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Biomedical subjects

E Goldberg

Publications and source records attributed to E Goldberg.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hypercarotenemia and transaminitis in female adolescents with eating disorders: a prospective, controlled study.

PURPOSE: Hypercarotenemia and transaminitis are reported as laboratory features of anorexia nervosa. However, the specificity and sensitivity of an elevation in serum carotene and transaminase are not known. Therefore, a prospective study was undertaken to determine the clinical utility of these serum markers. METHODS: Serum carotene was measured in 46 female adolescents between 13 years and 18 years of age (21 anorexia nervosa, 17 bulimia nervosa, 8 unclassified eating disorders). Findings were compared to levels of carotene in serum samples obtained from similarly aged females with either chronic inflammatory bowel disease (22 Crohn disease, 11 ulcerative colitis) or acute medical symptoms not associated with undernutrition or intestinal inflammation (N = 26), and 21 children of either sex with dyspeptic symptoms. RESULTS: Serum carotene was elevated in 6/46 (13.0%) females with eating disorders compared with only 2/80 (2.5%) children in the three comparison groups (p < 0.01). Hypercarotenemia was present in 4/21 girls with anorexia nervosa compared with 0/17 females with bulimia nervosa (p = 0.11). Transaminitis was present in 38.5% (AST) and 7.7% (ALT) of eating disorder patients. Liver enzyme abnormalities, however, did not correlate with hypercarotenemia. Transaminitis was also not specific for eating disorders since transaminitis was observed with comparable frequency in the three comparison groups. CONCLUSIONS: These findings confirm that hypercarotenemia is a laboratory feature in some subjects with eating disorders, in particular, anorexia nervosa. The low sensitivity (13.0%) does not provide justification for its use as a screening test. However, in complicated diagnostic settings a serum carotene determination could prove useful because the specificity (97.5%), positive predictive value (75.0%), and negative predictive value (66.1%) of an elevated carotene were high. These data also show that elevated carotene levels are not associated with hepatic abnormalities. Although transaminitis is reported as a laboratory feature of eating disorders, the prevalence of such abnormalities in this study was not higher than in age-matched comparison groups.

Adolescent↗
PubMed1994

Human testis cDNAs identified by sera from infertile patients: a molecular biological approach to immunocontraceptive development.

Sera from patients with known or suspected immunological infertility were used to screen a human testis cDNA library. A total of 59 sera detected 38 unique cDNA inserts of which four were testis specific by Northern blot analyses. One of these is a testis-specific isoform of calpastatin. Five additional clones, although not testis specific, were found to be testis abundant. The number and type of clones identified by these human sera suggests a possible aetiology for immunologic infertility. The testis-specific clones will be further characterized to establish their usefulness as contraceptive vaccine candidates.

Antigens↗
PubMed1994

Characterization of a human antigen with sera from infertile patients.

We report the cDNA cloning and subsequent characterization of a novel antigen implicated in antibody-mediated human infertility. This antigen, designated AgX (unknown antigen), was identified originally by screening a human testis lambda gt11 cDNA expression library with infertile patients' sera known to contain anti-sperm antibodies. AgX cDNAs isolated from testis and placenta cDNA libraries (AgX-1 and AgX-2, respectively) differed by a 48-bp deletion in the open-reading frame (ORF). The AgX-1 and AgX-2 ORFs encoded putative peptide chains of 505 and 521 amino acids (approximately 55.5 and approximately 57.3 kDa), respectively. The AgX amino acid sequences contained consensus motifs indicative of NTP binding. However, computer homology searches did not identify any significant similarity with known sequences. Quantitative analysis using the reverse transcriptase-polymerase chain reaction (RT-PCR) indicated that the AgX-1 mRNA was fiftyfold more abundant than AgX-2 in the testis, while AgX-2 was more abundant than AgX-1 in somatic tissues. An anti-AgX peptide antiserum identified two AgX isoforms on Western blots of human tissue extracts. An abundant 56-kDa isoform was detected only in testis and sperm. These data suggest that the 56- and 58-kDa isoforms are AgX-1 and AgX-2, respectively. AgX was localized by immunofluorescence to the principal piece of the sperm tail. Therefore, antibodies against an AgX isoform may reduce fertility by affecting sperm function.

Amino Acid Sequence↗
PubMed1994

A 60-bp core promoter sequence of murine lactate dehydrogenase C is sufficient to direct testis-specific transcription in vitro.

A clone containing the 5' flanking region of the testis-specific murine lactate dehydrogenase C (Ldhc) gene was isolated from a mouse genomic library. Promoter activity was demonstrated within a 720-bp fragment in testis nuclear extract (TN). Interestingly, the addition of liver nuclear extract (LN) significantly repressed Ldhc promoter activity in the transcription assay system. Sequence analysis of this promoter region revealed several ubiquitous cis-regulatory elements, including one TATA box, one GC box, and two putative CCAAT elements. Analysis of a series of deletion mutants revealed that a 60-bp core promoter sequence was sufficient to direct basal, testis-specific transcription in an in vitro transcription system. A 103-kDa protein in TN and a 65-kDa protein in LN bind to the same palindromic sequences within the 60-bp core promoter region.

Animals↗
PubMed1994

Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.

The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete reverse transcriptase open reading frame and portions of flanking protease and integrase genes, were cloned and sequenced, using PCR-based procedures. Mutations were variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site-directed mutagenesis in order to confirm by viral replication assay the importance of this site in conferring resistance to ddC. The recombinant virus possessed greater than 10-fold resistance against this compound in comparison with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold, respectively, was detectable against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine and 2',3'-dideoxyinosine but not against 3'-azido-3'-deoxythymidine. Combinations of the site 65 and 184 mutations did not yield levels of resistance higher than those attained with the site 65 mutation alone. The presence of the site 65 mutation was confirmed by PCR analysis of peripheral blood mononuclear cells from patients on long-term ddC therapy in 4 of 11 cases tested. Viruses that possessed a ddC resistance phenotype were isolated from subjects whose viruses contained the site 65 mutation in each of four instances. Four of these clinical samples were also demonstrated to possess the Met-184-->Val mutation, and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions. Direct cloning and sequencing revealed the site 65 mutation in viruses isolated from these individuals.

Amino Acid Sequence↗
PubMed1994

Lateralization of frontal lobe functions and cognitive novelty.

The two hemispheres are functionally different in ways not adequately captured by the classic distinction between linguistic and nonlinguistic processes. The right hemisphere is critical for processing novel cognitive situations. The left hemisphere is key to the processes mediated by well-routinized representations and strategies. The left frontal systems appear to be critical for the cognitive selection driven by the content of working memory and for context-dependent behavior, the right frontal systems for cognitive selection driven by the external environment and for context-independent behavior. The crucial role of the right hemisphere in processing cognitively novel situations underscores the importance of the right frontal systems in task orientation and in the assembly of novel cognitive strategies.

Animals↗
PubMed1993

Testis-specific expression of a metallothionein I-driven transgene correlates with undermethylation of the locus in testicular DNA.

Mice carrying a chimeric transgene of the human testis-specific lactate dehydrogenase cDNA driven by mouse metallothionein I promoter have been reported to express the transgene in a testis-specific manner in six founder lines. To study the mechanism by which this testis-specific expression is mediated, we have examined genomic placement, expression pattern, and methylation status of the transgene. Our results indicate that transgene expression is repressed in all somatic tissues examined even when heavy metals are administered. Nuclear run-on assays indicate that failure of expression in the liver (in which the metallothionein I promoter is highly active) occurs at the transcriptional level. In contrast, the transgene mRNA is transcribed in male germ cells and is developmentally regulated during spermatogenesis. Examination of the transgene methylation status reveals that expression is inversely correlated with hypermethylation of the locus; all CpG dinucleotides examined in the promoter region were found to be fully methylated in kidney and liver but were undermethylated in testis. Since methylation of the murine metallothionein I promoter is sufficient to inhibit its activity, it is likely that suppression of the transgene in somatic tissues is mediated by methylation.

Animals↗
PubMed1993

Differences in regulation of testis specifc lactate dehydrogenase in rat and mouse occur at multiple levels.

The testis specific form of lactate dehydrogenase (LDH-C4) is encoded by a single locus, Ldh-c, and is tightly regulated in a tissue specific manner. Here we show differences in expression of Ldh-c between rat and mouse, and describe the levels at which regulation of this gene differs in the two species. Our results demonstrate that the Ldh-c message level is nearly nine fold greater in mouse testis and remains high post-meiotically. In contrast, rat Ldh-c mRNA is highest in primary spermatocytes and reduced in spermatids. The results of nuclear run-on assays indicate that the transcription rate of Ldh-c is only moderately higher in mouse than rat, and cannot account for a significant portion of the observed differences. Similar decay rates for both rat and mouse Ldh-c mRNA in actinomycin-D clearance assays indicate comparable cytoplasmic stabilities for the two messages. From these results we infer that nuclear prostranscriptional events contribute to the differences in Ldh-c message levels.

Animals↗
PubMed1993

Tracing the incorporation of the sperm tail in the mouse zygote and early embryo using an anti-testicular alpha-tubulin antibody.

The mechanism of sperm tail incorporation and the fate of the tail during mouse fertilization and early embryogenesis were examined. Time-lapse video microscopy and anti-tubulin immunofluorescence show that the incorporation of the sperm tail, but not the sperm head, is sensitive to cytochalasin B (a microfilament inhibitor). Colcemid, a microtubule inhibitor, does not affect tail incorporation. High-resolution, low-voltage scanning electron microscopy demonstrates that the plasma membrane covering the sperm tail does not appear to fuse with the oocyte membrane during in vitro fertilization in the presence of cytochalasin. In control and colcemid-treated oocytes, the plasma membrane along the sperm tail, which is oriented tangential to the egg surfaces, appears to fuse with the oocyte membrane at multiple sites. An antibody to testicular alpha-tubulin detects sperm-derived, but not egg, microtubules and this has permitted us to trace the behavior and disappearance of the sperm tail during embryogenesis. Conventional and confocal microscopy show that following sperm incorporation, the tail often splays into multiple fibers. At the two-cell stage, the axoneme may be localized in either blastomere or it may be found to run through the midbody between both blastomeres. The tail appears to shorten by the 8-cell stage and is undetectable after the 16-32 cell stage. In morulae, tail fragments have been found in outer cells but not in inner ones, and fragments have not be found in blastocysts. These data suggest that microtubules of sperm and oocytes contain different isotypes of alpha-tubulin, nongenomic sperm-derived components survive at least to the morula stage of mouse development, and egg microfilaments are involved in the incorporation of the sperm tail but not the sperm head, which demonstrates that motility during sperm incorporation is different in mammals when compared to lower vertebrates and invertebrates.

Actin Cytoskeleton↗
PubMed1993

An inexpensive microdrive for chronic single-unit recording.

A microdrive and microelectrode costing about $2.67 is described. The assembly is lightweight, compact, and versatile and is ideal for chronic single-unit recording from behaving rats. It is easy to assemble and operate and has been used successfully by undergraduates in the teaching and research laboratory.

Animals↗
PubMed1993

Immunoelectron microscopic localization of testicular and somatic cytochromes c in the seminiferous epithelium of the rat.

Somatic and testis-specific cytochromes c were localized ultrastructurally in the seminiferous epithelium by immunocytochemistry using monospecific antibodies. Cytochrome cS was lost from the mitochondria as spermatogenesis advanced, while there was a relative increase in cytochrome cT during the zygotene-to-pachytene transition; this was in agreement with other studies that have suggested activation of the cytochrome cT gene during prophase of the first meiotic division. Cytochrome cT was highly concentrated in mitochondria that were being degraded within cytoplasmic lobes of spermatids and in residual bodies that were phagocytized by Sertoli cells. The two isoforms were found to coexist within the same mitochondrion during the transitional period from cytochrome cS to cytochrome cT predominance. In addition, both cytochromes c were present in the chromatoid bodies of spermatocytes and round spermatids; this suggests that the chromatoid body may be involved in the storage of these isozymes and possibly in their differential expression within germ cell mitochondria. Apocytochrome c was concentrated in mitochondria and chromatoid bodies of the germ cells and also scattered in the cytoplasm. The presence of the holoprotein and apoprotein immunoprobes within the chromatoid bodies of spermatocytes and spermatids was an interesting observation that raises questions regarding the precise location of the synthesis of cytochromes c in spermatogenic cells.

Animals↗
PubMed1993

Genomic structure and promoter activity of the human testis lactate dehydrogenase gene.

The structure of the gene encoding the human testis-specific isozyme of lactate dehydrogenase (LDH) has been characterized and a regulatory region identified by promoter activity. The single-copy ldh-c gene has two alternative 5' noncoding exons and seven coding exons comprising an approximately 40-kb locus. The gene does not contain the canonical TATA or CAAT promoter sequences, and ribonuclease protection experiments suggest multiple transcription start sites. In the present study an immortalized murine germ cell line was used to detect promoter activity driven by 5' sequence of human ldh-c with lacZ as the reporter gene. Reporter gene activity was nondetectable when promoter constructs were transfected into nongerminal cells.

Animals↗
PubMed1993

Removal of nasal foreign bodies in children.

Among the foreign bodies most often found in children's nostrils are hair, beads, toy parts, paper wads, and food. Sometimes extraction of nasal foreign bodies can be difficult, especially if they are spherical. The classical presentation is a unilateral, persistent, foul-smelling, purulent, or bloody nasal discharge. Ulceration, dislodgement of the foreign body into the nasopharynx, and aspiration of the foreign body can complicate the problem.

Child, Preschool↗
PubMed1993

A randomized controlled trial of home exercise on the rheumatoid hand.

OBJECTIVE: To study differing home hand exercise interventions to determine effects on grip strength, and secondarily any immediate or short term effects on range of motion, pain, deformities, hand disease activity, and dexterity. METHODS: Randomized controlled trial of 12 weeks of home hand exercise performed for 10-20 min twice daily. Study exercise interventions were range of motion exercises, balanced resistive exercises, and range of motion plus balanced resistive exercises. RESULTS: Aside from transient, mild to moderate discomfort, exercises were well tolerated. Range of motion exercises were associated with improved right hand joint count. Range of motion plus balanced resistive exercises were associated with increased left hand dexterity. Home hand exercise (exercise groups combined) significantly increased left grip strength. CONCLUSIONS: Temporary use of home hand exercise has acceptable side effects and is an effective means of increasing grip strength.

Ambulatory Care↗
PubMed1993

Correlates of military tank simulator sickness.

A military tank driving simulator is currently widely used as a training aid for tank drivers. The purpose of this study was to investigate the relationship between possible correlates of simulator sickness and the occurrence of sickness and performance test results among simulator drivers. The average number of motion sickness-like symptoms reported after driving the simulator among subjects with a history of susceptibility to motion sickness was 3.4, significantly higher than the average of 1.6 reported among subjects who did not report previous susceptibility to motion sickness (p < 0.05). Subjects driving the simulator while screen image quality was disturbed had a longer reaction time (42.0 s) than when driving the simulator without screen interferences (18.4 s, p = 0.001). Subjects driving the simulator for a short period had the same number of symptoms as did those driving for a longer period, but had better digit symbol test results. There was no statistically significant association between the development of sickness and tank driving experience. Suggested countermeasures are expected to prevent simulator sickness among some of the simulator trainees and to make simulator training more effective.

Adolescent↗
PubMed1993

Spinal subdural hematoma: a rare cause of recurrent postoperative radiculopathy.

Spinal subdural hematoma is a rare condition with numerous etiologies. It is even more rare in the postoperative period and must be differentiated from the more common causes of postoperative pain and radiculopathy. We report a 36-year-old man presenting 6 weeks after surgery with incapacitating pain who was found to have a subdural but extraarachnoid fluid collection. We describe clinical presentation, radiological findings, etiology, and treatment. We conclude that, although rare, the spinal subdural hematoma should be considered in patients with postoperative pain. Prompt recognition and surgical evacuation are important for optimal recovery.

Adult↗
PubMed1992

Design and immunological properties of topographic immunogenic determinants of a protein antigen (LDH-C4) as vaccines.

Antibodies elicited by immunization with short peptides containing antigenic determinants have been shown, in general, to bind with greatly reduced affinity to the corresponding region in the native proteins. Thus, contiguous linear peptides have not proven to be effective immunogens in generating high affinity neutralizing or protective antibodies and consequently appear to be poor prospects for vaccines. The molecular basis for such reduced reactivity is clear from the crystal structure determination of antibody Fabs bound to protein antigens, which showed the complementarity between interfaces to be lock-and-key-like and extending over a large area (750 A2) involving discontinuous segments of the polypeptide chain. Thus, small perturbations in the secondary and tertiary structure of the antigen have profound effects on the fit of the antigen and its corresponding antibody. Because short peptides are unlikely to assume any particular conformation in solution, the fit is likely to be poor. New strategies are therefore required to produce conformationally stable peptides that mimic the critical structural features of the protein antigenic site. Here we show that a putative topographic determinant of the testis-specific isozyme of lactate dehydrogenase C4 (LDH-C4), designed and synthesized to adopt a well defined alpha-helical secondary and tertiary structure (four-helix bundle motif) in aqueous solutions, is highly immunogenic in both rabbits and mice, inducing IgG antibodies that bind to native LDH-C4. This engineered conformational 40-residue peptide is considerably more effective in inducing antibodies, as compared with the corresponding linear peptide. The antibody response is obtained without coupling the peptide to a carrier protein, suggesting that the peptide contains a T-cell antigenic determinant. The strategy described here to produce a conformationally stable peptide that mimics the native structure may have general applications in vaccine design.

Amino Acid Sequence↗