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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 127 records · Page 7Linked to original sources

Hospitalization and the cognitive deficits of schizophrenia. The influences of age and education.

The study investigated the relationship between length of hospitalization and increasing cognitive deficit in schizophrenics. Using Halstead-Reitan Battery data obtained from 245 schizophrenic patients, multiple regression analyses were performed using age, education, and length of hospitalization as independent variables and various summary test indices as dependent variables. These analyses showed that there was not a statistically significant change in percentage of explained variance when length of hospitalization was entered into the multiple regression equations. On the basis of these analyses, it was concluded that the association between increasing deficit and length of hospitalization experienced by schizophrenic patients is no greater than what would be anticipated on the basis of aging.

Adult↗

Diel Patterns of Water Potential Components for the Crassulacean Acid Metabolism Plant Opuntia ficus-indica when Well-Watered or Droughted.

Under well-watered conditions, chlorenchyma acidity in cladodes of Opuntia ficus-indica increased substantially at night, fully accounting for the 0.26-megapascal nocturnal increase in osmotic pressure in the outer 2 millimeters. Osmotic pressure in the inner part of the chlorenchyma and in the water-storage parenchyma did not change significantly over 24-hour periods. Three months of drought decreased nocturnal acid accumulation by 73% and essentially abolished transpiration; also, 27% of the chlorenchyma water and 61% of the parenchyma water was lost during such drought, but the average tissue osmotic pressure was little affected. Turgor pressure was maintained in the chlorenchyma after 3 months of drought, although it decreased sevenfold in the water-storage parenchyma compared with the well-watered condition. Moreover, the nocturnal increases in turgor pressure of about 0.08 megapascal in the outer part of the chlorenchyma was also unchanged by such drought. The water potential magnitudes favored water movement from the parenchyma to the chlorenchyma at the end of the night and in the reverse direction during the late afternoon. Experiments with tritiated water support this pattern of water movement, which is also in agreement with predictions based on electric-circuit analog models for Crassulacean acid metabolism plants.

Journal Article↗

Changes in Osmotic Pressure and Mucilage during Low-Temperature Acclimation of Opuntia ficus-indica.

Opuntia ficus-indica, a Crassulacean acid metabolism plant cultivated for its fruits and cladodes, was used to examine chemical and physiological events accompanying low-temperature acclimation. Changes in osmotic pressure, water content, low molecular weight solutes, and extracellular mucilage were monitored in the photosynthetic chlorenchyma and the water-storage parenchyma when plants maintained at day/night air temperatures of 30/20 degrees C were shifted to 10/0 degrees C. An increase in osmotic pressure of 0.13 megapascal occurred after 13 days at 10/0 degrees C. Synthesis of glucose, fructose, and glycerol accounted for most of the observed increase in osmotic pressure during the low-temperature acclimation. Extracellular mucilage and the relative apoplastic water content increased by 24 and 10%, respectively, during exposure to low temperatures. These increases apparently favor the extracellular nucleation of ice closer to the equilibrium freezing temperature for plants at 10/0 degrees C, which could make the cellular dehydration more gradual and less damaging. Nuclear magnetic resonance studies helped elucidate the cellular processes during ice formation, such as those revealed by changes in the relaxation times of two water fractions in the chlorenchyma. The latter results suggested a restricted mobility of intracellular water and an increased mobility of extracellular water for plants at 10/0 degrees C compared with those at 30/20 degrees C. Increased mobility of extracellular water could facilitate extracellular ice growth and thus delay the potentially lethal intracellular freezing during low-temperature acclimation.

Journal Article↗

Biologically active conformations of thymopentin. Studies with conformationally restricted analogs.

Four cyclic analogs of thymopentin were synthesized and evaluated for biological activity on the human T cell line CEM. Three of these conformationally restricted analogs were biologically active. The one analog which most closely mimicked the conformation predicted from NMR and theoretical energy minimization calculations proved to be inactive. These studies establish that the biologically active conformations of thymopentin differ from the most probable conformation predicted from solution NMR and theoretical energy minimization studies.

Amino Acid Sequence↗

Use of monoclonal antibodies to identify thymopoietin in cultured human thymic epithelial cells.

Murine monoclonal antibodies (mAbs) were developed to discriminate thymopoietin, a human thymic hormone, and thysplenin, a closely related molecule found in spleen. Three of these recognized both native and synthetic thymopoietin as well as thysplenin. Together they define two non-overlapping epitopes which withstand sodium dodecyl sulfate denaturation and can be detected by western blotting. We used these three mAbs to demonstrate the production of thymopoietin by cultured thymic epithelial cells for up to several weeks. Three additional mAbs were selective for thysplenin. Highly specific mAbs will be useful for characterizing further these physiologically distinct polypeptides.

Antibodies, Monoclonal↗

Thymopoietin, a potent antagonist at nicotinic receptors in C2 muscle cell cultures.

Recent work has shown that thymopoietin, a polypeptide with actions in the immune and nervous systems, potently binds to the alpha-bungarotoxin (alpha-BGT) receptor. The present study was done to characterize the interaction of thymopoietin at the nicotinic alpha-BGT binding site in cultured muscle cells and to correlate these findings with the effects of the polypeptide on nicotinic receptor-mediated function. Inhibition studies showed that thymopoietin potently inhibited 125I-alpha-BGT binding in C2 muscle cells in culture, with an IC50 of 1.1 nM, a value similar to that for alpha-BGT. Thymopoietin bound to the alpha-BGT receptor in the cells in culture relatively slowly; at 10(-8) M thymopoietin, maximal inhibition occurred after 45 to 75 min of exposure to the polypeptide. Dissociation of thymopoietin from the receptor exhibited a much longer time course; recovery of alpha-BGT binding to control values after exposure to 10(-8) M thymopoietin occurred approximately 16 hr after removal of the polypeptide. The effects of thymopoietin on 125I-alpha-BGT binding correlated well with those on nicotinic function. Thymopoietin potently inhibited nicotinic receptor-mediated 22Na uptake in muscle cells in culture, with an IC50 of 2 nM. This effect was dependent on the length of the preincubation period with thymopoietin, with maximal inhibition occurring after 60 min of exposure to the polypeptide. Recovery of the functional response after thymopoietin (10(-8) M) exposure required about 16 hr. The mode of inhibition of receptor-mediated ion flux by thymopoietin was similar to that observed with alpha-BGT but distinct from that obtained with d-tubocurarine and gallamine. To conclude, thymopoietin, a thymic polypeptide associated with the immune system, potently inhibited both 125I-alpha-BGT binding and nicotinic receptor-mediated function in C2 muscle cells. These findings may have implications for myasthenia gravis and/or other neuromuscular disorders.

Animals↗

Peptide analogs of thymopentin distinguish distinct thymopoietin receptor specificities on two human T cell lines.

Thymopoietin, a polypeptide hormone of the thymus, and the synthetic pentapeptide thymopentin, corresponding to thymopoietin32-36, both induced elevations of intracellular cyclic GMP in two human T cell lines, CEM and MOLT-4. In contrast, the closely related polypeptide thysplenin, which differs from thymopoietin at position 34, induced intracellular cyclic GMP elevation in MOLT-4 but not in CEM. We synthesized a series of penta- and tetrapeptide analogs of amino acids 32-36 of human thymopoietin and thysplenin, and now show that distinct patterns of activity can be obtained in these small peptides, with selectivity for cyclic GMP elevation in MOLT-4 alone or CEM alone. This suggests that the thymopoietin receptors (TPR) on these two human T cell lines are distinguishable by their differing ligand specificities, and we have termed them alpha TPR and beta TPR for CEM and MOLT-4 receptors, respectively.

Cell Line↗

Neuronal nicotinic alpha-bungarotoxin receptors.

Recent evidence has indicated that the nicotinic acetylcholine receptor and the nicotinic alpha-bungarotoxin (alpha-BGT) site may be distinct in neuronal tissues. With regard to function, the former receptor appears to be involved in mediating synaptic events; however, the role of the nicotinic alpha-BGT site in nervous tissue is currently not known. Since the binding of alpha-BGT exhibits such high affinity and selectivity for a specific receptor, this may implicate an involvement of the toxin binding site in some aspect of neuronal activity with the receptor possibly mediating functions other than nicotinic cholinergic transmission. A further hypothesis to explain the nature of the toxin binding site may be that the natural ligand for the alpha-BGT site is one other than acetylcholine, with acetylcholine acting as a modulator of the site. Current studies in our laboratory are exploring these possibilities by determining whether specific peptides and/or polypeptides can interact at the nicotinic alpha-BGT site in nervous tissue. Studies using both in vivo and in vitro approaches suggest that thymopoietin may serve a role as a modulator of the nicotinic alpha-BGT site in neuronal tissues.

Adrenal Medulla↗

Thymopentin therapy reduces the clinical severity of atopic dermatitis.

One hundred patients with moderate to severe atopic dermatitis were entered into a two-center, double-blind trial. Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks. Clinical extent of disease and severity parameters were measured at baseline and at regular time intervals during the study. Both the placebo- and thymopentin-treated groups demonstrated a progressive and statistically significant (p less than 0.001) decline in the overall severity of their disease, but reduction in the clinical severity score was higher in the thymopentin-treated group and statistically significant (p = 0.04) in comparison with the placebo-treated group after 6 weeks of treatment. Of the individual symptoms comprising the total severity score, pruritus (p = 0.02) and erythema (p = 0.04) were reduced significantly when thymopentin therapy was compared to placebo therapy. In addition, both the extent of body involvement and severity index (a combined severity/extent index) were significantly reduced after 6 weeks in the thymopentin-treated group in comparison to the placebo-treated group (p = 0.04). There were no serious adverse experiences in either treatment group. We conclude that treatment with thymopentin is safe and offers significant therapeutic promise for atopic dermatitis.

Adolescent↗

Thymopoietin interacts at the alpha-bungarotoxin site of and induces process formation in PC12 pheochromocytoma cells.

Thymopoietin, a polypeptide isolated from thymus and involved in immune regulation, potently inhibited [125I]alpha-bungarotoxin binding in both pheochromocytoma (PC12) cells in culture (IC50 of 3.9 nM) and in PC12 cell membranes (IC50 of 2.2 nM). The degree of inhibition produced by thymopoietin was similar to that observed with alpha-bungarotoxin; in contrast, nicotinic receptor ligands affected alpha-bungarotoxin binding only at micromolar concentrations, in agreement with previous work. Binding of thymopoietin was reversible. Studies with PC12 cell membranes suggested that the interaction between alpha-bungarotoxin and thymopoietin at the receptor was competitive. The effect of thymopoietin was subsequently assessed on various morphological characteristics of PC12 cells in culture. Exposure of the cells to the polypeptide resulted in neurite extension, which was evident as early as 1-2 days in culture and was maximal after 4-6 days; this response was observed with concentrations of thymopoietin as low as 10(-8) M. Nerve growth factor also induced neurite extension in PC12 cells; however, the effects of nerve growth factor were qualitatively and quantitatively distinct from those which occurred with thymopoietin. Moreover, a monoclonal antibody to nerve growth factor completely prevented the nerve growth factor-induced process formation without affecting the thymopoietin-induced response. On the other hand, alpha-bungarotoxin resulted in the formation of processes which appeared morphologically similar to those induced by thymopoietin, although alpha-bungarotoxin appeared less potent than the thymic polypeptide. The effect of thymopoietin appeared to be specific; thysplenin, a polypeptide with approximately 80% homology with thymopoietin, did not elicit process formation. The thymopoietin-induced effect was reversed upon removal of the polypeptide from the culture medium. These results show that thymopoietin, a polypeptide endogenous to mammalian systems, potently interacted at the alpha-bungarotoxin site in a neuronal cell line. Furthermore, thymopoietin could elicit process formation in PC12 cells, suggesting that it may be a neuronotrophic factor.

Adrenal Gland Neoplasms↗

Monoclonal antibody OKT3 therapy in pediatric kidney transplant recipients.

Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.

Acetaminophen↗

Treatment of chronic osteomyelitis complicating nonunion and segmental defects of the tibia with open cancellous bone graft, posterolateral bone graft, and soft-tissue transfer.

Forty-two consecutive patients with chronic osteomyelitis complicating persistent tibial nonunion and chronic osteomyelitis complicating tibial fracture with segmental bone loss were treated from January 1979 through December 1986 using a protocol including either open cancellous bone grafting (Friedlaender-Papineau technique), posterolateral bone grafting (Harmon technique), or local or microvascular soft-tissue transfer before cancellous bone grafting. Each patient had undergone surgical debridement and intravenous antibiotic therapy before inclusion in this study. Patients were classified using a staging system which included consideration of anatomic location of the infection within the bone; extent of bone involvement; quality of soft-tissue envelope and vascular integrity; and generalized host status. The overall success rate for arresting the osteomyelitis and healing the nonunion was 62% (26/42). If the six patients who refused additional bone graft surgery, the one patient who represented poor patient selection, and the patient who refused ankle arthrodesis are eliminated, the success rate for healing of the nonunion and resolving the osteomyelitis in this difficult patient population is: open bone cell graft, 66% (12/18); soft-tissue transfer 87.5%, (7/8); and posterolateral bone grafting, 87.5% (7/8). Use of a standardized classification system allows comparison of treatment results. Adequate debridement is crucial in treating osteomyelitis complicating established long bone fractures and nonunions. Determining the extent of debridement has proven to be the single most difficult aspect technically. Patient selection and pretreatment education are crucial. Caring for these patients is not only labor intensive and demanding of personnel and hospital resources, but demanding of the patients as well.

Adolescent↗

Carbon Isotope Discrimination in Coffee Genotypes Grown under Limited Water Supply.

Photosynthetic gas exchange, plant-water relations characteristics, and stable carbon isotope discrimination (Delta) were evaluated for five Coffea arabica L. genotypes growing under two soil moisture regimes in the field. The Delta of leaf tissue was strongly correlated (r = -0.95) with inherent water use efficiency (ratio of assimilation to stomatal conductance; A/g). The variation in inherent water use efficiency (WUE) among genotypes was 30% for plants irrigated weekly. The higher WUE exhibited by some of these plants resulted from reduced g rather than increased photosynthetic capacity at a given g. Withholding irrigation for 1 month caused Delta to decline substantially in expanding leaf tissue of all genotypes. A strong correlation (r = 0.92) was found between Delta and plant hydraulic efficiency estimated as the ratio of g to the diurnal range in leaf water potential (Psi(l)). The Delta values for plants irrigated weekly adequately predicted drought-induced changes in Delta (r = 0.99) and midday Psi(l) (r = 0.95). The results indicated that Delta might be used to evaluate several aspects of plant performance and response to specific environmental conditions, once suitable background physiological data have been gathered.

Journal Article↗

Leaf water relations and maintenance of gas exchange in coffee cultivars grown in drying soil.

Plant water status, leaf tissue pressure-volume relationships, and photosynthetic gas exchange were monitored in five coffee (Coffea arabica L.) cultivars growing in drying soil in the field. There were large differences among cultivars in the rates at which leaf water potential (Psi(L)) and gas exchange activity declined when irrigation was discontinued. Pressure-volume curve analysis indicated that increased leaf water deficits in droughted plants led to reductions in bulk leaf elasticity, osmotic potential, and in the Psi(L) at which turgor loss occurred. Adjustments in Psi(L) at zero turgor were not sufficient to prevent loss or near loss of turgor in three of five cultivars at the lowest values of midday Psi(L) attained. Maintenance of protoplasmic volume was more pronounced than maintenance of turgor as soil drying progressed. Changes in assimilation and stomatal conductance were largely independent of changes in bulk leaf turgor, but were associated with changes in relative symplast volume. It is suggested that osmotic and elastic adjustment contributed to maintenance of gas exchange in droughted coffee leaves probably through their effects on symplast volume rather than turgor.

Journal Article↗

Bursin localization in mammalian bone marrow and epithelial cells of intrahepatic bile ducts.

Bursin is a tripeptide (lysyl-histidyl-glycyl-amide) found in follicular and dendritic reticular epithelial cells of the avian bursa of Fabricius that selectively induces the differentiation of committed B-lymphocyte precursor cells but not of committed T-lymphocyte precursor cells. We now show, in immunoassays with tissue extracts, that bursin is also present in avian and bovine bone marrow. There was, however, a categorical difference between avian liver (bursin-negative) and bovine liver (bursin-positive). Bursin was therefore isolated from bovine liver and bone marrow and the structure of mammalian bursin was determined; it was identical to avian bursin. Immunohistochemical examination of bovine liver showed the presence of bursin within epithelial cells of the intrahepatic bile ducts. These cells have previously been suspected of having an endocrine function because of the rich periductal capillary plexus, which coalesces to form a portal system draining into the liver sinusoids. These findings suggest that bone marrow is a site of bursin production and associated B-cell differentiation in both birds and mammals. The bursin-containing cells of the intrahepatic bile ducts are not associated with developing B cells and it would appear that mammals have evolved a local hepatic function for bursin.

Animals↗

An unusual presentation of a congenital benign apocrine hamartoma.

A case of an unusual benign apocrine hamartoma was studied by light microscopic, immunohistochemical, and electron microscopic methods. This tumor clinically showed a linear configuration and was located on the midline chest of a pubescent male. Microscopic studies revealed features of both a tubular apocrine adenoma and a syringocystadenoma papilliferum.

Biopsy↗

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.

Aged↗