and metastasis. It has been suggested that tissue destruction in disease processes often correlates with an imbalance of MMPs over their protein inhibitors, tissue inhibitors of MMPs (TIMPs). Levels of MMP-3 (also termed stromelysin-1, transin-1, proteoglycanase, and pro-collagenase activating protein) have been found to be elevated in a number of unrelated diseases, including meningococcal meningitis, chronic transplant nephropathy, coronary aneurysms, rheumatoid arthritis (especially in the presence of cartilage damage), psoriatic arthritis, systemic lupus erythematosus, and mixed connective tissue disease.

MATRIX METALLOPROTEINASE 9(MMP-9)

Matrix metalloproteinases (MMPs) are enzymes that break down the structural proteins that hold tissues together. The blood levels of several of these enzymes may be elevated during normal wound healing, pregnancy, and the creation of new blood vessels, but these levels may also be elevated in various diseases involving tissue destruction and/or inflammation, including various cancers, periodontitis, rheumatoid arthritis, osteoarthritis, ulcerated wounds, and certain autoimmune diseases. Under physiologic conditions, MMPs are involved in extracellular degradation and breakdown of matrix proteins during normal tissue remodeling processes such as wound healing, pregnancy, and angiogenesis. However, the release of these enzymes by various cell types has also been implicated in the pathogenesis of many diseases, including periodontitis, rheumatoid arthritis, osteoarthritis, glomerulonephritis, chronic ulcerations, uterine involution, autoimmune disorders of skin and dermal photoaging, and tumor progression and metastasis. It has been suggested that tissue destruction in disease processes often correlates with an imbalance of MMPs over their protein inhibitors, tissue inhibitors of MMPs (TIMPs). MMP-9 (also known as gelatinase B) is often expressed by human cancer cells. Elevated plasma levels have been observed in patients with abdominal aortic aneurysm and giant cell arteritis, and elevated CSF levels in patients with multiple sclerosis.

MEAN CORPUSCULAR HEMOGLOBIN(MCH)

Mean corpuscular hemoglobin (MCH) is an estimate of the amount of hemoglobin carried by each red blood cell. Hemoglobin is the iron-binding protein that carries oxygen. MCH may be low due to blood loss or anemia. An abnormally elevated MCH (over 34%) may result from macrocytic anemia, while an abnormally low MCH (below 26%) may occur due to blood loss over time, too little iron in the body, microcytic anemia, or hemoglobinopathies.

MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION(MCHC)

Mean corpuscular hemoglobin concentration (MCHC) is an estimate of the level of hemoglobin (the iron-binding protein that carries oxygen) in a given number of packed and transfusable red blood cells. An abnormally elevated MCHC (over 36%) may be due to spherocytosis, unstable hemoglobin, or vitamin B12 or folic acid deficiency. An abnormally low MCHC (below 28%) may be due to blood loss over time, iron deficiency, or hypochromic anemia.

MEAN CORPUSCULAR VOLUME(MCV)

Mean corpuscular volume is the average amount of space occupied by each red blood cell. Causes of a high MCV include liver disease, alcohol abuse, hypothyroidism, reticulocytosis, marrow aplasia, vitamin B12 or folic acid deficiency, and myelofibrosis. Causes of a low MCV include iron deficiency anemia, lead poisoning, chronic kidney failure, hemoglobinopathy, and certain other anemias.

MITOCHONDRIAL ANTIBODY

Mitochondria are the parts of our cells that produce energy. Antibodies against mitochondria are produced in some autoimmune conditions. The detection of mitochondrial antibodies is useful in the evaluation of a number of conditions. Various subtypes of these antibodies have been associated with primary biliary cirrhosis, syphilis, pseudosyphilis, and isoniazid-induced hepatitis. A titer of above 50 IU/ml of M2 mitochondrial antibodies suggests primary biliary cirrhosis even in the absence of symptoms and the presence of normal alkaline phosphatase levels.

MONOCYTE CHEMOTACTIC PROTEIN-1(MCP-1)

Monocyte chemotactic protein-1 (MCP-1) is a cell signaling protein produced by the body in response to inflammation. It attracts white blood cells to the inflamed area to combat disease-causing organisms (such as bacteria or viruses). MCP-1 levels are elevated in a variety of infections and inflammatory processes. Monocyte chemotactic protein-1 (also called small inducible cytokine A2 and monocyte chemotactic and activating factor) plays a role in the recruitment of monocytes to sites of injury and infection. It has been found in the joints of rheumatoid arthritis patients, where it may recruit macrophages and perpetuate joint inflammation. Elevated levels of MCP-1 have also been found in the urine of systemic lupus erythematosus patients as a sign of renal inflammation.

MONOCYTE COUNT

Monocytes are a type of white blood cell involved in the immune response to foreign substances. The monocyte number is often increased in response to chronic infections, inflammatory bowel disease, leukemia, and certain cancers. It may be decreased in people who have anemia or are taking corticosteroids. Monocytes help to remove necrotic tissues and account for 2% to 8% of circulating leukocytes. After a few hours in the bloodstream, they migrate into tissues and mature into macrophages. An increased monocyte number (monocytosis) occurs in response to viral or parasitic infection, inflammatory bowel disease, sarcoidosis, monocytic leukemia, lymphoma, multiple myeloma, and certain neoplasms. A low monocyte number (monocytopenia) can occur in aplastic or lymphocytic anemia and in patients receiving corticosteroids.

MONOCYTE PERCENTAGE

Monocytes are a type of white blood cell involved in the immune response to foreign substances. The monocyte number is often increased in response to chronic infections, inflammatory bowel disease, leukemia, and certain cancers. It may be decreased in people who have anemia or are taking corticosteroids. Monocytes help to remove necrotic tissues and account for 2% to 8% of circulating leukocytes. After a few hours in the bloodstream, they migrate into tissues and mature into macrophages. An increased monocyte number (monocytosis) occurs in response to viral or parasitic infection, inflammatory bowel disease, sarcoidosis, monocytic leukemia, lymphoma, multiple myeloma, and certain neoplasms. A low monocyte number (monocytopenia) can occur in aplastic or lymphocytic anemia and in patients receiving corticosteroids.

MUMPS ANTIBODY

Antibodies against the paramyxovirus that causes mumps indicate either prior exposure or vaccination. Children with type 1 diabetes mellitus tend to have unusually low IgG mumps virus antibody levels.

MYCOBACTERIA TUBERCULOSIS ANTIBODY(M. TUBERCULOSIS Ab)

Mycobacteria tuberculosis is the bacterium that causes tuberculosis (TB). The presence of antibodies against this bacterium indicates recent exposure to or infection with it. Ninety percent of those infected have asymptomatic latent TB infection, with a 10% lifetime risk of progression to active disease. Tuberculosis is the most common major infectious disease in the world, with about 2 billion people infected. The World Health Organization declared tuberculosis to be a global health emergency in 1993.

MYCOPLASMA PNEUMONIAE ANTIBODY(M. PNEUMONIAE Ab)

Mycoplasma pneumoniae is a bacterium that causes respiratory infections, including pneumonia. The presence of antibodies to Mycoplasma pneumoniae indicates recent exposure to or infection with these bacteria. Mycoplasma pneumoniae is the causative organism in 15% to 20% of pneumonia cases but can also cause asymptomatic respiratory infections, acute tracheobronchitis, or Stevens-Johnson syndrome. Levels of IgG and IgM antibodies vary according to time after the onset of illness and patient age; adults tend to have higher IgG antibody levels than do children.

MYELOPEROXIDASE ANTIBODY(MPO Ab)

Myeloperoxidase (MPO) is an enzyme primarily found in neutrophils (a type of white blood cell). Antibodies against this enzyme appear to play a role in the development of certain kidney and blood vessel diseases. Antibodies against MPO are a subclass of anti-neutrophil cytoplasmic antibodies (ANCAs). They are associated with various disorders, including Churg-Strauss syndrome, crescentic glomerulonephritis, microscopic polyangiitis, polyarteritis nodosa, Wegener’s granulomatosis, and possibly lupus nephritis, Henoch-Schonlein purpura, and giant cell arteritis.

MYOGLOBIN

Myoglobin is the primary oxygen-carrying protein in muscle tissues. Its presence in the blood indicates muscle injury, either to skeletal muscles or to the heart muscle during a heart attack. When muscles are severely damaged by injury or disease, the release of myoglobin may cause kidney damage. Myoglobin is a monomeric heme protein that is structurally related to hemoglobin and found predominantly in skeletal and cardiac muscle. During the course of a myocardial infarction, myoglobin is released from the ischemic myocardium. Elevated levels may be detected as early as 30 minutes after chest pain begins and generally peak after 6 to 12 hours and return to baseline within 24 to 36 hours. Skeletal muscles can be damaged by a wide variety of pathological processes, causing release of myoglobin into the circulation (rhabdomyolysis) and myoglobinuria. In rhabdomyolysis, a high serum myoglobin level, especially with a low urine myoglobin clearance rate, indicates a high risk for renal failure due to the damage done to the kidneys by myoglobin and its metabolites.

NEUTROPHIL COUNT

Neutrophils are a type of white blood cell whose numbers are elevated in the presence of bacterial and other infections, tissue injury and inflammation, stress, certain metabolic conditions, myeloproliferative disorders, metastatic cancer, and some medications. The neutrophil number is decreased in cases of depressed neutrophil production, such as leukemia or aplastic anemia, and in cases of neutrophil destruction, such as sepsis or systemic lupus erythematosus.

NEUTROPHIL PERCENTAGE

Neutrophils are a type of white blood cell involved in the immune response to infection, primarily bacterial infection. The neutrophil percentage is often increased in the presence of bacterial infection and other conditions such as tissue injury, stress, inflammation, and certain metabolic conditions. The neutrophil percentage may be decreased in conditions that suppress production or increase destruction.

PANCREATIC ISLET CELL ANTIBODY

Type 1 (“juvenile”) diabetes mellitus is most likely an autoimmune disease in which the body’s own antibodies have destroyed the insulin-producing islet cells of the pancreas. This produces a deficiency of insulin, which normally regulates glucose levels in the blood. Autoantibodies against various pancreatic islet cell antigens are present in more than 80% of type 1 diabetes patients and predict the development of this disease, particularly if high, persistent titers are present and the patient is young. The seroprevalence of these antibodies in healthy children is about 4%, corresponding to the prevalence of type 1 diabetes. Islet cell antibodies are also present in some patients with autoimmune disorders or schistosomiasis.

PARAINFLUENZA TYPE 1 ANTIBODY

Parainfluenza viruses typically cause respiratory infections. The presence of antibodies against a parainfluenza virus indicates recent exposure or infection. Parainfluenza viruses are categorized into types 1, 2, 3, and 4, of which types 1, 2, and 3 are most common. Types 1 and 2 can cause epidemic laryngotracheobronchitis (croup) and sometimes colds, pharyngitis, and tracheobronchitis in children during the fall. Localized outbreaks may occur in nurseries, schools, pediatric wards, and similar settings. Reinfection generally causes mild upper respiratory illnesses and may be asymptomatic in adults.

PARAINFLUENZA TYPE 2 ANTIBODY

Parainfluenza viruses typically cause respiratory infections. The presence of antibodies against a parainfluenza virus indicates recent exposure or infection. Parainfluenza viruses are categorized into types 1, 2, 3, and 4, of which types 1, 2, and 3 are most common. Types 1 and 2 can cause epidemic laryngotracheobronchitis (croup) and sometimes colds, pharyngitis, and tracheobronchitis in children during the fall. Localized outbreaks may occur in nurseries, schools, pediatric wards, and similar settings. Reinfection generally causes mild upper respiratory illnesses and may be asymptomatic in adults.

PARAINFLUENZA TYPE 3 ANTIBODY

Parainfluenza viruses typically cause respiratory infections. The presence of antibodies against a parainfluenza virus indicates recent exposure or infection. Parainfluenza viruses are categorized into types 1, 2, 3, and 4, of which types 1, 2, and 3 are most common. Types 1 and 2 can cause epidemic laryngotracheobronchitis (croup) and sometimes colds, pharyngitis, and tracheobronchitis in children during the fall. Localized outbreaks may occur in nurseries, schools, pediatric wards, and similar settings. Reinfection generally causes mild upper respiratory illnesses and may be asymptomatic in adults.

PARATHYROID HORMONE(PTH)

Parathyroid hormone (PTH) is made in the parathyroid tissues near the thyroid gland in the neck. Levels of this hormone tightly control the level of calcium in the body. PTH levels may be abnormal in several kidney and metabolic disorders. Parathyroid hormone is a major regulator of the extracellular calcium concentration. It increases extracellular calcium by increasing calcium reabsorption in the kidneys and stimulating the release of calcium from skeletal calcium stores. Rising levels of extracellular calcium normally suppress PTH production through a negative feedback mechanism. High PTH levels may be associated with renal failure, hypomagnesemia, and gastrointestinal malabsorption, while low levels may occur in adrenal insufficiency, hyperthyroidism, and parathyroid malignancies.

PHOSPHORUS(P)

Phosphorus (P) is a basic element that is found throughout the body. Most of the body’s phosphorus is bound to calcium in the bones, but about 15% exist in the blood and other soft tissues and body fluids. Phosphorus is very important in metabolism. More than 80% of the body’s phosphorus exist as calcium phosphate in the skeleton; the remainder is a component of phospholipids, nucleic acids, and ATP. Nearly all serum phosphorus is present as inorganic phosphate, levels of which are controlled by parathyroid hormone, vitamin D, and calcitonin. Hyperphosphatemia has been observed in bone metastasis, hypocalcemia, hypoparathyroidism, liver disease, sarcoidosis, Addison’s disease, hypervitaminosis D, magnesium deficiency, myelogenous leukemia, and renal failure. Hypophosphatemia may occur in rickets, osteomalacia, diabetic ketoacidosis, hyperparathyroidism, hyperinsulinism, hypercalcemia, vitamin D deficiency, Gram-negative sepsis, and alcoholism, and in patients taking diuretics, corticosteroids, or aluminum hydroxide antacids.

PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1(PAI-1)

Plasminogen activator inhibitor type 1 (PAI-1) blocks the activity of tissue plasminogen activator, which is the key enzyme involved in the breakdown of blood clots. Elevated levels of PAI-1 are associated with increased clotting and an increased risk of heart attack. Plasminogen activator inhibitor type 1 is an inhibitor of tissue plasminogen activator (tPA), a key enzyme in fibrinolysis. PAI-1 is synthesized by endothelial cells, activated platelets, and hepatocytes. As PAI-1 levels increase, active levels of tPA decrease, causing impaired fibrinolytic function. Elevated levels of PAI-1 have been observed in patients with deep vein thrombosis and myocardial infarction, as well as in normal pregnancy and sepsis.

PLATELET COUNT

Platelets are cellular elements involved in the blood clotting process. When a blood vessel is damaged, platelets clump together and help to initiate clotting. Abnormal platelet levels are found in a variety of blood-related and autoimmune diseases. Platelets are necessary for normal hemostasis, both because they aggregate to form clots and because they activate Factor VIII and release phospholipids necessary for coagulation. Potential causes of thrombocytopenia include various drugs, radiation, disseminated intravascular coagulation, aplastic or hemolytic anemia, hemolytic uremic syndrome, idiopathic thrombocytopenic purpura, leukemia, lymphoma, vasculitis, systemic lupus erythematosus, HIV, cytomegalovirus, sepsis, prosthetic heart valves, and massive blood transfusions. Thrombocytosis may be associated with polycythemia vera, post-splenectomy syndrome, inflammatory bowel disease, alcohol abuse, pancreatitis, cirrhosis, hemophilia, myelofibrosis, certain drugs, certain malignancies, and chronic myelogenous leukemia.

PM-1 ANTIBODY

Polymyositis is an autoimmune inflammatory disease of the connective tissues. The presence of Pm1 antibodies strongly suggests polymyositis, although levels of this antibody may also be elevated in other autoimmune diseases. About 60% of patients with myositis (primary idiopathic polymyositis, childhood polymyositis or dermatomyositis, primary idiopathic dermatomyositis in adults, inclusion body myositis, polymyositis or dermatomyositis associated with malignant tumors, or polymyositis or dermatomyositis associated with various connective tissue disease overlap syndromes) have antibodies to either Pm1 or Jo-1, although the relationship between these autoantibodies and the disease process remains unclear. Myositis may appear at any age but occurs most commonly between ages 5 and 15 and between ages 40 and 60.

POLIO ANTIBODY

The polio antibody test determines whether an individual has been recently vaccinated against or infected with the virus that causes polio. Polio is an epidemic infection that affects the brain and spinal cord. It has been eliminated in much of the world through universal vaccination.

POTASSIUM(K)

Potassium (K) is a positively charged electrolyte whose levels are tightly controlled throughout the body. Potassium plays an important role in the electrical conduction of signals in nerve, muscle, and heart tissues. A variety of hormonal, metabolic, and kidney conditions can cause abnormal potassium levels. Potassium is particularly important for maintaining the electric charge on the cell membrane. Potassium levels are mainly controlled by aldosterone. Causes of hyperkalemia include hypoaldosteronism, diabetes mellitus, interstitial nephritis, renal insufficiency, congestive heart failure, acidosis, dialysis, coronary bypass, gastrointestinal bleeding, and the use of heparin, potassium-sparing diuretics, succinylcholine, beta-blockers, high- dose penicillin, digitalis, arginine, or NSAIDs. Causes of hypokalemia include renal potassium loss, vomiting, chronic diarrhea, acute leukemia, metabolic acidosis or alkalosis, delirium tremens, and the use of beta-agonists, insulin excess, aminoglycosides, or high-dose penicillin. Abnormal potassium levels can lead to cardiac arrest.

PREGNANCY-ASSOCIATED PLASMA PROTEIN A(PAPP-A)

Pregnancy-associated plasma protein A (PAPP-A) is an enzyme first identified in the blood of pregnant women. Unusually low blood levels of PAPP-A during the first trimester of pregnancy indicate an increased risk of premature delivery, stillbirth, or other problems with the pregnancy. PAPP-A levels can also predict the likelihood of a heart attack or death in patients experiencing acute chest pain due to coronary artery disease. PAPP-A is a metalloproteinase widely used for the screening of fetal trisomy during the first trimester of pregnancy. Unusually low levels at 8 to 14 weeks of gestation indicate an increased risk of intrauterine growth restriction, trisomy 21, premature delivery, preeclampsia, and stillbirth. PAPP-A is also abundantly expressed by unstable atherosclerotic plaques and as a marker of plaque stability; its level is a strong independent predictor of cardiovascular events in patients with acute coronary syndromes.

PROGESTERONE

Progesterone is an important female sex hormone. Progesterone levels are normally elevated during the reproductive period of a woman’s life and become lower during menopause. Progesterone is produced by the corpus luteum and is necessary for proper uterine and breast development and function. Its levels are low during the follicular phase of the menstrual cycle and high during the luteal phase; they continue to rise during early pregnancy. High progesterone levels suggest pregnancy, ovarian cancer, or adrenal cancer, while low levels may occur in amenorrhea, fetal death, and toxemia of pregnancy. Synthetic progestins have been linked to the risk of heart disease, but more research is needed to confirm this relationship.

PROLACTIN

Prolactin is a hormone that is made in the pituitary gland and helps to initiate and maintain milk production in women. Its levels are naturally high while breast-feeding, but high levels at other times may indicate disease. Physiologically, it initiates and maintains lactation; its release is primarily stimulated by suckling. Causes of hyperprolactinemia include pituitary tumors, hypothalamic disease or injury, chronic renal failure, multiple sclerosis, hypothyroidism, ectopic tumors, syringomyelia, tabes dorsalis, breast trauma, polycystic ovarian syndrome, and hepatic cirrhosis. Prolactin levels are useful in the evaluation of pituitary tumors and their treatment, as well as the assessment of hypothalamic abnormalities, infertility, amenorrhea, and galactorrhea.

PROLIFERATING CELL NUCLEAR ANTIGEN ANTIBODY(PCNA Ab)

Proliferating cell nuclear antigen (PCNA) is an important enzyme in the synthesis and repair of DNA. In patients with systemic lupus erythematosus, antibodies to PCNA are associated with kidney damage, nervous system damage, and low platelet counts. PCNA antibodies have also been found in patients with chronic hepatitis. The presence of PCNA autoantibodies is associated with renal and CNS involvement and thrombocytopenia in patients with systemic lupus erythematosus (SLE). PCNA autoantibodies have been detected in up to 31% of SLE patients; autoantibody titers are elevated prior to the development of proteinuria and decrease following corticosteroid treatment. Antibodies to PCNA have also been observed in patients with chronic hepatitis B or C infection. PCNA is also known as DNA polymerase-d auxiliary protein.

PROSTATE-SPECIFIC ANTIGEN, FREE(PSA, FREE)

Prostate-specific antigen (PSA) is highly specific for prostate tissue, and its levels may be increased in prostate cancer, benign prostatic hyperplasia (BPH), and prostatitis. Most of the measurable PSA in serum is complexed with alpha-1-antichymotrypsin, but PSA also occurs in a free form. A total PSA of 3.0 to 4.0 ng/ml with a free PSA less than 19% suggests prostate cancer, as does a total PSA above 4.0 ng/ml with a free PSA less than 24%. In about 70% of cases, a significant increase in PSA levels indicates prostate cancer, but because many prostate cancer patients have normal PSA levels, diagnosis also involves digital rectal examination and transrectal ultrasonography.

PROSTATE-SPECIFIC ANTIGEN, TOTAL(PSA, TOTAL)

Prostate-specific antigen (PSA) is highly specific for prostate tissue and its levels may be increased in prostate cancer, benign prostatic hyperplasia (BPH), and prostatitis. Most of the measurable PSA in serum is complexed with alpha-1-antichymotrypsin, but PSA also occurs in a free form. A total PSA of 3.0 to 4.0 ng/ml with a free PSA less than 19% suggests prostate cancer, as does a total PSA above 4.0 ng/ml with a free PSA less than 24%. In about 70% of cases, a significant increase in PSA levels indicates prostate cancer, but because many prostate cancer patients have normal PSA levels, diagnosis also involves digital rectal examination and transrectal ultrasonography.

PROSTATIC ACID PHOSPHATASE(PAP)

Prostatic acid phosphatase (PAP) is found primarily (but not solely) in the prostate gland and the semen. PAP levels may be abnormal in a number of conditions, including prostate cancer, Paget’s disease, anemia, infection, thrombophlebitis, Gaucher’s disease, hyperparathyroidism, myocardial infarction, and multiple myeloma. They may also be transiently elevated after prostatic massage, needle biopsy, or cystoscopy. PAP levels may be used in the staging of prostate carcinoma, the diagnosis of metastatic adenocarcinoma of the prostate, and the monitoring of prostate cancer therapy.

PROTEINASE 3 ANTIBODY(PR3 Ab)

The presence of antibodies against the proteinase 3 enzyme (which is produced by white blood cells in patients with certain autoimmune diseases) appears to be associated with autoimmune conditions such as Wegener’s granulomatosis. Levels of these antibodies can be used to monitor the activity of these diseases. Proteinase 3 (PR3), found in the granules of neutrophils and monocytes in patients with Wegener’s granulomatosis, is the major target antigen for anti-neutrophil cytoplasmic autoantibodies (ANCAs). PR3 autoantibodies are sensitive and specific markers for Wegener’s granulomatosis and can be used to monitor disease activity.

RED BLOOD CELL COUNT(RBC COUNT)

The red blood cell count (RBC count) indicates the absolute number of red blood cells in the blood. An abnormally high erythrocyte count may be associated with cardiovascular disease, polycythemia vera, tobacco abuse, renal cell carcinoma, stress, high altitude, or dehydration. An abnormally low count may indicate anemia, acute hemorrhage, marrow failure, or chronic renal failure.

RED CELL DISTRIBUTION WIDTH(RDW)

This test measures the variability in size of the red blood cell population. When used in conjunction with mean corpuscular volume (MCV), this test is useful in diagnosing a variety of conditions.

REGULATED UPON ACTIVATION, NORMAL T-CELL EXPRESSED AND SECRETED(RANTES)

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a protein that attracts various types of white blood cells and brings them to sites of inflammation. Levels of RANTES may be elevated in inflammatory and allergic conditions. RANTES (also called CCL5) is produced by T-cells and is chemotactic for T-cells, eosinophils, and basophils. It plays an active role in recruiting leukocytes to inflammatory sites and also activates eosinophils and basophils and stimulates IgE production.

RESPIRATORY SYNCYTIAL VIRUS ANTIBODY(RSV Ab)

Respiratory syncytial viruses (RSV) may cause serious respiratory tract infections in infants and young children. The presence of the antibody against RSV indicates exposure to or infection with this virus but does not protect against being infected with it again. RSV can be fatal, and sudden deaths occurring in infants with respiratory disease are often believed to be due to this virus. In older children and adults, RSV may cause an influenza-like syndrome, bronchopneumonia, or exacerbations of chronic bronchitis. Although about 70% of the population have serum antibodies to RSV by the age of 5, these antibodies are not considered protective, since reinfection can occur.

RHEUMATOID FACTOR(RF)

Rheumatoid factor (RF) is an immune system protein whose presence generally indicates one of a variety of autoimmune diseases. RF levels are particularly high in rheumatoid arthritis and Sjögren’s syndrome. Serum rheumatoid factor represents the immune system response to the presence of a “non-self” immunoglobulin molecule, which results in the formation of immune complexes. These bind complement and may eventually lead to synovium, cartilage, and bone destruction. RF may be found in a variety of autoimmune diseases, including rheumatoid arthritis (80% to 90%), Sjögren’s syndrome (75% to 95%), systemic lupus erythematosus (15% to 35%), scleroderma (20% to 30%), polymyositis or dermatomyositis (10%), and mixed connective tissue disease (50% to 60%). It also occurs in up to 10% of apparently healthy individuals, with an incidence that increases with age. In addition, RF assays may be positive in some patients with syphilis, osteomyelitis, tuberculosis, bacterial endocarditis, hepatitis, mononucleosis, cirrhosis, sarcoidosis, or diffuse interstitial pulmonary fibrosis.

RIBOSOMAL NUCLEAR PROTEIN ANTIBODY

Ribosomal nuclear protein (RNP) antibodies are antibodies against molecules in the nuclei of our cells. Antibodies to nuclear antigens are strongly associated with collagen vascular diseases including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), progressive systemic sclerosis (PSS), and Sjögren’s syndrome (SS). RNP antibodies are found in 95% to 100% of patients with MCTD and are considered specific for this syndrome if other antibodies are negative. They also occur in 20% to 30% of patients with SLE and 15% to 25% of patients with progressive systemic sclerosis (PSS).

RIBOSOMAL NUCLEAR PROTEIN A ANTIBODY(RNP A Ab)

Ribosomal nuclear protein A (RNP A) antibodies are antibodies against molecules in the nuclei of our cells. Antibodies to nuclear antigens are strongly associated with collagen vascular diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), progressive systemic sclerosis (PSS), and Sjögren’s syndrome. RNP antibodies are found in 95% to 100% of patients with MCTD and are considered specific for this syndrome if other antibodies are negative. They also occur in 20% to 30% of patients with SLE and 15% to 25% of patients with progressive systemic sclerosis (PSS).

RIBOSOMAL NUCLEAR PROTEIN C ANTIBODY(RNP C Ab)

Ribosomal nuclear protein C (RNP C) antibodies are antibodies against molecules in the nuclei of our cells. Antibodies to nuclear antigens are strongly associated with vascular diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), progressive systemic sclerosis (PSS), and Sjögren’s syndrome. RNP antibodies are found in 95% to 100% of patients with MCTD and are considered specific for this syndrome if other antibodies are negative. They also occur in 20% to 30% of patients with SLE and 15% to 25% of patients with progressive systemic sclerosis (PSS).

RIBOSOMAL P ANTIBODY

Ribosomal P antibodies are antibodies against one of the parts of our cells. Autoantibodies against cytoplasmic ribosomes are highly specific for systemic lupus erythematosus (SLE) and are considered markers. Ribosomal P antibodies are found in about 12% of patients with SLE and in 90% of those with lupus psychosis.

RUBELLA ANTIBODY

Rubella (also called “German measles”) is a contagious but mild disease that causes a rash, a fever, and swollen lymph glands. Rubella syndrome refers to the devastating birth defects that affect about a quarter of the fetuses exposed to rubella during pregnancy. Rubella syndrome is a spectrum of congenital defects that can include cataracts, deafness, glaucoma, congenital heart disease, microcephaly, growth retardation, and mental retardation. Between 10% and 20% of newborns infected in utero fail to survive for 12 months. Since these complications are so severe, diagnosis of infection during the first trimester may affect the decision to terminate or continue the pregnancy. It is important, therefore, to determine the rubella immune status in women of child-bearing age, pregnant women, and individuals who may have close contact with them. In a primary rubella infection, the appearance of both IgG and IgM antibodies is associated with the appearance of clinical signs and symptoms when present. IgM antibodies become detectable a few days after the onset of signs and symptoms and reach peak levels in 7 to 10 days. Their level then diminishes over the next 4 to 5 weeks until they are no longer clinically detectable. Rubella IgM antibodies in a newborn’s serum suggest congenital infection, since IgM from the mother is not transferred across the placenta, and may persist for several months.

RUBEOLA ANTIBODY

The presence of antibodies against rubeola (the measles virus) indicates recent vaccination against this virus, exposure to it, or infection with it. Since mass immunization began in the United States over two decades ago, the number of measles infections has been greatly reduced, although many individuals remain susceptible due to vaccine failure or non-immunization. The presence of measles antibodies confirms seroconversion after vaccination and is useful in the evaluation of the rare but fatal subacute sclerosing panencephalitis (SSPE), which may occur years after the original measles infection.

SCLERODERMA 70 ANTIBODY(Scl-70 Ab)

The presence of the scleroderma 70 (Scl-70) antibody indicates an autoimmune condition called scleroderma. However, it may also occur in other connective tissue and rheumatic diseases such as systemic lupus erythematosus. When Scl-70 antibody is the only autoantibody present, it is a specific marker for scleroderma, although Scl-70 antibodies are also seen in 25% of progressive systemic sclerosis patients. These antibodies are more prevalent in patients with diffuse scleroderma (>70%) compared with those with milder disease.

SERUM AMYLOID P(SAP)

Serum amyloid P (SAP) is a protein that is found in normal serum and in amyloid plaques (protein deposits in the tissues) and involved in immune system responses. Elevation of amyloid P levels may be an indicator of liver disease or neurological disorders such as Alzheimer’s disease. Amyloid P prevents fibrillar breakdown by enzymes, interacts with inflammatory and complement factors, modulates immunologic responses, and inhibits elastase.

SEX HORMONE-BINDING GLOBULIN(SHBG)

Abnormal levels of sex hormone-binding globulin (SHBG) may occur in a variety of diseases or in pregnancy. SHBG is a beta-globulin that binds sex hormones with a high affinity for dihydrotestosterone and a low affinity for estradiol. Levels of SHBG are under the positive control of estrogens and thyroid hormones and are suppressed by androgens. Decreased SHBG levels may occur in hirsutism, virilization, obese postmenopausal women, and women with diffuse hair loss. Increased levels may occur in hyperthyroidism, testicular feminization, cirrhosis, male hypogonadism, pregnancy, and during oral contraceptive use.

SMITH ANTIBODY(SM Ab)

The presence of the Smith (Sm) antibody suggests the presence of an autoimmune disease such as systemic lupus erythematosus, mixed connective tissue disease, progressive systemic sclerosis, or Sjögren’s syndrome. Sm antibodies (also called anti-Smith antibodies) are highly specific for SLE but occur in only 30% to 35% of cases; they are often associated with lupus nephritis. In SLE patients, the presence of RNP antibodies is associated with a relatively benign course, while the presence of Sm antibodies without RNP antibodies indicates a high risk of renal and central nervous system involvement. Increased titers of Sm antibody predict disease relapse in 50% of patients.

SODIUM(Na)

Sodium (Na) is an important positively charged electrolyte that is vital to cell functions. Its levels in the body are tightly controlled by many hormonal and metabolic mechanisms. Sodium levels may be abnormal in a variety of diseases. Sodium is the major positive ion in extracellular fluid. Many factors affect sodium levels, including aldosterone, which reduces sodium loss in the urine. Hypernatremia may occur in burns, excessive sweating, diarrhea, diabetes insipidus, hyperaldosteronism, Cushing’s syndrome, acute tubular necrosis, or after ingesting salt or sodium bicarbonate or using osmotic or loop diuretics. Hyponatremia may be due to dehydration, overdiuresis, ketonuria, vomiting, diarrhea, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, Addison’s disease, kidney failure, congestive heart failure, nephrotic syndrome, or cirrhosis.

SSA ANTIBODY

SSA antibodies react to molecules in the nuclei of our cells. Antibodies to nuclear antigens are hallmarks of collagen vascular diseases including systemic lupus erythematosus (SLE), mixed connective tissue disease, progressive systemic sclerosis (PSS), and Sjögren’s syndrome. SSA (Ro) antibodies are found in 70% to 75% of patients with Sjögren’s syndrome, 30% to 40% of patients with SLE, and 5% to 10% of patients with PSS. SSB (La) antibodies are found in about 50% to 60% of patients with Sjögren’s syndrome but are only specific markers when they are the sole antibodies to extractable nuclear antigen present. Some 15% to 25% of SLE patients and 5% to 10% of PSS patients also carry this antibody. SSA antibodies appear to be strongly associated with neonatal SLE and congenital heart block.

SSB ANTIBODY

SSB antibodies react to molecules in the nuclei of our cells. Antibodies to nuclear antigens are hallmarks of collagen vascular diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), progressive systemic sclerosis (PSS), and Sjögren’s syndrome (SS). SSA and SSB antibodies have been found in some patients who have clinical features of SLE, including prominent cutaneous features, but who frequently fail to demonstrate a positive anti-nuclear antibody. Several studies point to the use of SSB antibodies as a serological marker for Sjögren’s syndrome-sicca complex, since they are detected in about 60% of these patients.

STEM CELL FACTOR(SCF)

Stem cell factor (SCF) is a cytokine (cell signaling protein) synthesized by various connective tissues. It stimulates the production of stem cells, which mature into all the different types of blood cells. SCF may be useful in the treatment of a variety of bone marrow and blood disorders. SCF is a stromal cell-derived cytokine. Its ability to induce differentiation in lymphoid and erythroid progenitor cells and mast cells gives it potential relevance in the treatment of myelodysplastic syndromes and post-bone marrow transplant patients. SCF has been shown to improve in vitro erythropoiesis in several types of inherited marrow failure syndromes, including Diamond-Blackfan anemia, Fanconi’s anemia, dyskeratosis congenita, amegakaryocytic thrombocytopenia, and transient erythroblastopenia of childhood.

STREPTOLYSIN O ANTIBODY

Antibodies against streptolysin O indicate previous infection with a bacterium of the Streptococcus type. Group A streptococcal infection may cause acute rheumatic fever, acute kidney conditions, and skin infections. The streptolysin O antibody (ASO) test provides serologic evidence of previous group A streptococcal infection in patients suspected of having a non- suppurative complication, such as acute glomerulonephritis or acute rheumatic fever. Elevated serum ASO titers are found in 80% to 85% of individuals with rheumatic fever, but skin infections with group A streptococci are often associated with a poor ASO response.

TESTOSTERONE

Testosterone is the major male sex hormone and is produced in the testes. It controls male sexual development and reproduction. Testosterone levels increase during puberty to an adult peak but may decrease in the elderly male. Abnormal testosterone levels may also occur in several glandular conditions. Testosterone is produced by the Leydig cells of the testes. In adult males, testosterone levels show a diurnal variation, with the highest levels detected in the early morning. Levels also increase after exercise and gradually decrease with age. In women, testosterone levels are 5% to 10% of those in males. Only 2% to 3% of testosterone circulate in the free, biologically active form; the remainder is bound to sex hormone-binding globulin or albumin. Serum concentrations of free testosterone are less than 1.5 pg/ml in prepubertal children and increase during puberty to adult values at a rate determined by pubertal stage. Clinical syndromes, in which serum testosterone is increased, include gonadal and adrenal tumors, adrenal hyperplasia, and polycystic ovarian syndrome. Decreased testosterone levels occur in hypogonadism, hypopituitarism, orchiectomy, estrogen therapy, and some cases of Klinefelter’s syndrome.

TETANUS ANTIBODY

Tetanus is a serious infectious disease caused by bacteria. The presence of antibodies against tetanus indicates recent vaccination against, exposure to, or infection with tetanus. Immunization against the tetanus toxin is a very effective preventative measure.

THROMBOPOIETIN(TPO)

Thrombopoietin (TPO) is a protein that stimulates the increase in the size and number of the cells (called megakaryocytes) that are broken down to create platelets. TPO stimulates an increase in megakaryocyte size and number, DNA content, endomitosis, and maturation. It also increases the number of small acetylcholinesterase-positive cells that are early precursor cells of the megakaryocytic lineage. Although interleukin-6 stimulates megakaryocyte production in vitro and increases platelet counts in vivo, it does not appear to be the only factor with TPO activity. TPO is also referred to as c-Mp1 ligand, Mpl ligand, megapoietin, and magakaryocyte growth and development factor.

THYROGLOBULIN ANTIBODY

Antibodies against thyroglobulin may be present in patients with autoimmune thyroiditis (Hashimoto’s thyroiditis) and may confuse the results of thyroglobulin tests. However, detection of these antibodies can help to predict the progression of clinical thyroiditis, to substantiate thyroid disease in patients with non-thyroidal illnesses, and to predict postpartum thyroiditis. In addition, more than 90% of patients with autoimmune thyroiditis (Hashimoto’s thyroiditis) have thyroglobulin or thyroid microsomal antibodies.

THYROGLOBULIN ANTIGEN

Thyroglobulin is a protein that binds to thyroxine (T4). Its levels may be elevated in inflammatory conditions of the thyroid as well as in thyroid cancer. Serum thyroglobulin levels are particularly useful in thyroid cancer monitoring, since localized or metastatic thyroid carcinomas increase these levels, but they fall again after complete thyroidectomy and 131I ablation therapy. Thyroglobulin levels are also elevated in Graves’ disease, endemic goiter, and silent (painless) thyroiditis but are low or normal in patients with thyrotoxicosis factitia resulting from the surreptitious intake of thyroid hormone.

THYROID MICROSOMAL ANTIBODY

Combined with the test for thyroglobulin antibodies, the presence of antibodies against thyroid microsomal antigens (molecules in thyroid cells) can detect most autoimmune thyroid conditions. This combined testing for autoantibodies can detect almost all goitrous thyroiditis (Hashimoto’s disease), almost all atrophic thyroiditis (myxedema), and about 70% to 90% of cases of Graves’ disease. However, thyroid microsomal autoantibodies (TMAs) are found in about 6% to 7% of adult Caucasians, and their prevalence increases with age. Even in asymptomatic individuals, the presence of TMAs can be predictive of hypothyroidism and does not exclude thyroid cancer. When total and free thyroid hormone levels do not match clinical findings, the presence of autoantibodies should be determined. In addition, TMA testing is thought to be a cost-effective screening method for postpartum thyroid dysfunction.

THYROID STIMULATING HORMONE(TSH)

Thyroid stimulating hormone (TSH) is produced in the pituitary gland and stimulates the thyroid to secrete T4 and T3 thyroid hormones. Abnormal levels of TSH may indicate various thyroid and pituitary gland conditions. Thyroid stimulating hormone, or thyrotropin, is a glycoprotein synthesized and secreted by the pituitary gland. It stimulates synthesis and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Secretion of TSH is stimulated by thyrotropin-releasing hormone, a hypothalamic tripeptide, and regulated via negative feedback through thyroid hormone levels. Increased serum levels of free T4 and T3 depress TSH secretion (hyperthyroidism), while decreased serum levels of free T4 and T3 result in excess TSH secretion (primary hypothyroidism). Serum TSH concentration is inversely proportional to the free T4 concentration in a log/linear relationship, making TSH a sensitive marker for monitoring the effects of thyroid hormone replacement therapy.(TSH)

THYROXINE(T4)

Thyroxine (T4) is the most abundant thyroid hormone and plays an important role in the control of metabolism. The majority of circulating triiodothyronine (T3) results from the conversion of T4 in the peripheral tissues. In serum, T4 is bound to thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin. The serum-free T4 concentration is about 0.03% of the total T4 concentration. Increased free T4 levels may result from Graves’ disease, toxic adenoma, toxic multinodular goiter, thyroiditis, and (rarely) thyroid cancer. Decreased levels may result from thyroiditis, idiopathic myxedema, pituitary dysfunction, hypothalamic disease, or the use of certain medications.

THYROXINE ANTIBODY(T4 Ab)

The thyroxine antibody test measures antibodies to T4 thyroid hormone. Autoantibodies to T4 can alter the results of the T4 test and may indicate an underlying autoimmune condition.4

THYROXINE BINDING GLOBULIN(TBG)

Thyroxine binding globulin (TBG) binds to T4 thyroid hormone in the bloodstream. Determination of thyroxine binding globulin levels is particularly useful when total thyroid hormone levels do not correlate with the thyro- metabolic status, as in pregnancy, contraceptive steroid use, or hereditary excesses or deficiencies of TBG.

TISSUE FACTOR(TF)

Tissue factor (TF) is a membrane receptor protein that behaves like a cytokine (a cell signaling molecule). It is involved in blood coagulation and helps to signal other cells involved in inflammatory reactions. Levels of tissue factor may be elevated in cancer and certain inflammatory conditions. Tissue factor is an integral membrane receptor glycoprotein and a type-2 cytokine receptor. It initiates both extrinsic and intrinsic cascades by forming high- affinity complexes between its extracellular domain and circulating blood coagulation Factors VII and VIIa. These enzymatically active complexes then activate Factors IX and X, leading to thrombin generation and clot formation. TF is expressed on extravascular and perivascular cells but not vascular endothelial cells or monocytes. Up-regulation of tumor TF correlates with enhanced metastatic potential.

TISSUE INHIBITOR OF METALLOPROTEINASE 1(TIMP-1)

Tissue inhibitors of metalloproteinases (TIMPs) block the activity of matrix metalloproteinases (MMPs), enzymes that break down structural proteins and connective tissue. It is believed that levels of TIMPs and MMPs should be balanced for good health. Metalloproteinases of the extracellular matrix are proteolytic enzymes involved in the biosynthesis of connective tissue. The synthesis and secretion of matrix metalloproteinases (MMPs) are induced in various cell types by cytokines. MMPs degrade constituents of the basal membrane and the extracellular matrix (including collagens, proteoglycans, gelatin, fibronectin, laminin, and elastin) under physiological and pathological conditions. Their activities also facilitate the invasive migration of cells. These biological activities are subject to a complex regulation involving TIMPs (tissue inhibitors of metalloproteinases) and many MMP proforms form complexes with these inhibitors. TIMP-1 is a major regulator of extracellular matrix synthesis and degradation.

TISSUE TRANSGLUTAMINASE ANTIBODY(tTG Ab)

The presence of antibodies against tissue transglutaminase is associated with celiac disease, a digestive condition associated with poor absorption of nutrients. Symptoms include abdominal pain, constipation, diarrhea, and bloating. Celiac disease occurs most often in childhood and in the third to fifth decades of life but can develop at any age. The typical presentation is malabsorption, but subclinical disease, particularly in adults, can be intestinal or extraintestinal and can include symptoms similar to irritable bowel syndrome, including bloating, abdominal pain, constipation, or diarrhea. Other symptoms can include anemia, fatigue, dyspepsia, infertility, miscarriages, bone pain, tooth enamel defects, oral ulcers, elevated aminotransferases, and neurologic or neuropsychiatric manifestations. In children, initial manifestations include diarrhea, vomiting, failure to thrive, short stature, irritability, delayed puberty, and recurrent abdominal pain with bloating. Although many patients present with multiple symptoms, it is not uncommon for a patient to have a single sign or symptom.

TOTAL PROTEIN

Total protein is a measure of the total protein content in the blood. Total protein levels are used in the evaluation of nutritional status, nephrotic syndromes, malabsorption, neoplasia including myeloma, and Waldenstrom’s macroglobulinemia. Protein levels may be elevated due to dehydration, vomiting, diarrhea, Addison’s disease, diabetic acidosis, or multiple myeloma. They are decreased in nephrotic syndrome, salt retention syndromes, severe burns, extensive bleeding, open wounds, sprue, intestinal malabsorption, and severe protein starvation (kwashiorkor).

TOXOPLASMA GONDI ANTIBODY

Toxoplasmosis is a common infectious disease, caused by the Toxoplasma gondi parasite, that may be fatal to a fetus or immunocompromised patients. In healthy individuals, it causes only mild symptoms. Antibodies against the parasite that causes toxoplasmosis indicate recent infection with this parasite. Acute toxoplasmosis in pregnant women can result in severe damage to or the death of the fetus.

TRIGLYCERIDES

Triglycerides are common fats found in the food we eat and in our bodies. High blood levels of triglycerides are related to dietary intake as well as metabolic factors. Triglycerides are often measured as a reflection of fat ingestion and metabolism or as part of an evaluation of coronary risk factors. High triglyceride levels appear to be associated with an increased risk of cardiovascular events, particularly in conjunction with other risk factors. High triglyceride levels may occur in cirrhosis, chronic renal insufficiency, familial hyperlipoproteinemia (rare), acute myocardial infarction, hypothyroidism, diabetes mellitus, Cushing’s syndrome, nephrotic syndrome, glycogen storage disease, and pancreatitis. Low levels may indicate malabsorption syndrome, malnutrition, or abetalipoproteinemia.

TRIIODOTHYRONINE(T3)

Triiodothyronine (T3) is a thyroid hormone that is important in body metabolism. About 80% of triiodothyronine result from conversion of thyroxine (T4) to T3 in peripheral tissues, while the remaining 20% are synthesized by the follicular cells of the thyroid gland. Free T3 levels generally correlate closely with total T3 levels; however, total T3 is affected by levels of thyroid hormone- binding proteins, while free T3 is not. Thus, TBG elevations due to pregnancy, oral contraceptive use, or estrogen therapy will increase total T3 without affecting the free T3 concentration. Measurement of total T3 by immunoassay can be used to evaluate hyperthyroidism when an elevated free or total thyroxine (T4) level has been encountered.

TRIIODOTHYRONINE ANTIBODY(T3 Ab)

The triiodothyronine antibody test measures antibodies to T3 thyroid hormone. Autoantibodies to T3 can alter the results of the T3 test and may indicate an underlying autoimmune condition.

TRYPANOSOMA CRUZI ANTIBODY(T. CRUZI Ab)

Trypanosoma cruzi is an infectious parasite that can cause Chagas’ disease or American trypanosomiasis. This is relatively common in South America and other developing regions, but rare in the United States. The presence of antibodies against Trypanosoma cruzi indicates prior exposure to or infection with Trypanosoma cruzi.

TUMOR NECROSIS FACTOR ALPHA(TNF-ALPHA)

Tumor necrosis factor alpha (TNF-alpha) is produced by various white blood cells, including macrophages, monocytes, neutrophils, and some lymphocytes. It attacks cancer cells. Levels of TNF-alpha may be elevated in cancers (especially lung cancer and certain leukemias) and some inflammatory conditions. TNF-alpha is secreted after stimulation with interferon, interleukin-2, granulocyte/macrophage colony-stimulating factor, bradykinin, immune complexes, cyclooxygenase inhibitors, or platelet activating factor. Unlike chemotherapeutic drugs, TNF-alpha attacks only malignant cells; preclinical studies have documented a direct cytostatic and cytotoxic effect against cancer cells, as well as a variety of immunomodulatory effects on immune effector cells, including neutrophils, macrophages, and T-cells. Unfortunately, while clinical trials have confirmed the safety of TNF-alpha, they have so far failed to demonstrate significant efficacy. TNF-alpha is also found in the synovial fluid of arthritis patients, and it has been suggested that inhibitors would be therapeutically beneficial. Other disorders in which TNF- alpha may play a role include systemic inflammatory response syndrome, hairy cell leukemia, and fibrosarcoma.

TUMOR NECROSIS FACTOR BETA(TNF-BETA)

Tumor necrosis factor beta (TNF-beta) is produced by white blood cells and promotes the generation of cells involved in wound healing. TNF-beta may also inhibit the growth of some cancers by decreasing their production of new blood vessels. Levels of TNF-beta may be elevated in certain infections, especially meningococcal septicemia, and some tumors. TNF-beta is produced predominantly by mitogen-stimulated T-lymphocytes and secreted by fibroblasts, astrocytes, myeloma cells, endothelial cells, epithelial cells, and a number of transformed cell lines. Its synthesis is stimulated by interferons and interleukin-2. TNF-beta promotes the proliferation of fibroblasts and appears to be involved in wound healing processes and possibly anti-tumor activities. However, clinical applications are only in initial stages. In addition, TNF-beta levels in the sera of patients with meningococcal septicemia have been shown to correlate with morbidity and mortality.

TUMOR NECROSIS FACTOR RECEPTOR 2(TNF R2)

The tumor necrosis factor receptor 2 (TNF R2) molecule is involved in the destruction of various types of normal and abnormal proteins. Low levels of TNF R2 are associated with cancer of the kidney. This protein binds to the intracellular domain of the type 1 TNF receptor. It has been shown to be identical with subunit 2 of the 26S proteasome complex, which mediates the degradation of constitutively short-lived proteins, regulatory proteins, and abnormal and malfolded proteins. Its expression is down-regulated in renal carcinoma cells.

URIC ACID

Uric acid elevations may occur in gout, renal disease with renal failure, dehydration, diuretic use, alcoholism, lead poisoning, lymphoma, leukemia, infectious mononucleosis, acute inflammatory state, acidosis, hyperparathyroidism, hypothyroidism, sarcoidosis, toxemia of pregnancy, chemotherapy, and radiation therapy. Uric acid levels may also be useful as an indicator of renovascular involvement in essential hypertension. Causes of low uric acid levels include Wilson’s disease, Fanconi syndrome, hemochromatosis, xanthine-oxidase deficiency, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and the use of certain drugs.

VARICELLA ZOSTER IgG ANTIBODY(V. ZOSTER IgG Ab)

Varicella zoster virus is the infectious agent that causes chickenpox and shingles. The presence of IgG antibodies against Varicella zoster virus indicates prior exposure to this virus.

VARICELLA ZOSTER IgM ANTIBODY(V. ZOSTER IgM Ab)

Varicella zoster virus is the infectious agent that causes chickenpox and shingles. The presence of IgM antibodies against Varicella zoster virus indicates infection with this virus.

VASCULAR CELL ADHESION MOLECULE 1(VCAM-1)

Vascular cell adhesion molecule 1 (VCAM-1) is a molecule that helps in the adhesion of various white blood cells, including lymphocytes, monocytes, natural killer cells, eosinophils, and basophils. Levels of VCAM-1 may be elevated in certain inflammatory conditions. VCAM-1 interacts with leukocyte very late antigen-4 (VLA-4). This interaction mediates the firm adherence of circulating non-neutrophilic leukocytes to endothelium. VCAM-1 also participates in leukocyte adhesion outside the vasculature, mediating precursor lymphocyte adhesion to bone marrow stromal cells, and B-cell binding to lymph node follicular dendritic cells. VCAM-1 is not constitutively expressed on endothelium but is present on tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. A soluble form of VCAM-1 (sVCAM-1) has been described; sVCAM-1 has been found in the serum of healthy individuals, and increased levels have been detected in several diseases.

VASCULAR ENDOTHELIAL GROWTH FACTOR(VEGF)

Vascular endothelial growth factor (VEGF) promotes the development of new blood vessels. Its levels may be elevated in neuronal and other tumors. VEGF is important in the pathophysiology of neuronal and other tumors, probably as a potent promoter of angiogenesis. Its synthesis is also induced by hypoxia. Due to its effects on vascular permeability, VEGF may be involved in altering blood-brain-barrier functions under normal and pathological conditions. Its release by glioma cells may account for clinical features of glioblastoma multiforme tumors, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, and pulmonary embolism. VEGF secreted by stromal cells may be responsible for endothelial cell proliferation in capillary hemangioblastomas, and the production and secretion of VEGF by human retinal pigment epithelial cells may play a role in the pathogenesis of ocular neovascularization.

VITAMIN B12(ALSO CALLED COBALAMIN)

Vitamin B12 is important in normal cell growth and multiplication. Vitamin B12 deficiency may result in neurologic conditions or anemia. Vitamin B12 (cobalamin) is critical to normal DNA synthesis. The body excretes very little B12, instead reabsorbing it from the ileum and returning it to the liver. Clinical and laboratory findings in B12 deficiency include neurological abnormalities, decreased serum B12 levels, increased excretion of methylmalonic acid, and a macrocytic anemia characterized by the abnormal megaloblastic maturation of erythrocyte precursors. The neurologic abnormalities probably result from defective myelin synthesis and the accumulation of abnormal lipids. Causes of low vitamin B12 levels include low intake, pernicious anemia, gastrectomy, diseases of the small intestine, malabsorption, and transcobalamin deficiency.

von WILLEBRAND FACTOR(vWF)

The von Willebrand factor (vWF) is a protein made in the cells lining blood vessels and the large cells that eventually become platelets (megakaryocytes). It plays an important role in the clumping of platelets and resulting clot formation. Abnormal levels of von Willebrand factor may result in bleeding disorders. The von Willebrand factor antigen (vWF:Ag) is synthesized in endothelial cells and megakaryocytes as a number of subunits that polymerize and combine with Factor VIII to form a large complex. In the plasma, von Willebrand factor (also known as ristocetin cofactor or RCF) exists as a heterogenous population of large polymers to which Factor VIII is complexed by non-covalent bonds. The vWF:Ag level is an immunologic measure of vWF levels and one component of a “von Willebrand’s panel.” Patients with a chronic bleeding disorder and a family history of bleeding should be evaluated for von Willebrand’s disease; vWF:Ag levels are decreased in von Willebrand’s disease (vWD) patients and normal in hemophilia A patients and carriers. Since many variants of vWD exist, identification is more likely if Factor VIII activity, vWF:Ag, and vWF-RCF activity are all assayed. Because many vWD patients have mild disease, repeated testing may be necessary in order to make the diagnosis. Female patients with vWD who are pregnant or taking oral contraceptives may have normal vWF:Ag values.

WHITE BLOOD CELL COUNT(WBC COUNT)

This test measures the total number of white blood cells present in the blood. White blood cells are the major infection-fighting cells but are also involved in immune system responses to allergens, tumors, and cell stress. Leukopenia may indicate bone marrow failure, the presence of a cytotoxic substance, collagen vascular disease (such as systemic lupus erythematosus), liver disease, spleen disease, or radiation. Leukocytosis may indicate infectious disease, inflammatory disease (such as rheumatoid arthritis or allergy), leukemia, severe emotional or physical stress, or tissue damage.