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Biomedical subjects

E Goldberg

Publications and source records attributed to E Goldberg.

At least 55 records · Page 3Linked to original sources

Assessment of brain function in adolescent anorexia nervosa before and after weight gain.

This study assessed brain function in 20 adolescent females with anorexia nervosa (AN) and 20 controls using event-related potentials (ERPs) and a battery of neuropsychological tests. In the AN group, N4 latencies for a nonverbal memory task were significantly longer than for a verbal task, and P3 latencies for the verbal task were significantly longer among anorexics as compared to controls. On the nonverbal task, the AN group failed to show a right > left hemispheric asymmetry for P3 amplitudes which was observed for controls. These group differences for P3 latency and amplitude were particularly pronounced in the central-parietal region of the head. Body Mass Index (BMI) in the anorexic group significantly predicted N4 amplitudes for the verbal task in the left hemisphere and P3 amplitudes for the nonverbal task in the right hemisphere. The two groups did not differ on any of the tests used to assess neuropsychological functioning. Eight nutritionally recovered patients and their matched controls were retested using the same procedures. Anorexics showed larger P3 amplitudes for the verbal as compared to the nonverbal task at follow-up. These findings provide evidence for localized brain dysfunction in anorexia nervosa that only partially normalizes with weight gain.

Adolescent↗

Isolation and characterization of a molecular chaperone, gp57A, of bacteriophage T4.

A molecular chaperone of bacteriophage T4, gp57A, which facilitates the formation of the long and short tail fibers, was isolated and characterized by peptide analysis, sedimentation equilibrium, and circular dichroism (CD). Sequence analysis confirmed the predicted sequence of 79 amino acids from the nucleotide sequence of the gene with the N-terminal methionine removed. The result led to the conclusion that the apparent smaller molecular weight of 6,000 from Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the expected molecular weight of 8,710 was due to its abnormal electrophoretic behavior instead of cleavage or processing of the gene product. Estimation of the secondary structure from far-UV CD indicated a 94% alpha-helix content, which was in accord with the prediction from the primary structure. A sedimentation equilibrium study, on the other hand, revealed that gp57A assumes a tetrameric subunit structure.

Amino Acid Sequence↗

Cloning, sequencing, and characterization of LDH-C4 from a fox testis cDNA library.

A full-length cDNA encoding the sperm-specific enzyme lactate dehydrogenase-C4 was isolated from a fox testis cDNA expression library and sequenced. The deduced translated protein sequence was shown to be 86% identical to that of human LDH-C4. In the fox testis, mRNA encoding LDH-C4 was first detected in pachytene spermatocytes. The LDH-C4 protein monomer was identified in Western blots of sperm membrane extracts as having a molecular weight of approximately 35,000, consistent with the monomeric size of this subunit previously identified in sperm from other species. The LDH-C4 protein is localized on the sperm plasma membrane overlying the principal piece of the tail. Based on the available sequence data, we were able to identify an epitope within the N-terminal region of the LDH-C4 amino-acid sequence which when administered to female foxes is antigenic and produces antibodies capable of recognizing the native protein.

Amino Acid Sequence↗

A dual-function palindromic sequence regulates testis-specific transcription of the mouse lactate dehydrogenase c gene in vitro.

The promoter of the mouse lactate dehydrogenase c (Ldh-c) gene was assayed in an in vitro transcription system. Of the nuclear extracts isolated from several mouse tissues, only testis supported transcription from a 710 Ldh-c promoter fragment. Mutation analysis indicated that a canonical TATA box and a 30-bp palindromic sequence are both required for promoter activity. Liver nuclear extract (LN) can reduce transcriptional activity significantly when added to testis nuclear extract (TN). Deletion of the 3' palindromic sequence resulted in a low level of transcriptional activity in LN. Competition with a double-stranded synthetic palindromic oligonucleotide inhibited transcription in TN and rescued a low level of transcription in LN. Our results strongly indicate that the palindromic sequence contains both a negative element for repression in somatic tissues and a positive element for activation of the Ldh-c gene in testis.

Animals↗

The CpG-rich promoter of human LDH-C is differentially methylated in expressing and nonexpressing tissues.

A comparison of nucleotide sequences of murine Ldh-a and Ldh-c genes and human LDH-A, LDH-B, and LDH-C reveals that mouse Ldh-c has lost the CpG "island" present in the genes for the somatic isozymes. However, the human LDH-C gene has a CpG-rich region of 230 bp surrounding its promoter. Endonuclease sensitivity coupled with polymerase chain reaction (PCR) demonstrate the presence of nine heavily methylated sites in this region in different somatic cells. The same sites are specifically hypomethylated in expressing tissues. 3' sites bordering the CpG-rich region appear to be methylated in both expressing and nonexpressing tissues. Furthermore, the methylated promoter forms a specific complex in vitro with a methyl-DNA binding protein. Evolutionary and functional implications of these observations are discussed.

Base Sequence↗

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↗

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↗

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↗

The Cognitive Bias Task and lateralized frontal lobe functions in males.

The Cognitive Bias Task (CBT) is a multiple-choice response selection paradigm characterized by inherent ambiguity. All items offer a range from extremely context-dependent to extremely context-invariant responses. Lateralized prefrontal lesions produce extreme, and opposite, response biases on CBT in right-handed males. Healthy control subjects perform in the middle range. Findings suggest a dynamic balance between two synergistic decision-making systems in the frontal lobes: context-dependent in the left hemisphere and context-invariant in the right. The robust lateralized effects, which are dependent on task ambiguity, are sensitive and specific to frontal dysfunction. CBT is discussed in comparison with the Wisconsin Card Sorting Test as a potential cognitive activation task for functional neuroimaging of the frontal lobes.

Adult↗

Total quality management of a medical residency.

Although many hospitals have begun the long and difficult process of adapting to the concepts of total quality management, few have reported efforts to apply total quality management to a medical residency. We report here the initial results of the Western Pennsylvania Hospital's efforts, as part of the hospital's conversion of its management structure to total quality management.

Educational Measurement↗

Posttranscriptional regulation of primate Ldhc mRNA by its AUUUA-like elements.

The Ldhc locus encodes the testis-specific isozyme of lactate dehydrogenase in mammals. In our efforts to understand the regulatory mechanisms involved in expression of Ldhc, we recognized the possibility that this gene could be post-transcriptionally regulated in certain species as the 3'-untranslated region (3'-UTR) of Ldhc in primates, but not rodents, contains a number of AU-rich motifs and is conserved. To determine whether the primate Ldhc mRNA is posttranscriptionally regulated, comparison of baboon and mouse Ldhc mRNA stability was made in a cell-free system. The results indicated that the baboon mRNA is labile, while that of mouse, which does not contain the AU-rich motifs, is highly stable. Consistent with these results, the steady state level of primate Ldhc was found to be 8 to 12 fold lower than that of the mouse. We show that in a transformed murine germ cell line, the human Ldhc mRNA is moderately unstable, and removal of its 3'-UTR leads to stabilization of the mRNA. Mutations disrupting the AU-rich motifs of human Ldhc result in stabilization of the mRNA in vitro. On the basis of these observations, we conclude that stability of the primate Ldhc transcript is regulated by dispersed AU-rich elements found in its 3'-UTR. Because AU-rich motifs similar to these are found in many mRNAs, these findings may have broad implications.

Animals↗

Clustering of six human 11p15 gene homologs within a 500-kb interval of proximal mouse chromosome 7.

Homologs of genes mapping to human chromosome 11p15 are located in three distinct, widely separated regions of mouse chromosome 7 (Mmu7). To date, six genes have been localized to the most proximal HSA11p15/Mmu7 homology region, including Ldh3 (encoding lactate dehydrogenase C), Ldh1 (lactate dehydrogenase A), Myod1 (myogenic differentiation factor-1), Tph (tryptophan hydroxylase), Saa1 (serum amyloid-A-1), and Kcnc1 (encoding a Shaw-type voltage-gated potassium channel). To define the overall size and organization of this region of Mmu7, we have established a long-range physical map including the murine Ldh1, Ldh3, Saa, Tph, Kcnc1, and Myod1 genes. Our results demonstrate that these six genes are physically clustered and are distributed throughout a 500-kb interval located just proximal of the pink-eyed dilution (p) locus. These data, together with recent mapping studies within the related region of HSA11p15, demonstrate that gene content and organization within this proximal homology segment have been highly conserved throughout evolution.

Animals↗

Immortalized germ cells undergo meiosis in vitro.

Establishing mammalian germ-cell lines capable of differentiation in vitro would greatly facilitate the study of gametogenesis and the meiotic process that is so fundamental for reproduction and the maintenance of genetic diversity of the species. We have established two germ-cell lines [GC-2spd(ts) and GC-3spc(ts)] by cotransfecting primary mouse testicular germ cells with the simian virus 40 large tumor antigen gene and the gene coding for a temperature-sensitive mutant of p53. Both cell lines express the germ cell-specific lactate dehydrogenase C4 isozyme and cytochrome ct isoform. At the permissive temperature of 37 degrees C, the GC-2spd(ts) line generates cells with a haploid DNA content and morphologic and biochemical features of round spermatids, including the appearance of an acrosomic granule. The identification of a flagellar axoneme when these cells are cultured at 32 degrees C further indicates that these cells correspond to the early spermatid stages of spermiogenesis.

Animals↗

Activity of peptidergic neurons in the amygdala during sexual behavior in the male rat.

The medial amygdaloid nucleus (AME) occupies a central position in the circuitry that organizes sexual behavior in the male rat. It receives a projection from olfactory structures that are activated by pheromonal cues indicating receptivity in the female and projects in turn to limbic and hypothalamic structures that are thought to organize aspects of coitus. Electrical stimulation of the AME elicits a behavioral state that is indistinguishable by several measures from the post-ejaculatory interval. We used chronic single-unit recording techniques to determine the behavioral conditions in which the AME is normally active. We found that the cells indeed fired selectively during the presence of a receptive female, but that the discharge considerably anticipated copulation in time. We propose that sexual behavior in the male rat is a reaction chain of fixed action patterns, each one acting as a releaser for the next. The AME mediates an early event in the reaction chain, namely recognition of the receptive female, but electrical activation of the AME causes the reaction chain to proceed to its culminating behavior, the post-ejaculatory interval.

Amygdala↗