Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 325 records · Page 18Linked to original sources

PubMed1994

Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase.

Hereditary tyrosinemia type 1, due to a deficiency of fumarylacetoacetase (FAH), is characterized by progressive liver damage and renal tubular dysfunction and may occur in an acute or a chronic form. An Ala 134 to Asp (GCT to GAT) transition was found in one Turkish and two Norwegian patients with chronic tyrosinemia. SphI digestion of polymerase chain reaction (PCR) amplified genomic DNA identified the mutation and showed that the patients were heterozygous. All these patients had immunoreactive FAH protein in fibroblasts. Another Norwegian patient with chronic disease, without FAH immunoreactive material in fibroblasts, had a Pro 342 to Leu mutation (CCG to CTG). This mutation was identified by MspI digestion of PCR amplified genomic DNA, and the patient was heterozygous. Northern blotting showed FAH mRNA of normal size and amounts in all patients. Site directed mutagenesis and translation in a rabbit reticulocyte lysate demonstrated that both mutations abolished FAH activity.

Amino Acid Metabolism, Inborn Errors↗

PubMed1994

Chromosomal localization of the human histamine H1-receptor gene.

We have assigned the human histamine H1-receptor gene to chromosome 3 by Southern blot analysis of a chromosome mapping panel constructed from human-hamster somatic cell hybrids. This assignment was confirmed by in situ hybridization on metaphase chromosomes and involved bands 3p14-p21.

Animals↗

PubMed1994

Tyrosinemia type 1--complex splicing defects and a missense mutation in the fumarylacetoacetase gene.

Two mutations are reported in six tyrosinemia type 1 patients from northern Europe. In four patients, a G to A transition at nucleotide position 1009 (G1009-->A) of the fumarylacetoacetase (FAH) coding sequence caused aberrant splicing by introducing an acceptor splice site within exon 12, thereby deleting the first 50 nucleotides of this exon. The following exon-intron boundary was frequently missed, and a cryptic donor splice site within intron 12 caused a partial intron 12 retention of 105 bp. This point mutation alternatively gave a glycine 337 to serine substitution in instances of correct splicing. The mutation is rapidly detected by PvuII digestion of polymerase chain reaction (PCR)-amplified genomic DNA. Another mutation, g+5-->a in the intron 12 donor splice site consensus sequence (IVS12 g+5-->a), was found in five of the patients. This caused alternative splicing with retention of the first 105 nucleotides of intron 12, exon 12 skipping, and a combined deletion of exons 12 and 13. Rapid detection of this mutation is achieved by restriction digestion of PCR-amplified genomic DNA; a mismatch primer combined with the point mutation creates a Tru9I restriction site. One patient who was homozygous for the G1009-->A mutation had a chronic form of tyrosinemia. Three patients were combined heterozygotes for G1009-->A and IVS12 g+5-->a. Their clinical phenotypes varied from acute to chronic, indicating the impact of background genes and/or external factors on the presentation of tyrosinemia type 1.

Amino Acid Metabolism, Inborn Errors↗

PubMed1994

Ordering markers in the region of the ataxia-telangiectasia gene (11q22-q23) by fluorescence in situ hybridization (FISH) to interphase nuclei.

Fluorescence in situ hybridization (FISH) to interphase nuclei was performed to order probes corresponding to bands 11q22-q23 where the ataxia-telangiectasia (AT) gene(s) have been located. Cosmid probes and one phage probe previously localized to this chromosome 11 region by FISH to metaphase chromosomes, were hybridized to interphase nuclei of the somatic cell hybrid J1a, which contains chromosome 11 as the only human chromosome. Two-color FISH was used with a centromeric reference probe marker. The following order was obtained: cen-D11S385 (CJ52.75)-CJ52.3-D11S384 (CJ52.193)-CJ52.114-D11S424 (CJ52.77)-D11S132-NCAM-D11S351 (CJ52.208)-tel. The validity of using the centromeric probe was illustrated by showing that a probe corresponding to 11p13 hybridized more closely to the centromere than a probe corresponding to 11q22-q23, and by using cosmids hybridized three by three.

Ataxia Telangiectasia↗

PubMed1994

Peroxisomal disorders: a review.

Until recently peroxisomal disorders were considered to be extremely rare and the diagnostic procedures available for postanatal and prenatal diagnosis were not widely known. At present, 17 human disorders are linked to peroxisomal dysfunction. The clinical, biochemical and morphological peroxisome heterogeneity described in the different diseases illustrate that only combined analysis of all the different approaches will lead to a correct diagnosis and a coherent pathophysiological model to guide ongoing research. With the study of human peroxisomal disease, advances have been gained as to the function of the peroxisome in normal and pathological conditions. Genetic analysis of peroxisome biogenesis and research on peroxisomal targeting signals are now in progress. Peroxisomal disorders are usually classified according to the degree of biochemical impairment. In this paper, a tentative classification of peroxisomal disorders will be proposed, based on the degree of biochemical abnormalities combined with new data obtained on whether or not defective peroxisome assembly is involved: (1) disorders with peroxisome assembly deficiencies; (2) disorders with single enzyme deficiencies. The clinical onset and the major symptoms of the various disorders, and the recently discovered findings are discussed.

Biological Transport↗

PubMed1994

Protein synthesis and energy metabolism in hippocampal slices during extended (24 hours) recovery following different periods of ischemia.

Hippocampal slices were successfully maintained for 24 hours in vitro in a flow-through chamber by using a modified artificial CSF (amino acids included). Measurement of energy metabolism parameters (adenine nucleotides) and the slice response to KCl-induced depolarization (release of GABA and aspartate) indicated that hippocampal slices were metabolically stable for at least 24 hours. The preparation was used to study recovery of protein synthesis after different periods of in vitro ischemia (5, 10, or 15 min). Protein synthesis inhibition was only partly reversed after 15 min of ischemia, but fully reversible after 5- or 10-min ischemia at 24 hours of recovery. Furthermore, the model was used to study a possible role of glutamate in postischemic inhibition of protein synthesis. Glutamate receptor agonists (glutamate or quinolinic acid) or antagonist (kynurenic acid) were applied during ischemia. Neither treatment affected the late (24 hours) outcome of ischemia, arguing against the critical role of glutamate in ischemic cell damage. The present approach allows use of the hippocampal slice preparation in the study of delayed effects of ischemia of different duration.

Adenosine Triphosphate↗

PubMed1994

Group tests for selective screening of inborn errors of metabolism.

Selective screening for inherited metabolic disorders can be performed efficiently by chromatographic techniques. Each technique is suited for a well-defined group of substances present in urine, plasma and CSF. A comprehensive screening programme may involve the analysis of amino acids, organic acids, imidazoles, purines and pyrimidines, oligosaccharides and mucopolysaccharides in urine as well as very long-chain fatty acids in plasma. The experienced laboratory, in close co-operation with a specialized paediatrician, will make a positive diagnosis in 6% of the referred samples, provided a careful selection of the patients is made. Our experience of 10 years of screening revealed 100 different defects; 30% of these were so-called amino acid disorders, 50% organic acidurias and the remaining 20% miscellaneous defects. Chromatographic methods are well suited for the discovery of novel defects. In this respect group screening tests will remain of major importance for the study of inborn errors of metabolism.

Chromatography↗

PubMed1994

Selective screening for amino acid disorders.

The analysis of amino acids is the most frequently applied technique in the selective screening of inborn errors of metabolism. When urine is used as a starting material, simple techniques such as thin-layer chromatography or high-voltage electrophoresis is preferred as a first approach. The quantitative analysis requires instrumentation, usually an amino acid analyser. Both plasma and urine are needed for establishing renal transport defects. Apart from the accumulation of the 'usual' amino acids, the presence of unusual amino acids may be of diagnostic significance. Furthermore the finding of decreased plasma concentrations of specific amino acids may pinpoint several inherited defects. No amino acid screening procedure is complete without the availability of an organic acid and a purine/pyrimidine analytical system, both yielding important additional diagnostic information. Considerable clinical problems may occur in subjects with a decreased tolerance to protein amino acids without being homozygous for any inherited defect. Examples of these disorders that need further studies are homocysteinaemia associated with vascular disease and carriers of ornithine transcarbamylase deficiency.

Amino Acid Metabolism, Inborn Errors↗

PubMed1994

Sodium lactate increases sympathovagal ratios in normal control subjects: spectral analysis of heart rate, blood pressure, and respiration.

We used spectral analysis of heart rate (HR), blood pressure (BP), and respiration to examine the effects of lactate on cholinergic and adrenergic influences on HR and BP variability, a technique found to be very useful in cardiovascular research. We specifically used high frequency (0.2-0.5 Hz) and midfrequency (0.07-0.15 Hz) powers to study cholinergic and adrenergic activity in nine normal control subjects before and after lactate and placebo infusions. Our results demonstrate a marked decrease in cholinergic activity and a significant increase in sympathovagal ratios of HR modulation after lactate infusions. This altered sympathovagal balance may contribute to the panicogenic effects of lactate in panic disorder patients.

Adult↗

PubMed1994

Trisomy 6 as the sole chromosome abnormality in myeloid disorders.

Trisomy 6 was the sole chromosomal abnormality detected in two patients with myeloid disorders in relapse. One had a refractory anemia with excess of blasts and the other acute myeloblastic leukemia. Simple trisomy 6 has been reported in patients with myeloid disorders, marrow hypoplasia, acute myeloid leukemia, and "preleukemia." The prognostic significance of this nonrandom chromosomal abnormality is discussed.

Adult↗

PubMed1994

Long-term survival in acute myelogenous leukemia: a second follow-up of the Fourth International Workshop on Chromosomes in Leukemia.

Patients with acute myeloid leukemia (AML, equivalent to acute non-lymphoblastic leukemia [ANLL]) who were studied at the Fourth and Sixth International Workshops on Chromosomes in Leukemia and who have long survival have been re-assessed to identify factors which may be associated with good prognosis in AML. In a long-term survivor (LTS) group, there were more cases than expected in each age decade below 50, more cases than expected with FAB type M3, and fewer cases than expected of secondary leukemia. Of the distribution of chromosome abnormalities, t(15;17), t(8;21), and inv/del(16) were over-represented, and -5, -7, and rearrangements of 11q were under-represented. Multivariate analysis of all patients showed that age group, cytogenetic classification, FAB type, and sex all had independent, significant effects on survival. A new observation from a very small subgroup of patients was that deletion of 7q without concurrent abnormality of chromosome 5 appeared to be associated with a good prognosis.

Adolescent↗

PubMed1994

Cytogenetic studies in patients with Richter's syndrome.

Cytogenetic studies in six patients with Richter's syndrome (RS) showed complex chromosome abnormalities and chromosomal instability in five. No specific chromosomal abnormality was detected. Chromosomes 14 and 11 were the most frequently involved. Neither deletion of 13q14 nor complete trisomy 12 was observed. Two patients had structural rearrangement of 12q with t(5;12)(q21-q22;q23-q24). The involvement of this region of chromosome 12 may be significant, although not specific for chronic lymphocytic leukemia. These results were compared to those found in cytogenetically studied RS patients from the literature.

Aged↗

PubMed1994

Inadequate response to intradermal hepatitis A vaccine.

To assess the efficacy of the intradermal route of administration of hepatitis A vaccine we conducted a study in hospital laboratory workers. Forty-three volunteers were given three different combinations of intradermal and intramuscular hepatitis A vaccine and compared with 18 controls given intramuscular vaccine only. The geometric mean titres (GMT) after one, two and three intradermal doses of 0.1 ml each were 4.5, 28 and 143 IU l-1 respectively. The GMT after one intramuscular dose in the controls was 163 IU l-1. The results indicate that the response to intradermal hepatitis A vaccine is poor and its use cannot be recommended.

Administration, Cutaneous↗

PubMed1994

Extension of the 2-deoxyglucose method to the fetus in utero: theory and normal values for the cerebral glucose consumption in fetal guinea pigs.

Fetal cerebral metabolism changes during development. The normal fetal metabolic rate must be known to evaluate pathophysiological changes. Therefore, we determined the regional cerebral glucose consumption in the fetal guinea pig. This required the application of the 2-deoxyglucose method to this species. We measured both the transfer coefficients of deoxyglucose and glucose between the maternal arterial plasma and the fetal brain and the lumped constant in chronically prepared undisturbed guinea pig dams using a three-compartment model. Furthermore, the ratio between the initial clearances of deoxyglucose and glucose between the maternal arterial plasma and the fetal brain and the ratio between the phosphorylation coefficients of these substrates in the fetal brain were determined. The total cerebral glucose consumption measured by the deoxyglucose method (10 +/- 1.2 mumol/100 g/min) was similar to that calculated from the glucose concentration and the phosphorylation coefficient of glucose in the cerebrum (10 +/- 0.4 mumol/100 g/min). We conclude that the 2-deoxyglucose method is applicable to the guinea pig, and we further conclude that in the fetal guinea pig cerebral glucose consumption is 10 times lower than that in the adult.

Animals↗

PubMed1994

A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1.

We have established a hybridoma clone, designated 2F5, secreting a neutralizing human monoclonal antibody (MAb) specific for gp41 of human immunodeficiency virus type 1 (HIV-1). The epitope of MAb 2F5 was mapped to amino acid sequence Glu-Leu-Asp-Lys-Trp-Ala on the ectodomain of gp41. In this study different in vitro test systems were used to characterize the neutralizing properties of MAb 2F5. In syncytium inhibition assays, fusion inhibition experiments, and neutralization assays on different HIV-susceptible cells (H9, U937, and peripheral blood mononuclear cells) MAb 2F5 showed broad-spectrum neutralizing capacity against HIV-1 laboratory isolates IIIB, MN, RF, and SF2. In addition, primary isolates from AIDS patients were also neutralized.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

OBJECTIVE: To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DESIGN: Prospective, placebo-controlled, randomized, single-blind study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). INTERVENTIONS: Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. MEASUREMENTS AND MAIN RESULTS: The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. CONCLUSION: PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.

Alprostadil↗

PubMed1994

Treatment options in sulfamethoxazole-trimethoprim-induced thrombocytopenic purpura.

We describe two female patients who had severe sulfamethoxazole-trimethoprim-induced thrombocytopenic purpura. One case occurred shortly after initiating therapy, whereas the other began on the seventh day of treatment. Both patients presented a platelet count below 5,000/microL, extensive purpura, and significant vaginal bleeding. Treatment with systemic corticosteroids resulted in rapid resolution of the thrombocytopenia in the first patient, but had no immediate effect in the other. High-dose intravenous immunoglobulin was effective in correcting the thrombocytopenia in this second instance. Both patients were discharged with a tapering 4-week course of oral prednisone and have remained well since.

Adult↗

PubMed1994

Translocation t(5;12)(q31-q33;p12-p13): a non-random translocation associated with a myeloid disorder with eosinophilia.

A t(5;12)(q33;p13) translocation has been detected in two patients with myeloid disorder and eosinophilia. Six other patients with haematological disease with eosinophilia with similar translocation have been published previously. The existence of a new entity, a myeloproliferative disorder with eosinophilia and t(5;12) (q31-q33;p12-p13), is suggested by the results of the present study.

Aged↗