Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent.Antibiotics, Antitubercular: Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.Tuberculosis, Multidrug-Resistant: Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.Galactans: Polysaccharides composed of repeating galactose units. They can consist of branched or unbranched chains in any linkages.Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Pentosyltransferases: Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.Tuberculosis, Pulmonary: MYCOBACTERIUM infections of the lung.Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.Mycobacterium Infections, Nontuberculous: Infections with nontuberculous mycobacteria (atypical mycobacteria): M. kansasii, M. marinum, M. scrofulaceum, M. flavescens, M. gordonae, M. obuense, M. gilvum, M. duvali, M. szulgai, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. xenopi (littorale), M. ulcerans, M. buruli, M. terrae, M. fortuitum (minetti, giae), M. chelonae.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Tuberculosis: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.EthylenediaminesMycobacterium kansasii: A slow-growing, photochromogenic species that is the etiologic agent of a tuberculosis-like disease in humans and is frequently isolated from human pulmonary secretions or tubercles. The incidence of infection is sharply increased among immunocompromised individuals. (Dorland, 28th ed)Mycolic AcidsCapreomycin: Cyclic peptide antibiotic similar to VIOMYCIN. It is produced by Streptomyces capreolus.Nontuberculous Mycobacteria: So-called atypical species of the genus MYCOBACTERIUM that do not cause tuberculosis. They are also called tuberculoid bacilli, i.e.: M. buruli, M. chelonae, M. duvalii, M. flavescens, M. fortuitum, M. gilvum, M. gordonae, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. kansasii, M. marinum, M. obuense, M. scrofulaceum, M. szulgai, M. terrae, M. ulcerans, M. xenopi.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Aminosalicylic Acid: An antitubercular agent often administered in association with ISONIAZID. The sodium salt of the drug is better tolerated than the free acid.Rifamycins: A group of ANTI-BACTERIAL AGENTS characterized by a chromophoric naphthohydroquinone group spanned by an aliphatic bridge not previously found in other known ANTI-BACTERIAL AGENTS. They have been isolated from fermentation broths of Streptomyces mediterranei.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections.Aza CompoundsAmikacin: A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.Mycobacterium xenopi: A slow-growing, scotochromogenic species occurring usually harmlessly in human secretions but occasionally associated with chronic pulmonary disease. (Dorland, 28th ed)Mycobacterium marinum: A moderate-growing, photochromogenic species found in aquariums, diseased fish, and swimming pools. It is the cause of cutaneous lesions and granulomas (swimming pool granuloma) in humans. (Dorland, 28th ed)Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.Sputum: Material coughed up from the lungs and expectorated via the mouth. It contains MUCUS, cellular debris, and microorganisms. It may also contain blood or pus.Mycobacteriophages: Viruses whose host is one or more Mycobacterium species. They include both temperate and virulent types.Extensively Drug-Resistant Tuberculosis: Tuberculosis resistant to ISONIAZID and RIFAMPIN and at least three of the six main classes of second-line drugs (AMINOGLYCOSIDES; polypeptide agents; FLUOROQUINOLONES; THIOAMIDES; CYCLOSERINE; and PARA-AMINOSALICYLIC ACID) as defined by the CDC.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Mycobacterium smegmatis: A rapid-growing, nonphotochromogenic species of MYCOBACTERIUM originally isolated from human smegma and found also in soil and water. (From Dorland, 28th ed)Ethionamide: A second-line antitubercular agent that inhibits mycolic acid synthesis.Tuberculosis, Miliary: An acute form of TUBERCULOSIS in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the blood stream.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Tuberculosis, Lymph Node: Infection of the lymph nodes by tuberculosis. Tuberculous infection of the cervical lymph nodes is scrofula.Nitrate Reductase: An enzyme that catalyzes the oxidation of nitrite to nitrate. It is a cytochrome protein that contains IRON and MOLYBDENUM.AIDS-Related Opportunistic Infections: Opportunistic infections found in patients who test positive for human immunodeficiency virus (HIV). The most common include PNEUMOCYSTIS PNEUMONIA, Kaposi's sarcoma, cryptosporidiosis, herpes simplex, toxoplasmosis, cryptococcosis, and infections with Mycobacterium avium complex, Microsporidium, and Cytomegalovirus.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Color Perception: Mental processing of chromatic signals (COLOR VISION) from the eye by the VISUAL CORTEX where they are converted into symbolic representations. Color perception involves numerous neurons, and is influenced not only by the distribution of wavelengths from the viewed object, but also by its background color and brightness contrast at its boundary.Dominican Republic: A republic in the Greater Antilles in the West Indies. Its capital is Santo Domingo. With Haiti, it forms the island of Hispaniola - the Dominican Republic occupying the eastern two thirds, and Haiti, the western third. It was created in 1844 after a revolt against the rule of President Boyer over the entire island of Hispaniola, itself visited by Columbus in 1492 and settled the next year. Except for a brief period of annexation to Spain (1861-65), it has been independent, though closely associated with the United States. Its name comes from the Spanish Santo Domingo, Holy Sunday, with reference to its discovery on a Sunday. (From Webster's New Geographical Dictionary, 1988, p338, 506 & Room, Brewer's Dictionary of Names, 1992, p151)Cell Wall: The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.Carps: Common name for a number of different species of fish in the family Cyprinidae. This includes, among others, the common carp, crucian carp, grass carp, and silver carp.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Cord Factors: Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals.QuinolinesMycobacterium Infections: Infections with bacteria of the genus MYCOBACTERIUM.Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as MULTIPLE SCLEROSIS, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis).Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Levofloxacin: The L-isomer of Ofloxacin.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.Corynebacterium glutamicum: A species of gram-positive, asporogenous, non-pathogenic, soil bacteria that produces GLUTAMIC ACID.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Radiometry: The measurement of radiation by photography, as in x-ray film and film badge, by Geiger-Mueller tube, and by SCINTILLATION COUNTING.Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Cycloserine: Antibiotic substance produced by Streptomyces garyphalus.Colony Count, Microbial: Enumeration by direct count of viable, isolated bacterial, archaeal, or fungal CELLS or SPORES capable of growth on solid CULTURE MEDIA. The method is used routinely by environmental microbiologists for quantifying organisms in AIR; FOOD; and WATER; by clinicians for measuring patients' microbial load; and in antimicrobial drug testing.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.ArabinoseCuba: An island in the Greater Antilles in the West Indies, south of Florida. With the adjacent islands it forms the Republic of Cuba. Its capital is Havana. It was discovered by Columbus on his first voyage in 1492 and conquered by Spain in 1511. It has a varied history under Spain, Great Britain, and the United States but has been independent since 1902. The name Cuba is said to be an Indian name of unknown origin but the language that gave the name is extinct, so the etymology is a conjecture. (From Webster's New Geographical Dictionary, 1988, p302 & Room, Brewer's Dictionary of Names, 1992, p132)Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Colorimetry: Any technique by which an unknown color is evaluated in terms of standard colors. The technique may be visual, photoelectric, or indirect by means of spectrophotometry. It is used in chemistry and physics. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)PolysaccharidesQuinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.Skin Diseases, Bacterial: Skin diseases caused by bacteria.Organic Cation Transporter 1: An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis.Memantine: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.Xanthenes: Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.Magnesium Sulfate: A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083)Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Lung Diseases: Pathological processes involving any part of the LUNG.Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Bacterial Proteins: Proteins found in any species of bacterium.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Tetrazolium Salts: Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)Reagent Kits, Diagnostic: Commercially prepared reagent sets, with accessory devices, containing all of the major components and literature necessary to perform one or more designated diagnostic tests or procedures. They may be for laboratory or personal use.Carbocyanines: Compounds that contain three methine groups. They are frequently used as cationic dyes used for differential staining of biological materials.Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Dark Adaptation: Adjustment of the eyes under conditions of low light. The sensitivity of the eye to light is increased during dark adaptation.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Mycobacterium bovis: The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Bacteriological Techniques: Techniques used in studying bacteria.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Evaluation Studies as Topic: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)IndiaGenes, Bacterial: The functional hereditary units of BACTERIA.Spleen: An encapsulated lymphatic organ through which venous blood filters.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.Mice, Inbred C57BLMacrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Injections: Introduction of substances into the body using a needle and syringe.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Visual Acuity: Clarity or sharpness of OCULAR VISION or the ability of the eye to see fine details. Visual acuity depends on the functions of RETINA, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast.Retinal Ganglion Cells: Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.