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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 343 records · Page 19Linked to original sources

Profound hyperkalemia without electrocardiographic manifestations.

Although the electrocardiogram (ECG) is not considered a reliable indicator of mild to moderate hyperkalemia, profound elevations of serum potassium concentration generally produce classic ECG manifestations. We report two cases of severe hyperkalemia (greater than 9.0 mEq/L) in which the ECGs did not reveal the expected manifestations of hyperkalemia. Thus, even with profound serum potassium elevations, the ECG cannot reliably be used to exclude the presence of hyperkalemia or to monitor therapy designed to lower the serum potassium concentration.

Aged↗

Serial amniocenteses in the treatment of twin to twin transfusion complicated with acute polyhydramnios.

Twin to twin transfusion, complicated by acute polyhydramnios in a monozygous twin pregnancy, is a difficult clinical problem. A precipitous course usually results in termination of the pregnancy within a few days and often is associated with a high perinatal mortality rate. Two cases are presented that were treated with repeated amniocenteses for the relief of extreme abdominal discomfort and to prevent imminent premature labor. The amount of amniotic fluid removed each time varied from 300 cc to 1200 cc, which was enough to relieve symptoms but not enough to induce uncontrolled uterine activity. A total of 3500 cc and 4750 cc of amniotic fluid were removed from the first and the second patient, respectively. The procedure was found to be safe and resulted in prolonging the pregnancies by 14 and 11 days, respectively. This management, with the addition of tocolysis and close fetal surveillance can offer some hope in an otherwise hopeless situation.

Adult↗

Increased prostaglandin synthesis by low calcium-regulated keratinocytes.

The effect of calcium concentration on the in vitro prostaglandin production by murine keratinocytes was studied using radioimmunoassay. Keratinocytes grown in low-calcium medium (0.02 mM) maintained intracellular calcium levels adequate for arachidonic acid metabolism and actually showed increased prostaglandin production. Baseline, unstimulated PGE2 production was 4.5 times higher in cells growing in low- compared to normal-calcium (1.2 mM) medium (p = 0.001). PGF2 alpha production was increased 2.5 times in the low-calcium cells (p = 0.002). The calcium ionophore A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) exhibited differing calcium requirements for activation of the arachidonic acid pathway. A23187 ionophore stimulated prostaglandin synthesis only in cells growing in normal-calcium medium while TPA stimulated prostaglandin production by both low- and normal-calcium cells. Paradoxically, short-term exposure of low calcium-grown cells to normal-calcium medium abolished the TPA effect. These results suggested that calcium can control arachidonic acid metabolism at a number of regulatory points.

Arachidonic Acid↗

Mouse endometrial stromal cells produce basement-membrane components.

During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The decidualization of stromal cells is characterized by the accumulation of pericellular basement-membrane material. Decidualized stromal cells of pregnancy differ in this respect from stromal cells obtained from nonpregnant uteri, which are not associated with any significant amounts of basement-membrane components. Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells synthesize laminin, entactin, fibronectin, type-IV collagen, and heparan sulfate proteoglycan. Stromal cells isolated from nonpregnant uteri and explanted in vitro produced the same basement-membrane components. Apparently, these cells were stimulated by the procedure used during isolation and explanation to undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components.

Animals↗

Environmental modulation of lipopolysaccharide chain length alters the sensitivity of Escherichia coli to the neutrophil bactericidal/permeability-increasing protein.

We have shown previously that the sensitivity of Escherichia coli to the neutrophil bactericidal/permeability-increasing protein (BPI) depends mainly on the polysaccharide chain length of outer membrane lipopolysaccharides (LPS) (J. Weiss, S. Beckerdite-Quagliata, and P. Elsbach, J. Clin. Invest. 65:619-628, 1980). Thus, rough strains of E. coli producing only short-chain LPS are more sensitive to BPI than smooth strains that produce LPS with varied chain lengths. We now show that changes in the bacterial growth environment can modify BPI sensitivity of smooth E. coli as much as 30-fold depending on the bacterial strain and the growth conditions examined. Changes in BPI sensitivity paralleled differences in binding affinity of E. coli for BPI and closely correlated with changes in the chain length of LPS produced under different growth conditions, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No concomitent changes in either the number of LPS molecules per cell or the bacterial protein profile were detected. Rough strains showed little or no growth-dependent variation in BPI sensitivity, further indicating that subtle alterations in bacterial constituents other than LPS do not significantly affect bacterial sensitivity to BPI. Thus, the BPI sensitivity of E. coli can be modulated not only by the genotypic conversion of the LPS phenotype, but also by environmental effects on LPS-polysaccharide formation in wild-type strains.

Antimicrobial Cationic Peptides↗

Effects of heart rate on extracellular [K+] accumulation during myocardial ischemia.

The effect of heart rate on extracellular [K+] ([K+]o) accumulation during total global ischemia was investigated in the isolated arterially perfused (37 degrees C) rabbit interventricular septum using intramyocardial K+-sensitive electrodes (tip diameter, 0.3 mm) and intracellular microelectrodes. The heart rates tested were 0, 25, 75, 125, and 150 beats/min in aqueous-perfused septa and 25, 75, and 125 beats/min in blood-perfused septa. In the lower range of heart rates (0-75 beats/min) the rate and magnitude of [K+]o accumulation during 10 min of ischemia were markedly rate dependent, but in the higher range of rates (75-150 beats/min) the rate dependence was markedly attenuated in both aqueous and blood-perfused preparations. The latter finding could be largely attributed to the more rapid shortening of the action potential duration during ischemia at the higher rates and demonstrates that the amount of time the myocardium spends in the depolarized state is an important determinant of the rate of cellular K+ loss during ischemia. Progressive shortening of the action potential duration during ischemia is also a major factor determining the onset of the plateau phase of [K+]o accumulation. The findings help to resolve previous conflicting reports on the effects of heart rate on [K+]o accumulation during ischemia.

Action Potentials↗

Appraising endocrine pulse signals at low circulating hormone concentrations: use of regional coefficients of variation in the experimental series to analyze pulsatile luteinizing hormone release.

We have developed a regional dual-threshold method for detecting endocrine pulses at variably low hormone concentrations such as those that occur in the pediatric age group. This algorithm uses the local intra-series coefficient of variation to test for a significant increase and decrease (peak or pulse) in the experimental series. The method is unique in combining the following considerations: 1) use of internal measurement error present in the actual sample replicates (rather than that estimated from external standards); 2) an ability to accommodate a wide range of nonuniformity in intraassay coefficients of variation; 3) utilization of both upstroke and downstroke threshold criteria; and 4) adaptability to specify a physiologically relevant proximity of the postpeak nadir to the center of the peak. We have validated the behavior of this method in relation to false-positive rates for various program parameters and have illustrated the application of this new regional dual-threshold method to luteinizing hormone pulse detection in pubertal boys who have relative hypogonadotropism, which renders reliable luteinizing hormone pulse detection particularly difficult.

Adolescent↗

Ontogeny of epididymal sperm reserves during the reproductive lifespan of rats after previous sexual experiences.

Epididymal sperm quantity and quality were examined throughout the reproductive lifespan of sexually experienced and inexperienced rats. Males were housed with gonadally intact or ovariectomized females for 2 weeks to 1 year, and epididymides were analysed 1 week to 9 months after the females were removed. Results for the virgin males suggest a peak in sperm numbers at 6 months of age followed by a gradual decline and then notable decrements in sperm numbers and motility by 24 months of age. The same general pattern emerged for sexually experienced males, with two exceptions. There was a chronic increase of sperm numbers relative to those of virgin males at every age examined, and the decline in spermatozoa with ageing was slowed by previous sexual contact. The implications of these data for the ontogeny of fertility are not readily apparent because the epididymis remained reproductively functional throughout the lifespan. We do, however, suggest that epididymides are sensitive to experiential and hormonal changes during adulthood and, most important, the effects of these changes are maintained chronically and into old age.

Aging↗

[Intestinal lipodystrophy (M. Whipple). Synopsis of radiology, endoscopy and histology].

The case of a 48 years old man with intestinal lipodystrophy (Whipple's disease) is clinically, roentgenologically, endoscopically and histologically documented. The diagnosis was established by endoscopic biopsy and laparatomy. The patho-histologic changes of the mucosa of the proximal small bowel are pathognomonic. Roentgenologically the characteristic mucosal and lymphadenoid changes can be demonstrated as well as the extent of the process.

Endoscopy↗

In vivo and in vitro effects of WR-2721 in experimental hypercalcemia in the rat.

The effects of WR-2721 [S-2-(3-aminopropylaminoethyl)phosphorothioic acid] in two in vivo and in vitro models of experimental hypercalcemia in the rat were examined. Chronic WR-2721 administration by osmotic minipump (250 mg/kg/24 hr) reduced serum calcium from 12.0 +/- 0.1 to 9.5 +/- 1.0 mg/dl (P less than .01) in rats receiving 1,25-(OH)2 Vitamin D3. Control rats receiving Vitamin D without WR-2721 had a rise in serum calcium to 13.4 +/- 0.2 mg/dl over the same 5-day period. In an experimental form of humoral hypercalcemia of malignancy, the Walker carcinosarcoma tumor-implanted rat, WR-2721 reduced serum calcium from 13.6 +/- 0.3 to 8.4 +/- 0.6 mg/dl by 5 to 6 days (P less than .001). In vitro bone resorption assays utilizing fetal rat long bones in organ culture showed complementary results. WR-2721 (10(-4) M) blocked bone resorption (assayed as percentage of 45Ca release) induced by both conditioned medium derived from cell lines of Walker carcinosarcoma (7.6 +/- 1.4 vs. 24.0 +/- 1.8%, P less than .01) and by addition of 1,25-(OH)2 Vitamin D3 (10(-8) M) (9.8 +/- 0.8 vs. 17.3 +/- 1.0%, P less than .01). These results suggest that WR-2721 may be effective in controlling clinical hypercalcemia due to excess bone resorption.

Amifostine↗

An acousto-optically steered laser scanning system for measurement of action potential spread in intact heart.

An optical scanning device that combines a voltage-sensitive dye and an acousto-optically steered He-Ne laser beam is described. This device is capable of scanning 128 sites every 4 ms and recording and storing the fluorescence signals for a duration of up to 1 s (several beats). Comparison of an activation map constructed from laser scanning to those obtained from multiple extracellular electrodes suggests that this technique is highly reliable. Although motion-induced light scattering appears to alter the shape of the action potential, the upstroke can be distinguished quite reliably even in a vigorously contracting muscle. This technique provides high resolution (up to 50 micron) and high flexibility (i.e., the scanned sites can be concentrated over a small or very large area) in measuring the spread of activation in heart muscle. By having only one excitation and one measurement element, the approach offers simplicity and high flexibility to the user. We have shown that this system can be readily applied to the task for which it was intended--probing the mechanisms of arrhythmias in the mammalian myocardium. It has been demonstrated, for example, that arrhythmias due to automaticity can be readily distinguished from those due to reentry through the mapping capability of the laser scanner. In addition, the ability of laser scanner to measure membrane depolarization directly during arrhythmias may make this technique superior to conventional electrocardiographic mapping techniques.

Acoustic Stimulation↗

The role of intramembrane Ca2+ in the hydrolysis of the phospholipids of Escherichia coli by Ca2+-dependent phospholipases.

Ca2+-dependent phospholipases A require Ca2+ concentrations in the millimolar range for optimal activity toward artificial substrates. Because Ca2+-dependent phospholipases A2 degrade the phospholipids of Escherichia coli, treated with the membrane-active antibiotic polymixin B equally well with and without added Ca2+ (Weiss, J., Beckerdite-Quagliata, S., and Elsbach, P. (1979) J. Biol. Chem. 254, 11010-11014), we have examined the possibility that intramembrane Ca2+ can provide the Ca2+ needed for phospholipase action. We studied the effect of Ca2+ depletion on the hydrolysis of the phospholipids of polymixin B-killed E. coli by 1) added pig pancreas phospholipase A2 in E. coli S17 (a phospholipase A-lacking mutant) and 2) endogenous Ca2+-dependent phospholipase A1 in the parent strain E. coli S15. Transfer of E. coli from nutrient broth (Ca2+ concentration approximately 3 X 10(-5) M) to Ca2+-depleted medium (Ca2+ concentration less than 10(-6)M) reduced polymixin B-induced hydrolysis by 50-75%, in parallel with a reduction of bacterial Ca2+ from 19.6 +/- 2.8 to 3.9 +/- 0.6 nmol (mean +/- standard error) per 3 X 10(10) bacteria. The bacterial Ca2+ content was repleted and the sensitivity of the bacterial phospholipids to hydrolysis by both exogenous phospholipase A2 (E. coli S17) and endogenous phospholipase A (E. coli S15) was restored by adding Ca2+ back to the suspensions. Complete restoration occurred at low Ca2+ levels in the reaction mixture (3 X 10(-5) - 10(-4) M) and required time, suggesting that hydrolysis was restored because bacterial Ca2+ stores were gradually replenished and not because extracellular Ca2+ concentrations were raised to levels that were still at least 10X lower than needed for optimal phospholipase A activity. This conclusion is supported by the finding that Ca2+ depletion or addition caused respectively decreased and increased release of lipopolysaccharides by EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), suggesting that the bacterial Ca2+ pool bound to lipopolysaccharides in the outer membrane shrinks or expands depending on extracellular Ca2+ levels. Thus, the cationic membrane-disruptive polymixin B, thought to compete with Mg2+ and Ca2+ for the same anionic sites on lipopolysaccharides, may liberate the Ca2+ near where the phospholipids are exposed to phospholipase.

Calcium↗

Chronic changes in male rats' hormone-sensitive systems after suprathreshold pulses of testosterone.

Adult male rats were castrated and maintained on daily SC injections of a threshold amount (200 micrograms) of testosterone propionate (TP). To mimic naturally occurring pulses of suprathreshold testicular hormones in intact males, animals in the experimental groups also received either one (single TP) or five (multiple TP) injections of 800 micrograms TP over 12 days. The rats were examined on the following day (acute) or 15 days later (chronic) for changes in hormone-sensitive behavior, physiology, and morphology. The hypothesis tested was that the hormonal pulses function to provoke chronic changes in substrates underlying the reproductive system. The results were that multiple doses of suprathreshold TP provoked acute modifications in aggressive behavior, sex accessory glands, and glans penis integrity. Chronic changes were observed in sex accessory gland functioning and penile morphology, particularly in the size of penile papillae. A single exposure to suprathreshold TP was considerably less effective, though there was some evidence of acute changes in sex accessory glands and chronic changes in penile papillae. There was substantial variation in the responses of individual animals, particularly the chronic responses. The data were interpreted as supporting the hypothesis.

Animals↗