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Biomedical subjects

M Wilcox

Publications and source records attributed to M Wilcox.

At least 19 recordsLinked to original sources

Asymptomatic carotid atherosclerosis study: role of the clinical coordinator.

This article introduces the reader to the role of the clinical coordinator in the Asymptomatic Carotid Atherosclerosis Study. The main responsibility lies in recruiting patients into the study and managing their follow-up period very closely for the next three to five years. Each coordinator is vital to its individual center in order to actively participate in this multicenter trial.

Adult

Respiratory disease in a textile factory in Nicaragua.

This is the first epidemiologic study conducted in a textile mill in Nicaragua using techniques and diagnostic criteria similar to those used in the United States and England. The prevalence of byssinosis and nonspecific respiratory symptoms were studied in 194 workers in a cotton mill in Managua. Limited environmental sampling, performed using a vertical elutriator in yarn preparation and weaving areas, indicated that exposures were similar to those reported in other parts of the developing world. A modified translated version of the Medical Research Council respiratory questionnaire was administered. Pulmonary function tests were performed before and after the Monday workshift to measure across-shift change in ventilatory function. The prevalence of byssinosis was 5.9% and all the cases occurred among exposed women. Nonspecific respiratory symptoms were also more prevalent among exposed workers. After adjusting for age, gender, smoking habit, and work tenure, the exposure odds ratios for usual cough and usual phlegm were 3.3 and 2.2, respectively. The association between exposure and across-shift decrement in FEV1 was not significant. Byssinotic workers, however, had greater decrements in FEV1% than those without byssinosis: 5.5% versus 1.8%. A consistent gender effect was observed in which both exposed and unexposed women were found to have greater across-shift decrements in FEV1 than men. The gender difference existed among long-term workers as well as workers who had been employed less than 2 years. Results are related to cotton dust exposure, as has been documented elsewhere. The poorer health status of the women in this study population deserves follow-up.

Adult

Developmentally regulated alternative splicing of Drosophila integrin PS2 alpha transcripts.

We report the characterization of a chromosomal integrin gene that encodes the Drosophila PS2 alpha subunit. The gene is composed of 12 exons spanning 31 kb. By employing a novel method for directed cDNA cloning, we have analyzed over 300 independent cDNA clones for the existence of alternate RNA products. Two forms of PS2 alpha mRNA are frequently observed: a canonical (C) form and a form lacking the 75 nucleotide exon 8 (m8). The relative ratio of these two forms varies widely during development. Although region A, derived from exon 8 and the adjacent 25 amino acids, shows weak conservation among the sequences of alpha subunits that bind to different ligands, it is highly conserved in the homologous PS2 alpha gene of the distantly related Mediterranean fruitfly. We suggest that the variable region A may be important in determining the specificity and affinity of integrin receptors for their ligands.

Amino Acid Sequence

The function of PS integrins during Drosophila embryogenesis.

The Drosophila position-specific (PS) antigens are homologous to the vertebrate fibronectin receptor family, or integrins. A Drosophila gene required for embryonic morphogenesis, l(1)myospheroid, codes for a product homologous to the beta subunit of the vertebrate integrins. l(1)myospheroid mutants die during embryogenesis. We show here that they lack the beta subunit of the PS antigens. In the absence of the beta subunit in mutant embryos, the PS alpha subunits are not expressed on the cell surface. We conclude that the l(1)myospheroid phenotype represents the lack-of-function phenotype for these Drosophila integrins. In wild-type embryos, PS antigens are found at the interface between mesoderm and ectoderm, and later mainly at the attachment sites of muscles to the epidermis and gut. Together these results indicate that during embryogenesis, Drosophila integrins are used to attach mesoderm to ectoderm, and are required for the proper assembly of the extracellular matrix and for muscle attachment.

Animals

Improved method for calculating calcium fractions in plasma: reference values and effect of menopause.

Multiple linear regression analysis showed that total calcium was significantly and positively related to albumin, globulin, anion gap, and bicarbonate in plasma from 556 normal postmenopausal women. The residual constant of 1.21 mmol/L approximated the normal mean for ionized calcium in plasma. The coefficients derived from the multiple regression analysis were used to calculate ionized calcium from total calcium and ligand concentrations in a series of 105 clinical cases in whom ionized calcium was measured with the calcium electrode. The regression equation was y = 1.00x -0.0039 mmol/L, where x is measured and y calculated Ca2+ (r = 0.78, P less than 0.001). The protein-bound, ultrafiltrable, and complexed fractions of the calcium were also calculated for plasma from 69 normal young men, 66 normal young women, and 305 normal postmenopausal women. The increased plasma calcium in the postmenopausal group was accounted for by an increase in the complexed fraction, due to increases in plasma bicarbonate and anion gap.

Adult

Evidence that the Abdominal-B r element function is conferred by a trans-regulatory homeoprotein.

The Abdominal-B gene is a homeotic gene located in the distal-most region of the bithorax complex (BX-C). Based on complementation analysis it has been proposed that the gene contains two separable genetic elements, called the m and r elements. The r element has a chiefly regulatory function confined to parasegment 14. In a reverse Northern screen of the distal-most BX-C DNA, we found four distinct areas that are transcribed in the embryo. One of the transcripts spans a large genomic region which, upon disruption by rearrangement breakpoints, causes loss of r element function. This transcript is expressed in the early embryo in a single domain apparently corresponding to parasegment 14. We propose that the small homeoprotein encoded by the transcript acts as a trans-regulator to confer r element function.

Amino Acid Sequence

Morphometry of nerve fiber bundle pores in the optic nerve head of the human.

The axons of retinal ganglion cells form fascicles that leave the globe through pores in the optic nerve head formed by beams of glia and collagen. In eyes obtained at time of autopsy of 17 normal subjects of various ages, these pores were counted and measured in the lamina choroidalis and lamina scleralis of the nerve heads. The number of pores at the scleral level was 1.48 times (0.18, 95% confidence interval) greater than at the choroidal level, and the pores were proportionately smaller at the scleral level. No significant change in the numbers of pores or the area of the nerve head at either level was found with age. The proportion of the nerve head devoted to pores decreased significantly with age. Since the pores contain primarily nerve fibers, the slope of this decrease suggests the loss to be about 5% of fibers per decade after age 30.

Adult

The Drosophila PS2 antigen is an invertebrate integrin that, like the fibronectin receptor, becomes localized to muscle attachments.

We establish that the position-specific antigen 2 (PS2), a Drosophila cell surface glycoprotein complex, is an invertebrate member of the vertebrate fibronectin receptor (integrin) family. New monoclonal antibodies show that in Drosophila embryos and larvae PS2 alpha subunits have a size of ca. 140 kd. Analysis of cDNA and genomic clones revealed that the canonical PS2 alpha subunit contains 1394 amino acids and has extensive homology to the heavy and light chains of integrin alpha subunits. The distribution of the PS2 antigen is regulated at the level of PS2 alpha subunit mRNA. In early Drosophila development the protein is restricted to mesoderm and appears to be involved in muscle attachment. We suggest that PS2, like vertebrate fibronectin receptors, mediates changes in cell shape and cell-extracellular matrix adhesion by binding to a basement membrane protein.

Amino Acid Sequence

Drosophila position-specific antigens resemble the vertebrate fibronectin-receptor family.

The Drosophila position-specific (PS) antigens are a family of cell surface glycoprotein complexes thought to be involved in morphogenesis. Their overall structures and biochemical properties are similar to those of a group of vertebrate receptors, including those for fibronectin, fibrinogen and vitronectin, and also the leukocyte antigens Mac-1, LFA-1 and p150,95 and the VLA family of cell surface antigens. The N-terminal sequences of the alpha subunits of some of these molecules are homologous to the N-terminus of a PS antigen component. The Drosophila PS antigens thus appear to be homologous to these vertebrate receptors.

Animals

Stimulated drug uptake in a photoreceptor cell.

In many cells, organelle translocation requires structural integrity of microtubules [2,6,11,14, 5]. We have found that extracellular application of the antimicrotubular drug colchicine, which was expected to enter cells simply by diffusion, was ineffective at blocking pigment granule migration (PGM) inside fly photoreceptors. However, illumination of these receptors in the presence of colchicine resulted in complete PGM block. From a combined study using microphotometry, microfluorometry and intracellular recordings, we inferred that light permeabilized the cell to the drug. This hypothesis was supported by the observation that illumination caused the photoreceptor to take up an inert dye. The results show that target cells optically selected from a homogeneous population can be induced to take up an agent from the extracellular fluid. Remarkably, this process of light-induced drug uptake does not affect cell viability.

Animals

Illumination induces dye incorporation in photoreceptor cells.

Illumination of fly photoreceptors in the presence of the fluorescent dye Lucifer yellow initiates incorporation of the dye, which stains each cell down to its synaptic terminal. Unilluminated cells do not become stained. Experiments on animals in vivo show that selected cells can be stained without loss of viability. "Induced endocytosis" provides a plausible mechanism underlying this phenomenon.

Animals