Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 163 records · Page 9Linked to original sources

PubMed1998

Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency.

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is an inborn error of serine biosynthesis. Patients are affected with congenital microcephaly, psychomotor retardation, and intractable seizures. The effects of oral treatment with amino acids were investigated in 2 siblings. L-Serine up to 500 mg/kg/day was not sufficient for seizure control. Addition of glycine 200 mg/kg/day resulted in complete disappearance of seizures. Electroencephalographic abnormalities gradually resolved after 6 months. We conclude that 3-PGDH can be treated effectively by a combination of L-serine and glycine.

Carbohydrate Dehydrogenases↗

PubMed1998

[Problems and possible solutions in evaluation of dichotic discrimination tests for children].

Uttenweiler's dichotic discrimination test is a valuable contribution to the diagnosis of auditory perception disorders. With this test it is possible to establish whether there is a deficit in a patient's ability to discriminate between differing spoken signals to each ear, as shown in a study contrasting elementary school age children with normal hearing with children having auditory perception disorders. Until now only a limited comparison of test results has been possible, as previous test modes have required an increase in volume when words could not be completely distinguished. A further problem is that very different hearing abilities may give rise to the same test configurations. This study presents an alternative test method that allows a direct individual comparison of results. The volume of the words spoken is no longer increased when words are not adequately understood. In addition, a point system is introduced that enables a quantitative analysis of the same test performances. This new evaluation scale is explained on the basis of actual examples.

Auditory Perceptual Disorders↗

PubMed1998

Structural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene.

The third step in the mitochondrial beta-oxidation spiral of short-chain fatty acids is catalyzed by short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADHSC; EC 1.1.1.35). We have determined the structural organization of the human HADHSC gene by sequencing of cloned genomic amplification products, obtained using HADHSC-specific cDNA-based primers, as well as by direct sequencing of an isolated PAC clone containing the HADHSC gene. Upon comparison with the HADHSC cDNA sequence, HADHSC was shown to encompass at least eight exons, ranging in size from 73 to 158 bp, and 7 introns. The total HADHSC gene spans approximately 49 kb. The HADHSC 5'-flanking region was characterized with an AluI plasmid library constructed from a partially AluI-digested PAC clone containing the human HADHSC gene. Several typical promoter elements such as a CAAT-box, Sp1, AP1, and AP2 sites were found, while a TATA-box was apparently absent. Among other putative regulatory elements, a NRRE-1 site was identified. By radiation hybrid panel, assisted fine-mapping HADHSC was linked to marker AFM070TH5, corresponding to Chromosome (Chr) 4q22-26, and a putative HADHSC pseudogene was linked to marker D15S1324, located at Chr 15q17-21. Knowledge of the genomic organization and 5'-flanking region of HADHSC will enable genomic mutation analysis of patients suspected of HADHSC deficiency, as well as facilitate the investigation into the transcriptional regulation of short-chain fatty acid oxidizing gene products in general and HADHSC expression in particular.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1998

Refined mapping and characterization of the recessive familial amyotrophic lateral sclerosis locus (ALS2) on chromosome 2q33.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that shows familial, autosomal dominant inheritance in 10%-15% of cases. Previous genetic analysis of one large family linked a recessive form of familial ALS (FALS-AR type 3) to the chromosome 2q33-35 region. Using additional polymorphic markers, we have narrowed the size of the linked region to approximately 1.7 cM by linkage and haplotype analysis. We have also established a yeast artificial chromosome contig across the locus that covers an approximate physical distance of 3 million bases. Based on this contig, genes and expressed sequences that map near the 2q33 region have been examined to determine whether they are located within this ALS2 candidate locus. Five identified genes and 34 expressed sequence tags map within the region defined by crossover analysis and merit further consideration as candidate genes for this disease.

Chromosome Mapping↗

PubMed1998

Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia.

OBJECTIVES: Impedance monitoring has been proposed as a method to assess the adequacy of tissue heating during catheter ablation procedures. The purpose of this study was to evaluate the relation among initial impedance, fall in impedance, and electrode temperature during catheter ablation procedures. METHODS AND RESULTS: Data from 248 applications of radiofrequency energy in 45 consecutive patients (26 with accessory pathways and 19 with atrioventricular nodal reentrant tachycardia) referred for catheter ablation were analyzed. The initial impedance was higher during ablation of accessory pathways than during atrioventricular nodal reentrant tachycardia (116+/-66 versus 106+/-80 omega, P < .001). In both groups, a significant correlation was observed between the initial impedance and temperature (R = 0.98, P < .001). After accounting for differences between patients and ablation targets, an even closer correlation was observed (accessory pathways: R = 0.95, P < .0001; atrioventricular nodal reentrant tachycardia: R = 0.94, P < .0001). CONCLUSION: These data suggest that monitoring of the initial impedance and the fall in impedance during ablation procedures may provide clinically valuable information to assess the efficacy of tissue heating and lesion formation.

Adolescent↗

PubMed1998

Evidence of chromosomal inversion using fluorescence in situ hybridization to stretched DNA.

The resolution of fluorescence in situ hybridization techniques (FISH) can be improved using techniques of DNA stretching. The so-called DIRVISH technique has been used to demonstrate the existence of an inversion involving a small chromosomal segment of the long arm of chromosome 14. This inversion was suspected, but not proven, in patients with familial Alzheimer disease. Two-colour FISH using YAC and cosmid probes allowed us to limit the rearranged region around YAC 964e2, which encompasses the Presenilin 1 (PR1) gene. The existence of small-sized inversions within the genome becomes, thus, open to microscope analysis.

Age of Onset↗

PubMed1998

Novel rhenium complexes derived from alpha-tropanol as potential ligands for the dopamine transporter.

A series of rhenium complexes was synthesized as model compounds for the corresponding radioactive technetium-99m complexes for preliminary biological investigations. In a '3 + 1' mixed-ligand approach the tropanol molecule was linked with the metal core through a omega-mercaptoester group as monodentate ligand. Bis(thioethyl)sulphide was used as the tridentate dithiol ligand to block the remaining free coordination sites. The omega-mercaptoesters were synthesized via the trityl-protected precursors. Binding tests on the cloned human dopamine transporter revealed moderate binding affinities for some of the prepared compounds. The complexes were characterised by X-ray and the lipophilicity as well as pKa values were determined.

Carrier Proteins↗

PubMed1998

A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis.

Cholestasis, or impaired bile flow, is an important but poorly understood manifestation of liver disease. Two clinically distinct forms of inherited cholestasis, benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis type 1 (PFIC1), were previously mapped to 18q21. Haplotype analysis narrowed the candidate region for both diseases to the same interval of less than 1 cM, in which we identified a gene mutated in BRIC and PFIC1 patients. This gene (called FIC1) is the first identified human member of a recently described subfamily of P-type ATPases; ATP-dependent aminophospholipid transport is the previously described function of members of this subfamily. FIC1 is expressed in several epithelial tissues and, surprisingly, more strongly in small intestine than in liver. Its protein product is likely to play an essential role in enterohepatic circulation of bile acids; further characterization of FIC1 will facilitate understanding of normal bile formation and cholestasis.

Adenosine Triphosphatases↗

PubMed1998

The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases. EU Concerted Action 11q23 Workshop participants.

Thirty patients representing 5.5% of those collected by the 11q23 workshop had a t(6;11)(q27;q23). They included 27cases of acute myeloid leukemia (AML) (M1, three cases; M2, two cases; M4, nine cases; M4/M5, one case; M5, 12 cases) of age range 3-72 years and three cases of acute lymphoblastic leukemia (ALL) (B-lineage ALL, two cases; T-ALL, one case) of age range 0.5-13 years. In 20 cases the t(6;11) was the sole abnormality. In 10 cases the recurrent additional abnormalities were extra copies of chromosomes 8, 19, 21, or the der(6). Translocation t(6;11) was identified by cytogenetics alone in 13 cases. In three cases it was confirmed by fluorescence in situ hybridization (FISH) using whole chromosome paints (wcps) 6 and 11. In a further 14 cases involvement of MLL was demonstrated by FISH, by reverse transcriptase polymerase chain reaction (RT-PCR), by Southern blotting (SB) or by a combination of these methods. One case had a direct insertion of 11 into 6-dir ins(6;11)(q27;q13q23). Molecular investigations showed that one case had a 3' deletion of MLL. The median overall survival for the patients was 12 months, indicating a poor prognosis for patients with a t(6;11) translocation.

Acute Disease↗

PubMed1998

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.

The clinical, haematological and cytogenetic data for 20 patients with an acquired abnormality of 11q23 and 10p have been reviewed at this workshop. Patients predominantly presented with de novo AML M5a and the most common cytogenetic finding was an inversion of part of the long arm of chromosome 11 followed by a translocation between 11q and 10p. Band p12 represented the most common breakpoint on chromosome 10. The t(10;11) subgroup defined a subset of younger 11q23 patients, the majority of whom achieve a first complete remission despite the differing treatment regimens.

Adolescent↗

PubMed1998

Abnormalities of the short arm of chromosome 12 in T cell prolymphocytic leukemia.

Abnormalities of the short arm of chromosome 12 are nonrandom events in T cell prolymphocytic leukemia (T-PLL). Fluorescence in situ hybridization (FISH) studies were performed in three patients with T-PLL and one patient with T cell peripheral lymphoma and rearrangement of 12p. Whereas the rearrangements of 12p were different in the four patients, a breakpoint centromeric to the ETV6 gene was present in the three T-PLL patients. In addition, loss of heterozygosity for a chromosomal segment telomeric to ETV6 with loss of the RAD52 locus was also shown by FISH studies. In contrast, the breakpoint was telomeric to ETV6 in the patient with peripheral lymphoma.

Aged↗

PubMed1998

Non-Hodgkin's lymphomas and myeloid disorders: deletions associated with t(2;5) and t(3;5) detected by FISH.

The nucleophosmin (NPM) gene is involved in two recurrent translocations in hematological malignancies: t(2;5) (p23;q35) in anaplastic large cell lymphoma (ALCL) and t(3;5)(q25.1;q34-35) in myelodysplasia and acute non-lymphocytic leukemia (ANLL). Using eight YACs encompassing the 5q34-q35 region, we could easily detect these two translocations. In both types of translocation, probable unexpected deletions were also discovered downstream of the breakpoint at 5q35.

Adolescent↗

PubMed1998

Reduction of plasma volume after storage of platelets in CP2D.

BACKGROUND: There has been concern that further deterioration might occur if stored platelets are centrifuged to reduce their volume. Although such centrifugation appears to have minimal effect on platelets in CPDA-1 (osmolarity, 470 mOsm) there is no information on the situation with CP2D (580 mOsm). STUDY DESIGN AND METHODS: Platelet concentrates from CP2D packs were sampled at 1 and 5 days and after centrifugation was used to reduce the plasma volume to 10 mL. The aggregation, hypotonic shock response, morphology, pH, and lactate, glucose, pCO2 and pO2 levels were assessed, and values were compared to those seen with CPDA-1. In addition, blood was collected from the same donors into both CP2D and standard sodium citrate anticoagulant in an anticoagulant-to-blood ratio of 1:8 and the aggregation response of the fresh platelets was measured. RESULTS: Collection of blood into CP2D results in an immediate reduction of the platelet aggregation response when compared to that found after collection of blood into sodium citrate or CPDA-1. Aggregation is further decreased after storage; however, these changes and those for hypotonic shock, pH, lactate, glucose, and pCO2 are similar to those seen for CPDA-1. Additional centrifugation did not cause further change. CONCLUSION: Platelets stored in CP2D have reduced in vitro function after 5 days of storage, but subsequent centrifugation to reduce the plasma volume does not further alter these platelets.

Anticoagulants↗

PubMed1998

A non-invasive selective assessment of type I fibre mitochondrial function using 31P NMR spectroscopy. Evidence for impaired oxidative phosphorylation rate in skeletal muscle in patients with chronic heart failure.

BACKGROUND: Skeletal muscle abnormalities contribute considerably to the clinical expression of heart failure. Deconditioning, underperfusion and an increased number of type IIb glycolytical fibres lead to early lactate production and muscle fatigue at low exercise levels. Aerobic muscle metabolism may also be impaired, as suggested by biopsy studies. Thus far, no data are available from non-invasive studies to indicate the extent of aerobic muscle dysfunction during low-grade exercise which does not induce acidosis. METHODS AND RESULTS: Mitochondrial function of skeletal muscle during fibre type I activation was studied in 22 patients with chronic heart failure [NYHA class III, left ventricular ejection fraction 28 +/- 2%, (patients)] on ACE inhibitors, diuretics and digoxin, and in 20 normal subjects, using 31P NMR spectroscopy of a single right forearm flexor muscle during three mild intermittent exercise levels (0-40% of maximum voluntary contraction) and recovery time. At rest, the inorganic phosphate/phosphocreatine ratio was different [0.13 +/- 0.005 (patients) vs 0.09 +/- 0.002 (normal subjects), P = 0.0001]. However, intracellular pH was comparable. Local acidosis (tissue pH < 6.9) was avoided to prevent fibre type IIb activation. Calculated resting phosphate potential levels were comparable, but the slope and intercept of the linear relationship of phosphate potential and workload were significantly lower in patients than in normal subjects (11.7 +/- 0.7 vs 15.8 +/- 0.6 and 139 +/- 7 vs 196 +/- 7, patients vs normal subjects, indicating early exhaustion of intracellular energy at lower exercise levels. Also, maximum calculated workload at which tissue ADP stabilized was lower in patients than in normal subjects (88 +/- 7% vs 120 +/- 4% of maximum voluntary workload, patients vs normal subjects, P < 0.05). Time to recovery to pre-test phosphocreatine levels was prolonged by 46% in patients compared to normal subjects (P < 0.05). CONCLUSIONS: In heart failure, oxidative fibre mitochondrial function in skeletal muscle is impaired, as reflected by the reduced phosphate potential and oxidative phosphorylation rate, early exhaustion and slowed recovery of intracellular energy reserve at workloads, which do not affect intracellular pH.

Adenosine Triphosphate↗

PubMed1998

Low-dose flunarizine does not affect short-term fetal circulatory responses to acute asphyxia in sheep near term.

Asphyxia is one of the major causes of perinatal brain damage and neuronal cell loss, which may result in psychomotor deficits during later development. It has been shown previously that the immature brain can be protected from ischemic injury by flunarizine, a class IV calcium antagonist. However, cardiovascular side-effects of flunarizine, when applied at the dosages used in those studies, have been reported. Recently, the present authors were able to demonstrate that even by injecting flunarizine at a far lower dosage (1 mg kg-1 estimated bodyweight) neuronal cell damage, caused by occlusion of both carotid arteries for 30 min, can be reduced in fetal sheep near term. The aim of the present study was, therefore, to examine whether low-dose flunarizine affects fetal cardiovascular responses to acute asphyxia in sheep near term. Ten fetal sheep were chronically instrumented at a mean gestational age of 132 +/- 1 days (term is at 147 days). Fetuses from the study group received a bolus injection of flunarizine (1 mg kg-1 estimated fetal weight) 60 min before asphyxia, whereas the solvent was administered to the fetuses from the control group. Organ blood flows, physiological variables and plasma concentrations of catecholamines were measured before, during and after a single occlusion of uterine blood flow for 2 min (i.e. at 0, 1, 2, 3, 4, and 30 min). Before asphyxia, the distribution of combined ventricular output and physiological variables, as well as concentrations of catecholamines, in fetuses from the control group were in the normal range for chronically prepared fetal sheep near term. During acute asphyxia there was a redistribution of cardiac output towards the central organs accompanied by a pronounced bradycardia and a rapid increase in arterial blood pressure. After asphyxia circulatory centralization did not resolve quite as rapidly as it developed, but was almost completely recovered at 30 min after the insult. There were nearly no differences in the time course of physiological and cardiovascular variables measured before, during and after acute intrauterine asphyxia between the control and study groups. From the present study it was concluded that low-dose flunarizine does not affect short-term fetal circulatory responses to acute asphyxia in sheep near term.

Adrenal Glands↗

PubMed1998

A dose-response study of a live attenuated varicella-zoster virus (Oka strain) vaccine administered to adults 55 years of age and older.

Decreased cell-mediated immune (CMI) response to varicella-zoster virus (VZV) is correlated with an increased risk of reactivation of latent virus from dorsal root sites, leading to herpes zoster. The cell-mediated and humoral immunogenicity of three concentrations (3200, 8500, and 41,650 pfu/dose) of a live attenuated VZV vaccine (Oka strain; VZV/Oka) was compared with a control pneumococcal polysaccharide vaccine in 200 healthy adults who were > or = 55 years old. Six weeks after vaccination, the VZV-specific CMI response (as measured by stimulation index values and precursor cell frequencies) was enhanced in all VZV/Oka vaccine groups compared with the control group (for all VZV/Oka groups combined vs. controls, tested with VZV crude antigen: stimulation index, P < .001; precursor cell frequency, P < .001). Geometric mean titers of anti-VZV antibodies increased in all VZV/Oka vaccine groups but remained unchanged in the control vaccine group. No dose effect of VZV/Oka vaccine was observed for CMI or humoral responses.

Aged↗

PubMed1998

The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily.

The BCMA gene is a new gene discovered by the molecular analysis of a t(4;16) translocation, characteristic of a human T cell lymphoma. It has no significant similarity with any known protein or motif, so that its function was unknown. This report describes the cloning of murine BCMA cDNA and its genomic counterpart. The mouse gene is organized into three exons, like the human gene, and lies in murine chromosome 16, in the 16B3 band, the counterpart of the human chromosome 16p13 band, where the human gene lies. Murine BCMA cDNA encodes a 185 amino acids protein (184 residues for the human), has a potential central transmembrane segment like the human protein and is 62% identical to it. The murine BCMA mRNA is found mainly in lymphoid tissues, as is human BCMA mRNA. Alignment of the murine and human BCMA protein sequences revealed a conserved motif of six cysteines in the N-terminal part, which strongly suggests that the BCMA protein belongs to the tumor necrosis factor receptor (TNFR) superfamily. Human BCMA is the first member of the TNFR family to be implicated in a chromosomal translocation.

Amino Acid Sequence↗

PubMed1998

Increased anticoagulation during cardiopulmonary bypass by prostaglandin E1.

UNLABELLED: Prostaglandin E1 (PGE1) inhibits tissue factor/factor VIIa-dependent thrombin formation and platelet procoagulant activity. These pathways may trigger thrombin generation during cardiopulmonary bypass (CPB). We hypothesized that the therapeutic combination of PGE1 and heparin increases the degree of anticoagulation as measured by reduced thrombin generation during CPB. Patients undergoing primary coronary artery bypass grafting using CPB were anticoagulated with unfractionated porcine heparin and 12.5 ng x kg(-1) x min(-1) PGE1 (n = 20) or placebo (n = 20). Plasma markers that reflect thrombin generation (prothrombin fragment F1+2, thrombin-antithrombin complex) were determined, and postoperative bleeding was documented. Thrombin generation gradually increased in both groups during and after CPB but was lower in the PGE1 group. After CPB, the difference between mean levels of prothrombin fragment F1+2 was 1.9 nmol/L (95% confidence interval for difference 1.1 to 2.8; P = 0.001). The difference between mean levels of thrombin-antithrombin complex was 43.6 ng/mL (21.2 to 66.1; P = 0.001). A trend in reduced postoperative bleeding was observed in the PGE1 group with a difference of sample means of 183 mL (-5 to 371; P = 0.056). Adding PGE1 to unfractionated heparin enhances anticoagulation during CPB. The results suggest that reduced thrombin generation during surgery may decrease postoperative bleeding. IMPLICATIONS: Cardiopulmonary bypass is associated with extensive thrombin generation even in the presence of clinically sufficient heparin anticoagulation. The addition of prostaglandin E1 to heparin enhances the degree of anticoagulation as measured by reduced thrombin formation during cardiopulmonary bypass.

Aged↗