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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 325 records · Page 18Linked to original sources

Kinetics of HIV-1 replication and intracellular accumulation of particles in HTLV-I-transformed cells.

The replication kinetics of HIV were examined in HTLV-I-transformed MT-2 cells. The duration of the initial replication cycle was 20 hours, determined by the first detection of infectious progeny virus, development of syncytia, and production of viral RNA and protein. A phase of exponential virus production followed until 62 h postinfection. Cell death occurred in the final phase of infection during which infectious virus production remained constant even though viral RNA and protein production increased at an exponential rate. Accumulations of HIV particles were observed within cytoplasmic vacuoles of infected MT-2 cells. Although cell lysates contained high titers of infectious virus, our data show that an increasing proportion of particles produced late in infection were not infectious.

Cell Line, Transformed↗

Nutritional epidemiology of cancer of the esophagus.

This study of 178 cases of cancer of the esophagus from three counties in western New York, as compared with sex- and age-matched neighborhood controls in 1975-1986, replicated some earlier findings, particularly with regard to the increased risks associated with use of cigarettes and alcohol. The concentration of alcohol in an alcoholic beverage apparently did not affect risk: Beer carried a substantial risk, whereas less-dilute forms of alcohol carried no risk. These findings also suggest that the risk of cancer of the esophagus increases with ingestion of foods containing retinol but not carotene. Although increased risks were found to be associated with increases in total calories and fat ingested, as well as calcium, they appeared to be confounded with the risk associated with retinol, as distinct from carotene. Inasmuch as a difference in risk associated with retinol and carotene has been shown in a few previous inquiries dealing with esophageal cancer and cancer at other sites, a need for further investigations distinguishing risks associated with the two compounds is apparent.

Beer↗

Substrate kinetics of the tonoplast h-translocating inorganic pyrophosphatase and its activation by free mg.

To clarify the kinetic characteristics and ionic requirements of the tonoplast H(+)-translocating inorganic pyrophosphatase (H(+)-PPiase), PPi hydrolysis and PPi-dependent H(+) transport were studied in tonoplast vesicles isolated from leaf mesophyll tissue of Kalanchoë daigremontiana Hamet et Perrier de la Bâthie. The tonoplast H(+)-PPiase showed an absolute requirement for a monovalent cation and exhibited hyperbolic kinetics with respect to cation concentration. H(+)-PPiase activity was maximal in the presence of K(+) (K(50) approximately 3 millimolar), with PPi-dependent H(+) transport being more selective for K(+) than PPi hydrolysis. When assayed in the presence of 50 millimolar KCl at fixed PPi concentrations, H(+)-PPiase activity showed sigmoidal kinetics with respect to total Mg concentration, reflecting a requirement for a Mg/PPi complex as substrate and free Mg(2+) for activation. At saturating concentrations of free Mg(2+), H(+)-PPiase activity exhibited Michaelis-Menten kinetics towards MgPPi(2-) but not Mg(2)PPi, demonstrating that MgPPi(2-) was the true substrate of the enzyme. The apparent K(m) (MgPPi(2-)) for PPi hydrolysis (17 micromolar) was significantly higher than that for PPi-dependent H(+) transport (7 micromolar). Free Mg(2+) was shown to be an allosteric activator of the H(+)-PPiase, with Hill coefficients of 2.5 for PPi hydrolysis and 2.7 for PPi-dependent H(+) transport. Half-maximal H(+)-PPiase activity occurred at a free Mg(2+) concentration of 1.1 millimolar, which lies within the range of accepted values for cytosolic Mg(2+). In contrast, cytosolic concentrations of K(+) and MgPPi(2-) appear to be saturating for H(+)-PPiase activity. We propose that one function of the H(+)-PPiase may be to act as an ancillary enzyme that maintains the proton-motive force across the vacuolar membrane when the activity of the tonoplast H(+)-ATPase is restricted by substrate availability. As ATP levels decline in the cytosol, free Mg(2+) would be released from the MgATP(2-) complex, thereby activating the tonoplast H(+)-PPiase.

Journal Article↗

Survey of the teaching of disability and rehabilitation to medical undergraduates in the UK.

The objective of the following survey was to attempt to establish to what extent the undergraduates in medical schools in the UK were being exposed to structured teaching of disability and rehabilitation (i.e. seminars, lectures, group discussions). A questionnaire and covering letter were sent to 25 medical schools exploring how the teaching was performed and whether it utilized the active involvement of disabled people and/or their carers. It also attempted to ascertain the degree of interdisciplinary teaching occurring. Results showed that rheumatology, general practice and geriatrics were predominantly responsible for this teaching, with little structured teaching in ENT and ophthalmology. Five schools (25%) reported back that no structured teaching was occurring in any department. As expected, there was a larger proportion of positive responses on opportunistic teaching (ward rounds, outpatients). Additional invited comments on the questionnaire revealed a variety of innovative activities taking place in different medical schools. It is recognized that a questionnaire of this nature has limitations; nevertheless, it did reveal gaps in the teaching of disability and rehabilitation, with several responses indicating that excess pressure on the curriculum from other subjects left little or no space at the present time. Our survey suggests that disability and rehabilitation are given insufficient emphasis in undergraduate teaching. In particular, more active involvement of patients and their carers should be encouraged. The small proportion of schools which teach rehabilitation as a defined specialty no doubt reflects the inadequate academic structure at present in this field.

Persons with Disabilities↗

Stoichiometry of cellular and viral components in the polyomavirus middle-T antigen-tyrosine kinase complex.

Our results indicate that only one type of tyrosine kinase is present within each middle-T antigen-tyrosine kinase complex, suggesting that middle-T antigen forms separate complexes with different tyrosine kinases. Furthermore, we determined that there is only one molecule of middle-T antigen within any one of these complexes. We interpret this to mean that in any given cell, polyomavirus transformation involves, at least in part, the simultaneous deregulation of a number of separate pathways controlling cellular proliferation. Finally, we also demonstrate that the separate middle-T:pp60c-src and middle-T:pp59c-fyn complexes are each able to interact with the same cellular p81/85-kDa phosphoprotein, a possible component of the phosphatidylinositol kinase.

1-Phosphatidylinositol 4-Kinase↗

Diode laser trabeculoplasty (DLT) for primary open-angle glaucoma and ocular hypertension.

A pilot study has been carried out to examine the efficacy of diode laser trabeculoplasty in the treatment of primary open-angle glaucoma and ocular hypertension. The device used was portable and could be attached to a standard slit-lamp microscope. Powers of 0.8-1.2 W were used, with a spot size of 100 microns and a pulse of 0.20 second. Laser trabeculoplasty carried out on 20 eyes for glaucoma resulted in a mean ocular hypotensive effect of 10.2 mmHG at two weeks after treatment and of 9.55 mmHg at 6 months. It is concluded that diode laser trabeculoplasty is an effective mode of treatment for eyes with open-angle glaucoma or with ocular hypertension.

Aged↗

Quantification of lens opacification with a commercially available lensometer.

A clinical trial was undertaken to determine whether a commercially available lens opacity meter (LM701), which measures backward scattered light from the lens, provides reliable clinical information about the effect of lens opacities on visual acuity. At the 0.001 level of probability we found a significant relationship between the lens opacity meter reading and both the Snellen acuity and patient's age. For a given individual there was also a relationship between the difference in the lens opacity readings between eyes and the difference in the Snellen acuities. We could not demonstrate a relation between the lens opacity reading and either the refractive error, pupil size, or near visual acuity at this level of significance.

Adult↗

Chronically ill psychiatric patients in a district general hospital unit. A survey and two-year follow-up in an inner-London health district.

A survey was undertaken at the end of 1984 of all patients occupying psychiatric beds for more than six months in an inner-London health district. Excluding those with senile dementia, 30 patients were identified. Two years later, a follow-up survey traced the original cohort and the accumulation of additional patients on the wards. The finding that the rate of discharge from the original group matches the accumulation of new patients into the survey suggests a need for new types of community provision within the district.

Adult↗

Survival of structure and function in postmortem rat and human retinas: rhodopsin regeneration, cGMP and the ERG.

Procedures for regenerating visual pigment and restoring phototransduction have been established with freshly isolated, bleached rat retinas. Phosphatidyl choline liposomes containing a 500 microM mixture of retinal isomers, including the 9-cis and 11-cis forms, were employed and the results compared with dark-adapted retinas, incubated similarly but without retinal. The following were recovered in a 60 min incubation, rhodopsin (plus isorhodopsin) to 91% of the original rhodopsin concentration, 87% of cGMP and 89% of PIII amplitude at saturation. PIII amplitude vs. log intensity curves gave values of n between 0.6 and 1/2.0 and sigma between 85 and 439 quanta/micron 2. Human retinas, ranging from 18 to 58 hours postmortem and treated as above, also produced photoresponses. Of the 7 retinas studied so far, rhodopsin has been regenerated to 0.1-0.35 nmol/mg protein, cGMP to 23.5-49.2 pmol/mg protein, and PIII to 20-50 microV: in some cases a b-wave was also seen. Values of n varied between 0.6 and 1.0, and sigma between 132 and 3700 quanta/micron 2. PIII responses were also seen after retinas, approximately 30 hours postmortem, were incubated for a further 24 hours in fortified medium. After incubation, retinal vacuolation was reduced.

Adolescent↗

Gauze-induced granuloma ("gauzoma"): an uncommon complication of gauze reinforcement of berry aneurysms.

Incompletely and even adequately clipped berry aneurysms are often reinforced with finely shredded gauze. In seven female patients this practice led to a series of events including headache, pyrexia, seizures, cranial nerve deficits, endocrinopathy, cerebrospinal fluid pleocytosis, and an enhancing mass demonstrated by computerized tomography at the aneurysm site. One patient with blindness, hydrocephalus, and panhypopituitarism died and was examined at autopsy. Three additional female patients have been identified in the literature with similar case histories. It is suggested that in these patients the gauze induced a foreign-body granuloma, accompanied by progressive occlusion of neighboring small arteries. It would seem prudent to reserve gauze reinforcement for aneurysms that cannot be securely obliterated surgically.

Adult↗

Aging changes in Bruch's membrane. A histochemical and morphologic study.

Using histochemical staining techniques and electron microscopy, the authors have examined the histochemical properties and ultrastructure of Bruch's membrane in 30 human eyes with an age range of 1 to 95 years. The results analyzed in three age groups (0-30 years, 31-60 years, and older than 60 years) show that there is a progressive accumulation of lipids in Bruch's membrane with relation to age. Differences were found in the specific types of lipids in individual eyes. Five eyes stained for neutral lipids alone, four stained predominantly for phospholipids, and nine stained intensely for both neutral lipids and phospholipids. The deposits were associated with the progressive destruction of the native architecture of Bruch's membrane but no correlation was identified between specific inclusions in Bruch's membrane with a particular lipid. These results are significant to age-related macular disease (ARMD), and the lipid rich barrier in Bruch's membrane is implicated as a cause of photoreceptor dysfunction and pigment epithelial detachment.

Adolescent↗

Purification and properties of pyruvate kinase from Dictyostelium discoideum.

Pyruvate kinase (EC 2.7.1.40) from aggregating Dictyostelium discoideum cells has been purified to homogeneity. It has a monomeric molecular weight of 66kD and is tetrameric in low ionic strength buffers. The enzyme is not regulated by fructose 1,6-bisphosphate or by alanine and appears to resemble the M1 isoenzyme from rat liver most closely, although its activity is not inhibited by ATP.

Dictyostelium↗

An intervention to reduce the sale of cigarettes to minors.

This study reports the results of an intervention to stop the illegal sale of cigarettes to minors. Sixty-two of 120 stores in Erie County, New York, were randomly selected to receive in the mail an informational packet requesting their help in stopping the illegal sale of tobacco to minors. The packet included a letter to the store manager citing the law prohibiting the sale of tobacco products to minors and requesting their assistance in observing the law; a supply of warning signs; and a tip sheet designed to assist store managers in educating their employees about the law. Two weeks after the mailing, stores in the study were visited by study teenagers aged 14 to 16 who attempted to purchase cigarettes. The intervention resulted in an increased number of stores posting warning signs, but had no effect on deterring the sale of cigarettes to minors. Minors purchased cigarettes in 77% of stores that received the special mailing and in 86% of nonintervention stores. Warning signs were visible in 40% of stores that received the special mailing and in none of the nonintervention stores. The findings from this study suggest that a merchant education program to increase awareness of the law and posting of warning signs is not sufficient to discourage the sale of tobacco products to minors.

Adolescent↗

Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium.

We have investigated the activities of four lysosomal enzymes in RPE cells isolated from three regions of the canine fundus: the tapetal area, the central pigmented area and the peripheral area. The results obtained with freshly isolated cells showed that the activities of acid phosphatase, B-glucuronidase and N-acetyl-B-glucosaminidase were significantly higher in RPE cells derived from the peripheral region when compared to those from the two central regions. In contrast, the activity of cathepsin D was significantly higher in the tapetal region than in the periphery. The regional distribution of both acid phosphatase and B-glucuronidase observed in fresh RPE cells was progressively lost when these cells were grown in culture. Estimations of photoreceptor density per RPE cell from each of the regions indicated that the number of photoreceptors per RPE cell did not vary significantly with retinal location and suggested that variations in enzyme content were not related to differences in photoreceptor cell distribution.

Animals↗

Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease II.

Antigen (egg albumin) injections, which stimulate mucosal mast cells to secrete mediators, were paired with an audiovisual cue. After reexposure to the audiovisual cue, a mediator (rat mast cell protease II) was measured with a sensitive and specific assay. Animals reexposed to only the audiovisual cue released a quantity of protease not significantly different from animals reexposed to both the cue and the antigen; these groups released significantly more protease than animals that had received the cue and antigen in a noncontingent manner. The results support a role for the central nervous system as a functional effector of mast cell function in the allergic state.

Acoustic Stimulation↗

Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease.

Circulating levels of vasoactive intestinal peptide (VIP) in plasma were measured in gauging activity in inflammatory bowel disease (IBD). One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD). Sequential samples of plasma were assayed for VIP by specific radioimmunoassay. Sixty males and 55 females, ranging in age from 22 to 76 years were studied over six months. The results revealed a strong, positive association between VIP levels and clinical activity, both at baseline (r = 0.38, P less than 0.001) and follow-up (r = .41, P less than 0.001). The ability of the VIP immunoassay to gauge clinical activity was also evaluated where VIP concentrations above 30 pg/ml were defined as abnormal. At baseline, sensitivity (specificity) was found to be 81% (55%). The predictive value of a positive (negative) test was 57% (80%). These estimates did not differ at follow-up. Examination of paired plasma samples from intermittently active patients revealed nearly twofold increases (P less than 0.05) in VIP concentration during active periods of disease. The data suggest that plasma VIP levels may be a valuable laboratory parameter in gauging activity in inflammatory bowel disease.

Adult↗