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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 469 records · Page 26Linked to original sources

Postirradiation angiosarcoma of the breast--a case report.

Angiosarcoma of the breast is an uncommon neoplasm but coincident angiosarcoma with infiltrating ductal carcinoma is not yet reported. This paper describes a case of angiosarcoma which developed after 4 years of a wide excision and adjuvant radiotherapy for a ductal carcinoma of the breast. Due to latent period of only 4 years radiotherapy cannot be blamed as an aetiological factor in this case but neither is it possible to exclude it as a causative factor.

Aged↗

Regulation of erythroid cell-specific gene expression during erythropoiesis.

The aim of our group's work over the past few years has been to investigate the molecular mechanisms regulating erythroid cell-specific gene expression during erythroid cell differentiation. In addition to the alpha-globin gene, we have focussed on two non-globin genes of interest encoding the rabbit red cell-specific lipoxygenase (LOX) and the mouse glutathione peroxidase (GSHPX), an important seleno-enzyme responsible for protection against peroxide-damage. Characterisation of the GSHPX gene showed that the seleno-cysteine residue in the active site of the enzyme is encoded by UGA, which usually functions as a translation-termination codon. This novel finding has important implications regarding mRNA sequence context effects affecting codon recognition. The regulation of the GSHPX and red cell LOX genes has been investigated by functional transfection experiments. The 700 bp upstream of the GSHPX promoter seems to function equally well when linked to the bacterial chloramphenicol acetyl transferase (CAT) gene and transfected into mouse erythroid or fibroblast cell lines. However, the presence of tissue-specific DNase I hypersensitive sites (DHSS) in the 3' flanking region of the GSHPX gene suggests that such sites may be important in its regulation in the various cell types in which it is highly expressed, i.e., erythroid cells, liver and kidney. The transcription unit of the RBC LOX gene has also been defined and 5' and 3' flanking regions are being investigated for erythroid-specific regulatory elements: a region upstream of the LOX gene gives increased expression of a linked CAT gene when transfected into mouse erythroid cell lines compared to non-erythroid cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Observer bias in blood pressure studies.

Observer variation in blood pressure measurement following training with standard techniques has been investigated in a study of 7735 middle-aged men. The initial training produced consistent results between observers, but there were progressive deteriorations in the ensuing months. Subsequent re-training led to marked though inconsistent reductions in variation, but within 1 or 2 months, observers reverted back to an individual level of bias. The magnitude of observer variation is in line with the few other published accounts, and is sufficient to have important implications for group comparisons, clinical trials, and the clinical care of individual patients. Four methods of reducing observer variation are considered: regular re-training, self-measurement and ambulatory monitoring, automatic sphygmomanometers, and adjustment in the analysis. The adjustment procedure used in the British Regional Heart Study is described. Regular and frequent re-training with monitoring of performance, or the use of automatic machines are presently considered the two most practical methods of reducing observer variation.

Adult↗

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Adult↗

Alcohol and ischaemic heart disease in middle aged British men.

The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease.

Adult↗

Evidence for isoaspartyl (deamidated) forms of mouse epidermal growth factor.

A variant form of mouse submaxillary gland epidermal growth factor (EGF) was identified by isocratic reversed-phase HPLC of EGF obtained by Bio-Gel P-10 column chromatography ("culture grade"). The variant form was essentially absent in preparations of EGF further purified by chromatography on DEAE-cellulose ("receptor-grade" EGF). The spectral properties and amino acid composition of the variant form (EGF-I) could not be distinguished from those of the intact polypeptide isolated by HPLC (alpha-EGF). Receptor-binding and mitogenic properties of EGF-I were also equivalent to those of alpha-EGF. These data suggested that EGF-I was structurally very similar to EGF. However, the very low yield (less than 4%) obtained by Edman degradation indicated that the N-terminal (Asn1) of the polypeptide was modified. Isoelectric focusing of EGF-I revealed two major immunoreactive bands: one with a pI equivalent to that of alpha-EGF (pI 4.6) and another at pI 4.1. Alkaline treatment of alpha-EGF (0.1 M NH4OH) yielded peak material by HPLC that coeluted with EGF-I; the alkaline-generated EGF-I yielded bands that also focused at pH 4.6 and 4.1. Ammonium hydroxide treatment of [des-Asn1]-EGF (beta-EGF) did not produce conversion to EGF-I. On the basis of these data, we propose that EGF-I was formed by selective deamidation of the N-terminal Asn of intact EGF. This notion is also supported by liquid secondary ion mass spectrometry, which showed that EGF-I was approximately 1.5 mass units greater than alpha-EGF. The heterogeneity observed by isoelectric focusing supports previous studies which have shown that, following deamidation of N-terminal asparagine, a beta-aspartyl shift can occur, which in the present study might yield succinimido-aspartyl1-EGF and beta-aspartyl1-EGF. Low yields observed during Edman degradation indicate that negligible amounts occur as the alpha-aspartyl1-EGF isomer.

Amino Acid Sequence↗

Molecular characterization by high-resolution isoelectric focusing of the products encoded by the class II region loci of the major histocompatibility complex in humans. I. DR and DQ gene variants.

We describe a new approach to the analysis of the structural polymorphism of the DR beta, DQ alpha, and DQ beta polypeptide chains of human histocompatibility class II antigens. In comparison to conventional two-dimensional gel studies, this method provides sharper definition of the protein bands and side-by-side comparisons within the same gel, thereby permitting the detection of minor differences in the isoelectric points of the protein chains. Using this methodology we have analyzed the IEF polymorphism and the variability in the number of the DR beta chains encoded by different DR haplotypes. Twenty DR beta chain variants, which include the products of no less than two separate DR beta loci, have been thus far identified. Alleles at one of these loci are assumed to code for DR beta chains carrying the DR alloespecificities DR1, DR2, DR3, DR4, DR5, DRw6, DR7, and DR8. Alleles at a second DR beta locus encode DR beta chains that may be shared by serologically DR-different haplotypes and carry supertypic serologic specificities (i.e., DRw52 and DRw53). We also demonstrate here that the structural polymorphisms of the DQ alpha and DQ beta chains are more extensive than previously thought, report the characterization of 14 DQ beta variants, and define their relationship to the previously described DQw serologic specificities. In addition, we describe the class II haplotype associations observed for the different DR and DQ variants characterized.

Alleles↗

Ovarian follicular structure of White Leghorns fed ad libitum and dwarf and normal broiler breeders fed ad libitum or restricted until point of lay.

1. Yellow follicle numbers when the first egg was laid were 6.3, 9.0 and 12.4 for ad libitum reared Leghorns, sex-linked Dwarf (AL Dwarf) and Normal broiler breeders respectively. Multiple ovulation resulted in low egg production and a high proportion of defective egg shells in AL Dwarf and Normal broiler breeders during early lay. 2. Restricting the growth of broiler breeders during rearing by restricting food intake (R Dwarfs) reduced the number of yellow follicles to 6.8 and increased the rate of lay. 3. Atretic yellow follicles were common among broiler breeders but not in Leghorns or R Dwarfs when the first egg was laid. 4. Poor egg production in older broiler breeders was caused by birds with few or no developing yellow follicles, atresia in yellow follicles and the continued occurrence of multiple ovulations. 5. There was no relationship between the number of yellow follicles and the number of white follicles less than 5 mm diameter but atresia in white follicles 2 to less than 5 mm was negatively related to the number of yellow follicles. 7. No relationship was observed between abdominal fat weight and yellow follicle number, though birds which ate more had more yellow follicles. 8. The sex-linked dwarfing gene dw was associated with increased atresia among the white follicles and low numbers of yellow follicles compared with the Normal DW broiler breeder genotype.

Animals↗

A comparative experimental study of the organization of arterial and venous thrombi.

Organization of a venous thrombus proceeds much faster than that of an arterial thrombus. Two different double-ligation procedures were used for study of the time sequence of thrombus organization by the vascularized (in situ) and devascularized (dissected) walls of the external jugular vein and common carotid artery in 21 mongrel dogs. Blood in the ligated segments of the in situ veins remained mostly fluid. In these segments, intimal hyperplasia was observed after 4 weeks with apparent preservation of an endothelial lining. However, in the dissected veins, the trapped blood rapidly thrombosed. Remarkable cell proliferation quickly occurred in these dissected walls with rapid invasion of the thrombus to achieve complete organization by 4 weeks. In contrast, a thrombus formed in the ligated segments of all arteries, whether in situ or dissected, and organization was much slower, requiring about 4 months for completion. Full-wall viability was maintained in 100% of the in situ veins and in 95% of the devascularized veins, but inner wall viability was lost in 30% of the in situ arteries and in 95% of the devascularized arteries.

Animals↗

Non-participation and mortality in a prospective study of cardiovascular disease.

Men who did not participate in a prospective study of cardiovascular disease (The British Regional Heart Study) were younger than the participants, more likely to be unmarried, and more likely to be less skilled workers. In the first three years of follow-up, their total mortality rate was significantly higher than that of the participants; thereafter it declined to levels not significantly different from those of the participants. This excess of early deaths could not be attributed to age. There was a small but non significant excess mortality in non-participants due to neoplasms and cardiovascular disease and a somewhat greater excess from all other causes combined. The social characteristics of the non-participant population appear to contribute to their significantly higher total mortality rate, and allowance needs to be made for this in interpreting the study findings. However the death rate from cardiovascular disease was similar in participants and non-participants, suggesting that any analysis related to this particular cause of death should not be biased by non-participation.

Adult↗

Effects of transplantation on atrioventricular nodal accommodation and hysteresis.

In the present study, atrioventricular nodal accommodation and hysteresis characteristics were evaluated in awake, unsedated dogs, before (n = 10) and after cardiac transplantation (n = 10). Chronically instrumented animals were atrially paced at a cycle length (CL) of 400 ms, followed by an abrupt decrease in pacing CL to 300 ms, followed by an abrupt return in pacing CL to 400 ms (with pacing sustained for 60 s at each CL). Atrioventricular nodal conduction characteristics (assessed by AH intervals) were simultaneously monitored. Under control conditions, AH intervals lengthened rapidly after an abrupt decrease in pacing CL [mean time for AH interval lengthening to stabilize (Tonset) = 2 +/- 1 s], whereas AH intervals lengthened more slowly (P less than 0.05) after transplantation (Tonset = 41 +/- 4 s). Similarly, after an abrupt increase in pacing CL, control AH intervals shortened rapidly [mean time for AH interval to return to base line (Tonset) = 5 +/- 1 s], whereas AH intervals shortened more slowly (P less than 0.05) after transplantation (Tonset = 42 +/- 5 s). Thus accommodation appears to be an intrinsic atrioventricular nodal response (present after cardiac denervation by transplantation) to abrupt, sustained atrial CL changes. Furthermore equivalence (P = NS) in atrioventricular nodal accommodation responses to symmetric CL decreases and increases after transplantation suggests that hysteresis [i.e., nonequivalence (P less than 0.05) in atrioventricular nodal accommodation responses], as seen under control conditions, results primarily from extrinsic (neural) modification of intrinsic atrioventricular nodal responses to symmetric CL changes.

Adaptation, Physiological↗

Influence of adrenergic receptors on ovarian progesterone secretion in the pseudopregnant cat and oestradiol secretion in the oestrous cat.

The infusion of isoprenaline or propranolol into the abdominal aorta of the pseudopregnant cat caused an increase or decrease respectively in the ovarian progesterone secretion rate. These observations suggest that the sympathetic innervation of the ovary has a physiological influence on normal progesterone secretion, and this mechanism may explain stress-related increases in progesterone concentrations. The infusion of isoprenaline or propranolol after the stimulation of follicular growth had no consistent or convincing effect on oestradiol secretion.

Animals↗

A scoring system to identify men at high risk of a heart attack.

A scoring system for identification of men at high risk of a heart attack within 5 years of screening is presented. The full scoring system includes an electrocardiogram and blood cholesterol measurement and the top fifth of the distribution of this full score yields 59% of the major ischaemic heart disease events occurring in the 5 years after screening. An intermediate scoring system, without an electrocardiogram but retaining blood cholesterol, yields 58% of cases from the top fifth of the score distribution. A basic (GP) score, without electrocardiogram or blood cholesterol measurement, yields 54% of cases and is recommended for use in opportunistic screening in general practice. This high risk strategy would increase public awareness of the size of the problem, help to prevent premature death and provide a useful complement to the population strategies of health education and government policy.

Adult↗

Candida sepsis.

Thirty cases of Candida sepsis occurring at Howard University Hospital between January 1983 and December 1985 were studied. A retrospective analysis was done to determine which risk factors or methods of treatment led to higher morbidity and mortality. Nosocomial infections with fungi are becoming more widespread as patients survive illnesses once deemed terminal. Patients had positive blood cultures for Candida accompanied by signs of systemic sepsis. Risk factors included diabetes, central hyperalimentation, malignancy, intraabdominal abscesses, and fistulae. The correlation between the total dose of amphotericin administered and patient recovery was analyzed.

Adult↗