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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 307 records · Page 17Linked to original sources
PubMed1991

Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas.

Cytogenetic analysis of eight human hepatoma-derived cell lines and one primary hepatocellular carcinoma biopsy revealed multiple chromosome abnormalities; however, only chromosome 1 was consistently affected by rearrangements. Pseudopolysomy 1 as well as chromosome 1 deletions and/or translocations that resulted in loss of the distal 1p region from at least one copy of chromosome 1 were observed in all but one of the cell lines analysed. Molecular analyses of tumor-derived and normal genomic DNA from six cases of hepatocellular carcinoma and from two of hepatoblastoma, using a panel of chromosome 1p-specific DNA probes indicated allelic loss in the distal 1p region in five of the six hepatocellular carcinomas but not in either hepatoblastoma. These results suggest the location of a gene in the distal 1p region whose functional loss may be involved in hepatocellular carcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1991

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function.

The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.

Adult↗
PubMed1991

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition.

Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis.

Adult↗
PubMed1991

Resolution of Cryptosporidium infection in an AIDS patient after improvement of nutritional and immune status with octreotide.

An AIDS patient with severe large volume diarrhea and malnutrition due to cryptosporidial infection is presented. The patient, who was not receiving zidovudine, was treated with octreotide with resolution of diarrhea leading to improvement in nutritional status, immune functions, and subsequently, resolution of the Cryptosporidium infection. This case points out the need for adequate nutrition in AIDS patients and highlights the relationship of nutrition and the immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pain syndromes: case studies.

RSD is a complex syndrome in which large-scale prospective research is needed to provide additional answers regarding variations in presentation and therapeutic outcomes. Only with the early administration of sympathetic blocks in addition to adjunctive therapies will pain relief and return to normal function be most assured.

Adult↗
PubMed1990

Transcription inhibition of SV40 by in vitro DNA methylation.

SV40 DNA was methylated in vitro with prokaryotic or eukaryotic DNA cytosine-5-methyltransferases and the inhibition of transcription by methylation was studied in Xenopus oocytes. Methylation with the prokaryotic HhaI or HpaII methyltransferases did essentially not inhibit transcription of SV40. Methylation with a rat liver methyltransferase led only to minor inhibition of the SV40 early genes, but to a complete shut shut off of the SV40 late genes. Partial methylation showed that methylation of both, the regulatory region and the 5' end of the SV40 late genes, was necessary for the effect on transcription. The TK gene could be inactivated by eukaryotic methylation of either the promoter and the first 50 nucleotides of the gene or the 3' rest of the gene. Insertion of the SV40 enhancer, not containing methylatable CpGs, into the TK upstream region, had no influence on the inhibition of TK gene transcription by methylation.

Animals↗
PubMed1990

[Nissen fundoplication for reflux esophagitis].

Nissen fundoplication was performed in 20 patients suffering from esophageal reflux. Failure of medical therapy was the indication in 60% of the patients, and complications of reflux (bleeding, stricture, Barrett's esophagus) in the others. There was no operative mortality; wound infection was the most common postoperative complication (4 patients). Follow-up after 1-8 years showed good results in 85%. The results of Nissen fundoplication in the world literature, as well as in this series, prove it to be effective for esophageal reflux. Those not responding to appropriate medical therapy should be referred earlier for surgery, prior to development of the complications of reflux.

Esophagitis, Peptic↗
PubMed1990

[Gastrointestinal bleeding and ascending biliary infection secondary to duodenal diverticulum].

We describe a 77-year-old man with recurrent upper gastrointestinal tract bleeding and ascending biliary infection secondary to a duodenal diverticulum. Although such diverticula are relatively common, the great majority are asymptomatic and are only discovered incidentally. Only 1% manifest clinically, usually secondary to a variety of complications such as bleeding, perforation, ascending biliary infection or pancreatitis. Most often the diagnosis is made by exclusion, which accounts for the usual delay in starting treatment. When present, one must consider the possibility that the duodenal diverticulum may be responsible for the patient's symptoms. The preferred approach to a bleeding diverticulum is complete excision, while bypassing the diverticulum by Roux-en-Y duodenojejunostomy is the operation of choice for pancreaticobiliary complications.

Aged↗
PubMed1990

DNA methylation inhibits transcription by RNA polymerase III of a tRNA gene, but not of a 5S rRNA gene.

Methylation of cytosine in the DNA inhibits the transcription by RNA polymerase II in higher eukaryotes, but has no influence on RNA polymerase I transcription. The effect on RNA polymerase III was unknown, so far. Two polymerase III genes: a type 1 5S rRNA gene and a type 2 tRNA gene were methylated in vitro with a purified eukaryotic DNA methyltransferase (EC2.1.1.37) and their transcription was analyzed in Xenopus oocytes. The 5S rRNA gene, an oocyte 5S rRNA gene from X. laevis which is subject to developmental inactivation, was not affected by methylation. Conversely, transcription of the tRNA gene was 80% inhibited by methylation with the eukaryotic methyltransferase. HhaI and HpaII methylation left its transcription unaffected.

Animals↗
PubMed1990

Is chromosome 10 a primary chromosomal abnormality in endometrial adenocarcinoma?

Seven cases of endometrial adenocarcinoma (EC) are reported. Two of these cases exhibited diploid chromosome ranges and showed simple rearrangements involving a chromosomal abnormality of chromosome 10. In four cases, the chromosome number ranged between 50 and 70; rearrangements were more complex, with many abnormalities such as homogeneously stained regions, minutes, dicentrics, and ring chromosomes. In one case, two subpopulations of cells were detected, one in a diploid chromosome range with chromosome 10 altered, and the second, very pleomorphic. These abnormalities are probably due to the evolution of a destabilized genome and represent a consequence of the advanced stage of the disease. The importance of simple abnormalities as clues to the primary chromosomal change, and the possibility that chromosome 10 represents the primary chromosomal alteration event in EC, are discussed.

Adenocarcinoma↗
PubMed1990

Transcription of HIV1 is inhibited by DNA methylation.

A possible role of DNA methylation as a factor in HIV latency was studied by methylating a HIV1-LTR-CAT plasmid in vitro and measuring its expression after transfection on Vero cells. Methylation with a eukaryotic DNA methylase resulted in a 70% inhibition of chloramphenicol acetyltransferase expression, in the absence as well as in the presence of the HIV1 trans-activator protein TAT in the cell. A similar degree of transcription inhibition was obtained by methylation of the only Hpa II site at position-143 in the HIV1-LTR with the bacterial Hpa II methylase. In contrast to the effect by eukaryotic methylation, the inhibition by Hpa II methylation could be partially reversed by cotransfection of the TAT gene. The reason may lie in an about 40% demethylation at the Hpa II site which was concomitantly observed.

Animals↗