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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 433 records · Page 24Linked to original sources
PubMed1986

Somatomedin inhibitors from diabetic rat serum alter growth and development of mouse embryos in culture.

Offspring of diabetic humans and laboratory animals have been shown to have a higher incidence of congenital malformations with attendant growth retardation. These defects have been attributed to alterations in the intrauterine environment and specifically to changes in maternal serum factors, e.g., glucose and ketone bodies. Our investigation examines the potential teratogenicity of a low-molecular-weight (940) serum fraction with demonstrated somatomedin inhibitory activity isolated by column chromatography from streptozocin-induced diabetic rats. Mouse embryos were exposed to control or the inhibitor fraction at concentrations of 0.25-0.6% vol/vol (0.9-3.0 micrograms protein/ml culture medium) in whole embryo culture and evaluated for the presence of malformations and growth retardation. Embryos exposed to inhibitor during the period of neurulation (3-5 somites) exhibited neural tube and craniofacial defects, whereas those exposed during early limb bud stages (18-19 somites) exhibited abnormalities of the forebrain and face. In addition, both stages were growth retarded. Control fractions produced no abnormalities. These results demonstrate a potential role for somatomedin inhibitors in diabetic embryopathy and suggest that factors other than hyperglycemia and hyperketonemia may contribute to the higher incidence of malformations among infants of diabetic mothers.

Animals↗
PubMed1986

When do metal complexes protect the biological system from superoxide toxicity and when do they enhance it?

Many copper and iron complexes can be reduced by O2- as well as by H2O2. According to the rates of reduction and the concentration of O2- and H2O2, the metal complexes may serve either as catalyst of O2- dismutation or as catalysts of the reaction between O2- and H2O2 to form OH. radical (Haber-Weiss reaction). Various factors which influence whether metal complexes protect the biological systems from superoxide toxicity or enhance it are discussed.

Chelating Agents↗
PubMed1986

A clinical study with brain brachytherapy for malignant gliomas.

A clinical trial with neutron brachytherapy for malignant glioma is now in progress at the University of Kentucky Medical Center. In the initial three year period, 32 patients entered the study. There were 24 males and eight females, and the peak incidence was seen in the seventh decade. All patients underwent surgical resection of tumor followed by Cf-252 implantation and external radiotherapy. The implantation procedure was well tolerated by the patients and demonstrated a short-term benefit in survival of patients who were able to complete planned radiotherapy. Older patients had less tolerance to radiotherapy. The evaluation of the beneficial effects of Cf-252 brachytherapy will require patients who are able to tolerate the whole course of therapy.

Adult↗
PubMed1986

Oncocytic adenoma of the parotid gland with psammoma bodies.

An unusual slow-growing tumor was found in the superficial lobe of the right parotid gland. It was multilobulated and encapsulated and consisted of sheets of epithelial oncocytes and minor foci of myoepithelium and ducts. Psammoma bodies were abundant. An antibody directed against keratin protein was localized in all tumor cells and in ductal but not acinar elements of adjacent parotid tissue. Ultrastructurally, the neoplastic cells proved to be ductal epithelial and myoepithelial oncocytes.

Adenoma↗
PubMed1985

Human alphoid family of tandemly repeated DNA. Sequence of cloned tetrameric fragments and analysis of familial divergence.

Three tetramers of the 170 base-pair monomer repeat unit of human centromeric DNA (alphoid DNA) have been cloned and sequenced. Adjacent subunits differed in sequence by 30 to 45%, while dimers varied by 13 to 20% whether adjacent or not. Divergence was distributed unevenly across the monomeric sequence, such that two highly conserved segments adjoined clusters of insertions/deletions. Divergence, calculated from the cloned sequences or measured in uncloned DNA by thermal destabilization of mismatched reassociated duplexes, was far greater than previously estimated for the total human alphoid family. The population of these repeats within the human genome was not uniformly diverged, however, since restriction subsets of alphoid DNA contained as little as one-tenth the overall level of divergence. This indicates a hierarchical or familial structure of the genomic repeat population. Using cloned probes, human alphoid DNA was shown to be highly methylated and transcriptionally inactive. These data, along with evidence of conserved segments and periodicities (dimeric and higher-order) overlying considerable sequence diversity, support a structural role for this DNA family.

Base Composition↗
PubMed1985

Methylation patterns in the gene for the alpha subunit of chorionic gonadotropin are inherited with variable fidelity in clonal lineages of human fibroblasts.

Cytosine methylation in DNA of an endogenous single-copy gene locus, the alpha-subunit of human chorionic gonadotropin (alpha-hCG), was assessed in a mass culture and individual clonal lineages of human diploid fibroblasts. Progressive hypomethylation at -CCGG- sites in this gene occurred during the replicative lifespan of the mass culture and was shown to arise randomly during clonal expansion. Thus, some clones and subclones lost -CCGG- methylation in the alpha-hCG gene region while others maintained essentially complete methylation. These data indicate significant interclonal variability in the fidelity with which DNA methylation is transmitted in an endogenous gene.

5-Methylcytosine↗
PubMed1985

Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts.

Extrachromosomal covalently closed circular DNA (cccDNA) was isolated from human diploid fibroblasts by alkaline denaturation/renaturation and CsCl-ethidium bromide isopycnic centrifugation. Probing across these gradient fractions showed a higher proportion of cccDNA sequences homologous to the interspersed highly repetitive Alu I and Kpn I sequences than to the human tandemly-repetitive Eco RI (alphoid) DNA. Cloning of these cccDNAs was then carried out following digestion with restriction endonucleases Hind III, Bam HI or Pst I, and ligation into plasmid pBR322. Many isolated recombinant clones were unstable as seen by a high rate of loss over four cycles of antibiotic selection, and frequent plasmid modifications including deletions adjoining the site of insertion. Of 107 cloned sequences which appeared relatively stable, i.e., survived four cycles of antibiotic selection without incurring detectable deletions, 28% and 11% showed homology to Alu I and Kpn I families, respectively, while 4% contained sequences homologous to both. In contrast, less than one percent hybridized to probes for tandemly-repetitive sequences, Eco RI and Satellite III. The average insert size of cloned cccDNA derived from human fibroblasts, 2.52 Kbp, was larger than previously reported for similar clones derived from genetically less stable permanent lines, which may reflect differences in the process of cccDNA generation.

Cell Line↗
PubMed1985

c-Ha-ras-1 proto-oncogene amplification and overexpression during the limited replicative life span of normal human fibroblasts.

The cellular proto-oncogene c-Ha-ras-1 undergoes up to 4-fold amplification during the limited replicative life span of normal human diploid fibroblasts in vitro. Levels of c-Ha-ras-1 messenger RNA and its p21 protein product are correspondingly elevated. Cellular proto-oncogene amplification and overexpression, although frequently associated with tumorigenesis, may thus occur during normal cellular growth.

Cell Cycle↗