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R Berger

Publications and source records attributed to R Berger.

At least 199 records · Page 11Linked to original sources
PubMed1997

The TEL gene products: nuclear phosphoproteins with DNA binding properties.

The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.

Animals↗
PubMed1997

Asymptomatic and late-onset ornithine transcarbamylase deficiency caused by a A208T mutation: clinical, biochemical and DNA analyses in a four-generation family.

We describe a 4-generation family in which a previously healthy 10-year-old boy died of late-onset ornithine transcarbamylase (OTC) deficiency. Pedigree analysis and allopurinol loading tests in female relatives were not informative. A missense mutation (A208T) in the OTC gene was detected in the deceased patient and in several clinically healthy male and female relatives, the oldest male being 97 years old. OTC deficiency was established in autopsy liver tissue of the propositus and liver biopsy samples of his sister, mother, and a maternal uncle. The males had 4% and 6% residual activity, respectively, the females 58% and 67%, respectively. The observed relation between the mutation and the decreased OTC activity in liver tissue of these subjects suggests that the mutation is a deleterious one. Late-onset, "mild" OTC deficiency can have a fatal or a favorable outcome. The disease can segregate undetected in families.

Adult↗
PubMed1997

The use of upper extremity anthropometrics in the clinical assessment of patients with amyotrophic lateral sclerosis.

We evaluated the feasibility of using upper extremity anthropometrics to monitor the clinical status of 18 patients with amyotrophic lateral sclerosis (ALS). The bone-free arm muscle area (AMA) was computed using measurement of triceps skinfold thickness and the mid-upper arm circumference according to published formulae. The AMA correlated significantly with body mass, isokinetic muscle force generation, cross-sectional muscle area on computerized tomography scanning, and pulmonary functions including forced vital capacity and maximal voluntary ventilation. Serial determinations of AMA demonstrated a decline in 10 of 13 patients over 6 months. We pilot tested the use of AMA in a clinical trial of ciliary neurotrophic factor (CNTF) in the treatment of ALS. The AMA progressively decreased by 13%, 15%, and 30% in ALS patients treated with 0 microg CNTF/kg, 15 microg CNTF/kg, and 30/microg CNTF/kg, respectively, over a 9-month treatment period. We conclude that measurement of AMA provides a simple, inexpensive method to monitor the progression of muscle atrophy in ALS patients. The technique does not require effort on the part of the patient and as such, appears to have potential utility as an outcome measure in clinical drug trials.

Adult↗
PubMed1997

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake.

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT2A receptor-binding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pKa value leads to ionization of the molecule at blood pH, the pKa value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pKa value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pKa cannot be simply explained by the increase in the pKa-governed proportion of the neutral species.

Animals↗
PubMed1997

Characterization of in vitro culture of HIV-negative Kaposi's sarcoma-derived cells. In vitro responses to alfa interferon.

We established long-term cultures from skin tumors of nine patients suffering from classical Kaposi's sarcoma (KS). Spindle cells obtained after enzymatic digestion were cultured on gelatin- or fibronectin-coated flasks in DMEM with 15% fetal calf serum, aFGF and heparin. Immunohistochemical staining was positive for MHC class I, laminin, type IV collagen, vimentin, alpha smooth muscle actin (20-40% of cells), caldesmon (20%), calponin (20-40%) and smooth muscle myosin (20-40%), and was negative for common leukocyte antigen, CD4, LFA1, CD34 and cytokeratin. Around 20% of cells up to the third passage in culture expressed the endothelial markers CD36, BMA 120 but were negative for UEA and Fc von Willebrand. Smooth muscle proteins were detected with immunoblotting. Using the polymerase chain reaction, human herpes virus 8 (HHV8) sequences were detected in primary cultures of three out of seven cell lines but were rapidly lost during in vitro passaging. KS-derived cells did not proliferate in serum-free medium, had a normal karyotype and did not grow in soft agar medium. Tumors formed in nude mice injected with KS-derived cells. The tumors were composed of mouse cells and were highly vascularized. Our results suggest that KS-derived cells are heterogeneous: the majority of cells have either a smooth muscle cell or a fibroblastic phenotype. Another minor cell compartment was composed of endothelium-derived cells. KS cells do not possess the characteristics of transformed cells in vitro and may be composed of polyclonal activated cells. Recombinant alpha interferon (rIFN) slightly inhibited the growth of KS-derived cells and increased the expression of MHC class I antigens. While cells were resistant to natural killer (NK) cell-mediated cytotoxicity, they became sensitive to rIFN-primed NK cells. Thus, the antitumor potential of rIFN against KS in vivo could result from immunomodulatory rather than from direct antiproliferative effects.

Animals↗
PubMed1997

Total energy expenditure in infants with bronchopulmonary dysplasia is associated with respiratory status.

UNLABELLED: Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 +/- 13 days) and nine matched controls (36 +/- 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 +/- 9 vs 63 +/- 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min-1]; r2 = 0.82, P < 0.001), and was the single most significant determinant of Ee. CONCLUSION: Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD.

Anthropometry↗
PubMed1997

Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. Moreover, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype.

Cholestasis, Intrahepatic↗
PubMed1997

Acute lymphoblastic leukemia and chromosome 21.

A short review of chromosome 21 abnormalities in acute lymphoblastic leukemia (ALL) is presented. Trisomy and polysomy 21 are nonrandom anomalies that are frequently observed in ALL. Their occurrence, although not specific, as well as the high incidence of acute leukemia in subjects with constitutional trisomy 21, suggests that chromosome 21 plays a particular role in leukemogenesis. More specific to ALL, t(12;21)(p13;q22), resulting in a fusion TEL-AML1, gene has recently been shown to be the most frequent translocation in childhood B-cell lineage ALL (20-30% of cases). In addition, the importance of analysis of marker chromosomes with fluorescence in situ hybridization (FISH) techniques is underscored as partial amplifications or rearrangements of chromosome 21 may be implicated.

Chromosome Aberrations↗
PubMed1997

Peri/intraventricular haemorrhage: a cranial ultrasound study on 5286 neonates.

OBJECTIVE: We launched a prospective cranial ultrasound study at the Department of Obstetrics and Gynaecology of the University of Giessen. In this study we examined the incidence and severity of brain damage in neonates and related them to various obstetrical risk factors. STUDY DESIGN: More than 90% of all neonates born between 1984 and 1988 were included in the study (n = 5286) and were screened by ultrasound for cerebral abnormalities on 5-8 days post-partum. The relation between the incidence of peri/intraventricular haemorrhages (PIVH) and obstetrical risk factors were analyzed by contingency tables. RESULTS: The most frequent abnormality was PIVH (3.6%) of various degrees (grade I-III). Periventricular leucomalacia, porencephalia, subarachnoidal haemorrhages, and hydrocephali were rare (< or = 0.2%). The incidence of PIVH increased progressively with decreasing gestational age, e.g. from 1.6% at 38-43 weeks up to 50.0% at 24-30 weeks of gestation. A large percentage of babies with PIVH were clinically normal. In immature neonates there was a close inverse relationship between Apgar score at 1, 5 and 10 min and both incidence and severity of PIVH. This was in contrast to findings in mature neonates where a marked increase in the incidence of PIVH was found only with Apgar scores as low as 0-4 points. The relation between the incidence of PIVH and both cardiotocography and arterial cord blood pH was poor, independent of the gestational age. The incidence of PIVH was increased in growth retarded fetuses (pH < or = 7.29), premature rupture of membranes, fever sub partu and gestosis. It is interesting to note that in mature fetuses there was no difference in the incidence of PIVH between vaginally delivered (0.8%) and sectioned breech presentations (2.1%). In preterms at 35-37 weeks with prolonged labour and secondary cesarean section, the incidence of PIVH was very high (11.2%). CONCLUSION: From the present study we conclude that the incidence of PIVH especially in immature neonates is highly associated with low Apgar scores at birth. Since the Apgar score reflects the clinical condition and the degree of circulatory centralisation of neonates that is influenced by various ante- and intranatal risk factors, a protective obstetrical management is necessary to reduce the incidence of PIVH in neonates.

Acid-Base Equilibrium↗
PubMed1997

Inherited defects of purine and pyrimidine metabolism: laboratory methods for diagnosis.

The diagnosis of the majority of the known inherited defects of purine and pyrimidine metabolism can be achieved by analysing urinary excretion profiles. A quantitative measurement of the urinary uric acid/creatinine ratio should be the first approach for purine defects. The general screening system involves separation of the bases and nucleosides by reversed-phase high-performance liquid chromatography and multiwavelength UV detection. The catabolic defects of pyrimidine degradation can be diagnosed by gas chromatography-mass spectrometry as used for organic acids. For the detection of adenylosuccinase deficiency, several simple but effective thin-layer chromatographic methods are available. Techniques such as liquid chromatography-mass spectrometry, direct nega-tiveion fast-atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy give promising results, but are not yet being used on a large scale. Patients should keep to a simple diet and preferably be free of medication in order to allow a reliable interpretation of the analytical data.

Animals↗
PubMed1997

A new breakpoint, telomeric to TEL/ETV6, on the short arm of chromosome 12 in T cell acute lymphoblastic leukemia.

Abnormalities of the short arm of chromosome 12 frequently involve the TEL/ETV6 gene in acute leukemias. In two cases of T cell acute lymphoblastic leukemia with translocation t(12;14)(p13;q11) and t(7;12)(q35;p13), respectively, the breakpoints were located telomeric to the TEL/ETV6 locus. Further fluorescence in situ hybridization (FISH) studies showed that the breakpoint was located between two markers, FGF6 (centromeric) and D12S983 (telomeric) on 12p in both patients. This result suggests that a new chromosomal breakpoint can nonrandomly involve rearrangements in T cell malignancies. The breakpoint on chromosome 14 was localized centromeric to the TRCA/D locus.

Adult↗
PubMed1997

Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.

A wide variety of abnormalities of the short arm of chromosome 12 has been reported in hematologic malignancies. The most frequent rearrangements result from t(12;21)(p13;q22) of childhood acute lymphoblastic leukemia, a translocation cryptic when leukemic cells are analyzed with chromosome banding techniques. This translocation results in a fusion of the TEL/ETV6 and AML1 genes. In this report, examples of rearrangements of 12p are presented. Study of two complex chromosome abnormalities associated with t(12;21) emphasizes the importance of using FISH in detection of such translocations. Three novel translocations involving the TEL/ETV6 gene localized on 12p13 are also reported: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). Finally, the presentation of two translocations with breakpoints located centromeric to TEL/ETV6 highlights the not uncommon involvement of genes other than TEL/ETV6 on 12p.

Adolescent↗
PubMed1997

Autosomal recessive phosphorylase kinase deficiency in liver, caused by mutations in the gene encoding the beta subunit (PHKB).

The association of autosomal recessive phosphorylase kinase deficiency in liver of a 3 1/2-year-old female child with mutations in the gene encoding the common part of the beta subunit of phosphorylase kinase is reported. The proband had a severe deficiency of phosphorylase kinase in liver, while the phosphorylase kinase activity in erythrocytes was only slightly diminished. She had no symptoms of muscle involvement. The complete coding sequences of the liver gamma subunit and of the beta subunit of phosphorylase kinase of the proband were analyzed for the presence of mutations, by either reverse-transcribed PCR or SSCP analysis. Three deviations from the normal sequence were found in the region encoding the common part of the beta subunit of phosphorylase kinase-namely, a 1827G-->A (W609X) transition, a 2309A-->G (Y770C) transition, and a deletion of nucleotides 2896-2911-whereas no mutations were detected in the sequence encoding the liver gamma subunit of phosphorylase kinase. The 1827G-->A mutation and the deletion both result in the formation of early stop codons. Investigation of DNA showed that the deletion is caused by a splice-acceptor site mutation (IVS30(-1),g-->t). Family analysis revealed that the 1827G-->A and IVS30(-1),g-->t substitutions are located on different parental chromosomes and that compound heterozygosity for these mutations segregates with the disease. The 2309A-->G mutation was detected in 2%-3% of the normal population. Thus, it is concluded that the deficiency of phosphorylase kinase in this proband is caused by compound heterozygosity for the 1827G-->A and the IVS30(-1),g-->t mutations and that the 2309A-->G mutation is a polymorphism. This implies that a defect in the sequence encoding the common part of the beta subunit of phosphorylase kinase may present as liver phosphorylase kinase deficiency.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1997

Prostaglandin E1--bridge to cardiac transplantation. Technique, dosage, results.

BACKGROUND: Heart transplantation candidates who remain severely symptomatic despite therapy are normally hospitalized. Continuous infusion of intravenous drugs from a portable pump may allow such patients to live a fairly active life until a donor heart is found. AIM: To investigate in an open pilot study if heart transplantation can be safely accomplished if these patients are continuously bridged with various regimens including inotropic support with low-dose dobutamine in conjunction with dopamine and prostaglandin E1. METHODS: We report on 5 years' experience with prostaglandin E1, a potent vasodilator with proven efficacy in severe heart failure when coupled with catecholamines. From 1990 to 1995 54 heart transplantation candidates were bridged with prostaglandin E1 in addition to dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 (group A; n = 32) or in addition to 3 micrograms.kg-1 min-1 dopamine alone (group B; n = 22), and 11 heart transplantation candidates were bridged with dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 only (group C; n = 11). In an initial dose-ranging test, prostaglandin E1 was uptitrated to side effect limit (29 +/- 1 ng.kg-1.min-1). Haemodynamics, except for stroke volume index, were similar in all patients at baseline and a sufficient haemodynamic response (20% increase in stroke volume) was observed during the acute study. Fifty percent of the peak dose was used for initiating chronic therapy; the dose of prostaglandin E1 was further reduced if side effects recurred. RESULTS: Twenty-nine (54%) patients in groups A and B and six in group C could be discharged home with chronic therapy via a Hickman catheter connected to a portable pump. After 4 weeks in six patients in group A and in 13 patients in group B, when prostaglandin E1 had been reduced from 15 +/- 2 ng.kg-1.min-1 to 8 +/- 1 ng.kg-1 min-1 increases in cardiac index and decreases in systemic vascular resistance were sustained, and a permanent decrease in pulmonary vascular resistance index was observed in group B. Intravenous therapy was changed in nine patients (3/1/5) because of side effects and worsening heart failure. Prostaglandin E1 was withdrawn in three of these patients because of an increase in serum creatinine (3 mg.100 ml-1), and in one because of noncompliance. In total, there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6) and six (1/2/3) weaned survivors (including one non-cardiac death) in this study. Overall outcome was similar in groups A and B, but distribution after 2 months appeared to be different (P < 0.05) based on more transplantations in group A. CONCLUSION: We concluded that chronic infusions with prostaglandin E1 at reduced dosages is a feasible and safe therapeutic adjunct to bridge end-stage heart failure patients and may yield desirable effects in a subset of patients in the absence of inotropic support by dobutamine.

Alprostadil↗
PubMed1997

Fatal trauma: the modal distribution of time to death is a function of patient demographics and regional resources.

BACKGROUND: Unlike previous studies in an urban environment, this study examines traumatic death in a geographically diverse county in the southwestern United States. METHODS: All deaths from blunt and penetrating trauma between November 15, 1991, and November 14, 1993, were included. As many as 150 variables were collected on each patient, including time of injury and time of death. Initial identification of cases was through manual review of death records. Information was supplemented by review of hospital records, case reports, and prehospital encounter forms. RESULTS: A total of 710 traumatic deaths were analyzed. Approximately half of the victims, 52%, were pronounced dead at the scene. Of the 48% who were hospitalized, the most frequent mechanism of injury was a fall. Neurologic dysfunction was the most common cause of death. Two distinct peaks of time were found on analysis: 23% of patients died within the first 60 minutes, and 35% of patients died at 24 to 48 hours after injury. CONCLUSIONS: Although there appears to continue to be a trimodal distribution of trauma deaths in urban environments, we found the distribution to be bimodal in an environment with a higher ratio of blunt to penetrating trauma.

Adult↗
PubMed1997

Tissue magnesium levels and the arrhythmic substrate in humans.

INTRODUCTION: Magnesium deficiency has been implicated in the pathogenesis of sudden death, but the investigation of arrhythmic mechanisms has been hindered by difficulties in measuring cellular tissue magnesium stores. METHODS AND RESULTS: To see if magnesium deficiency is associated with a propensity toward triggered arrhythmias, we measured tissue magnesium levels and QT interval dispersion (as an index of repolarization dispersion) in 40 patients with arrhythmic complaints. Magnesium was measured in sublingual epithelium using X-ray dispersive analysis. QT interval dispersion was assessed on 12-lead surface ECGs in all patients, and programmed stimulation was performed in 28. The sublingual epithelial magnesium level ([Mg]1), but the not the serum level, correlated inversely with QT interval dispersion in 40 patients (r = 0.58, P < 0.005); in 12 patients undergoing repeat testing on therapy, the change in magnesium also correlated inversely with the change in QT dispersion (r = 0.61, P < 0.05). Patients with left ventricular ejection fractions > 40% had significantly higher tissue magnesium and lower QT dispersion (34.5 +/- 0.5 mEq/L, 81 +/- 8 msec) than those with left ventricular ejection fractions < 40% (32.7 +/- 0.5 mEq/L, P < 0.01, and 114 +/- 9 msec, P < 0.05). There was no difference in either [Mg]1 or QT dispersion in the 16 patients with inducible monomorphic ventricular tachycardia versus the 12 noninducible patients. CONCLUSION: Reduced tissue magnesium stores may represent a significant risk factor for arrhythmias associated with abnormal repolarization, particularly in patients with poor left ventricular systolic function, but may not represent a risk for excitable gap arrhythmias associated with a fixed anatomic substrate (e.g., monomorphic ventricular tachycardia).

Adult↗
PubMed1997

Molecular cytogenetics of childhood acute myelogenous leukaemias.

Chromosome abnormalities of childhood acute myeloblastic leukaemia, observed at least in 70-80% of cases, are presently recognized as important parameters for diagnostic, prognostic and follow-up purposes. These abnormalities are numerical, structural or both numerical and structural. They are also classified in "primary" abnormalities, usually more or less related with one subtype of leukaemia, and "secondary" abnormalities thought to appear in a second time. Chromosome abnormalities of childhood acute myeloblastic leukaemia (AML) are not basically qualitatively different from those of adult AML. The main difference lies in the incidence of the various types of abnormalities, and these differences appear to be more marked for age extremes such as infants and elderly patients. In total, 3 common abnormalities are more frequently observed in childhood than in adult AML; t(8;21) in AML-M2, monosomy 7 in AML-M4, der(11q) in AML-M5. In addition, molecular rearrangements associated with chromosomal abnormalities are dependent on the type of rearrangement and not on age. As in adult AML, the prognostic value of chromosome abnormalities has been diversely evaluated; some anomalies seem to be related to a shorter survival than others independent of the various therapeutic protocols used. In the present work, chromosome abnormalities of childhood AML have been reviewed according to cytologic subtypes as well as to some clinical settings. Special attention has been paid to abnormalities frequently or exclusively encountered in children.

Antineoplastic Agents, Alkylating↗