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Biomedical subjects

R A Kramer

Publications and source records attributed to R A Kramer.

At least 73 records · Page 4Linked to original sources
PubMed1985

Effects of buthionine sulfoximine on the nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU).

Administration of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1 1-nitrosourea (MeCCNU; 50-500 mg/kg) to male F344 rats caused a time- and dose-related decrease of glutathione (GSH) preferentially in the liver, but not in the kidney. A 500-mg/kg dose of MeCCNU decreased liver, lung and kidney GSH by 69, 15 and 3%, respectively, 2 hr after dosing. However, MeCCNU had no effect on the ratio of GSH/oxidized GSH or on GSH reductase activity in any tissue tested. A single i.p. dose of DL-buthionine-SR-sulfoximine, an inhibitor of GSH biosynthesis, caused tissue GSH levels to decrease at a rate which reflected the biological half-life of GSH in the respective organs. The T 1/2 for GSH in kidney, liver and lung was found to be 1.5, 5 and 9 hr, respectively. MeCCNU administered s.c. to DL-buthionine-SR-sulfoximine-pretreated rats resulted in a depletion of hepatic and renal GSH concentrations which was additive to the effects of either of these treatments alone. DL-Buthionine-SR-sulfoximine also markedly increased the nephrotoxicity of MeCCNU and resulted in a hepatotoxicity not ordinarily seen when MeCCNU was administered alone. These results suggest that a reactive electrophilic intermediate may be involved in the mechanism of MeCCNU nephrotoxicity. Moreover, that renal GSH may play a protective role against MeCCNU-induced nephrotoxicity.

Animals↗
PubMed1984

Regulated expression of a human interferon gene in yeast: control by phosphate concentration or temperature.

The promoter/regulator region from the yeast repressible acid phosphatase gene was used to construct a vector for the regulated expression of cloned genes in yeast. The gene for human leukocyte interferon was inserted into this vector. Yeast cells transformed with the resulting plasmid produced significant amounts of interferon only when grown in medium lacking inorganic phosphate. Mutants in two acid phosphatase regulatory genes (coding for a defective repressor and a temperature-sensitive positive regulator) were used to develop a yeast strain that grew well at a high temperature (35 degrees C) but produced interferon only at a low temperature (23 degrees C), independent of phosphate concentration.

Acid Phosphatase↗
PubMed1983

Modulation of chromatin structure associated with derepression of the acid phosphatase gene of Saccharomyces cerevisiae.

We have analyzed the chromatin structure of a phosphate-repressible acid phosphatase gene (PHO5) within yeast nuclei. Under derepressed conditions (low Pi media), the gene is much more sensitive to either DNAse I or micrococcal nuclease digestion than is the repressed gene. We have mapped DNase I hypersensitive sites unique to the active gene near the 5'-end of the acid phosphatase mRNA and within a region presumed to function in the regulation of the gene by Pi. Although the gene is packaged into regularly spaced nucleosomes, no detectable phase relationship exists between nucleosomes and DNA sequence under derepressed conditions, whereas in the repressed state the nucleosomes occur in one predominant phase. These results demonstrate reversible changes in the chromatin structure of a eukaryotic gene system that directly correlate with the functional state of the gene.

Acid Phosphatase↗
PubMed1983

Transcriptional mapping of two yeast genes coding for glyceraldehyde 3-phosphate dehydrogenase isolated by sequence homology with the chicken gene.

Homology between the coding regions of the chicken and yeast glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes was directly demonstrated by the hybridization of a cDNA clone coding for GAPDH in the chicken with EcoRI-digested yeast DNA. A yeast EcoRI fragment library in bacteriophage lambda was screened using the chicken cDNA plasmid as probe, and two recombinant phages were isolated, each one containing a different GAPDH gene. The initiation and termination sites for the GAPDH mRNA were localized for the two different GAPDH genes and compared to those of other yeast genes. Measurements of the relative mRNA levels for the two genes show that both genes are transcribed at about the same level when yeasts are grown on glucose media.

Animals↗
PubMed1983

RNA and homology mapping of two DNA fragments with repressible acid phosphatase genes from Saccharomyces cerevisiae.

Two EcoRI restriction fragments carrying Saccharomyces cerevisiae repressible acid phosphatase genes were analyzed. Transcripts were mapped by restriction endonuclease cleavage of glyoxal-stabilized R-loops and by gel blot hybridizations to cDNA. Homology between the two fragments was examined by gel blots and heteroduplex analysis. Each fragment carried a region of about 1.5 kilobases that coded for a repressible acid phosphatase, and these regions showed homology to one another. In addition, one fragment carried a second region of somewhat lower homology that probably codes for the so-called constitutive acid phosphatase.

Acid Phosphatase↗
PubMed1983

Comparative analysis of the 5'-end regions of two repressible acid phosphatase genes in Saccharomyces cerevisiae.

The nucleotide sequence of 5'-noncoding and N-terminal coding regions of two coordinately regulated, repressible acid phosphatase genes from Saccharomyces cerevisiae were determined. These unlinked genes encode different, but structurally related polypeptides of molecular weights 60,000 and 56,000. The DNA sequences of their 5'-flanking regions show stretches of extensive homology upstream of, and surrounding, a "TATA" sequence and in a region in which heterogeneous 5' ends of the p60 mRNA were mapped. The predicted amino acid sequences encoded by the N-terminal regions of both genes were confirmed by determination of the amino acid sequence of the native exocellular acid phosphatase and the partial sequence of the presecretory polypeptide synthesized in a cell-free protein synthesizing system. The N-terminal region of the p60 polypeptide was shown to be characterized by a hydrophobic 17-amino acid signal polypeptide which is absent in the native exocellular protein and thought to be necessary for acid phosphatase secretion.

Acid Phosphatase↗
PubMed1983

Nephrotoxicity of semustine.

Semustine is an investigational cancer chemotherapeutic agent in widespread use. This agent has now been documented to produce nephrotoxicity and renal failure with long-term administration. We collected 29 cases of semustine nephrotoxicity from the literature and six unpublished cases brought to the attention of the National Cancer Institute. Using these 35 cases as a data base, we have analyzed the incidence, dose and treatment duration relationships, clinical and histologic manifestations, and clinical course of semustine nephrotoxicity. In addition, we discuss the possible mechanisms of this nephrotoxicity based upon ongoing laboratory work. We conclude that there is a high risk of severe nephrotoxicity from semustine when the cumulative dose exceeds 1200 mg/m2 and that there may be considerable delay in onset of the renal dysfunction.

Animals↗
PubMed1983

Nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) in the Fischer 344 rat.

A single s.c. injection of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU; 20-140 mg/kg) resulted in rapid decreases in renal function as well as leading to a chronic progressive nephropathy in male Fischer 344 rats. Disturbances in renal function were proportional to the dose of MeCCNU administered and included impaired tubular transport of p-aminohippuric acid, a decrease in urine concentrating ability, an increase in urine pH, polyuria, proteinuria and enzymuria. The tubular accumulation of p-aminohippuric acid by kidney slices was decreased as early as 1 hr after MeCCNU administration (100 mg/kg), was maximal within 12 hr and remained depressed for at least 28 days after a single injection of either 40 or 80 mg/kg. Changes in other measures of renal function (increased lactate dehydrogenase excretion, alkalinuria and decreased urine concentrating ability) were delayed from 1 to 6 days after MeCCNU administration and in some cases progressed in severity throughout the 28-day duration of the experiment. The delay between the first evidence of renal damage (decreased p-aminohippuric acid uptake) and the subsequent appearance of enzymuria, proteinuria, polyuria and alkalinuria appears to correspond to a similar delay between the initial insult and the eventual development of cellular necrosis and other histopathological changes. These results demonstrate that MeCCNU is a nephrotoxicant in rats and indicate that even a single acute dose may lead to chronic and irreversible effects on the kidney. The in vivo toxicity model defined herein appears to be an appropriate one for further study of the mechanism of nephrotoxicity of MeCCNU.

Animals↗
PubMed1981

Molecular cloning and comparative analyses of the genomes of simian sarcoma virus and its associated helper virus.

Closed circular viral DNA of simian sarcoma virus (SSV) and simian sarcoma-associated virus (SSAV) obtained from acutely infected dog cells was purified on preparative agarose gels, cleaved with EcoRI, and cloned in the phage lambda vector Charon 21A. The cloned 9-kilobase SSAV genome (B11) has the same restriction map as the bulk of the unintegrated linear SSAV DNA intermediate. Heteroduplex analysis between an SSV clone (lambda-C60) and an SSAV clone (lambda-B11) showed two substitution loops and one deletion loop. By using detailed restriction enzyme mapping and electron microscopic analysis, we showed that one of the substitution loops corresponds to an inversion of one of the two long terminal repeat units and adjacent cellular sequences in C60. The other substitution loop mapped close to the 3' long terminal repeat. At least part of this region was shown to contain SSV-specific sequences not shared by SSAV. The 1.9-kilobase deletion mapped at 3.5-5.5 kilobases of the linear SSAV genome, corresponding to most, if not all, of the pol gene.

Chromosome Inversion↗
PubMed1980

Restriction mapping of deletions in the nif region of the Klebsiella pneumoniae chromosome.

Chromosomal DNA restriction fragments carrying the nitrogen fixation (nif) and his genes of Klebsiella pneumoniae were identified in hybridization experiments using a plasmid derived from pRD1 as a radioactive probe. Restriction mapping of 26 genetically characterized chromosomal nif deletions provided a map showing the physical location of nif genes along the chromosome.

Base Sequence↗
PubMed1980

Isolation of yeast genes with mRNA levels controlled by phosphate concentration.

A library of DNA from the yeast, Saccharomyces cerevisiae, was constructed in phage lambda Charon 4 vector and then screened by differential plaque filter hybridization for genes induced by phosphate starvation. Two EcoRI fragments of 7.9 and 5.0 kilobase pairs that contained such genes were isolated. These cloned fragments may each carry one of the several copies of the genes for the repressible acid phosphatase of yeast. The fragments were use to examine mRNA levels of these genes in regulatory mutants of acid phosphatase.

Gene Expression Regulation↗
PubMed1979

Rupture of intracranial aneurysms during cerebral angiography: report of ten cases and review of the literautre.

Ten new cases of intracranial aneurysms that ruptured during cerebral angiography, obtained from four local hospitals and the practices of eight angiographers, are detailed. A review of the literature reveals 28 other well-documented cases. An analysis of this clinical material shows that internal carotid injections are not necessarily more dangerous than common carotid injections. Although critically ill patients are at higher risk and must be treated with caution, there is not enough evidence to warrant a delay in angiography to avoid rupture. The recent trend toward early angiography in cases of subarachnoid hemorrhage is reflected in the statistical analysis. A plea for meticulous angiographic technique is advanced.

Adult↗
PubMed1978

Therapeutic angiography. Its value to the surgical patient.

Standard angiographic techniques formerly used exclusively as diagnostic modalities have been modified to serve as definitive or adjunctive therapeutic measured. The techniques include transcatheter embolization; infusion of vasoactive drugs, chemotherapeutic agents and radioactive particles; tamponade of bleeding arteries and balloon catheters; extraction of vascular foreign bodies and retained biliary tract stones and transluminal arterial dilation. These techniques have been proved effective and safe when used judiciously.

Adult↗
PubMed1978

Detection of yeast ribosomal RNA sequences in E. coli infected with hybrid bacteriophage.

Yeast ribosomal DNA was inserted into Escherichia coli on a bacteriophage vector and the host cell RNA was then extracted and analyzed for the presence of yeast ribosomal RNA sequences. RNA complementary to yeast rDNA was detected by hybridization. The transcription of yeast rDNA was found to be independent of phage RNA synthesis and to occur on the same DNA strand as rRNA transcription in yeast. However, hybridization to restriction fragments of yeast rDNA suggested that the RNA species detected in E. coli differ somewhat from authentic yeast rRNA.

Base Sequence↗