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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 271 records · Page 15Linked to original sources
PubMed1992

A comparative analysis of two preparations of human chorionic gonadotrophin.

A biophysical analysis of two pharmaceutical preparations of human chorionic gonadotrophin (Endo and Profasi) demonstrated that both contained high hCG specific activity. HCG protein analysis by occlusion HPLC and SDS gel electrophoresis showed similar profiles for both products. Although the purified protein components of both preparations were similar their were differences in the contents of the unpurified preparations. The Endo preparation exhibited greater inter-vial variability and contained an unidentified aromatic substance which interacted with the desalting column.

Chemical Phenomena↗
PubMed1992

Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane Cl- channel regulated by cyclic AMP-dependent phosphorylation and by intracellular ATP. Mutations in CFTR cause cystic fibrosis partly through loss of cAMP-regulated Cl- permeability from the plasma membrane of affected epithelia. The most common mutation in cystic fibrosis is deletion of phenylalanine at residue 508 (CFTR delta F508) (ref. 10). Studies on the biosynthesis and localization of CFTR delta F508 indicate that the mutant protein is not processed correctly and, as a result, is not delivered to the plasma membrane. These conclusions are consistent with earlier functional studies which failed to detect cAMP-stimulated Cl- channels in cells expressing CFTR delta F508 (refs 16, 17). Chloride channel activity was detected, however, when CFTR delta F508 was expressed in Xenopus oocytes, Vero cells and Sf9 insect cells. Because oocytes and Sf9 cells are typically maintained at lower temperatures than mammalian cells, and because processing of nascent proteins can be sensitive to temperature, we tested the effect of temperature on the processing of CFTR delta F508. Here we show that the processing of CFTR delta F508 reverts towards that of wild-type as the incubation temperature is reduced. When the processing defect is corrected, cAMP-regulated Cl- channels appear in the plasma membrane. These results reconcile previous contradictory observations and suggest that the mutant most commonly associated with cystic fibrosis is temperature-sensitive.

3T3 Cells↗
PubMed1992

The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. A prospective, randomized, double-blind trial.

In this study, we report the results of a prospective, double-blind trial to determine whether high-dose topical corticosteroids have an effect on refractive outcome or anterior stromal haze after photorefractive keratectomy. A total of 113 patients were allocated randomly to either placebo- or steroid-treated groups (0.1% dexamethasone metasulphobenzoate for 3 months) and underwent either -3.00-diopter (D) or -6.00-D procedures. At 6 weeks, the mean change in refraction was significantly greater in the steroid-treated group than in the placebo-treated group (-3.00-D group, P = .0015; -6.00-D group, P = .0011). However, when corticosteroids were discontinued at 3 months, this difference became statistically insignificant. There was no statistically significant effect on anterior stromal haze at any stage. Since long-term use of corticosteroids to maintain the initial beneficial effect on refraction would be unacceptable, we conclude that these agents should not be used after photorefractive keratectomy.

Administration, Topical↗
PubMed1992

Karyotypic evolution of a murine mammary adenocarcinoma in vitro and during progression from primary to metastatic growth in vivo.

We have previously described a murine mammary tumor cell line (SP1) that metastasizes when transplanted into the mammary gland, but not when injected into the subcutaneous site. We used cytogenetic markers to assess genetic heterogeneity, and to monitor the selection and evolution of karyotypically distinct cell types during primary tumor growth and in metastases. The SP1 tumor cells are hypotetraploid (mean chromosome number = 72), and have at least four karyotypically distinct cell types. We found no consistent pattern of selection of tumor cell types in primary tumors. However, metastases were derived from a cell type that was present in the corresponding primary tumor. In addition, novel, karyotypically distinct cell types also appeared in the metastatic nodules. Markers that appeared in metastases included two translocations, t(10;18) and t(1;19). By injecting a mixture of cells from a metastatic nodule with a non-metastatic clone into mice, we showed that the new cell types in metastases displayed a stable increased growth and metastatic potential when compared to the non-metastatic clone, or when compared to the initial cell type from which the metastases derived. These results indicate that metastases are derived from a distinct cell type in the primary tumor, but that additional chromosome and cell evolution occurs, resulting in new cell types that are selected in metastases.

Adenocarcinoma↗
PubMed1992

Glycoprotein glycosylation and the immunosuppressive effects of human pregnancy serum.

Pregnancy serum contains a factor or factors which suppress T lymphocyte proliferation, although the identity of the factor(s) is still unclear. We have demonstrated that the immunosuppressive activity of pregnancy sera can be destroyed by treatment with periodate which oxidises protein-linked oligosaccharides. Similar effects have been noted with uromodulin, a potent immunosuppressive glycoprotein initially isolated from pregnancy urine. We find, however, that uromodulin is present in both pregnancy and non-pregnancy sera, and that removal of uromodulin from pregnancy serum by lectin affinity chromatography is not associated with loss of activity, ruling out this glycoprotein as the immunosuppressive factor. The possible role of protein-linked oligosaccharides of other serum glycoproteins in causing the pregnancy-related immunosuppression is discussed.

Female↗
PubMed1992

Long-term results of Goode's tympanostomy tubes in children.

The results of a retrospective study of the complications of middle ear ventilation by Goode's T-tubes in children are presented. 248 T-tubes were inserted into 119 patients. 16.9% progressed to spontaneous extrusion with a mean period of ventilation approaching 20 months. 54.9% of patients experienced otorrhoea which was found to be significantly more common in those ears with a mucoid effusion at the time of T-tube insertion. 21.1% of ears developed a persistent perforation where spontaneous extrusion had occurred or the T-tubes had been removed. Perforation also occurred more frequently in those with otorrhoea.

Child↗
PubMed1992

Correlation between biochemical composition and fluorescein binding of deposits in Bruch's membrane.

PURPOSE: The fluorescence of drusen during fluorescein angiography is believed to have important prognostic and pathogenetic implications in age-related maculopathy. It is believed that deposits containing predominantly neutral lipids would be hydrophobic, resulting in hypofluorescence on fluorescein angiography, while the presence of polar phospholipids would be indicated clinically by hyperfluorescence because of its hydrophilic properties. To identify the potential determinants of fluorescence of drusen and Bruch's membrane, a series of macular specimens from human donors older than 60 years of age was examined. No clinical information was available concerning any previous eye disease. METHODS: In vitro fluorescein binding was recorded microscopically, and the presence of fibronectin was sought by immunohistochemistry. The results were correlated with the proportions of phospholipids to neutral lipids identified by histochemical and biochemical studies. RESULTS: It was found that high content of neutral fats was associated with lack of both fluorescein binding and fibronectin, and, conversely, in those specimens with high proportions of phospholipids, fluorescein binding was strong and fibronectin was present. CONCLUSIONS: These observations support the central hypothesis concerning biophysical changes in Bruch's membrane with age and the potential importance of fluorescein angiography in the characterization of Bruch's membrane deposits.

Aged↗
PubMed1992

Excimer laser photorefractive keratectomy. 18-month follow-up.

PURPOSE: This study, comprising 120 patients (follow-up, 12 to 22 months; mean, 18 months), was designed to evaluate the efficacy and safety of excimer laser photo-refractive keratectomy. METHODS: Ablation zone diameter (4 mm), ablation rate (0.22 microns/pulse), fluence (180 mJ/cm2), and frequency (10 Hz) were kept constant, and all patients used a standard topical corticosteroid regimen. RESULTS: Overcorrection was followed by regression to a stable refraction by 4 months. At 1 year, 95% and 70%, respectively, of patients undergoing - 2.00 diopters (D) and -3.00 D corrections and 40% and 20% of those undergoing -6.00 D and -7.00 D corrections were within +/- 1.00 D of intended refraction. Anterior stromal "haze," maximal at 6 months and diminishing thereafter, was detected in 110 patients (92%). However, best-corrected Snellen visual acuity was reduced in only 22 (18%). Good correlation existed between haze and regression (r = 0.68). Night "halos," due to the relatively small 4-mm diameter ablation zone, were reported by 94 patients (78%) in the early postoperative period, and, at 1 year, 12 (10%) declined treatment of the other eye because of persistence of this problem. CONCLUSION: Marked individual variation was found after photorefractive keratectomy. However, in low myopia, predictability is "fair," and the procedure is safe. The authors conclude that excimer laser photorefractive keratectomy holds considerable promise for refractive surgery in the future.

Adult↗
PubMed1992

Production of cystic fibrosis transmembrane conductance regulator in the milk of transgenic mice.

Here we describe the production of cystic fibrosis transmembrane conductance regulator (CFTR), the product of the gene associated with cystic fibrosis, in the milk of transgenic mice. Mammary specific expression was achieved by placing the CFTR cDNA under the control of the goat beta-casein gene promoter. By fractionation, CFTR was shown to be associated with the membranes that envelop milk fat globules as they are discharged from the apical surface of the mammary epithelia. Since milk fat globules may comprise up to 10% of whole milk, this represents a novel, inexpensive and efficient approach to produce CFTR and possibly other membrane-associated proteins. The availability of large quantities of CFTR could have important implications for the development of new therapies for cystic fibrosis.

Animals↗
PubMed1992

Diet in the epidemiology of bladder cancer in western New York.

We present the dietary epidemiology of bladder cancer while controlling for a number of lifestyle and environmental risk factors in a study of 351 white male cases with histologically confirmed transitional cell carcinoma of the bladder and 855 white male controls selected from Erie, Niagara, and Monroe counties of western New York from 1979 to 1985. Usual diet was estimated by comprehensive interviews with use of a detailed food frequency questionnaire. An increased risk of bladder cancer was associated with higher kilocalorie intake, but only among those under 65 years of age, with the strongest pattern associated with fat intake. Further analyses of fat, carbohydrates, and protein, with adjustment for total kilocalories, resulted in a positive association of risk with fat intake and a decreasing risk with higher protein intake. Of the vitamins, carotenoid consumption appeared to decrease risk with increased consumption for those under 65 years of age. No significant differences between cases and controls were seen for intake of calcium, retinol, thiamin, riboflavin, niacin, vitamin C, vitamin D, and vitamin E. After adjustment for kilocalories and other confounders, higher intake of dietary sodium was associated with increased risk among both age groups, and the trends were statistically significant. The importance of diet in the etiology of bladder cancer is suggested by our findings.

Adult↗
PubMed1992

The effect of dilution rate and pH on biomass and proteinase production by Micrococcus sedentarius grown in continuous culture.

Micrococcus sedentarius, an organism associated with pitted keratolysis, produced two proteinases in culture supernatant fluids, as shown by non-denaturing PAGE with overlaying with a casein substrate. A mixture had optimal activity at pH 10 with azocasein substrate. At pH 7.1 and 8.1 in continuous culture with varying dilution rates high proteinase production occurred at relative specific growth rates (mu rels) 0.39 and 0.77 and biomass concentrations decreased with increasing dilution rate. One proteinase was constitutive and varied little in production with different growth rates. The other proteinase was under control with high production at low growth rates and no production at high growth rates. With varying pH at mu rels 0.39 and 0.77 maximum biomass concentration and proteinase production occurred between pH 8.0 and 9.0 as did the highest specific growth rate. These results support the hypothesis that Mic. sedentarius produces pitting in the stratum corneum when the skin is hydrated and the pH rises above neutrality.

Cell Division↗
PubMed1992

Confocal imaging of the fundus using a scanning laser ophthalmoscope.

A confocal scanning laser ophthalmoscope (cSLO) was used to examine the effects of confocal optics on the image of the human fundus in vivo. Patients from a retinal clinic and a glaucoma clinic were examined using the cSLO in the confocal mode. A degree of optical sectioning could be achieved, and the results agree with a best axial resolution of 300 microns measured in a model eye. The main advantage of using a confocal system was found to be the improved contrast of the images. This improved the resolution of structures such as the lamina cribrosa and optic disc drusen which are seen in low contrast in conventional images. The improved contrast of the confocal images is partly achieved by excluding light which has been scattered within the plane of focus. Structures which multiply scatter light will become less visible with confocal optics and hard exudates were found to be an example of such a structure. The cSLO and the fundus camera are seen as complementary instruments rather than as alternatives for imaging the fundus. It is envisaged that confocal imaging will enable details of the fundus to be revealed which are at present not seen in conventional images.

Fundus Oculi↗
PubMed1992

Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain.

1. The gene for a mammalian Shaw K+ channel has recently been cloned and has been shown, by alternative splicing, to give rise to two different transcripts, Kv3.1 alpha and Kv3.1 beta. To determine whether these channels are associated with specific types of neurons and to determine whether or not the alternately spliced K+ channel variants are differentially expressed, we used ribonuclease (RNase) protection assays and in situ hybridization histochemistry to localize the specific subsets of neurons containing Kv3.1 alpha and Kv3.1 beta mRNAs in the adult and developing rat brain. 2. In situ hybridization histochemistry revealed a heterogeneous expression pattern of Kv3.1 alpha mRNA in the adult rat brain. Highest Kv3.1 alpha mRNA levels were expressed in the cerebellum. High levels of hybridization were also detected in the globus pallidus, subthalamus, and substantia nigra reticulata. Many thalamic nuclei, but in particular the reticular thalamic nucleus, hybridized well to Kv3.1 alpha-specific probes. A subpopulation of cells in the cortex and hippocampus, which by their distribution and number may represent interneurons, were also found to contain high levels of Kv3.1 alpha mRNA. In the brain stem, many nuclei, including the inferior colliculus and the cochlear and vestibular nuclei, also express Kv3.1 alpha mRNA. Low or undetectable levels of Kv3.1 alpha mRNA were found in the caudate-putamen, olfactory tubercle, amygdala, and hypothalamus. 3. Kv3.1 beta mRNA was also detected in the adult rat brain by both RNase protection assays and by in situ hybridization experiments. Although the beta splice variant is expressed at lower levels than the alpha species, the overall expression pattern for both mRNAs is similar, indicating that both splice variants co-expressed in the same neurons. 4. The expression of Kv3.1 alpha and Kv3.1 beta transcripts was examined throughout development. Kv3.1 alpha mRNA is detected as early as embryonic day 17 and then increases gradually until approximately postnatal day 10, when there is a large increase in the amount of Kv3.1 alpha mRNA. Interestingly, the expression of Kv3.1 beta mRNA only increases gradually during the developmental time frame examined. Densitometric measurements indicated that Kv3.1 alpha is the predominant splice variant found in neurons of the adult brain, whereas Kv3.1 beta appears to be the predominant species in embryonic and perinatal neurons. 5. Most of the neurons that express the Kv3.1 transcripts have been characterized electrophysiologically to have narrow action potentials and display high-frequency firing rates with little or no spike adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The Wellcome Trust tropical diseases videodisc project.

This presentation sets out the aims and methodology involved in creating a sophisticated teaching archive in tropical medicine based on the Wellcome Museum of Medical Science. This visual archive will take the form of a videodisc database containing 30,000 video stills combined with a limited amount of moving material. While authoring tools will ensure the continuing production of interactive learning material from the archive, users will have access to several hundred hours of ready made tutorials, and an expert system to teach clinical skills. They will also be able to browse through any part of the archive. Successful management strategies have involved a close and supportive relationship with the project sponsors, the formation of expert groups to solve specific problems, and a process of continuous formative evaluation.

Humans↗
PubMed1992

High cost HMO enrollees. Analysis of one physician's panel.

This report examines health care costs in the panel of one HMO physician in relation to enrollee health status. High cost enrollees, 15% of the practice panel, accounted for 64% of total costs. For all 722 patients included in the study, the components of costs were: ambulatory visits, 40% of total costs; impatient care, 31%; pharmacy services, 10%; radiology services, 5%; and laboratory services, 4%. Patients with severe physical disease (8% of all enrollees) accounted for about one-third of total costs, while those with moderate physical disease (27% of all enrollees) accounted for an additional one-third. Patients treated for 12 chronic conditions accounted for almost two-thirds of total costs. These conditions were (in order of the contribution of patients with each condition to total costs): hypertension, cancer, abdominal pain, heart disease, diabetes, back pain, headache, depression, arthritis, chronic obstructive pulmonary disease, fatigue, and anxiety. Enrollees treated for one or more of these 12 conditions (37% of the practice panel) accounted for 61% of the high cost enrollees and 63% of total costs. Controlling health care costs will require cost effective systems of care for these common chronic conditions. At present, HMOs typically rely on individual providers to manage these common chronic conditions on a case by case basis, rather than organizing clinic-and HMO-wide systems of care. HMO research and quality improvement programs aimed at improving cost effectiveness might productively focus on how practice teams, clinics and the delivery system as a whole could improve the management of the common chronic conditions which affect high cost enrollees.

Chronic Disease↗