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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 289 records · Page 16Linked to original sources
PubMed1992

Use of scrolled text in a scanning laser ophthalmoscope to assess reading performance at different retinal locations.

A new technique is described for assessing reading performance using a scanning laser ophthalmoscope. Letters of different sizes and contrasts were projected onto specific retinal locations of normal and low vision observers. Successive letters were scrolled in a horizontal direction at different speeds through a 'window'. Throughout the experiments the subjects' fundus and the retinal location of the stimuli could be visualized. With this scanning laser ophthalmoscope text-scrolling computer program the subject does not search for adjacent letters, and because the eye is held relatively stationary the tedious eye movement analysis incurred in other studies is reduced. Five retinal areas were investigated in two normal observers. The percentage of letters correctly identified decreased with eccentricity, increased velocity of the text and reduced text contrast. The reading performance of two patients, one with age-related macular degeneration and the other with juvenile macular disease, was investigated. Decrements in performance were related to morphology of the lesions.

Adult↗
PubMed1992

[Corneal opacity after photorefractive keratectomy with an excimer laser. Cause, objective measurement and functional consequences].

A marginal loss of corneal transparency or 'haze' is a phenomenon commonly experienced after photorefractive keratectomy using excimer lasers (193 nm). The putative causes of this phenomenon are the presence in the surgical site of (1) activated keratocytes, (2) vacuoles and (3) newly synthesized collagen. A CCD camera device was employed in order to measure the corneal transparency. Both scattered and reflected light in the slit image of patients' corneas was measured using polarizing filters and image analysis software. We observed an increase in reflected and scattered light until the second postoperative month, followed by a subsequent decline. However, the combined signal generated by reflected and scattered light showed a second increase at 4 months postoperatively, whereas the signal generated by scattered light alone stayed at lower levels. These objective measures of changes in corneal transparency were correlated with changes in visual performance using psychophysical tests measuring visual acuity at different contrast levels (100%, 20% and 5%). In all patients we observed a good correlation between the signal generated by scattered light alone and the reduction in the 5% contrast visual acuity performance. These disturbances in low contrast visual performance were only significant during the first 3-4 months postoperatively, and thereafter most patients returned to their preoperative value. Eighteen percent of our patients discontinued topical steroids postoperatively. No difference in corneal transparency was observed.

Adult↗
PubMed1992

Ultrastructural changes of human trabecular meshwork after photocoagulation with a diode laser.

A diode laser, which emitted infrared radiation at a wavelength of 810 nm, was used to perform trabecular photocoagulation in a human eye due for enucleation for malignant melanoma. For comparison, burns were applied with an argon blue-green laser (488-514.5 nm). With each laser, the treatment spot size was 100 microns and the pulse duration was 0.20 sec. Visible lesions were produced with a power of between 750 mW and 1.2 W with the diode laser, and 500-900 mW with the argon laser. The pattern of damage produced by both modalities was similar and essentially consisted of contraction or expansion of trabecular beams, with trabecular destruction occurring only in relation to high power exposures. These findings confirm that trabecular photocoagulation is not a process that depends upon the wavelength of the incident energy at the two spectral extremes of 488 nm and 810 nm.

Aged↗
PubMed1991

Identification and localization of a dogfish homolog of human cystic fibrosis transmembrane conductance regulator.

Chloride channels in the apical plasma membrane of cells in the dogfish rectal gland have served as a model system for the study of regulation of chloride flux by changes in intracellular cyclic AMP levels. Similar regulation by cyclic AMP has been described for channels in cells of human secretory epithelia where defective regulation by cyclic AMP-dependent protein phosphorylation is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). We have isolated a cDNA clone from the rectal gland encoding a protein that is 72% identical to the human CFTR. One of the major phosphorylation sites in CFTR is absent in the dogfish protein. The dogfish protein has, however, four additional putative substrate sites for the cyclic AMP-dependent protein kinase. A peptide antibody, which was raised against an amino acid sequence common to both the human and dogfish CFTR sequences, recognizes proteins with similar molecular masses (160 kDa) in the dogfish gland and in mammalian lung. Immunolocalization studies with this antibody show that the putative dogfish CFTR is localized to the apical membrane of cells lining the lumen of the rectal gland.

Amino Acid Sequence↗
PubMed1991

Nitromethylene actions on in situ and expressed insect nicotinic acetylcholine receptors.

Single channel recordings from dissociated housefly (Musca domestica) neurons show that a novel type of nitromethylene insecticide, 2(nitro-methylene)tetrahydro-1,3-thiazine (NMTHT) gates a channel, the conductance and open time histogram of which resemble those obtained when acetylcholine is the agonist. Injection into Xenopus oocytes of a locust (Schistocerca gregaria) alpha-subunit mRNA results in the expression of functional nicotinic receptors sensitive to NMTHT. Control oocytes injected with distilled water are insensitive to the same concentration of this compound. Thus NMTHT exhibits agonist actions at both in situ and expressed insect nicotinic receptors, and one site of action of this compound is on an insect nicotinic receptor alpha-subunit.

Acetylcholine↗
PubMed1991

Nutritional epidemiology of postmenopausal breast cancer in western New York.

The authors studied 439 postmenopausal breast cancer cases, identified in hospitals throughout western New York, with an interview schedule that considered frequency and amount ingested of 172 foods and provided data for an estimate of total calories ingested. These were compared with age-matched controls comprising a random sample of the same communities as the cases. The extensive interviews, requiring 2.0 hours on average to administer, also covered alcohol ingestion, Quetelet index, and a wide variety of reproductive factors. The authors found, as have most investigators over the past 25 years, that risk increased with increases in age at first pregnancy, decreased with increases in numbers of children and pregnancies, and increased in those with history of benign breast disease and in those with female relatives previously affected with breast cancer. Risk adjusted for potential confounders was highest among women with the lowest ingestion of carotene or a substance correlated with its ingestion. Risk was not associated with retinol ingestion. It increased with increases in Quetelet index. Fat intake, whether studied in terms of quantity or the proportion of total calories derived from fat, was not associated with risk of breast cancer. Our analyses of these factors were adjusted for age, education, and the reproductive history traits described above.

Adult↗
PubMed1991

Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel.

CFTR, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to cAMP agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase A. The SPQ fluorescence assay revealed that mutagenesis of any one of these sites did not affect Cl- channel activity. Indeed, concomitant mutagenesis of three of the four sites still resulted in cAMP-responsive Cl- channel activity. However, mutagenesis of all four sites abolished the response. One interpretation of these results is that the CFTR Cl- channel is blocked by the R domain and that phosphorylation on serines by protein kinase A electrostatically repels the domain, allowing passage of Cl-. The four phosphorylation events appear to be degenerate: no one site is essential for channel activity, and, at least in the case of serine 660, phosphorylation at one site alone is sufficient for regulation of Cl- channel activity.

Chloride Channels↗
PubMed1991

Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA.

Amino Acid Sequence↗
PubMed1991

Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation.

We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose-dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

Basophils↗
PubMed1991

Outgrowth of stable class I major histocompatibility complex-expressing subsets from immunogenic variants of a murine mammary carcinoma: association with a differentially staining region on chromosome 9.

We have examined interactions among intratumor subpopulations during the rejection of immunogenic variants of a murine mammary carcinoma (SPI) and in the outgrowth of tumorigenic "revertant" subsets. Analysis of subclones isolated during the early phase of rejection of one immunogenic variant revealed extensive cellular heterogeneity of tumor-forming ability and class I major histocompatibility complex (MHC) expression. Two main categories of subclones were identified. One set expressed high levels of class I MHC (MHCH) and grew poorly or not at all in normal syngeneic mice. The second set of clones expressed generally low levels of class I MHC (MHCL) and exhibited progressive growth in vivo, similar to the parent tumor. The steady-state mRNA levels for class I MHC and beta 2-microglobulin were constitutively elevated in MHCH clones compared to MHCL clones or the parent tumor. However, in vivo tumorigenic outgrowths from immunogenic variants always expressed the MHCH phenotype. A cytogenetic analysis was carried out to determine the clonal origin and lineage relationship of in vivo selected tumor outgrowths. Surprisingly, tumor outgrowths from mixtures of karyotypically distinct MHCH and MHCL subclones were derived from one lineage within the MHCH subset, despite the fact that MHCH subclones exhibited slower growth in vivo than MHCL subsets when analyzed individually. These results suggest that in polyclonal populations the various subsets sometimes interact in a way that overrides the influence of immunogenic and MHC phenotypes of individual subclones.

Adenocarcinoma↗
PubMed1991

Prebiotic chemistry in clouds.

In the traditional concept for the origin of life as proposed by Oparin and Haldane in the 1920s, prebiotic reactants became slowly concentrated in the primordial oceans and life evolved slowly from a series of highly protracted chemical reactions during the first billion years of Earth's history. However, chemical evolution may not have occurred continuously because planetesimals and asteroids impacted the Earth many times during the first billion years, may have sterilized the Earth, and required the process to start over. A rapid process of chemical evolution may have been required in order that life appeared at or before 3.5 billion years ago. Thus, a setting favoring rapid chemical evolution may be required. A chemical evolution hypothesis set forth by Woese in 1979 accomplished prebiotic reactions rapidly in droplets in giant atmospheric reflux columns. However, in 1985 Scherer raised a number of objections to Woese's hypothesis and concluded that it was not valid. We propose a mechanism for prebiotic chemistry in clouds that satisfies Scherer's concerns regarding the Woese hypothesis and includes advantageous droplet chemistry. Prebiotic reactants were supplied to the atmosphere by comets, meteorites, and interplanetary dust or synthesized in the atmosphere from simple compounds using energy sources such as ultraviolet light, corona discharge, or lightning. These prebiotic monomers would have first encountered moisture in cloud drops and precipitation. We propose that rapid prebiotic chemical evolution was facilitated on the primordial Earth by cycles of condensation and evaporation of cloud drops containing clay condensation nuclei and nonvolatile monomers. For example, amino acids supplied by , or synthesized during entry of, meteorites, comets, and interplanetary dust would have been scavenged by cloud drops containing clay condensation nuclei. Polymerization would have occurred within cloud systems during cycles of condensation, freezing, melting, and evaporation of cloud drops. We suggest that polymerization reactions occurred in the atmosphere as in the Woese hypothesis, but life originated in the ocean as in the Oparin-Haldane hypothesis. The rapidity with which chemical evolution could have occurred within clouds accommodates the time constraints suggested by recent astrophysical theories.

Aluminum Silicates↗
PubMed1991

Non-competitive NMDA-receptor antagonists and anoxic degeneration of the ERG B-wave in vitro.

Studies have been undertaken to see if the non-competitive NMDA antagonists, ketamine, MK-801 and dextromethorphan would preserve the b-wave of the electroretinogram (ERG) in vitro. The drugs had no effect on the ERG b-wave, nor prolonged its survival postmortem. The present results support previous evidence suggesting that NMDA-receptors are not involved directly in synaptic transmission between photoreceptors and ON-bipolar cells. Further, loss of the b-wave in post-mortem anoxia does not appear to be mediated via NMDA-receptors.

Animals↗
PubMed1991

Structural elements that regulate pp59c-fyn catalytic activity, transforming potential, and ability to associate with polyomavirus middle-T antigen.

Except for its unique amino-terminal region (residues 1 through 83), which possibly dictates substrate recognition, pp59c-fyn bears a high degree of homology with other members of the src family of tyrosine kinases. Here we show that the carboxy terminus of pp59c-fyn is necessary for stable middle-T-antigen association, that pp59c-fyn is normally phosphorylated on both serine and tyrosine residues, and that Tyr-531 and Tyr-420 are phosphorylation sites in vivo and in vitro, respectively. Analysis of a spontaneously generated mutant encoding a truncated form of pp59c-fyn and of variants specifically mutated at the Tyr-531 and Tyr-420 phosphorylation sites indicates that pp59c-fyn has regulatory elements analogous to those that have already been identified for other src-like tyrosine kinases. However, further examination of the pp59c-fyn variants suggests the likelihood of additional means by which its activities might be regulated. Although alteration of Tyr-531 to phenylalanine (531F) in pp59c-fyn results in a protein which is more active enzymatically that the wild type, the enhancement is much less than that for the analogous variant of pp60c-src. Furthermore, contrary to results of similar experiments on other src-like proto-oncogene products, 531F did not induce transformation of NIH 3T3 cells. Studies involving pp59c-fyn-pp60c-src chimeras in which the unique amino-terminal sequences (residues 1 through 83) of the two kinases were precisely interchanged implied that the inability of 531F to induce transformation is probably not caused by the absence of substrates for pp59c-fyn in NIH 3T3 cells but rather by the insufficient enhancement of pp59c-fyn kinase activity. It is therefore probable that the kinase and transforming activities of pp59c-fyn are repressed by additional regulatory elements possibly located in the amino-terminal half of the molecule.

Amino Acid Sequence↗
PubMed1991

Excimer laser treatment of corneal surface pathology: a laboratory and clinical study.

The argon fluoride excimer laser emits radiation in the far ultraviolet part of the electromagnetic spectrum (193 nm). Each photon has high individual energy. Exposure of materials or tissues with peak absorption around 193 nm results in removal of surface layers (photoablation) with extremely high precision and minimal damage to non-irradiated areas. This precision is confirmed in a series of experiments on cadaver eyes and the treatment of 25 eyes with anterior corneal disease (follow-up 6 to 30 months). Multiple zone excimer laser superficial keratectomy is considered the treatment of choice for rough, painful corneal surfaces. All patients in this group were pain-free postoperatively. Where good visual potential exists, ablation of a single axial zone is recommended and results in improved visual acuity and reduction of glare. A hyperopic shift was noted in this group.

Adolescent↗
PubMed1991

Iris clipping of a diode laser beam when performing retinal photocoagulation.

The Microlase infrared diode laser has recently become available for retinal photocoagulation. It uses a laser beam with a large convergence angle (23 degrees). This gives rise to a laser beam with a relatively large cross section at the subject's pupil. In this study the pupillary area required to view the fundus at the slit-lamp with a 90-dioptre lens is determined. It is found that the pupillary area required to view the fundus is smaller than the cross section of the Microlase laser beam at the pupil. Thus iris clipping of the laser beam can occur even though the surgeon has a clear and bright view of the fundus. Care should be taken to use the Microlase only in the presence of a widely dilated pupil.

Fundus Oculi↗
PubMed1991

Epilepsy and employment. A community based survey in an area of high unemployment.

A community based survey was undertaken to assess the work record of patients with epilepsy in an area of high unemployment. One hundred and thirty seven epileptic patients were identified from a population of 23,837 persons of employable age registered with three urban group practices in North East England. The unemployment rate for economically active patients with epilepsy was 46% compared with 19% for an age and sex matched control population (p less than 0.01). Fifty nine per cent of patients with active epilepsy were unemployed. In those with an associated neurological or psychiatric handicap and those who were unskilled manual workers the unemployment rates were 79% and 77%, respectively. Patients with epilepsy were less likely to leave school with qualifications or undergo subsequent training or apprenticeships. They were more likely to be unskilled manual workers, single and living in rented accommodation. In an area of high unemployment patients with epilepsy have disproportionately greater difficulty finding work. High unemployment rates among patients with epilepsy are only one aspect of a spectrum of social and economic disadvantage.

Adolescent↗