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Biomedical subjects

R M Brown

Publications and source records attributed to R M Brown.

At least 109 records · Page 6Linked to original sources
PubMed1987

Morphometric studies of the rat hippocampus following chronic delta-9-tetrahydrocannabinol (THC).

Persistent behavioral effects resembling those of hippocampal brain lesions have been reported following chronic administration of marijuana or its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) to rats. We used morphometric techniques to investigate the effects of chronic THC on the anatomical integrity of the hippocampus. Rats dosed orally for 90 days with 10 to 60 mg/kg THC or vehicle were evaluated by light and electron microscopy up to 7 months after their last dose of drug. Electron micrographs revealed a striking ultrastructural appearance and statistically significant decreases in mean volume of neurons and their nuclei sampled from the hippocampal CA3 region of rats treated with the highest doses of THC. A 44% reduction in the number of synapses per unit volume was demonstrated in these same rats. Golgi impregnation studies of additional groups of rats treated with 10 or 20 mg/kg/day THC and sacrificed 2 months after their last treatment with THC revealed a reduction in the dendritic length of CA3 pyramidal neurons, despite normal appearing ultrastructure and no changes in synaptic density. The hippocampal changes reported here may constitute a morphological basis for behavioral effects after chronic exposure to marijuana.

Administration, Oral↗
PubMed1987

Post-transplant peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.

Two patients previously managed by continuous ambulatory peritoneal dialysis for end stage renal failure received cadaveric renal transplants. The peritoneal catheter was capped off and left in situ postoperatively. Both patients developed bacterial peritonitis shortly after transplantation. It was felt that the infections were associated with the presence of the indwelling peritoneal catheter as there was no clinical evidence of peritonitis at the time of transplantation.

Aeromonas↗
PubMed1987

Empirical treatment of febrile, neutropenic patients with tobramycin and latamoxef.

One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings.

Agranulocytosis↗
PubMed1987

Localization of the human dihydropteridine reductase gene to band p15.3 of chromosome 4 by in situ hybridization.

We report the localization of the gene for dihydropteridine reductase (DHPR) to the human chromosome region 4p15.3 by in situ hybridization using a cDNA probe to the enzyme. The distal end of the short arm of chromosome 4 is of considerable interest because the gene responsible for Huntington's disease is located in this region. Although this part of the chromosome is being extensively studied, DHPR is the first well-characterised gene to be assigned to the region. Restriction enzyme fragment length polymorphisms have been detected with a number of restriction endonucleases, including AvaII and MspI. These features may make the DHPR cDNA clone a useful probe not only for prenatal diagnosis of DHPR deficiency but also for linkage studies of Huntington's disease.

Base Sequence↗
PubMed1987

In vitro synthesis of cellulose II from a cytoplasmic membrane fraction of Acetobacter xylinum.

The cytoplasmic and outer membranes of Acetobacter xylinum (ATCC 53582) were isolated by discontinuous sucrose density ultracentrifugation. Both lysozyme (EC 3.2.1.17) and trypsin (EC 3.4.21.4) were required for efficient crude membrane separation. Primary dehydrogenases and NADH oxidase were used as cytoplasmic membrane markers, and 2-keto-3-deoxyoctulosonic acid was used to identify the outer membranes. Cellulose synthetase (UDP-glucose:1,4-beta-D-glucan 4-beta-D-glucosyltransferase; EC 2.4.1.12) activity was assayed as the conversion of radioactivity from UDP-[(14)C]glucose into an alkali-insoluble beta-1,4-D-[(14)C]glucan. This activity was predominantly found in the cytoplasmic membrane. The cellulose nature of the product was demonstrated by (i) enzymatic hydrolysis followed by TLC, (ii) methylation analysis followed by TLC, and (iii) GC/MS. Further, the weight-average and number-average degree of polymerization of the in vitro product, determined by high-performance gel permeation chromatography, were 4820 and 5270, respectively. In addition, x-ray diffraction analysis indicated that the in vitro product is cellulose II, which is in contrast to the in vivo product-namely, cellulose I.

Journal Article↗
PubMed1987

UDP-Glucose: (1-->3)-beta-Glucan Synthases from Mung Bean and Cotton: Differential Effects of Ca and Mg on Enzyme Properties and on Macromolecular Structure of the Glucan Product.

A re-examination of the kinetic properties of UDP-glucose: (1-->3)-beta-glucan (callose) synthases from mung bean seedlings (Vigna radiata) and cotton fibers (Gossypium hirsutum) shows that these enzymes have a complex interaction with UDP-glucose and various effectors. Stimulation of activity by micromolar concentrations of Ca(2+) and millimolar concentrations of beta-glucosides or other polyols is highest at low (<100 micromolar) UDP-glucose concentrations. These effectors act both by raising the V(max) of the enzyme, and by lowering the apparent K(m) for UDP-glucose from >1 millimolar to 0.2 to 0.3 millimolar. Mg(2+) markedly enhances the affinity of the mung bean enzyme for Ca(2+) but not for beta-glucoside; with saturating Ca(2+), Mg(2+) only slightly stimulates further production of glucan. However, the presence of Mg(2+) during synthesis, or NaBH(4) treatment after synthesis, changes the nature of the product from dispersed, alkali-soluble fibrils to highly aggregated, alkali-insoluble fibrils. Callose synthesized in vitro by the Ca(2+), beta-glucoside-activated cotton fiber enzyme, with or without Mg(2+), is very similar in size to callose isolated from cotton fibers, but is a linear (1-->3)-beta-glucan lacking the small amount of branches at C-0-6 found in vivo. We conclude that the high degree of aggregation of the fibrils synthesized with Mg(2+)in vitro is caused either by an alteration of the glucan at the reducing end or, indirectly, by an effect of Mg(2+) on the conformation of the enzyme. Rate-zonal centrifugation of the solubilized mung bean callose synthase confirms that divalent cations can affect the size or conformation of this enzyme.

Journal Article↗
PubMed1987

Contact behaviour during the reassociation of dissociated epithelial cells in primary culture.

The behaviour in culture of dissociated epithelial cells from chick embryo pigmented retina epithelium (PRE), corneal epithelium (CE) and epidermis has been studied using time-lapse cinematography. The analysis concentrated on the contact behaviour of 60 previously isolated cells of each type during a 24 h period starting 3.5 h after the cells were plated out. During the period analysed the number of isolated cells in cultures of all three types gradually decreased as they became incorporated into islands and sheets of cells. However, there were significant differences in behaviour between the cell types during the establishment of these sheets and islands. In PRE cell cultures, islands of cells developed because, throughout the period of analysis, collisions involving previously isolated cells almost invariably resulted in the development of a stable contact. Once having established contact with another cell these cells rarely broke away again to become reisolated. In contrast the contacts formed between colliding CE and epidermal cells were, at least initially, much less stable and cells of both these types were frequently seen to break away and become reisolated after colliding with other cells. Sheets and islands of cells eventually developed in these cultures because the frequency with which isolated cells become reisolated decreased with increasing time in culture. The possible reasons underlying the different behaviour of PRE cells, when compared with that of CE and epidermal cells, are discussed. It is suggested that the decreasing tendency of isolated CE and epidermal cells to become reisolated may be related to the formation of desmosomes.

Animals↗
PubMed1986

Bacteraemia in diabetics.

During a period of 22 months one or more episodes of bacteraemia were detected in 168 patients in hospital. Of these, 29% also had diabetes compared with 10% of the total number of patients admitted to hospital during this time (P less than 0.001). The diabetics with bacteraemia were elderly and diabetes had usually been present for many years. Most of them were not receiving insulin at the time bacteraemia was diagnosed. Escherichia coli was the commonest pathogen (33%) in the diabetics, the main source of infection being the urinary tract. This finding may be due to diabetic autonomic neuropathy, which leads to a poorly emptying, chronically infected bladder. Urinary tract infections with bacteraemia in elderly diabetics are often accompanied by vague non-specific symptoms and poor diabetic control. Fever is infrequent. Prompt antibiotic therapy and insulin injections to control the diabetes usually cure these serious infections.

Aged↗
PubMed1985

Amplification and expression of phenylalanine hydroxylase in mouse erythroleukemia cells.

A cell line, CY-1, was selected in tyrosine free (tyr-) medium after fusion of mouse erythroleukemia (MEL) cells with mitomycin C-treated rat hepatoma cells. MEL cells do not express the enzyme phenylalanine hydroxylase (PH) and are unable to grow in tyr- medium, whereas the rat hepatoma cells constitutively express PH and are able to grow in tyr- medium. CY-1 cells resemble MEL cells morphologically, karyotypically, and in being inducible for hemoglobin synthesis. In contrast to MEL cells, CY-1 expresses PH and is therefore able to grow in tyr- medium. Using a rat cDNA probe for the PH gene, Southern blot analyses were carried out on DNA isolated from CY-1 and parental cells. CY-1 showed the characteristic mouse PH gene pattern but the gene copy number was amplified four- to eightfold compared to parental MEL cells.

Animals↗
PubMed1985

Cellulose microfibril assembly and orientation: recent developments.

A brief history of the literature dealing with cellulose microfibril assembly is presented, and a current summary of cellulose microfibril synthesizing complexes among eukaryotic cells is given. Terminal complexes not described before include the following: linear terminal complexes (TCs) with three rows in Eremosphaera, Microdictyon and Chaetomorpha; globular terminal complexes in Ophioglossum, Psilotum, Equisetum and Gingko. Cellulose microfibril assembly in Acetobacter xylinum is described very briefly and compared with the process among eukaryotic cells. Particular emphasis on structures that may be involved in the spatial control of cellulose synthesis is given. Among these are cytoplasmic structures such as microtubules and microfilaments. Microfilament structures are shown to clearly surround individual microtubules that lie adjacent to the plasma membrane. Using freeze-fracture techniques, these labile associations have been shown for the first time. Microfibril orientation may be mediated through an interaction of cortical microtubules in association with microfilaments. A review of Mueller and Brown's membrane flow model for microfibril orientation is presented. Cellulose terminal complex clustering and its role in gravitropic response is covered. Definitive membrane changes with TC clustering/disaggregation and intramembranous particle frequencies, occur within 12 min following gravistimulation. These differences are pronounced in the cells from upper and lower hemicylinders of rapidly frozen tissue, which was studied by the freeze-fracture method. A hypothesis for cellulose microfibril interaction in controlling the constraint of the growth axis is presented, and the supporting data for terminal complex clustering/disaggregation as well as fluorescent brightener inhibition of the gravitropic response support this hypothesis. The onset and regulation of cellulose microfibril assembly is presented for synchronized protoplasts generated by Boergesenia, using inhibitors of transcription and translation. These results suggest dynamic turnover of terminal complex subunits during the assembly of the cellulose microfibril. This study is concluded with a brief discussion of possible phylogenetic trends in the evolution of cellulose synthesis. A principal underlying theme is that the specific arrangement and consolidation of the terminal complex subunits determine to a large degree the size and shape of the microfibril, its crystallinity, as well as intramicrofibrillar associations. Three basic types of TCs appear among all eukaryotic cells studied so far: namely, the rosette, the globular and the linear complex.

Cell Membrane↗
PubMed1985

Morphology and locomotion of individual epithelial cells in culture.

The behaviour in culture of epithelial cells derived from chick embryo pigmented retina epithelium (PRE), corneal epithelium (CE) and epidermis has been studied using time-lapse cinemicrography. The analysis concentrated on the morphology and movement of individual isolated cells, lacking contacts with other cells, during a 24h period starting 1-3 h after the cells were plated out in primary cultures. Isolated cells from all three sources could change morphology and reversibly exhibited either a poorly spread or a well-spread morphology. While poorly spread, the different cell types all appeared similar and all blebbed vigorously. In contrast, while well spread, the cells did not bleb significantly but there were other differences between them. Well-spread CE cells were always polarized by the presence of a dominant leading lamella but well-spread PRE cells were always unpolarized. Well-spread epidermal cells exhibited both a polarized and an unpolarized morphology. The tendency of individual isolated cells to change morphology varied with cell type. PRE cells were the most stable. Nearly 80% of them retained the same morphology throughout the period of analysis and only 1% of them showed three or more changes in morphology during this period. In contrast, 22% of CE cells and 37% of epidermal cells showed three or more changes in morphology during the period of observation. Isolated cells of all three types spent a greater proportion of the time exhibiting a poorly spread morphology than they spent exhibiting any alternative well-spread morphology. The analysis revealed a relationship between the morphology of isolated cells and the speed of their locomotion. Only cells with a well-spread polarized morphology showed significant movement. CE and epidermal cells with this morphology moved three to four times faster than their counter-parts with a poorly spread morphology or, in the case of epidermal cells, with a well-spread but unpolarized morphology. Actively moving PRE cells were not seen and this correlates with the absence of cells with a well-spread polarized morphology from cultures of this type. These findings are discussed in the light of similar investigations of cell behaviour in other epithelial cell types and fibroblasts.

Animals↗
PubMed1985

Pharmacokinetics and tissue penetration of temocillin.

The pharmacokinetics of intravenous (bolus) temocillin 1 g were studied in 6 healthy male volunteers, and a cantharides blister method was used to estimate tissue penetration of the antibiotic. The mean elimination half-life was 4.5 hours. Temocillin penetrated blister fluid rapidly and reached concentrations of about 50% of those in serum by 2 to 3 hours after administration. Over an 8-hour period, the serum and blister fluid concentrations exceeded the MIC90 of susceptible bacteria by 2-fold or greater, suggesting that twice or even once daily dosing with temocillin may be sufficient.

Blister↗
PubMed1984

Observations on the Menkes' and brindled mouse phenotypes in cell hybrids.

Somatic cell fusion was used to study the genetic defect in Menkes' disease and in the brindled mouse mutant. Eight hybrids derived from fusion of Menkes' fibroblasts with HeLa cells and 11 hybrids between a brindled mouse fetal cell line and a mouse A9 cell were studied. The hybrids showed copper isotope uptake intermediate between the mutant and nonmutant lines and copper isotope efflux similar to that of the nonmutant parent. These results indicate that complementation studies between the mutants should be possible.

Animals↗
PubMed1983

Elimination of Mycoplasma orale from the human hepatoma cell line, PLC/PRF/5.

We have tried without success to eliminate M. orale from a human hepatoma line, PLC/PRF/5, using five different methods. We report here the successful elimination of the contamination by a modification of the technique of Marcus et al. [1] using 5-bromodeoxy-uridine (BrdU) instead of 5-bromo-uracil (5-BrUra) and light. We believe that this method may prove useful when rare and valuable cell lines carry the more common mycoplasma contaminant M. orale.

Bisbenzimidazole↗
PubMed1983

Phonetic coding in marginally competent readers.

Findings from recent studies suggest that children with reading disorders are deficient in coding the phonetic features of letters in memory, and that this deficiency is apparent whether the letters are presented visually or auditorily. The present investigation represents an additional test of the phonetic-deficit hypothesis. Ss in this experiment were 16 children classified as marginally competent readers and 16 children classified as good readers. Their task was to recall rhyming or nonrhyming letter sequences presented either visually or auditorily. Marginal readers showed less evidence of phonetic coding than good readers, whether letter presentations were visual or auditory, as in previous studies. However, analyses carried out separately on the data of each reading group suggest that marginal readers were capable of phonetic coding, at least when letter presentations were auditory. These findings raise the possibility that the phonetic-coding deficiency shown by children who are subaverage readers is not as pervasive as has been suggested previously.

Child↗