Search PubMed⌕ Search

Biomedical subjects

M Bergmann

Publications and source records attributed to M Bergmann.

At least 73 records · Page 4Linked to original sources

Obesity, body fat distribution and body build: their relation to blood pressure and prevalence of hypertension.

OBJECTIVE: To determine the relation of skeletal body build and obesity to blood pressure and the prevalence of hypertension. DESIGN: Cross-sectional data obtained from the baseline recruitment of the EPIC-Potsdam Study, which is part of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: A total of 10,303 subjects (4387 men, aged 40-65 y and 5916 women, aged 35-65 y) were recruited between January 1995 and July 1996. MEASUREMENTS: Anthropometric measures included body mass index (BMI), waist-hip ratio (WHR) and metrik index (MIX) as a measure of body build that is derived from the relation of chest depth and breadth to body height. Systolic and diastolic blood pressure was obtained using automatic oscillometric devices. Hypertension was defined as blood pressure > or = 160/95 mmHg or current use of antihypertensive medication. Information on lifestyle factors were obtained by personal interview. STATISTICAL ANALYSIS: Logistic regression was used to define the association of categories of BMI, WHR, and MIX and the prevalence of hypertension. Odds ratios (ORs) of being hypertensive were estimated comparing the highest to the lowest quintile, adjusting for age, smoking status, alcohol intake level, educational attainment, physical activity categories, and each of the anthropometric variables. RESULTS: The simultaneously adjusted OR of being hypertensive, comparing the highest vs the lowest category, was for BMI 2.3 (95% confidence interval (CI) = 1.6-3.2) in men and 1.8 (95% CI = 1.4-2.5) in women, for WHR 1.8 (95% CI = 1.4-2.4) in men and 1.5 (95% CI = 1.2-2.0) in women, and for MIX (largest chest size vs lowest chest size relative to body height) 2.0 (95% CI = 1.4-2.8) in men and 2.2 (95% CI = 1.6-3.1) in women. CONCLUSION: In addition to measures of overall obesity (BMI) as well as central obesity (WHR), skeletal body build (MIX) was independently associated with the prevalence of hypertension. The biological mechanism relating MIX to hypertension, however, is still unclear and needs further exploration.

Adipose Tissue↗

Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant recipients. A fibroproliferative process involving mesenchymal cells is observed histopathologically. In order further to evaluate the pathomechanisms of BOS, the gene expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung transplant recipients and appropriate controls was studied. Equal amounts of total RNA were submitted to semiquantitative reverse transcription/polymerase chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using established protocols and primer sets. The signal/actin ratio was calculated based on laser densitometry measurements. TGF-beta 1 transcripts were detected in all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was increased in BAL samples from BOS patients compared to unaffected recipients and controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression in BOS patients revealed an increased PDGF signal preceding lung function deterioration. The data were consistent with the hypothesis based mainly on in vitro findings that PDGF and TGF-beta contribute to the development of BOS.

Adult↗

Intrapartum labetalol for the treatment of maternal and fetal thyrotoxicosis.

Maternal thyrotoxicosis complicates approximately 0.2% of pregnancies. Simultaneous occurrence of maternal and fetal thyrotoxicosis during labor is rare, and control of maternal tachycardia and hypertension, as well as fetal manifestations of thyrotoxicosis, are cornerstones of management. An 18-year-old nulliparous female at 33 weeks gestational age presented in labor with thyrotoxicosis. Fetal tachycardia was present as well. Labetalol therapy resulted in a decrease in maternal pulse and blood pressure, and resolution of fetal tachycardia. Vaginal delivery occurred. Subsequent evaluation demonstrated neonatal thyrotoxicosis and high maternal titers of thyroid-stimulating immunoglobulin. In conclusion, labetalol was beneficial in the treatment of maternal and fetal thyrotoxicosis during labor.

Adolescent↗

Abnormal surface expression of sialoglycans on B lymphocyte cell lines from patients with carbohydrate deficient glycoprotein syndrome I A (CDGS I A).

The carbohydrate-deficient glycoprotein syndromes (CDGS) are genetic, multisystemic diseases characterized by deficiencies in the glycosylation of many secretory glycoproteins, lysosomal enzymes, and possibly cell surface glycoproteins resulting in central nervous system abnormalities and frequent early death by infection. Here we examined whether membranous glycoconjugates of lymphocytes are affected by this disorder. For this, we analyzed cell surface-expressed sialoglycans of Epstein Barr virus (EBV)-transformed B cell lines derived from peripheral B lymphocytes of several patients with CDGS I A. These CDG-LCL (lymphoblastoid cell lines) expressed differentiation markers comparable to those of other EBV-transformed B cell lines. No apparent defects in the gross glycosylation process of defined complex glycosylated proteins such as the surface-expressed major histocompatibility complex class I glycoprotein or secreted immunoglobulin (IgM) were identified. However, using a novel flow cytometric enzyme assay to measure cell surface alpha2,6 sialylation on live cells we found that CDG-LCL express less alpha2,6 sialylated glycans in comparison to other EBV-transformed B cell lines. Also, CDG-LCL bound less of the B lymphocyte lectin CD22, specific for alpha2,6 sialylated lactosamines and known to modulate B cell receptor mediated signaling, as demonstrated by using a soluble CD22-immunoglobulin fusion protein in flow cytometry. CDG-LCL showed stronger surface staining with the monoclonal antibody 1B2 which detects a distinct group of surface-expressed lactosaminyl epitopes. After pretreatment with neuraminidase of Newcastle disease virus (NDVN) it became apparent that in CDG-LCL a significantly larger portion of the 1B2 epitopes was sialylated in alpha2,3 linkage as compared to other B cell lines. Intracellular alpha2,6 sialyltransferase activity as well as polymerase chain reaction products specific for four different sialyltransferases did not significantly differ in CDG-LCL as compared to other EBV-B cell lines. Differences in sialylation may be caused by the respective oligosaccharide core structures available for alpha2,6 or alpha2,3 sialylation in CDG-LCL. Therefore, lymphocytes derived from CDGS patients have distinct deviations in their surface-expressed lactosaminoglycan structures which may affect functions as exemplified by reduced interactions of CD22 with its ligands.

B-Lymphocytes↗

Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial.

To examine the role of recombinant human follicle stimulating hormone (rhFSH) in male idiopathic infertility a randomized, double-blind, placebo-controlled study was performed. Of 211 patients screened, 67 were finally included. After two pre-examinations, patients were randomized and treated for 12 weeks, either with 150 IU rhFSH or with placebo. Examinations (physical examination, scrotal ultrasonography, semen analysis, hormone measurements, and in 31 patients electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after treatment initiation and 6 and 12 weeks after completion of treatment. Pregnancies were recorded for a further 3 months after the last examination. Of the 67 patients included in the study, 34 treated and 31 placebo patients could be analysed. In the treated group, FSH was elevated compared to baseline values (P < 0.001). At the end of treatment testicular volume in the treated group was increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA condensation (P < 0.001) in the treated group no significant changes were observed in semen parameters. Two spontaneous pregnancies in partners of men in the treated group and none in the placebo group occurred. However, two pregnancies occurred in partners of men in the placebo group induced by intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at the chosen dose and duration, rhFSH did not lead to an improvement of conventional or EM sperm parameters nor to an increase in pregnancy rates. However, the increased testicular volume and sperm DNA condensation give reason for further investigations.

DNA↗

Testicular cAMP responsive element modulator (CREM) protein is expressed in round spermatids but is absent or reduced in men with round spermatid maturation arrest.

Mice lacking the functional cAMP responsive element modulator (CREM) gene, a component of cAMP-mediated signal transduction, exhibit a specific arrest of round spermatid development although follicle stimulating hormone (FSH) and androgen secretion are not impaired. We studied testicular expression of CREM protein by immunocytochemistry in four patients with complete spermatogenesis (obstructive azoospermia), in 20 infertile patients with round spermatid maturation arrest (n = 10) or mixed atrophy (n = 10) and in six prostate cancer patients undergoing orchidectomy. Concentrations of testosterone were below normal in three patients. Concentrations of luteinizing hormone (LH) were lowered in two patients and elevated in one patient. FSH concentrations were above normal in ten patients. During normal spermatogenesis, CREM was expressed in nuclei of round spermatids in stages I-III of spermatogenesis but not in elongating spermatids. Western blot analysis of testes from prostate cancer patients indicated a major CREM band of approximately 35 kDa. Among patients with predominant round spermatid maturation arrest, CREM expression was significantly reduced (P < 0.05) or undetectable as revealed by quantitative image analysis. CREM-negative spermatids failed to progress beyond stage III of spermatogenesis. Our observations suggest a role for CREM in human spermatid development and raise the possibility that altered CREM expression could be associated with spermatid maturation defects in some cases of idiopathic male infertility.

Adolescent↗

Expression of mRNA and protein of nucleoproteins during human spermiogenesis.

The most important event determining the nuclear status of sperm cells is the replacement of histones by protamines, which are the basic nuclear proteins of mature spermatozoa. A first step in this exchange is the displacement of histones by transition proteins (TP). Our study demonstrates, for the first time, the sequential expression of the testis-specific histone (H1t) and the transition proteins (TP1 and TP2) during normal human spermatogenesis. H1t mRNA could only be detected in the cytoplasm of mid and late pachytene spermatocytes. Concomitant with the onset of H1t transcription, the H1t protein appeared in the nuclei of pachytene spermatocytes and remain as a nuclear protein constituent up to step 5 spermatids. While transition protein 1 gene TNP-1 mRNA was present in spermatids from step 2 to early step 4, the TP1 protein occured, with temporal delay, in the nuclei of step 3 and step 4 spermatids. The TP2 protein was observed in the nuclei of spermatids from step 1 to step 5. The transition protein 2 gene TNP-2 mRNA was only detected by reverse transcription-polymerase chain reaction, but not on paraffin sections. These data demonstrate a strong temporal association between H1t gene transcription and synthesis of the H1t protein. Since the TP1 protein appeared with temporal delay we can assume that the corresponding TNP-1 mRNA is translationally delayed.

Blotting, Western↗

The proliferation of spermatogonia in normal and pathological human seminiferous epithelium: an immunohistochemical study using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen.

The quantitative distribution pattern of Ki-67 protein and proliferating cell nuclear antigen (PCNA) immunoreactivity was studied in human testis biopsies. In normal seminiferous epithelium Ki-67 is expressed in nuclei of spermatogonia, while PCNA additionally occurs in nuclei of primary spermatocytes. The staining pattern of spermatogonia is as follows (Ki-67-positive/PCNA-positive): 26.6 +/- 12.4%/46.3 +/- 9.5%. No stage-dependent differences were found. Biopsies with mixed atrophy (score < or =7) showed a significant (P < 0.05) decrease of immunopositive spermatogonia to 19.9 +/- 3.0%/31.4 +/- 5.7% (score 1) with minimal variation between different samples (score 7 to 1). Associated with defined histological defects such as hypospermatogenesis (hyp), spermatogenic arrest at the level of spermatids (sda), spermatocytes (sca) or spermatogonia (sga), however, there was a significant (P < 0.05) decrease of Ki-67 staining in tubules showing hyp (28.6 +/- 8.8%), sda (25.6 +/- 9.3%), sca (23.7 +/- 9.3%) and sga (16.2 +/- 6.0%) and of PCNA staining in sca (32.2 +/- 11.8%) and sga (20.0 +/- 9.5%), respectively. The decrease of immunoreactive spermatogonia did not correspond to elevation of follicle stimulating hormone (FSH). These data demonstrate that the low spermatogenic efficiency in infertile men is not only due to postmeiotic events, but also to a decrease in the meiotic activity of spermatogonia, and is not related to serum FSH.

Antibodies, Monoclonal↗

Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions.

Oligodendrocyte and axon pathology was studied in 11 autopsy cases of clinically silent multiple sclerosis. A total of 54 lesions, either demyelinated or late remyelinated, were distributed through the whole brain and spinal cord with 39% of the lesions located in periventricular areas. Determination of axon density revealed an average reduction of 64% and 59% in demyelinated and remyelinated lesions with an extreme variation between different plaques and cases. Oligodendrocytes were identified by immunocytochemistry for myelin oligodendrocyte glycoprotein (MOG) and in situ hybridization for proteolipid protein (PLP) mRNA. Oligodendrocytes were almost completely lost in demyelinated lesions; remyelinated lesions revealed preservation of a considerable number of oligodendrocytes within the lesions. At the border between plaques and the periplaque white matter, similar oligodendrocyte numbers as in remyelinated lesions were found. Different factors including lesion site, axonal preservation and remyelination may thus contribute to the clinical nonappearance of multiple sclerosis lesions.

Adult↗

A simple model for learning stereotactic skills in ultrasound-guided amniocentesis.

BACKGROUND: Amniocentesis is an important procedure for antenatal diagnosis but requires stereotactic skill acquisition that may be facilitated by the use of a model. TECHNIQUE: A model using a gelatin mold with "targets" within is created. The model is used to facilitate development of stereotactic skills and to demonstrate technique principles for ultrasound-guided amniocentesis. EXPERIENCE: The model has been incorporated into an educational program for antenatal diagnosis within a residency and provides a reasonable simulation of clinical features important in learning genetic amniocentesis. CONCLUSION: The use of this model augments the learning of important skills needed for ultrasound-guided amniocentesis.

Amniocentesis↗

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes.

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.

Adolescent↗

The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr.

bcr-abl, the oncogene causing chronic myeloid leukemia, encodes a fusion protein with constitutively active tyrosine kinase and transforming capacity in hematopoietic cells. Various intracellular signaling intermediates become activated and/or associate by/with Bcr-Abl, including the Src family kinase Hck. To elucidate some of the structural requirements and functional consequences of the association of Bcr-Abl with Hck, their interaction was investigated in transiently transfected COS7 cells. Neither the complex formation of Hck kinase with Bcr-Abl nor the activation of Hck by Bcr-Abl was dependent on the Abl kinase activity. Both inactivating point mutations of Hck and dephosphorylation of Hck enhanced its complex formation with Bcr-Abl, indicating that their physical interaction was negatively regulated by Hck (auto)phosphorylation. Finally, experiments with a series of kinase negative Bcr-Abl mutants showed that Hck phosphorylated Bcr-Abl and induced the binding of Grb2 to Tyr177 of Bcr-Abl. Taken together, our results suggest that Bcr-Abl preferentially binds inactive forms of Hck by an Abl kinase-independent mechanism. This physical interaction stimulates the Hck tyrosine kinase, which may then phosphorylate the Grb2-binding site in Bcr-Abl.

Adaptor Proteins, Signal Transducing↗

Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta.

The cyclooxygenase (COX) isoforms COX-1 and COX-2 convert arachidonic acid to prostaglandin (PG) precursors and are a limiting step in PG production. Interleukin-1beta (IL-1beta) treatment of type II A549 cells increases PGE2 synthesis via transcription- and translation-dependent induction of COX-2. IL-1beta produces a 10-fold induction of COX-2 mRNA and an 8-fold increase in COX-2 transcription that was temporally preceded by activation of the transcription factor nuclear factor-kappaB (NF-kappaB). The protein-tyrosine phosphatase inhibitor phenylarsine oxide (PAO) prevented both NF-kappaB activation and induction of COX-2 mRNA. We show that two putative NF-kappaB motifs, kappaBu (-447/-438) and kappaBd (-224/-214), from the COX-2 promoter bind p50/p65 NF-kappaB heterodimers in an IL-1beta-dependent manner and that the upstream element has the greater affinity. Finally, we demonstrate that the two NF-kappaB subunits, p50 and p65, synergistically activate a -917/+49 COX-2 promoter construct. We conclude that IL-1beta stimulates PG production via transcriptional activation of COX-2 and provide evidence that this may involve NF-kappaB.

Arsenicals↗

Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases.

BACKGROUND: Secretory meningioma is a rare histologic variant characterized by a unique epithelial differentiation of meningothelial cells resulting in the production of hyaline inclusions. Most previous reports have presented single case observations. The authors selected 31 cases for a clinicopathologic study to characterize this type of tumor further. METHODS: Clinical data were compiled and the extent of peritumoral edema was assessed from preoperative computed tomography or magnetic resonance imaging scans. Preparations of surgical specimens of all tumors were studied after both conventional histologic and immunohistochemical preparations were made. Immunostaining was performed by either the avidin-biotin complex method or the alkaline phosphatase-antialkaline phosphatase method using 22 primary antibodies. RESULTS: In the tumor collection used in this study, secretory meningiomas represented 3% of meningiomas. The female-to-male ratio was 9:1. Most tumors were located at the sphenoid ridge or at the frontal convexity, and recurrences were not observed. Eighty-four percent of tumors presented with slight to marked peritumoral edema. The MIB-1 staining index showed a mean of 3.8%. Inclusions and surrounding cells consistently expressed epithelial membrane antigen, cytokeratins, carcinoembryonic antigen, and carbohydrate antigen 19-9. In decreasing frequency, they also contained alpha1-antitrypsin, immunoglobulin (Ig)A, alpha1-antichymotrypsin, IgM, and IgG. Cells positive for vimentin and S-100 did not contain inclusions. All tumors were positive for progesterone receptors. Macrophages were stained with antibodies to factor XIIIa, human leukocyte antigen-DR, and alpha1-antitrypsin. In 64% of cases, tumor vessels lacked expression of glucose transporter protein 1. CONCLUSIONS: The classification of secretory meningioma as a distinct variant has been justified on clinical, histologic, and immunohistochemical grounds. The unique epithelial features call attention to the broad spectrum of differentiation properties found in meningiomas.

Adult↗

Primary malignant rhabdoid tumours of the central nervous system: an immunohistochemical and ultrastructural study.

Three cases of primary rhabdoid tumour of the CNS (RT-CNS) are presented. In case 1 a hemispheric tumour developed in a 10.5 months old girl, who survived for 6 months after incomplete resection, radio- and polychemotherapy. Case 2 was a 4 years and 8 months old boy with a large IIIrd ventricle tumour, who died of leptomeningeal tumour dissemination 7 months after diagnosis despite radiotherapy. In case 3 a pineal mass occurring in a 14 month old female was radioresistant and totally exstirpated. The child died due to tumour recurrence two months later. Autopsy examination revealed widespread leptomeningeal dissemination. All three cases fulfilled light and electron microscopic criteria of RT-CNS including abundant eosinophilic cytoplasm, vesicular nuclei with large nucleoli and conspicuous anti-vimentin positive filaments. Extensive immunohistochemical studies showed expression of epithelial (EMA, KL1), macrophage (alpha-1 antichymotrypsin), neuro-ectodermal (GFAP, NSE, beta-tubulin III) and myogenic markers (desmin, actin). Different stress proteins (alpha-B crystallin, HSP70) were also expressed. Tumour cells showed a proliferation (MIB1) index of 28.4% (case 1) and 33.4% (case 2). From our study it can be concluded that RT-CNS reveals significant immuno-morphological heterogeneity thus supporting the view that it is not a specific pathological entity but merely a phenotypic appearance of different neoplasms, some of which are linked to primitive neuro-ectodermal tumours.

Biomarkers, Tumor↗

Expression of synaptophysin in sprouting neurons after entorhinal lesion in the rat.

Expression of the synaptic vesicle protein synaptophysin was studied in lesion-induced sprouting neurons of the contralateral entorhinal cortex and in the contralateral dentate gyrus using immunocytochemistry at the light- and electron-microscopic level. Perikaryal immunoreactivity for synaptophysin was found between 8 and 10 days postlesion. Light microscopy revealed that synaptophysin immunostaining was present in almost all neurons of layers II and III of the contralateral medial entorhinal cortex. These neurons give rise to the sprouting, crossed temporodentate pathway. In addition, some hilar neurons of the contralateral dentate gyrus, which are the parent cells of sprouting commissural fibers, were immunostained for synaptophysin. Transient immunostaining for synaptophysin was observed within cell bodies and dendrites. Additionally, the cell bodies were outlined by immunoreactive puncta, identified by electron microscopy as nerve terminals. Our results revealed that sprouting neurons express the major synaptic vesicle protein synaptophysin during reactive synaptogenesis in a pattern that reflects biosynthesis and sorting of this protein as seen in developing neurons during synapse formation.

Animals↗

Distribution of heat-shock protein 60 immunoreactivity in testes of infertile men.

The immunohistochemical localization of heat-shock protein 60 (hsp60) was investigated in testicular biopsies obtained from 121 adult men with disturbed fertility. In normal unaffected tubules, hsp60 immunoreactivity was localized to spermatogonia, primary spermatocytes and Sertoli cells. In spermatogonia, cytosolic and mitochondrial labelling could be differentiated. In general, the number of stained spermatogonia decreased with the loss of spermatogenic function. A significant (P<0.01) reduction of stained spermatogonia was observed in testes with maturation arrest of spermatogenesis at the level of primary spermatocytes (30.2+/-21.6%) compared with testes exhibiting normal spermatogenesis. In addition, the decrease in the score correlated significantly with the diminution of cytosolic hsp60 immmunolabelling (coefficient r=0.25, P=0.03). There was a significant difference (P<0.01) in the percentage of cytosolic-stained spermatogonia in testes with a score equal to or greater than 5 (14.7+/-9.8%) and a score less than 5 (8. 9+/-6.9%). These observations suggest that a low level of hsp60 expression in spermatogonia may lead to a different pattern of protection, which in turn could be involved in low spermatogenic efficiency.

Adult↗