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Biomedical subjects

D Braun

Publications and source records attributed to D Braun.

At least 91 records · Page 5Linked to original sources
PubMed1987

A bicistronic Epstein-Barr virus mRNA encodes two nuclear proteins in latently infected, growth-transformed lymphocytes.

EBNA2 is a nuclear protein expressed in all cells latently infected with and growth transformed by Epstein-Barr virus (EBV) infection (K. Hennessy and E. Kieff, Science 227:1230-1240, 1985). The nucleotide sequence of the EBNA2 mRNA (J. Sample, M. Hummel, D. Braun, M. Birkenbach, and E. Kieff, Proc. Natl. Acad. Sci. USA 83:5096-5100, 1986) revealed that it begins with a 924-base open reading frame that has an unusual potential translational initiation site (CAAATGG). This open reading frame is followed by 138 nucleotides with only one highly unlikely translational initiation site (TACATGC), which would translate a pentapeptide before the next stop codon. The last part of the mRNA is the open reading frame which encodes EBNA2. In this paper, we demonstrate that the 924-base open reading frame translates a 40-kilodalton protein in vitro or in murine cells transfected with the EBNA2 cDNA under control of the murine leukemia virus long terminal repeat. A protein of identical size was detected in EBV-transformed, latently infected human lymphocyte nuclei by using antibody specific for the leader open reading frame expressed in bacteria. Therefore, this is a rare example of a mRNA which translates two proteins from nonoverlapping open reading frames. Since the protein encoded by the leader of the EBNA mRNA is expressed in all nuclei of a latently infected cell line, it was designated EBNA-LP. EBNA-LP localizes to small intranuclear particles and differs in this respect from EBNA1, EBNA2, or EBNA3. EBNA-LP is not expressed in an EBV-transformed marmoset lymphocyte cell (B95-8) or in one EBV-infected Burkitt tumor cell line (Raji) but is expressed in three other Burkitt tumor cell lines (Namalwa, P3HR-1, and Daudi).

Amino Acid Sequence↗
PubMed1987

Lung vascular effects of lipid infusion in awake lambs.

Numerous reports have shown that intravascular lipid infusion may cause pulmonary dysfunction in a variety of species, including humans. To determine the effects of parenteral lipid on neonatal pulmonary hemodynamics, lung fluid filtration, and respiratory gas exchange, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, and partial pressures of oxygen and carbon dioxide in arterial blood of 11 awake chronically catheterized lambs that received a 2-3 h control infusion of glucose-saline solution followed by Intralipid at a dose of 67.5, 125, or 250 (mg/h)/kg body weight for 6 h. Intralipid caused an acute dose-dependent increase in pulmonary arterial pressure, with no significant change in cardiac output or left atrial pressure. The pulmonary hypertension, which lasted for at least 2 h, was accompanied by a greater than 50% increase in lung lymph flow and a significant decrease in lymph protein concentration relative to plasma protein concentration. Pulmonary artery pressure gradually decreased to control values during the final 2 h of lipid infusion, but lymph flow remained 35% above control and lymph protein concentration remained low. Lipid infusion also was associated with a modest decrease in PaO2. Both arterial and venous administration of lipid gave similar results. In separate studies, lipid infusion caused a significant increase in plasma concentrations of thromboxane B2, the stable metabolite of thromboxane A2, without affecting plasma concentrations of 6-keto prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment with imidazole, which attenuated the lipid-induced increase in thromboxane B2 concentration, completely blocked the pulmonary hemodynamic response to lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site.

Three cDNA clones of the second Epstein-Barr virus nuclear antigen (EBNA2) mRNA and two of the EBNA1 mRNA were analyzed. Two EBNA2 clones begin 42 bases 3' to a promoter in the Epstein-Barr virus long internal repeat, which is likely to be the EBNA2 promoter. Surprisingly, the first splice creates an AUG at the beginning of the first of two nonoverlapping open reading frames. The second open reading frame encodes EBNA2. Two incomplete EBNA1 mRNA cDNA clones begin with parts of two of the EBNA2 exons and contain two other exons that map 19 and 59 kilobases 3' to the EBNA2 coding domain. The 3' exon of this mRNA encodes EBNA1. A model for regulation of transcription of these RNAs is presented.

Antigens, Viral↗
PubMed1983

Metastatic colorectal carcinoma. A prospective randomized trial of Methyl-CCNU, 5-Fluorouracil (5-FU) and vincristine (MOF) versus MOF plus streptozotocin (MOF-Strep).

A prospective randomized trial evaluated semustine (Methyl CCNU) 5-Fluorouracil (5-FU) and vincristine (MOF) versus MOF plus streptozotocin (MOF-Strep) in 75 patients with advanced, measurable colorectal carcinoma. The complete and partial remission rate with MOF-Strep was significantly better, 34 versus 5% with MOF (P = 0.003). Gastrointestinal toxicity was increased with the addition of streptozotocin. Initial patient characteristics such as age, sex, performance status, time from diagnosis to metastatic disease, site of metastatic disease, and most initial laboratory values were not predictive of response. However, certain initial laboratory values (lactic dehydrogenace and leukocyte count) and one tumor site pulmonary metastases did influence survival regardless of response.

Adult↗
PubMed1982

Absence of HLA association or linkage for variations in sensitivity to the odor of androstenone.

Sensitivity to the odor of 5-androst-16-en-3-one (androstenone), a testosterone metabolite, shows wide variations among unrelated individuals. Analysis of correlations in sensitivity between monozygotic twin pairs, dizygotic twin pairs, and nontwin sib pairs now shows that at least a portion of this variation is genetically determined. However, although data from some mouse studies have suggested a relationship between olfaction and the murine histocompatibility system (H-2), we were unable to demonstrate any role of the human HLA system in explaining the wide individual variations in human sensitivity to androstenone. An additional analysis of HLA antigens among 61 human mating pairs also provided no evidence that HLA phenotypes play a role in human mating preference. These data fail to support a role for the human HLA system in the recognition of an odorant of potential biological significance.

Adolescent↗
PubMed1982

Distribution of HLA genotypes in families of patients with acute leukemia. Implications for transplantation.

The HLA genotypes of members of 104 families of patients with acute myelogenous leukemia (AML), 89 families of patients with acute lymphocytic leukemia (ALL), and 40 control families were analyzed. The results indicate that the HLA genotype of both ALL and AML leukemic patients is found more frequently than the expected 25% among their siblings; the increase for AML patients is statistically significant. This suggests that an HLA-linked factor(s) conferring susceptibility to leukemia may also be associated with increased gametic survival. The chance of finding an HLA-matched sibling for bone marrow transplantation is increased.

Acute Disease↗
PubMed1981

Technical and theoretical considerations in the HLA typing of amniotic fluid cells for prenatal diagnosis and paternity testing.

HLA typing of amniotic fluid cells has been used for the prenatal diagnosis of the HLA linked diseases congenital adrenal hyperplasia (21-OH-deficiency (21-OH-def) type) and complement C4 deficiency and it has also been used for the prenatal determination of paternity. There are, however, technical difficulties in this test associated with the weak expression of some B locus antigens on amniotic fluid cells, and theoretical difficulties related to associations between particular HLA antigens and the 21-OH-def allele. Since certain HLA-B locus antigens are found in significantly increased frequencies among patients with 21-OH-def, there is a relatively high incidence of HLA-B homozygosity among the patients and over 40 per cent of the parents of these patients share one or more HLA-B locus antigens. Results of some prenatal HLA typing tests may thus be difficult to interpret, and supplementary tests should be used whenever possible. HLA typing of amniotic cells is, however, the only available procedure for prenatal diagnosis of C4 deficiency and it is the best available procedure for prenatal determination of paternity. A modification of our original procedure allows HLA typing to be performed with increased numbers of HLA typing sera, and sera with optimum reactivity for amniotic fluid cells have now been selected for the definition of most of the more commonly expressed HLA antigens. Although amniotic fluid cells do not express DR Antigens, amniotic fluid cells can be typed for the HLA-linked marker glyoxalase I (GLO) and this may be the informative for prenatal diagnosis in some cases.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Enzymuria (the output of gamma-glutamyl-transpeptidase and of N-acetyl-beta-D-glucosaminidase) in the course of experimental renovascular hypertension.

The urinary output of gamma-glutamyl-transpeptidase (gamma GT) and of N-acetyl-beta-D-glucosaminidase (NAG) was studied with "two-kidney Goldblatt hypertension' 3-6, 16-19 and 30-33 weeks after eliciting high blood pressure. gamma GT excretion rate of normotensive males was higher than that of females, while the activity of the renal tissue was on the same level. gamma GT output of hypertensive males was elevated in the early and in the middle stages of the disease, it was subnormal in the late stage. In females gamma GT output increased in animals with excessively high blood pressure (less than 200 mm Hg) only. gamma GT output correlated with the tissue activity in males only. In all animals there was an inverse, linear correlation between tissue gamma GT activity and the hydroxyproline content. The pattern of the NAG output was similar to that of gamma GT, however, excretion of NAG showed no sex differences and remained high in the late stage of the disease, too. Nephrosclerosis was less pronounced in female Goldblatt rats than in males.

Acetylglucosaminidase↗
PubMed1980

Therapy for metastatic colorectal carcinoma with a combination of methyl-CCNU, 5-fluorouracil vincristine and streptozotocin (MOF-Strep).

Seventy-seven previously untreated patients with measurable metastatic colorectal carcinoma were treated with a combination of methyl-CCNU, 5-fluorouracil (5-FU), vincristine and streptozotocin (MOF-Strep). The treatment schedule consisted of methyl-CCNU, 30 mg/m2 for 5 consecutive days q 10 weeks; 5-FU, 300 mg/m2 IV for five consecutive days q 5 weeks; vincristine, 1 mg IV q 5 weeks; and streptozotocin, 500 mg/m2 IV weekly. Two (3%) patients achieved complete remission (CR); 22 (29%) patients, a partial remission (PR); and 13 (18%) patients, a minor remission (MR). The median duration of remission was eight months (range, 4-25+months) for patients obtaining CR/PR status, and six months (range, 4-15 months) for MR status. The median survival time was 14 months for patients achieving CR/PR versus seven months for non responders. Comparison with a previous study of MOF at Memorial Sloan-Kettering Cancer Center, showed that the MOF-Strep combination produced a significant (P = 0.004) increase in the number of complete and partial remissions, 32% versus 11%, and in survival, 11 versus 9 months, (P = 0.003), respectively.

Adult↗
PubMed1980

Influenza immunization of children with neoplastic diseases.

During the National Influenza Immunization Program in 1976, 147 children with neoplastic diseases received Wyeth split-product bivalent influenza vaccine: A/New Jersey/8/76 (HSW1N1), A/Victoria/3/75 (H3N2). Thirteen normal siblings served as controls. Seventy-one patients received two doses of the vaccine four weeks apart. After the second injection of A/NJ/8/76, there was a difference between the response of the patients on chemotherapy and those off therapy greater than or equal to 30 days--38% vs. 76%, P less than 0.01 for four-fold rise and 26% vs. 57%, P less than 0.05 for the attainment of protective (greater than or equal to 32) hemagglutination inhibition (HI) titers. These differences were observed in both leukemia-lymphoma and solid tumor patients. There was a difference in HI titers to A/Vic/75 between patients on and off chemotherapy after a single injection, 34% vs. 71%, P less than 0.001 for a four-fold rise. After the second immunization, only 52% on, and 86% off therapy (P less than 0.05) had a four-fold rise in titers. Thirty-two percent of the patients on treatment who achieved "protective" titers did so only after the second immunization. Immunoglobulin levels and neutropenia did not correlate with the inability to obtain a four-fold rise in titers. Our findings suggest that patients on chemotherapy cannot be effectively vaccinated by a new antigen, and that single yearly boosters may be insufficient for recall of old antigens. Patients off chemotherapy greater than or equal to 30 days respond as normal controls.

Antibodies, Viral↗
PubMed1980

Impairment of phagocytosis by moderate hyperoxia (40 to 60 per cent oxygen) in lung macrophages.

Exposure of isolated mouse lung macrophages to 40 and 60 per cent oxygen in tissue culture for 48 hours resulted in significant depression of phagocytosis as compared to air-exposed controls. The impairment of phagocytosis was reversed when the cells were reexposed to normoxic conditions for 48 hours. The impairment of phagocytosis occurred despite significant increases in intracellular superoxide dismutase activity, an enzyme felt to play a protective role in oxygen toxicity. Exposure to 40 and 60 per cent oxygen increased the susceptibility of lung macrophages to functional impairment by 95 per cent oxygen, rather than producing tolerance. The precise biologic and clinical significance of these findings will require additional studies in integrated systems. However, these studies show unequivocal lung macrophage injury with moderate hyperoxic exposure.

Animals↗
PubMed1979

A randomized study of two different schedules of methyl CCNU, 5-FU and vincristine for metastatic colorectal carcinoma.

Sixty-seven patients with measurable colorectal carcinoma were randomized to receive two different schedules of Methyl CCNU, 5-FU and Vincristine (MOF). The treatment schedule consisted of Methyl CCNU 150 mg/m2 po q 70 days, 5-FU 300 mg/m2 iv for 5 consecutive days q 35 days, and Vincristine 1 mg/m2 IV q 35 days. The same total dose was used in each arm; in MOF A, the Methyl CCNU was given on day 1, while in MOF B, the Methyl CCNU was divided and given over 5 consecutive days. In MOF A, there was a 10% partial response rate and a 10% minor response rate. In MOF B, the partial response rate was 12% and the minor response rate was 21%. This difference is not statistically significant, but the patients in MOF B experienced less gastrointestinal toxicity (p less than .001).

Adult↗
PubMed1979

Adrenergic and dopaminergic response to chronic chair restraint in the rhesus monkey.

Prolonged chair restraint and social isolation in the rhesus monkey led to a reduction in the urinary excretion of HVA (4-hydroxy-3-methoxyphenylacetic acid), DOPAC (3,4-dihydroxyphenylacetic acid), VMA methoxy-4-hydroxymandelic acid), and MHPG (3-methoxy-4-hydroxyphenylethylglycol) over a 3 week period. This adaptation to a chronically "stressful" situation corresponds to earlier studies on the rhesus monkey indicating a gradual reduction in the urinary excretion of norepinephrine and epinephrine after initiation of restraint. The following basic information on the urinary excretion of catecholamine metabolites was obtained: (1) the rate of excretion of the dopamine metabolites (HVA and DOPAC) is about four times higher than the rate of excretion of adrenergic metabolites (VMA and MHPG): (2) MHPG is the major adrenergic metabolite in the rhesus monkey; and (3) the excretion rates of the urinary metabolites varied considerably between animals.

3,4-Dihydroxyphenylacetic Acid↗