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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 109 records · Page 6Linked to original sources
PubMed1993

Possible action of human placental aminopeptidase N in feto-placental unit.

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.

Amino Acid Sequence↗
PubMed1992

Thymopoietin, a thymic polypeptide, prevents nicotinic agonist-induced morphological changes in neonatal muscle cells in culture.

Thymopoietin, a polypeptide hormone isolated from thymus and involved in immune function, potently inhibited [125I]alpha-bungarotoxin binding to neonatal muscle cells in culture (IC50 = 3.8 nM) and blocked carbachol-stimulated 22Na uptake with an IC50 of 1.9 +/- 0.2 nM and 23 +/- 7 nM at a half-maximal and maximal concentration of carbachol, respectively. Studies were subsequently done to evaluate potential long-term functional consequences of this interaction of thymopoietin at the nicotinic receptor. Exposure (1-3 days) of neonatal muscle cells in culture to nicotine (3 x 10(-6) M) or carbachol (1 x 10(-6) M) resulted in a decline in myotube branching and a decrease in myotube length. Thymopoietin did not appreciably alter myotube morphology on its own; however, it prevented the effects of nicotine and carbachol on muscle cell morphology at concentrations (1-10 nM) which corresponded well to those with which thymopoietin interacted at the receptor. The action of alpha-bungarotoxin on the myotubes was very similar to that of thymopoietin. These studies suggest that the endogenously occurring polypeptide, thymopoietin, has the potential to modulate muscle cell morphology through an interaction at the nicotinic receptor.

Analysis of Variance↗
PubMed1992

Language comprehension in schizophrenics and their brothers.

Disturbances in language functioning may be associated with familial vulnerability to schizophrenia. Language comprehension, measured by the Luria-Nebraska Relational Concepts Factor Scale, was evaluated in 36 schizophrenic probands and their nonschizophrenic adult brothers (n = 41), and in 18 normal controls. Language comprehension performance was a function of psychiatric diagnosis in the brothers. Brothers who met criteria for schizophrenia-spectrum disorders showed significantly reduced language performance compared with unaffected brothers and normal controls. Moreover, abnormal language performance was exhibited by significantly more probands and spectrum-disordered brothers than by the normal controls and the brothers without schizophrenia-spectrum disorders. Finally, language performance was not significantly different for 31 pairs of schizophrenic probands and their brothers. Impaired language comprehension appeared comparatively specific in this sample of relatives, as groups were not significantly different on measures of nonlinguistic concept formation (Wisconsin Card Sorting Test) and general intellectual functioning (WAIS-R Information and Block design). Results suggest that impaired language comprehension is associated with familial vulnerability to schizophrenia, and that this disturbance may be most severe in relatives diagnosed with schizophrenia-spectrum disorders.

Adult↗
PubMed1992

Combined effects of a thymic peptide, thymopoietin and myasthenic patient sera in rat myotube culture.

We investigated in a rat myotube assay the combined effect of 26 myasthenic (MG) patient sera and a thymic peptide, thymopoietin (Tpo) which had previously been shown to bind Torpedo and human AChR and to compete with alpha-bungarotoxin (alpha-Bgt) binding. Cultures were first exposed to Tpo alone for 3 h (0.3, 7.5, 15 nM), then MG sera (5% final dilution) were added for an additional 18 h. Reduction in the amount of 125I-alpha-Bgt binding sites in the presence of various concentrations of Tpo were similar with control sera and in all the patients with low or undetectable anti-AChR Ab (11 cases). In cultures exposed to Tpo and sera with high anti-AChR Ab titre (15 cases), Tpo and anti-AChR Ab have an additive capacity to reduce the number of alpha-Bgt binding sites. The results are compatible with the hypothesis that anti-AChR Ab and Tpo could impair neuromuscular transmission by complementary mechanisms.

Acetylcholinesterase↗
PubMed1992

Thymopoietin, a polypeptide ligand for the alpha-bungarotoxin binding site in brain: an autoradiographic study.

Thymopoietin, a 48-49-amino acid polypeptide present in the thymus gland, was investigated as a potential ligand for the neuronal nicotinic alpha-bungarotoxin binding site in rat brain. Binding of [125I]alpha-bungarotoxin to whole rat brain sections was inhibited by thymopoietin in a concentration-dependent manner with an IC50 of 30.0 +/- 8.2 nM as compared to 1.1 +/- 0.3 nM for alpha-bungarotoxin. However, at concentrations of thymopoietin of up to 1 microM, [3H]nicotine binding to high affinity sites was not inhibited. Thysplenin, a polypeptide with considerable homology to thymopoietin did not affect [125I]alpha-bungarotoxin binding. These results suggest that thymopoietin selectively interacts with the nicotinic alpha-bungarotoxin binding site labelled by [125I]alpha-bungarotoxin rather than the neuronal nicotinic receptor(s) labelled by [3H]nicotine. Autoradiographic studies revealed that 1 microM thymopoietin almost completely inhibited [125I]alpha-bungarotoxin binding in all brain regions. Computer-assisted image analysis of displacement curves was performed on various brain areas rich in alpha-bungarotoxin binding, such as the dorsal endopiriform nucleus, fields 1 and 2 of Ammon's horn, the polymorph cell layer of the dentate gyrus and cortical layers 4 and 5. Thymopoietin inhibited [125I]alpha-bungarotoxin binding with similar potency in all these regions, suggesting that it interacted at the same site in the different brain areas. The IC50 values averaged over the six regions were 24.6 +/- 2.8 nM for thymopoietin and 1.2 +/- 0.2 nM for alpha-bungarotoxin. These results show that thymopoietin specifically interacted with the alpha-bungarotoxin site with a similar potency in different brain regions. It is suggested that thymopoietin represents a selective ligand for alpha-bungarotoxin binding sites in brain.

Animals↗
PubMed1992

Neuropsychological functioning in nonmentally retarded autistic individuals.

To investigate several neurobiological theories we evaluated the neuropsychological functioning of 15 non-mentally retarded autistic adolescents and young adults and 15 controls matched on age, gender, IQ, and race. The autistic subjects were found to perform less well than controls on measures of abstraction involving cognitive flexibility, verbal reasoning, complex memory, and complex language comprehension in the absence of significant differences on measures of attention, associative memory, and the rule-learning aspects of abstraction. These findings are most consistent with a generalized abnormality in complex information processing and would not support theories purporting fundamental deficits in attention or information acquisition.

Adolescent↗
PubMed1992

Maintenance of CD4+ cells by thymopentin in asymptomatic HIV-infected subjects: results of a double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of thymopentin in HIV-infected patients who had not yet developed AIDS. DESIGN: Patients were stratified into asymptomatic or symptomatic groups and randomized to receive either thymopentin (50 mg) or placebo, subcutaneously, double-blind for 24 or 52 weeks, three times a week. SETTING: Patients were enrolled at three sites (two hospital clinics and one private practice). PATIENTS: Of 91 HIV-seropositive patients (52 asymptomatic and 39 symptomatic) from whom HIV could be isolated from peripheral blood, 45 were enrolled for 24 weeks and 46 for 52 weeks of double-blind evaluation. MAIN OUTCOME MEASURES: Virological, immunological and clinical evaluations were performed before and during treatment. RESULTS: Thymopentin-treated asymptomatic patients had more CD4+ cells, as demonstrated by a greater area under the percentage CD4+ cells curve (P = 0.03) and a shorter median time to a 20% increase in percentage of CD4+ cells (P = 0.04) in the first 24 weeks, with similar trends in the 52-week study. By 24 weeks no asymptomatic thymopentin-treated and two placebo-treated patients (9.1%, Kaplan-Meier estimate) had progressed to constitutional symptoms (P = 0.12; two-tailed Wilcoxon-Gehan test), with only one further progression in a placebo-treated patient in the subset followed for 52 weeks. Symptomatic patients receiving thymopentin or placebo were similar in both CD4+ cell levels and disease progression (two progressions to AIDS in each group). No serious adverse effects attributable to thymopentin were observed. CONCLUSIONS: These results, if confirmed, indicate that thymopentin, by maintaining CD4+ cells, could slow or arrest immune decline and consequent disease progression at the asymptomatic stage of HIV infection.

Amino Acid Sequence↗
PubMed1992

Node-negative breast carcinoma treated without adjuvant systemic therapy.

In this prospective study, 167 consecutive patients with node-negative invasive breast cancer were treated without adjuvant systemic therapy in a community hospital from 1974 through 1984. The median follow-up for living patients was 84 months. Ninety-three percent of patients had disease classified as T1, N0, M0 or T2, N0, M0. Overall survival at 5 years was 81% and at 10 years, 66%. Adjusted survival rates, which excluded patients who died without breast cancer, were 91% at 5 years and 83% at 10 years. Relapse-free survival rates were 74% at 5 years and 61% at 10 years. T status, age, menopausal status, histology, estrogen receptor status, nuclear grade, and sinus histiocytosis were evaluated as prognostic indicators. It was difficult for the pathologists to assign a single value for nuclear grade; however, univariate analysis showed a significant difference in outcome between patients with nuclear grade 1 versus nuclear grade 4 lesions. Patient age is important in the decision regarding adjuvant therapy in that patients aged 70 and older are much more likely to die without breast cancer recurrence. By multivariate analysis, tumor size was the only independently significant factor (P less than .0125).

Adenocarcinoma↗
PubMed1992

Water relations, gas exchange, and nutrient response to a long term constant water deficit.

Wheat plants (Triticum aestivum) were grown for 43 days in a micro-porous tube nutrient delivery system. Roots were unable to penetrate the microporous tube, but grew on the surface and maintained capillary contact with the nutrient solution on the inside of the tube through the 5-micron pores of the porous tube. Water potential in the system was controlled at -0.4, -0.8, and -3.0 kPa by adjusting the applied pressure (hydrostatic head) to the nutrient solution flowing through the microporous tubes. A relatively small decrease in applied water potential from -0.4 to -3.0 kPa resulted in a 34% reduction of shoot growth but only a moderate reduction in the midday leaf water potential from -1.3 to -1.7 MPa. Carbon dioxide assimilation decreased and water use efficiency increased with the more negative applied water potentials, while intercellular CO2 concentration remained constant. This was associated with a decrease in stomatal conductance to water vapor from 1.90 to 0.98 mol m-2 s-1 and a decrease in total apparent hydraulic conductance from 47 to 12 micromoles s-1 MPa-1. Although the applied water potentials were in the -0.4 to -3.0 kPa range, the actual water potential perceived by the plant roots appeared to be in the range of -0.26 to -0.38 MPa as estimated by the leaf water potential of bagged plants. The amount of K, Ca, Mg, Zn, Cu, and B accumulated with each unit of transpired water increased as the applied water potential became less negative. The increase in accumulation ranged from 1.4-fold for K to 2.2-fold for B. The physiological responses observed in this study in response to small constant differences in applied water potentials were much greater than expected from either the applied water potential or the observed plant water potential. Even though the micro-porous tube may not represent natural conditions and could possibly introduce morphological and physiological artifacts, it enables a high degree of control of water potential that facilitates the investigation of many aspects of water relations not practical with other experimental systems.

Boron↗
PubMed1992

Genotypic variability in vulnerability of leaf xylem to cavitation in water-stressed and well-irrigated sugarcane.

Genotypic variability in vulnerability of leaf xylem to water-stress-induced cavitation was determined in four sugarcane (Saccharum sp.) clones using detached leaf segments in a hydraulic conductivity apparatus. Vulnerability curves were constructed by plotting the percentage of maximum conductivity versus leaf water potential (psi(I)) and fitting curves using a Weibull function. The psi(I) at which each clone lost 10, 50, and 80% of maximum conductivity was determined. Maximum conductivity per unit of leaf width was positively associated with metaxylem vessel diameter. The commercial clone H65-7052 exhibited the highest and the nondomesticated S. spontaneum exhibited the lowest conductivity. All four clones lost substantial conductivity at values of psi(I) less negative than -1.4 MPa, but H65-7052 was able to maintain 50% conductivity to lower psi(I) than the other clones. S. spontaneum sustained the most negative psi(I) (-1.99 MPa) before reaching the 80% conductivity loss point. Clone H69-8235 was consistently the most vulnerable to initial loss of conductivity. These vulnerability functions were used in conjunction with field measurements of psi(I) to estimate diurnal losses in leaf hydraulic conductivity under irrigated and droughted conditions. H69-8235 lost up to 50% of its conductivity during the day, even when well irrigated, and more than 80% when subjected to drought. The other clones exhibited lower conductivity losses. These losses are apparently reversed overnight by root pressure. Despite their close genetic relationships, these clones exhibited large differences in conductivity, in the vulnerability of their xylem to cavitation, and in gas exchange behavior. The potential for altering water relations by selecting for particular hydraulic characteristics is discussed.

Journal Article↗
PubMed1992

Fluorescence Quenching in the Varied Photosynthetic Modes of Portulacaria afra (L.) Jacq.

The kinetics of chlorophyll fluorescence were measured in Portulacaria afra (L.) Jacq. when the plants were functioning in either Crassulacean acid metabolism (CAM) or C(3)/CAM cycling (called cycling) modes, as determined by fluctuation in titratable acidity and gas exchange properties. Cycling plants showed primarily daytime CO(2) uptake typical of C(3) plants, but with a slight diurnal acid fluctuation, whereas CAM plants showed nocturnal CO(2) uptake, daytime stomatal closure, and a large diurnal acid fluctuation. Results from fluorescence measurements indicated no significant differences in photochemical quenching between cycling and CAM plants; however, sizable differences were detected in nonphoto-chemical quenching (q(n)), with the largest differences being observed during the middle of the day. Cycling plants had lower q(n) than CAM plants, indicating altered photosynthetic regulation processes. This q(n) difference was believed to be related to reduced internal CO(2) concentration in the CAM plants because of daytime stomatal closure and reduced deacidification rates in the late afternoon when most of the malic acid has been utilized. Experimentally, higher external CO(2) given to plants in the CAM mode resulted in a decline in q(n) in comparison to that measured in plants in the cycling mode. No changes were observed in photochemical quenching when CO(2) was added.

Journal Article↗
PubMed1992

Reciprocal neurological developments of twins discordant for hydrocephalus.

Studies of 10 sets of twins discordant for hydrocephalus in early life revealed striking differences in degree and nature of development of verbal vs. non-verbal cognitive functions, birth order, and hand and eye preference. Despite similar (four dizygotic pairs) or identical (six monozygotic pairs) genetic endowment and grossly similar intra- and extra-uterine environmental and socio-economic influences, the consistency of the differences between the hydrocephalic children and their seemingly normal twins indicate systematic differences in pre-, peri- and/or early postnatal organization and development of hemispheric function. Follow-up studies also documented development of above-average intelligence, despite drastically reduced cerebral mantle size in hydrocephalus of early onset. The atypical patterns of development of the non-hydrocephalic twins also confirm previously described qualifications reported in studies of the significance of genetic vs. environmental factors in twins.

Adolescent↗
PubMed1991

Evidence for thymopoietin and thymopoietin/alpha-bungarotoxin/nicotinic receptors within the brain.

Thymopoietin, a polypeptide hormone of the thymus that has pleiotropic actions on the immune, endocrine, and nervous systems, potently interacts with the neuromuscular nicotinic acetylcholine receptor. Thymopoietin binds to the nicotinic alpha-bungarotoxin (alpha-BGT) receptor in muscle and, like alpha-BGT, inhibits cholinergic transmission at this site. Evidence is given that radiolabeled thymopoietin similarly binds to a nicotinic alpha-BGT-binding site within the brain and does so with the characteristics of a specific receptor ligand. Thus specific binding to neuronal membranes was saturable, of high affinity (Kd = 8 nM), linear with increased tissue concentration, and readily reversible; half-time was approximately 5 min for association and 10 min for dissociation. Binding of 125I-labeled thymopoietin was displaced not only by unlabeled thymopoietin but also by alpha-BGT and the nicotinic receptor ligands d-tubocurarine and nicotine; various other receptor ligands (muscarinic, adrenergic, and dopaminergic) did not affect binding of 125I-labeled thymopoietin. Thymopoietin was shown by ELISA to be present in brain extracts, displacement curves of thymus and brain extracts being parallel to the standard thymopoietin curve, and Western (immuno) blot identified in brain and thymus extracts a thymopoietin-immunoreactive polypeptide of the same molecular mass as purified thymopoietin polypeptide. We conclude that thymopoietin and thymopoietin-binding sites are present within the brain and that the receptor for thymopoietin is the previously identified nicotinic alpha-BGT-binding site of neuronal tissue.

Animals↗
PubMed1991

Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.

Aged↗
PubMed1991

Bovine probursin tetradecapeptide contains amino acid sequence from somatostatin, tuftsin and bursin.

The B cell differentiating tripeptide bursin (lysyl-histidyl-glycyl-amide) is found in avian and mammalian bone marrow and in epithelial cells of the avian bursa of Fabricius and mammalian intrahepatic bile ducts. We now report the structure of probursin (Phe-Phe-Trp-Lys-Thr-Lys-Pro-Arg-Lys-His-Gly-Gly-Arg-Arg) isolated from bovine bone marrow and liver. Amino acids 1-5 correspond to the active site of somatostatin, 5-8 to tuftsin and 9-11 to bursin. Intact probursin has the biological activity of both somatostatin and bursin, and known enzyme cleavages could release free tuftsin, although intact probursin has low tuftsin activity. Probursin and its component peptides could regulate other bone marrow functions in addition to B cell differentiation, and, in mammals, could also regulate the function of hepatocytes and Kupffer cells after transport to the hepatic sinusoids via a local portal system involving the peribiliary capillary plexus.

Amino Acid Sequence↗