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Biomedical subjects

M Wilcox

Publications and source records attributed to M Wilcox.

At least 55 records · Page 3Linked to original sources

The perspective of patients with vascular disease on participation in clinical trials.

Very little objective data are available concerning the patient's perspective on clinical trial participation. Participants from the Asymptomatic Carotid Atherosclerosis Study and Clopidogrel vs. Aspirin in Patients at Risk for Ischemic Events Trial were personally interviewed by the nurse coordinator to document their views. A questionnaire including both closed-ended and open-ended questions was used. The main advantages to participation in a study were close follow-up and the opportunity for improved health. More than half of the subjects saw no disadvantages to participation. The physician was the primary motivator for entering trials. Most patients expressed an interest in future study participation.

Adult↗

A Drosophila gene encoding an epithelial membrane protein with homology to CD36/LIMP II.

The human cell surface transmembrane protein CD36 has important roles in cell adhesion and signal transduction. There is a related rat protein, LIMP II (also known as rLGP85), which is a well-characterized lysosomal membrane protein. The two proteins define a distinct family of receptor molecules with two membrane-spanning domains. We have identified a new member of this family, encoded by a Drosophila gene called emp (epithelial membrane protein). The emp protein, as predicted from the nucleotide sequence, is 519 amino acid residues long. It shows striking similarity throughout most of its sequence to both CD36 and LIMP II. Drosophila emp transcripts are expressed during embryogenesis in various epithelial cell types derived from the ectoderm. During larval development, we detect emp transcripts in the epithelial cells of wing imaginal discs, in the precursor cells for adult epidermal structures. These expression patterns suggest a role of emp protein in the development or cellular function of epithelial cells.

Amino Acid Sequence↗

Birth weight from pregnancies dated by ultrasonography in a multicultural British population.

OBJECTIVE: To produce standard curves of birth weight according to gestational age validated by ultrasonography in the British population, with particular reference to the effects of ethnic origin. DESIGN: Retrospective analysis of computerised obstetric database. SETTING: Three large maternity units associated with Nottingham University with over 16,000 deliveries a year. PATIENTS: 41,718 women with ultrasound dated singleton pregnancies and delivery between 168 and 300 days' gestation. MAIN OUTCOME MEASURES: Length of gestation, ethnic origin, parity, maternal height and weight at booking, smoking during pregnancy; the effect of these variables on birth weight. RESULTS: Birth weights from ultrasound dated pregnancies have a higher population mean and show less flattening of the birthweight curve at term than those of pregnancies dated from menstrual history. Significant differences were observed in mean birth weights of babies of mothers of European origin (3357 g), of Afro-Caribbean origin (3173 g), and from the Indian subcontinent (3096 g). There were also significant interethnic differences in length of gestation, parity, maternal height, booking weight, and smoking habit which affected birth weight. The ethnic differences in birth weight were even greater when the effect of smoking was excluded. CONCLUSIONS: Birthweight standards require precise dating of pregnancy and should describe the population from which they were derived. In a heterogeneous maternity population the accurate assessment of an individual baby's weight needs to take the factors which affect birthweight standards into consideration.

Birth Weight↗

Airborne endotoxin concentrations in various work areas within a cotton mill in Central America.

Gram-negative bacteria and their endotoxins have been shown to cause profound changes in the structure and function of mammalian lungs. Airborne exposures in humans have resulted in bronchoconstriction and symptoms of chest tightness and dyspnea. Cotton dust is often heavily contaminated and endotoxin has been postulated to be the agent in cotton dust which is responsible for the byssinosis syndrome. Previous studies of cotton dust have revealed variable amounts of contamination by bacterial endotoxin, with the variability determined in large part by botanical and climatic characteristics. We report here the results of an environmental study conducted in a cotton mill located in the tropics of Central America using locally grown cotton. Results indicate that airborne endotoxin was present in all yarn preparation and weaving areas and ranged from a low of 18 EU/m3 in weaving to a high of 3138 EU/m3 in opening areas. Airborne levels and the amount of endotoxin per nanogram of dust were not higher than values obtained in temperate climates.

Air Pollutants, Occupational↗

Cloning and characterization of alpha PS1, a novel Drosophila melanogaster integrin.

The Drosophila position-specific integrins (PS integrins or PS antigens) comprise two heterodimeric complexes, alpha PS1 beta PS and alpha PS2 beta PS. With the cloning of alpha PS1 described here, we complete the characterization of the primary structure of the three PS integrin subunits. We have purified the alpha PS1 subunit, obtained peptide sequence and isolated genomic and cDNA clones. The encoded alpha PS1 protein contains the cysteine pattern of the cleaved alpha integrins, three putative metal binding domains and shows the other characteristic features of alpha integrins. Regions of sequence variation indicate that alpha PS1 is distinct from all other alpha chains. The transcript analysis shows that the patterns of both alpha PS1 mRNA and protein expression are the same, suggesting that the gene is controlled transcriptionally. We compare the gene structures of the Drosophila alpha PS1, alpha PS2, the human alpha IIb and alpha X (p150,95) and the C. elegans F54G8.3 integrins. We find several positions and phases of introns conserved which, supported by conservation also in the amino acid sequence, indicates that they all derive from a common ancestral gene.

Amino Acid Sequence↗

A Minute encoding a ribosomal protein enhances wing morphogenesis mutants.

E(Dl)KP135 has been isolated previously as a recessive lethal Drosophila P element insertion line with a dominant enhancing effect on the phenotype of Delta, a gene encoding a surface membrane protein. We show here that this P insertion also enhances the wing phenotype of nd1, an allele of Notch encoding another transmembrane protein, the putative receptor of Delta, as well as that of if3, an allele of the integrin gene PS2 alpha. Moreover, we noticed that this P insertion causes a severe Minute phenotype. Molecular characterisation revealed that the P element disrupts the putative mRNA leader sequence of the ribosomal protein L19 gene. We tested further Minute genes and found that two of them, similarly to E(Dl)KP135, strongly enhance the nd1 wing phenotype. Our results suggest that the pleiotropic Minute syndrome can affect, probably indirectly, one or more steps of wing morphogenesis that involve surface adhesion of epithelial cells.

Amino Acid Sequence↗

The distribution of PS integrins, laminin A and F-actin during key stages in Drosophila wing development.

We first summarize wing development during metamorphosis of Drosophila and identify four critical steps in the conversion of a folded single layered wing disc to a flat bilayered wing. Each step occurs twice, once during the 12 hour prepupal period and again during the 84 hour pupal period. (1) Apposition in which basal surfaces of dorsal and ventral epithelia come close together. (2) Adhesion in which basal junctions form between the apposed basal surfaces. (3) Expansion in which wing area increases as a result of cells flattening. (4) Separation in which dorsal and ventral epithelia are separated by a bulky extracellular matrix but remain connected by slender cytoplasmic processes containing the microtubules and microfilaments of the transalar cytoskeleton. Disc ultrastructure is correlated with the distribution of the beta chain of integrin, laminin A, and filamentous actin for each key stage of pupal development. Integrin and laminin exhibit a mutually exclusive distribution from the adhesion stage onwards. Integrin is present on the basal surface of intervein cells but not on vein cells whereas laminin A is absent from the basal surfaces of intervein cells but is present on vein cells. We conclude that laminin is not a ligand for integrin in this context. During apposition and adhesion stages integrin is broadly distributed over the basal and lateral surfaces of intervein cells but subsequently becomes localized to small basal foci. These foci correspond to basal contact zones between transalar processes. The distribution of filamentous actin is dynamic, changing from an apical distribution during hair morphogenesis to a basal distribution as the transalar cytoskeleton develops. Basal adherens-type junctions are first evident during the adhesion stage and become closely associated with the transalar cytoskeleton during the separation stage. Thus, basal junction formation occurs in two discrete steps; intercellular connections are established first and junction/cytoskeletal connections are formed about 20 hours later. These observations provide a basis for future investigations of integrin mediated adhesion in vivo.

Actins↗

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↗

The function of PS integrins in Drosophila wing morphogenesis.

Integrins are found on many cell types during the development of most organisms. In Drosophila their functions can be analysed genetically. An analysis of lethal mutations in a PS integrin gene showed that the integrins were required for muscle attachment and for certain cell sheet migrations during embryogenesis. In this paper we use viable mutations in integrin component genes to look at integrin function in the later stages of development of one adult structure, the wing. We show that two known viable mutations, one which has its primary effect on the fly's escape response, the other on wing morphogenesis, are mutations in the beta and PS2alpha subunits, respectively, of the PS integrins. The mutation non-jumper (mys(mj42)) in the beta subunit leads to wasting of the thoracic jump muscles. Flies in which the dosage of this allele is reduced (and no wildtype copy is present) show defects also in wing morphogenesis. The two surfaces of the wing fail to connect properly, resulting in 'blistering' of the wing and the formation of extra crossveins. The mutation in the gene for the PS2alpha integrin subunit, inflated, also leads to a failure in wing surface apposition and consequent wing blistering. When the two mutations are combined, the mutant phenotype is greatly enhanced. Thus, one of the roles of the PS integrins in late Drosophila development is to ensure the correct apposition and patterning of the wing epithelia.

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↗