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Biomedical subjects

K M Williams

Publications and source records attributed to K M Williams.

At least 145 records · Page 8Linked to original sources

Electrodermal activity among subtypes of depression.

To determine whether subgroups of depressed patients could be differentiated on the basis of electrodermal activity (EDA), the skin conductance of 36 depressed patients was recorded for two experimental conditions. In the first condition, subjects heard 10 85-dB tones after receiving instructions that were intended to relax the patients. In the second experimental condition, subjects heard 12 105-dB tones, one-half of which were signal tones containing a brief gap in the middle. The subjects were required to respond to the tones containing the gap by pressing a foot pedal. No differences in tonic or phasic EDA were detected on the basis of unipolar or bipolar subtype, response to the dexamethasone suppression test, severity of depression, medication status, or sex. However, patients who exhibited features of psychomotor retardation had significantly lower levels of tonic EDA than did their nonretarded counterparts. The EDA of the depressed patients as a group was uniformly low. These results are consistent with other reports indicating that, with the exception of the retarded/nonretarded distinction, there are no differences in EDA among the various subtypes of depression.

Adult↗

Subcellular and taxonomic specificity of monoclonal antibodies to New World Leishmania.

Murine monoclonal antibodies to flagellar, surface membrane and cytoplasmic antigens of New World Leishmania were assessed for their taxonomic specificity in enzyme-linked immunosorbent assays with three genera of the family Trypanosomatidae and three species and seven subspecies of the genus Leishmania. Antibodies exhibiting exclusive reactivity with either the flagellum, flagellar pocket, kinetoplast, or nucleus lacked specificity at all phylogenetic levels and, in fact, recognized epitopes common to cultured mammalian cells. Monoclonals to intracellular antigens were capable of distinguishing Leishmania from Trypanosoma and Endotrypanum. Antibodies reactive at the surface membrane could separate six isolates of L. braziliensis from three isolates of L. mexicana but the differences in antigen expression were frequently quantitative rather than qualitative. Antigenic variability within species and/or subspecies often exceeded that which was observed between species and/or subspecies. At least one monoclonal antibody was specific for a surface antigen peculiar to a subpopulation of promastigotes of an L. braziliensis panamensis isolate.

Animals↗

Plasma apolipoprotein pattern in fish-eye disease examined by high-resolution two-dimensional electrophoresis.

We compared the plasma protein patterns of the two living patients suffering from fish-eye disease with those of appropriate controls, using high-resolution two-dimensional electrophoresis. Quantitative abnormalities were detected in plasma polypeptides corresponding to the isoforms of apolipoproteins A-I and A-II. The disease was characterized by normal concentrations of proapo A-I but dramatically subnormal concentrations of the other apo A-I isoforms and apo A-II. No significant difference was detected in the concentrations of other plasma proteins. These findings are discussed in relation to other apolipoprotein disorders.

Apolipoprotein A-I↗

Liquid chromatographic determination and plasma concentration profile of optical isomers of ibuprofen in humans.

A sensitive and specific high-performance liquid chromatographic assay for the optical isomers of ibuprofen in plasma is reported. The isomers were converted to their diastereoisomeric S(+)-2-octyl esters and were resolved with two silica columns in series and a mobile phase containing 0.05% isopropyl alcohol in heptane. The lower limit of sensitivity was 0.5 micrograms/mL. The plasma concentrations of the optical isomers in a normal volunteer following administration of racemic, S(+)-, and R(-)-ibuprofen are reported. Following administration of R(-)-ibuprofen, there was stereoselective inversion of R(-)- to S(+)-ibuprofen.

Chromatography, High Pressure Liquid↗

Artifacts associated with 2-mercaptoethanol upon high resolution two-dimensional electrophoresis.

The presence of 2-mercaptoethanol in the protein denaturing solution used to prepare samples for high resolution two-dimensional electrophoresis can result in artifacts when the two-dimensional patterns are detected by silver staining. These are (i) spots of discrete isoelectric point and electrophoretic mobility, (ii) horizontal bands of the same electrophoretic mobility as the spots (corresponding predominantly to molecular weights of 54,000 and 68,000), and (iii) vertical streaks of variable length and intensity. Although the nature and source of artifacts have not been positively identified the evidence suggests that they are probably not inherent in the 2-mercaptoethanol itself but rather released by the latter from some component common to both the first- and second-dimension constituents of the electrophoretic system.

Electrophoresis, Polyacrylamide Gel↗

Kinetics of misonidazole enantiomers.

The kinetics of misonidazole enantiomers were followed in nine healthy subjects after a single oral dose of racemic misonidazole (1.0 gm/m2). Mean clearance of (+)-misonidazole was 14% greater than that for (-)-misonidazole and mean volume of distribution was slightly greater (3%) for the (+)-enantiomer. After treatment of four of the subjects with cimetidine, there was a small increase in (-)-misonidazole distribution volume, but there was no significant change in other kinetic parameters for either enantiomer. Phenytoin (three subjects) and phenobarbital (two subjects) increased the clearance of both enantiomers (the increase was greater for (+)-misonidazole). The use of (+)-misonidazole together with induction of metabolism may reduce the neurotoxicity associated with racemic misonidazole.

Administration, Oral↗

Two-dimensional electrophoresis of proteins in human serum: improved resolution by use of narrow pH gradients and prolonged electrophoresis.

The limited resolution of serum proteins achieved with a simplified technique of two-dimensional electrophoresis (Clin. Chim. Acta 103: 51-59, 1980) has been improved by using different ampholyte (Ampholine) mixtures in the first dimension, to obtain relatively shallow pH gradients, and prolonged electrophoresis time in the second dimension. The technique has been further simplified, without negative effect, by decreasing the concentration of non-ionic detergent (first dimension), omitting both sodium dodecyl sulfate equilibration and the use of a stacking gel (second dimension), and by using an improved silver-staining procedure. Reverse-polarity isoelectric focusing and non-equilibrium pH-gradient electrophoresis have been successfully used to resolve the basic polypeptides in serum after deleting sodium dodecyl sulfate from the sample preparation. These combined techniques reveal over 1100 polypeptides in human serum. After immunodeletion of albumin, additional serum polypeptides are seen. Immunodeletion of serum proteins from plasma reveals polypeptides that are relatively specific to plasma.

Ampholyte Mixtures↗

Identification of minor metabolites of 5-fluorocytosine in man by chemical ionization gas chromatography mass spectrometry.

A new minor metabolite of 5-fluorocytosine, 5-hydroxy-5-fluorocytosine, was found in the urinary gravel excreted by a patient being treated with this drug. A metabolite of 5-fluorocytosine in animals, alpha-fluoro-beta-alanine, was identified and quantitated in the urine of nine patients. In general, alpha-fluoro-beta-alanine represented 0.05--0.25% of the daily dose of 5-fluorocytosine, both for orally and intravenously administered drug. Minor metabolites have been implicated in the occasional toxicity observed in patients receiving 5-fluorocytosine.

Biotransformation↗

Solute leakage resulting from leaf desiccation.

The leakage of solutes from foliar tissue is utilized as a dynamic measure of apparent changes in membrane integrity in response to desiccation. It is found that rehydrating leaf discs of cowpea (Vigna sinensis [L.] Endl.) show increasing leakiness in proportion to the extent of prior desiccation, whereas Selaginella lepidophylla Spring., a resurrection plant, does not. The elevated leakage rate of cowpea after desiccation recovers with time, and the passage of time in the stressed condition results in reduced subsequent leakiness. These characteristics are interpreted as suggesting that the leakage of solute reflects the condition of cellular membranes, and that desiccation stress leads to lesions in the membranes. The kinetics of solute leakage is suggested as a simple means of following changes in membrane lesions and associated features of membrane repair and hardening.

Journal Article↗

Crystalluria during flucytosine therapy.

A case of urinary crystalluria occurring in a patient during treatment with flucytosine (5-fluorocytosine) is presented. A reduction in the dosage of the 5-fluorocytosine resulted in a marked decrease in the excretion of urinary gravel which was shown to be a coprecipitate of 5-fluorocytosine and uric acid.

Cryptococcosis↗

Chlorbutol toxicity and dependence.

A case of chlorbutol toxicity and dependence is presented. A very long elimination half-life (13.2 days) was found in the patient. The data suggest that chlorbutol is an unsuitable sedative to be available freely to the public.

Adult↗

A critical evaluation of the application of amino acid racemization to geochronology and geothermometry.

In this review we have critically evaluated the application of the diagenetic racemization of amino acids to geochronology and geothermometry. Although there has been enthusiastic support given to this new method, it is our opinion that recent developments suggest a more cautious approach. We have discussed the pitfalls and inhereent complications, while outlining the advances which have been accomplished. We conclude that this is an innovative approach which will add valuable information to the scientific literature. However, since our fundamental understanding of diagnetic racemization is still limited, many of the age and paleotemperature estimates which have been assigned to fossil specimens may be unreliable.

Amino Acids↗

The pharmacokinetics of chlorbutol in man.

The pharmacokinetics of chlorbutol were studied after oral administration in 4 healthy subjects on two occasions. Following the rapid attainment of peak concentrations, plasma concentrations fell by approximately 50 per cent in 24 h. After the first dose of chlorbutol, the terminal elimination half-life was 10.3 +/-1.3 days (mean +/- S.E.M), the volume of distribution was 233 +/- 141 and the plasma clearance was 11.6 +/- 1.0 ml min-1. The binding to plasma proteins was 57 +/- 3 per cent. In 3 of the 4 subjects, there was a small but significant decrease in the terminal half-life of chlorbutol after the second dose. The mean urinary recovery over 17 days in two of the subjects accounted for only 9.6 per cent of the dose, 7.4 per cent of the total as the glucuronide and sulphate conjugates and 2.2 per cent as unchanged chlorbutol. A significant factor in the elimination of chlorbutol may be its instability under physiological conditions. Its half-life in vitro is 37 days at pH 7.4. The long terminal half-life of chlorbutol makes it unsuitable as a sedative drug because of the considerable accumulation which will occur when the drug is taken in multiple doses.

Adult↗

Heterogeneity of serum creatine kinase isoenzyme-MM in acute myocardial infarction.

Isoelectric focusing of serum creatine kinase (CK;EC 2.7.3.2) reveals up to 14 CK-MM subbands following acute myocardial infarction (AMI). The "normal" subbands 1 (pI 6.91), 2 (pI 6.65) and 3 (pI 6.35) are faintly present in normal serum and the "abnormal" subbands c (pI 7.25), e (pI 6.85), g (pI 6.50), i (pI 6.28), j (pI 6.20) and k (pI 6.15) are prominently detected in sera with elevated CK. "Abnormal" subbands a (pI 7.55),b(pI7.35),d(pI7.05),f(pI6.72) and h(pI6.40) have only been detected in AMI. The "abnormal" subbands appear, and reach maximum intensity (together with CK-MM 1-3), 3-12 h after infarction, and become faint and anodally convert (as do CK-MM 1-3) within 36 h. Similar changes are detected by nonequilibrium pH gradient electrophoresis which combines CK-MM and CK-MB analysis. In vitro incubation of serum with 0.015 M 2-mercaptoethanol induces conversion of CK-MM 1, 2 and 3 to b and c, d and e, and f and g, respectively. Thus, the complexity of the patterns is explained by a secondary conversion of "normal" to "abnormal" subbands superimposed upon anodal conversion of CK-MM 1----3. The clinical significance of these findings is discussed.

Adult↗