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Biomedical subjects

E Goldberg

Publications and source records attributed to E Goldberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adaptive decision making, ecological validity, and the frontal lobes.

Existing neuropsychological procedures assess veridical, but not adaptive, decision making, which are based on different mechanisms. This severely curtails the tests' ecological validity, because most real-life decision making situations are adaptive, rather than veridical. Veridical decision making entails finding the correct response intrinsic to external situations and is actor-independent. Adaptive decision making is actor-centered and priority-based. Prefrontal cortex is critical for adaptive decision making. Innovative actor-centered decision-making tasks are required to better understand frontal lobe functions. We have designed a prototype for such procedures, the Cognitive Bias Task (CBT). CBT elicited strong gender and hemispheric differences in the effects of focal frontal lesions, which are more robust than those elicited with veridical tasks, such as the Wisconsin Card Sorting Test.

Adaptation, Psychological↗
PubMed2000

Identification of a novel testis-specific leucine-rich protein in humans and mice.

A novel testis-specific protein, termed LRTP, was identified by screening both human and mouse testis and mouse pachytene spermatocyte cDNA libraries. Sequence analyses (GenBank accession number: AF092208) revealed that LRTP contains an amino terminus leucine-rich repeat domain. There are several acidic regions rich in glutamic acid in the C-terminus. The sequence, by GenBank search, shows similarities to LANP and SDS22+, leucine-rich repeat proteins localized to the nucleus and involved in the regulation of protein phosphatases. In mouse, the mRNA is first detected at about Day 14 postpartum, presumably when mid-pachytene spermatocytes are first seen. In situ hybridization confirmed the expression of the LRTP mRNA at this stage of spermatogenesis. Immunohistochemical analysis revealed that the protein is most abundant in the cytoplasm of pachytene and diplotene cells, corresponding to late prophase of meiosis I. Immunohistochemical localization is markedly reduced in secondary spermatocytes, suggesting a functional association of LRTP with meiosis. An LRTP cDNA probe did not bind to mouse ovary RNA in a dot blot assay.

Amino Acid Sequence↗
PubMed2000

Molecular cloning and characterization of functional domains of a human testis-specific isoform of calpastatin.

Human serum containing sperm-agglutinating antibodies was used to screen a testis cDNA expression library to identify the cognate antigens that may be responsible for this biological effect. The longest positive phage clone (1.9 kb) was sequenced and found to be a testis-specific isoform of calpastatin (tCAST). The testis-specific segment of tCAST is encoded by a single exon within intron 14 of the calpastatin gene. A unique protein isoform is produced that differs in domain structure from the somatic calpastatins (sCAST). Human sCAST most commonly has an N-terminal domain L plus the four functional calpain inhibitory domains. Human tCAST consists of a 40-amino-acid N-terminal T domain plus a part of domain II and all of domains III and IV from the somatic isoform. Our data show that the T domain can target cytosolic localization and membrane association of tCAST, whereas domain I of sCAST exhibits a nuclear localization function. Calpastatin is the endogenous inhibitor of calpain. The calpain/calpastatin system is involved in membrane fusion events for several cell types, and calpain has been localized to the sperm acrosome. We detected tCAST in human sperm and testes extracts by Western blotting with specific antisera. These observations suggest that tCAST may modulate calpain in the calcium-mediated acrosome reaction that is required for fertilization.

Amino Acid Sequence↗
PubMed2000

A novel N-terminal domain directs membrane localization of mouse testis-specific calpastatin.

Multiple isoforms of calpastatin have been identified with unique N-terminal regions followed by identical calpain inhibitory domains (II-IV). In many instances the isoforms are cell-type specific, although the precise functional differences among these N-terminal regions are largely unknown. Here we report a germ cell-specific isoform of calpastatin (tCAST) that consists of a novel N-terminal peptide of 40 amino acids (domain T) followed by domains II to IV of somatic calpastatin (sCAST). Domain T is responsible for membrane association of tCAST through a protein modification by myristylation. Mutation of the myristylation site eliminates membrane targeting. Unlike most of the isoforms of calpastatin that are generated through alternative RNA splicing or post-translational proteolysis, the testis-specific isoform is transcribed from an intronic promoter in haploid germ cells of the testis. The intronic promoter directs specific expression of a reporter transgene in developing germ cells of the mouse testis.

Animals↗
PubMed1999

DNA-protein interactions in the CCAAT box region of the murine lactate dehydrogenase C promoter.

Electrophoretic Mobility (EMSA), using oligonucleotides containing CCAAT box sequences from the murine Idhc promoter show the presence of CCAAT binding proteins in nuclear extracts from liver and testis. In a liver extract, a single shifted band is seen. However, in the testis extract, two shifts are observed, one of which may be due to a testis specific isoform of CCAAT binding factor (CBF). Southwestern analysis with an oligonucleotide probe containing these sequences reveals the presence of a protein of approximately 120 kD in the testis extract. In the liver extract, a 70-kD protein binds the probe. An antibody against HeLa CBF causes a supershift in testis nuclear extract.

Animals↗
PubMed1999

Adaptive versus veridical decision making and the frontal lobes.

Adaptive decision making and veridical decision making are based on different mechanisms. Veridical decision making is based on the identification of the correct response, which is intrinsic to the external situation and is actor-independent. Adaptive decision making is actor-centered and is guided by the actor's priorities. The prefrontal cortex is particularly critical for adaptive decision making and less so for veridical decision making. However, most experimental procedures used in cognitive psychology and neuropsychology focus on veridical decision making and ignore adaptive decision making. Innovative experimental procedures are required to characterize the contribution of the prefrontal cortex to adaptive decision making. We have designed a prototype for such procedures, the Cognitive Bias Task, and present the novel findings generated by this task.

Adaptation, Physiological↗
PubMed1999

Task-specific deactivation patterns in functional magnetic resonance imaging.

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.

Adult↗
PubMed1999

Toronto street youth and HIV/AIDS: prevalence, demographics, and risks.

PURPOSE: The purposes of this study were: (a) to identify human immunodeficiency virus (HIV) prevalence in Toronto street youth through paired blood and saliva specimens; (b) to identify the HIV risk and prevention behaviors of street involved youth; and (c) to identify demographic or other factors that may contribute to the risk of street youth becoming infected with HIV/acquired immunodeficiency syndrome (AIDS) in the future. METHODS: This was a cross-sectional convenience study of street-involved youth aged 14-25 years. The youth participated in interviews to identify HIV-related knowledge and personal risk and preventive behaviors. Following interviews, they were asked to provide a saliva sample, blood spot, or both. They could refuse one or both samples without jeopardizing their involvement or receiving an honorarium. Two males were the only participants who declined to provide a sample. RESULTS: Fifteen of 695 (2.2%) youth tested positive for HIV infection. All were male, ranging in age from 18 to 25 years. Same and opposite sex, intravenous (IV) drug use, prostitution, and incarceration were risk factors associated with positive HIV test results. The rate of HIV infection was seven times greater for the group 20 years of age and older (20-25) compared to the younger group aged 14-9 years. The proportion testing positive for HIV from small cities, towns, and rural communities in Ontario was 40%; yet, they represented 21% of the study population. Most (57%) youth had been on their own for no more than 3 years and had moved frequently. Nearly two thirds (60%) had stayed in hostels or homeless shelters in the previous 6 months. CONCLUSION: Street youth in Canada are at high risk of HIV infection with their risk increasing with age. Unprotected (same and opposite) sex, IV drug use, prostitution and incarceration were linked to their HIV infections. The high level of mobility identified by street youth challenges governments, communities, and public health officials to develop appropriate prevention strategies and to carefully monitor the spread of HIV infection in this vulnerable population.

Adolescent↗
PubMed1999

Limits to the value of mental health review tribunals for offender patients. Suggestions for reform.

BACKGROUND: Reform of mental health legislation for England and Wales is due. MHRTs offer an important check in the balance between patient and public rights. AIMS: To study the quantity and outcome of MHRTs in special (high-security) hospitals. METHOD: Data were extracted from the records of 1670 patients detained under mental illness or psychopathic disorder classifications in special hospitals during 1992. RESULTS: There were 661 MHRT hearings, mostly requested by patients. Forty-three (7%) discharges were ordered, often without key data about continuing care in the written evidence. There were 56 recommendations for transfer to lesser security. Correlates of MHRT discharge were: female gender, younger age (in women), a legal classification of psychopathic disorder and shorter length of stay. Conditional discharge did not necessarily mean departure from special hospital. CONCLUSIONS: Special hospital MHRTs result in few changes in patient status. A probable need for improvement in the evidence put before an MHRT was found. Legislation reformers should consider an extension of MHRT powers to order transfer between levels of security.

Adult↗
PubMed1998

Transgenic mice demonstrate a testis-specific promoter for lactate dehydrogenase, LDHC.

The mammalian genome encodes a family of lactate dehydrogenase (LDH) isozymes. Two of these, ldha and ldhb, are expressed ubiquitously. The ldhc gene is active only in the germinal epithelium during spermatogenesis. In our analysis of ldhc gene regulation, we found that a 60-base pair promoter sequence was sufficient for testis-specific expression in an in vitro transcription assay. To confirm these findings, a genomic fragment containing 100 base pairs overlapping the transcription start site was isolated and linked to the Escherichia coli lacZ gene. We report that this genomic fragment drives testis-specific expression in transgenic mice. We conclude that transcription of the transgene and possibly of the endogenous ldhc gene is restricted to leptotene/pachytene primary spermatocytes.

Animals↗
PubMed1998

The effect of full-time faculty hospitalists on the efficiency of care at a community teaching hospital.

BACKGROUND: Hospitalists are increasingly being used for inpatient care. OBJECTIVE: To investigate whether the use of hospitalists is beneficial. DESIGN: Retrospective cohort study. SETTING: Inpatient medical service of a 500-bed community teaching hospital. PARTICIPANTS: 1620 patients in the study group, seen during the hospitalist year; 1679 patients from the same outpatient practice as the study group, seen during the previous year (prehospitalist year); an unselected comparison group of 3413 patients seen during the prehospitalist year and 3223 patients seen during the hospitalist year; and a subset of the unselected comparison group, cared for by outpatient practices, who had a prehospitalist length of stay similar to that of the study group (743 patients in the prehospitalist year and 786 in the hospitalist year). INTERVENTIONS: Full-time faculty hospitalists cared for the study group, were in the hospital during normal working hours, and made decisions throughout the day. In the prehospitalist year and in the comparison groups, primary care physicians managed their own hospitalized patients. MEASUREMENTS: Length of stay; cost of care; costs of hematology and chemistry evaluation, pharmacy, and radiology; and readmissions were determined for the prehospitalist and hospitalist years. RESULTS: In the study group, median length of stay decreased from 6.01 to 5.01 days (P < 0.001). Median cost of care decreased from $4139 to $3552 (P < 0.001), and the 14-day readmission rate decreased from 9.9 to 4.64 readmissions per 100 admissions (P < 0.001). In the comparison groups, length of stay decreased but both cost of care and readmission rates increased. CONCLUSION: Hospitalists may improve the efficiency of inpatient care. Further study in various settings is needed to verify these findings.

Case Management↗
PubMed1998

Expression of the human antigen SPAG2 in the testis and localization to the outer dense fibers in spermatozoa.

ABSTRACT Antisperm antibodies (ASAs) have been implicated in some instances of infertility. To characterize sperm antigens relevant to immunologic and immunocontraceptive development, SPAG2 (sperm-associated antigen 2) was identified by screening a human testis cDNA library with human sera positive for ASAs. Subsequently, two isoforms, SPAG2-1 and SPAG2-2, were identified in testis and placenta libraries, respectively. In the current study, Southern analysis of human genomic DNA with a probe common to the two SPAG2 isoforms indicated a single SPAG2 gene; therefore, alternative splicing is a likely mechanism for production of variant mRNAs. In situ hybridization of human testis sections demonstrated the expression of SPAG2 in primary spermatocytes, with decreased or arrested expression in postmeiotic cells. Immunofluorescence of Triton X-100-extracted spermatozoa with an anti-SPAG2 peptide antiserum indicate that SPAG2 is an intracellular component of the sperm flagellum. Electron microscopy refined this localization to the outer dense fibers (ODFs), structural filaments associated with the mammalian sperm axoneme. The ODFs have been reported to be composed of keratin-like intermediate filament proteins. However, SPAG2 does not exhibit the molecular characteristics of such proteins, nor does SPAG2 demonstrate sequence homology with previously characterized ODF proteins. Therefore, SPAG2 represents a novel protein of human sperm ODFs. Characterization of SPAG2 will further our understanding of ODF function in normal sperm motility and of flagellar abnormalities that lead to male infertility.

Antigens, Surface↗
PubMed1998

Deoxyribonucleic acid-protein interactions and expression of the human testis-specific lactate dehydrogenase promoter: transcription factor Sp1 plays a major role.

The human testis-specific lactate dehydrogenase c gene (ldh-c) shows an exceptionally large window of expression throughout pre- and postmeiotic stages of the male germ cell lineage. In order to characterize the multiple stage-specific transcription factors necessary for ldh-c expression, we previously characterized the human ldh-c core promoter. Here, we used a combination of gel retardation assays and an in vitro transcription system derived from human tissues to better define the elements that govern ldh-c transcription. Three classes of transcriptional regulators were defined by these experiments. 1) The Sp1 transcription factor is a testis-"enriched" protein that is absent from most somatic tissues and that appears to play a major role in determining ldh-c expression in the testis. Highest levels of Sp1 during spermatogenesis correlate with maxima of ldh-c expression. 2) The testis-specific cAMP response element modulator (CREM) transcription factor binds a cAMP response element (CRE)-like sequence located at position -433. This transcriptional activator might contribute to postmeiotic transcription of ldh-c. 3) Factors present in tissues negative for ldh-c expression appear to bind both the CRE-like sequence and an adjacent hormone response element. The presence of this element could be involved in regulating ldh-c through the glucocorticoid/androgen pathways at the early stages of ldh-c expression.

Base Sequence↗
PubMed1998

Wisconsin Card Sorting Test performance in above average and superior school children: relationship to intelligence and age.

This study explores the relationship of intelligence and age to scores on the Wisconsin Card Sorting Test, a measure of executive function. A sample of 26 normal children with Wechsler Intelligence Scale for Children-III (WISC-III) Full-Scale IQS above 130 and 24 normal children with WISC-III Full-Scale IQS between 110 and 129 were administered the test. A comparison to published norms revealed that above average children outperformed the average 9- to 14-year-old child on every measure at every age. Multiple regression analyses statistically related the Wisconsin Card Sorting Test, perseverative, nonperseverative, total errors, and trials to the first category of intelligence. Intelligence proved to be a significant qualifier of age trends. Gender relationships were nonsignificant in a preliminary analysis.

Journal Article↗
PubMed1997

Colinear synthesis of an antigen-specific B-cell epitope with a 'promiscuous' tetanus toxin T-cell epitope: a synthetic peptide immunocontraceptive.

Carrier conjugation is commonly used to provide T-cell help for small, linear peptides containing antigen-specific B-cell epitopes. However, carrier conjugation is expensive, variable and often results in adverse side effects if the conjugate is administered repeatedly. To eliminate the need for carrier conjugation, we examined two synthetic peptides for their ability to elicit sustained antibody titres in female rabbits and baboons. One peptide (hC1-20) was based on the sequence of the sperm-specific isozyme of human lactate dehydrogenase (LDH-C4). This peptide stimulates helper T-cell responses. The other peptide (bC5-19:TT) was a chimera between an LDH-C4 B-cell epitope and a 'promiscuous' T-cell epitope from tetanus toxin which has been shown to bind to and stimulate many different major histocompatibility complex alleles. Both peptides were immunogenic in rabbits and baboons. The chimera elicited consistently high antibody titres and was immunogenic in 19/19 wild-caught female baboons. When 14 bC5-19:TT immunized baboons were mated, their fertility was reduced by 62% compared with controls (P < 0.02). This carrier-free construct can be incorporated into biodegradable microspheres which may provide long-term protection from pregnancy with a single dose.

Amino Acid Sequence↗
PubMed1997

Counseling sexually active teenagers treated with potential human teratogens.

Adolescents with hemoglobinopathies need daily chelation therapy with drugs which are known or suspected to be teratogenic. The prevention of fetal exposure to such drugs is therefore a major task for health professionals caring for these patients. We describe a pilot program aiming to prevent pregnancy among sexually active adolescents treated with iron chelators in Toronto. Most of them had normal response to GnRH, suggesting endocrinologic fertility, and unlike the literature concerning their healthy peers, all sexually active patients in this study reported use of at least one form of contraception.

Adolescent↗
PubMed1997

Perseverative behavior in Alzheimer's disease and subcortical ischemic vascular dementia.

Perseverative behavior has not been extensively studied in patients with dementia. In this study, perseverative behavior was elicited with the dementia version of the Graphical Sequence Test. A control group and participants with Alzheimer's disease (AD) and subcortical ischemic vascular dementia (IVD) were studied. A factor analysis revealed a 3-factor model consisting of perseverations related to semantic knowledge, motor functioning, and a third, intermediary factor. IVD participants made more total perseverations than did AD participants. Perseverations made by AD participants were correlated with deficits on tests of semantic knowledge, whereas the perseverations made by IVD participants were correlated with motor and frontal systems tests. Results are consistent with the view that perseverative behavior is hierarchically arranged in terms of specific levels of cognitive complexity and the overall pattern of cognitive deficits associated with each type of dementia.

Aged↗