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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1996

Neuropsychological differences between schizophrenic patients with heterogeneous Wisconsin Card Sorting Test performance.

This report compares neuropsychological test results of schizophrenic patients with good (5-6 categories achieved) and poor (0-1 categories achieved) performance on the Wisconsin Card Sorting Test (WCST). It was found that the subjects with poor performance also had substantial deficits on the subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Battery. The subjects with good WCST performance demonstrated a relatively mild degree of impairment on these tests, except for normal performance on the verbal subtests of the WAIS-R. It was concluded that: (1) not all schizophrenic patients have dense perseverative behavior as identified by impaired performance on the WCST; (2) impaired performance on the WCST is accompanied by a variety of other cognitive deficits; and (3) there appear to be measures more sensitive to cognitive dysfunction in schizophrenia than the WCST.

Adult↗
PubMed1996

A preliminary neuropsychological study of Persian Gulf veterans.

A neuropsychological investigation of 21 Persian Gulf veterans and 38 demographically matched controls was conducted in order to make a preliminary determination concerning presence of neuropsychological deficits associated with the Persian Gulf War experience. The neuropsychological test battery consisted of measures of complex attention, memory, and motor skills previously shown to be sensitive to exposure to environmental toxins. It was found that the Persian Gulf veteran group did not demonstrate substantial impairment, but an impairment index derived from 14 test variables was statistically significantly different from controls in the direction of poorer performance.

Adult↗
PubMed1996

The prognostic significance of serum viral load, codon 215 reverse transcriptase mutation and CD4+ T cells on progression of HIV disease in a double-blind study of thymopentin.

OBJECTIVE: To determine in asymptomatic HIV-infected subjects the prognostic value of virion reverse transcriptase (RT) codon 215 mutation, serum HIV RNA level, CD4+ T-cell count and immune complex dissociated (ICD) p24 level. The retrospective evaluation of thymopentin treatment effect on subjects in high risk groups for progression was a secondary objective. PARTICIPANTS: Zidovudine (ZDV)-experienced asymptomatic HIV-infected subjects (n = 352) who had been enrolled in a 48-week placebo-controlled double-blind trial of thymopentin treatment were studied. METHODS: Post hoc analyses were conducted to determine which subjects at study entry were at greater risk for progression to AIDS-related complex (ARC), AIDS or death, and to determine the effect of treatment on these subjects. Four potential prognostic variables (virion RT codon 215 mutation, circulating HIV virion RNA copies, CD4+ T-cell count, and ICD p24) were evaluated by dichotomizing subjects for each variable based on the median of the observed values. CD4+ T-cell count was evaluated prospectively, whereas frozen samples were evaluated under blinded conditions for the other variables after the study was completed. RESULTS: The presence of the codon 215 mutation [P = 0.044; relative hazard (RH), 2.6], > or = 20,000 HIV RNA copies/ml (P = 0.002; RH, 5.5), and < 350 CD4+ cells 10(6)/l (P = 0.042; RH, 2.2) were prognostic factors, and > or = 30 pg/ml ICD p24 level (P = 0.52; RH, 1.4) was not a prognostic factor in predicting progression. Subjects were prestratified by previous ZDV use (< or = 6 or > 6 months). Across both strata thymopentin delayed treatment progression to ARC, AIDS, or death (P = 0.015; RH, 3.0). This effect was magnified in the ZDV-experienced subjects at greater risk, where thymopentin delayed progression compared to placebo in the presence of the codon 215 mutation (P = 0.007; RH, 10.1), > or = 20,000 RNA copies/ml (P = 0.012; RH, 8.9), and CD4+ T-cell count < 350 x 10(6)/l (P = 0.005; RH, 10.4). CONCLUSIONS: Codon 215 mutation, serum HIV RNA and CD4 T-cell count are independent predictors of progression in ZDV-experienced asymptomatic subjects. Furthermore, thymopentin delays HIV disease progression in the presence of a key ZDV resistance mutation as well as high viral load and low CD4+ T-cell counts.

Adjuvants, Immunologic↗
PubMed1996

A clarification of the Russell, Neuringer, and Goldstein Process Key: implications for outcome.

The purpose of this study was that of attempting to clarify discrepant results regarding classificatory accuracy of the Russell, Neuringer and Goldstein (1970) Process Key. The Process Key is the component of the neuropsychological keys that classifies cases as having recently or remotely acquired brain damage on the basis of level of performance and severity of lateralizing signs. A correct classification of acute brain damage occurs when onset of illness began within 3 months of time of testing. A study of stroke patients indicated that time since onset is an inadequate criterion for producing a satisfactory classificatory level, but time of onset in combination with type of stroke was associated with a high degree of classificatory accuracy. In particular, patients with recent thrombotic/hemorrhagic type strokes were classified as acute with a very high accuracy level, but the classification was substantially less accurate for recent stroke patients with other types of stroke, and for cases that were not of recent onset.

Journal Article↗
PubMed1996

IRI-514, a synthetic peptide analogue of thymopentin, reduces the behavioral response to social stress in rats.

Thymopentin, a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) corresponding to amino acids 32-36 of the thymic polypeptide thymopoietin, has been reported to block adrenocorticotrope responses to stress. The purpose of the present study was to explore potential antistress properties of a synthetic analogue of thymopentin, IRI-514 (Ac-Arg-Pro-Asp-Phe-NH2) using a behavioral response to a stressor. The behavioral response to social conflict stress (resident-intruder paradigm) was evaluated by the elevated plus-maze test of anxiety in adult Wistar rats. A single subcutaneous (SC) administration of IRI-514, 48 h before stress, dose-dependently reversed the anxiety-like behavior induced by the social stress. The effect of IRI-514 was present over an extended period (24-72 h) following SC administration and was maximally effective at a dose of 1 mg/kg. These results indicate that IRI-514 has a long-lasting modulatory effect on behavioral responses to a stressor, and suggest that thymopoietin-derived peptides may have a role in modulating both behavioral and neuroendocrine responses to stress.

Aggression↗
PubMed1995

Peptide chiral purity determination: hydrolysis in deuterated acid, derivatization with Marfey's reagent and analysis using high-performance liquid chromatography-electrospray ionization-mass spectrometry.

A high-performance liquid chromatography-electrospray ionization-mass spectrometric (LC-ESI-MS) method is presented that allows rapid and accurate determination of amino acid chiral purity in a peptide. Peptides are hydrolyzed in hydrochloric acid-d1/acetic acid-d4 and then converted to diastereomers by derivatization with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA, Marfey's reagent). Mixtures of D- and L-amino acid diastereomeric pairs are resolved in one chromatographic separation using conventional reversed-phase high-performance liquid chromatography. Hydrolysis in a deuterated solvent is necessary because the original ratio of D-/L-amino acids present in a peptide changes during acid hydrolysis due to racemization. Peptide hydrolysis in deuterated acids circumvents this problem by labeling each amino acid that racemizes with one deuterium at the alpha-carbon. An increase in molecular mass of one atomic mass unit allows racemized amino acids to be distinguished from non-racemized amino acids by mass spectrometry. This procedure was used to determine the chiral purity of each amino acid in a purified, hexapeptide by-product (Arg-Lys-Lys-Asp-Val-Tyr) present in a kilogram batch of the synthetic pentapeptide, thymopentin (Arg-Lys-Asp-Val-Tyr).

Alanine↗
PubMed1995

Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2.

Thymopoietins (TMPOs, previously abbreviated TPs) alpha (75 kDa), beta (51 kDa), and gamma (39 kDa) are related nuclear proteins expressed in many or all tissues. TMPO alpha is present diffusely throughout the nucleus, while TMPOs beta and gamma are localized to the nuclear membrane. Here we report the cloning and analysis of a single TMPO gene encoding TMPOs alpha, beta, and gamma, which are produced by alternative mRNA splicing, as previously inferred from cDNA sequences. The eight exons of the TMPO gene are spread over approximately 35 kb. Exon 4, which is spliced into TMPO alpha mRNA, contains sequences that encode a putative basic nuclear localization motif. Exon 8, which is spliced into TMPO beta and gamma mRNAs, encodes a hydrophobic putative membrane-spanning domain that is thought to target TMPOs beta and gamma to the nuclear membrane. TMPO beta appears to be the human homologue of the recently described rat protein LAP2 (lamina-associated polypeptide 2), which is thought to play an important role in the regulation of nuclear architecture by binding lamin B1 and chromosomes in a manner regulated by phosphorylation during mitosis (K. Furukawa and L. Gerace, La Jolla, pers. comm., 22 Nov. 1994). The human TMPO gene maps to chromosome band 12q22.

Amino Acid Sequence↗
PubMed1995

Whole blood culture for measuring mitogen induced T cell proliferation provides superior correlations with disease state and T cell phenotype in asymptomatic HIV-infected subjects.

Proliferative responses to a panel of mitogens were compared in parallel for two sources of cells, whole blood (WB) and conventionally prepared peripheral blood mononuclear cells (PBMC), obtained from asymptomatic HIV seropositive and control subjects. Weak but statistically significant correlations of the proliferative responses were observed. Use of either lymphocyte source produced significant differences in the proliferative responses between the HIV seropositive and control subjects, but the use of WB was more powerful, with a smaller sample size being required to discriminate between the proliferative responses of the two study groups. Furthermore, proliferative responses using WB gave strong and highly significant correlations with a number of important changes in the surface marker phenotype of the lymphocyte populations in the HIV seropositive subjects including CD4, CD8, CD4:CD8 ratio and certain CD8 subsets, whereas strong correlations were not observed with the PBMC. The response of WB lymphocytes to staphylococcal enterotoxin B (SEB) was highly reproducible and provided the best discrimination between HIV-infected and control subjects. We conclude that the use of WB for measuring lymphoproliferation is easy, rapid, accurate, and discriminative for assessing and following the changes in immune function which occur in HIV seropositive subjects, applicable in the clinical as well as in the research setting.

Adult↗
PubMed1995

Safety and efficacy of thymopentin in zidovudine (AZT)-treated asymptomatic HIV-infected subjects with 200-500 CD4 cells/mm3: a double-blind placebo-controlled trial.

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.

Adult↗
PubMed1995

Subacute combined degeneration of the spinal cord: MRI detection of preferential involvement of the posterior columns in a child.

Subacute combined degeneration of the spinal cord (vitamin B12-deficient myelopathy) is a neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. As shown by pathology, it initially involves the posterior columns of the thoracic cord. We present a case of vitamin B12 deficiency with preferential posterior column involvement of the thoracic cord in a child. Theoretically, this should be the earliest, most reversible stage of the disease, making recognition of this MRI pattern of critical importance.

Child↗
PubMed1995

Influences on cognitive heterogeneity in schizophrenia.

A study was conducted of diagnostic reliability, clinical, demographic, iatrogenic, and neurological comorbidity influences on heterogeneity in cognitive function among schizophrenic patients. Comparisons were made between a previously described (Goldstein, 1990) retrospective sample of clinically diagnosed schizophrenic patients and a new sample based on a prospective study of patients meeting strict DSM-III-R diagnostic criteria for schizophrenia. A cluster analysis of a brief battery of cognitive tests suggested a four cluster solution in both samples. The cluster pattern was found to be similar in both samples, indicating that diagnostic unreliability is unlikely to be strongly associated with heterogeneity. Age, general intelligence, and education were found to have significant influences on cluster membership, with length of illness and hospitalization having less robust influences. It was concluded that heterogeneity has a relatively mild relationship with the various influences studied, but a great deal of the diversity in level and pattern of cognitive function found among schizophrenic patients is likely to be a function of heterogeneity within the disorder itself.

Adult↗
PubMed1995

Health and Environment Analysis for Decision-Making (HEADLAMP): field study in Accra, Ghana.

This field study assesses the feasibility of routine data linkage of health and environmental indicators in Accra, Ghana. In Accra, as in most low-income developing countries, there is no coherent management information system available covering environmental, demographic and health aspects of the city. These categories of data are, however, collected either routinely or on an ad hoc basis by different agencies within the city. These data bases, even though of variable quality, can be adapted for the purpose of health and environment data linkage. A number of studies have already been undertaken within Accra linking health and environment data with a good measure of success. These include: an intra-urban environment and health differentials study using mortality data; a household survey of environmental problems and the urban household in which morbidity data and environmental data were linked, also indicating intra-urban differentials together with the isolation of high risk factors from a logistical regression analysis; simple cholera mapping; and an initiative to pilot-test a community-based environmental management information system in a low-income community in which health and environmental data will be linked. All these studies have created a greater awareness of the need for such data linkage and of the value of such studies for the sustainable management of the city.

Adolescent↗
PubMed1994

Determination of nanogram levels of peptide drug in rabbit and human plasma using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry.

High-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) using an electrospray ionization (ESI) interface provides a sensitive method for the quantitative analysis of peptide drugs in complex biological matrixes. ESI HPLC-MS was applied to the analysis of a pentapeptide drug (IRI-514) in rabbit and human plasma. Prior to analysis, the plasma samples were prepared using protein precipitation followed by solid-phase extraction. The lower limit of quantitation using selected ion monitoring was determined to be 2 ng/mL, when 8 mL of human plasma spiked with 1-40 ng/mL was extracted. Rabbit plasma (1 mL) samples spiked with 10-40,000 ng of authentic drug/mL gave a linear response when a deuterated peptide analog was employed as an internal standard. A commercial ESI interface was modified to permit higher flow rates (10-20 microL/min) to enter the mass spectrometer source. The revised interface provided a 10-fold increase in sensitivities and permitted the use of standard HPLC columns (2.0-mm i.d.) and HPLC instrumentation. ESI HPLC-MS analysis was automated to provide unattended, precise, and sensitive detection of small peptides in both human and rabbit plasma. Using this methodology, a toxicokinetic study of intravenously administered IRI-514 at three dose levels indicated that the area under the curve values were dose proportional.

Amino Acid Sequence↗
PubMed1994

Three distinct human thymopoietins are derived from alternatively spliced mRNAs.

Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine thymus in studies of the effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T-cell differentiation and function. We now report the isolation of cDNA clones for three alternatively spliced mRNAs that encode three distinct human T-cell TPs. Proteins encoded by these mRNAs, which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa), contain identical N-terminal regions, including sequences nearly identical to that of the originally isolated 49-aa protein, but divergent C-terminal regions. TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal liver of the tissues so far examined. Distinct structural domains and functional motifs in TPs alpha, beta, and gamma suggest that the proteins have unique functions and may be directed to distinct subcellular compartments.

Alternative Splicing↗