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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 397 records · Page 22Linked to original sources

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↗

Control of erythroid differentiation: possible role of the transferrin cycle.

A monoclonal antibody to the chicken transferrin receptor (JS-8) blocked temperature-induced and spontaneous differentiation of avian erythroid cells transformed by ts- and wt-retroviral oncogenes. In cells committed to differentiate, JS-8 caused an arrest at the erythroblast or early reticulocyte stage, followed by premature cell death, whereas proliferation of noncommitted erythroid cells or other hematopoietic cells remained unaffected. JS-8 had no effect on transferrin binding or internalization, but blocked subsequent receptor-recycling resulting in reduced iron uptake. Restoration of high intracellular iron levels neutralized the action of JS-8, whereas an inhibitor of porphyrine biosynthesis (4,6-dioxoheptanoic acid) closely mimicked the effect of JS-8. This suggests that erythroid differentiation might involve coordinate synthesis of erythrocyte proteins subject to regulation by hemin or hemoglobin.

Alpharetrovirus↗

Mortality of a municipal worker cohort: III. Police officers.

Very little is known about the long-term health risks associated with the high stress police officer occupation. We report here on a retrospective cohort of 2,376 ever-employed white male police officers employed between January 1950 and October 1979. Vital status was obtained for 96%, the officers accumulating a total of 39,462 person-years. Six-hundred sixty-one deaths were observed. Total mortality from all causes was comparable to that of the overall U.S. white male population (standardized mortality ratio [SMR] = 106). Significantly increased mortality was seen for all malignant neoplasms combined (SMR = 127), cancer of the esophagus (SMR = 286), and cancer of the colon (SMR = 180). Significantly lower than expected mortality was seen for infectious diseases (SMR = 26), respiratory diseases (SMR = 64), and accidents (SMR = 60). Internal cohort comparisons revealed that policeman exhibited significantly higher mortality from suicide compared to all other municipal employees (rate ratio = 2.9). Analysis of mortality by length of service as a police officer showed that those employed 10-19 years were at significantly increased risk of digestive cancers and cancers of the colon and lymphatic and hematopoietic tissues and decreased risk for all diseases of the circulatory system. Policeman employed more than 40 years had significantly elevated SMRs for all causes, all malignant neoplasms combined, digestive cancers, cancers of the bladder and lymphatic and hematopoietic tissues, and arteriosclerotic heart disease. Risk of mortality from arteriosclerotic heart disease tended to increase with increasing years employed. These findings are discussed in light of the police stress literature. The hypotheses generated in this study must be tested through study of the role of important confounders including reactions to stress on the job.

Adult↗

Extensive subretinal pigment epithelial deposit in two brothers suffering from dominant retinitis pigmentosa. A histopathological study.

The eyes of two brothers with retinitis pigmentosa were removed after death and examined by a variety of techniques, including conventional histology, fluorescence microscopy and both scanning and transmission electron microscopy. Their condition was considered to be of an autosomal dominant type but with some atypical clinical features. The outstanding histological feature in both pairs of eyes was a predominantly acellular deposit of amorphous material situated between the retinal pigment epithelium and Bruch's membrane. This material extended from the disc to beyond the ora serrata. In some regions of the retinae of both brothers, there was a cellular infiltrate into the deposit and this included multinucleate cells. In one brother the deposit was lined externally by a fibrovascular membrane in some few locations. All retinae were degenerate, but all showed preservation of abnormally short and sparse photoreceptor cells in both the peripheral and macular areas. There was only patchy loss of the choriocapillaris, which could have been age-dependent rather than disease-dependent, and the remaining choroidal vessels were patent in all cases. The widespread distribution of the deposit is unusual and suggests that it arises from disordered metabolism of the retinal pigment epithelium. We could not determine whether it was a primary disease process or if it arose as a secondary phenomenon.

Electron Probe Microanalysis↗

Primitive series embryonic chick erythrocytes express the transferrin receptor.

A monoclonal antibody specific for the chicken transferrin receptor was used to study receptor expression on circulating red cells from chick embryos of different ages. The use of indirect immunofluorescence with this antibody showed that all circulating immature reticulocytes and primitive series erythrocytes--but not erythrocytes from the definitive series--expressed the receptor. In all cells, the protein was synthesized as a 90-95-kD form. The retention of the transferrin receptor (and another proliferation-dependent cell surface protein) contrasted with the behaviour of a series of other developmentally regulated antigens which are lost during maturation of both primitive and definitive series erythroid cells.

Animals↗

Studies on regional cerebral haematocrit and blood flow in patients with cerebral tumours using positron emission tomography.

Regional cerebral haematocrit has been measured in seven patients with brain tumours, and in one normal subject, using positron emission tomography (PET). Red cell and plasma volumes of distribution were assessed using 11CO and [methyl-11C]albumin, respectively. Haematocrit values were compared with values of regional cerebral blood flow (rCBF) measured using steady-state inhalation of C15O2. Only two of the seven cerebral tumours studied showed any increase in uptake of [methyl-11C]albumin over 45 min. Values of r, the regional ratio of cerebral small-to-large vessel haematocrit, varied from 0.52 to 0.84 for the seven tumours studied. No correlation between r and tumour blood flow was observed. The normal subject yielded an r value of 0.69 for the mean whole brain small-to-large vessel haematocrit ratio. No significant difference between gray and white matter r values was found. The contralateral hemispheres of the seven tumour patients studied yielded an overall mean r value of 0.71 +/- 0.05. We conclude that it is reasonable to assume an r value of 0.7 in tomographic calculations of regional cerebral blood volume (rCBV) from red cell or plasma volumes of distribution in normal brain. Such an assumption for tumours, however, may lead to errors of 35% in estimated rCBV.

Blood Volume↗

Monoclonal antibodies to novel erythroid differentiation antigens reveal specific effects of oncogenes on the leukaemic cell phenotype.

A panel of new monoclonal antibodies to antigens on the surface of chick erythroid progenitor cells is described. These are characterised with respect to their binding to different classes of normal haemopoietic cells of both the erythroid and myeloid lineages. Using these antibodies, we have examined the phenotype of avian leukaemic cells transformed by retroviruses carrying defined oncogenes. Our data show that these cells, although similar to the normal haematopoietic precursor from which they are derived, aberrantly express certain markers in an oncogene specific manner.

Animals↗

Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

The kinetics of the regional cerebral uptake of [11C]3-O-methyl-D-glucose ([11C]MeG), a competitive inhibitor of D-glucose transport, have been studied in normal human subjects and patients with cerebral tumours using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and blood flow enabled corrections for the contribution of intravascular tracer signal in PET scans to be carried out and regional unidirectional cerebral [11C]MeG extractions to be determined. A three-compartment model containing an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [11C]MeG uptake data. Under fasting, resting conditions, normal controls had mean unidirectional whole-brain, cortical, and white matter [11C]MeG extractions of 14, 13, and 17%, respectively. Mean values of k1 and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for [11C]MeG and [18F]2-fluoro-2-deoxy-D-glucose (18FDG), a second competitive inhibitor of D-glucose transport. k3, a rate constant describing FDG phosphorylation, was 20 times higher for cortical FDG uptake than the k3 fitted for [11C]MeG cortical uptake. Glioma [11C]MeG extractions ranged from normal levels of 12% to raised levels of 30%. Transport of [11C]MeG in and out of contralateral cortical tissue was significantly depressed in patients with gliomas. It is concluded that under fasting, resting conditions, regional cerebral glucose extraction remains relatively uniform throughout normal brain tissue. Gliomas, however, may have raised levels of glucose extraction. The nature of the second cerebral compartment required to describe [11C]MeG uptake is unclear, but it could represent either a useless phosphorylation-dephosphorylation cycle or nonspecific tracer uptake by a cerebral subcompartment.

3-O-Methylglucose↗

Studies on regional cerebral pH in patients with cerebral tumours using continuous inhalation of 11CO2 and positron emission tomography.

Regional cerebral pH (rpH) was measured in 12 patients with cerebral tumours and in 5 normal subjects using continuous inhalation of 11CO2 and positron emission tomography (PET). Cerebral tumours with a disrupted blood-brain barrier (BBB) on computed tomography scanning had a similar rpH to that of equivalent regions of contralateral brain tissue (mean tumour rpH, 6.98; mean contralateral brain pH, 6.99). Cerebral tumours with an intact BBB were consistently found to be more alkaline than contralateral brain tissue (mean tumour rpH, 7.09). There was no significant difference between the mean rpH values obtained for peripheral cortical gray and central white matter in normal subjects (7.02 and 6.98, respectively). It is concluded that in spite of reports of raised levels of aerobic glycolysis in neoplastic tissue, there is no evidence that cerebral tumour rpH values are depressed.

Blood-Brain Barrier↗

[Wound healing of the corneal posterior surface in animal experiments].

Autoradiographic studies using tritiated thymidine as a precursor of DNA synthesis show that the process of wound healing of the corneal endothelium in both rhesus monkeys and rabbits following scarification and cryocoagulation takes place for the most part by means of cell proliferation. After injection of tritiated thymidine into the anterior chamber immediately prior to sacrifice, autoradiographically labeled flat mounts and cross-section preparations of the corneas of 7 rhesus monkeys and 14 rabbits were examined at lesion ages ranging from 4 hours to 10 days. In the monkeys scarcely 10% of the endothelial cells in the areas of the corneal lesions or at their borders were in the S-phase in the autoradiographically labeled flat mounts 24 hours to 3 days after injury, whereas up to 39% of those in the rabbits were seen to be so after 18 hours. In the monkeys one could discern mitoses between the 2nd and 5th days, and amitoses (binuclear cells) were found in 1-day and 3-day animals. In rabbits numerous mitoses could be discerned between the 1st and 5st days, but no multinuclear cells were seen. Healing of the corneal endothelium in the monkeys occurred some-what later and was less pronounced than in the rabbits.

Animals↗

Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes.

Several cDNA clones coding for the high molecular weight (alpha) subunit of the voltage-sensitive Na channel have been selected by immunoscreening a rat brain cDNA library constructed in the expression vector lambda gt11. As will be reported elsewhere, the amino acid sequence translated from the DNA sequence shows considerable homology to that reported for the Electrophorus electricus electroplax Na channel. Several of the cDNA inserts hybridized with a low-abundance 9-kilobase RNA species from rat brain, muscle, and heart. Sucrose-gradient fractionation of rat brain poly(A) RNA yielded a high molecular weight fraction containing this mRNA, which resulted in functional Na channels when injected into oocytes. This fraction contained undetectable amounts of low molecular weight RNA. The high molecular weight Na channel RNA was selected from rat brain poly(A) RNA by hybridization to a single-strand antisense cDNA clone. Translation of this RNA in Xenopus oocytes resulted in the appearance of tetrodotoxin-sensitive voltage-sensitive Na channels in the oocyte membrane. These results demonstrate that mRNA encoding the alpha subunit of the rat brain Na channel, in the absence of any beta-subunit mRNA, is sufficient for translation to give functional channels in oocytes.

Animals↗

Dietary vitamin A and cancer--a multisite case-control study.

The relationship between an index of dietary vitamin A and cancer risk at 25 sites was assessed in retrospective case-control studies. Common control groups for males and females were used in all analyses. Relative risk estimates were derived from multiple logistic regression analyses that controlled for age, alcohol consumption, and smoking exposure. We found that among males, dietary vitamin A is associated with lower risk for cancers of the tongue, floor and other mouth, pharynx, larynx, esophagus, and lung but higher risk for Hodgkin's disease and leukemia. Among females, we found that dietary vitamin A had less effect on risk generally but was associated with lower risk for bladder cancer. These findings are consistent with previous research that showed dietary vitamin A to be associated with decreased risk of squamous epithelial cancers. The association of dietary vitamin A and increased risk of Hodgkin's disease and leukemia among males in addition to the disparity in effect of dietary vitamin A on risk between males and females are areas worthy of further research.

Adult↗

Studies on cerebral oxygen metabolism, blood flow, and blood volume, in patients with hydrocephalus before and after surgical decompression, using positron emission tomography.

Cortical oxygen utilization, oxygen extraction, blood flow, and blood volume, have been measured in patients with hydrocephalus before and after surgical decompression using positron emission tomography (PET). The hydrocephalus subjects fell into two categories: patients with recent-onset obstructive hydrocephalus and symptoms of raised intracranial pressure due to obstruction of cerebrospinal fluid (CSF) drainage by posterior fossa or third ventricular cerebral tumours, and patients with hydrocephalus of more insidious onset that was associated either with congenital abnormalities, or which was idiopathic. The hydrocephalus subjects had a significantly reduced level of mean cortical oxygen utilization (rCMRO2) and mean cortical blood flow (rCBF) compared with age-matched normal controls. Patients with recent-onset obstructive hydrocephalus associated with cerebral neoplasia had inappropriately low levels of cortical blood flow compared with their levels of cortical oxygen utilization, all having elevated levels of cortical oxygen extraction (rOER). Levels of cortical blood flow in the group of patients with more insidious-onset hydrocephalus matched levels of cortical rCMRO2, all these subjects having normal levels of rOER. All those hydrocephalus subjects who had a raised cortical oxygen extraction preoperatively increased their cortical blood flow following cerebral decompression. No improvement, however, was noted in their mean cortical oxygen utilization. By contrast, those hydrocephalus subjects with normal baseline levels of cortical extraction showed no improvement in mean cortical blood flow, oxygen utilization, or cognitive function after surgical intervention. It is concluded that if cortical oxygen extraction is elevated, hydrocephalic patients are likely to improve their cortical blood flow following cerebral decompression.

Adult↗

Histopathology of mitochondrial cytopathy and the Laurence-Moon-Biedl syndrome.

Clinical and histopathological studies of two patients with distinctly different inherited juvenile retinal dystrophies indicate that the ocular defect in mitochondrial cytopathy involves the underlying pigment epithelium, whereas in the Laurence-Moon-Biedl syndrome the photoreceptor cells are primarily affected.

Child↗

Effects of increasing numbers of phagocytic inclusions on human retinal pigment epithelial cells in culture: a model for aging.

Cultures of human retinal pigment epithelial cells have been challenged with a number of biological (lipofuscin, melanin, and rod outer segments) and non-biological (latex microspheres) particles at a variety of concentrations. The particles were chosen to include examples of both degradable and non-degradable systems. A range of morphological changes were observed by phase contrast microscopy, and these became more atypical with increasing concentration. At the highest concentration cells had ingested so many particles that many had died and others had ruptured. The time course of these changes indicated a relationship between cellular lytic activity and the capacity of the particle to degrade. The potential of this system as a model for studying senescence is discussed.

Aging↗