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Biomedical subjects

A Rogers

Publications and source records attributed to A Rogers.

At least 19 recordsLinked to original sources

Effect of calcium and phosphate ions on hemolysis induced by Pyrularia thionin and Naja naja kaouthia cardiotoxin.

Pyrularia thionin is a strongly basic bioactive peptide of 47 amino acids isolated from nuts of Pyrularia pubera. It is hemolytic, cytotoxic and activates an endogenous phospholipase A2 in 3T3 cells. Earlier studies have shown that the cardiotoxin from Naja naja kaouthia has similar activities and binds to the same site as Pyrularia thionin. Since the peptides appear to bind to the phospholipids of cell membranes to elicit their cellular responses, the effect of modifying the electrostatic environment was studied by separately adding phosphate ion and Ca2+, and by removing Ca2+ from the membrane by treatment with EGTA. Analysis of erythrocyte hemolysis for both Pyrularia thionin and cardiotoxin shows that the reactions follow Michaelis-Menten kinetics, with the peptides serving as the substrate. The basal rate of hemolysis in physiological saline is markedly increased by the addition of phosphate in the 5-10 mM range and also by removing membrane-bound Ca2+ by incubation of the cells with 10 mM EGTA. These treatments do not change the apparent K(m) values, but increase the V(max), indicating that more binding sites are made available by these treatments. On the other hand, added Ca2+ in the 5-10 mM range competitively inhibits the reaction by inhibiting the binding of the peptide to the membrane.

Antimicrobial Cationic Peptides

Binding properties of Pyrularia thionin and Naja naja kaouthia cardiotoxin to human and animal erythrocytes and to murine P388 cells.

Pyrularia thionin and snake venom cardiotoxin are strongly basic peptides which induce hemolysis, depolarization of muscle cells and activation of endogenous phospholipase A2. An earlier study of the hemolysis reaction indicated that the two peptides bind to and compete for the same site on human erythrocytes. A recent study examined the hemolysis induced by both peptides as the phosphate and Ca2+ content of the reaction mixture was varied. The results of the recent study (VERNON, L. P. and ROGERS, A., Toxicon 30, 701-709) agree with this companion study on the binding of 125I-labeled pyrularia thionin and cardiotoxin to erythrocytes under the same conditions. Added phosphate ion at 5 mM and removal of membrane-bound Ca2+ by treatment with 10 mM EGTA make more binding sites of the same affinity available to both peptides, which are shown to bind in a competitive fashion to the same site. Addition of 10 mM Ca2+ to the medium decreases peptide binding due to competitive binding of Ca2+ to the same site on the membrane. For human erythrocytes the number of binding sites/cell for the thionin ranged from 0.7 to 1.7 x 10(5) and for cardiotoxin from 0.82 to 1.6 x 10(5). The calculated dissociation constants (Kd) from the Scatchard plots ranged from 0.43 to 1.1 microM for the thionin and from 0.40 to 0.98 microM for the cardiotoxin. The binding sites for thionin and cardiotoxin with sheep erythrocytes were 1.7 and 2.0 x 10(4) sites/cell, respectively, and both cow and horse erythrocytes demonstrated 2.7 x 10(4) sites/cell for the thionin. Binding studies with murine P388 cells showed 7.0 and 9.5 x 10(6) sites per cell for Pyrularia thionin and cardiotoxin, respectively.

Animals

Development of the Virginia Congenital Anomalies Reporting and Education System (VaCARES): two pilot projects.

In 1986 legislation established the Virginia Congenital Anomalies Reporting and Education System (VaCARES). The system has three goals: to collect data that can be used to evaluate possible causes of congenital anomalies, to improve diagnosis and treatment, and to let parents and physicians know what resources are available to aid children born with anomalies. All children (from birth to age 2) with congenital anomalies admitted to Virginia hospitals after January 1, 1987, are being reported to VaCARES; VaCARES then contacts their families and physicians. Before the system was implemented statewide, its procedures were thoroughly tested through two pilot projects in selected hospitals. During the pilots, it was concluded that birth certificates alone are inadequate for case ascertainment. According to hospital reports, the incidence of all congenital anomalies during Pilot II was 562 out of 10,034 births (5.6%); birth certificates showed an incidence of only 83 out of 10,034 births (0.8%). During Pilot I, 3,466 (73.8%) of the diagnoses reported were perinatal conditions; the list of reportable conditions was accordingly altered, reducing perinatal conditions reported in Pilot II to 5 diagnoses (0.4%). It was estimated that there will be about 5000 to 7000 reports submitted to VaCARES each year. It was also shown that parents should be sent general rather than specific information about their child's birth defect and that quality control and close contact with reporting hospitals are essential to maintain the integrity of the registry data.

Congenital Abnormalities

Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study.

We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Heterogeneity and selection in multistate population analysis.

If one subgroup of individuals in a population has a higher death rate than the others, then over time the surviving population will include a larger share of those with the lower death rate. As a result, the aggregate average death rate for this increasingly more robust population will decline. This conclusion, however, can be drawn only for nonrecurrent events experienced by populations that do not exchange members with one another--that is, for noninteracting populations. Studies of changes in marital status, labor force activity, residential location, and active life, for example, all should focus on patterns of recurrent events among interacting populations (that is, multistate populations). Selection arising from heterogeneity will occur, but the consequences for average measures become unpredictable a priori. This paper explores such aspects of the selection effects of heterogeneity in multistate populations and illuminates some of their consequences for commonly used rates.

Aged

Expression of the Wilms' tumor gene WT1 in the murine urogenital system.

The Wilms' tumor gene WT1 is a recessive oncogene that encodes a putative transcription factor implicated in nephrogenesis during kidney development. In this report we analyze expression of WT1 in the murine urogenital system. WT1 is expressed in non-germ-cell components of the testis and ovaries in both young and adult mice. In situ mRNA hybridization studies demonstrate that WT1 is expressed in the granulosa and epithelial cells of ovaries, the Sertoli cells of the testis, and in the uterine wall. In addition to the 3.1-kb WT1 transcript detected by Northern blotting of RNA from kidney, uterus, and gonads, there is an approximately 2.5-kb WT1-related mRNA species in testis. The levels of WT1 mRNA in the gonads are among the highest observed, surpassing amounts detected in the embryonic kidney. During development, these levels are differentially regulated, depending on the sexual differentiation of the gonad. Expression of WT1 mRNA in the female reproductive system does not fluctuate significantly from days 4 to 40 postpartum. In contrast, WT1 mRNA levels in the tesis increase steadily after birth, reaching their highest expression levels at day 8 postpartum and decreasing slightly as the animal matures. Expression of WT1 in the gonads is detectable as early as 12.5 days postcoitum (p.c.). As an initial step toward exploring the tissue-specific expression of WT1, DNA elements upstream of WT1 were cloned and sequenced. Three putative transcription initiation sites, utilized in testis, ovaries, and uterus, were mapped by S1 nuclease protection assays. The sequences surrounding these sites have a high G + C content, and typical upstream CCAAT and TATAA boxes are not present. These studies allowed us to identify the translation initiation site for WT1 protein synthesis. We have also used an epitope-tagging protocol to demonstrate that WT1 is a nuclear protein, consistent with its role as a transcription factor. Our results demonstrate regulation of WT1 expression during development of the gonads, implicate WT1 in genitourinary development, and provide a molecular framework toward understanding genitourinary defects observed among hereditary cases of Wilms' tumor.

Amino Acid Sequence

A prospective trial comparing Biobrane, Duoderm and xeroform for skin graft donor sites.

Many new dressings have been introduced for use on split-thickness skin graft donor sites in an effort to reduce pain at the donor site and decrease healing time, while maintaining a low infection rate and cost. To assess these factors in two such dressings, Biobrane (temporary wound dressing) (Winthrop) and Duoderm (hydrocolloid dressing) (Convatec), we compared them with a conventional fine mesh gauze dressing, xeroform, in a prospective, randomized study of 30 donor sites in the same number of patients. Wounds were considered healed when they were 100 per cent re-epithelialized and required no further dressings. Patient self-assessment of pain was quantified on a scale of zero to ten, with ten being the most severe pain. Donor sites dressed with xeroform had a healing time of 10.5 days, which was significantly better (p less than 0.05) than Duoderm (15.3 days) or Biobrane (19.0 days), although the protocol for Duoderm use (wound visualization at seven day intervals) extended the apparent healing times in this group. Duoderm was the most comfortable dressing (0.53 grade) when compared with Biobrane (1.44) and xeroform (2.41, p less than 0.05). No infections occurred in donor sites dressed with xeroform, but two developed in patients using Biobrane. One patient with a Duoderm dressing had a donor site infection during a drug-related neutropenic reaction. Xeroform was the least expensive dressing to use ($1.16 per patient), followed by Duoderm ($54.88 per patient) and Biobrane ($102.57 per patient). The results of our study confirm the usefulness of xeroform as a donor site dressing as it promotes relatively rapid healing, is easy to use and is inexpensive. We found Duoderm to be ideal for smaller donor sites when pain could be significantly reduced with minimal increase in cost. Biobrane is too costly and the infection rate too high for it to be used routinely as a skin graft donor site dressing.

Bandages

Return migration to region of birth among retirement-age persons in the United States.

This study addresses some of the methodological difficulties one encounters in assessing the question of whether older persons display an increasing tendency to return to their state of birth after reaching retirement age. It reanalyzes previously studied data on the question and concludes that there is no indication that elderly people are more prone than nonelderly to "return home" to their native state.

Aged

Longer life but worse health? Measurement and dynamics.

A number of recent cross-sectional studies of longevity and health among the elderly have concluded that recent positive trends in the prolongation of life have not been matched by similar trends in the extension of healthy life. This paper challenges that pessimistic conclusion by examining conceptual issues related to the measurement and dynamics of the mortality-disability process. It uses data from the 1986 Longitudinal Study of Aging (U.S. Department of Health and Human Services, 1988) to illustrate its principal points.

Aged

Interregional elderly migration and population redistribution in four industrialized countries. A comparative analysis.

Though differing in cultures, languages, and socioeconomic attributes, the industrialized nations of the world share a common characteristic: relatively low fertility levels and relatively high proportions of elderly people. These elderly persons are not spread uniformly across their national territories; they exhibit distinct population geographies. This article examines the elderly migration and population redistribution process in four industrialized countries, identifies their principal retirement regions, and analyzes the sources of regional elderly population growth in these regions. It concludes that the United Kingdom and the United States are approaching the final stages of their "elderly mobility transition," whereas Japan is only entering the first stage, with Italy occupying a position somewhere in between.

Aged

Transitional cell carcinoma of upper urinary tract: some prognostic indicators.

Thirty cases of transitional cell carcinoma were reviewed over a twenty-year period. The incidence of bladder tumor recurrence was no different in those who had complete or incomplete nephroureterectomy. Grade and stage correlated well with survival. Intravenous urogram findings at presentation were important prognostic indicators.

Adult

Cancer pain management with a controlled-release oral morphine preparation.

An open-label pilot study was conducted to assess the efficacy and acceptability of a controlled-release oral morphine formulation, MS Contin tablets, when administered "by the clock" two to three times daily as a substitute for opioids given on request to patients with pain caused by advanced cancer. Initially, four-hourly does of standard "immediate-release" oral morphine sulfate tablets were substituted for the patients' prior analgesic medication and titrated to individual needs. Forty of the 47 patients enrolled in the study were subsequently switched to an eight-hourly MS Contin regimen (three patients became too ill to continue the study, and four left the study during the immediate-release titration phase because of adverse reactions that may have been drug related). Small "rescue" doses of standard oral morphine were available to the patients, but they were taken infrequently. Twenty-one of the 37 patients maintained on the eight-hourly schedule consented to be treated with, and were subsequently stabilized on, MS Contin administered every 12 hr, with a reduction of over 20% in their average daily morphine dose. Most of the patients rated the controlled-release medication superior to the standard oral morphine tablets in terms of both convenience and adequacy of relief.

Administration, Oral

Treatment of a murine model of systemic candidiasis with liposomal amphotericin B bearing antibody to Candida albicans.

Survival of mice infected with an intravenous injection of Candida albicans was observed in a short-term (21-day) survival study. Concentration of C. albicans in the kidneys, liver, and spleen was determined at various times. The effects of treatment with the commercial formulation of amphotericin B (fAMB), liposomal amphotericin B (LAMB), and liposomal amphotericin B bearing external antibody specific for C. albicans (LAMB-Ab) were compared. In single intravenous treatment dosages of 0.6 mg of amphotericin B/kg, the liposomal forms of the drug (LAMB and LAMB-Ab) enhanced the percentage survival and mean survival time of mice in comparison with those treated with the unencapsulated antifungal compound, fAMB (p less than 0.03 and p less than 0.001, respectively). LAMB-Ab, at this dosage, produced an increase in the survival (p less than 0.007) of mice over that produced by LAMB. LAMB-Ab treatment caused a greater than 3-fold increase over fAMB. The percentage of LAMB-Ab-treated mice which survived for 21 days was almost double that of the LAMB-treated mice. The increase in survival following this treatment did not, however, lead to the eradication of C. albicans in all mice which survived to the end of the experiment.

Amphotericin B

The elderly mobility transition. Growth, concentration, and tempo.

The redistribution of the elderly population in the United States is receiving increased attention as the sociodemographic consequences of the uneven geography of the aged are becoming more evident to state and local policymakers. Prospects for the future may be illuminated with the development of a conceptual framework for analyzing such redistribution processes. This article suggests that the notion of an Elderly Mobility Transition may be useful in such analyses, and it sets out three measures that could be used to depict the evolution of the transition: growth, concentration, and tempo.

Aged