Search PubMed⌕ Search

Biomedical subjects

J Seifter

Publications and source records attributed to J Seifter.

At least 19 recordsLinked to original sources
PubMed1998

Calcium-regulated renal calcium handling in healthy men: relationship to sodium handling.

Several studies have shown an increase in urinary calcium excretion in response to a calcium load. However, because of the inverse changes in PTH levels with a calcium load, the effect of changes in serum calcium per se on its own excretion is unclear in humans. In this study we used a PTH clamp protocol to further characterize calcium-regulated renal calcium and magnesium handling and the relationship of the former to sodium excretion. Eight normal male subjects were evaluated using a calcium clearance protocol with graded calcium infusions under a PTH clamp while in balance during a high and then during a low sodium diet. The curves describing calcium and magnesium excretion as a function of serum ionized calcium on the high sodium diet were best fitted by sigmoidal functions, with midpoints (the levels of calcium resulting in half-maximal increases in urinary cation excretion) of 1.51 and 1.49 mmol/L, respectively. The curve describing urinary sodium as a function of serum calcium was also sigmoidal on the high sodium diet, with a midpoint of 1.55 mmol/L. Our data taken in conjunction with those of previous studies evaluating sodium and calcium excretion in diseases characterized by inactivating or activating mutations in the calcium receptor, are consistent with the hypothesis that PTH-independent, calcium-dependent changes in renal calcium, magnesium, and sodium handling may be mediated at least in part by this receptor, which is known to be located in the loop of Henle.

Adult↗
PubMed1991

Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies.

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.

Adult↗
PubMed1985

Sodium and chloride transport across rabbit ileal brush border. II. Evidence for Cl-HCO3 exchange and mechanism of coupling.

An inside-alkaline pH gradient (pH 7.7 inside, 5.5 outside) stimulated Cl uptake in brush-border vesicles from rabbit ileum. The addition of HCO3 without changing the pH gradient further stimulated Cl uptake to a level fourfold greater than equilibrated Cl uptake. Although a K diffusion potential stimulated Cl uptake, this was insensitive to inhibition by 4,4-diisothiocyanostilbene-2,2'-disulfonate (DIDS), whereas pH and HCO3 gradient-stimulated Cl uptake was inhibited by DIDS. pH and HCO3 gradient-stimulated Cl uptake was found to be a saturable function of the Cl concentration with a Km of 3.5 mM and a Vmax of 49 nmol X mg prot-1 X min-1. To distinguish between coupling of Na and Cl transport by cotransport or dual exchange (Na-H and Cl-HCO3 exchange), we determined uptake with high (134 mM Tris-HEPES-MES) internal buffer and low (1.34 mM Tris-HEPES-MES) internal buffer concentrations. Inwardly directed gradients of 50 mM Na, 50 mM K, or 50 mM Na and K did not stimulate Cl uptake, and 50 mM Cl, 50 mM K, or 50 mM KCl did not stimulate Na uptake, with high internal buffer, excluding cotransport. In contrast, 50 mM Na stimulated Cl uptake (inhibited by 1 mM DIDS) and 50 mM Cl stimulated Na uptake (inhibited by 1 mM amiloride) in low buffer media. To determine a role for carbonic anhydrase, Na-stimulated Cl uptake was determined in low buffer media, equilibrated with either 100% N2 or 95% N2-5% CO2. Na stimulated Cl uptake 80% (compared with trimethylammonium control) with CO2 but only 30% with N2 (P less than 0.05). Acetazolamide partially inhibited (P less than 0.025) the stimulation of Cl uptake with CO2 but not with N2. Carbonic anhydrase activity was measured in homogenate and brush-border membrane and was enriched 7.9 +/- 0.4-fold, whereas sucrase was enriched 14.0 +/- 1.1-fold. We conclude that coupled Na and Cl transport occurs by dual exchange (Na-H and Cl-HCO3) and carbonic anhydrase, apparently located on the brush-border membrane, facilitates dual exchange by providing HCO3.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1980

Spontaneous mechanical activities of dog trachealis muscle in vivo.

Isometric strain gauge arches attached transversely and longitudinally to cervical trachealis muscle (CTM) recorded spontaneous mechanical activities (SMA), passive constriction, and longitudinal tension in 64 dogs anesthetized with pentobarbital. Inspiratory tracheal elongation increased longitudinal tension and passively constricted CTM. Occasional overlapping of tracheal cartilages observed on initial exposure of cervical trachea appeared to be due to unprovoked persistent increases in SMA. Three major types of rhythmic SMA oscillations occurred in 42 lightly anesthetized dogs: slow oscillations 50 - 200 s/cycle (19 dogs); sinelike waves 20-30 s/cycle (12 dogs); and sinelike waves superimposed on slow oscillations (11 dogs). These rhythms were dampened by pharmacologically induced incrases or decreases in SMA. They disappeared following deeper anesthesia, atropinization, or bilateral vagotomy. Intravenous acetylcholine increased while isoproterenol decreased SMA before and after bilateral vagotomy in spontaneously breathing dogs as well as in artificially ventilated curarized dogs whose tracheas were isolated in situ. Atropine blocked acetylcholine actions and propranolol blocked those of isoproterenol. Changes in SMA induced pharmacologically did not correlate with simulatenous alterations in systemic arterial pressure of ventilatory patterns.

Acetylcholine↗
PubMed1980

Contraction of dog trachealis muscle in vivo: role of alpha-adrenergic receptors.

Contraction, relaxation, and longitudinal tension were recorded by isometric strain gauge arches attached to cervical tracheal muscle (CTM) in 60 spontaneously breathing dogs anesthetized with pentobarbital. Intravenous norepinephrine (NE) (3 X 10(-9), 6 X 10(-9), 1.2 X 10(-8), and 2.4 x 10(-8) mol/kg) increased spontaneous mechanical activities (SMA) and caused dose related contraction of CTM in all dogs even though there was no pretreatment with beta-blockers. These activities were first potentiated by propranolol and then prevented by phentolamine. NE briefly decreased SMA and induced CTM relaxation prior to the onset of contraction in one-third of dogs. Propranolol prevented this initial relaxation. CTM responses induced by NE were 1) not significantly altered by atropine, tripelennamine, bilateral vagotomy, curarization, and complete tracheal transection below transducer sites; 2) unrelated to passive constriction of cervical trachea associated with airway elongation; and 3) independent of reflexes initiated by elevations of systemic arterial pressure. The moles per kilogram doses of acetylcholine were found to exceed those of NE when their intravenous administration caused equal CTM contractions in the same dog. These findings are consistent with the existence of alpha-adrenergic receptors in CTM.

Acetylcholine↗
PubMed1979

Effects of polybrominated biphenyl on a discrimination task in rats.

Learning or performance of an operant discrimination task by laboratory rats in Skinner boxes was studied as a function of subchronic treatment with polybrominated biphenyl (PBB) (1.0 mg/kg, 3.0 mg/kg or 6.0 mg/kg for 20 days). Acquisition of the discrimination task was similar for experimental and control rats at each dose level. Response times were slower for the 1.0 mg/kg rats but were like controls for the 3.0 and 6.0 mg/kg animals. Extra responses occurring in the absence of auditory discriminative stimuli increased significantly for the 1.0 mg/kg rats (hyperactivity), were no different from controls for the 3.0 mg/kg rats and decreased significantly for the 6.0 mg/kg animals (CNS depression). The weights of PBB animals did not differ significantly from controls. Analyses of brains and plasma by electron capture gas chromatography yielded detectable levels of PBB as long as 10 months following the last PBB administration. PBB in brains and plasma varied directly as a function of dose administered.

Animals↗
PubMed1979

Correlation of systemic and biochemical effects of PBB with behavioral effects.

Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals.

Animals↗
PubMed1979

Use of discrimination behavior for the evaluation of toxicants.

This study involved the application of discrimination behavior for the study of effects of environmental contaminants on the behavior of laboratory animals. Polybrominated biphenyl (PBB) was evaluated for effects on the acquisition and performance of a simple auditory discrimination by rats. Methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) and carbon monoxide (CO) were evaluated for effects on a delayed match-to-sample discrimination task in the juvenile baboon. All of the contaminants slowed response times and increased extra responses. These findings suggest that discrimination behavior may be of value for the evaluation of environmental contaminants for effects on the central nervous system.

Animals↗
PubMed1978

Assessment of the hazards of polybrominated biphenyls.

During their peak use period, PBBs represented under 1% of the total sales of fire retardant chemicals, and very probably would have escaped intensive study if they had not been mixed accidentally with animal feed preparations. Instead, international attention was drawn to PBBs by the state-supervised killing of over 35,000 cattle which had been contaminated with PBBs. Interestingly, low doses of PBBs exert a broad spectrum of toxicological, pharmacological, and biochemical effects despite low acute toxicity. These effects and the intensive bioaccumulation of PBBs derive from their structure and their consequent resistance of biotransformation and high solubility in fat. In rodents, PBBs are teratogenic, immunosuppressive, and potentially carcinogenic. In bovine, rodent, and avian species, PBBs reduce feed intake and induce mixed function oxidases of liver microsomes. The latter effect may be responsible for steroid level changes which underline hormonal toxicities observed in cows, mink, rats, and chickens. The effects of PBBs on humans are controversial, but data suggestive of immunological, skin, and liver disorders continue to accumulate. Concern about the clinical effects of PBBs is heightened by the knowledge that these compounds readily enter the fetus by crossing the placental barrier and can be transferred to newborn children after extensive passage into breast milk.

Adult↗
PubMed1977

Toxicity of vinylidene chloride in mice and rats and its alterations by various treatments.

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various compounds to alter parameters of toxicity was evaluated. Mice were more sensitive than rats to the lethal, hepatotoxic, and renal toxic effects of VDC. Disulfiram protected mice from these toxic effects of inhaled VDC and reduced the levels of covalently bound radioactivity in the liver and kidney after the ip administration of [14C] VDC. Diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.

Animals↗
PubMed1977

Effect of various treatments on toxicity of inhaled vinylidene chloride.

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various treatments to alter parameters of toxicity was evaluated. Mice were more sensitive than rats both to the acute lethal and hepatotoxic effects of VDC. Disulfiram treatment reduced the acute lethal and hepatotoxic effects of inhaled VDC and reduced the levels of covalent bound radioactivity in the liver and kidney after the intraperitoneal administration of 14C-VDC. Treatment with diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.

Amino Acids, Sulfur↗