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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 37 records · Page 2Linked to original sources
PubMed1990

Diversity of Conus neuropeptides.

Conus venoms contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations.

Amino Acid Sequence↗
PubMed1990

Implications of olfactory agnosia for understanding sex differences in schizophrenia.

In our studies, 50 percent of the male patients with schizophrenia have an olfactory agnosia. This finding is of interest because the olfactory neuroanatomical network involves brain regions found to be abnormal in patients with schizophrenia, and this olfactory deficit appears to be sex dependent. This article reviews conceptual models for assessing olfactory function, describes the neuroanatomical structures involved, and reviews the findings of olfactory performance in patients with neurological dysfunction. The findings are then integrated with neuropathological studies of patients with schizophrenia. Finally, as there is increasing evidence for a sex difference in patients with schizophrenia, a model is suggested to account for these differences based on neuro-developmental and latent lesion hypotheses.

Agnosia↗
PubMed1990

Human immunodeficiency virus pseudotypes with expanded cellular and species tropism.

One mechanism for expanding the cellular tropism of a virus is through the formation of phenotypically mixed particles or pseudotypes, a process commonly occurring during viral assembly in cells infected with two or more viruses. We report here that dual infection of cells with human immunodeficiency virus (HIV) and a murine amphotropic retrovirus leads to the production of HIV pseudotypes that have acquired the host range of the amphotropic retrovirus and are capable of infecting not only CD4- human cells but also mouse cells. The replication of the HIV pseudotypes in the various CD4- cells was determined by measuring the appearance of HIV antigens in the supernatants, by cocultivation of CD4+ CEM cells with the infected CD4- cells, and in some cases by assaying the culture supernatants directly for infectious virus. Of the cells tested, human foreskin fibroblasts were the best host cells, and by in situ cytohybridization, we were able to document that all cells in the culture were infected. In addition, the temporal appearance of HIV-specific proteins in the HIV pseudotype-infected fibroblasts was similar to that seen in CD4+ CEM cells. If the human fibroblasts were first infected with the amphotropic retrovirus, they demonstrated the property of superinfection exclusion and were resistant to subsequent infection by the HIV pseudotype. In other cell lines, including the human glioblastoma-derived cell line U373MG, HeLa cells, BALB/c mouse embryo cells, and SC-1 wild mouse cells, although the HIV pseudotype infection appeared to be less efficient, substantial amounts of HIV were nevertheless produced. These results indicate that the HIV (amphotropic retrovirus) pseudotypes may be useful for studying the molecular biology of HIV infections in a wide range of cells.

Animals↗
PubMed1990

An empirical model for analysing and interpreting ventricular measures.

Given the abundant and, at times, contradictory studies of ventricular enlargement in neurological and psychiatric disorders, the current study was carried out to provide an empirical basis for analysing and interpreting these measures. A sample of CT scans on 100 control subject was drawn from the files of the University of British Columbia Department of Radiology and 19 measures of ventricular and head diameter or area were made. The interrelationships of these measures were then examined using factor analytic procedures. Three ventricular dimensions were found. To validate these three dimensions, the relationship of each with age was examined and then the age-corrected scores of seven clinical groups were compared on each of these dimensions. The magnitude of the relationship between these dimensions and age was impressive and each dimension contributed unique information regarding these age-related changes. Moreover, the analysis of the clinical groups suggested that differential patterns of ventricular change were present dependent upon the disease. These results are discussed with a view to integrating the findings of previous studies and planning future studies.

Adult↗
PubMed1979

The effect of topical crude coal tar treatment on unstimulated hairless hamster skin.

Topical treatment of hairless hamster skin with crude coal tar has been shown to induce epidermal thickening, an increased labelling index in the basal cell layer, an elevation in NADP-dependent glucose-6-phosphate dehydrogenase activity throughout the epidermis, an increased squame count, comedo formation, and atrophy of the sebaceous glands. Ultraviolet light fluorescence microscopy of sections of treated skin suggests that the hair follicle is an important route for skin penetration by coal tar.

Acne Vulgaris↗
PubMed1979

Characterization and quantitation of murine-delayed hypersensitivity responses elicted with particle-associated human gamma-globulin.

Parameters delineating the utilization of particle-associated human gamma-globulin to quantitate murine-delayed hypersensitivity (DHS) responses include: (1) the conditions used to prepare HGG-coated polystyrene latex particles; (2) the marked increase in sensitivity of detection of delayed immune responsiveness using particle-bound HGG; (3) a histologic analysis of the lesions induced by HGG-latex in DHS mice, and (4) the increased retention of particle-associated as opposed to soluble HGG at the site of challenge. The potential utilization of particle-bound antigens as a sensitive method of assessing the role of delayed-type responsiveness in tumor and transplantation immunity is discussed.

Animals↗
PubMed1979

Recovery of the gastric mucosa from bile-induced injury.

Bile salts are known to injure the gastric mucosa and may be involved in the pathogenesis of gastric stress ulceration, a feared sequela of shock. Although the induction of bile injury to the stomach has been extensively studied, recovery from such an injury has not. In the studies reported here the period after removal of bile was examined to see whether the mucosa could return to pre-bile-exposure status under various circumstances. Recovery from a bile salt-induced injury was studied in three mongrel dogs with Heidenhain pouches. Net acid back diffusion (NABD) was measured with a recirculating system incorporating a pH stat and was measured with a recirculating system incorporating a pH stat and autoburette, and transmucosal electrical potential difference (PD) was measured by usual methods. The effects of exposure to 5 mM taurodeoxycholate at pH 2 for 30 minutes were studied. This exposure increased net acid back diffusion from 23 +/- 5 to 184 +/- 16 micro Eq/10 min (P less than 0.01) and reduced PD from 56 +/- 2 to 18 +/- 2 mV (P less than 0.01). After injury the pouches were copiously irrigated with saline to remove bile, and then recovery was observed as the pouches were perfused with pH 1, 2, or 7 HCl solution made isotonic with NaCl. The recovery values were compared with the same dog's preinjury values at the same pH perfusion. The data showed that at pH 2 and pH 7, PD and NABD returned to preinjury levels within 90 minutes after bile injury. At pH 1, however, recovery did not occur. The pH dependence of recovery from bile-induced injury may have relevance to patients with episodic reflux of bile into the stomach.

Animals↗
PubMed1978

Niemann-Pick disease: prenatal diagnoses and studies of sphingomyelinase activities.

Five pregnancies were monitored for couples at-risk for having a child with some form of Niemann-Pick disease (NPD). Three of these were for the classic Type A form in which affected children usually have less than 1% of normal sphingomyelinase activity. Two of these pregnancies were terminated after the cultured amniotic-fluid cells were determined to have less than 1% of normal sphingomyelinase activity (0.4 and 0.6 nmole/mg protein/hr versus the control mean of 61.7). In the other pregnancy at risk for Type A NPD near normal activity was measured and it was continued to term. The two other pregnancies were monitored for couples in which severely affected children were found to have partially deficient sphingomyelinase activity (about 20% of normal) in cultured skin fibroblasts. Cultural amniotic-fluid cells from one of these pregnancies also had about 20% of control sphingomyelinase activity, but the woman underwent a spontaneous abortion soon after the cells were received and no studies on the fetus were done. The other sample was taken at the time of abortion for social reasons. In this case the cultured amniotic-fluid cells and cultured fetal skin fibroblasts gave normal sphingomyelinase activity. Enzymatic studies on tissues from the two fetuses predicted to be affected with Type A NPD confirmed the prenatal diagnosis. Studies of sphingomyelinase activity in the brains from these fetuses and from a child who died with Type A NPD indicated significant levels of activity when measured at pH 7.4 in the presence of magnesium. The higher level of the pH 7.4 sphingomyelinase activity in developing brain may indicate some important role in normal brain development.

Adult↗
PubMed1978

The measurement of histochemically-stained NADP-dependent isocitrate dehydrogenase in the sebaceous glands of hairless hamster.

The effect of substrate, co-factor and Nitroblue Tetrazolium concentration on the production of formazan by the action of NADP-dependent isocitrate dehydrogenase was studied in the sebaceous glands of the hairless hamster. The measurement (in average optical density units per unit area) of formazan in histochemically stained skin sections was carried out by television scanning microdensitometry (Quantimet 720D). Having established optimal conditions for this enzyme, a second study was carried out to determine the effect of different power objectives and wide-band wavelength light instead of white light on the average optical density per unit area, recorded by the instrument, of the formazan produced in a defined number of sebaceous glands in a single skin section. It was found that there was no difference in the average optical density per unit area recorded by the instrument at different power objectives and a peak value of average optical density per unit area could be obtained using a K4 or a K5 Balzer filter (550-650 nm).

Animals↗
PubMed1978

Hypoglycorrhachia and coxsackie B3 meningoencephalitis.

The case of a 3-week-old infant with Coxsackie B3 meningoencephalitis is discussed. Hypoglycorrhachia and neutrophils in the cerebrospinal fluid characterized the first ten days of her illness. Coxsackie B3 should be added to the list of enteroviruses that can cause hypoglycorrhachia during infections of the central nervous system in children.

Cerebrospinal Fluid↗
PubMed1978

Relation between pressure difference across the aortic valve and left ventricular outflow.

Equations are presented to relate left ventricular-aortic pressure difference and flow. The relative importance of fluid inertia and friction are evaluated and the errors introduced by the neglect of compliance are estimated. The equations are used to calculate pressure differences for both normal conditions and simulated aortic stenosis and to explain the timing of the reversal of the pressure difference.

Aortic Valve↗