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Biomedical subjects

M Bergmann

Publications and source records attributed to M Bergmann.

At least 91 records · Page 5Linked to original sources

Solitary Langerhans cell histiocytosis lesion of the parieto-occipital lobe: a case report and review of the literature.

A 38 year-old woman with a solitary intracerebral Langerhans cell histocytosis (LCH) lesion is presented, in whom, cerebral magnetic resonance imaging (MRI) revealed a non-enhancing mass in the right parieto-occipital lobe. The surgical specimen consisted of a nodular polymorphic infiltrate of mononuclear histiocytic cells, macrophages, eosinophilic granulocytes, lymphocytes and Langerhans giant cells involving leptomeninges, cerebral cortex and white matter. The histiocytes displayed features of Langerhans cells such as CD1a and S-100 immunopositivity, and of reticulum cells such as Ki-M4P and X-12 immunopositivity. This case as well as ten other cases from the literature are reviewed.

Adult↗

Binding and distribution of Na2B12H11SH on cellular and subcellular level in tumor tissue of glioma patients in boron neutron capture therapy.

To determine binding and distribution of Na2B12H11SH (BSH) in glioma tissue in case of boron neutron capture therapy, an antibody to this compound was produced and used in immunohistochemical investigations. It is possible to trace BSH in immunohistochemistry, because BSH is firmly bound to the glioma tissue. The antibody against BSH is specific for that antigen, as tumor tissue from patients without BSH administration did not stain. In areas of healthy brain from BSH infused patients, no staining of tissue was detectable. In tumor tissues, BSH is presenting as a strong staining in cytoplasm and nucleus areas.

Antibodies↗

Apoptosis as a mechanism of germ cell loss in elderly men.

In comparison with other mammals, human spermatogenesis is known to be an inefficient process, of which germ cell degeneration is a normal part. This study was performed to determine the mechanism of cell death in the testes of elderly men. Testes from 20 patients undergoing orchidectomy for prostate cancer were fixed, sectioned and processed for the detection of apoptosis using the in situ end-labelling technique. In addition, the formation of DNA ladders, a hallmark of apoptosis, was also investigated. Occurrence of apoptosis was not confined to a particular germ cell population but comprised all types of germ cells. Sertoli cell apoptosis was not encountered. The numbers of degenerating germ cells were determined per standard reference area, but no significant relationship was found between the mean values and age or testis weight. Analysis of the median values for germ cell death per reference area suggested that apoptosis occurs in clusters within the testis but is a rare occurrence outside these areas. It is concluded that spontaneous apoptosis can mediate germ cell death in a variety of cell types in the aged human testis.

Aged↗

Does the gonadotrophic axis play a role in the pathogenesis of Sertoli-cell-only syndrome?

Infertile men with Sertoli-cell-only syndrome (SCO) have highly elevated serum FSH immunoactivity related to the degree of histological damage. The activity that serum FSH exerts at the target site depends on its glycosylation pattern and FSH receptor (FSHR) function. Either could be impaired, leading to failure of spermatogenesis. The aim of the present investigation was to study bioactivity and the glycosylation pattern of serum FSH and the occurrence of mutations in the FSH receptor in infertile patients with SCO compared to normal men. Blood was taken from 19 patients with bilateral testicular focal or complete SCO and eight normozoospermic controls. FSH bioactivity in serum was measured using an in-vitro FSH bioassay based on recombinant rat FSHR. The glycosylation pattern of serum FSH was determined by concanavalin A chromatography. Inhibin B was determined in serum using a recently available assay. Genomic DNA extracted from blood lymphocytes was amplified by PCR using primers specific for the FSHR and screened by single-stranded conformation polymorphism gel electrophoresis. Men with SCO showed significantly higher FSH in-vitro bioactivity (34.9 +/- 5.0 IU/l) than controls (9.6 +/- 0.8 IU/l: p < 0.01), as well as significantly elevated FSH immunoactivity (14.9 +/- 1.7 IU/l) compared to controls (3.1 +/- 0.5; p < 0.01). Immunoactivity of serum FSH was correlated with in-vitro bioactivity (r = 0.9; p < 0.001) and was related to the degree of testicular damage (proportion of SCO-tubules) (ANOVA: p < 0.001) and total testicular volume (r = -0.76; p < 0.01). An inverse relationship between serum FSH and inhibin B levels (r = -0.93; p < 0.001) was found. In the serum of SCO patients a slight increase in less glycosylated FSH isoforms was found (6.7 +/- 0.6% versus 3.6 +/- 0.3%; p < 0.05). No mutations of the FSHR were observed in SCO patients. We conclude that the spermatogenic failure observed in infertile patients with SCO histology and elevated FSH serum levels can be explained neither by a change in FSH bioactivity nor by mutations in the FSHR. The slight change in the FSH glycosylation pattern is probably related to higher hormonal secretion rates in SCO patients. The inverse relationship between serum FSH and inhibin B points to an intact endocrine testicular-pituitary circuit responsible for the compensatory increase of FSH in SCO.

Adult↗

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies.

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.

Adult↗

CADASIL: skin biopsy allows diagnosis in early stages.

OBJECTIVES: Our aim was to investigate the diagnostic impact of skin biopsies in CADASIL patients. MATERIALS AND METHODS: Eight consenting CADASIL patients belonging to a German-Caucasian kindred were assessed clinically, genetically, by MRI and skin biopsy. Skin biopsy results were compared to 5 patients suffering from sporadic leucoencephalopathies (control group). RESULTS: Six CADASIL patients presented with symptoms ranging from migraine to severe tetraparesis with dementia. Two clinically unaffected patients had abnormal MRIs. On MRI 7 patients showed various degrees of leucoencephalopathy. One 22-year-old woman with migraine had a normal MRI. Granular, electron dense, osmiophilic material (GEM) was found in skin biopsies of all 8 patients including the 22-year-old woman with migraine and a normal MRI. As shown by genetic linkage analysis she was carrying the disease haplotype. GEM was not found in the control group. CONCLUSION: Our findings substantiate the impact of skin biopsies in defining the carrier status in CADASIL families.

Adult↗

Analysis of immunoglobulins in sarcoidosis.

BACKGROUND: Assessment of local immunoglobulin(Ig)-production in sarcoidosis may be indicative of disease activity. However, in interstitial lung disease an increase in protein leakage across the alveolar-capillary membrane complicates determination of local Ig-production. In order to overcome this problem, techniques successfully used for the evaluation of local Ig-production in cerebrospinal fluid were applied to bronchoalveolar lavage (BAL)-analysis. METHODS: Ten patients with biopsy-proven sarcoidosis, seven patients with respiratory infections and ten patients as controls without any sign of interstitial lung disease or infection underwent BAL. Equal amounts of total protein (2 micrograms/lane) from BAL and serum samples were run on SDS-PAGE gradient-gel and blotted to a nitro-cellulose membrane. The blots were stained for total protein, IgA, IgM, IgG and IgG1-4-subgroups. RESULTS: Densitometric analysis revealed a significant increase of the IgG/albumin-ratio in BAL of sarcoidosis patients compared to the control group. In all control patients a single IgG band of identical molecular weight was detected both in serum and BAL. In sarcoidosis and pneumonia the serum showed multiple bands distinct from the BAL-band in regard to molecular weight. Subclass analysis of this group revealed an increased band intensity and different molecular weight of IgG1, IgG2 and IgG4-bands in BAL compared to serum indicative of local production. IgA and IgM were detected in all samples without any significant differences between the three groups. CONCLUSIONS: Molecular weight analysis of IgG-subgroups revealed local production of IgG1,2+4 in sarcoidosis and respiratory infection. This technique may prove useful with regard to the assessment of disease activity in sarcoidosis.

Adult↗

[Analysis of lymphocyte populations with flow cytometry in routine bronchoalveolar lavage diagnosis: comparison of a 3-color method with the alkaline phosphatase anti-alkaline phosphatase immunohistochemistry].

BACKGROUND: Identification of lymphocyte phenotypes in bronchoalveolar lavage (BAL) plays a crucial role in the diagnosis of interstitial lung disease. Cells staining positive for specific monoclonal antibodies may be detected by immunocytochemistry or flow cytometry (FCM). The present study compares a three-colour FCM-approach to a standard APAAP protocol for immunocytochemistry. METHODS: BAL-specimens of 22 patients with various lung diseases were investigated. Inclusion criteria was a lymphocytosis of > 10% of all BAL-cells. After the preparation of cytocentrifuge slides, staining was performed with monoclonal antibodies to CD3, CD4 and CD8 following the APAAP-protocol. FCM-analysis was performed with the following panel of conjugates: CD3-FITC, CD4- or CD8-PE, CD45-perCP. Lymphocytes were gated by their SSC/CD45 characteristics. T-helper and T-suppressor percentages were evaluated by quadrant analysis of CD3/CD4 or CD3/CD8 histograms. RESULTS: With the exception of CD3, where the range of values was quite narrow (10% variance), the correlation between the two methods was excellent (CD4: r = 0.98; CD8: r = 0.99; CD4/CD8: r = 0.96; p < 0.0001). CONCLUSION: Flow cytometry reveals similar results compared to immunocytochemistry in the determination of lymphocyte subsets characterised by CD3, CD4 and CD8 antigens.

Adult↗

Expression and subcellular distribution of glutamate receptor subunits 2/3 in the developing cerebellar cortex.

The expression and subcellular location of glutamate receptor subunits 2&3 was investigated in the developing postnatal cerebellum. Immunoblotting revealed that glutamate receptor subunits 2/3 is expressed in an identical pattern of immunoreactive bands of approximately 108 kDa from postnatal day zero to adult animals. Light microscopy showed that within the cerebellar cortex, GluR 2/3 immunoreactivity was essentially confined to Purkinje neurons. Strong immunostaining could be observed at postnatal days 1-3 within Purkinje cell bodies and primary dendrites. With ongoing development, the cell body and an increasingly elaborate dendritic tree was outlined by immunoreaction product. In adult animals, staining of Purkinje cell dendrites was patchy, and staining intensity of the cell body, in particular, was greatly reduced. Ultrastructural analysis revealed that during early postnatal development, immunoreaction product was localized to the cell membrane, but was not confined to postsynaptic densities. From the second postnatal week, glutamate receptor subunits 2/3 immunoreactivity was largely restricted to postsynaptic densities. These observations reveal a developmentally regulated refinement of the subcellular distribution of defining subunits of the AMPA-type glutamate receptor. The presence of membrane bond receptors prior to the formation of synapses also provides a rationale for the known transmitter-mediated modulation of Purkinje cell dendritogenesis.

Age Factors↗

[Giant axonal neuropathy. A case report].

We report a sporadic case of giant axonal neuropathy (GAN) starting in a 5-year-old boy with gait disturbance. At the age of 10 years he showed signs of a sensomotoric polyneuropathy and central neurological symptoms: intention tremor, nystagmus and visual disturbance. The boy also had curly hair. Sural nerve biopsy showed many giant axons with accumulation of microfilaments, which were also found in cytoplasma of Schwann cells, endothelial cells and fibrocytes. Similar changes were detected in endothelial cells of a muscle biopsy, which additionally displayed neurogenic atrophy and target fibers. Immunohistochemically, desmin, vimentin, heat shock protein 70, and ubiquitin were not detectable in giant axons, which, however, contained neurofilament protein 68, 200 and beta-tubulin. Our case shows that careful ultrastructural examination of a muscle biopsy may point to the diagnosis of GAN.

Axons↗

Different variants of frontotemporal dementia: a neuropathological and immunohistochemical study.

Histological and immunohistochemical findings in 20 cases of frontotemporal dementias-8 cases of dementia of frontal lobe type (DFT), 7 cases of Pick's disease (PD), and 5 cases of motor neuron disease with dementia (MND/D)-are presented. Common features of all three syndromes were: frontotemporal atrophy, involvement of subcortical nuclei, and swollen chromatolytic cells. Ubiquitin (Ub)-positive and tau-negative inclusions in cortical, hippocampal, and motor neurons were found in MND/D and DFT cases, suggesting a common pathogenesis of MND/D and DFT. MND/D showed the same cytoskeletal alterations in motor nuclei as MND without dementia: Bunina bodies and skein-like, Ub-positive inclusions. DFT differed from PD in the preponderance of histopathological changes in upper cortical layers, the sparseness of chromatolytic cells, and the absence of tau-positive Pick bodies (PBs). There were, however, two transitional cases showing Pick-type histology but no PBs, thus linking DFT and PD. PBs expressed chromogranin B and secretoneurin strongly, but chromogranin A only weakly. They were negative for the 70-kDa heat-shock protein, metallothionein, and glutathione-S-transferase.

Adult↗

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): a morphological study of a German family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by recurrent cerebral infarcts, subcortical dementia and pseudobulbar palsy, and morphologically by a granular degeneration of cerebral and, to a lesser degree, extracerebral blood vessels. We present morphological findings in a further German family affected by CADASIL. The index case showed the typical periodic acid-Schiff-positive granular degeneration of vascular smooth muscle cells (VSMC) in cerebral vessels, which did not react with antibodies against various immunoglobulins or complement factors. Ultrastructurally, granular osmiophilic material (GOM) covered the VSMC in different cerebral regions as well as in extracerebral organs (muscle, nerve, skin, small and large intestine, liver, kidney and heart). Skin biopsy samples from other family members of the last two generations also revealed GOM irrespective of the clinical symptomatology (CADASIL, migraine only or asymptomatic). Patients in the third generation had higher amounts of GOM in skin vessels than did asymptomatic or migraine patients in the fourth generation. We conclude that skin biopsy is a useful and less invasive screening method for the differential diagnosis of CADASIL.

Adult↗

Mutations in the nonconserved noncoding sequences of the influenza A virus segments affect viral vRNA formation.

Influenza A virus replication and packaging is mediated by cis-acting signals, which are located at the 3' and the 5' end of the viral segments. The terminal residues can be divided into conserved and nonconserved residues. We have constructed a mutant influenza A/WSN/33 virus, which contains multiple mutations in the nonconserved residues of the neuraminidase (NA) segment. This virus shows a segment-specific reduction of the genomic RNA content in the infected cell and in the progeny virus. Further mutants and revertant viruses revealed that it was not possible to define specific residues, which were responsible for the reduction of the NA-specific RNA. Thus, it appears that an efficient vRNA formation is dependent on the synergistic effect of the terminal sequences.

Animals↗

Macrophages in multiple sclerosis.

Macrophages are important effector cells involved in the pathogenesis of demyelination in multiple sclerosis (MS). Macrophage differentiation was studied in a series of 158 MS plaques from 43 patients obtained at different stages of the disease. Macrophages were identified by immunocytochemistry using a panel of antibodies recognizing different formalin- and paraffin-resistant macrophage activation antigens. The number of cells stained with each antibody was related to the demyelinating activity of the lesions as detected by the presence of myelin degradation products as well as to the category of MS tissue. Highest numbers of macrophages were observed in actively demyelinating and early remyelinating lesions using immunocytochemistry for the panmacrophage marker Ki-M1P. Lower numbers were encountered in inactive, demyelinated or late remyelinated lesions. The acute stage inflammatory macrophage markers MRP14 and 27E10 were selectively expressed in early and late active lesions, thus allowing the identification of actively demyelinating lesions. The chronic stage inflammatory macrophage marker 25F9, in contrast, showed a continuous expression also in inactive lesions. The different types of MS tissue revealed significant differences in their macrophage response. The most intense macrophage infiltration was seen in acute MS cases whereas lesions of early and late chronic MS showed lower macrophage levels. These findings indicate a differentiated pattern of macrophage activation in MS depending on the stage of the demyelinating activity as well as on the category of MS tissue. Furthermore, these macrophage markers give new parameters for staging the inflammatory and demyelinating activity of MS lesions.

Acute Disease↗

Ubiquitin-positive inclusions in different types of multiple system atrophy: distribution and specificity.

Multiple system atrophy (MSA) is a neurodegenerative disorder that encompasses different clinicopathological syndromes, either occurring alone or with a variable degree of overlap. Oligodendroglial, intracytoplasmic argyrophilic and ubiquitin-reactive inclusions are regarded as a histologic hallmark. We examined the distribution and specificity of these ubiquitin-reactive inclusions (UBRI) in 20 cases of MSA (7 cases of sporadic adult olivoponto-cerebellar atrophy [OPCA], 1 case of hereditary adult OPCA, 4 cases of infantile OPCA, 2 cases of Shy-Drager-Syndrome [SDS], 4 cases of striatonigral degeneration [SND] and 2 cases of non-classified atrophy of multiple systems) and 93 control cases with various disorders. Antibodies were used against ubiquitin, PGP 9.5, TAU-protein, glutathion-S-transferase (GST) and metallothionein (MT). Oligodendroglial UBRI were detected in all but 2 cases of sporadic adult MSA and 3 controls, whereas they were absent in hereditary and infantile OPCA. They could also be recognized with Gallyas stain and anti-TAU. Immunopositivity was also seen with GST (11 cases), PGP 9.5 (4 cases) and MT (1 case). Distribution of oligodendroglial UBRI, although not showing topographical linkage to neuronal degeneration in all cases, does not seem to occur in a haphazard pattern.

Adolescent↗

Ki-67 and biological behaviour in meningeal haemangiopericytomas.

The biological behaviour of meningeal haemangiopericytomas was retrospectively studied using immunohistochemical staining with MIB1, a monoclonal antibody against the Ki-67 antigen, a nuclear protein related to cell proliferation. Paraffin-embedded material from 62 tumours from 40 patients were investigated. The proliferating compartment of the tumours was estimated by evaluating the MIB1 staining index, i.e. the percentage of MIB1 positive nuclei in at least 1000 counted tumour cells in representative areas. The staining index ranged from 1.24% to 39.01%. Statistical analysis revealed no significant correlation between the staining index and recurrence-free survival (chi 2 = 0.3922, P = 0.5311). Long-term observation (> 100 months), however, revealed a tendency to longer survival in the group with a staining index less than 5%. According to our results, the MIB1 staining index does not contribute to the accuracy of predicting the clinical outcome of meningeal haemangiopericytomas.

Adolescent↗