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R Berger

Publications and source records attributed to R Berger.

At least 73 records · Page 4Linked to original sources
PubMed2001

Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic leukemia.

Fluorescence in situ hybridization (FISH) studies were performed in three cases of acute lymphoblastic leukemia (ALL) with marker chromosomes to analyze the contribution of chromosome 21 in these markers. FISH with a chromosome 21 painting probe confirmed that chromosome 21 was involved in all three cases. FISH with YAC probes showed that the number of extra copies varied according to their location on chromosome 21. Attention was focused on the AML1 gene, which was present as five copies in most of the cells exhibiting the marker chromosomes. As controls, 11 cases of childhood ALL were studied with PAC probes covering AML1. The results agreed with the banded karyotypes in 10 patients. FISH uncovered a clone with four copies of AML1 which were only observed by FISH analysis of interphase nuclei in one patient. No point mutation was detected in exons 3-5, encoding the runt domain of AML1, in the three cases, suggesting an oncogenic role of wild-type AML1 amplification.

Adolescent↗
PubMed2001

Smoking and mental illness.

Patients with mental illness have a higher incidence of smoking than the general population and are the major consumers of tobacco products. This population includes subjects with schizophrenia, manic depression, depression, posttraumatic stress disorder (PTSD), attention-deficit disorder (ADD), and several other less common diseases. Smoking cessation treatment in this group of patients is difficult, often leading to profound depression. Several recent findings suggest that increased smoking in the mentally ill may have an underlying biological etiology. The mental illness schizophrenia has been most thoroughly studied in this regard. Nicotine administration normalizes several sensory-processing deficits seen in this disease. Animal models of sensory deficits have been used to identify specific nicotinic receptor subunits that are involved in these brain pathways, indicating that the alpha 7 nicotinic receptor subunit may play a role. Genetic linkage in schizophrenic families also supports a role for the alpha 7 subunit with linkage at the alpha 7 locus on chromosome 15. Bipolar disorder has some phenotypes in common with schizophrenia and also exhibits genetic linkage to the alpha 7 locus, suggesting that these two disorders may share a gene defect. The alpha 7 receptor is decreased in expression in schizophrenia. [(3)H]-Nicotine binding studies in postmortem brain indicate that high-affinity nicotinic receptors may also be affected in schizophrenia.

Animals↗
PubMed2001

FIC1, the protein affected in two forms of hereditary cholestasis, is localized in the cholangiocyte and the canalicular membrane of the hepatocyte.

BACKGROUND/AIMS: FIC1 (familial intrahepatic cholestasis 1) is affected in two clinically distinct forms of hereditary cholestasis, namely progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis. Here we examined the subcellular localization of this protein within the liver. METHODS: Antibodies raised against different epitopes of human FIC1 were used for immunoblot analysis and immunohistochemical detection of FICI. RESULTS: Immunoblot analysis of intestine and liver tissue extracts from human, rat and mouse origin indicated that the antibodies raised against FIC1 specifically detected FIC1 as a 140-kDa protein. In the liver homogenate of a PFIC1 patient, FIC1 could not be detected. Analysis of isolated rat liver membrane vesicles indicated that this protein is predominantly present in the canalicular membrane fraction. Immunohistochemical detection of the protein in liver sections confirmed that FIC1 was present in the canalicular membrane, whereas no staining was observed in the PFIC1 patients liver. Double label immunofluorescence of murine liver revealed that FIC1 colocalized with cytokeratin 7 in cholangiocytes. CONCLUSIONS: The localization of FIC1 in the canalicular membrane and cholangiocytes suggests that it may directly or indirectly play a role in bile formation since mutations in FICI are associated with severe symptoms of cholestasis.

Adenosine Triphosphatases↗
PubMed2001

Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction.

OBJECTIVES: The study assessed the relative predictive potency of neurohumoral factors in patients with advanced left ventricular (LV) dysfunction during neurohumoral blocking therapy. BACKGROUND: The course of heart failure is characterized by progressive LV deterioration associated with an increase in cardiac (natriuretic peptides) and predominantly extracardiac (norepinephrine, big endothelin [big ET]) hormone plasma levels. METHODS: Plasma hormones were measured at baseline and months 3, 6, 12 and 24 in 91 patients with heart failure (left ventricular ejection fraction [LVEF] <25%) receiving 40 mg enalapril/day and double-blind atenolol (50 to 100 mg/day) or placebo. After the double-blind study phase, patients were followed up to four years. Stepwise multivariate regression analyses were performed with 10 variables (age, etiology, LVEF, symptom class, atenolol/placebo, norepinephrine, big ET, log aminoterminal atrial natriuretic peptide, log aminoterminal B-type natriuretic peptide [N-BNP] and log B-type natriuretic peptide [BNP]). During the study, the last values prior to patient death were used, and in survivors the last hormone level, New York Heart Association class and LVEF at month 24 were used. RESULTS: Thirty-one patients died from a cardiovascular cause during follow-up. At baseline, log BNP plasma level (x2 = 13.9, p = 0.0002), treatment allocation (x2 = 9.5, p = 0.002) and LVEF (x2 = 5.6, p = 0.017) were independently related to mortality. During the study, log BNP plasma level (x2 = 21.3, p = 0.0001) remained the strongest predictive marker, with LVEF (x2 = 11.2, p = 0.0008) log N-BNP plasma level (x2 = 8.9, p = 0.0027) and treatment allocation (x2 = 6.4, p = 0.0109) providing additional independent information. CONCLUSIONS: In patients with advanced LV dysfunction receiving high-dose angiotensin-converting enzyme inhibitors and beta-blocker therapy BNP and N-BNP plasma levels are both independently related to mortality. This observation highlights the importance of these hormones and implies that they will likely emerge as a very useful blood test for detection of the progression of heart failure, even in the face of neurohumoral blocking therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Long-term effect of atenolol on ejection fraction, symptoms, and exercise variables in patients with advanced left ventricular dysfunction.

AIMS: We recently reported a beneficial clinical effect of atenolol, a beta(1) selective adrenergic antagonist, in 100 ambulatory heart failure patients with low left ventricular ejection fraction (LVEF, <or=25%) who were receiving background therapy with 40 mg/day enalapril. In this sub-study, we investigated the effects of atenolol vs placebo on LVEF, New York Heart Association (NYHA) class, workload, and peak oxygen consumption (Vo(2)). METHODS AND RESULTS: We included 43 patients (23 receiving atenolol, 20 receiving placebo) who had similar entry characteristics. We evaluated LVEF once a year and evaluated workload, pVO(2), and NYHA class before and after 6, 12, and 24 months. Repeated measures of analysis of variance were used for comparison of serial measurements. After 2 years, both atenolol (18% +/- 5% vs 36% +/- 18%, p < 0.05) and placebo (18% +/- 5% vs 23% +/- 5%, p < 0.05) increased LVEF, with a more pronounced effect of atenolol (p = 0.02), which also changed NYHA class distribution more favorably over time (p < 0.05). Workload and peak Vo(2) increased after atenolol (110 +/- 47 vs 140 +/- 48 watts, p < 0.05, and 18 +/- 5 vs 21 +/- 5 ml/kg/min, p < 0.05) but not after placebo (100 +/- 35 vs 110 +/- 38 watts, p < 0.05, between groups and 17 +/- 4 vs 19 +/- 7 ml/kg/min, not significant, between groups). CONCLUSIONS: In patients with advanced heart failure who tolerate long-term atenolol vs placebo treatment added to high-dose enalapril for 2 years without cardiac events, systolic left ventricular function is markedly improved. These patients experience greater relief of symptoms and increased exercise tolerance.

Adrenergic beta-Antagonists↗
PubMed2001

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.

Humans↗
PubMed2001

Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting.

Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44,000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.

Acute Disease↗
PubMed2001

A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.

FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia (ALL), whereas it was not observed in B ALL samples. This translocation is present in five out of 23 (22%) children and adolescents with T ALL tested. RanBP17, a gene coding for a member of the importin beta protein family, and Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5 breakpoints and CTIP2, which is highly expressed during normal T cell differentiation, was localized in the vicinity of the chromosome 14 breakpoints. The Hox11L2 gene was found to be transcriptionally activated as a result of the translocation, probably under the influence of CTIP2 transcriptional regulation elements. These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis.

Adolescent↗
PubMed2001

A novel, automated method of temperature cycling to produce cryoprecipitate.

BACKGROUND: Cryoprecipitate continues to find wide application in transfusion practice. Current AABB standards call for a minimum of 80 units (U) of factor VIII and 150 mg of fibrinogen per bag of cryoprecipitate. However, individual cryoprecipitates can vary greatly in content, with as many as 20 different factors known to affect the yield. STUDY DESIGN AND METHODS: Plasma was processed in a new, rapid, automated device (CryoSeal, Thermogenesis) with computer-controlled temperature cycling to produce cryoprecipitate. RESULTS: In repeat runs (n = 20), the automated procedure yielded a product containing 184 mg of fibrinogen and 158 U of factor VIII in 55 minutes. Additional studies using plasma pools to compare the quality of the machine-generated products to those of traditionally prepared cryoprecipitate showed comparative recoveries of 182 and 187 mg of fibrinogen and 172.1 and 129.7 U of factor VIII and no significant difference in the levels of plasminogen, protein C, or protein S. CONCLUSION: The new system offers an automated method of cryoprecipitate production in which the steps involved in temperature cycling are initiated sequentially, producing within 1 hour a preparation that is equivalent to standard cryoprecipitate.

Cryopreservation↗
PubMed2001

Transmission of hepatitis C in a pharmacologic study.

OBJECTIVE: To describe an outbreak of hepatitis C in a clinical research study. DESIGN: Observational study. SETTING: Tertiary-care hospital. PATIENTS: Healthcare workers who volunteered to be subjects in a study of the metabolic effects of inhaled and oral corticosteroids who were unwittingly exposed to hepatitis C virus (HCV). METHODS: Epidemiological investigation and serological analyses. RESULTS: One chronic carrier of HCV was identified. Four fellow workers volunteering in the studies became infected with HCV, with 96% homology among strains. There was no evidence of spread from infected healthcare workers to patients on whom they had performed arterial punctures (2 of 214 positive, unrelated to each other and to the outbreak strain). CONCLUSION: Infection control standards in clinical research must be maintained vigorously to prevent transmission of blood-borne pathogens such as HCV.

Adrenal Cortex Hormones↗
PubMed2001

Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link.

OBJECTIVE: To look for a quantitative model linking departmental consumption of antibiotic drugs to the subsequent isolation of resistant hospital-acquired coliform pathogens. MATERIALS AND METHODS: Included in the study were all patients with hospital-acquired bloodstream infections caused by a coliform pathogen, detected in six departments of internal medicine of one university hospital during the period 1991-1996, who had not been hospitalized in the month before the infection (n = 394). Departmental consumption of antibiotics in the year before the infection [expressed as defined daily dosages (DDD)/100 patient days], antibiotic treatment given to the individual patient before the infection, the day of hospital stay on which the infection occurred, and the department and the calendar year were all included in a logistic model to predict the isolation of a resistant pathogen. We looked at five drugs: gentamicin, amikacin, cefuroxime, ceftazidime and ciprofloxacin. RESULTS: Five logistic models were fitted for the resistance to each of the antibiotic drugs. The multivariable-adjusted odds ratios for a pathogen resistant to the specific antibiotic were 1.03 [95% confidence interval (CI) 0.70-1.50] for gentamicin, 1.80 (95% CI 1.00-3.24) for amikacin, 1.12 (95% CI 1.02-1.23) for cefuroxime, 1.45 (95% CI 1.19-1.76) for ceftazidime and 1.06 (95% CI 0.57-1.97) for ciprofloxacin, per 1 DDD/100 patient days. CONCLUSIONS: The departmental consumption of cephalosporin drugs and amikacin in six autonomous departments of medicine in the same hospital was associated with a measurable and statistically significant increase in the probability of infection caused by a resistant pathogen.

Amikacin↗
PubMed2001

Insulin-like growth factors and leucine kinetics during exercise training in children with cystic fibrosis.

BACKGROUND: Little is known about the metabolic effects of exercise training in children with cystic fibrosis. The hypothesis for the current study was that in patients with declining clinical status, exercise increases circulating insulin-like growth factors (IGFs) and improves protein kinetics. METHODS: This was a prospective intervention study in 10 children with cystic fibrosis who participated in a structured isoenergetic exercise (cycling) training program for 3 months. Measurements of IGFs, protein kinetics (using intravenous [13C]-1-leucine tracer infusions) and nutritional balance studies were conducted at baseline and after 3 months. RESULTS: Standard deviation scores of plasma IGF-I, IGF-II, and IGF binding protein (BP)-3 were all decreased at baseline (mean +/- SE: -2.0+/-0.2, -2.0+/-0.2. -0.6+/-0.2, respectively). IGF-I and IGF-II concentrations were significantly higher after exercise training (standard deviation scores -1.4+/-0.3 and -1.3 +/-0. 1, respectively; compared with baseline: one-tailed t-test P = 0.03 and 0.002). The standard deviation score of the IGF-I/IGF BP-3 ratio, an indicator of free IGF-I in the circulation, normalized during exercise training (0.0+/-0.6 vs. -1.3+/-0.2 SD units at baseline, one-tailed t-test P = 0.04). There was no significant difference in protein intake and fasting protein breakdown, oxidation, and protein synthesis or in energy balance and fat absorption. CONCLUSIONS: These results show that isoenergetic exercise training can be safely recommended to patients with cystic fibrosis. It provides a positive anabolic stimulus to IGF status but is not sufficient to adequately augment protein accretion in patients with diminished nutritional status.

Adolescent↗
PubMed2001

Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.

A female infant of nonconsanguineous Indian parents presented at 4 months with a hypoglycemic convulsion. Further episodes of hypoketotic hypoglycemia were associated with inappropriately elevated plasma insulin concentrations. However, unlike other children with hyperinsulinism, this patient had a persistently elevated blood spot hydroxybutyrylcarnitine concentration when fed, as well as when fasted. Measurement of the activity of L-3-hydroxyacyl-CoA dehydrogenase in cultured skin fibroblasts with acetoacetyl-CoA substrate showed reduced activity. In fibroblast mitochondria, the activity was less than 5% that of controls. Sequencing of the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) genomic DNA from the fibroblasts showed a homozygous mutation (C773T) changing proline to leucine at amino acid 258. Analysis of blood from the parents showed they were heterozygous for this mutation. Western blot studies showed undetectable levels of immunoreactive SCHAD protein in the child's fibroblasts. Expression studies showed that the P258L enzyme had no catalytic activity. We conclude that C773T is a disease-causing SCHAD mutation. This is the first defect in fatty acid beta-oxidation that has been associated with hyperinsulinism and raises interesting questions about the ways in which changes in fatty acid and ketone body metabolism modulate insulin secretion by the beta cell. The patient's hyperinsulinism was easily controlled with diazoxide and chlorothiazide.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2001

Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less).

LAP2beta is an integral membrane protein of the nuclear envelope involved in chromatin and nuclear architecture. Using the yeast two-hybrid system, we have cloned a novel LAP2beta-binding protein, mGCL, which contains a BTB/POZ domain and is the mouse homologue of the Drosophila germ-cell-less (GCL) protein. In Drosophila embryos, GCL was shown to be essential for germ cell formation and was localized to the nuclear envelope. Here, we show that, in mammalian cells, GCL is co-localized with LAP2beta to the nuclear envelope. Nuclear fractionation studies reveal that mGCL acts as a nuclear matrix component and not as an integral protein of the nuclear envelope. Recently, mGCL was found to interact with the DP3alpha component of the E2F transcription factor. This interaction reduced the transcriptional activity of the E2F-DP heterodimer, probably by anchoring the complex to the nuclear envelope. We demonstrate here that LAP2beta is also capable of reducing the transcriptional activity of the E2F-DP complex and that it is more potent than mGCL in doing so. Co-expression of both LAP2beta and mGCL with the E2F-DP complex resulted in a reduced transcriptional activity equal to that exerted by the pRb protein.

Amino Acid Sequence↗
PubMed2000

Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.

3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were homozygous for a single nucleotide substitution predicted to change valine at position 490 to methionine. The sixth patient was homozygous for a valine to methionine substitution at position 425; both mutations are located in the carboxyterminal part of PHGDH. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA-blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurological impairment in our patients, the data presented in this paper suggest an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

CALM-AF10 fusion gene in leukemias: simple and inversion-associated translocation (10;11).

A translocation (10;11)(p12;q14) was observed in two children, one with acute eosinophilic leukemia and the other with acute T-cell lymphoblastic leukemia. The presence of CALM-AF10 fusion was ascertained by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Fluorescence in situ hybridization (FISH) analysis showed that AF10 gene splitting was associated with partial inversion of chromosome 11 in the first patient. In addition, FISH analysis also determined the orientation of the CALM gene, 5' telomere to 3' centromere on 11q.

Adolescent↗