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Biomedical subjects

B Clark

Publications and source records attributed to B Clark.

At least 19 recordsLinked to original sources

Prevalence of hepatitis C virus antibodies in Sydney blood donors.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibodies in the Sydney blood donor population. DESIGN: All blood donations collected from Red Cross blood donors in Sydney from February 1990 until April 1991 were tested for HCV antibodies. For those samples found reactive in an anti-HCV screening test, a confirmatory test was carried out for the presence of HCV antibodies and the alanine aminotransferase level was measured. RESULTS: The prevalence of repeated reactivity to the screening test was 0.45% among blood donations overall, and 1.02% in donors giving blood for the first time in the study period. The confirmatory test result was positive for 30.8% of donations found to be repeatedly reactive in the screening test. There was little change over the study period in the HCV antibody prevalence of donors giving blood for the first time, but there was a clear decrease in the prevalence among all donations. Prevalence in males was nearly twice the prevalence in females--a difference which was consistent across age groups. The highest prevalence in both sexes was in the age group 30-34 years. Among samples for which the screening test results was positive, there was a strong correlation between the reactivity recorded for the screening test and both the proportion found positive by the confirmatory test and the proportion with an elevated alanine aminotransferase level. CONCLUSION: The small proportion of blood donations found to be repeatedly reactive by anti-HCV screening and the relatively good correlation with the confirmatory test and liver function assay indicate that a policy of discarding these donations will decrease the risk of transfusion-transmitted HCV infection without materially affecting the supply of blood.

Adult

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.

Biogenic Amines

Transmitter-operated channels in rabbit retinal astrocytes studied in situ by whole-cell patch clamping.

Glutamate and GABA open ion channels in the membranes of astrocytes found on the vitreal surface of the rabbit retinal visual streak. The glutamate-operated channels are opened by kainate, quisqualate, and AMPA, but not by NMDA, aspartate, or the metabotropic agonist 1-aminocyclopentane-1 S,3R-dicarboxylic acid. The effects of glutamate and its analogs can be blocked by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione. The conductance increase evoked by 10 microM glutamate, a concentration of this transmitter near to that found in the vitreous humor that bathes these cells, was equivalent to 22% of the cell's resting conductance. The conductance increase evoked by 1 microM GABA, a concentration near that found in the vitreous, was equivalent to 131% of the cell's resting conductance. The effects of GABA can be blocked by bicuculline. These data show that GABA, and non-NMDA-type glutamate receptors play an important part in determining the resting potential of visual streak astrocytes in situ and that these channels may be of general importance for the functions of astrocytes in vivo.

Animals

The accuracy of ultrasound in the detection of cirrhosis of the liver.

The association of high amplitude echoes returned from the liver and cirrhosis is well recognized. There have been no reports in the literature as to the overall incidence of this finding in the clinical situation. We report our experience in a series of 67 patients with proven cirrhosis who had liver biopsy and an ultrasound examination within three months of one another. In 43 patients cirrhosis was suggested by recognition of a bright liver echo pattern. In 23 patients the liver echo pattern was normal, although additional relevant information was shown in half of this group. The detailed pathology has been analysed in an attempt to account for the false negative examinations, revealing a strong trend for cases of micronodular cirrhosis to give positive ultrasound examinations and macronodular cirrhosis negative examinations.

False Negative Reactions

A simple method for removing the luminal epithelium of the mouse uterus for biochemical studies.

The luminal epithelium of the mouse uterus was removed simply and rapidly by opening the uterine horns longitudinally and 'vortexing' them in buffer with glass balls. This procedure, which requires no specialized apparatus, was developed for use with uteri in different hormonal states, and 2 uterine horns/tube, 5 glass balls and vortexing for 2 min are suggested for routine use. Under these conditions, 79--100% of the cells were removed, yielding epithelial fractions of 65--90% purity. The suspension of cell constituents recovered contained intact nuclei which could be further purified. Extensive histological examination demonstrated that the other uterine tissues were minimally damaged.

Animals

Heteroantiserum against acute lymphocytic leukemia raised to the lymphoblastoid cell line NALM-1.

Antisera have been raised in rabbits to the lymphoblastoid cell line NALM 1 precoated with anti-lymphocyte serum (ALS). Following absorption with chronic lymphocytic leukemia cells (CLL) the antisera reacted mainly with acute lymphocytic leukemia (ALL) cells, and were very similar in specificity to antisera raised to ALL cells precoated with ALS. Leukemia cells from the following numbers of patients were positive for the anti-NALM 1 sera in a complement-dependent cytotoxicity test; 11/14 ALL, 3/15 acute myelocytic leukemia (AML), 1/5 chronic myelocytic leukemia (CML) and 0/8 CLL. Normal B and T peripheral blood lymphocytes were negative. The titer of the anti-NALM 1 sera against positive cells was 1:64 to 1:256 whereas the undiluted sera did not react with negative cells. Ten out of 11 of the positive ALL cells were of the non-B non-T type. However, cells from 1/4 T ALL patients and a cultured T ALL line 8402 were also positive. Six of 12 cultured lymphoblastoid cell lines were positive, all of which were of malignant origin. The molecular weight of the ALL antigen detected by anti-NALM-1 serum was determined by immunoprecipitation and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) to be approximately 98,000 daltons.

Absorption

Regulation of cholesterol synthesis in the hyperlipoproteinaemias. Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia.

A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.

Cells, Cultured

Reaction time to accelerating lines and dots on a cathode-ray tube.

Two experiments recorded the simple RT of 13 and 10 airline pilots, respectively, to accelerating lines and dots on a cathode-ray tube. In Exp. 1, dotted lines of six lengths moved in-line or frontally, and downward or to the right. Exp. 2 compared seven different in-line-moving solid lines with dot pairs of corresponding separations, and with single dots. RT increased with the length of in-line-moving solid lines but not when dotted lines were used. RT decreased with frontal movement of dotted lines. RT to dot pairs was shorter than to solid lines or single dots. Results indicate the importance of three factors: amount of movement information, visual angle, and inhibition of the retinal area stimulated.

Humans

Acute lymphocytic leukemia-associated cell membrane antigen.

Antisera were raised in New Zealand White rabbits against non-B, non-T acute lymphocytic leukemia (ALL) cells coated with antilymphocyte serum. Following minimal absorption with chronic lymphocytic leukemia (CLL) cells, the antiserum reacted mainly with non-B, non-T ALL cells. The following numbers of patients had leukemia cells that reacted with the ALL antisera: 13 of 18 with ALL, 3 of 27 with acute myelocytic leukemia, 1 of 8 with chronic myelocytic leukemia (CML), and 0 of 12 with CLL. The positive CML was a patient in CML blast crisis. Normal peripheral blood B- and T-lymphocytes and normal bone marrow were negative. Reactions of the anti-ALL serum (136K) were compared with the reactions of a rabbit anti-B-cell antiserum (63K) that reacted with approximately 70% of leukemia cells. Cultured lymphoblastoid cell lines from normal donors were negative by both cytotoxicity and immunofluorescence tests. However, by immunofluorescence testing, 8 of 17 known malignant lines from a variety of lymphoproliferative disorders were positive; 4 of these lines were of T-cell origin. By immunoprecipitation and polyacrylamide gel electrophoresis, the ALL antigen appeared to consist of a single polypeptide chain of approximately 98,000 daltons. The anti-ALL antiserum was not cytotoxic for normal myeloid stem cells (colony-forming units).

Adult

Pterin-6-aldehyde, a cancer cell catabolite: identification and application in diagnosis and treatment of human cancer.

Active folic acid degradation with the formation pterin-6-aldehyde is a previously undescribed characteristic of cancer cells in tissue culture. Neither normal adult epithelial and fibroblastic cells nor human amniotic cells nor mouse embryonic fibroblasts degrade folic acid to a measurable degree. Twenty-nine patients whose diagnoses were not revealed until after the test of their first morning urine for pterin-6-aldehyde was completed were studied for the presence or absence of pterin-6-aldehyde by thin-layer chromatography. Pterin-6-aldehyde was found in the urine at about 300 nmol/ml or greater only in those 13 patients with a tissue diagnosis of cancer. When the cancer was totally resected, the pterin-6-aldehyde was no longer found in the urine postoperatively. Pterin-6-aldehyde is not found in the urine of healthy patients at this level of detection unless their diets are supplemented with folic acid.

Adolescent

Studies on ventilation of Caiman crocodilus (Crocodilia: Reptilia).

The ventilatory mechanics of freely moving Caiman crocodilus were studied by cinefluorescopy and electromyography. The buccal oscillations serve only to flush the internal nares in olfaction. Ventilations are coincident with abdominal oscillations. The larynx ordinarily lies adpressed to the internal nares so that the posterior buccal chamber is excluded from the path of air flow during ventilation and does not contribute to respiratory dead space. The pulmonary pressures may be variably polyphasic and the tracheal flows diphasic. Exhalation involves an anterior shift of the liver by action of the transverse abdominal muscles, while inhalation proceeds due to contraction of the diaphragmatic muscle pulling the liver caudad. The various costal muscles facilitate air flow by shifting the position of the ribs. They also play a role in fixation of the flexible rib cage so that it resists the aspirating and compressing actions of the hepatic piston. The pattern of muscular activity shifts as the trunk is immersed; expiration becomes passive and inspiration requires increased muscular effort. The ribs, instead of changing position with each breath are comparatively fixed by the costal muscles, while changes in the volume of the pleural cavity are caused almost exclusively by movements of the hepatic piston.

Alligators and Crocodiles

Control of the sequential utilization of glucose and fructose by Escherichia coli.

In Escherichia coli (ATCCI5224; ML308), glucose and fructose phosphotransferase systems (PT-systems) are constitutive but activities are increased five and 10-fold respectively by aerobic growth on their respective substrates in defined media. In mixtures, glucose is used preferentially and the fructose PT-system activity is kept at its minimum; but, on glucose exhaustion, it overshoots its steady-state level and growth continues on fructose without lag. Cyclic AMP prevents overshoot. Continuous cultures operating as turbidostats on mixtures of glucose and fructose do not use fructose if sufficient glucose is present to support growth. If less glucose is available, it is all used and sufficient fructose is metabolized concurrently to maintain the growth rate characteristic of glucose. Both PT-systems are inhibited by hexose phosphates. Presence of homologous substrate specifically sensitizes each PT-system to inactivation by N-ethylmaleimide (NEM). Glucose diminishes the ability of fructose to sensitize its PT-system to NEM. This effect parallels the inhibition of fructose utilization by glucose and suggests that glucose denies fructose access to the fructose-specific part of the PT-system.

Aerobiosis