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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 217 records · Page 12Linked to original sources
PubMed1995

Decreasing hydraulic conductivity of Bruch's membrane: relevance to photoreceptor survival and lipofuscinoses.

Deterioration of visual performance leading to blindness is particularly severe in the early-onset forms of Batten disease. Metabolic support of the neural retina is critically dependent on the choroidal blood supply and on efficient transport pathways through Bruch's membrane and the retinal pigment epithelium (RPE). Conversely, degradation products and, in particular, damaged membranous components of photoreceptor outer segments must be removed in the opposite direction. Incomplete breakdown of damaged "spent" discs leads to the age-related accumulation of lipofuscin-like pigments in the RPE, and these in turn influence the degenerative changes in Bruch's membrane. The generalized and extensive deposition of lipofuscin-like material in Batten disease is therefore likely to exacerbate the degenerative changes in Bruch's membrane, and thereby compromise local fluid dynamics. The hydrodynamic properties of Bruch's membrane were examined in normal donor eyes and showed a precipitous decline of hydraulic conductivity during early life. In fact, the maximal capacity for fluid transport was halved for every 17 years of life. This finding is therefore highly relevant to the development of ensuing pathology in the neuronal ceroid-lipofuscinoses.

Adolescent↗
PubMed1995

Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients. STUDY DESIGN: Multicenter, prospective, randomized clinical trial. PATIENT POPULATION: Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission. INTERVENTIONS: Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group. RESULTS: Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44). CONCLUSION: In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.

APACHE↗
PubMed1995

The effects of ablation diameter on the outcome of excimer laser photorefractive keratectomy. A prospective, randomized, double-blind study.

OBJECTIVE: To determine the effects of the ablation diameter on the outcome of excimer laser photorefractive keratectomy. DESIGN: Eighty patients were randomized to either a 5.00-mm or a 6.00-mm treatment group and within these groups underwent either a -3.00-diopter (D) or a -6.00-D correction based on their preoperative refraction. A Summit Omnimed excimer laser was used throughout the study. RESULTS: In eyes treated with a 6.00-mm-diameter ablation, the initial hyperopic shift was reduced, with significant differences at 1 week with -3.00-D corrections and at 1 and 4 weeks with -6.00-D corrections (P < .01). At 6 months, the refractive changes were greater and closer to that intended with 6.00-mm-diameter ablations. The predictability of photorefractive keratectomy was significantly improved with 6.00-mm zones, with a reduction in variance of the refractive changes at all stages postoperatively (P < .05 to P < .001). With -3.00-D corrections, objective measurements showed significantly less anterior stromal haze in eyes treated with 6.00-mm zones at 6 months (P < .05). With -6.00-D corrections, haze was significantly reduced at 1, 3, and 6 months in the eyes treated with 6.00-mm zones (P < .05). Five eyes treated with 5.00-mm zones experienced severe regression of the correction, with marked corneal haze and a reduction of 3 or more lines of best corrected Snellen visual acuity at 6 months. No eyes treated with 6.00-mm zones were similarly affected. Computerized measurements of "night" halo were significantly lower in the 6.00-mm treatment groups at 1 week and at 1 and 6 months in the eyes with -3.00-D corrections and at 1 week and at 1 month in the eyes with -6.00-D corrections (P < .05). At 6 months, seven patients treated with 5.00-mm zones complained of severe disturbances of night vision. No eyes in the 6.00-mm group were similarly affected. CONCLUSIONS: Treatment with 6.00-mm ablation diameters precipitated less initial overcorrection, greatly improved the predictability of photorefractive keratectomy, and was associated with a reduction in complications impairing postoperative visual performance.

Adult↗
PubMed1995

Cytokines suppress the shear stress-stimulated release of vasoactive peptides from human endothelial cells.

Endothelial cells from human umbilical vein perfused at 0.5 ml/min released vasopressin, endothelin, and substance P. Upon perfusion of the cells at 3.0 ml/min, the release of endothelin and vasopressin was significantly increased whereas the release of substance P was significantly decreased. Endothelial cells precultured for 24 h with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) released more endothelin and less substance P at low flow and there was no further increase in release at high flow rate. These results suggest that cytokines suppress the normal responses of endothelial cells to increased fluid shear stress.

Cells, Cultured↗
PubMed1995

The jellyfish green fluorescent protein: a new tool for studying ion channel expression and function.

Two methods are described for using the jellyfish green fluorescent protein (GFP) as a reporter gene for ion channel expression. GFP fluorescence can be used to identify the transfected cells, and to estimate the relative levels of ion channel expression, in cotransfection experiments. A GFP-NMDAR1 chimera can be constructed that produces a functional, fluorescent receptor subunit. These methods should facilitate studies of ion channel expression, localization, and processing.

Animals↗
PubMed1995

Trichomonas vaginalis and cervical cancer. A prospective study in China.

The relationship between Trichomonas vaginalis infection and cervical cancer was investigated prospectively in a cohort of 16,797 women aged 25 years or more who were followed from 1974 to 1985 within the framework of a cervical screening program in Jingan, China. Personal interviews were conducted by trained interviewers when the women first entered the screening program. At initial screening, 421 (2.51%) women had a positive cytologic diagnosis of T. vaginalis infection. Ninety-nine incident cases of pathologically confirmed squamous cell carcinoma were identified from the cohort, with a total of 140,018 person-years of observation. T. vaginalis infection was found to contribute to the risk of cervical cancer, as determined by crude estimates and after adjustment for potential confounding effects. In a multiple proportional hazards model, the relative risk for cervical cancer was 3.3 (95% confidence interval: 1.5 to 7.4) among women with T. vaginalis infection. Furthermore, in the multivariate analysis, increased risk of cervical cancer was associated with the following factors: number of extramarital sexual partners of both the subjects and their spouses, cigarette smoking, and irregular menstruation. Having a large number of negative Pap smears was associated with lower risk. This study suggests that there might be an association between T. vaginalis infection and the risk of cervical cancer, but only 4 to 5% of cervical cancer in Chinese women may be attributable to T. vaginalis infection.

Adult↗
PubMed1995

A prospective, randomized, double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy.

PURPOSE: To investigate the role of 1% tetracaine in controlling pain after photo-refractive keratectomy (PRK) and determining its effect, if any, on epithelial healing, refractive outcome, and visual performance. METHODS: In this study, 44 patients were randomized to receive either Gutt. 1% tetracaine or placebo after undergoing PRK. Drops were instilled at 30-minute intervals during waking hours for 24 hours postoperatively. In addition, all patients received two coproxamol (paracetamol + dextropropoxyphene) tablets every 6 hours for 2 days. Visual Analogue Pain Charts were used to record pain levels for 4 days after surgery. Serial digitized retro-illumination photography was used to assess rates of epithelial healing, and surface epithelial quality was monitored using topography. At fixed intervals over a 6-month period visual performance was assessed by measuring refractive outcome, best-corrected visual acuity, objective haze, halo, and glare. RESULTS: Patients in the tetracaine group had significantly less pain (P < 0.0001). Both groups demonstrated full epithelial closure within 72 hours. Similar numbers of patients in both groups at 1 week showed topographic irregularity that completely resolved by 1 month. No statistically significant difference was seen in any of the parameters monitoring visual performance. CONCLUSIONS: Tetracaine in conjunction with coproxamol is effective in reducing pain after PRK without adversely affecting corneal wound healing or visual performance.

Acetaminophen↗
PubMed1995

Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study.

BACKGROUND: The pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains obscure. The placoid lesions and characteristic findings on fluorescein angiography have been interpreted as representing either primary disease of the retinal pigment epithelium or disease of the choroidal vasculature. This study used indocyanine green (ICG) choroidal videoangiography to investigate this controversy. METHODS: Sequential choroidal videoangiography was performed with ICG and a scanning laser ophthalmoscope on patients with acute posterior multifocal placoid pigment epitheliopathy. Image analysis was used to differentiate between masking and ischemia as to the cause of hypofluorescence on the angiograms. RESULTS: Indocyanine green angiograms of acute posterior multifocal placoid pigment epitheliopathy showed areas of hypofluorescence in both the early and late pictures that correlated with the placoid lesions. Image analysis identified these as areas of choroidal hypoperfusion. Successive films showed partial or complete resolution of these hypofluorescent areas. CONCLUSIONS: Indocyanine green choroidal videoangiography has shown choroidal hypoperfusion to underlie the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy.

Acute Disease↗
PubMed1995

Biochemical and molecular characterization of a novel starch synthase from potato tubers.

An isoform of starch synthase from potato tubers which is present both in the stroma of the plastid and tightly bound to starch granules has been identified biochemically and a cDNA has been isolated. The protein encoded by the cDNA is 79.9 kDa and has a putative transit peptide and a distinct N-terminal domain which is predicted to be highly flexible. It is similar in both amino acid sequence and predicted structure to the granule-bound starch synthase II (GBSSII) of pea embryos. When expressed in Escherichia coli, the mature protein has starch synthase activity. The importance of the isoform has been assessed by biochemical measurements and antisense transformation experiments in which the amount of the isoform in the tuber is severely and specifically reduced. Both approaches indicate that the isoform contributes a maximum of 15% of the total starch synthase activity of the tuber. It is suggested that this isoform and the GBSSII of pea embryos represent a widely distributed class of isoforms of starch synthase. The contribution to total starch synthase activity of members of this class probably varies considerably from one type of storage organ to another.

Amino Acid Sequence↗
PubMed1995

Dietary correlates of fat intake.

Dietary fat intake has been associated with the development of chronic diseases, including heart disease and cancer, in human populations; however, associations demonstrated between disease and fat intake may be confounded by related dietary factors. Therefore, description of the correlates of fat intake in free-living adults may help identify important confounders independent of disease status. In a population of 863 women and 538 men between the ages of 50 and 85 randomly selected from two counties in western New York, we found that most nutrients were correlated with grams of total fat intake including protein, carbohydrates, cholesterol, dietary fiber, retinol, iron, and calcium. Carbohydrates and dietary fiber were not related to the concentration of fat in the diet (% of energy from fat). Alcohol intake was negatively associated with fat concentration for men but not for women. Particularly important for the study of cancers, the antioxidants carotene and ascorbic acid were negatively associated with fat concentration in the diet.

Aged↗
PubMed1995

Hospital services for patients with acute stroke in the United Kingdom: the Stroke Association Survey of consultant opinion.

A national postal survey of all UK hospital consultant geriatricians, general physicians and neurologists was performed in 1992/3 in order to describe the provision of hospital stroke services in the United Kingdom and to assess whether the recommendations of the King's Fund consensus conference on stroke had been widely implemented. Of 3478 survey forms, 2923 (84%) were returned and, of these 1953 (67%) consultants indicated that they routinely cared for patients with acute stroke. On their stated estimates, the survey respondents had admitted approximately 107,000 patients with acute stroke in the previous year, 40% of whom were cared for by geriatricians. Sixty-three per cent (1239/1953) worked in District General Hospitals. Few (5%) had access to an acute stroke unit, and a majority (51%) of consultants were uncertain of the benefits of such units. Less than half (44%) had access to a specialized stroke rehabilitation unit, but a majority (68%) were certain of the benefits of stroke rehabilitation units. Although a majority of consultants had on-site CT scanning, about a third of all UK stroke patients were admitted to a hospital without on-site CT facilities. Most (90%) consultants would want a CT scan themselves if they had a stroke. Only about a third of consultants were aware of a recent audit of stroke care in their hospital, or had a hospital policy for the implementation of minimum standards of stroke care, and less than half routinely provided written information for patients or carers. This survey illustrated that five years after the publication of the King's Fund consensus statement on the treatment of patients with acute stroke UK hospital stroke services are still poorly organized. Access to CT scanning for stroke patients is improving, but is still insufficient.

Acute Disease↗
PubMed1995

Irradiation of rabbit retina with diode and Nd:YAG lasers.

AIMS: This study was carried out to compare the effects of continuous wave infrared laser radiation on pigmented and albino rabbit retinas at two wavelengths: 810 nm (diode) and 1064 nm (Nd:YAG). METHODS: Transpupillary laser pulses were applied with a spot size of 200 microns and durations of 200 ms (pigmented rabbits) and 0.5-1 s (albino rabbits). Light and electron microscopic analyses were performed immediately after exposure. RESULTS: In pigmented rabbits, threshold lesions were induced using a power of 100 mW with the diode and 200 mW with the Nd:YAG lasers. Damage was incurred by the retinal pigment epithelium with extension into the superficial and mid choroid posteriorly and into the outer retina anteriorly. In albino rabbits, lesions of comparable anteroposterior extension were identified using a power of 10 W with the Nd:YAG laser. Using diode laser irradiation, a maximum power output of 1.2 W failed to produce discernible lesions. CONCLUSIONS: The observed patterns of morphological damage are produced by complex tissue radiation interactions. In pigmented animals, this was primarily related to absorption of radiant energy by melanin within the retinal pigment epithelium and the choroidal melanocytes. In albino rabbits, laser induced effects occurred as a consequence of multiple scattering, together with absorption within haemoglobin and possibly also within tissue water. The data obtained provide further insight into the biological mechanisms arising from retinal photocoagulation with near infrared lasers.

Acute Disease↗
PubMed1995

Functional activation of the cystic fibrosis trafficking mutant delta F508-CFTR by overexpression.

The most common mutation in the gene associated with cystic fibrosis (CF) causes deletion of phenylalanine at residue 508 (delta F508) of the gene product called CFTR. This mutation results in the synthesis of a variant CFTR protein that is defective in its ability to traffic to the plasma membrane. Because earlier studies showed delta F508-CFTR retains significant phosphorylation-regulated chloride (Cl-) channel activity, processes capable of restoring the mislocalized delta F508-CFTR to the correct cellular destination may have therapeutic benefit. Here we report one such process that involves overexpression of the mutant protein and appears to result in the escape of a small amount of delta F508-CFTR to the plasma membrane. In recombinant cells where expression of delta F508-CFTR is controlled by the metallothionein promoter, this effect can be brought about by treatment with sodium butyrate. Although cAMP-activated Cl- channel activity could also be detected in immortalized human airway epithelial cells homozygous for the delta F508 mutation at the single cell level, treatment with butyrate did not generate a measurable cAMP-stimulated Cl- current in polarized monolayers of primary CF airway epithelia. However, the observation that overexpression can effect the presence of recombinant delta F508-CFTR at the plasma membrane suggests that perhaps other butyrate-like compounds that are more potent and more specific for the promoter of the CF gene may be efficacious in alleviating the Cl- channel defect associated with CF.

Animals↗
PubMed1995

Giardia gene predicts a 183 kDa nucleotide-binding head-stalk protein.

Previously described extended proteins from the cytoskeleton of Giardia lamblia (beta-giardin, median body protein) have been found to be segmented coiled coils with regular structural repeat patterns in their amino acid sequences. Screening a lambda ZAPII library derived from Giardia genomic DNA with an antibody directed against a 34 x 10(3) M(r) giardin isoform selected a gene encoding a much larger polypeptide chain (HPSR2), the sequence of which was determined by chromosome walking the open reading frame. The complete gene has been cloned and expressed as a recombinant protein of 183 x 10(3) M(r). The predicted amino acid sequence of the protein has identifiable features suggesting that it might be a motor protein with an amino-terminal hydrolytic domain attached to a long coiled coil stalk. The presumed head domain is 211 residues and contains a P-loop sequence conserved in purine nucleotide-binding proteins. The remaining 1409 amino acids mainly make up a region of heptad repeats such as in myosin or the kinesin stalk, ending in a small (67 amino acids) carboxy-terminal domain. Fourier analysis of the predicted stalk shows the presence of a strong physical repeat created by regular heptad phase changes dividing the coil into segments of 25 residues. This structure most closely resembles the smaller microtubule-associated median body protein which has segments of 24 residues.

Amino Acid Sequence↗
PubMed1995

Age-related variation in the hydraulic conductivity of Bruch's membrane.

PURPOSE: To determine whether alterations in local fluid dynamics are associated with aging of the Bruch's membrane-choroid complex. In the macula, such changes have been postulated as causative factors underlying some pathologic manifestations of age-related macular degeneration (AMD). METHODS: The pressure-induced flow of physiological buffer through isolated human Bruch's membrane-choroid complex was measured using a modified Ussing chamber. Values of flow facilitated the calculation of hydraulic conductivity (flow per unit pressure), for individual complexes, which subsequently allowed for the development of an age-related profile. RESULTS: In all specimens, flow across the Bruch's membrane-choroid complex was found to be directly proportional to the applied pressure, whereas hydraulic conductivity was independent of pressure over the range studied. The hydraulic conductivity of the complex exhibited an exponential decrease with increasing age of donor, the most rapid decline occurring during the first four decades of life. The age-related change was most pronounced in the macula, where hydraulic conductivity halved every 9.5 years, compared to a t1/2 for the periphery of 19 years. CONCLUSIONS: The decline in the hydraulic conductivity of the Bruch's membrane-choroid complex with age implies a decreased capacity for the exchange of fluid between the choroidal and retinal pigment epithelial compartments. The relevance of these findings to the development of AMD is discussed.

Adolescent↗
PubMed1994

Cystic fibrosis transmembrane conductance regulator protein expression in brain.

The cystic fibrosis transmembrane conductance regulator protein (CFTR) has been identified in bovine brain clathrin-coated vesicles, rat brain and a human neuroblastoma cell line using affinity-purified polyclonal peptide antibodies against CFTR. Immunocytochemical staining of multiple dendrites and soma of neurons of the diencephalon, midbrain, pons and medulla oblongata, has also been demonstrated. Whole cell lysates and membranes derived from rat brain, neuroblastoma cells and bovine brain clathrin-coated vesicles express the mature 150-165 kDa and 130 kDa unglycosylated forms of CFTR. The localization of CFTR to brain regions controlling homeostasis and energy expenditure may relate to the pathogenesis of non-pulmonary manifestations of cystic fibrosis. CFTR expression in neurons and coated vesicles suggests a possible effect on neuropeptide vesicle trafficking by mutant CFTR.

Amino Acid Sequence↗
PubMed1994

Stoichiometry of recombinant cystic fibrosis transmembrane conductance regulator in epithelial cells and its functional reconstitution into cells in vitro.

We have generated several clones of Chinese hamster ovary, mouse epitheloid C127, and pig kidney epithelial LLCPK1 cells producing high levels of functional recombinant human cystic fibrosis transmembrane conductance regulator (CFTR). Processing of CFTR to the mature and fully glycosylated form in these cells is inefficient with only approximately 40% of all newly synthesized CFTR being converted to the mature form. Furthermore, expression of the most frequent mutant allele of the cystic fibrosis (CF) gene, the delta F508 mutant in these epithelial cells, indicated that it is biosynthetically arrested at the endoplasmic reticulum and fails to traffic to the plasma membrane. Using a combination of CFTR mutants and monoclonal antibodies, all the detectable recombinant CFTR in these cells was determined at least under the conditions used, to be present as a monomer. To demonstrate the feasibility of protein replacement therapy, we were able to effect the physical transfer of functional recombinant CFTR produced in Chinese hamster ovary cells to the plasma membranes of Ha3b fibroblasts, a cell line devoid of cAMP-stimulated chloride channels. Transfer of CFTR was mediated by the hemagglutinin viral fusion protein of influenza virus present on the Ha3b cells. Efficiency of transfer was up to 25% of the target cells, and CFTR chloride channel activity was detectable for up to 12 h post-fusion. Therefore, with the development of an appropriate formulation of fusogenic proteoliposome or virosome containing reconstituted purified CFTR, it should be feasible to introduce functional CFTR into CF-affected cells.

Adenosine Triphosphate↗