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Biomedical subjects

D Goldman

Publications and source records attributed to D Goldman.

At least 307 records · Page 17Linked to original sources
PubMed1984

Effect of supplemental vitamin A on the healing of colon anastomosis.

The effect of dietary supplementation with vitamin A on the healing of colon anastomoses was studied. Fifty adult male Sprague-Dawley rats were divided into two groups: (1) rats fed a standard chow which contains the equivalent of about 15 IU vitamin A/g diet; (2) rats fed the chow supplemented with an additional 150 IU vitamin A/g diet. Rats were prefed for 5 days; on Day 6 under ether anesthesia the colon was divided 1-in. distal to the ileocecal junction and then reanastomosed. The rats were maintained on the above diets for 5 days and killed on the sixth postoperative day with ether and the segment of colon containing the anastomosis was resected. In 15 rats of each group, the breaking strength of the anastomosis was measured. In the remaining 10 rats of each group, the bursting strength of the anastomotic site and a segment of normal distal colon was measured. Samples of colon from the anastomotic site and the normal segment were analyzed for hydroxyproline. There was a significant decrease in hydroxyproline content at the anastomotic site when compared to the normal distal colon segment in each group of rats (P less than 0.01). The hydroxyproline content of both normal colon and the anastomotic site was significantly higher in the vitamin A-supplemented rats than in the control diet rats (P less than 0.01). There was also a significant increase in bursting strength in the vitamin A-supplemented rats both of the anastomotic site (P less than 0.01) and of the normal colon segment (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Maternal transmission in Huntington's disease.

The effect of maternal transmission on age at onset of Huntington's disease (HD) was examined in 100 unrelated pedigrees. The age at which abnormal movement disorder first appeared could be estimated in 238 patients. More than twice as many of the late-onset cases (age 50 or later) inherited the HD gene from an affected mother than from an affected father. Affected offspring of late-onset females also had late-onset disease while those of late-onset males had significantly earlier ages of onset. This pattern of maternal inheritance suggests a model where the late-onset form of HD is related to a maternally transmitted factor such as the mitochondrion and its genome.

Adult↗
PubMed1983

Clinical research in neuropsychiatry.

This paper presents the thesis that rapidly developing areas of knowledge in neuroscience will rekindle interest in neuropsychiatry, and increase scientific and clinical interaction between psychiatrists and neurologists in teaching hospitals. A neuropsychiatric clinical research unit at the National Institute of Mental Health is described. Examples of research conducted on the unit illustrate areas of biological science that are likely to increase the interface between psychiatry and neurology. Hopefully, the explosion of knowledge in the basic neurosciences in the last decade will be followed in this decade by clinical research of increasing specificity and sophistication of central nervous system disorders.

Brain↗
PubMed1983

Sensation seeking, augmenting-reducing, and absolute auditory threshold: a strength-of-the-nervous-system perspective.

The following measures were obtained from 42 student volunteers: the General and the Disinhibition subscales of the Sensation Seeking Scale (Form IV), the Reducer-Augmenter Scale, and the Absolute Auditory Threshold. General sensation seeking correlated significantly with the Reducer-Augmenter Scale, r(40) = .59, p less than .001, and the Absolute Auditory Threshold, r(40) = .45, p less than .005. Both results proved general across sex. These findings, that high-sensation seekers tend to be reducers and to lack sensitivity to weak stimulation, were interpreted as supporting strength-of-the-nervous-system theory more than the formulation of Zuckerman and his associates.

Adolescent↗
PubMed1983

Protein variations associated with in vitro aging of human fibroblasts and quantitative limits on the error catastrophe hypothesis.

Two-dimensional electrophoresis was used to examine protein alterations associated with in vitro cellular aging. Patterns of cellular proteins from early and late passage human fibroblasts of two strains (normal and trisomy 21) were analyzed in silver-stained gels and autoradiograms with computerized microdensitometry. Four proteins were significantly altered in density in both cell strains. In late passage cells, these proteins were from 6 to 66% the density in early passage cells. The error catastrophe hypothesis predicts that random amino acid substitutions accumulate with cellular aging. No new proteins or satellite spots due to such substitutions, however, were detected in late passage cells. An upper bound of 2.5% was set by high resolution densitometry for the fraction of abnormal protein that could be present but undetected by these methods.

Aging↗
PubMed1983

Human lymphocyte polymorphisms detected by quantitative two-dimensional electrophoresis.

A survey of 186 soluble lymphocyte proteins for genetic polymorphism was carried out utilizing two-dimensional electrophoresis of 14C-labeled phytohemagglutinin (PHA)-stimulated human lymphocyte proteins. Nineteen of these proteins exhibited positional variation consistent with independent genetic polymorphism in a primary sample of 28 individuals. Each of these polymorphisms was characterized by quantitative gene-dosage dependence insofar as the heterozygous phenotype expressed approximately 50% of each allelic gene product as was seen in homozygotes. Patterns observed were also identical in monozygotic twins, replicate samples, and replicate gels. The three expected phenotypes (two homozygotes and a heterozygote) were observed in each of 10 of these polymorphisms while the remaining nine had one of the homozygous classes absent. The presence of the three phenotypes, the demonstration of gene-dosage dependence, and our own and previous pedigree analysis of certain of these polymorphisms supports the genetic basis of these variants. Based on this data, the frequency of polymorphic loci for man is: P = 19/186 = .102, and the average heterozygosity is .024. This estimate is approximately 1/3 to 1/2 the rate of polymorphism previously estimated for man in other studies using one-dimensional electrophoresis of isozyme loci. The newly described polymorphisms and others which should be detectable in larger protein surveys with two-dimensional electrophoresis hold promise as genetic markers of the human genome for use in gene mapping and pedigree analyses.

Autoradiography↗
PubMed1983

Mapping and quantitation of proteins from discrete nuclei and other areas of the rat brain by two-dimensional gel electrophoresis.

A map of the location and relative concentration of a number of different proteins present in 25 distinct neuroanatomical regions of the male rat brain has been established utilizing two-dimensional polyacrylamide gel electrophoresis. The regions examined include cortical areas as well as nuclei from the hypothalamus, amygdala, thalamus, forebrain, and hindbrain. Tissue samples were obtained from each region of interest by microdissection. Proteins within these samples were first separated by charge using the technique of isoelectric focusing. In the second dimension, proteins were separated by mass on polyacrylamide slab gels containing sodium dodecyl sulfate. Proteins were visualized using a highly sensitive silver stain and quantitated by computerized scanning densitometry. The results demonstrate that all proteins examined varied somewhat in concentration among the different brain regions. The majority (53%) of polypeptides selected for quantitation were found to vary less than 4-fold in concentration between the neuroanatomical areas with the lowest and highest detected amounts. In contrast, approximately 10% of the proteins examined varied widely in the quantity measured in each brain region, with concentration values ranging more than 10-fold between the regions with the lowest and highest detected amounts. This atlas is a first attempt at systematically classifying the mass, charge, and relative concentration of proteins present in a variety of regions of the rat brain. The system presented here will serve as a basis for future studies in this area.

Animals↗
PubMed1982

Changes in gene expression accompanying chemically-induced malignant transformation of human fibroblasts.

The modulation of gene expression accompanying neoplastic transformation has been assessed by computerized microdensitometry or autoradiographic patterns of [35S]methionine labeled polypeptides separated by two-dimensional polyacrylamide gel electrophoresis. Nearly 1000 polypeptide species of parent diploid human fibroblasts (KD strain) and clonally-derived malignant fibroblasts (HUT-14 strain) were compared. HUT-14 fibroblasts express a mutation in one of the two functional beta-actin genes and possess properties that distinguish them as neoplastic cells. Of the 700 more abundant polypeptides measured, 13 were lost and 14 were gained following this neoplastic transformation. It is estimated that less than or equal to 2% of the genes expressing abundant polypeptides were either activated or shut off, but at least 32% were modulated quantitatively as a consequence of this neoplastic transformation. Classes of "highly variable" and "marginally variable" polypeptides were assigned. Among the "highly variable" polypeptides, two related species barely detectable in KD parental cells were synthesized at a 25-31-fold higher rate in the transformed cells, and the cell-associated and extracellular matrix forms of fibronectin were each diminished by greater than 90%. Principles emerging from this study may form a basis for interpretation of the role of individual genes in the expression of neoplastic characteristics of HUT-14 cells.

Autoradiography↗
PubMed1982

Lymphocyte proteins in Huntington's disease: quantitative analysis by use of two-dimensional electrophoresis and computerized densitometry.

We used quantitative two-dimensional electrophoresis to study lymphocyte proteins in Hungtington's disease. Three hundred and six polypeptides from 14C-labeled, phytohemagglutinin-stimulated lymphocytes were measured for variation in relative spot density and 186 for variation in spot position by use of a computer program requiring operator interaction. Each polypeptide was measured in a total of 30 electrophoretograms from 28 individuals, including 13 with Huntington's disease, 2 at risk for it, and 13 controls. The study included two sets of identical twins and, as neurological controls, individuals with neurofibromatosis, Alzheimer's disease, or Shy-Drager syndrome. Seven protein polymorphisms were identified among the 186 most dense polypeptides of each gel, corresponding to a minimum average heterozygosity of 1.4%. Stringent criteria were used to define polymorphic proteins, including observation of at least one individual with each of two homozygous phenotypes and one with the heterozygous phenotype, demonstration of the expected gene dosage relationship by quantitative densitometry, consistency with genetic relationships, and reproducibility. One polymorphic protein showed three electrophoretically variant alleles. Our identification of seven polymorphisms among the 186 proteins measured on a single electrophoretogram illustrates the potential of this technique for performing linkage analysis in diseases of genetic origin. However, we observed no quantitative or positional protein variations that were characteristic of (i.e. specific for) Huntington's disease.

Blood Proteins↗
PubMed1982

Quantitative two-dimensional protein electrophoresis for studies of inborn errors of metabolism.

High-resolution electrophoretic methods and sensitive protein-detection techniques permit new approaches to understanding and diagnosis of the inborn errors of metabolism. These approaches encompass: the search for protein alterations that represent primary mutations effects; observation of alterations in protein patterns due to secondary effects, as might occur in major metabolic pathway abnormalities; and identification of protein polymorphisms that are genetically linked to an inborn metabolic disease. With the aid of computer analysis of the electrophoretograms, all three approaches are being developed. Protein density and position are evaluated with an interactive computer program that requires that gel polypeptides be indexed by the investigator. Proteins on the gels are made visible with an inexpensive, rapid silver stain, which can be used quantitatively. The Lesch-Nyhan syndrome, one of a few neuropsychiatric diseases for which the molecular defect is known, was chosen for study with these techniques. Four hundred proteins were analyzed for positional or quantitative variation. Eleven significant (2p less than 0.01) quantitative differences were found in autoradiograms from gels of phytohemagglutinin-stimulated lymphocytes. Specific patterns of polypeptide variation are now being sought in an expanded clinical study primarily focusing on Huntington's disease. Large studies are required to establish the specificity of observed alterations. As the number and variety of analyses increase, a correlative catalog of molecular variation and polymorphism will be generated.

Autoradiography↗
PubMed1982

Actin mutations in a human fibroblast model for carcinogenesis.

We assessed the modulation of gene expression accompanying neoplastic transformation by computerized microdensitometry of autoradiographic patterns of [35S]-methionine-labeled polypeptides separated by two-dimensional polyacrylamide gel electrophoresis. Nearly 1000 polypeptide species of parent diploid human fibroblasts (KD strain) and clonally-derived malignant fibroblasts (HUT-14 strain) were compared. We found that the neoplastic HUT-14 fibroblasts express a mutation in one of the two functional beta-actin genes. In addition, of the 700 more-abundant polypeptides measured, 13 were lost and 14 new ones gained after this neoplastic transformation. We estimate that although 2% of fewer of the genes expressing abundant polypeptides were either activated or shut off, at least 32% were modulated quantitatively. A substrain of HUT-14--HUT-14T--shows increased tumorigenicity, producing larger, faster-growing fibrosarcomas in the nude mouse than does the present parent HUT-14 strain, and with fewer inoculated cells. This increase in tumorigenicity is accompanied by three subsequent changes in the mutant beta-actin polypeptide expression. A more variant mutant actin species is synthesized in HUT-14T, which differs from the original mutant polypeptide by (i) one additional negative net charge, (ii) a short half-life in the cell, (iii) a greatly diminished ability to incorporate into the detergent-resistant cytoskeleton, (iv) a decrease in affinity for deoxyribonuclease I (EC 3.1.21.1), and (v) a faster rate of synthesis. Our results suggest that a second-site mutation in the mutant beta-actin of HUT-14 was selected for during a subcloning step in the presence of 6-thioguanine before derivation of the HUT-14T substrain. This apparent mutation and two subsequent defective beta-actin expressions are accompanied by incremental increases of malignant potential.

Actins↗