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Biomedical subjects

B A Clark

Publications and source records attributed to B A Clark.

At least 55 records · Page 3Linked to original sources
PubMed1992

Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment.

OBJECTIVE: The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity. STUDY DESIGN: Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women. RESULTS: Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05). CONCLUSION: Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.

Adult↗
PubMed1992

In-vivo and in-vitro studies on the effect of amphotericin B on endothelin release.

Since amphotericin B nephrotoxicity is mediated, in part by hypoxic tubular injury, the role of endothelin in the renal vasoconstriction, characteristic of amphotericin toxicity has been studied. Intact and salt depleted rats were infused with amphotericin B (20 micrograms/kg per min) or 5% dextrose over 20 min. Plasma endothelin levels determined at the conclusion of the infusion period, did not differ between the experimental groups, despite a marked reduction in renal blood flow noted in rats infused with amphotericin B. Amphotericin B (10(-5)-10(-7) M) did not stimulate endothelin release from cultured bovine aortic endothelial cells. However, in a model of chronic amphotericin nephrotoxicity produced by repeated daily intraperitoneal injections of amphotericin B (5 mg/kg) to salt depleted rats, renal failure was associated with elevated plasma endothelin levels (29.3 +/- 4.4 fmol/mL, vs 10.8 +/- 1.2 fmol/mL in salt depleted controls, P less than 0.01). We conclude that while plasma endothelin may be increased in chronic amphotericin B nephropathy, this peptide does not mediate the acute renal vasoconstriction associated with the infusion of this drug.

Amphotericin B↗
PubMed1992

Unsuspected morbid hypermagnesemia in elderly patients.

This study was designed to determine the incidence, etiology and consequences of severe hypermagnesemia. We retrospectively reviewed all hospital admissions over a 5-year period from 1984 to 1989 and identified 8 cases of severe hypermagnesemia (serum Mg > or = 6.0 mg/dl) due to magnesium ingestion. All but 1 patient were elderly (mean age 70 +/- 6 years). The etiology when identified was due to magnesium-containing cathartics (n = 3) or antacids (n = 3). The total amount of magnesium ingested was not excessive, but bowel disorders that may have enhanced absorption (such as active ulcer disease, gastritis, colitis, perforated viscus, massive gastric dilatation) were present in 7 of the 8 patients. Unexpectedly, only 1 had preexisting renal failure. Renal function was found to be normal in 1, only mildly to moderately impaired in 5 (creatinine < 3.6 mg/dl) and severely impaired in 2 (creatinine 7.6, 15.7 mg/dl). Clinical sequelae of hypermagnesemia were hypotension (n = 7), bradycardia (n = 2), respiratory depression (n = 3), EKG abnormalities (n = 6), depressed mental status (n = 5). Hypocalcemia (range 5.7-7.4 mg/dl) more severe than could be attributed to either hypoalbuminemia or acute renal failure was present in 7. A low anion gap (range-2 to 9) was present in 5. Most striking was the fact that despite clinical sequelae, the hypermagnesemia was unsuspected in 6 of the 8 cases. Hypermagnesemia can occur without severe renal insufficiency in association with bowel disease, particularly in elderly individuals, and may be a clinically unrecognized cause of cardiovascular dysfunction, hypocalcemia and neurologic or respiratory depression.

Aged↗
PubMed1992

Altered dopaminergic responses in hypertension.

Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine.

Aged↗
PubMed1992

Effect of atrial natriuretic peptide on potassium-stimulated aldosterone secretion: potential relevance to hypoaldosteronism in man.

Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion under certain circumstances, although the physiological significance of this is uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone secretion in man and, if so, whether we might find high circulating levels of ANP in patients with the syndrome of acquired hypoaldosteronism. We studied seven healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg) over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We also evaluated ANP levels in eight elderly subjects with the syndrome of acquired hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L) associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In the normal subjects, ANP almost completely suppressed the aldosterone response to KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but did not change during the infusion of KCl alone. ANP levels were approximately 800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/- 340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level that would be capable of suppressing the potassium-mediated aldosterone response. Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia, and ANP levels were found to be markedly elevated in a group of patients with hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to clinically significant hypoaldosteronism and hyperkalemia in the syndrome of acquired hypoaldosteronism.

Adult↗
PubMed1992

Radiocontrast agents induce endothelin release in vivo and in vitro.

The intravascular administration of the ionic radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of radiocontrast nephropathy.

Animals↗
PubMed1991

The breast tumor-associated epitope defined by monoclonal antibody 3E1.2 is an O-linked mucin carbohydrate containing N-glycolylneuraminic acid.

The breast cancer-associated epitope (mammary serum antigen or MSA) defined by monoclonal antibody (Mab) 3E1.2 is a neuraminidase-sensitive carbohydrate expressed on MUC-1-encoded molecules. However, the reactivity of Mab 3E1.2 is also reduced by protease treatment of the mucin, which suggests that 3E1.2 binds to multimers of the sialylated carbohydrate in a protein conformation-dependent manner. The common N-acetyl derivative of neuraminic acid (5-acetylneuraminic acid) is not involved in the epitope, since lectins specific for 5-acetylneuraminic acid (linked to GalNAc or Gal) are nonreactive with MSA-positive molecules. However, the N-glycolyl derivative, 5-glycolylneuraminic acid (Neu5Gc), forms a major part of the epitope since both free Neu5Gc and porcine stomach mucin (greater than 90% neuraminic acid as Neu5Gc) inhibit the binding of Mab 3E1.2, while bovine or ovine submaxillary mucins, fetuin, bovine gangliosides, and other carbohydrates do not. Indeed, the presence of Neu5Gc on human tumor mucin was confirmed by electrospray mass spectrometry. Neu5Gc is attached to an O-linked carbohydrate, since the expression of MSA by MCF-7 breast cancer cells is inhibited by the O-glycosylation inhibitor phenyl-N-acetyl-alpha-D-galactosaminide, but not by the N-glycosylation inhibitor tunicamycin, and the epitope is removed by treatment with O-glycanase but not N-glycanase F, endoglycosidase F, or endoglycosidase H, which are specific for N-linked glycans. This is likely to be a core glycan since 3E1.2 reacts after treatment of the mucin with trifluoromethanesulfonic acid, which removes most backbone and peripheral carbohydrates. Treatment with galactosidase or N-acetyl glucosaminidase enhances the binding of Mab 3E1.2, indicating that the Neu5Gc is not attached to galactose or N-acetyl galactosamine. Furthermore, the susceptibility of MSA to treatment with Arthrobacter urea-faciens neuraminidase [which is specific for alpha (2-6)-linked NeuNAc] and the loss in reactivity of GalNAc-specific lectins after periodate oxidation [alpha (2-3)-linked but not alpha (2-6)-linked NeuNAc protects GalNAc from periodate oxidation] indicate that the Neu5Gc may be attached alpha (2-6) to peptide-linked GalNAc. These results show that MSA is a Neu5Gc-containing O-linked core glycan, which represents a unique tumor-associated epitope not previously identified on human mucins.

Animals↗
PubMed1991

Production of MUC1 and MUC2 mucins by human tumor cell lines.

A mucus secreting, clonal derivative (HT29-SB) of the human colonic adenocarcinoma cell line HT29, and the LS174T colon cancer cell line, secrete mucin into the culture medium as a viscoelastic gel. Mab BC2, which defines a peptide epitope present in the variable number of tandem repeats (VNTR) of the MUC1 core protein, reacted with this material after deglycosylation. Two high molecular weight bands were detected in TFMSA treated gel-formed mucin from HT29-SB and LS174T by western blotting (Mr 580 kDa and 420 kDa). A similar pattern of reactivity was seen with the culture supernatants from HT29-SB, the ovarian tumor cell line COLO-316, and the breast cancer cell line MCF-7. Mab CCP58 (anti-MUC2 VNTR) reacted with a 580 kDa band in gel-formed mucin produced by LS174T, but was not reactive with mucin produced by the other cell lines. The findings indicate that human colonic cell lines, in addition to breast and ovarian cell lines, may both express and secrete the MUC1 protein core, and that the LS174T cell line expresses and secretes both the MUC1 and MUC2 core proteins.

Adenocarcinoma↗
PubMed1991

Influence of age and dose on the end-organ responses to atrial natriuretic peptide in humans.

To test the hypothesis that age differentially affects the natriuretic, hemodynamic, and humoral response to exogenous ANP, we studied seven young (Y, 20 to 39 years) and five old (O, 65 to 83 years) healthy, normotensive, nonobese men during infusion of synthetic human ANP1,28 at two different rates: 1) 0.05 microgram/kg/min (high dose) for 1 h and 2) 0.005 microgram/kg/min (low dose) for 1 h. Compared to young, the old had higher basal ANP levels (O = 142 +/- 41 v Y = 29 +/- 4 pmol/L, P less than .025), achieved higher plasma levels with low-dose infusion (O = 327 +/- 24 v Y = 155 +/- 37 pmol/L, P less than .001) and had a longer ANP half-life (O = 7.8 +/- 0.6 v Y = 4.3 +/- 0.6 min, P less than .001), suggesting decreased catabolism in the old compared to the young. Despite these age-related differences in ANP levels, there was no difference in urinary sodium or cyclic GMP excretion. After termination of the low-dose infusion, plasma ANP and urinary cGMP promptly returned to baseline levels. Despite this, a sustained natriuresis (2-fold above control) was observed for 3 h in both groups. Low-dose infusion was associated with sustained suppression of aldosterone with minimal hemodynamic changes. During high-dose infusions there was no difference in natriuresis or peak ANP levels between the two groups (O = 1299 +/- 93 v Y = 1140 +/- 54 pmol/L). In contrast to the low-dose infusion, the high-dose infusion produced a transient natriuresis lasting only for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Atrial natriuretic peptide suppresses osmostimulated vasopressin release in young and elderly humans.

Atrial natriuretic peptide (ANP) may suppress vasopressin release, but the dynamics of this interaction as well as the influence of age have not been defined. We studied six or seven young (19-40 yr old) and seven elderly volunteers (65-83 yr old) under two circumstances: 1) after infusion of 5% saline (0.04 ml.kg-1.min-1) for 2 h and 2) after the same infusion given with simultaneous synthetic human ANP (0.05 micrograms.kg-1.min-1). Hypertonic saline alone produced a progressive rise in plasma vasopressin with increasing serum sodium. During hypertonic saline alone, vasopressin levels began to rise at an increment in serum sodium of 1.67 +/- 0.35 mM in the young and 1.43 +/- 0.32 mM in the elderly and rose linearly with increasing serum sodium. When ANP was infused with hypertonic saline (with peak ANP levels of approximately 1,000 pM), vasopressin levels began to rise at an increment in serum sodium of 4.43 +/- 0.67 mM in the young and 4.57 +/- 0.43 mM in the elderly (P less than 0.01 vs. saline alone). Furthermore, the vasopressin response for any given serum sodium was significantly reduced in both young and elderly subjects, resulting in a rightward displacement of the curve relating vasopressin response to sodium concentration (P less than 0.001). In conclusion, ANP not only suppresses vasopressin but raises the threshold for release of vasopressin in response to osmotic stimulation in both young and elderly individuals. High circulating ANP levels may be responsible in part for the suppression of vasopressin levels and water diuresis seen during states of volume expansion.

Adult↗
PubMed1991

Islet cell responses to glucose in human transplanted pancreas.

Postsurgery, pancreas transplantation results in alterations of carbohydrate metabolism. Additionally, immunosuppressive therapy impacts on glucose regulation. We evaluated the hormonal and metabolic responses of pancreas allografts, utilizing the hyperglycemic clamp technique coupled with the tritiated glucose methodology, in 11 volunteers who had received simultaneous pancreas-kidney transplantation (P-K) with systemic drainage. Their responses were compared with seven volunteers who had received only a kidney (K) graft and with seven normal control (C) volunteers. Although basal glucose and hepatic glucose output were similar in all three groups, basal insulin, C-peptide, glucagon, and pancreatic polypeptide were highest in the P-K group and lowest in normal subjects. During hyperglycemia, all groups showed a similar characteristic, initial complete suppression of hepatic glucose production, with recovery followed by a later suppression. Peripheral glucose uptake was similar in P-K and C subjects but decreased in K patients. Systemic insulin levels were fourfold higher in the pancreas transplant patients than in healthy subjects. Thus, under basal and hyperglycemic stimulation, 1) hepatic glucose homeostasis is regulated normally, even with pancreatic drainage into the systemic circulation; 2) overall glucose disposal is normal in P-K patients because of marked hyperinsulinemia; and 3) there is loss of tonic inhibition of endocrine pancreatic function secondary to pancreatic denervation.

Adolescent↗
PubMed1991

Predictors of improvement in the 12-minute walking distance following a six-week outpatient pulmonary rehabilitation program.

We evaluated the relationship of clinical characteristics, pulmonary function, and exercise test data to the degree of improvement in the 12-minute walking distance (12MD) in 50 ambulatory outpatients completing a six-week pulmonary rehabilitation program. The 12MD increased by 27.7 +/- 32.5 percent, or 462 +/- 427 ft, by the end of the program. There were no significant relationships between improvement in the 12MD and age, sex, oxygen requirement, arterial blood gas levels, and pulmonary function; however, patients with a greater ventilatory reserve (1-[VEmax/MVV] x 100) had more improvement in their 12MD, both with respect to distance and percentage of increase over baseline. Additionally, patients with a lower peak oxygen consumption (VO2) and peak oxygen pulse (O2P) showed greater percentage of improvement in their 12MD. The magnitude of the initial 12MD was inversely related to its improvement, both with regard to distance (r = -0.43; r2 = 0.18; p less than 0.003) and percentage of increase (r = -0.71; r2 = 0.51; p less than 0.0001). Using stepwise regression, the combination of smaller initial 12MD and greater FEV1 was significantly predictive of improvement in the 12MD. Patients with poor performance on either a 12MD or maximal exercise test are not necessarily poor candidates for a pulmonary rehabilitation program.

Ambulatory Care↗
PubMed1990

Calibration of photodiode measurements of cell motion by a transmission optical lever method.

A method of calibrating photodiode measurements of cell motion is described. A transparent glass plane is inserted perpendicular to the light path, in front of the photodiode. When the glass plane is rotated, changing the angle between the plane and the light path, the image is displaced. The rotatable glass plane acts as an optical lever to simulate cell motion. The optical lever is easy to construct and offers excellent linearity and accuracy.

Calibration↗
PubMed1990

The influence of gender, age, and the menstrual cycle on plasma atrial natriuretic peptide.

To examine the influence of gender, age, and the menstrual cycle on atrial natriuretic peptide (ANP) levels, we measured daily levels of ANP, aldosterone, estrogen, and progesterone in 13 young women (ages 25-35 yr) during the luteal phase of the menstrual cycle and daily ANP and aldosterone levels in 9 young men (ages 25-43 yr) for 10 consecutive days. In addition, fasting plasma ANP levels were assayed in 12 elderly male (ages 62-86 yr) and 9 elderly female subjects (ages 64-80 yr) on at least two separate occasions. The average daily ANP levels in the young women were much higher than those in the men (68.1 +/- 5.5 vs. 39.8 +/- 3.4 pmol/L; P less than 0.001), although no cyclical changes in ANP levels were observed. ANP levels were 94.0 +/- 17.9 pmol/L in elderly men and 78.3 +/- 19.4 pmol/L in elderly women. Aldosterone levels were higher in women than men during the luteal phase of the menstrual cycle (1154 +/- 125 vs 488 +/- 42 pmol/L; P less than 0.001), but not during the periovulatory period (580 +/- 103 pmol/L) or during menses (563 +/- 61 pmol/L). In conclusion, ANP levels in young women average approximately twice those in young men, but do not fluctuate with the cyclical changes in estrogen, progesterone, and aldosterone seen during the menstrual cycle. However, ANP levels in postmenopausal women are not greater than those in age-matched elderly men. Thus, gender appears to affect the secretion or metabolism of ANP during the premenopausal years of life.

Adult↗
PubMed1989

Photoreactions of human lens monomeric crystallins.

Human lens beta s- and gamma A-crystallins exhibit very similar tryptophan fluorescence emission maxima (329 nm). gamma A isolated from infant human lenses is photo-oxidized by 300 nm irradiation and forms water-insoluble aggregates; beta s or gamma A from young human lenses form a small amount of water-soluble crosslinked species. At least part of the mechanism of photodamage by 300 nm irradiation is photogeneration of the oxidant H2O2 via the generation of O2- radical, this reaction occurs via photosensitization by the tryptophan photo-oxidation product N-formylkynurenine (N-FK) or related species. These results indicate that even though the tryptophan residues of beta s- and gamma A-crystallins are in hydrophobic (buried) microenvironments as compared to those of the alpha- and beta-crystallins, the photogeneration of N-FK is sufficient to produce O2- and H2O2.

Adolescent↗
PubMed1989

Pregnancy loss in a small chorionic villus sampling series.

Two previous reports have suggested that the pregnancy loss rate with chorionic villus biopsy is high in the initial 100 to 300 cases. In the initial 211 cases of this study, the total pregnancy loss rate (7.1%) and losses not attributed to induced abortion or cytogenetic abnormality (2.8%) do not support this contention.

Abortion, Spontaneous↗
PubMed1989

Human papillomavirus DNA in adenocarcinoma in situ, microinvasive adenocarcinoma of the uterine cervix, and coexisting cervical squamous intraepithelial neoplasia.

Previously, human papillomavirus (HPV) DNA, mainly HPV-18 DNA, was detected in more than 40% (17/40 cases) of invasive adenocarcinoma of the uterine cervix in our laboratory. In order to identify HPV DNA in the precursor lesions of adenocarcinoma of the cervix, 11 cases of adenocarcinoma in situ containing microinvasive adenocarcinoma and 10 cases of adenocarcinoma in situ were studied for the presence of HPV DNA by in situ hybridization using highly sensitive 3H-labeled HPV-16 and HPV-18 DNA probes. HPV types present in cervical squamous intraepithelial neoplasia (CIN) coexisting with adenocarcinoma in situ and microinvasive adenocarcinoma were also studied. Apart from the coexisting CIN II-III with glandular neoplasms, 48 cases of CIN III (severe dysplasia and squamous carcinoma in situ) removed by conization or hysterectomy and known to be free of adenocarcinoma were used for comparison. HPV DNA was detected in 64% of microinvasive adenocarcinoma, 70% of adenocarcinoma in situ, and 63% of the control CIN III. HPV-18 DNA was the preponderant type of HPV DNA found in adenocarcinoma in situ and microinvasive adenocarcinoma. All cases of HPV DNA-positive microinvasive adenocarcinoma contained the same type of HPV DNA as the lesions of coexisting adenocarcinoma in situ. CIN coexisting with microinvasive adenocarcinoma or adenocarcinoma in situ contained the same type of HPV as identified in the glandular lesions, whereas all of the HPV DNA-positive control CIN III cases contained HPV-16 DNA. These results suggest that adenocarcinoma in situ is a precursor lesion of adenocarcinoma of the cervix that contains HPV DNA, and that CIN coexisting with adenocarcinoma may be a result of a metaplastic process of adenocarcinoma or of bidirectional differentiation of the affected reserve cells.

Adenocarcinoma↗