Developmental expression of lactate dehydrogenase isozymes during spermatogenesis.
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Animals↗
Biomedical subjects
E Goldberg
Publications and source records attributed to E Goldberg.
Expression of the human lactate dehydrogenase-C gene in transgenic mice.
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Amino Acid Sequence↗
Immunogenicity of synthetic peptides corresponding to flexible and antibody-accessible segments of mouse lactate dehydrogenase (LDH)-C4.
The immunological properties of a panel of synthetic peptides that represent the most accessible and mobile segments of the lactate dehydrogenase (LDH)-C4 molecule were characterized. Peptides corresponding to mouse LDH-C4 amino acid sequences: 1-14b, 5-15, 49-58, 97-110, 211-220, 231-243, 274-286, 304-316, and 318-330 were synthesized and compared in terms of binding antibodies raised in rabbits against the intact protein. Six of these sequences were covalently coupled to diphtheria toxoid and used to immunize groups of rabbits. LDH-C4-specific antibodies were detectable in immune sera by enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation assays. The immunogenicity of the mouse LDH-C4 peptides in rabbits could be ranked in the following order: 5-15, 304-316 greater than 211-220, 274-286 greater than 49-58, 97-110. The immunological properties of these short synthetic peptides did not correlate with features of the mouse LDH-C4 structure except that the most active sequences appeared to be those that differed from the somatic isozymes to the greatest extent. These results have direct bearing on the selection of immunogenic LDH-C4 peptides for contraceptive vaccine studies in humans and non-human model systems.
Amino Acid Sequence↗
The neuropsychology of schizophrenic speech.
Recent interest in the biological basis of schizophrenia has led to a reexamination of many symptomatic aspects of the disorder in terms of brain-behavioral models. Schizophrenic speech disturbances have traditionally been described in terms of a model of acquired aphasia. We review some of the limitations of this model and provide an alternative model for the study of some characteristics of schizophrenic speech based on neuropsychological theories of frontal lobe dysfunction in schizophrenia. The emphasis is placed on the study of productive errors noted in schizophrenic speech, most notably verbal perseverations. In a study of errors observed during a sample of 15 schizophrenics performance on a confrontation naming test, we were able to reliably identify and classify hierarchic categories of verbal perseverations occurring at both semantic and phonemic levels. These perseverations constituted 20% of the total errors. We argue that these perseverations represent a special case of executive dysfunction resulting from a disturbance of language monitoring mechanisms. We examine the implications of these findings for a hypothesis of schizophrenic speech disturbances in terms of frontal lobe dysfunction and the developmental neuropathological processes involved in the illness.
Adult↗
Shifts in hemispheric advantage during familiarization with complex visual patterns.
Twenty females unfamiliar with kanji were given a recognition task involving tachistoscopic presentation of kanji to the right and left visual fields. Repeated exposure to these novel stimuli resulted in significantly increased competence at the task. To analyze different approaches to the task, subjects were divided into an initial left visual field advantage and an initial right visual field advantage group. Over the course of the experiment subjects in the initial left visual field advantage group shifted from a left to a right visual field advantage, showing both a linear trend and a quadratic trend, while the initial right visual field advantage group showed only a quadratic trend. The results are consistent with observations in other novel stimuli situations which have demonstrated a shift in hemispheric advantage from right to left with increased competence and which have demonstrated individual differences in the pattern of shifting hemispheric advantage.
Adult↗
A reticulo-frontal disconnection syndrome.
Persistent executive deficit, usually seen following prefrontal damage, is reported in a patient recovering from head trauma. Repeated neuroradidological examinations failed to reveal a lesion within the frontal lobes, but a circumscribed lesion in the ventral mesencephalic tegmentum was found. It is proposed that the observed syndrome was caused by damage to mesencephalic reticular nuclei and their projections into prefrontal cortex. The concept of a "reticulo-frontal disconnection syndrome" is introduced and its possible role in head trauma and schizophrenia discussed.
Adult↗
Gradiental approach to neocortical functional organization.
Examination of neuropsychological syndromes suggests strong congruence between neuroanatomical and functional neocortical metrics. Two cortical syndromes disrupt cognitively close functions if and only if their neuroanatomical territories are close. To capture this relationship, the concept of a cognitive gradient is introduced as a basic unit of macroscopic neocortical brain-behavioral analysis. A cognitive gradient is a continuous distribution of related functions along an axis defined at its extremes by a pair of sensory projection or motor areas. Cortical gradiental structure is viewed as a fundamental symmetric organization on which hemispheric elaborations are superimposed. The gradiental structure of the left hemisphere is presented in detail as an illustration of the concept. It is presumed that a similar set of elaborations can be uncovered for the right hemisphere. The gradiental model implies that at least from the macroscopic standpoint, functional neocortical organization is to a substantial degree continuous, interactive, and emergent, as opposed to mosaic, modular, and prededicated. It is proposed that a shift from latter to former properties signified a major development in the evolution of the brain. Thalamo-cortical integration may represent coexistence of evolutionally early and recent principles of cerebral organization.
Agnosia↗
Regional localization of the sperm-specific lactate dehydrogenase, LDHC, gene on human chromosome 11.
A cDNA clone complementary to the mRNA encoding the sperm-specific lactate dehydrogenase, LDHC, has been used to map the LDHC locus to the short arm of human chromosome 11. In situ hybridization data and analysis of mouse/human somatic cell hybrids carrying deletions of human chromosome 11 suggest that the gene is localized at p15.3-p15.5 close to the LDHA gene.
Animals↗
High-dose naloxone in tardive dyskinesia.
Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed.
Adult↗
Energy expenditure and body composition in patients with anorexia nervosa.
Blood biochemistry, body composition, and resting energy expenditure were studied in 25 patients with anorexia nervosa admitted to hospital during a period of 18 months. The patients' ages ranged from 12.9 to 17.2 years, and the abnormal feeding history from 3 to 12 months. Blood chemistry values were in the normal range, but fat body mass and lean body mass were reduced and extracellular water volume was expanded beyond normal values. Resting energy expenditure was reduced to 49% to 91% of values predicted by the Harris-Benedict equations. Substrate use after overnight fast indicated an abnormally high use of carbohydrates. Significant correlations were found between extracellular water volume and triceps skin-fold thickness, mid-arm muscle circumference and lean body mass, and substrate use and weight loss as a percentage of initial weight. We suggest that these simple anthropometric measurements can be used to assess and monitor the refeeding of patients with anorexia nervosa.
Adolescent↗
Changes in body composition during refeeding of patients with anorexia nervosa.
Changes in body composition were studied in 13 girls with anorexia nervosa before and during 2 months of refeeding. Fat body mass and fat-free body mass were derived from skin-fold measurements. Total body potassium was measured by whole body counter, and intracellular water was calculated from it. Extracellular water was measured as the bromide space after oral bromide administration. A gradual increase was noted in weight, fat body mass, fat-free body mass, and total body potassium during refeeding. Extracellular water was expanded on admission and increased in all patients in the first weeks of treatment; later it fell to normal. Most of the changes in fat-free body mass over the first weeks of refeeding could be accounted for by an expansion in extracellular water. Particular care must therefore be taken with fluid balance during the first few weeks of refeeding.
Adipose Tissue↗
Localization of a highly divergent mammalian testicular alpha tubulin that is not detectable in brain.
Sequence analysis of a mouse testicular alpha-tubulin partial cDNA, pRD alpha TT1, reveals an isotype that differs from both the somatic and the predominant testicular alpha tubulins at approximately 30% of the 212 amino acid residues determined. Although this mouse testicular cDNA retains the highly conserved sequence, Glu-Gly-Glu-Glu, found in the carboxyl termini of many alpha tubulins, the protein extends substantially beyond this sequence and does not terminate with a C-terminal tyrosine. Using rabbit antiserum prepared to a novel synthetic peptide predicted from this mouse testis alpha-tubulin cDNA, we have have detected by immunoblot and indirect immunofluorescence an antigenic epitope present in testicular alpha tubulin that is not detectable in brain alpha tubulins. We find that the antiserum specifically binds to the manchettes and meiotic spindles of the mouse testis but not with neural fibers or tubulin extracts of the adult mouse brain. These results demonstrate that at least one of the multiple alpha-tubulin isotypes of the mammalian testis is expressed and used in male germ cells but not in the brain.
Amino Acid Sequence↗
Characterization of the antigenic sites on the refined 3-A resolution structure of mouse testicular lactate dehydrogenase C4.
The atomic structure of mouse testicular apolactate dehydrogenase C4 has been refined to 3.0-A resolution yielding a final crystallographic R-factor of 0.256. Comparison with the refined structure of dogfish apolactate dehydrogenase A4 shows that equivalent secondary structure elements are essentially in the same position relative to the molecular 2-fold axes, except for the helices alpha D, alpha E, and alpha 2G in the vicinity of the active center, and the carboxyl-terminal helix alpha H. The positions of antigenic peptides correlate best with surface accessibilities of the monomer rather than of the full tetrameric molecule.
Amino Acid Sequence↗
Use of unresolved transition arrays for plasma diagnostics.
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Journal Article↗
Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA.
From the data presented in this report, the human LDHC gene locus is assigned to chromosome 11. Three genes determine lactate dehydrogenase (LDH) in man. LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes. A human LDHC cDNA clone was used as a probe to analyze genomic DNA from rodent/human somatic cell hybrids. The pattern of bands with LDHC hybridization is easily distinguished from the pattern detected by LDHA hybridization, and the LDHC probe is specific for testis mRNA. The structural gene LDHA has been previously assigned to human chromosome 11, while LDHB maps to chromosome 12. Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man. However, the data presented in this paper show conclusively that LDHC is syntenic with LDHA on human chromosome 11. The terminology for LDH genes LDHA, LDHB, and LDHC is equivalent to Ldh1, Ldh2, and Ldh3, respectively.
Animals↗
Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence.
The sequence and structure of human testis-specific L-lactate dehydrogenase [LDHC4, LDHX; (L)-lactate: NAD+ oxidoreductase, EC 1.1.1.27] has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme. From the deduced amino acid sequence, human LDHC4 is as different from rodent LDHC4 (73% homology) as it is from human LDHA4 (76% homology) and porcine LDHB4 (68% homology). Subunit homologies are consistent with the conclusion that the LDHC gene arose by at least two independent duplication events. Furthermore, the lower degree of homology between mouse and human LDHC4 and the appearance of this isozyme late in evolution suggests a higher rate of mutation in the mammalian LDHC genes than in the LDHA and -B genes. Comparison of exposed amino acid residues of discrete antigenic determinants of mouse and human LDHC4 reveals significant differences. Knowledge of the human LDHC4 sequence will help design human-specific peptides useful in the development of a contraceptive vaccine.
Amino Acid Sequence↗
Evaluation of the vasodilator vs inotropic effect of milrinone using an animal model of left ventricular failure: reversal of disopyramide depression of the myocardium with milrinone.
Milrinone (M) has been shown to improve left ventricular (LV) performance in animal and human studies. M has strong vasodilator action, and whether increased LV performance is due primarily to vasodilation or to a direct positive inotropic effect is unclear. Ten mongrel dogs were studied. Disopyramide caused a significant and sustained decrease in LV function and was a good model for myocardial depression. At equal reduction in systemic vascular resistance (SVR), M reversed this LV depression to a significantly greater degree than nitroprusside (NP) did. At equal levels of vasodilation, M produced significantly greater improvement in indices of LV function than NP did in our model of disopyramide-induced LV failure. This suggest that its effect on LV function is not due entirely to afterload reduction, or to reflex sympathetic stimulation, but has a substantial component of direct inotropic stimulation. This study also demonstrated a reversal of disopyramide-induced LV dysfunction by M, which may be clinically useful since, as in many antiarrhythmics, myocardial depression may be a limiting factor in its use.
Animals↗
Motor perseverations in schizophrenia.
Classical neuropsychological descriptions of prefrontal syndromes emphasize qualitative, productive symptoms, among which the phenomena known as motor perseverations occupy a central position. The now popular assertions that selective prefrontal dysfunction characterizes chronic schizophrenia would be more compelling if such productive symptoms could be reliably elicited in these patients. The present study demonstrated the presence of conspicuous motor perseverations in a sample of chronic schizophrenic inpatients, elicited using techniques that were developed and validated in studies of patients with known frontal lobe lesions. The observedperseverations closely resemble, both in severity and typology, those documented in cases with focal damage to prefrontal cortex. The findings support the contention that prefrontal dysfunction exists in chronic schizophrenia.
Journal Article↗