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Biomedical subjects

E Goldberg

Publications and source records attributed to E Goldberg.

At least 19 recordsLinked to original sources
PubMed1995

Expression profile of Ldh-a in the developing rat (Rattus norvegicus) testis suggests regulation at the translational level.

Expression of Ldh-a and Ldh-c mRNAs was examined in the rat testis. The mRNA levels of both Ldh-a and Ldh-c increase during testicular maturation. In the adult testis, Ldh-a mRNA is expressed maximally in primary spermatocytes. Comparison of the Ldh-a mRNA expression profile with its translation product suggests that this gene is translationally down-regulated during spermatogenesis.

Animals↗
PubMed1995

Rise and fall of modular orthodoxy.

The premise of cortical modularity is based on strong dissociations caused by focal lesions. These dissociations are rare, and their explanatory power and theoretical importance are vastly overrated. The effects of brain lesions must be considered in their totality, rather than in idiosyncratic selectivity. These effects are more consistent with a continuous, graded functional neocortical geometry, than with a modular neocortex. Distinction must be drawn between strong intrinsic modularity, and weak emergent modularity. Strong intrinsic modularity is more characteristic of the thalamus than of the cortex. The advent of neocortex may have represented an evolutionary escape from strong modularity as the dominant principle of neural organization, and a shift toward a more interactive principle of neural organization dominated by emergent properties. The latter may take the form of weak modularity, reflective of cognitive skill routinization. The extent of weak, emergent modularization may be asymmetric, more pronounced in the left hemisphere, while the right hemisphere is essentially amodular.

Agnosia↗
PubMed1995

Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase.

In previous experiments, the sperm-specific isozyme of lactate dehydrogenase (LDH-C) had been purified from mouse testes and shown to suppress the fertility of female baboons by 70% compared to controls. Although these results demonstrated the feasibility of this approach for contraceptive vaccine development, it is not practical to purify enough of the protein from natural sources for human use. Therefore, a need exists to develop a contraceptive vaccine based on synthetic peptides. In the current study, baboon LDH-C cDNA was amplified by the reverse transcriptase-polymerase chain reaction technique. The amino acid sequences of human and baboon LDH-C were 99.3% identical, indicating that the human LDH-C would be an effective antigen in nonhuman primates. The immunodominant epitope of human LDH-C was identified, synthesized, and conjugated to diphtheria toxoid (DT). This construct was used to immunize 15 female baboons; 15 control animals were immunized with DT alone. The fertility of the experimental group was reduced by 75% as compared to the controls (p < 0.02). One year after the last immunization, the contraceptive effect was completely eliminated (no statistical difference between the groups). These results show that a synthetic peptide based on the sequence of human LDH-C is effective in preventing pregnancy in nonhuman primates. The effect is completely reversed 1 yr after the last immunization. The contraceptive effect is not related to serum antibody titers, and human LDH-C is only slightly more effective than mouse LDH-C in female baboons.

Adjuvants, Immunologic↗
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

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↗
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↗
PubMed1992

Protein turnover and resting energy expenditure in patients with undernutrition and chronic lung disease.

Whole-body protein metabolism was studied in 11 undernourished cystic fibrosis (CF) patient (7 female), 12 normally nourished CF patients (3 female), 7 anorexia nervosa (AN) patients (all female), and 15 normal control subjects (9 female). Protein turnover was studied by the single dose [15N]glycine method and the cumulative excretion of labeled urinary urea and ammonia. Energy metabolism was studied by open-circuit indirect calorimetry. Contrary to previous reports, no differences were found between the protein turnover of CF groups and the normal control group. However, patients with AN had a negative net protein deposition. Resting energy expenditure was significantly reduced in AN patients and increased in CF patients. The gender of CF patients did not affect protein and energy metabolism but fat mass was higher and fat-free mass was lower in CF females.

Adolescent↗
PubMed1992

Hypertrophic obstructive cardiomyopathy presenting with profound hypotension. Role of two-dimensional and Doppler echocardiography in diagnosis and management.

Five patients, all women, age ranges 59 to 84 years, with underlying hypertrophic obstructive cardiomyopathy (HOCM) presented with profound hypotension. Initial clinical and hemodynamic evaluation suggested cardiogenic shock in two cases, acute myocardial ischemia in two cases, and hypovolemia in one case. The two patients thought to be in cardiogenic shock were given inotropes without improvement. One patient in whom myocardial ischemia was suspected received nitroglycerin, followed by a marked fall in blood pressure. All five patients remained hypotensive until two-dimensional and Doppler echocardiography were performed, identifying HOCM as the cause of the hypotension, thereby allowing for corrective therapeutic measures.

Aged↗
PubMed1992

Associations between sexual experiences and fantasies in a nonpatient population: a preliminary study.

We have been interested in devising some methodology short of psychoanalytic therapy to study the relationship of conscious fantasy to personality trends and behavior. Presented here is a pilot study, utilizing the questionnaire technique, the sample consisting of 193 students enrolled at one prestigious urban university, that reports on the prevalence and content of conscious sexual fantasies in a normal (nonpatient) population and their relationship to sexual behaviors. Factor analysis suggested four experience and four fantasy clusters. Those individuals who score high on one experience factor are apt to score high on all other experience factors as well. The same is true of the fantasy factors. Our findings indicate that low sexual activity and low levels of sexual fantasy go together, whereas more sexual experience is connected to a greater range of sexual fantasy. Consequently, erotic fantasies cannot be viewed as compensation for lack of sexual outlet. Instead, there is a positive correlation between the two domains of sexual fantasies and sexual behaviors. Our overall results lead us to conclude that by and large, people are sexual generalists not specialists.

Adult↗
PubMed1992

Combined ovarian vein catheterization with ovarian stimulation in the diagnosis of androgen overproduction.

A 28-year-old woman was evaluated for late onset secondary amenorrhea, progressive hirsutism and an elevated serum testosterone concentration. Her serum cortisol, androstenedione, dehydroepiandrosterone sulfate and 17-hydroxyprogesterone levels were normal. Bilateral ovarian and adrenal vein catheterization demonstrated mild elevated testosterone and androstenedione levels in the right ovarian vein. Fifteen minutes after administering the intravenous injection of 5,000 IU human chorionic gonadotropin, there was a six and a half to sevenfold increase in the level of these two hormones in the right ovarian vein with no significant change in hormone levels from other sources. Based on the ovarian peripheral vein gradients obtained during venography following ovarian stimulation, the diagnosis of right ovarian hyperthecosis was made. This diagnosis could not have been reached without the combination of selective ovarian vein catheterization and ovarian stimulation. We recommend that this combined test, which may provide additional information on the source of the androgens in women with hyperandrogens, be performed in selected cases, when a virilizing tumor is suspected.

Adult↗
PubMed1991

Properties of human testis-specific lactate dehydrogenase expressed from Escherichia coli.

The cDNA encoding the C4 isoenzyme of lactate dehydrogenase (LDH-C4) was engineered for expression in Escherichia coli. The Ldh-c open reading frame was constructed as a cassette for production of the native protein. The modified Ldh-c cDNA was subcloned into the prokaryotic expression vector pKK223-3. Transformed E. coli cells were grown to mid-exponential phase, and induced with isopropyl beta-D-thiogalactopyranoside for positive regulation of the tac promoter. Induced cells expressed the 35 kDa subunit, which spontaneously formed the enzymically active 140 kDa tetramer. Human LDH-C4 was purified over 200-fold from litre cultures of cells by AMP and oxamate affinity chromatography to a specific activity of 106 units/mg. The enzyme was inhibited by pyruvate concentrations above 0.3 mM, had a Km for pyruvate of 0.03 mM, a turnover number (nmol of NADH oxidized/mol of LDH-C4 per min at 25 degrees C) of 14,000 and was heat-stable.

Base Sequence↗
PubMed1991

Rapid desalting of ammonium sulfate solutions by hydrophobic interaction chromatography.

Open-air hydrophobic interaction chromatography with alkyl carbon functional groups coupled to agarose beads has been used to desalt large volumes of ammonium sulfate-fractionated bacterial cell lysates. The protein of interest can be simultaneously desalted and concentrated in less than 4 h, and the yield is significantly better than that obtained by the standard technique of precipitation, centrifugation, and dialysis.

Ammonium Sulfate↗
PubMed1991

Transperineal ultrasound examination in the evaluation of prostatic size.

Eighty patients with benign prostatic hyperplasia underwent transperineal ultrasonographic evaluation of prostatic size and calculation of prostatic volume. In 10 patients transabdominal prostatic ultrasonography was also performed and the findings compared with those of transperineal examination. The estimated prostatic volume measured by transperineal ultrasonography was compared to the actual weight of the surgically removed gland. The correlation coefficient was 0.89 (P less than 0.0001). The transperineal and transabdominal ultrasonographic estimated volumes were also compared. The correlation coefficient was 0.92 (P less than 0.0001). No pain or discomfort were reported by the patients. Transperineal ultrasonography appears to be an accurate, fast and easy method to evaluate prostatic volume.

Humans↗
PubMed1991

DNA methylation and expression of the genes coding for lactate dehydrogenases A and C during rodent spermatogenesis.

The testis chromatin undergoes profound structural alterations and functional changes during spermatogenesis. Changes in DNA methylation have been correlated with gene expression in a number of systems, but the relationship between methylation and gene expression for testicular genes is unclear. To address this question, DNA methylation patterns and mRNA expression for a somatic form of lactate dehydrogenase (LDH), LDH-A, were compared with those of the testis-specific form, LDH-C, in preparations from testes of prepubertal and sexually mature mice, from isolated testicular cells, and from somatic tissues. At specific sites, LDH-A was less methylated in adult testis than in spleen DNA; the decreased methylation in the testicular DNA occurred as early as type A spermatogonia. In contrast, DNA methylation patterns for LDH-C did not differ between spleen and testis DNAs. In Northern blots, the levels of LDH-A transcripts were low in total testis RNA obtained from 6-12-day-old mice, and in type A and B spermatogonia from 8-day-old mice. LDH-A mRNA levels increased gradually in testes from 16-45-day-old mice. LDH-C transcripts were first detectable in the testes of 12-day-old mice and increased as spermatogenesis proceeded. Both LDH-A and LDH-C mRNA levels were low in preleptotene spermatocytes and leptotene/zygotene spermatocytes and increased substantially in pachytene spermatocytes and round spermatids. Reduced levels of LDH-A and LDH-C mRNAs were found in the residual bodies/cytoplasts fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hepatitis B and human immunodeficiency virus infection in street youths in Toronto, Canada.

Hepatitis B and human immunodeficiency virus are transmitted by venereal contact or by the sharing of used needles during drug use. A questionnaire was administered to street youths admitting to prostitution and to a group denying prostitution, as well as to sexually active adolescents who lived with their family and were attending an adolescent medical clinic. The age, gender, race, number of sexual partners, condom use, illicit drug use, anal intercourse and admission to prostitution were recorded for each of the subjects. Serology was obtained for hepatitis B markers and human immunodeficiency virus antibody. Multiple regression analysis was performed to determine the factors which might predict hepatitis B serologic status. A single subject, who admitted to prostitution, was found to be human immunodeficiency virus-seropositive. Seven of 43 (16%) admitted prostitutes compared with 1 of 44 (2%) other street youth and none of 27 controls demonstrated anti-hepatitis B surface antibodies. The higher rate of seropositivity in admitted prostitutes was statistically significant (P less than 0.0097). Two seropositive prostitutes had IgM hepatitis B core antibody suggesting recent infection. Two factors, number of partners (P less than 0.0007) and practice of anal intercourse (P less than 0.05), were identified in the multiple regression analysis as predictive of seropositivity. Thus adolescents who live on the street are at increased risk for becoming infected with hepatitis B virus. The difficulty in ensuring vaccine coverage in this population would support calls for including hepatitis B vaccination as part of childhood immunization.

Adolescent↗