Search PubMed⌕ Search

Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 289 records · Page 16Linked to original sources
PubMed1995

Partial chromosome 21 amplification in a child with acute lymphoblastic leukemia.

Monosomy 21 and metacentric markers corresponding in size to chromosomes 8 to 12 were found as the only clonal chromosomal changes in a child with acute lymphoblastic leukemia (ALL). chromosome painting with a whole chromosome 21-specific probe showed that the marker originated from chromosome 21. Fluorescence in situ hybridization with yeast artificial chromosome (YAC) probes to chromosome 21 showed genomic amplification with two, four, or more copies of the probed DNA sequences present on the marker. The most amplified regions of chromosome 21 were centromeric and telomeric to the Down's syndrome region. This observation supports the notion that amplification of only parts of chromosome 21 may be important in the leukemogenic process in spite of the high incidence of complete trisomy 21 in ALL.

Child↗
PubMed1995

Human and mouse Krüppel-like (MOK2) orthologue genes encode two different zinc finger proteins.

We have isolated the human homologue of Mok2 gene encoding a Krüppel-like protein. The identification of three cDNAs and genomic clones reveals that the human protein shows substantial structural differences with the mouse MOK2 protein. The mouse MOK2 protein is composed of seven tandem zinc-finger motifs with five additional amino acids at the COOH-terminal. This structural feature is also present at the end of the human MOK2 protein. The seven zinc-finger motifs show 94% identity between the two proteins. In addition, the human protein contains three additional zinc-finger motifs in tandem with the others and a nonfinger acidic domain of 173 amino acids at the NH2-terminal. The Southern analysis indicates that a single copy of these two genes is present in the genome. The human gene has been localized on chromosome 19 on band q13.2-q13.3. The comparison of human and mouse cDNA sequences reveals a strong identity in the sequences localized outside the seven highly conserved zinc-finger motifs. The divergence from their common ancestor results in the loss of a potential transcription activator domain in mouse MOK2 protein.

Amino Acid Sequence↗
PubMed1995

Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis.

Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to lead to a subset of autosomal dominantly inherited familial amyotrophic lateral sclerosis (ALS). These findings have led to the hypothesis that defects in oxygen radical metabolism may be involved in the pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in other forms of ALS. We report here analysis of two genes encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region recently shown to contain a gene responsible for a familial form of ALS with autosomal recessive inheritance (FALS-AR). The AO gene appears to be located within 280,000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO gene is highly expressed in glial cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a region previously shown to contain a highly homologous but different form of XDH. Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR.

Aldehyde Oxidase↗
PubMed1995

Translocation (2;3)(p22;q28) is associated with myeloid disorders.

Chromosome studies carried out in two children with acute myeloblastic leukemia (AML, M2) showed a t(2;3)(p22;q28). This abnormality was associated with monosomy 7 and del(12)(p12) in the first patient and was found only in relapse in the second patient. Comparison with the other previously published t(2;3) suggests that this translocation is a nonrandom abnormality involving a pluripotent stem cell and occurring as a secondary chromosome abnormality in AML.

Child↗
PubMed1995

Virosomes as carriers for combined vaccines.

Immunopotentiating reconstituted influenza virosomes (IRIV) are liposomes which carry the two glycoproteins of the influenza virus on their surface. A hepatitis A vaccine using IRIV as carrier has very good immunogenicity and is well tolerated. The objective of this study was to produce a fivefold combined vaccine against hepatitis A and B, diphtheria, tetanus and influenza A/B, and to show that in principle IRIVs can serve as carriers for multiple antigens which have good immunogenicity and are well tolerated. A total of four studies were carried out. Either the combined vaccine or the corresponding adequately tested alum-adsorbed single vaccines were tested for reactogenicity and immunogenicity in young adults. A hepatitis A and B combination on an IRIV base showed the same immunogenicity and toleration as the single vaccines. However, with the simultaneous coupling of all five vaccines on the same IRIV or the binding of Di-Te and HAV on different IRIVs there was a suppression of the humoral immune response against HAV (p = 0.03). The possibility that epitope-specific suppression had occurred could be ruled out. The suppression of the response against HAV could be circumvented by halving the quantity of Di-Te antigen in the combined vaccine so as to avoid antigenic competition. Surprisingly, the immunogenicity of Di-Te vaccination in the combination proved superior to that of a separate vaccination. All vaccinations were well tolerated.

Adult↗
PubMed1995

Leukaemic non-Hodgkin's lymphomas with hyperdiploid cells and t(11;14)(q13;q32): a subtype of mantle cell lymphoma?

The present study describes five patients with leukaemic non-Hodgkin's lymphoma (NHL) detected on the basis of particular morphology and cytogenetic findings. With respect to histological, immunological and cytogenetic features these NHL are closely related to mantle cell lymphoma/intermediate differentiated lymphocytic lymphoma. However, the presence of unusual large cells associated with the t(11;14)(q13;q32) translocation and numerical chromosome changes, in the near triploid or near tetraploid range, could delineate a particular subtype of mantle cell lymphoma.

Aged↗
PubMed1995

Assessment of clonal evolution at Ig/TCR loci in acute lymphoblastic leukaemia by single-strand conformation polymorphism studies and highly resolutive PCR derived methods: implication for a general strategy of minimal residual disease detection.

Junctional sequences of immunoglobulin (Ig)/T-cell receptor (TCR) gene rearrangements are used as patient-specific PCR targets for the detection of minimal residual disease (MRD) in acute lymphoblastic leukaemias (ALLs). Clonal evolution of gene rearrangements is a major pitfall of this strategy. Using high-resolution PCR-based analyses (including denaturing gel electrophoresis and single-stranded conformation polymorphism (SSCP)) we have compared Ig/TCR gene rearrangements at presentation and relapse in a series of ALLs. These methods allow an unambigous comparison of rearrangements taking into account junctional size and nucleotide sequence information and allow a precise assessment of the clonal evolution. V gamma-J gamma and V delta 1-J delta 1 rearrangements were analysed in 12 T-ALLs. VH-JH, V gamma-J gamma, V delta 2-D delta 3 and, in selected cases, DH-JH rearrangements were studied in 14 B-lineage ALLs. Clonal evolution, regarding major rearrangements, occurs for at least one of these loci in 2/12 T-ALLs and in 5/14 B-lineage ALLs. Clonal evolution is more marked for minor rearrangements than for major ones. As shown using SSCP analysis, rearrangements observed at relapse are sometimes found in minor clones at presentation which are therefore selected in vivo by a proliferative advantage. These data, as well as those from the available literature, suggest the use of at least two patient-specific probes to detect MRD in ALLs. A general strategy including selected Ig/TCR rearrangements and chromosomal abnormalities as PCR targets is proposed.

Adolescent↗
PubMed1995

Successful epilepsy surgery without intracranial EEG recording: criteria for patient selection.

Twenty-two patients with intractable complex partial seizures (CPS) were treated with temporal lobectomy. Eighteen of 22 (82%) are seizure-free while receiving medication, with a mean follow-up time of 4 years. In each case, the clinical seizure pattern, interictal and ictal scalp EEG, magnetic resonance imaging (MRI), neuropsychological testing, and results of the intracarotid amobarbital procedure (IAP) converged to indicate a localized abnormality. None of the patients in this series had mass lesions, vascular malformations, or cortical scars, but 18 of 22 had hippocampal atrophy on MRI and 20 had hippocampal sclerosis (HS) on pathologic examination. We believe it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively. Such patients do not require invasive EEG monitoring, and they represent approximately 20% of the patients treated surgically in our epilepsy unit in the past several years.

Adolescent↗
PubMed1995

Sudden death and staged therapy for hemodynamic stabilization in patients enrolled in a heart transplantation program.

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14% +/- 5%, New York Heart Association Class II/III/IV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirty-seven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninety-nine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE1 for pre- and afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 +/- 9 months; patients who underwent staged therapy for 9 +/- 5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1995

H714Q mutation in Wilson disease is associated with late, neurological presentation.

Wilson disease is an autosomal recessive copper storage disease resulting from an inability of the liver to excrete copper. Patients can present at a young age, generally with symptoms of liver copper intoxication, or later on, generally with neurological symptoms. The gene for Wilson disease has recently been cloned. Five mutations have been described so far, but only one is found frequently, H714Q. We analysed 38 Dutch symptomatic Wilson disease patients for the H714Q mutation and correlated this finding with age and symptoms at presentation. Ten patients homozygous for the H714Q mutation presented at a mean age of 20.3 (SD 6.1) years, with either neurological symptoms or a Kayser-Fleischer ring. Six patients with a H714Q mutation in one chromosome and an unknown mutation in the other chromosome presented at a mean age of 17.8 (SD 5.8) years, with either neurological or hepatic symptoms. With the exception of one, all 22 patients with an uncharacterised mutation in both chromosomes presented with liver involvement, at a mean age of 9.9 (SD 2.4) years. The difference in age at presentation between the H714Q/H714Q group and the patients with an unknown mutation was highly significant (p < 0.0001). This suggests that the H714Q mutation represents a relatively mild mutation, possibly with some residual function in the copper transporting protein, resulting in a slower build up of copper.

Adenosine Triphosphatases↗
PubMed1995

Efficiency of oxidative work performance of skeletal muscle in patients with cystic fibrosis.

BACKGROUND: Exercise intolerance in patients with cystic fibrosis is commonly attributed to reduced pulmonary and nutritional status. The possible role of diminished efficiency of mitochondrial oxidative phosphorylation in relation to skeletal muscle performance was investigated in patients with cystic fibrosis. METHODS: In vivo synthesis of ATP in skeletal muscle during submaximal exercise was studied in eight patients with cystic fibrosis aged 12-17 years, and in 19 healthy control subjects aged 8-36 years. The intracellular pH and concentrations of phosphate compounds were calculated at four steady states from phosphorus-31 labelled nuclear magnetic resonance spectroscopy measurements in the forearm muscle during bulb squeezing in an exercise protocol. Normalised power output, expressed as percentage maximal voluntary contraction (Y, in %MVC), was related to the energy force of ATP hydrolysis (X = ln [ATP]/[ADP][Pi]). This relationship provides an in vivo measure of efficiency of oxidative work performance of skeletal muscle. RESULTS: During all workloads (but not at rest) intracellular pH was higher in the patients with cystic fibrosis than in the controls. The linear least square fit for Y = a-bX showed high correlations in both groups; the slope b was 19% lower in the patients than in the controls (11.8% v 14.5% MVC/ln M; 95% confidence interval for difference 0.3 to 5.0). CONCLUSIONS: In patients with cystic fibrosis oxidative work performance of skeletal muscle is reduced. This may be related to secondary pathophysiological changes in skeletal muscle in cystic fibrosis.

Adolescent↗
PubMed1995

Quasi-linear relationship between Gibbs free energy of ATP hydrolysis and power output in human forearm muscle.

The postulated strictly linear descriptions of the rate dependence of oxidative phosphorylation in skeletal muscle on the free energy of ATP hydrolysis (delta GP) over the range of physiological steady states fail to harmonize with reported findings of identical basal respiration rates in mammalian muscles at different delta GP values. The relevance of an extension of the strictly linear description to a description deriving from enzyme kinetics that predicts a sigmoidal dependence was investigated in human finger flexor muscle using 31P-nuclear magnetic resonance spectroscopy. At constant pH 7.0, the experimental variation of adenine nucleotide concentrations with power output, which reflects the rate of oxidative phosphorylation, was compared with predictions by various formulations of adenine nucleotide control of respiration. The quasi-linear sigmoidal description was found to be statistically equivalent but physiologically superior to the strictly linear description. The predicted maximal oxidatively sustained steady-state power output and rate-dependent sensitivity of respiration to changes in delta GP were in agreement both with theoretical considerations and with experimental observations in the present study and other studies of intact mammalian skeletal muscle.

Adenosine Diphosphate↗
PubMed1995

Demonstration of thymopoietin transcripts in different hematopoietic cell lines.

We have cloned and characterized the human thymopoietin (TP) coding region and studied the mRNA expression of this gene in different hematopoietic cell lines. The 150-bp PCR fragment that encodes the 49-amino-acid human TP peptide was isolated from genomic placental DNA. Its colinearity with the cDNA sequence suggests lack of introns within the coding region. TP mRNA expression was demonstrated in lymphocytes from all the differentiation stages investigated, as well as in a myeloid cell line (K-562). These findings suggest a further expansion of the proposed TP functions.

Amino Acid Sequence↗
PubMed1995

[Cerebral ischemia: ontogenetic differences in energy metabolism and protein biosynthesis].

OBJECTIVE: Are ontogenetic differences in the resistance of the brain towards ischemia reflected by differences in the postischemic disturbance of cerebral protein synthesis (PS) independently from energy metabolism (EM)? METHODS: We studied hippocampal slices from immature (E60) and mature (E60) fetal guinea pigs as well as from adult guinea pigs. Cerebral EM and PS were measured during and up to 24 h after ischemia. RESULTS: After in vitro ischemia there was no inhibition in cerebral PS in immature fetuses, a transient inhibition in mature fetuses, and a permanent inhibition in adults. During and after in vitro ischemia cerebral EM was hardly disturbed in immature fetuses. No differences in cerebral EM could be observed between mature fetuses and adults. CONCLUSION: Ontogenetic differences in the resistance of the brain towards ischemia are reflected by differences in the postischemic disturbance of cerebral PS. The differences between mature fetuses and adults are independent from cerebral EM.

Animals↗