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J Berger

Publications and source records attributed to J Berger.

At least 145 records · Page 8Linked to original sources
PubMed1999

A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro.

The Polycomb group of (PcG) genes were originally described in Drosophila, but many PcG genes have mammalian homologs. Genetic studies in flies and mice show that mutations in PcG genes cause posterior transformations caused by failure to maintain repression of homeotic loci, suggesting that PcG proteins have conserved functions. The Drosophila gene Sex comb on midleg (Scm) encodes an unusual PcG protein that shares motifs with the PcG protein polyhomeotic, and with a Drosophila tumor suppressor, lethal(3)malignant brain tumor (l(3)mbt). Expressed sequence tag (EST) databases were searched to recover putative mammalian Scm homologs, which were used to screen murine cDNA libraries. The recovered cDNA encodes two mbt repeats and the SPM domain that characterize Scm, but lacks the cysteine clusters and the serine/threonine-rich region found at the amino terminus of Scm. Accordingly, we have named the gene Sex comb on midleg homolog 1 (Scmh1). Like their Drosophila counterparts, Scmh1 and the mammalian polyhomeotic homolog RAE28/mph1 interact in vitro via their SPM domains. We analyzed the expression of Scmh1 and rae28/mph1 using northern analysis of embryos and adult tissues, and in situ hybridization to embryos. The expression of Scmh1 and rae28/mph1 is well correlated in most tissues of embryos. However, in adults, Scmh1 expression was detected in most tissues, whereas mph1/rae28 expression was restricted to the gonads. Scmh1 is strongly induced by retinoic acid in F9 and P19 embryonal carcinoma cells. Scmh1 maps to 4D1-D2.1 in mice. These data suggest that Scmh1 will have an important role in regulation of homeotic genes in embryogenesis and that the interaction with RAE28/mph1 is important in vivo.

Amino Acid Sequence↗
PubMed1999

The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression.

Four ATP-binding cassette (ABC) half-transporters have been identified in mammalian peroxisomes: adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related protein (ALDRP), 70-kDa peroxisomal membrane protein (PMP70) and PMP70-related protein (P70R). Inherited defects in ALDP cause the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). By comparative Northern blot analyses we found each of the four murine peroxisomal ABC transporter mRNA species at maximum abundance only in a few tissues, which differed for each family member. The four genes were also regulated differentially during mouse brain development: ALDP mRNA was most abundant in embryonic brain and gradually decreased during maturation; ALDRP and P70R mRNA accumulated in the early postnatal period; and the amount of PMP70 transcript increased slightly during the second and third postnatal week. The different expression patterns could explain why beta-oxidation is defective in X-ALD, although ALDRP and PMP70 can replace ALDP functionally in fibroblasts. Dietary fenofibrate had no effect on the ALD and P70R genes, but strongly increased expression of the ALDR and PMP70 genes in mouse liver. However, in P-glycoprotein Mdr1a-deficient mice fenofibrate treatment increased ALDR gene expression also in the brain, suggesting that the multidrug-transporter P-glycoprotein restricts entry of fenofibrate to the brain at the blood-brain barrier. Analysis of the promoter sequences revealed a cryptic nuclear hormone receptor response element of the DR+4 type in the ALDR promoter and a novel 18-bp sequence motif present only in the 5' flanking DNA of the ALDR and PMP70 genes. The mouse ALDR gene uses a single transcription start site but alternative polyadenylation sites. These data are of importance for the use of ALDP-deficient mice as a model in pharmacological gene therapy studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[In Process Citation]

Empirical studies showed that alcohol and drug addicted delinquents are problematic patients whose treatment is under strain due to difficulties resulting from hospitalisation by court. In the course of treatment it turned out that there is usually a high rate of relapses to addictive drugs and alcohol as well as break-outs. Between 11 and 47% of the patients have to be returned to the penal system. This study investigates which patient groups can very probably be treated successfully and which patient groups have to be classified as risk groups. An analysis of files of 103 concluded treatments at a psychiatric centre in South Germany, ZfP Weinsberg (Massregelvollzug according to section 64 German Penal Code), showed that the factors low age at the time of hospitalisation, lacking education and vocational qualification, drug addiction, early first-time sentencing, and a broken home in the family of origin are accompanied by unsuccessful treatment attempts. A cluster analysis on the basis of these factors identified several patient groups: a completely successful group (delinquents with several previous convictions and a high tendency to offences), a very probable unsuccessful group (delinquents with several previous convictions and a high tendency to offences), and a poorly predictable group (young patients with an early onset of delinquency). The results suggest to thoroughly consider the "prospect of successful treatment" according to section 64 German Penal Code regarding identified risk groups when deciding on hospitalisation by court. Considering the profile of unsuccessful patients, it is advisable to supplement a therapy programme focussing on the treatment of drug addiction with elements that focus on delinquency.

Journal Article↗
PubMed1999

[Evidence-based medicine--a critical overview].

BACKGROUND: Evidence-based medicine (EBM) is a strategy for the standardization of medical decision-making. The purpose of this review was to demonstrate the most important tools of EBM and to critically appraise them. METHODS: The current literature concerning the subject is reviewed. A clinical example for the systematic use of EBM in diagnostic tests is explained in detail. RESULTS: The risk of an increasing bureaucratic hindrance of medical procedures by EBM is weighed against the advantages of a systematic strategy for the valid assessment of medical information. According to the clinical example EBM proves to be a valuable tool in the quantitative estimation of residual risk and reliability of diagnostic tests in everyday clinical practice. CONCLUSION: The critical use of the systematic tools of EBM for clinical decision-making is recommended.

Decision Support Techniques↗
PubMed1999

Expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors or non-Hodgkin's and Hodgkin's lymphoma and of healthy donors is inversely correlated with the amount of mobilized CD34+ cells.

The yield of CD34+ PBPC and colony-forming units-granulocyte-macrophage (CFU-GM) in leukapheresis products and the expression of the adhesion molecules CD11a, CD31, CD49d, CD49e, CD54, CD58, CD62L, c-kit (CD117), Thy-1 (CD90), CD33, CD38, and HLA-DR on CD34+ PBPC were analyzed in patients with cancer of the testis (n = 10), breast cancer (n = 10), Hodgkin's disease (n = 20), high-grade (n = 20) and low-grade (n = 20) non-Hodgkin's lymphoma, and healthy donors (n = 20) undergoing G-CSF (filgrastim)-stimulated PBPC mobilization. For each disease entity, G-CSF was administered in two different doses, 10 microg G-CSF/kg body weight (BW)/day s.c. vs. 24 microg G-CSF/kg BW s.c./day in steady-state condition. Data were compared for each dose group separately. Patients with cancer of the testis and breast cancer mobilized significantly more CD34+ cells than patients with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkin's disease (p<0.05). Correspondingly, expression of CD49d on CD34+ PBPC was significantly lower in the same patients with cancer of the testis compared with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkins' disease and in patients with breast cancer compared with high-grade and low-grade non-Hodgkin's lymphoma, Hodgkins's disease, and healthy donors. Similar results were obtained for CD49e. These data suggest that the expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors, non-Hodgkin's lymphoma, Hodgkin's disease, and healthy donors is inversely correlated with the amount of mobilized CD34+ cells.

Adolescent↗
PubMed1999

Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy.

Inherited defects in the peroxisomal ATP-binding cassette (ABC) transporter adrenoleukodystrophy protein (ALDP) lead to the lethal peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), for which no efficient treatment has been established so far. Three other peroxisomal ABC transporters currently are known: adrenoleukodystrophy-related protein (ALDRP), 70 kDa peroxisomal membrane protein (PMP70) and PMP70- related protein. By using transient and stable overexpression of human cDNAs encoding ALDP and its closest relative ALDRP, we could restore the impaired peroxisomal beta-oxidation in fibroblasts of X-ALD patients. The pathognomonic accumulation of very long chain fatty acids could also be prevented by overexpression of ALDRP in immortalized X-ALD cells. Immunofluorescence analysis demonstrated that the functional replacement of ALDP by ALDRP was not due to stabilization of the mutated ALDP itself. Moreover, we were able to restore the peroxisomal beta-oxidation defect in the liver of ALDP-deficient mice by stimulation of ALDRP and PMP70 gene expression through a dietary treatment with the peroxisome proliferator fenofibrate. These results suggest that a correction of the biochemical defect in X-ALD could be possible by drug-induced overexpression or ectopic expression of ALDRP.

ATP Binding Cassette Transporter, Subfamily D↗
PubMed1999

Characterization of a novel, antifungal, chitin-binding protein from Streptomyces tendae Tü901 that interferes with growth polarity.

The afp1 gene, which encodes the antifungal protein AFP1, was cloned from nikkomycin-producing Streptomyces tendae Tü901, using a nikkomycin-negative mutant as a host and screening transformants for antifungal activity against Paecilomyces variotii in agar diffusion assays. The 384-bp afp1 gene has a low G+C content (63%) and a transcription termination structure with a poly(T) region, unusual attributes for Streptomyces genes. AFP1 was purified from culture filtrate of S. tendae carrying the afp1 gene on the multicopy plasmid pIJ699. The purified protein had a molecular mass of 9,862 Da and lacked a 42-residue N-terminal peptide deduced from the nucleotide sequence. AFP1 was stable at extreme pH values and high temperatures and toward commercial proteinases. AFP1 had limited similarity to cellulose-binding domains of microbial plant cell wall hydrolases and bound to crab shell chitin, chitosan, and cell walls of P. variotii but showed no enzyme activity. The biological activity of AFP1, which represents the first chitin-binding protein from bacteria exhibiting antifungal activity, was directed against specific ascomycetes, and synergistic interaction with the chitin synthetase inhibitor nikkomycin inhibited growth of Aspergillus species. Microscopy studies revealed that fluorescein-labeled AFP1 strongly bound to the surface of germinated conidia and to tips of growing hyphae, causing severe alterations in cell morphogenesis that gave rise to large spherical conidia and/or swollen hyphae and to atypical branching.

Amino Acid Sequence↗
PubMed1999

Inhibition of adipocyte differentiation by HIV protease inhibitors.

Patients with AIDS who are receiving therapy with HIV protease inhibitors have been widely reported to be afflicted with a syndrome characterized by lipodystrophy (fat redistribution favoring the accumulation of abdominal and cervical adipose tissue), hyperlipidemia, and insulin resistance. HIV protease inhibitors have been suggested to have a direct role in modulating adipocyte differentiation. To address this hypothesis, several HIV protease inhibitors were studied for their ability to either augment or inhibit the differentiation of murine 3T3-L1 preadipocytes. Dose-responsive inhibition of adipogenesis by several protease inhibitors was noted as measured by reduced triglyceride accumulation and attenuated induction of three differentiation marker genes -- aP2, lipoprotein lipase, and Adipo Q. Potential mechanisms for altered adipocyte function, including direct binding to PPARgamma or inhibition of PPARgamma-mediated gene transcription were effectively excluded.

3T3 Cells↗
PubMed1999

Pneumothorax post CT-guided lung biopsy: a comparison between detection on chest radiographs and CT.

Pneumothorax is reported to be a more common complication of lung biopsy performed under computed tomography (CT) than under fluoroscopic guidance. This may simply reflect the greater sensitivity of CT over chest radiographs (CXRs) in the detection of small pneumothoraces. This study aimed to determine the incidence of pneumothorax detected by CXR and by CT after CT-guided biopsy of non-pleurally based pulmonary masses, and to compare these incidences with previous reports in the literature of pneumothorax incidence post fluoroscopic biopsy. 88 consecutive CT-guided lung biopsies of masses not abutting the pleural surface were included. Immediate post-biopsy CT images, and 1 and 4 h CXRs were assessed independently by two observers for the presence and size of pneumothorax. 72 biopsies were fine needle aspirations (FNAs) performed with 22 G spinal needles only, seven were cutting needle biopsies (CNBs) performed with 18 G cutting needles only, and nine were both. 37 patients (42%) developed a pneumothorax. 35 were detected on CT (40%) and 22 on CXR (25%). None required tube drainage. Of the patients in whom CT demonstrated a pneumothorax, the average depth of this was significantly greater for those in whom CXR also detected a pneumothorax compared with those in whom CXR was negative (7.3 mm versus 3.4 mm, p < 0.05). The incidence of pneumothorax detected on CXR post CT-guided biopsy is similar to the reported incidence post fluoroscopic biopsy.

Adult↗
PubMed1999

Health care trends in today's marketplace.

As the year 2000 approaches, it is apparent that employer-sponsored health plans will again begin to experience high rate increases. Employers will need to utilize an up-to-date benefits philosophy and health plan purchasing strategy coupled with monitoring tools and vendor performance guarantees to deal with the situation. While many of the cost drivers are beyond an employer's control, taking a preemptive strike at health care inflation through design, cost sharing and other focused initiatives will minimize its impact.

Data Collection↗
PubMed1998

The difference in recognition of terminal tripeptides as peroxisomal targeting signal 1 between yeast and human is due to different affinities of their receptor Pex5p to the cognate signal and to residues adjacent to it.

Pex5p is the receptor for the peroxisomal targeting signal 1 (PTS1) that consists of a C-terminal tripeptide (consensus (S/A/C)(K/R/H)(L/M)). Hexadecapeptides recognized by Pex5p from Homo sapiens and Saccharomyces cerevisiae were identified by screening a two-hybrid peptide library, and the targeting ability of the peptides was demonstrated using the green fluorescent protein as reporter. The PTS1 receptors recognized in a species-specific manner a broad range of C-terminal tripeptides, and these are reported herein. In addition, residues upstream of the tripeptide influenced the strength of the interaction in the two-hybrid system as well as in an in vitro competition assay. In peptides interacting with the human protein, hydrophobic residues were found with high frequency especially at positions -2 and -5, whereas peptides interacting with S. cerevisiae Pex5p were more hydrophilic and frequently contained arginine at position -2. In instances where the terminal tripeptide deviated from the consensus, upstream residues exerted a greater influence on the ability of the hexadecapeptides to bind Pex5p.

Amino Acid Sequence↗
PubMed1998

Development of HIV encephalitis in AIDS and TNF-alpha regulatory elements.

Tumor necrosis factor-alpha (TNF-alpha) appears to play an important role in HIV encephalitis (HIVE). TNF2, a polymorphism of TNF-alpha, associates with higher levels of TNF-alpha and severe manifestations of some infections. We studied 44 acquired immunodeficiency syndrome (AIDS) patients with autopsy-proven HIVE and/or HIV leukoencephalopathy (HIVLE) (HIVE/LE) and 30 AIDS patients without HIVE/LE. TNF2 did not associate with presence of HIVE/LE (p > 0.5). Moreover, the TNF-alpha regulatory element TTATTTAT within the 3'-untranslated region was intact in HIVE/LE brains, and HLA-DR3 did not associate with HIVE/LE. Other host factors or, more likely, viral factors may be responsible for the development of HIVE/LE.

AIDS Dementia Complex↗
PubMed1998

Interphase cytogenetic study of preoperative core biopsies for the prediction of early serum prostate specific antigen recurrence after radical prostatectomy of clinically localized prostate carcinoma.

BACKGROUND: Current clinical and pathologic methods are imprecise in predicting the extent of prostate carcinoma progression. This study was conducted to evaluate the role of interphase cytogenetics (ICG) with chromosome enumeration probes relative to the role of conventional pathologic characteristics in the preoperative prediction of postoperative tumor classification and recurrence of elevated serum concentrations of prostate specific antigen (PSA). METHODS: The authors performed ICG with enumeration probes for chromosomes 7, 17, and X on 6-microm sections of core biopsies from 75 patients with clinically localized adenocarcinoma of the prostate. Results were compared with pathologic findings (tumor classification, volume, and status of surgical margins) of the corresponding radical prostatectomy specimens and data on serum PSA measurements taken for 72 patients during a follow-up period of up to 42 months (mean, 19.8 months). In addition to ICG, biopsies were reviewed for primary, secondary, highest, and combined Gleason grades, number and bilaterality of positive biopsies, amount of carcinoma (percentage and core length of infiltration), amount of high grade carcinoma, and perineural invasion. RESULTS: Chromosome categories were unevenly distributed among pathologic tumor classification groups (P = 0.0008) and between groups with positive and negative surgical margins (P = 0.0116). Tumors with aneusomic chromosome numbers had larger volumes than those with eusomy and tetrasomy (P = 0.0022). Kaplan-Meier analysis demonstrated that PSA recurrences (> or = 0.4 ng/mL) were more frequent and observed earlier in patients with detected chromosomal aneusomies than in those with eusomic and tetrasomic chromosome numbers (P < 0.0001). Cox regression analysis indicated that ICG was the most valuable independent factor in predicting PSA recurrences. CONCLUSIONS: The detection of numeric chromosomal aberrations in preoperative core biopsies is an adverse prognostic sign. Grading based on the quantification of genetic changes might prove useful in the prognostic stratification of patients with clinically localized prostate carcinoma.

Adenocarcinoma↗
PubMed1998

A high-capacity assay for activators of glucose incorporation into glycogen in L6 muscle cells.

Skeletal muscle is the major tissue responsible for insulin-stimulated glucose uptake and incorporation into glycogen. Skeletal muscle insulin resistance and the resulting postprandial hyperglycemia are hallmarks of non-insulin-dependent diabetes. Therefore, compounds that serve as insulin mimetics or insulin sensitizers in skeletal muscle may be effective in the treatment of diabetes. In order to identify such hypoglycemic agents, a novel assay for activators of glucose incorporation into glycogen has been developed utilizing differentiated L6 muscle cells in 96-well plates. We found that glucose incorporation occurs in a time- and concentration-dependent manner. It is inhibitable by phloretin, an inhibitor of glucose transport. Both insulin and the insulin-mimetic compound pervanadate activate L6 cell glucose incorporation in dose-responsive manners. We conclude that this assay should serve as a high-capacity screen to identify novel compounds that upregulate glucose anabolic metabolism in skeletal muscle. Such chemical entities may prove useful as antidiabetic agents.

Animals↗
PubMed1998

A novel relative of the very-long-chain acyl-CoA synthetase and fatty acid transporter protein genes with a distinct expression pattern.

Based on its relationship to very-long-chain acyl-CoA synthetase (VLACS), we have cloned and identified a novel, VLACS-related (VLACSR) cDNA from mouse liver. The 2067-bp open reading frame encodes a 689-amino-acid protein with a predicted molecular mass of 76.2 kDa. The carboxy-terminal 500 amino acids of VLACSR show 48% identity and 70% similarity to mouse VLACS and 43% identity and 60% similarity to mouse fatty acid transporter (FATP), respectively. In addition, a partial cDNA of the human VLACSR ortholog was identified. By Northern blot analysis, a 2.6-kb VLACS mRNA was highly abundant only in mouse liver. Low levels of shorter mRNAs were present in brain, lung, testes, and spleen (2.5 kb) and in skeletal muscle (2.2 kb). In heart, but not in kidney, transcripts undetectable by Northern blot analysis could be demonstrated by RT PCR. Southern blot analysis indicated single-copy VLACSR genes in the mouse and human genomes.

Amino Acid Sequence↗
PubMed1998

cDNA cloning and mRNA distribution of a mouse very long-chain acyl-CoA synthetase.

The interaction of the adrenoleukodystrophy protein (ALDP), mutated in the peroxisomal disorder X-linked adrenoleukodystrophy, and the very long-chain acyl-CoA synthetase (VLACS), the enzyme whose function is missing in this disease, remains obscure. As a first step to studying this interaction in wild type versus ALDP-deficient mice, we have cloned a VLACS cDNA from mouse liver. The 1860 bp open reading frame encodes a 620 amino acid protein with a predicted molecular mass of 70.3 kDa. By Northern blot analysis, a 2.6 kbp VLACS mRNA was highly abundant in liver and kidney and present at low levels in brain and testes. By RT-PCR VLACS mRNA was also detected in heart and lung but remained undetectable in skeletal muscle and spleen. In contrast to the peroxisomal beta-oxidation marker acyl-CoA oxidase, whose mRNA level steadily increases during brain development, the VLACS transcript was found at a constant low level from embryo through adulthood, suggesting that additional isoforms may exist in brain.

Amino Acid Sequence↗
PubMed1998

[Reduced visual capacity increases the risk of accidents in street traffic].

BACKGROUND: This study was carried out to investigate the relationship between the frequency of traffic accidents and impaired vision. MATERIALS AND METHODS: Seven hundred and fifty-four drivers involved in accidents were recruited, in addition to 250 accident-free drivers similar in age and driving experience as an control group. The age distribution of the persons involved in traffic accidents (mean 56.3 years) was similar to that of the control group (mean 57.7 years), the difference was not statistically significant. Both groups underwent a complete ophthalmological examination. RESULTS: All three types of accidents (night-time accidents, violations of right of way, accidents during an overtaking manoeuvre) had a statistically significantly higher incidence of reduced photopic visual acuity, mesopic vision and an increased sensitivity to glare. Some other visual functions were also abnormal, with differences according to the type of accident. In particular, there were noticeable differences between the control group and those who were involved in night-time accidents regarding mesopic vision and sensitivity to glare. Concerning mesopic vision, 15% of the 261 persons involved in night-time accidents did not reach the contrast limit of 1:5; with glare, 20.7% failed. In comparison 4% of the control group reached this critical limit without glare and 7.6% with glare. These differences are highly statistically significant. In contrast to these findings, many of the drivers involved in accidents assessed their own visual capability as "excellent". CONCLUSIONS: The results of this study show that reduced mesopic vision and increased sensitivity to glare are accompanied by an increased risk of night-time accidents (for example, collisions with a non-illuminated obstacle). This emphasizes the importance of regular ophthalmological check-ups including visual functions such as mesopic vision and sensitivity to glare, which currently are not required by the traffic laws in Germany.

Accidents, Traffic↗