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Biomedical subjects

S Albrecht

Publications and source records attributed to S Albrecht.

At least 109 records · Page 6Linked to original sources
PubMed1995

Dynamics of the intracerebral and splenic cytokine mRNA production in Toxoplasma gondii-resistant and -susceptible congenic strains of mice.

Oral infection with a low-virulence strain of Toxoplasma gondii (Tg) induced a persisting encephalitis in resistant strains of mice. In the present study we have examined transcripts of various cytokines during acute and chronic stages of murine Tg encephalitis. In the brain of infected animals, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10 and IL-12 mRNA were induced to a significant extent, but only low levels of IL-4 mRNA were detectable. A similar cytokine profile was observed in the spleen. However, in contrast to the brain, the increase of IL-2 mRNA was particularly pronounced in the spleen, whereas the opposite was found for IFN-gamma and TNF-alpha mRNA. Thus, cytokines involved in T-cell proliferation were more prevalent in the spleen, but in the brain, where Tg actively multiplies, the effector molecules IFN-gamma and TNF-alpha were preferentially up-regulated. In addition, a detailed analysis of cytokine mRNA levels in major histocompatibility complex (MHC)-congenic strains of BALB and B10 mice revealed that the genetically regulated susceptibility to Tg was correlated with the amount of intracerebrally produced cytokine mRNA for IFN-gamma, TNF-alpha and IL-6. Mice with a strong increase of these cytokine mRNA were significantly better protected against Tg. This indicates that the outcome of toxoplasmosis may be critically dependent on an adequately regulated intracerebral immune response.

Animals↗
PubMed1994

Transforming growth factor-beta and interleukin-10, but not interleukin-4, down-regulate procoagulant activity and tissue factor expression in human monocyte-derived macrophages.

The effect of IL-4, IL-10, and TGF-beta on expression of procoagulant activity (PCA) and of surface-associated tissue factor (TF) by human monocyte-derived macrophages was determined. Monocytes were allowed to mature to macrophages in teflon bags, and were primed either in suspension cultures, or after subculturing in microtiter plates. PCA was determined in PBS-stimulated cells (constitutive PCA) or after stimulation with LPS for 6 hr. TGF-beta significantly reduced constitutive and LPS-induced PCA. This effect was associated with a reduction in surface-expressed TF, but was not correlated with TNF-alpha production in LPS-stimulated cells. The TGF-beta effect was seen both in suspension cultures and in adherent cultures. IL-10 strongly down-regulated LPS-induced PCA, an effect closely correlated with TNF production. It had a weaker, albeit significant effect on constitutive PCA, when tested on suspended cells, and PCA down-regulation was associated with reduction in TF surface expression. IL-4 reduced neither constitutive nor induced PCA in macrophages, and had little effect on TF surface expression, although it strongly down-regulated CD14 expression. Also in monocytes, IL-4 influenced TF expression to a lesser degree than IL-10 and TGF-beta. In the monocytoid cell line, THP-1, PCA/TF was down-regulated preferentially by TGF-beta. Our findings point to a complex cytokine-mediated regulation of PCA at the level of TF expression and possibly at additional levels.

Blood Coagulation Factors↗
PubMed1994

Loss of maternal alleles on chromosome arm 11p in hepatoblastoma.

Hepatoblastoma is the most common primary malignant liver tumor in children, yet little is known about molecular genetic changes in these tumors. Previous studies report loss of heterozygosity on chromosome arm 11p in some hepatoblastomas. We used the polymerase chain reaction to amplify multiple microsatellites on chromosome arm 11p to assess loss of heterozygosity in 18 hepatoblastomas. Loss of heterozygosity on 11p was found in six of them. The common region of overlap was restricted to the telomeric portion of 11p (11p15.5) and therefore excluded the WT-1 tumor suppressor gene at 11p13. Parental origin of the lost allele could be determined in all six cases and was exclusively maternal. These results indicate that a tumor suppressor gene at 11p15.5 is involved in the pathogenesis of hepatoblastoma and also suggest that this chromosomal region is imprinted.

Child, Preschool↗
PubMed1994

Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system.

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs.

Animals↗
PubMed1994

Loci associated with malignant progression in astrocytomas: a candidate on chromosome 19q.

WHO grades II and III astrocytomas frequently exhibit loss of genetic material on chromosomes 9p, 11p, 17p, 19q, and 22q, indicating that these chromosomal regions harbor tumor suppressor genes involved in the pathogenesis of astrocytic neoplasms. The present study was conducted to examine whether these genetic regions are involved in the process of malignant progression from astrocytoma WHO grade II (A II) to anaplastic astrocytoma WHO grade III (A III). We have analyzed 44 astrocytomas, i.e., 18 A II and 26 A III for loss of heterozygosity (LOH) on chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q, and 22q and for amplification of the epidermal growth factor receptor gene. A polymerase chain reaction-based assay with microsatellite repeat sequences was used for the detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was seen in 1 of 18 (6%) informative cases of A II and 4 of 24 (17%) informative cases of A III. LOH on 17p was observed in 9 of 17 (53%) informative cases of A II and 15 of 26 (58%) informative cases of A III. LOH on 19q was detected in 2 of 18 (11%) informative cases of A II and in 12 of 26 (46%) informative cases of A III. The association of LOH on 19q with anaplasia in astrocytoma was significant (P = 0.015). Amplification of the epidermal growth factor receptor gene was not detected in A II or A III. These data suggest that a putative tumor suppressor gene on the long arm of chromosome 19 is a candidate for a gene associated with tumor progression in astrocytic gliomas.

Adult↗
PubMed1994

Immunohistochemical detection of tissue factor (TF) on paraffin sections of routinely fixed human tissue.

Tissue factor (TF), a 47 kDa transmembrane glycoprotein, is the essential receptor and cofactor for factor VII/VIIa. Its distribution in normal tissues and in tumours has been recently investigated immunohistochemically with monoclonal and polyclonal anti-TF antibodies in frozen sections. The cardinal problem of this technique is the difficulty of determining exactly the localization of the reaction product at least in certain tissues. Here, we demonstrate a method using monoclonal anti-TF antibodies to detect TF in routinely fixed, microwaved, paraffin-embedded tissues. Generally, there were no fundamental differences in TF distribution in frozen and paraffin-embedded material. However, in most cases, the paraffin sections allow a better cellular localization of TF. For example, the staining pattern for TF in both kinds of sections is identical in kidney, brain and skin. The paraffin-embedded material, however, clearly shows that TF expression is restricted to the parietal and the visceral epithelia of Bowman's capsule of glomeruli in the kidney, and to astrocytes and their processes in the brain. TF reactivity in the skin is revealed to be cell membrane-bound; in cardiomyocytes TF shows an exclusively sarcolemmal localization. The immunohistological detection of TF in paraffin sections is a powerful tool for systematic studies on the possible role of TF in the context of physiological and pathological studies.

Antibodies, Monoclonal↗
PubMed1994

Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11p and 17p in medulloblastomas.

Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Malignant meningioma in Gorlin's syndrome: cytogenetic and p53 gene analysis. Case report.

Gorlin's syndrome, also known as multiple basal cell carcinoma syndrome, is a familial tumor condition with autosomal-dominant inheritance. Patients develop multiple basal cell carcinomas beginning in childhood. They also have a typical dysmorphic facies, skeletal malformations, and a particular type of epithelial cyst of the jaws. Recent evidence localizes a Gorlin's syndrome locus on chromosome 9 at band q31. Both tumors and malformations of the central nervous system occur with Gorlin's syndrome. Medulloblastoma is the primary brain tumor most frequently associated with this syndrome; over 40 such cases have been reported. However, only seven cases of meningioma associated with Gorlin's syndrome have been described. The authors report the case of a woman with Gorlin's syndrome whose mother and maternal grandfather also had the condition. The patient was found to have a medulloblastoma at 4 years of age and presented with a large bifrontal meningioma at 19 years of age. The meningioma was histologically malignant and had a complex karyotype with multiple translocations including a t(5;9) with the breakpoint on chromosome 9 located at 9q32. The constitutional karyotype of the mother was normal. No mutations of exons 5 to 9 of the p53 gene were detected using single-stranded conformational polymorphism analysis.

Adult↗
PubMed1994

[Progression-associated gene regions in astrocytomas: a candidate locus on chromosome 19q].

A study was carried out to examine whether genetic loci which have been shown to exhibit loss of heterozygosity in gliomas are involved in the process of malignant progression from low grade astrocytomas to anaplastic variants. We have analyzed 18 well differentiated astrocytomas WHO grade II (A II) and 26 anaplastic astrocytomas WHO grade III (A III) for loss of heterozygosity (LOH) on chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q and 22q and for amplification of the EGFR receptor. A PCR-based assay with microsatellite repeat sequences was employed for the detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was seen in 1/18 (6%) informative cases of A II and 4/25 (16%) informative cases of A III. LOH on 17p was observed in 10/17 (53%) informative cases of A II and 15/28 (54%) informative cases of A III. LOH on 19q was detected in 2/18 (11%) informative cases of A II and in 12/26 (46%) informative cases of A III. Thus, the majority of chromosomal regions examined in this study do not appear to play a role in malignant progression of astrocytomas. LOH 17p is a frequent event in astrocytoma but has not been detected at a higher incidence in anaplastic variants. However, a putative tumor suppressor gene on chromosome 19q emerges as an interesting novel candidate for a progression-associated gene in human astrocytic gliomas.

Astrocytoma↗
PubMed1994

Intracoccygeal and pericoccygeal glomus bodies and their relationship to coccygodynia.

BACKGROUND: Coccygodynia is an uncommon condition of diverse causes. A few cases were attributed to so-called pericoccygeal glomus tumors. However, the pericoccygeal soft tissues normally contain numerous small glomus bodies and a larger one known as the glomus coccygeum, which can reach several millimeters in diameter. Most reported cases of alleged pericoccygeal glomus tumors represent normal, incidentally discovered coccygeal glomus bodies. Recently, an intracoccygeal glomus tumor was reported as a cause of coccygodynia. However, we suspected that glomera can also occur normally within the coccyx itself. METHODS: Twenty coccyges from fetuses, newborns, infants, and adults were obtained at autopsy, embedded in toto, and examined histologically in step sections. RESULTS: Intracoccygeal glomera were present in six of the nine pediatric specimens and all 11 adult specimens. All were microscopic structures, and none appeared to have caused bony destruction or erosion. They did not differ from the structures previously reported as alleged intracoccygeal "glomus tumors." CONCLUSIONS: Pericoccygeal and intracoccygeal glomus bodies are normal findings in humans at all ages. They should not be mistaken for tumors, and their role in the pathogenesis of coccygodynia is questionable.

Adult↗
PubMed1993

Immunoglobulin heavy chain rearrangements in primary brain lymphomas. A study using PCR to amplify CDR-III.

Primary brain lymphomas (PBLs) have only rarely been analysed for immunoglobulin heavy chain (IgH) rearrangements. In this study, DNA was extracted from paraffin blocks in 23 cases of PBL and examined for IgH rearrangements using the polymerase chain reaction (PCR) to amplify the complementarity-determining region III (CDR-III) of rearranged IgH genes. Fifteen of the cases were phenotyped on paraffin-embedded tissue using a pan-B and pan-T antibody (L26 and UCHL-1, respectively). The remaining eight cases were not phenotyped for lack of tissue. For comparison, we used DNA extracted from paraffin blocks of normal brain, lymph nodes with lymphoid hyperplasia, and non-lymphoid malignancies. PCR products were examined by polyacrylamide gel electrophoresis. Among the ten B-cell PBL; four had a pattern indicative of IgH rearrangement, one had a germline pattern, and five had no detectable PCR products. Among the five T-cell PBLs, one had a germline pattern and four had no detectable products. Among the eight untyped PBLs, two had IgH rearrangement, four had a germline pattern, and two gave no detectable products. DNA from non-lymphoid tissues gave a consistent germline pattern, while DNA from polyclonal lymphoid populations (lymph node) had a pattern of polyclonal IgH rearrangement. In a dilution study, a clonal rearrangement could be detected as long as the clone's DNA constituted at least 10 per cent of the total DNA. PCR to amplify CDR-III can be successfully applied to DNA extracted from paraffin blocks, and it detected a clonal rearrangement in 50 per cent of cases that gave a detectable pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Distribution of p53 protein expression in gliosarcomas: an immunohistochemical study.

The wild-type p53 gene product is a nuclear phosphoprotein that suppresses cell and tumor growth. Mutations of the p53 gene are by now the most frequently recognized genetic alterations in human malignancies and occur in many types of carcinomas as well as in astrocytomas and sarcomas. Wild-type p53 protein has a short half-life, is present in very low quantities in normal cells and cannot be detected immunohistochemically. Mutant p53 proteins have longer half-lives and are usually present in immunohistologically detectable amounts. It is generally agreed that the presence of p53 immunostaining indicates the presence of an abnormal p53 protein and is strongly suggestive of a mutation in the p53 gene. In this study, we stained paraffin sections from eight samples of gliosarcomas from seven patients with an antibody to p53. All tumors contained p53-immunoreactive nuclei in both the glial and the sarcomatous component. In five tumors, a majority of nuclei was positive in the sarcomatous component while only a minority of nuclei was positive in the glial areas. In one tumor, the reverse was seen. In another tumor, approximately half the nuclei were positive in both components and in one tumor, only a minority of nuclei were positive in either component (this lesion was the recurrence of a tumor in which the majority of the sarcoma's nuclei had been positive). These data indicate that p53 mutations may play a role in the pathogenesis of gliosarcomas and suggest an origin of both the glial and sarcomatous components from a common progenitor.

Adult↗
PubMed1993

Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings.

We report three siblings born with severe neonatal encephalopathy, manifested clinically by microcephaly, myoclonus, and muscular hypertonus. Karyotypic analyses and all biochemical investigations were unrevealing. All three patients died during infancy. Postmortem examination of the brain in one child disclosed severe neuronal loss in the inferior olives and the pontine nuclei. There was also severe hypoplasia of the cerebellum and micrencephaly. There was diffuse gliosis of the white matter in all areas of the brain. We believe this may represent a previously undescribed form of familial infantile encephalopathy with olivopontocerebellar hypoplasia.

Brain↗
PubMed1993

Reactivity of locally produced CSF antibodies in patients with neurosyphilis against antigens of Treponema pallidum.

The reactivity and specificity of locally produced cerebrospinal fluid (CSF) antibodies against antigens of Treponema pallidum were assessed by Western blotting in patients with clinical signs of parenchymal or meningovascular neurosyphilis. All nine patients showed local production of treponeme-specific antibodies in the central nervous system (CNS). In most of the patients serum and CSF antibodies were bound to the same antigens: the common treponemal 48/45 kDa protein and the putative specific T. pallidum protein in the range of 12-14 kDa. In some patients the intensity of staining obtained by CSF antibodies was higher than that derived from serum, indicating locally produced antibodies. In contrast to other more acute inflammatory CNS diseases, no expanded or different antigen binding of the CSF antibodies compared with serum antibodies was found in neurosyphilic patients. The results presented are discussed with regard to the role of the blood-brain barrier in antibody concentrations of CSF and serum.

Adult↗
PubMed1993

Cellular localization of tissue factor in human breast cancer cell lines.

Expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumours. The TF gene has been classified as an immediate early gene responsive to serum and cytokines. Thus, the regulation of TF gene expression seems to play a role in cell growth. Recently, we have shown that constitutive TF expression in MCF-7 breast cancer cells is modulated by such growth factors as EGF, TGF alpha, and IL-1. The present study deals with the immunocytochemically detectable cellular distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by EGF and TGF alpha. In MCF-7 cells growing logarithmically, stimulation led to a significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot) and to maximum TF expression after 6 h (immunohistochemistry). When decorated by monoclonal antibodies, TF protein showed a pronounced localization at ruffled membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In more flattened cells TF was concentrated in peripheric lamellae and microspikes communicating with neighbouring cells. After epithelial colony pattern had established, TF was predominantly accumulated at the intercellular boundaries. The vary same distribution patterns as seen in MCF-7 cells were true for the stimulated MaTu cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Primary pulmonary lymphoma. Diagnosis by immunoglobulin gene rearrangement study using a novel polymerase chain reaction technique.

A 63-yr-old-woman presented with pulmonary infiltrates and macroglobinemia. Open lung biopsy revealed an interstitial plasma cell infiltrate. Immunocytochemical staining to determine clonality of the infiltrate was negative for both kappa and lambda light chains and therefore was not helpful. Polymerase chain reaction (PCR) amplification of the CDR-III region of the immunoglobulin heavy chain gene revealed that the plasma cells were either monoclonal or biclonal, thus suggesting the diagnosis of a plasmacytoid pulmonary lymphoma. The advantages and limitations of the PCR technique over the traditional method of detecting gene rearrangements, i.e., restriction-digestion of DNA and Southern blotting, are discussed. To our knowledge this patient represents the first reported application of the PCR technique for detecting gene rearrangements to determine the clonality of a lymphoid infiltrate in the lung. This technique can also be applied to determine the clonality of lymphocytes obtained by bronchoalveolar lavage or needle biopsy, or from a pleural effusion.

Biopsy↗