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Biomedical subjects

H Steinberg

Publications and source records attributed to H Steinberg.

At least 127 records · Page 7Linked to original sources
PubMed1985

Tricyclic antidepressant and metabolite levels in chronic renal failure.

Serial blood samples were drawn from 12 patients undergoing hemodialysis who were receiving tricyclic antidepressants (TCAs). Samples were drawn before, during, and after a dialysis session (two to 17 sessions per subject). Samples were analyzed by HPLC before and after hydrolysis with beta-glucuronidase/sulfatase to determine the conjugated and nonconjugated metabolites. Analysis of these data in comparison with those of controls with depression and normal renal function showed that: (1) at steady state, tertiary and secondary amine TCA levels did not differ; (2) levels of the hydroxylated metabolites had greater variability and were somewhat higher at steady state; (3) levels of the conjugated hydroxylated compounds were markedly elevated, reaching 500% to 1500% normal; (4) the time to reach a steady-state level appeared to be slightly increased; and (5) elimination t1/2 s of unconjugated and conjugated drug forms were longer in our patients with normal renal function than those reported in the literature. Levels of the tertiary, secondary, and hydroxylated metabolites were not changed by dialysis, whereas there were substantial decrements in glucuronidated metabolite levels. These findings demonstrate increased concentrations of conjugated drug forms and suggest an abnormal distribution or delayed elimination of unconjugated and conjugated metabolites. These observations may shed some light on the apparent hypersensitivity of these patients to TCA side effects, particularly because glucuronides may exert peripheral pharmacologic effects.

Adult↗
PubMed1985

Oblique hilar tomography, computed tomography, and mediastinoscopy for prethoracotomy staging of bronchogenic carcinoma.

Preoperative oblique hilar tomography was used to evaluate hilar lymph nodes in 150 patients with clinically resectable bronchogenic carcinoma. CT was also used in the evaluation of mediastinal lymph nodes in 50 of these patients. Subsequently, all patients underwent mediastinoscopy and/or thoracotomy. Hilar and mediastinal nodes were evaluated for the presence of metastasis, and these findings were then correlated with the radiographic findings of oblique hilar tomography and CT. CT was found to be a reliable method for prethoracotomy staging of bronchogenic carcinoma and for selecting patients for mediastinoscopy. The sensitivity of CT for evaluation of mediastinal nodal metastasis was 83% and the specificity was 90%. Thus patients with negative mediastinal CT need not undergo mediastinoscopy prior to thoracotomy, while mediastinoscopy and biopsy should be done in patients with enlarged mediastinal nodes on CT. Oblique hilar tomography is an accurate method for evaluation of hilar adenopathy and for predicting mediastinal involvement by extrapolation.

Adult↗
PubMed1985

Specific binding of serotonin in rat lung.

Mammalian lungs have been shown to store and to inactivate serotonin (5-HT) by an active process involving uptake and metabolism. 5-HT has direct action on lung including constrictor effects of pulmonary vascular and tracheobronchial smooth muscle, suggesting the presence of 5-HT receptors in lung. We have identified specific 5-HT binding of high affinity to the different lung portions and have shown that there was a different capacity for this binding. Two different 5-HT-binding capacities are present in a purified mitochondrial fraction. Saturation analysis of 5-[3H]HT binding to outer mitochondrial membranes demonstrates a single, temperature-sensitive, high-affinity and high-capacity binding (Kd = 8.3 +/- 1.2 nM, maximum binding capacity = 0.819 +/- 0.046 pmol/mg protein). The dissociation constant of inner mitochondrial membrane demonstrates a low-capacity site (Kd = 25.2 +/- 2.2 nM, maximum binding capacity = 0.453 +/- 0.037 pmol/mg protein). The purified microsomal fraction of lung exhibits a high-capacity binding site for 5-[3H]HT (Kd = 14.8 +/- 1.6 nM, maximum binding capacity = 0.760 +/- 0.03 pmol/mg protein). In addition to the lung being the major site for its inactivation, the presence of several specific 5-HT receptors may be related to some of the known 5-HT actions in lung and may suggest other unknown actions of this amine.

Animals↗
PubMed1985

Nutritional and hormonal control of glucose and fructose utilization by lung.

Whereas glucose is a major substrate for pulmonary lipid synthesis, fructose has also been suggested as a potential substrate. In vivo pulmonary fatty acid synthesis is depressed in hormonally deprived conditions, such as diabetes, and this can be modified by fructose feeding, but not by glucose feeding. In this study the glucose and fructose utilizations were compared in normal, diabetic and fasting states using isolated perfused rat lungs. When (U-14C)- or (5-3H)-glucose was used as substrate, glucose utilization by lung was reduced by 50% in both the fasting and diabetic animals compared to the normal controls. Using (U-14C)-glucose as substrate, the incorporation of (14C)-label in various metabolites of glucose was significantly depressed. For example, this reduction was 50% in lactate, pyruvate and CO2, 15% in ethanol-insoluble fraction, 65% in neutral lipids, 75% in phospholipids, 80% in fatty acid moiety, 40% in deacylated fraction and 10% in the polysaccharide fractions. Refeeding the fasted animals or insulin treatment to the diabetic animals restored these depressed (14C)-recoveries to the normal levels. Fructose utilization was less than 10% of glucose utilization, but remained unaffected by fasting and diabetic states. In addition, pulmonary hexokinase enzyme activity was lowered significantly in fasting and diabetic animals, whereas fructokinase enzyme activity was not altered. Despite the low rate of fructose utilization, these results suggest that fructose may serve as an alternative substrate for pulmonary phospholipid synthesis when glucose utilization is significantly depressed.

Animals↗
PubMed1984

A biphasic effect of chlordiazepoxide on animal locomotor activity.

Centrally acting drugs often act 'biphasically', especially on animal locomotor activities: the same drug stimulates and depresses, depending either on dose or on time since administration. We propose a third, hitherto neglected, type of biphasic effect, well illustrated by chlordiazepoxide, which depends, instead, on the length of time an animal is exposed to a test environment: in an unfamiliar Y-maze, rats' spontaneous locomotion (number of entries into the arms of the Y) was stimulated to begin with, but switched to depression in a few minutes. The stimulant phase appeared to be independent of dose, while the depressant phase showed log linear dose dependence.

Animals↗
PubMed1984

Fructose utilization by lung.

We have examined the role of fructose as a substrate for the mammalian lung. Isolated and ventilated rat lungs were perfused for 2 h in the presence of either [U-14C]- or [5-3H]fructose. Fructose utilization, 3H2O production, and lactate and pyruvate production were measured. Insulin had no effect on the production of radiolabeled lactate. The 14C label from [U-14C]fructose was incorporated into the neutral lipids, phospholipids, fatty acid moiety, and deacylated fraction of lung. The apparent Km and maximum velocity of enzyme reaction for fructose utilization were 0.5 mM and 75 nmol X h-1 X g dry wt-1, respectively. Recovery of fructose 1-phosphate and fructose 1,6-diphosphate after perfusion with fructose, as well as detection of fructokinase, aldolase, and triokinase activities in the lung homogenates, suggested that fructose had been metabolized via phosphorylation through fructose 1-phosphate. Activities of fructose-metabolizing enzymes were not altered by the induction of diabetes, hypophysectomy, or starvation. These results suggest that mammalian lungs may utilize fructose to synthesize fatty acids, which in turn are used for phospholipid biosynthesis. The utilization of fructose by lung does not seem to be affected by nutritional or hormonal conditions.

Animals↗
PubMed1984

Potentiation of surfactant release in fetal lung by thyroid hormone action.

Thyroid hormone has been shown to accelerate fetal lung development, but the mechanisms by which this hormone acts are yet unknown. Since this hormone may act indirectly by potentiating the action of endogenous catecholamines, we studied this mechanism by measuring beta-adrenergic receptors in fetal lung. Fetal rabbits at 27 days of gestation were treated with triiodothyronine (T3), 100 micrograms/100 g, in the presence and absence of propranolol, 200 micrograms/100 g, or actinomycin D, 20 micrograms/100 g. Fetuses were killed by decapitation either after 4 or 24 h of T3 treatment. The beta-adrenergic antagonist l-[3H]dihydroalprenolol was used to directly estimate the number and affinity of beta-adrenergic receptor in lung membranes. T3 increased the number of beta-adrenergic receptors in fetal lung, but the affinity of binding did not change. The enhancement of binding capacity after 4 h of T3 treatment was not inhibited by actinomycin D. However, 24-h T3-mediated stimulation was partially blocked by actinomycin D. In addition, T3 stimulated the catecholamine content, adenylate cyclase activity, and adenosine 3',5'-cyclic monophosphate content of lung. T3 increased the lecithin-to-sphingomyelin ratio, phosphatidylglycerol, and disaturated phosphatidylcholine content of the pulmonary lavage fluid. These parameters were completely inhibited by propranolol after 4 h and partially inhibited by actinomycin D after 24 h. Thus thyroid hormone enhances lung maturation by increasing the number of beta-adrenergic receptors in fetal lung.

Animals↗
PubMed1984

A confirmation of NIMH training objectives for consultation-liaison residents.

Data from a 4-year prospective study suggest that the objectives of the NIMH Psychiatry Education Branch for psychiatry residents in regard to consultation-liaison training can be achieved. Residents developed a more positive view about consultation-liaison psychiatry and saw themselves more as integral members of the general hospital; some were influenced to pursue postgraduate consultation-liaison positions.

Attitude of Health Personnel↗
PubMed1984

Sinus histiocytosis presenting as a mediastinal mass.

A 32-year-old man with a ten-year history of bilateral cervical adenopathy, parotid gland swelling, and a posterior mediastinal mass, presented with headaches. A CAT scan of the head revealed a suprasellar mass. Craniotomy and biopsy of this lesion led to a diagnosis of sinus histiocytosis.

Adult↗
PubMed1984

Oblique hilar tomography and mediastinoscopy. A correlative prospective study in 100 patients with bronchogenic carcinoma.

One hundred patients with bronchogenic carcinoma had oblique hilar tomography preoperatively to evaluate the pulmonary hila. Subsequently, all of these patients underwent mediastinoscopy or thoracotomy or both. Hilar and mediastinal nodes were evaluated for the presence of metastasis. These findings were then correlated with the radiographic findings of oblique hilar tomography. We found oblique hilar tomography to be a useful method of selecting patients for mediastinoscopy. The negative predictive value of oblique hilar tomography for mediastinal involvement was 95 percent, while the positive predictive value was 75 percent. Thus, patients with negative findings on oblique hilar tomography need not undergo mediastinoscopic examination prior to thoracotomy.

Adult↗
PubMed1984

Effect of starvation and diabetes on glucose transport in the lung.

Transport of glucose by the isolated and perfused rat lung was studied using 2-deoxy-D-(1-14C)-glucose, 2-(1-14C)-DG, and 3-O-methyl-(U-14C)-glucose, 3-(U-14C)-MG. Uptake of 3-(U-14C)-MG was reduced by 20% in the lungs of fasting and diabetic rats, the uptake was restored by refeeding and insulin treatment, respectively. Although the intracellular accumulation of unphosphorylated 2-(1-14C)-DG in lungs was altered by a small amount in diabetes and fasting, the intracellular accumulation of phosphorylated 2-(1-14C)-DG was significantly reduced and restored by insulin treatment and refeeding, suggesting that phosphorylation was inhibited in these conditions. The reduction of glucose utilization in fasting or diabetic state was shown to be due to the inactivation of hexokinase II enzyme. Thus, a specific glucose-carrier system is present in the rat lung which appears to be insulin-sensitive and is under the nutritional and hormonal control.

Animals↗
PubMed1983

The effect of oxygen adaptation on oxyradical injury to pulmonary endothelium.

Rats exposed to 85% O2 for 7 days develop an increase in pulmonary tissue levels of antioxidant enzymes and are able to survive subsequent exposure to 100% O2. In order to examine endothelial cell function in O2-adapted rats, we chemically generated oxygen radicals within the pulmonary circulation of lungs isolated from 85% O2-exposed rats and used [14C]5-hydroxytryptamine (5-HT) uptake as an indicator of endothelial cell function. The [14C]5-HT uptake in lungs of O2-exposed rats was similar to that in air-exposed rats and was reduced by cyanide, anoxia, and by imipramine. After generation of O2-derived free radicals within the pulmonary circulation, there was a progressive decline in [14C]5-HT uptake in both groups, with a more rapid decline seen in the lungs of air-exposed rats. These data suggest that pulmonary endothelial cells that survive 85% O2 exposure for 7 days are capable of normal function and are more resistant to further oxyradical injury.

Adaptation, Physiological↗
PubMed1983

Inhibition of differentiation and proliferation of colony-stimulating factor-induced clonal growth of normal human marrow cells in vitro by retinoic acid.

Necessary for growth and differentiation in many normal tissues and capable of inducing differentiation in human promyelocytic cell lines, retinoids were the subject of this study. Specifically, effects of 13-cis-retinoic acid and 13-trans-retinoic acid on the growth of normal human bone marrow cells in soft-agar system were studied. Both short-term incubation and continuous exposure to retinoic acid caused a decreased number of granulocyte colonies and an increased cluster-to-colony ratio. This effect was concentration-dependent. Examination of specimens stained with Wright-Giemsa or nitro blue tetrazolium stains showed a progressive increase in the percentage of immature granulocytic precursors with increasing concentrations of retinoic acid. No effect of retinoic acid was seen on a number of human tumor cell lines. Retinoic acid blocked both differentiation and proliferation and appeared to do so by specific, noncytotoxic mechanisms in normal human bone marrow cells.

Bone Marrow↗
PubMed1982

The effect of oxygen-derived free radicals on pulmonary endothelial cell function in the isolated perfused rat lung.

Oxygen-derived free radicals have been shown to damage endothelial cells in tissue culture. We have extended these observations to demonstrate a direct toxic action of oxy radicals on endothelial cell function in the isolated perfused rat lung model. Using an enzymatic system of hypoxanthine and xanthine oxidase, we generated a superoxide flux of 5-7 nmol/min within the pulmonary circulation. This resulted in alteration of endothelial cell function, including a progressive fall in the cellular transport of (14C) 5-hydroxytryptamine, edema formation manifested by a falling dry weight ratio and increasing mean transit times appearance of thiobarbituric acid reactive material in the perfusate indicating lipid peroxidation, and histologic evidence of edema formation with disruption of the endothelial cell plasma membrane. Inhibitor studies confirmed that the observed effects were due to superoxide radical generation. Oxygen derived free radicals may play a role in the pulmonary endothelial cell damages seen in inflammatory disorders and oxidant lung injury.

Animals↗