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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

At least 217 records · Page 12Linked to original sources
PubMed1987

Double-blind study comparing aztreonam with placebo for prophylaxis of infection following prostatic surgery.

In a prospective, randomised, double-blind study, 179 patients undergoing retropubic or transurethral prostatectomy were given pre-operatively either 1 g aztreonam or a placebo. In patients treated with aztreonam there was a significant reduction in the number with post-operative bacteriuria and in the number requiring treatment of post-operative bacteriuria. Other differences were not significant. The mean duration of post-operative hospital stay for patients receiving aztreonam was 7.1 days compared with 6.9 days for those receiving placebo. In patients treated with aztreonam there was no increase in the frequency of infections due to Gram-positive bacterial species.

Aztreonam↗
PubMed1987

Topographical control of cell behaviour. I. Simple step cues.

The photolithographic techniques of the microelectronics industry have allowed us to fabricate patterned plastic substrata to investigate contact guidance of animal tissue cells. The reactions of cells to single steps on a substratum were examined using time-lapse videorecording and scanning electron microscopy. BHK cells and chick embryonic neural cell processes exhibited gradual inhibition of crossing steps with a concomitant increase in alignment at steps dependent on increasing step height. Comparison of these cells' reactions, with those of chick heart fibroblasts and rabbit neutrophils, at a 5 micron step revealed that the influence of topography is also dependent on cell type, the neutrophils being relatively unaffected. The presence of an adhesive difference at a series of steps altered BHK cells' reactions such that the frequency of crossing was dependent on the direction of approach to a step. Although our data are consistent with Dunn & Heath's proposal (1976) that the inflexibility of the cytoskeleton of a moving cell's protrusion is the cellular property determining such reactions to topography, we have found that, on encountering a topographical feature, the response of a cell may be predictable on a probabilistic basis, i.e. the topographical feature reduces the probability of a cell making a successful protrusion and contact in a given direction, that even the largest features tested did not act as absolute barriers to cell locomotion since a small proportion of a population of cells were able to overcome them, and that other guidance cues could significantly alter a cell's response. Even in situations where it is not the primary cue in directing cell locomotion, topographical control may be an important factor during morphogenesis since it must, at the very least, influence the efficiency of other cues.

Animals↗
PubMed1987

Novel methods for the guidance and monitoring of single cells and simple networks in culture.

The effects of the topography, adhesiveness and chemistry of surfaces in modulating the behaviour of cells in vivo and in vitro have been extensively researched. However, few natural systems are simple enough to allow straightforward conclusions to be drawn, as many different cues are likely to be present at one time. Microelectronic fabrication, normally employed in making integrated circuits, can produce substrates patterned on scales highly relevant to studies of cell behaviour. In this paper, we describe progress in fabricating simple artificial substrata both at the micrometre and sub-micrometre scales. The former can be considered as models for contact guidance along other cells or axonal processes: the latter, models for guidance along aligned collagen matrices. We have systematically studied the reactions of different cell types to simple cues (steps and grooves). Additionally, it may be possible to produce fine-resolution patterns with differential adhesiveness, or with other cell-specific surface-chemical properties, such as the differential deposition of proteins, e.g. cell adhesion molecules. We also describe early results in using topographic and other cues to guide cells onto patterned metal electrodes, forming simple electrically active networks of controlled design, from which long-term recordings can conveniently be made.

Animals↗
PubMed1987

Growth of retinal capillary endothelia using pericyte conditioned medium.

Long-term cultures of bovine retinal capillary endothelial cells (BRCEC) have been established using bovine retinal pericyte conditioned medium (PCM). PCM had greater mitogenic activity on BRCEC than unconditioned medium (P less than 0.01). The mitogenic activity of PCM was not cell specific since bovine Tenon's fibroblast conditioned medium also had significant activity. PCM's activity was not enhanced by heparin though it was additive to that of retinal crude extract.

Animals↗
PubMed1987

Does the PI polymorphism alone control alpha-1-antitrypsin expression?

Whether genetic factors other than the protease-inhibitor (PI) polymorphism itself contribute to variation in alpha-1-antitrypsin is of both theoretical and practical interest. We have measured the quantity of alpha-1-antitrypsin (by an immunoturbidometric assay) and its activity (by assaying elastase inhibitory capacity [EIC]) in 583 individuals from 114 twin kinships who were also typed for PI by isoelectric focusing. Models of variation were fitted directly to the raw observations by a maximum-likelihood method. Specification of phenotypic means led to highly significant improvements in fit over models including only individual environment variance and additive genetic variance. The 29 phenotype means could also be described as the appropriate additive combinations of the 12 allelic effects. Only small improvements in fit could then be obtained by addition of polygenic components of variance. We conclude that nearly all genetic variation in alpha-1-antitrypsin quantity and activity can be explained by detectable variation at the PI locus and that this variance is largely additive. Bivariate analysis of alpha-1-antitrypsin and EIC revealed marginal evidence for differences in specific activities of molecules coded by different PI alleles. The correlation between environmental deviations for the two measures was only .63, which may reflect, in part, the rather low reliability of the assays and account for the modest heritabilities (less than .5) of the two measures. An intriguing finding was the presence of significant differences in E1 variance for different PI types, suggesting that different phenotypes have differing capacities to react to environmental challenges.

Adolescent↗
PubMed1986

Expression of the myc gene locus in populations of leukocytes from leukaemia patients and normal individuals.

The relative abundances of c-myc-related RNA in the total cellular RNA of peripheral blood leukocytes from 36 patients with leukaemia have been compared with those in normal peripheral blood leukocytes and in HL60 cells. Varying amounts of c-myc-related RNA were found in RNAs from leukocytes from patients with ANLL, CGL and ALL. High concentrations (comparable with that in HL60 cells) were found in 13 (36%) of the leukaemias and lower, but still significant, concentrations in a further 15 (42%). Low concentrations of c-myc-related RNA, comparable to that in normal leukocytes, were found in 2 of 8 CGLs, 1 of 12 ANLLs, and 5 of 5 CLLs. DNAs from 11 leukaemia patients' leukocytes, in which c-myc-related RNA concentrations ranged from very high to very low, were examined for rearrangements and/or amplification of the c-myc gene. No rearrangements were detected, and the small degree of amplification (2- to 4-fold at most) found was not correlated with increased levels of c-myc RNA. There was, however, a noteworthy (though incomplete) correlation between elevated levels of c-myc-related RNA and the occurrence of higher proportions of blast cells in leukocyte populations from leukaemic patients. It is suggested that high levels of c-myc-related RNA in a population of peripheral blood leukocytes indicate the presence of a high proportion of leukaemic leukocytes that are maturation-arrested at early stages of development.

Base Sequence↗
PubMed1986

Lymphocyte subsets in normal bone marrow.

Bone marrow aspirates and biopsies from ten normal donors were stained directly with monoclonal antibodies specific for lymphocyte, monocyte, and myeloid antigens, and were analyzed by flow cytometry. To avoid cell loss, lymphocytes were not specifically isolated prior to staining. T cells comprised 46% of aspirate lymphocytes and 22% of biopsy lymphocytes. Further, the Leu-3:Leu-2 ratio of bone marrow T cells was below 1.0. B cells comprised 8% to 11% of bone marrow lymphocytes in both aspirates and biopsies, and there was a substantial percentage of cells in the lymphocyte window that was negative for all B and T cell markers. The lymphocyte window had very little myeloid contamination; however, when the myeloid window was examined, staining was greater than 90%.

Adult↗
PubMed1985

Alpha-1 antitrypsin phenotypes in demyelinating disease: an association between demyelinating disease and the allele PiM3.

Alpha-1 Antitrypsin, the major circulating protease inhibitor, has more than thirty alleles that can be identified by electrophoresis. In addition to its role as a protease inhibitor, alpha-1 antitrypsin may regulate the immune response. As there is evidence that both the inflammatory polyneuropathies and multiple sclerosis have an immune basis, and that genetic factors influence susceptibility, we have determined the alpha-1 antitrypsin phenotypes (protease inhibitor types) of 63 patients with Guillain-Barré syndrome, 52 patients with chronic inflammatory demyelinating polyneuropathy, and 178 patients with multiple sclerosis. In all 3 groups there was a significant increase in the proportion of patients with the protease inhibitor type M3 allele.

Alleles↗
PubMed1985

The influence of temperature on the function of renal cortical slices frozen in various cryoprotectants.

Renal cortical slices were frozen to various subzero temperatures after treatment with 2.1 M of one of three cryoprotectants, dimethyl sulfoxide (Me2SO), ethylene glycol, or glycerol. The effects on tissue [K+]/[Na+] of cooling to these temperatures were tested (using identical procedure times, cooling rates, and warming rates) by holding the slices at each experimental temperature for appropriate periods of time prior to rewarming. The effects of the holding time were assessed by comparison with slices which were cooled and rewarmed with no intermediate holding time. Slices treated with ethylene glycol or glycerol were found to exhibit a continuous decrease in [K+]/[Na+] with lowered temperatures, in contrast to those treated with Me2SO. Slices treated with Me2SO actually experienced a continuous increase in [K+]/[Na+] with lowered temperature (-12 to -33 degrees C). Me2SO does exhibit toxic effects at subzero temperatures. Adverse effects of holding time on viability are seen for Me2SO-treated slices at higher subzero temperatures. These effects were alleviated as the temperature is reduced, suggesting that temperature has a greater effect on survival of renal cortical tissue than Me2SO concentration. However, the toxicity observed at higher subzero temperatures is expected to be of importance, particularly for slowly cooled tissues which are exposed to these temperatures for relatively long periods of time.

Animals↗
PubMed1985

The influence of cooling rate and warming rate on the response of renal cortical slices frozen to -40 degrees C in the presence of 2.1 M cryoprotectant (ethylene glycol, glycerol, or dimethyl sulfoxide).

Renal cortical slices were treated with 2.1 M cryoprotectant in RPS-2 vehicle solution, cooled at one of four rates to -40 degrees C, then immediately warmed at one of four rates to 25 degrees C for determination of the [K+]/[Na+] after a standard incubation period. Results are presented in the form of survival "topographical maps" or surfaces with the x axis representing [K+]/[Na+]; the y axis, cooling rate; and the z axis, warming rate. The rate of temperature change fell in the range of 0.5 to 10 degrees C/min. The results suggest that when RPS-2 vehicle solution is used for 2.1 M cryoprotectants, Me2SO offers the prospect for greatest post-thaw recovery. With this vehicle-cryoprotective agent combination, the greatest post-thaw recovery is attained with cooling-warming combinations of -3, +4, and -0.5, +10 degrees C/min.

Animals↗