Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 127 records · Page 7Linked to original sources

PubMed1999

Chromosome 16 inversion-associated translocation: two new cases.

Two patients with chromosome 16 inversion-associated translocation were studied with conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques. The same chromosome 16 was involved in inversion and translocation in both patients. The chromosome translocation breakpoint was located within the heterochromatin of chromosome 16 but outside the alpha satellite domain in the t(10;16) of the first patient, whereas it was outside the heterochromatin area in the second case with t(1;16). These two types of rearrangements may be due to different mechanisms and illustrate the possible difficulties in recognizing the chromosome 16 inversion without FISH studies.

Adult↗

PubMed1999

Transcriptional analysis of the cyclophilin A gene (cypA) of Streptomyces chrysomallus.

Streptomyces chrysomallus produces a 17.5-kDa cyclophilin (CypA) as a major cytosolic protein. Northern blotting of total RNA from S. chrysomallus showed that cypA is transcribed as a monocistronic 500-nt transcript during the vegetative growth phase only. Consistently, Western blot analysis and enzyme activity determinations revealed a high level of CypA which declined drastically when cultures entered postexponential phase. Primer extension experiments revealed that cypA is transcribed as a leaderless transcript with the startpoint of transcription and translation being the same AUG codon. Analysis of -10 and -35 regions revealed an EohrdB-specific promoter consensus sequence in accordance with the observed transcription during vegetative growth of cultures. The leaderless cypA mRNA sequence between codons 5 to 12 shows complementarity to an internal antidownstream box of 16S rRNA of Streptomyces lividans. This may indicate a possible interaction of the leaderless cypA transcript with the 16S mRNA in translation initiation.

Base Sequence↗

PubMed1999

Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia.

Several features are characteristic for hairy cell leukemia (HCL). Among those are pancytopenia, bone marrow fibrosis, and the appearance of a defined tumor cell phenotype in peripheral blood (PB), bone marrow (BM), and spleen. Hairy cells (HC) coexpress antigens specific for B lymphocytes and monocytes/macrophages and thus the malignant cell does not seem to be restricted to a defined lineage. When serum or bone marrow aspirate was screened by enzyme-linked immunosorbent assay (ELISA) for basic fibroblast growth factor (bFGF), specimen derived from HCL (serum: mean value, 29 pg/mL; BM aspirate: mean value, 641 pg/mL) contained significantly higher levels than those from healthy subjects. To study whether peripheral blood mononuclear cells (PBMC) derived from patients suffering from HCL and healthy donors (HD) were capable of producing bFGF, culture supernatant (conditioned medium, [CM]) was tested for the presence of this cytokine. While bFGF was not detectable in cell cultures from HD, HCL-derived CM contained relatively high levels of bFGF. CM was successfully used for stimulation of mesenchymal cell proliferation, which could be inhibited by a neutralizing anti-bFGF antibody. Cellular activation by pokeweed mitogen (PWM) or the combination of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) plus calcium ionophore (Ca-Ip) led to an enhanced mRNA expression. Results of Western blot experiments showed that HC synthesize at least three isoforms (approximately 18, 23, and 25 kD), but only the 23-kD isoform is exported. To assess the nature of the producer cell, double immunofluorescence analysis using a bFGF-specific and an anti-CD11c monoclonal antibody (MoAb) was undertaken. The majority of cells scoring positive for CD11c were also reactive with the anti-bFGF MoAb. Furthermore, enrichment of CD19/CD11c-positive cells correlated with enhanced bFGF levels, thereby supporting the argument for HC being the producer cells of bFGF. A biological function of bFGF in HCL might be mediation of chemoresistance, as 2-chlorodeoxyadenosine (2-CdA)-induced inhibition of cell proliferation can be reversed by bFGF. Endogenous bFGF production by HC is not affected by this purine analogue and 2-CdA-induced apoptosis is diminished in bFGF-producing HC as compared with normal PBMC. Therefore, bFGF expression by HC might be important for resistance to chemotherapy and survival of the malignant cells.

Aged↗

PubMed1999

Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay.

BACKGROUND: Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. METHODS AND RESULTS: Aortic and LV pressures were measured in 18 heart failure patients (mean+/-SD: LV ejection fraction, 19+/-7%; LV end-diastolic pressure, 25+/-8 mm Hg; QRS duration, 157+/-36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7+/-19.0% and pulse-pressure by 18.0+/-18.4% (P<0.01). Biventricular pacing yielded less change (+12.8+/-9.3% in dP/dtmax, P<0.05 versus LV). Pressure-volume analysis performed in 11 patients consistently revealed minimal changes with RV pacing but increased stroke work and lower end-systolic volumes with LV pacing. Optimal AV intervals averaged 125+/-49 ms, and within this range, AV delay had less influence on LV function than pacing site. Basal QRS duration positively correlated with %DeltadP/dtmax (P<0.005), but pacing efficacy was not associated with QRS narrowing. Conduction delay pattern generally predicted pacing sites with most effect. CONCLUSIONS: VDD pacing acutely enhances contractile function in heart failure patients with intraventricular conduction delay. Single-site pacing at the site of greatest delay achieves similar or greater benefits to biventricular pacing in such patients. These data clarify pacing-effect mechanisms and should help in candidate identification for future studies.

Adult↗

PubMed1999

Duplication of band 12q24 in acute myeloblastic leukemia.

Cytogenetic studies of two patients with acute myeloblastic leukemia, classified as M1 and M2, showed a partial duplication of the distal part of the long arm of chromosome 12 (12q24) as the sole detectable chromosome abnormality. High white blood cell count was common to the two leukemic children. Fluorescence in situ hybridization analysis with the use of a whole-chromosome 12 painting probe and a telomeric probe confirmed the apparent absence of any translocation. The genes involved in the duplication could not be ascertained, but several candidate genes such as growth-factor receptors or genes encoding transcription factors localized to 12q22-q24 should be investigated in the molecular analysis of these duplications.

Adolescent↗

PubMed1999

Clinical management of carpal tunnel syndrome: a 12-year review of outcomes.

Carpal tunnel syndrome (CTS) is a disorder frequently encountered by occupational health care specialists. The health care management of this disorder has involved a diverse set of clinical procedures. The present article is a review of the literature related to CTS with an emphasis on occupational-related CTS. MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycLIT, and NIOSHTIC databases from 1985-1997 were searched for treatment outcome studies related to CTS. Treatments of interest included surgery, physical therapy, drug therapy, chiropractic treatment, biobehavioral interventions, and occupational rehabilitation. A systematic review of the effects of these interventions on symptoms, medical status, function, return to work, psychological well-being, and patient satisfaction was completed. Compared to other treatments, the majority of studies assessed the effects of surgical interventions. Endoscopic release was associated with higher levels of physical functioning and fewer days to return to work when compared to open release. Limited evidence indicated: 1) steroid injections and oral use of B6 were associated with pain reduction; 2) in comparison to splinting, range of motion exercises appeared to be associated with less pain and fewer days to return to work; 3) cognitive behavior therapy yielded reductions in pain, anxiety, and depression; and, 4) multidisciplinary occupational rehabilitation was associated with a higher percentage of chronic cases returning to work than usual care. Workers' compensation status was associated with increased time to return to work following surgery. Conclusions are preliminary due to the small number of well-controlled studies, variability in duration of symptoms and disability, and the broad range of reported outcome measures. While there are several opinions regarding effective treatment, there is very little scientific support for the range of options currently used in practice. Despite the emerging evidence of the multivariate nature of CTS, the majority of outcome studies have focused on single interventions directed at individual etiological factors or symptoms and functional limitations secondary to CTS.

Analgesia↗

PubMed1999

Outpatient exercise training in children with cystic fibrosis: physiological effects, perceived competence, and acceptability.

Exercise training is currently advocated as part of the treatment of patients with cystic fibrosis (CF). However, data are few that document physiologic benefits or changes in patients' perceptions of long-term training programs in children with CF. The aim of this study was to investigate the effects and acceptability of a home cycling program in children with CF. Fourteen patients (9 boys, 5 girls) with CF, mean (SD) age 14.1 (2.0) years, with mild to moderate impairment of lung function (forced expiratory volume in 1 s, mean (SD) 58.3 (16.3)% of predicted) were studied for 1 year. The first half of the study year was used to obtain baseline values at 0 and 6 months. During the second half of the year, a cycle program was carried out 5 times a week, for 20 min each day at a level of work that resulted in a heart rate of 140-160 beats/min. Once a week the cycle program was supervised by a physiotherapist. Measurements were repeated at 12 months. Effects of the exercise program were measured in terms of lung function, nutritional status, growth, muscle strength, exercise performance, perceived competence, and attitude towards the training program. Differences between the changes during the 6-month training period as compared to the 6-month control period were analyzed by multivariate statistics and nonparametric tests. Statistically significant differences (P < 0.05) between the two periods were found with respect to muscle strength of knee extensors and ankle dorsiflexors, and with respect to maximal oxygen consumption per kg body weight as well as per kg fat free mass. All changes were positive. No adverse effects were found. Perceived competence showed significant positive changes in feelings about physical appearance, general self-worth, and Total Perceived Competence Score. Scores concerning perceived acceptability of the program were significantly lower at the end of the training period; however, patients reported that they did want to continue with other sorts of training. We conclude that an exercise training program in the home can produce beneficial effects on oxygen consumption, muscle force, and perceived competence in children with CF. However, acceptability of the program was low, suggesting that long-term adherence would be poor, and hence, other sorts of training need to be identified.

Adolescent↗

PubMed1999

Fine-resolution mapping by haplotype evaluation: the examples of PFIC1 and BRIC.

Loci for two inherited liver diseases, benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis type 1 (PFIC1), have previously been mapped to 18q21 by a search for shared haplotypes in patients in two isolated populations. This paper describes the use of further haplotype evaluation with a larger sample of patients for both disorders, drawn from several different populations. Our assessment places both loci in the same interval of less than 1 cM and has led to the discovery of the PFIC1/BRIC gene, FIC1; this discovery permits retrospective examination of the general utility of haplotype evaluation and highlights possible caveats regarding this method of genetic mapping.

Cholestasis, Intrahepatic↗

PubMed1999

Skinfold measurements in children with cystic fibrosis: monitoring fat-free mass and exercise effects.

UNLABELLED: Monitoring fat free mass (FFM), an indicator of nutritional status and a predictor of exercise performance in children, is particularly important in patients with cystic fibrosis (CF). We assessed validity of the skinfold method for measuring FFM, and its changes with exercise training, in children with CF. A total of 14 children with moderately severe symptoms of CF (age 10-18 years) were followed longitudinally and measured three times, before (at 0 and 6 months) and after exercise training (at 12 months). Separately, single measurements were conducted in 12 children with mild symptoms of CF and in 13 healthy controls. FFM was calculated from four skinfold measurements, and compared with estimations from total body water measured with deuterium dilution. The FFM calculated from skinfolds was 1.7% (P < 0.05) and 3.3% (P < 0.005) higher than that estimated with deuterium oxide dilution in patients with CF and controls, respectively. Limits of agreement were similar in patients with moderate and mild symptoms and in controls. The measurements in patients with moderate symptoms showed similar bias and limits of agreement at 6 and 12 months as compared to 0 months. Changes in FFM measured with both methods were significantly correlated before exercise (r = 0.82, P < 0.0005), and after exercise training (r = 0. 60, P < 0.05). CONCLUSION: In children with cystic fibrosis, skinfold measurements are applicable to monitor fat free mass irrespective of clinical severity of the disease, and repeated measurements at intervals of 6 months are applicable to monitor changes in fat free mass during exercise training.

Adolescent↗

PubMed1999

Loss of the TEL/ETV6 gene by a second translocation in ALL patients with t(12;21).

Inactivation of the non translocated TEL/ETV6 gene is commonly associated with translocation (12;21) of acute lymphoblastic leukemia (ALL). Translocations involving the short arm of chromosome 12 were analysed in two children with t(12;21) ALL. Fluorescence in situ hybridation studies showed that these associated translocations resulted in loss of TEL/ETV6. While hybridization with a YAC probe covering TEL/ETV6 was positive in one patient, analysis with cosmid probes covering the gene demonstrated that the gene was in fact deleted. It is concluded that deletions involving TEL/ETV6 can remain undetected by FISH using only YAC probes.

Adolescent↗

PubMed1999

Pathophysiology of perinatal brain damage.

Perinatal brain damage in the mature fetus is usually brought about by severe intrauterine asphyxia following an acute reduction of the uterine or umbilical circulation. The areas most heavily affected are the parasagittal region of the cerebral cortex and the basal ganglia. The fetus reacts to a severe lack of oxygen with activation of the sympathetic-adrenergic nervous system and a redistribution of cardiac output in favour of the central organs (brain, heart and adrenals). If the asphyxic insult persists, the fetus is unable to maintain circulatory centralisation, and the cardiac output and extent of cerebral perfusion fall. Owing to the acute reduction in oxygen supply, oxidative phosphorylation in the brain comes to a standstill. The Na(+)/K(+) pump at the cell membrane has no more energy to maintain the ionic gradients. In the absence of a membrane potential, large amounts of calcium ions flow through the voltage-dependent ion channel, down an extreme extra-/intracellular concentration gradient, into the cell. Current research suggests that the excessive increase in levels of intracellular calcium, so-called calcium overload, leads to cell damage through the activation of proteases, lipases and endonucleases. During ischemia, besides the influx of calcium ions into the cells via voltage-dependent calcium channels, more calcium enters the cells through glutamate-regulated ion channels. Glutamate, an excitatory neurotransmitter, is released from presynaptic vesicles during ischemia following anoxic cell depolarisation. The acute lack of cellular energy arising during ischemia induces almost complete inhibition of cerebral protein biosynthesis. Once the ischemic period is over, protein biosynthesis returns to pre-ischemic levels in non-vulnerable regions of the brain, while in more vulnerable areas it remains inhibited. The inhibition of protein synthesis, therefore, appears to be an early indicator of subsequent neuronal cell death. A second wave of neuronal cell damage occurs during the reperfusion phase. This cell damage is thought to be caused by the post-ischemic release of oxygen radicals, synthesis of nitric oxide (NO), inflammatory reactions and an imbalance between the excitatory and inhibitory neurotransmitter systems. Part of the secondary neuronal cell damage may be caused by induction of a kind of cellular suicide programme known as apoptosis. Knowledge of these pathophysiological mechanisms has enabled scientists to develop new therapeutic strategies with successful results in animal experiments. The potential of such therapies is discussed here, particularly the promising effects of i.v. administration of magnesium or post-ischemic induction of cerebral hypothermia.

Animals↗

PubMed1999

A case of chronic neutrophilic leukemia with deletion (11)(q23).

We report a case of chronic neutrophilic leukemia (CNL) in a 68-year-old man. Karyotype showed a clonal abnormality, never described before in CNL: 46,XY,del(11)(q23). Southern blot analysis of the MLL gene did not reveal any rearrangement, and reverse transcriptase polymerase chain reaction (RT-PCR) analysis did not show any fusion of BCR-ABL. Treatment with hydroxyurea and cytosine arabisonide was ineffective.

Aged↗

PubMed1999

Dynamics of fetal circulatory responses to hypoxia and asphyxia.

This review will focus on the dynamic changes of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during hypoxia and asphyxia caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organ will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxaemia and asphyxia is a rapid centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory de-centralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia?

Asphyxia Neonatorum↗

PubMed1999

Bridging to heart transplantation: prostaglandin E1 versus prostacyclin versus dobutamine.

BACKGROUND: Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. METHODS: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm-5m-2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. RESULTS: Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. CONCLUSIONS: The findings from this prospective open pilot trial suggest that continuous PGE1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE1 among other bridging agents.

Alprostadil↗

PubMed1999

MLL-AF1q fusion resulting from t(1;11) in acute leukemia.

The MLL gene, located on chromosome band 11q23 is fused to different partner genes as a result of various chromosomal translocations in hematopoietic malignancies. A t(1;11) (q21;q23) resulting in a MLL-AF1q fusion gene has previously been reported. Cytogenetic studies on six cases are reported, including one three-way translocation. FISH analysis using a YAC encompassing the MLL gene and a YAC encompassing the AF1q locus showed splitting in three cases and two patients, respectively. PCR analysis of two cases confirmed that AF1q is specifically associated with t(1;11)(q21;q23). The MLL-AF1q fusion mRNA was similar to that previously described in one case and involved MLL exon 7 in the other. This study confirms the specific involvement of AF1q in t(1;11) (q21;q23)-positive acute leukemia with monocytic involvement.

Artificial Gene Fusion↗

PubMed1999

Centric and pericentric chromosome rearrangements in hematopoietic malignancies.

Cytogenetic and fluorescence in situ hybridization (FISH) analysis of 10 patients with various hematopoietic malignancies revealed the presence of dicentric chromosomes or pericentric chromosome rearrangements. Dicentrics were only ascertained by FISH studies in six patients. Two types of pericentric chromosome rearrangements have been observed: 'classical' dicentrics with two clearly separated centromeric regions, and more unusual rearrangements with a breakpoint within the centromeric or heterochromatic area, but outside the alphoid domain. FISH analysis of partial chromosome 1 q duplications present in three Burkitt lymphoma cell lines confirmed the partial involvement of the non-alphoid centromeric domain in the duplicated chromosome segment. The incidence of centromeric and pericentromeric rearrangements in hematopoietic malignancies may be higher than hitherto admitted. The chromosomal localization of these rearrangements suggests several mechanisms possibly involved in the malignant process and deserves more systematic study.

Adolescent↗

PubMed1999

Molecular analysis of chromosomal breakpoints in three examples of chromosomal translocation involving the TEL gene.

The TEL gene is involved in several chromosomal abnormalities of human hematopoietic malignancies. The chromosome 12 breakpoints frequently lie within the fifth intron of the gene, particularly in the most frequent translocation involving TEL, the t(12;21)(p13;q22). In order to search for a peculiar mechanism involved in the genesis of these translocations, we have established the sequence of two t(12;21) and a t(9;12)(q24;p13) breakpoints. Our data do not reveal the involvement of VDJ recombinase activity or Alu sequences but favor the occurrence of staggered breaks and DNA repair activity in the genesis of these translocations.

Alleles↗

PubMed1999

Fluorescence in situ hybridization analysis of chromosome 1 abnormalities in hematopoietic disorders: rearrangements of DNA satellite II and new recurrent translocations.

Using fluorescence in situ hybridization analysis, breakpoints involving the long arm of chromosome 1 (1q) were localized in 36 patients with various hematopoietic disorders and rearrangements of the proximal part of 1q, as ascertained with banding techniques. The breakpoint was localized within the satellite II (sat II) domain in 14 patients with various abnormalities, between the sat II domain and the BCL9 locus in eight, between the BCL9 and ARNT loci in two, between sat II and ARNT in two others, and distal to ARNT in seven. A dicentric chromosome 1 was present in two patients. A high incidence of heterochromatin heteromorphism of chromosome 1 was present in this series. Two recurrent translocations were identified, t(1;2)(q12;q37) in three patients suffering from three different acute leukemia subtypes, and t(1;16)(q12;q24) in two patients with different diseases. Two patients had jumping translocations. Most of the rearrangements of 1q were secondary abnormalities, included in complex karyotypes. The roles of methylation, interactions with the proteins interfering with heterochromatin and possible gene silencing due to heterochromatin rearrangements are discussed.

Adolescent↗