Biomedical subjects

J Berger

Publications and source records attributed to J Berger.

At least 73 records · Page 4Linked to original sources

PubMed2002

Gene expression profile in Neisseria meningitidis and Neisseria lactamica upon host-cell contact: from basic research to vaccine development.

Differential gene regulation in the human pathogen Neisseria meningitidis group B (MenB) and in Neisseria lactamica, a human commensal species, was studied by whole genome microarray after bacterial interaction with epithelial cells. Host-cell contact induced changes in the expression of 347 and 285 genes in MenB and N. lactamica, respectively. Of these, only 167 were common to MenB and N. lactamica, suggesting that a different subset of genes is activated by pathogens and commensals. Change in gene expression was stable over time in N. lactamica, but short-lived in MenB. A large part (greater than 30%) of the regulated genes encoded proteins with unknown function. Among the known genes, those coding for pili, capsule, protein synthesis, nucleotide synthesis, cell wall metabolism, ATP synthesis, and protein folding were down-regulated in MenB. Transporters for iron, chloride and sulfate, some known virulence factors, GAPDH and the entire pathway of selenocysteine biosynthesis were upregulated. Gene expression profiling indicates that approximately 40% of the regulated genes encode putative surface-associated proteins, suggesting that upon cell contact Neisseria undergoes substantial surface remodeling. This was confirmed by FACS analysis of adhering bacteria using mouse sera against a subset of recombinant proteins. Finally, a few surface-located, adhesion-activated antigens were capable of inducing bactericidal antibodies, indicating that microarray technology can be exploited for the identification of new vaccine candidates.

Bacterial Adhesion↗

PubMed2001

d Macro and (3)He macro production in square root of s(NN) = 130 GeV Au+Au collisions.

The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d macro and (3)He macro are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the (3)He macro freeze-out volume is smaller than the d macro freeze-out volume.

Journal Article↗

PubMed2001

Measurement of inclusive antiprotons from Au+Au collisions at square root of s(NN) = 130 GeV.

We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at square root of s(NN) = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<p( perpendicular)<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.

Journal Article↗

PubMed2001

Primary cultures as a model for studying ependymal functions: glycogen metabolism in ependymal cells.

Ependymal cells form a single-layered, ciliated epithelium at the interface between the cerebrospinal fluid and the brain parenchyma. Although their morphology has been studied in detail, ependymal functions remain largely speculative. We have established and characterized a previously described cell culture model to investigate ependymal glycogen metabolism. During growth in minimal medium lacking many non-essential amino acids including L-glutamate, but containing glucose at physiological concentration, the cells contained negligible amounts of glycogen (7+/-3 nmol glucosyl residues/mg protein) despite the presence of insulin. However, during a period of 24 h, the cells accumulated glycogen to very high levels after transferal to a medium containing insulin, glucose at a 5-fold higher concentration, and all proteinogenic amino acids except L-asparagine and L-serine (990+/-112 nmol glucosyl residues/mg protein). Omission of insulin resulted in a 50% reduction in glycogen accumulation. Upon glucose deprivation, glycogen was degraded with a half-life of 21 min. The ependymal primary cultures contained 80+/-5 mU glycogen phosphorylase (Pho)/mg protein and stained positively with antibodies raised against this enzyme. Astroglial cultures built up less glycogen and had less Pho activity under identical conditions. Ependymal glycogen was mobilized by noradrenaline and serotonin. Our results indicate that ependymal cells maintain glycogen as a functional energy store, subject to rapid turnover dependent on the availability of energy substrates and the presence of appropriate signal molecules. Thus ependymocytes appear to be active players in the multitude of processes resulting in normal brain function, and ependymal primary cultures are suggested as a suitable model for studying the role of ependymal cells in these processes.

Animals↗

PubMed2001

Multiplicity distribution and spectra of negatively charged hadrons in Au+Au collisions at square root of (sNN) = 130 GeV.

The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h(-)) in Au+Au interactions at square root of ([s(NN)]) = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dN(h(-))/d(eta)/(eta = 0) = 280+/-1(stat)+/-20(syst), an increase per participant of 38% relative to pp collisions at the same energy. The mean transverse momentum is 0.508+/-0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h(-) yield per participant is a strong function of p( perpendicular). The pseudorapidity distribution is almost constant within /eta/<1.

Journal Article↗

PubMed2001

Pion Interferometry of square root of (s(NN)) =130 GeV Au + Au collisions at RHIC.

Two-pion correlation functions in Au+Au collisions at square root of [s(NN)] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in square root of [s(NN)].

Journal Article↗

PubMed2001

Midrapidity antiproton-to-proton ratio from Au+Au collisions at sqrt [s(NN)]=130 GeV.

We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[s(NN)] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of /y/<0.5 and 0.4<p(t)<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65+/-0.01((stat))+/-0.07((syst)) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.

Journal Article↗

PubMed2001

Antibodies to chlamydial lipopolysaccharides in unstable angina pectoris.

Patients with coronary artery disease frequently have elevated antibody titers against Chlamydia pneumoniae, but whether antichlamydial antibody titers are correlated with prognosis in unstable angina remains unclear. We therefore investigated the sera of 1,096 patients with unstable angina regarding immunoglobulin (Ig) IgG, IgA, and IgM antibody titers against chlamydial lipopolysaccharides (LPS) and the concentrations of C-reactive protein (CRP) and troponin T (TnT). Anti-LPS IgG titers were increased in 45% of patients at enrollment and in 48% of patients at discharge (p <0.0001). Anti-LPS IgA titers were increased in 27% of patients at enrollment and in 33% of patients at discharge (p <0.0001). Patients who subsequently died had significantly lower IgM titers at enrollment than patients without events (p = 0.016). IgG, IgA, or IgM titers did not correlate with concentrations of CRP or TnT. In this large-scale study of patients with unstable angina, we frequently found elevated antichlamydial antibody titers. Patients with low IgM anti-LPS titers were at risk for subsequent death. However, there was no correlation between antichlamydial antibody titers and CRP or TnT.

Aged↗

PubMed2001

Lectin binding to cutaneous malignant melanoma: HPA is associated with metastasis formation.

Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan-Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P< 0.0001) being superior to the 'indirect' method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N -acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, beta1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma.

Adult↗

PubMed2001

CD95 signaling via ceramide-rich membrane rafts.

Clustering seems to be employed by many receptors for transmembrane signaling. Here, we show that acid sphingomyelinase (ASM)-released ceramide is essential for clustering of CD95. In vitro and in vivo, extracellularly orientated ceramide, released upon CD95-triggered translocation of ASM to the plasma membrane outer surface, enabled clustering of CD95 in sphingolipid-rich membrane rafts and apoptosis induction. Whereas ASM deficiency, destruction of rafts, or neutralization of surface ceramide prevented CD95 clustering and apoptosis, natural ceramide only rescued ASM-deficient cells. The data suggest CD95-mediated clustering by ceramide is prerequisite for signaling and death.

Apoptosis↗

PubMed2001

Recolonizing carnivores and naïve prey: conservation lessons from Pleistocene extinctions.

The current extinction of many of Earth's large terrestrial carnivores has left some extant prey species lacking knowledge about contemporary predators, a situation roughly parallel to that 10,000 to 50,000 years ago, when naive animals first encountered colonizing human hunters. Along present-day carnivore recolonization fronts, brown (also called grizzly) bears killed predator-naive adult moose at disproportionately high rates in Scandinavia, and moose mothers who lost juveniles to recolonizing wolves in North America's Yellowstone region developed hypersensitivity to wolf howls. Although prey that had been unfamiliar with dangerous predators for as few as 50 to 130 years were highly vulnerable to initial encounters, behavioral adjustments to reduce predation transpired within a single generation. The fact that at least one prey species quickly learns to be wary of restored carnivores should negate fears about localized prey extinction.

Alaska↗

PubMed2001

Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence and new insight in expression.

X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorder due to mutations in the ALD gene, which encodes a peroxisomal ABC half-transporter (ALDP). It has been suggested that ALDP assembles with ALDRP (adrenoleukodystrophy-related protein), a close homologous half-transporter, to form a functional heterodimer. For the first time full-length ALDRP cDNA (5.5 kb) was cloned, and 5' and 3' RACE analysis revealed that alternative usage of polyadenylation sites generates the two transcripts of 3.0 and 5.5 kb observed in the rat in Northern blot analysis. Southern blotting and chromosomal mapping demonstrated one ALDR locus in the rat genome. Characterisation of the 3' flanking region suggested that an ID sequence might be responsible for high expression of the 5.5 kb ALDRP transcript in rat brain. ALDR gene expression was found to be high in the liver of rats before weaning and very low in adult rats; the reverse developmental regulation was observed in the brain. Fenofibrate, which is a potent inducer of the ALDR gene in the liver of adult rats, could not induce the ALDR gene in suckling rats. The exact significance of this result with regard to development of an efficient pharmacological gene therapy for X-ALD is discussed.

3' Untranslated Regions↗

PubMed2001

Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to play an important role in the regulation of expression of a subclass of adipocyte genes and to serve as the molecular target of the thiazolidinedione (TZD) and certain non-TZD antidiabetic agents. Hypercorticosteroidism leads to insulin resistance, a variety of metabolic dysfunctions typically seen in diabetes, and hypertrophy of visceral adipose tissue. In adipocytes, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) converts inactive cortisone into the active glucocorticoid cortisol and thereby plays an important role in regulating the actions of corticosteroids in adipose tissue. Here, we show that both TZD and non-TZD PPARgamma agonists markedly reduced 11beta-HSD-1 gene expression in 3T3-L1 adipocytes. This diminution correlated with a significant decrease in the ability of the adipocytes to convert cortisone to cortisol. The half-maximal inhibition of 11beta-HSD-1 mRNA expression by the TZD, rosiglitazone, occurred at a concentration that was similar to its K(d) for binding PPARgamma and EC(50) for inducing adipocyte differentiation thereby indicating that this action was PPARgamma-dependent. The time required for the inhibitory action of the TZD was markedly greater for 11beta-HSD-1 gene expression than for leptin, suggesting that these genes may be down-regulated by different molecular mechanisms. Furthermore, whereas regulation of PPARgamma-inducible genes such as phosphoenolpyruvate carboxykinase was maintained when cellular protein synthesis was abrogated, PPARgamma agonist inhibition of 11beta-HSD-1 and leptin gene expression was ablated, thereby supporting the conclusion that PPARgamma affects the down-regulation of 11beta-HSD-1 indirectly. Finally, treatment of diabetic db/db mice with rosiglitazone inhibited expression of 11beta-HSD-1 in adipose tissue. This decrease in enzyme expression correlated with a significant decline in plasma corticosterone levels. In sum, these data indicate that some of the beneficial effects of PPARgamma antidiabetic agents may result, at least in part, from the down-regulation of 11beta-HSD-1 expression in adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2001

Back-casting sociality in extinct species: new perspectives using mass death assemblages and sex ratios.

Despite 150 years of interest in the ecology of dinosaurs, mammoths, proto-hominids and other extinct vertebrates, a general framework to recreate patterns of sociality has been elusive. Based on our recent discovery of a contemporary heterospecific mass death assemblage in the Gobi Desert (Mongolia), we fit predictions about gender-specific associations and group living in extant ungulates to extinct ones. We relied on comparative data on sex-ratio variation and body-size dimorphism, basing analyses on 38 additional mass mortality sites from Asia, Africa, Europe and North America that span 50 million years. Both extant and extinct species died in aggregations with biased adult sex ratios, but the skew (from 1:1) was greater for extinct dimorphic taxa, suggesting that sociality in these extinct species can be predicted from spatial and demographic traits of extant ones. However, extinct rhinos, horses and zebras were inconsistent with predictions about adult sex ratios, which underscores the inherent difficulty in backcasting historic patterns to some monomorphic taxa. These findings shed light not only on the sociality of extinct species but provide a sound, although limited, footing for interpretation of modern death assemblages within the context of the emerging science of taphonomy and palaeobehaviour.

Animals↗

PubMed2001

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗

PubMed2001

Symptomatic and syndromal anxiety and depression.

The diagnosis of anxiety disorders and major depression can be reliably made based on signs and symptoms. However there are significant limitations to the current system of classification including overlapping criteria, high comorbidity, and the issue of subthreshold syndromes. The literature on treatment response documents that selective serotonin reuptake inhibitors are effective in the treatment of the various anxiety disorders, including when comorbid major depression is present. The literature also suggests that tricyclic antidepressant medications have superior benefits over selective serotonin reuptake inhibitors in major depression. Examination of the functional anatomy of the fear and reward systems may shed light on the underlying processes in the anxiety and depressive disorders. Such an approach points out the importance of addressing avoidance behaviors, which may be more responsive to cognitive behavioral treatments than pharmacological agents.

Antidepressive Agents, Tricyclic↗

PubMed2001

Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange.

X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta-oxidation. We examined the ABCD1 gene in probands from 11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/T in the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively.

5' Untranslated Regions↗

PubMed2001

[MRI-assisted brachytherapy of nonresectable liver metastases. Preliminary technical and clinical experiences].

PURPOSE: To evaluate the feasibility and efficacy of MR-guided interstitial brachytherapy of non-resectable liver metastasis. METHODS: Liver metastases (0.8-5.2 cm in diameter) were treated during a prospective phase I/II study using an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen). MR-compatible brachytherapy applicators were placed percutaneously under MR-guidance in an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen) using fast T1-weighted sequences. Pretreatment and follow-up studies were performed using a 1.5 Tesla MR system. RESULTS: Preliminary results of an unpublished prospective study are discussed exemplary on 2 selected patients. The median procedure time was 4.9 h. No major complications were observed and late effects were acceptable. In large symptomatic metastases only a temporary relief of pain was achieved. In smaller metastases (DM 3 cm) a tumor control was observed. CONCLUSION: MR-guided brachytherapy is feasible and has the potential to ablate liver metastases with diameter of less than 3 cm. Further developments are necessary.

Adenocarcinoma↗