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P Berger

Publications and source records attributed to P Berger.

At least 91 records · Page 5Linked to original sources
PubMed1998

Structure of the mouse gene for the serine protease inhibitor neuroserpin (PI12).

Neuroserpin (PI12), initially identified as an axonally secreted protein in cultured chicken dorsal root ganglion neurons, belongs to the serpin family of the serine protease inhibitors and is mainly expressed by neurons of both the developing and the adult nervous system. Here we report on the cloning and structural characterization of the neuroserpin gene of the mouse. The murine neuroserpin gene spans over more than 55kb and consists of nine exons. The positions and phases of the exonīntron borders are completely conserved between neuroserpin and its nearest homologues, protease nexin-1 and plasminogen activator inhibitor-1. A single transcription initiation site, which is colocalized with a potential initiation (Inr) sequence, has been determined by primer extension and RNase protection. Sequence analysis revealed a TATA-less promoter with a CAAT box and several sites for the general transcription factor Sp1 and the neuron-specific transcription factor AP-2.

Amino Acid Sequence↗
PubMed1998

Sex steroids do not prevent amylin-induced apoptosis in human cells.

Formation of amylin-containing islet amyloid deposits may contribute to the progressive deterioration of beta cell function in non-insulin-dependent diabetes mellitus. As diabetes mellitus occurs in male, but rarely in female transgenic mice expressing human amylin in their pancreatic beta cells, it is of interest to study the influence of estradiol (E2) and testosterone (T) on amylin-induced cytotoxicity in human cells. The insulinoma cell line CM, thyroid epithelial cells (TEC) in primary culture, and nontransformed fibroblast lines were used. The occurrence of apoptotic cell death was assessed by nuclear labeling with propidium iodide. Amylin was cytotoxic on all cell types tested, but had the most pronounced effect on TEC and the weakest on the CM cell line. Although both E2 and T decreased the proportion of apoptotic cells in cultures kept in the absence of amylin, neither of the two hormones was able to counteract amylin-induced cytotoxicity. beta cell death and hyperglycemia can thus presumably not be prevented by the neutralization of amylin effects by sex steroids.

Amyloid↗
PubMed1998

Coexpression of gonadotropic hormones and their corresponding FSH- and LH/CG-receptors in the human prostate.

BACKGROUND: Benign prostatic hyperplasia (BPH) affects the majority of elderly men, and prostate cancer is the most common male cancer. Prostatic growth and function are thought to be regulated by steroid hormones, primarily androgens and estrogens, but nonandrogenic hormones must also be considered. The increasing evidence of para/autocrine functions of the gonadotropic glycoprotein-hormones (GPH), their allocation to the superfamily of cystine-knot growth factors, and luteinizing hormone (LH)/chorionic gonadotropin (CG)-receptor (R) gene expression in nongonadal tissues led us to investigate intraprostatic GPH and GPH-R gene expression. METHODS AND RESULTS: RT-PCR and subsequent Southern hybridization and/or restriction enzyme analysis of BPH and prostatic adenocarcinoma demonstrated that all three human (h) gonadotropic hormones, i.e., follicle-stimulating hormone (FSH), LH, and CG, as well as the corresponding FSH-R and LH/CG-R, are transcribed intraprostatically. Significant amounts of the alpha and beta subunits of hCG were secreted by short-term primary cultures of human BPH tissues, as detected by highly sensitive and specific time-resolved immunofluorometric assays (IFMAs). CONCLUSIONS: Our data suggest that prostatic- and pituitary-derived GPH act directly on the prostatic gland, particularly FSH via the FSH-R, thereby possibly modulating locally acting key hormones and growth factors involved in BPH development.

Chorionic Gonadotropin↗
PubMed1998

Role of replacement fluids in the immediate complications of plasma exchange. French Registry Cooperative Group.

OBJECTIVE: Comparison of side effects (fever shivering and/or allergic reactions, collapse, symptomatic hypocalcaemia) of the different substitution fluids used during therapeutical plasmapheresis. DESIGN: Multicentric retrospective comparative study designed to explore the side effects due to the replacements fluids (albumin alone or associated with dextran 40, modified fluid gelatin, hydroxyethyl starch), and to determine the best combination in patients undergoing plasmapheresis. PATIENTS: 46,895 procedures were performed on 5,167 patients between 1990 and 1994. The analysis concerns 33,962 sessions, divided into two groups (group 1: 21,079 sessions from 1990 to 1992 comparing albumin alone versus combined albumin-macromolecules and the different combinations among these, group 2: 12,883 sessions in 1993-1994 comparing albumin alone versus albumin-hydroxyethyl starch). Because of the diversity of the products used, 13,029 sessions were not studied because groups of small sample sizes were formed. MEASUREMENTS AND RESULTS: In group 1, the comparison of albumin + macromolecules with albumin alone, shows the best haemodynamic tolerance, lower frequency of fever shivering and/or allergic reactions in the albumin alone subgroup. On the other hand, hypocalcaemia is significantly higher in this subgroup. The combinations albumin + dextran 40 (but after hapten inhibition) and albumin + hydroxyethyl starch are equivalent. Albumin + modified fluid gelatin is the combination presenting the highest incidence in terms of allergic manifestations. In group 2, albumin + hydroxyethyl starch versus albumin alone, the former is preferable in terms of the three side effects studied. CONCLUSION: The results of this study show a combination of albumin 4% hydroxyethyl starch to replace plasma during plasma exchange to be the method presenting the lowest morbidity and the best cost/effectiveness ratio.

Cost-Benefit Analysis↗
PubMed1998

Production of trophoblastic hormones by transitional cell carcinoma of the bladder: association to tumor stage and grade.

Cancer registration statistics of economically advanced countries indicate that bladder carcinoma incidence ranks fourth in men and eighth in women, but a reliable tumor marker for predicting the disease course is still lacking. We designed an immunohistochemical study to comprehensively assess the trophoblastic hormone production profile of transitional cell carcinoma (TCC) of the bladder. Moreover, we correlated histological differentiation and tumor stages with marker expression and, finally, evaluated a potential tumor origin of hCGbeta core-fragment (hCGbetacf). To this end, formalin-fixed, paraffin-embedded tumor tissues from 104 patients with urothelial neoplasms of various histological grades (23 GI, 24 GII, and 38 GIII) and stage (19pTis, 21pTa, 29pT1, and 35pT2-T4) were analyzed by the immunoperoxidase technique using our own well-characterized monoclonal antibodies against the glycoprotein hormones human chorionic gonadotropin (hCG) and its derivatives hCGalpha, hCGbeta, hCGbetacf, luteinizing hormone (LH, LHbeta), follicle-stimulating hormone (FSH, FSHbeta), and the protein hormones placental lactogen (hPL) and growth hormone (hGH-V/N). Overall, trophoblastic hormone immunoreactivity was found in 36% of TCC. Detailed analysis showed 35% hCGbeta, 17% hCGbetacf, 9% hCGalpha, 4% hCG, and 2% hPL-positive cases. The tumors produced neither GH-N, placental GH-V, nor the pituitary gonadotropins FSH/FSHbeta and LH/LHbeta. Marker positivity significantly increased with high-grade lesions (26% GI- v 55% GIII-TCC) and advanced tumor stages (24% pTa v 63% > or = pT2). Hormone immunoreactivity was frequently observed in highly proliferating areas. Our findings, together with recent structural and clinical studies, strongly suggest that these hormones, or derivates thereof, might act as local tumor growth factors. Normal urothelium, urothelial papillomas, and carcinoma in situ showed no positive reactions. All tumors producing hCG-derived molecules were negative for the concommitantly analyzed neuroendocrine markers chromogranin A, synaptophysin, and neuron-specific enolase (NSE). In summary, one third of TCC ectopically produce trophoblastic hormones, which is specifically correlated with stage and grade. Apart from hCGbeta (97% of the marker-positive cases), the intracellular occurrence of hCGbetacf, apparently the second most frequently produced marker, was surprising, and there was also a lesser degree free hCGalpha and intact holo-hormone expression. The placental protein hormones PL and GH-V are not appropriate tumor marker candidates. Finally, our histogenetic findings support a metaplastic origin of the hCG producing choriocarcinomatous phenotype of some TCC.

Adult↗
PubMed1998

Reassessment of the role of human placental lactogen in physiological non-pregnant and pathological conditions.

The recent demonstration of ectopic production of human placental lactogen (PL) in the human testis and ovary prompted us to reassess its role under non-pregnant physiological and pathological conditions. Possible physiological hPL concentrations and potential age-related changes in the sera of healthy young and elderly individuals (n = 75) selected according to the SENIEUR-protocol were investigated by a highly sensitive (detection limit: 2 pg/ml) and specific (cross-reactivity with prolactin and human growth hormone (hGH) of less than 0.001% and 0.0001%, respectively) monoclonal antibody-based time-resolved fluoroimmunoassay (IFMA) established in our laboratory. All individuals, even the aged probands (mean age: 72 +/- 3a), had hPL-levels below 20 pg/ml, in contrast to glycoprotein hormones, such as luteinizing hormone or human chorionic gonadotropin (hCG). To determine the significance of hPL as a tumour marker, serum samples of 12 testicular cancer patients with highly elevated levels of holo-hCG (mean: 42.490 ng/ml) at diagnosis were followed over 6-12 months and analysed with the hPL-IFMA. Elevation of hPL was seen in 10 patients, but the respective levels were 2-3 orders of magnitude smaller than those of holo-hCG and returned earlier to undetectable values. These in vivo data were compared to the hPL secretion pattern of the choriocarcinoma cell lines JAR and BeWo in vitro. In tissue culture supernatants of the two cell lines hPL was detected only in JAR cells, whereas both cell lines secreted holo-hCG. In conclusion, the fact that hPL is not physiologically present in peripheral blood but is produced ectopically in the human testis and ovary suggest auto/paracrine functions of this molecule. The significance of hPL as a tumour marker for patients with testicular cancer is limited as it provides no additional information to holo-hCG.

Adult↗
PubMed1998

Partial face-sparing lipodystrophy (Köbberling-Dunnigan syndrome): report of a sporadic case.

A sporadic case is presented of a 20-year-old female with partial face-sparing lipodystrophy, also known as the Köbberling-Dunnigan syndrome with the Type 1 clinical phenotype. This disorder affects the limbs and spares the face. The trunk is spared in the Type 1 phenotype but is affected in the Type 2 phenotype. The patient had the associated features of this syndrome including the hyperinsulinaemia, acanthosis nigricans and mildly raised triglycerides, but not diabetes mellitus.

Acanthosis Nigricans↗
PubMed1998

The unified biosocial model of personality in schizophrenia families and controls.

This report describes the application of a unified biosocial model of personality developed by C.R. Cloninger to a sample of families identified through a proband with schizophrenia and a sample of controls. Families of schizophrenic patients were ascertained in USA and Austria. We could detect differences between females and males in their response to positive reinforcement (Reward Dependence) and differences between young and old people with respect to the response to new and/or exciting situations (Novelty Seeking). In general, results obtained for individuals from schizophrenia families and controls were similar. These results are not substantially influenced by psychiatric disorders in individuals. Psychiatric diagnosis may have an influence on the third dimension of Cloninger's model, designated Harm Avoidance. Analysis showed that patients with a diagnosis of schizophrenia or from the schizophrenia spectrum try harder to avoid punishment or aversive stimuli than family members with another psychiatric disorder or without a psychiatric diagnosis as well as controls. The results are promising and further research is needed to evaluate the structure of the proposed personality model in families and the relationship of personality to psychiatric status.

Adult↗
PubMed1998

Immunoglobulin E-induced passive sensitization of human airways: an immunohistochemical study.

In vivo, IgE production is related to bronchial hyperresponsiveness and, in vitro, passive sensitization of human airways with asthmatic serum containing a high concentration of IgE enhances the contractile response to a variety of agonists. However, cell types implicated in this IgE sensitization are not fully determined. The aim of this study was to determine IgE-bearing cells during passive sensitization with special reference to mast cells. Peripheral bronchi were dissected out from 10 lung specimens obtained at thoracotomy and processed into glycolmethacrylate resin. Sections, each 2 microm thick, were passively sensitized by incubation for 2 h at 37 degrees C in either buffer supplemented with monoclonal IgE or asthmatic serum with a high concentration of IgE (> or = 1,000 IU/ml). Immunohistochemistry was performed using monoclonal antibodies directed against the epsilon chain, and markers of the various IgE-bearing cells (e.g., AA1, antichymase). The number of IgE-bearing cells was significantly higher in passively sensitized specimens as compared with nonsensitized specimens (6.63 +/- 1.71 versus 4.29 +/- 1.35/mm2; p = 0.013, n = 10). Mast cells represented 65% of IgE-bearing cells, 41.6 and 23.4% for TC and T subtypes, respectively. These results indicate that mast cell is the main cell type involved in IgE-induced passive sensitization. The involvement of mast cell-derived tryptase in the mechanisms of IgE-related hyperresponsiveness should be further examined.

Adult↗
PubMed1998

Complex alternative splicing of the GH-V gene in the human testis.

The human growth hormone variant (GH-V) gene is expressed during pregnancy in the syncytiotrophoblast and, as shown recently, in the normal human testis. In addition to the classical transcript encoding for the 22 K major form, intron D-retaining processed mRNAs (GH-V2) have also been described in both tissues. In the present study we analyzed testicular GH-V RNA alternative splicing patterns, a major source of GH variability. We observed three types of GH-V-derived mRNAs by reverse transcription-polymerase chain reaction amplification of GH/placental lactogen mRNA, subsequent cloning into appropriate vectors, vector amplification, restriction-endonuclease map-analysis and double-strand sequencing of GH-V clones. Apart from the conventional splice product encoding classical hGH-V (22K, 191 amino acids (aa)) and intron D-retaining mRNA GH-V2 (230aa), we detected an additional GH-V mRNA variant, GH-Vdelta4, utilizing a competitive splice-donor site 4 bp 5'of the conventional exon 4/intron D splice-donor site, but retaining the genuine intron D/exon 5 splice-acceptor site. This mRNA encodes a putative 25 K protein of 219 amino acids in length, having the first 124 amino acids and, thus, two and a half structural alpha-helices in common with hGH-V.hGH-Vdelta4 has lost the N-glycosylation site at Asn 140 of hGH-V, but acquires a novel site at position 148 as well as a cystein-rich domain in the 65 carboxyl-terminal amino acids, potentially involved in multiple disulfide-bridge formation. Tissue specificity and possible functions for testicular physiology remain to be investigated.

Alternative Splicing↗
PubMed1998

Gonadotrophin secretion patterns in testicular cancer patients with greatly increased human chorionic gonadotrophin serum concentrations.

Despite the fact that a number of alterations of the hypothalamic-pituitary-gonadal hormone axis have been identified in patients with testicular cancer, little is known about the gonadotrophin secretion pattern in such patients who have greatly increased human chorionic gonadotrophin (hCG) serum concentrations. The aim of this study was to assess this issue in detail using a longitudinal study design and a panel of highly sensitive and specific immunoassays. Eleven patients with non-seminomatous (n=11), and one with seminomatous testicular cancer with pretreatment hCG serum concentrations exceeding 10(5) pg/ml (>1000 mIU/ml) were selected and followed for a mean of 166 days (mean of 14 serum samples/patient) after initial diagnosis. Serum concentrations of hCG, its free alpha- (hCGalpha) and beta- (hCGbeta) subunits, human follicle-stimulating hormone (hFSH) and human luteinizing hormone (hLH) were determined by highly sensitive and specific enzymometric immunoassays based on a panel of monoclonal antibodies (MCA) established in our laboratory. A potential FSH-like activity (FSA) of hCG in the respective sera was determined by radioreceptor assays (RRA) for LH/CG and FSH. Specificity of FSA at the level of the receptor was assessed by MCA-based immunoabsorption studies. At diagnosis, hCG (9.8x10(7)+/-4.84x10(7) pg/ml; range 1.1x10(5)-5x10(8) pg/ml) was greatly increased and serum hFSH was undetectable (<9 pg/ml) in 11 patients, and one patient had very low, albeit detectable (approximately 30 pg/ml) hFSH concentrations. hLH was below the limit of detection (<2 pg/ml) in five individuals. During successful chemotherapy, hCG rapidly declined to physiological concentrations and hFSH/hLH returned to normal or even reached supraphysiological values. There was a highly significant negative correlation between hCG and hFSH (P=0.0001) and, to a lesser extent, hLH (P=0.0265). The ability of serum hCG to block the binding of [125I]rFSH (rat FSH) to its receptor was found to be 0.01-0.1% compared with the FSH standard; this could be reversed by an anti-hCG MCA. Addition of a specific MCA against hFSH blocked 3 microg/ml of the hFSH standard, but had no effect on the FSA of serum hCG in the FSH RRA. As observed during pregnancy, secretion of gonadotrophin -- particularly that of FSH -- is substantially or completely suppressed in patients with testicular cancer when serum hCG concentrations exceed 10(5)-10(6) pg/ml (approximately 10(3)-10(4) mIU/ml). As determined by RRA, the intrinsic FSA of tumour-derived hCG is most probably responsible for the suppression of hFSH in this group of patients with testicular cancer.

Chorionic Gonadotropin↗
PubMed1997

[Immune reaction to tetanus in the elderly: what is the duration of vaccine protection?].

Infectious diseases represent one of the most frequent causes of morbidity and mortality in the elderly. Little information is yet available on the state of immunization against well-known antigens such as tetanus toxoid (TT) in old age. It was, therefore, the aim of this study to analyze antibody titres and peripheral blood mononuclear cell (PBMC) reactivity to TT in healthy SENIEUR compatible young (< 30 years, n = 25) and old (> 65 years, n = 32) blood donors. TT-specific antibodies were measured by the ELISA technique; PBMC proliferation was assessed by 3H-thymidine incorporation analysis. In the young group TT antibody titres were detectable in all but two individuals, whereas 60% of the old persons had no detectable TT antibodies. This seemed partly to be due to a shortened immunological memory in old age, since 32% of the aged persons without TT antibodies had been vaccinated within the past 10 years, 21% even 3 to 6 years prior to investigation. TT antibody concentrations were normal in aged individuals vaccinated within the past two years. Peripheral blood lymphocytes from all but two persons without antibody titres did not proliferate when stimulated with TT in vitro, indicating that no memory T cells were available to reinduce an efficient immune response. Our results suggest that the tetanus vaccination strategy practised in Austria does not guarantee full protection in the elderly.

Adult↗
PubMed1997

Organ-specific expression pattern of the human growth hormone/placental lactogen gene-cluster in the testis.

In addition to testosterone, the essential paracrine factor for spermatogenesis, a number of potential auto/paracrine regulatory substances such as beta-endorphins, enkephalins, chorionic gonadotropin beta, growth hormone-releasing hormone (GHRH) and insulin-like growth factor I (IGF-I) have been identified in the testis of various mammalian species. The latter findings prompted us to investigate a possible eutopic production of GH, placental lactogen (PL) and PRL in human testes. Specific expression of testicular GH/PL mRNA (n = 20) was shown by reverse transcription-polymerase chain reaction (RT-PCR) using a pair of primers designed to non-selectively amplify any transcript of the five GH/PL genes (GH-N, GH-V, PL-A, PL-B, PL-L). In contrast to the classical sites of production, the pituitary (exclusively GH-N transcripts) and the placenta (PL-A/B > 99%, GH-V < 1%), radioactive semiquantitative restriction enzyme analysis of the PCR-products revealed, that the testis has its own organ-specific pattern of GH/PL gene expression: PL-A/B > GH-V > or = PL-L = GH-N. All three organs express the single PRL gene, and testis and placenta show the alternative splice variant GH-V2. Immunological analyses by immunofluorometric assays for hPL-A/B, hGH-N and hPRL, demonstrated significant amounts of protein hormones in all testicular cytosolic homogenates (means: hPL 1.0 ng/g, hGH 5.1 ng/g and hPRL 58.7 ng/g tissue wet weight). Most noteworthy, hPL serum levels in an elderly age-matched healthy subjects (n = 18) were < 0.02 ng/ml. The concept of purely endocrine functions of placental and pituitary-derived GH/PL needs to be reassessed, since human testicular synthesis of these molecules suggest auto/paracrine functions in the male reproductive tract.

Aged↗
PubMed1997

[Clinical aspects of sleep disorders--experiences with 817 patients of an ambulatory sleep clinic; comment].

Between 1992, the year in which the Sleep Out-Patient Clinic at the Department of Psychiatry, University of Vienna, Allgemeines Krankenhaus (General Hospital) Vienna, was established, and 1996, 817 patients (58% females, average age 52 years; 42% males, average age 48 years) were treated for sleep disorder. According to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) of the World Health Organization (WHO), 70% of the patients presented with a non-organic sleep disorder and 30% with an organic sleep disorder as main diagnosis. Non-organic insomnia was by far the most frequently diagnosed sleep disorder (48%), while within the organic sleep disorders sleep apnea was dominant (12%). In regard to the additional non-organic (mental disorder) diagnoses rounding off the clinical picture, neurotic, stress related, and somatoform disorders were the most common (41%), followed by affective disorders (31%) and mental and behavioural disorders due to intake of psychoactive substances, e.g. alcohol, drugs (15%). Additional organic diagnoses related to sleep disorders involved primarily endocrine disorders such as adipositas (23%), followed by cardiovascular disorders (19%), and primary snoring (17%). The sleep out-patient clinic has at its disposal a supportive diagnostic armamentarium such as all-night sleep polysomnography, 24-hour polysomnography, the Multiple Sleep Latency Test, EEG and EEG-mapping in the affiliated sleep laboratory, the evaluation of event-related potentials (P300) and actometry in the psychophysiological laboratory, as well as psychological and psychophysiological tests in the clinical psychodiagnostic laboratory, in order to determine the right treatment or preventive measures for the individual patients.

Adult↗
PubMed1997

Human neuroserpin (PI12): cDNA cloning and chromosomal localization to 3q26.

Neuroserpin is a novel serine protease inhibitor of the serpin family. It has been reported as a 55-kDa glycoprotein that is secreted from the axons of cultured central and peripheral nervous system neurons. In situ hybridization and Northern blot analyses at different developmental stages of the chicken revealed that neuroserpin is predominantly expressed in the nervous system and that most cells expressing neuroserpin can be qualified as bona fide neurons. We have isolated the full-length cDNA for human neuroserpin from a fetal retina cDNA library. The open reading frame of the cDNA of human neuroserpin, like that of its chicken counterpart, encodes a protein of 410 amino acids. The human and the chicken neuroserpin exhibit an amino acid sequence identity of 80%. Northern blot analysis of human organs demonstrated predominant expression of neuroserpin in the brain. By fluorescence in situ hybridization the human neuroserpin gene (HGMW-approved symbol PI12) was mapped to region q26 of chromosome 3.

Amino Acid Sequence↗
PubMed1997

Embarrassment about the first panic attack predicts agoraphobia in panic disorder patients.

In order to find out whether contextual variables of the first panic attack and the person's reaction to it predict the development of agoraphobia in panic disorder patients, 60 patients with a DSM-III-R diagnosis of panic disorder with agoraphobia and 30 patients suffering from panic disorder without agoraphobia were interviewed about their first panic attack. Single comparisons between groups of agoraphobic and non-agoraphobic patients were carried out and a logistic regression model was applied. Occurrence of the first panic attack in public and the feeling of embarrassment were found to be significantly associated with the development of agoraphobia. It is concluded that eliciting this specific form of social concern at an early stage might help to identify patients at risk for later agoraphobia, which could, in turn, help to further specify early therapeutic interventions and concentrate therapeutic efforts on a high-risk group of panic disorder patients.

Adaptation, Psychological↗