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Biomedical subjects

M A Brown

Publications and source records attributed to M A Brown.

At least 19 recordsLinked to original sources
PubMed1992

A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer.

IL-4 is a potent immunoregulatory cytokine that exhibits extremely diverse effects on a number of target cells. Although IL-4 was originally described as a T cell-derived product, it is evident that cells of the basophil/mast cell lineage are also an important source of this cytokine. Based on their different tissue distribution, mast cell and T cell-derived IL-4 may have distinct effects on local immune responses. The physiologic production of IL-4 appears to be tightly regulated because most T and mast cells require activation to express significant levels of IL-4. In contrast, a majority of murine transformed mast cell lines constitutively express relatively high levels of IL-4. In this study, transformed mast cell lines were used as models to define cis acting sequences that regulate mast cell IL-4 transcription. Chloramphenicol acetyltransferase reporter gene constructs containing 6.3 kb of 5' IL-4 flanking sequence direct relatively low chloramphenicol acetyltransferase expression in these cells. These results indicated that additional sequences may be important in stimulating transcriptional activity of the IL-4 gene. Using DNAse I hypersensitive site analysis to define other potential IL-4 transcriptional regulatory regions, two sites were identified in the murine IL-4 gene that appear to be unique to IL-4 expressing transformed mast cells. One site defines an intronic sequence that exhibits prototypic enhancer activity in several independently derived transformed mast cell lines. This enhancer is also active in stimulated, non-transformed mast cells but not stimulated EL-4 T cells. Taken together, these data indicate that the IL-4 intronic sequence contains a mast cell specific enhancer that plays an essential role in the unregulated expression of IL-4 in transformed mast cells and may also be important in the inducible expression of IL-4 in normal mast cells.

Animals↗
PubMed1992

Thermoprotection of a functional epithelium: heat stress effects on transepithelial transport by flounder renal tubule in primary monolayer culture.

Primary monolayer cultures of winter flounder renal proximal-tubule cells were used to determine whether transepithelial transport could be protected from the damaging effects of extreme temperature by previous mild heat shock. Renal tubule epithelial cells were enzymatically dispersed and reorganized as confluent monolayer sheets on native rat tail collagen. Transepithelial electrical properties (potential difference, resistance, short-circuit current, and Na(+)-dependent glucose current) and unidirectional [35S]sulfate fluxes were measured in Ussing chambers at 22 degrees C. Examination of transepithelial electrical properties following acute 1-hr elevation of temperature over a range of 22-37 degrees C provided the basis for the "mild" versus "severe" thermal stress protocols. Severe elevation from 22 degrees C to 32 degrees C for 1.5 hr followed by 1.5 hr at 22 degrees C significantly decreased glucose current (7 +/- 0.7 to 3 +/- 0.8 microA/cm2) as well as net sulfate secretion [131 +/- 11 to 33 +/- 11 nmol/(cm2.hr)]. Mild heat shock of 27 degrees C for 6 hr prior to this severe heat shock completely protected both glucose transport (6 +/- 0.7 microA/cm2) and sulfate flux (149 +/- 13 nmol/(cm2.hr)]. Scanning electron microscopy showed that the number of microvilli on the apical (luminal) surface of the epithelium was decreased after a 32 degrees C heat shock. Monolayers exposed to 27 degrees C for 6 hr prior to incubation at 32 degrees C showed no loss of microvilli. SDS/PAGE analysis of protein patterns from the cultures showed that three classes of heat shock proteins were maximally induced at 27 degrees C. Inhibition of protein synthesis by cycloheximide prevented the thermoprotective effect of mild heat shock. This suggests that certain renal transport functions can be protected from sublethal but debilitating thermal stress by prior mild heat shock and that heat shock proteins may play a role in this protection.

Animals↗
PubMed1992

Diversity of blood pressure recording during pregnancy: implications for the hypertensive disorders.

OBJECTIVE: To determine the number and type of methods used to measure blood pressure (BP) in pregnant women. DESIGN: Questionnaires were distributed to obstetricians and midwives concerning: method of recording BP (arm used, subject position, Korotkoff sounds recorded); accuracy of recording BP (cuff size, sphygmomanometer calibration); and definitions of hypertension in pregnancy. PARTICIPANTS: Obstetricians (academic, staff and private) in Sydney; members of the New South Wales Midwives' Association. MAIN RESULTS: Responses were received from 85 obstetricians (55% of those surveyed) and 173 midwives (43%); the overall response rate was 46%. Almost 80% of respondents agreed that diastolic BP above 90 mmHg constituted hypertension during pregnancy but at least six different methods were used to obtain BP readings, with a potentially large variability in the BP so obtained. Forty-five per cent of obstetricians and 72% of midwives stated that they always used a large cuff when necessary. Few had had their sphygmomanometer calibrated within the previous two years. CONCLUSIONS: There is considerable variability in the way BP is recorded in pregnant women. Hypertension in pregnancy may therefore be over or under diagnosed according to the method employed and there is an urgent need for international consensus on how to measure BP accurately in pregnancy.

Blood Pressure↗
PubMed1992

Going public as an AIDS family caregiver.

Images of AIDS invoke fears of contagion, disability and formidable death, and moral overtones directed toward drug use, sexuality and sexual identity and freedom. Responses to these images are both private and public, and have profound consequences for individuals whose lives have been touched by the disease, both the person with AIDS and the family caregiver. The purpose of this paper is to analyze in detail 'going public,' one category of a substantive theory of AIDS family caregiving. This category was developed from a grounded theory study of 53 AIDS family members who were asked to describe their experiences as an AIDS family caregiver during an indepth interview. Data were content analyzed using constant comparative analysis. Going public referred to how AIDS family caregivers let others known that they were caring for a PWA. Specifically, going public entailed selecting appropriate persons and audiences to tell, formulating approaches to communicating information, and considering the risks and benefits of the possible choices. The description of going public as an AIDS family caregiver details the assertiveness involved in political action and social change, contrasted with the isolation and secrecy involved in maintaining relationships with others under the condition of a stigmatizing illness. Data revealed a particular emphasis on the phenomenon of 'guilt by association'. Because of their close relationship to a person with AIDS, caregivers were obligated to share the stigma of AIDS and were likewise discredited. Findings from our study emphasize the tremendous personal suffering experienced by caregivers which was associated with AIDS stigma in the form of rejection, loss of friends and harassment. Data also revealed the strong commitment of many caregivers to social activism which ranged from participating in educational efforts to marching in demonstrations. The rationale for the apparent increased activism among AIDS family caregivers compared to other groups of caregivers is explored. Going public highlights both the personal suffering and social manifestations of AIDS, significant issues to consider in planning health services for the second decade of the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The kidney in hypertensive pregnancies--victim and villain.

Many changes in renal function occur in normal pregnancy. Without a proper understanding of these changes, routine clinical investigations may easily be misinterpreted. Women with preeclampsia have further alterations in renal function and, in occasional cases, develop acute renal failure. Understanding of abnormal renal physiology and hormonal changes in these women allows the clinician to interpret biochemical tests appropriately and make proper use of vasodilator therapy with careful attention to volume homeostasis. Women who undertake pregnancy with a primary renal disease, most commonly glomerulonephritis or reflux nephropathy, have a higher risk of adverse fetal and maternal outcomes. Awareness of these risks provides a basis for proper preconceptual counseling, as well as careful monitoring of maternal blood pressure and renal function and fetal growth during such pregnancies. These strategies will optimize the chances of a successful pregnancy outcome for both mother and baby.

Female↗
PubMed1992

Endothelium-derived prostacyclin: effect of serum from women with normal and hypertensive pregnancy.

1. Pregnancy-induced hypertension (or pre-eclampsia) is characterized by vasoconstriction, platelet aggregation and altered capillary permeability, implying disordered endothelial function and/or structure. Serum from women with pregnancy-induced hypertension has been reported by others to be cytotoxic to endothelial cells in vitro. We hypothesized that such serum contains a factor that limits the ability of endothelial cells to produce and/or release prostacyclin. 2. Prostacyclin production by intact and damaged cultured human umbilical vein endothelial cells was measured after incubating these cells with serum from non-pregnant and normal pregnant women and women with pregnancy-induced hypertension. Confluent human umbilical vein endothelial cell monolayers (intact and damaged) were incubated with sera for 24 h at 37 degrees C followed by 1 h of incubation with added thrombin (stimulated production) or media (basal production). Supernatants were then collected for measurement of 6-keto-prostaglandin F1 alpha by radioimmunoassay. 3. Basal production of 6-keto-prostaglandin F1 alpha was greater in response to serum from non-pregnant women than to that from pregnant women. Within each group, sub-lethally damaged cells had a similar basal production of 6-keto-prostaglandin F1 alpha to that of intact cells. 4. Basal production of 6-keto-prostaglandin F1 alpha by intact or damaged cells incubated with sera from normal pregnant women and from women with pregnancy-induced hypertension was similar. 5. In all groups the addition of thrombin to intact endothelial cells increased 6-keto-prostaglandin F1 alpha production approximately 15-30-fold over basal levels, but only three- to five-fold in damaged endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Measurement of plasma volume in pregnancy.

1. Determination of the plasma volume in pregnant women is a useful research tool and may become an important clinical measurement. We used three methods to determine plasma volume using Evans Blue dye: (1) the 'usual' method, measuring serum absorbance at a wavelength of 610 nm, (2) a two-wavelength method, and (3) precipitation of non-albumin proteins by the addition of polyethyleneglycol before measuring serum absorbance at a wave-length of 620 nm. These were each compared with the standard 125I-human serum albumin method in 20 non-pregnant subjects. Subsequently, the polyethylene glycol method was considered the standard and the three Evans Blue dye methods were compared in 20 pregnant women. 2. In non-pregnant subjects mean plasma volumes did not differ significantly according to the method used. However, the limits of agreement with 125I-human serum albumin method were closest for the polyethyleneglycol method, for both clear and turbid sera. 3. In pregnant women, mean plasma volume values did not differ according to the Evans Blue dye method used, but the limits of agreement were significantly closer with the two-wavelength method than with the 'usual' method (P less than 0.05) largely owing to the effects of turbid sera. 4. These studies demonstrate that considerable error may occur when the Evans Blue dye concentration is determined in turbid sera by the 'usual' method. This can be overcome by the use of the two-wavelength method or the polyethyleneglycol method. The most accurate results will be obtained if the latter method is employed routinely to determine plasma volume in pregnant women.

Adult↗
PubMed1992

Structure-activity relationship of a series of sensory irritants.

The relative potencies for a series of sensory irritants, with structures based on toluene, were determined by measuring the airborne concentrations that caused a 50% decrease in respiratory rate in Swiss-Webster mice. This concentration is referred to as the RD50. Toluene, a relatively nonirritating compound, and compounds with chlorine, two chlorines, bromine, and iodine atoms substituted on the alpha carbon of toluene were tested. The RD50s for these compound types were determined to be 4900, 27, 27, 5.2, and 4.3 ppm, respectively. In addition, compounds with chlorine substituted at the ortho, meta, and para positions on the toluene ring were also tested. The RD50s were determined to be 4.9, 13, and 14 ppm, respectively. The structure-activity relationships of the compounds studied are explained by a model (Abraham et al., 1990; Nielsen and Alarie, 1982) that relates the interaction of sensory irritants with a receptor protein in a lipid bilayer. The trends in the RD50s, and thus sensory irritation, for the compounds studies are related to the development of a partial positive charge on the toluene alpha carbon by the positioning of a ring chlorine and the bond dissociation energies of the alpha carbon-halogen bond for the iodo, bromo, and chloro isomers of benzyl halide.

Animals↗
PubMed1992

Renin-aldosterone relationships in pregnancy-induced hypertension.

The relationship between plasma renin (PRC) and aldosterone (PAC) concentrations was determined in 83 normal third trimester pregnant women (P), 50 women with pregnancy-induced hypertension (PIH), and 80 age-matched nonpregnant women not taking oral contraceptives (NP). Normal pregnant women had a slightly higher 24-h urine sodium: creatinine ratio than the other groups (P less than .001) (NP: 10 +/- 4 v P: 15 +/- 8 v PIH: 12 +/- 7; mean +/- SD). Both PRC and PAC were higher in normal pregnant women as was the ratio PAC:PRC [normal pregnant 195 (158 to 337) v nonpregnant 130 (101 to 209), median (interquartile range); P less than .001]. This was accompanied by a slightly reduced slope (sensitivity) of the logPRC-logPAC relationship in normal pregnant women (P less than .05). Women with PIH had reduced PRC and PAC compared with normal pregnant women but a two-fold greater increase in PAC:PRC ratio [PIH 411 (277 to 598) v normal pregnancy 195 (158 to 337), P less than .001], with a rise in the slope (sensitivity) of the logPRC-logPAC relationship in women with PIH (P less than .001). Thus there is proportionately greater aldosterone release in the third trimester of normal pregnancy than in nonpregnant women. This preferential increase in aldosterone may be due to altered adrenal sensitivity to angiotensin II or may reflect enhanced nonangiotensin stimulation of aldosterone during pregnancy. Women with PIH have reduced PRC and PAC but relatively greater stimulation of aldosterone than normal pregnant women, possibly due to enhanced sensitivity of the adrenal glands to angiotensin II.

Aldosterone↗
PubMed1992

Extracellular fluid volumes in pregnancy-induced hypertension.

OBJECTIVES: Reduction in plasma volume (Pvol) of women with pregnancy-induced hypertension (PIH; preeclampsia) has both physiological and clinical implications. This study was undertaken to determine the following variables in women with PIH: (1) the incidence of reduced Pvol; (2) the distribution of total extracellular fluid volume (ECFV); (3) the relationship between Pvol and birth weight; and (4) whether any readily available clinical or laboratory parameters predict the presence of reduced Pvol. SETTING: Teaching hospital obstetric unit and antenatal clinic. PARTICIPANTS: Forty-nine primigravidae with PIH (28 mild, 21 severe), 54 normotensive primigravidae and 25 non-pregnant controls. DESIGN: Pvol was measured using Evans Blue dye and ECFV as the mannitol space. These measures were compared amongst groups, and also within groups for those with PIH, according to the severity of their disorder and the presence of proteinuria or oedema. Blood pressure, haematocrit, uric acid and serum albumin were also evaluated as predictive indices of reduced Pvol in women with PIH. RESULTS: Pvol, ECFV and the Pvol:ECFV ratio all increased during normal pregnancy. Pvol in women with PIH was reduced compared with normal pregnancy and correlated significantly with birth weight. Total ECFV was unchanged in women with PIH, but their Pvol:ECFV ratio was significantly reduced compared with normal pregnancy. Although there was a significant correlation between Pvol and haematocrit in women with PIH, haematocrit was a poor predictor for reduced Pvol. Diastolic blood pressure greater than 100 mmHg, persistent proteinuria and severe PIH were the only reliable positive predictors of a reduced Pvol. CONCLUSIONS: Pvol is related to birth weight, but is reduced in only approximately half of women with PIH. This reduced Pvol is the result of maldistribution, not loss, of total ECFV, and can be predicted by high diastolic blood pressure, proteinuria or other clinical signs of severity, but not by haematocrit.

Adult↗
PubMed1992

Atrial natriuretic peptide in pregnancy: response to oral sodium supplementation.

1. The control of extracellular fluid volume (ECFV) in normal pregnancy may be related to changes in atrial natriuretic peptide. Previous studies in non-pregnant subjects have suggested that plasma atrial natriuretic peptide (ANP) increases in response to dietary sodium supplementation because of an increase in plasma volume, although this has not been measured directly. 2. Nine women who were pregnant in the third trimester undertook oral sodium supplementation (136 mmol) for 5 days in addition to their usual diet. Twenty-four hour urinary sodium excretion increased by 125 +/- 54 mmol/day (mean +/- s.d.; P less than 0.01). Plasma volume was unchanged, although total ECFV tended to increase (P less than 0.09 and bodyweight increased (1.3 +/- 1.4 kg; P less than 0.01) at the end of these diets. 3. Plasma ANP increased by 30.7 [8.6, 34.5] pmol/L (median [25th, 75th percentile]; P less than 0.05), while plasma renin concentration decreased significantly from 7.3 [6.2, 11.2] to 2.6 [1.7, 3.9] pmol angiotensin I/mL (P less than 0.01), as did plasma aldosterone concentration (1435 [1162, 1722] to 753 [595, 1110] fmol/mL; P less than 0.01). Plasma vasoactive intestinal peptide was unchanged. 4. Pregnant women respond to increased dietary sodium with an increase in plasma ANP in the absence of a significant increase in plasma volume. The acute regulation of plasma ANP in response to increases in dietary sodium in pregnant women does not appear to be mediated by changes in intravascular fluid volume.

Adult↗
PubMed1992

Aerosolized lipopolysaccharide increases pulmonary clearance of 99mTc-DTPA in rabbits.

Bacterial endotoxins alter the permeability of endothelium, but little is known of their effect on epithelium. We exposed specific pathogen-free rabbits to aerosolized Pseudomonas aeruginosa LPS or saline and performed serial measurements of RL, Cdyn, BP, WBC count and differential, and platelet counts. Pulmonary 99mTc-DTPA half-life was measured 4, 6, or 8 h after exposure. The animals were sacrificed and BAL performed. Background and PMA-stimulated superoxide production was measured from individual AM using electrooptical determination of reduction of NBT. Lung tissue was processed for light microscopy and ratio of wet to dry weight. 99mTc-DTPA half-life was significantly shorter in LPS-exposed animals at 6 h (p < 0.05) and 8 h (p < 0.001). There were no differences in Cdyn, RL, BP, WBC, differential, platelet, or BAL cell count at any time between groups. No histologic changes or differences in lung wet to dry weight ratios were found. PMA-stimulated AM superoxide production was significantly increased (p < 0.01) in LPS-exposed animals. This effect was time dependent and could be duplicated in AM from control animals following a 4-h incubation with LPS, lavage fluid from LPS-exposed animals, or recombinant murine TNF. These results demonstrate that aerosolized Pseudomonas LPS increases pulmonary epithelial permeability and primes AM superoxide production.

Aerosols↗
PubMed1992

Nutritional patterns of centenarians.

This study compares the dietary patterns of centenarians (n = 24) with elderly adults in their sixties (n = 54) and eighties (n = 47). Compared to the younger cohorts, centenarians consumed breakfast more regularly, avoided weight loss diets and large fluctuations in body weight, consumed slightly more vegetables, and relied on their doctor and family more than on the news media for nutrition information. On the other hand, centenarians were less likely to consume diets low in fat and to comply with nutritional guidelines designed to reduce the risk of chronic disease. Elderly black men consumed diets higher in sweets and fat compared to black women and white men and women. Nearly three times as many blacks expressed the desire to eat more nutritiously. High nutrition risks, particularly in blacks, were associated with lower physical and mental health and impaired activities of daily living.

Activities of Daily Living↗
PubMed1992

Inhibition of differentiation in a murine F9 embryonal carcinoma cell subline by leukemia inhibitory factor (LIF).

Leukemia inhibitory factor (LIF) is a cytokine previously shown to maintain pluripotent embryonic stem cells in their undifferentiated state. We have examined the effects of LIF in nullipotent embryonal carcinoma cell lines, and have found that LIF blocks differentiation induced by retinoic acid and at low temperature in OTF9 cells. LIF did not block differentiation in a parent F9 cell line. For OTF9 cells, LIF acts early in differentiation, inhibiting the appearance of parietal endoderm-type product cells. However, it acts subsequent to retinoic acid, and at least one early retinoic acid-induced event is unaltered in the presence of LIF. This finding provides both a means of dissecting the cascade of events leading to EC cell differentiation, and a well-characterised target cell type for studying the mechanism of action of LIF.

Animals↗
PubMed1992

Haemodynamic and metabolic effects of short term administration of synthetic sex steroids in humans.

Synthetic sex steroid administration is a major cause of iatrogenic hypertension but little is known of the haemodynamic or metabolic consequences of these steroids. This study examined the short term blood pressure, volume and metabolic consequences of 5 day administration of synthetic androgen to normal men and synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6 men) on a constant diet took part in each of 3 studies. Males received testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol 0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8 mmHg) systolic pressure but the other steroids did not alter blood pressure. All 3 treatments increased body weight. There were no consistent changes in plasma electrolytes or glucose with any steroid, and no urinary sodium retention or changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid significantly increased plasma volume (measured as volume of distribution of 125I human serum albumin). Renin substrate and cortisol rose and renin concentration fell on ethinyloestradiol. These studies suggest that the progestogen component may contribute to the blood pressure raising effects of oral contraceptives.

Adult↗
PubMed1992

Acute and chronic regulation of atrial natriuretic peptide in human pregnancy: a longitudinal study.

OBJECTIVE: To determine whether the increase in extracellular fluid volume (ECFV) that occurs during pregnancy alters: (1) the baseline regulation of atrial natriuretic peptide (ANP); or (2) the ANP response to intravascular volume expansion with either haemaccel or hypertonic saline. DESIGN: A group of normal pregnant subjects was studied longitudinally on three occasions, commencing before 16 weeks of gestation. They were compared with a group of age-matched non-pregnant women. Dietary sodium intake and posture were carefully controlled. METHODS: Plasma volume and total ECFV were determined by tracer dilution methods, using Evans Blue and 20% mannitol, respectively. Plasma ANP and aldosterone concentrations were measured by radioimmunoassay. RESULTS: Plasma ANP did not increase during pregnancy despite increases in both plasma and total ECFV. The plasma ANP response to acute intravenous volume expansion in later pregnancy appears to be more sensitive than either in early pregnancy or in non-pregnant subjects. The initial ANP response to infusions of haemaccel during pregnancy was greater than the ANP response to saline. CONCLUSIONS: During a normal pregnancy, plasma ANP is maintained in the normal non-pregnant range, despite an increase in plasma volume when the effects of dietary sodium intake and posture are carefully accounted for. The ANP response to intravenous volume expansion is enhanced in late pregnancy. The greater ANP response to haemaccel infusions during pregnancy suggests that an increase in atrial stretch mediates the secretion of ANP following intravenous volume expansion.

Adult↗