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S Berthold

Publications and source records attributed to S Berthold.

15 recordsLinked to original sources
PubMed2001

Refinement of the gene locus for autosomal dominant medullary cystic kidney disease type 1 (MCKD1) and construction of a physical and partial transcriptional map of the region.

Autosomal dominant medullary cystic kidney disease (MCKD) is an adult onset tubulointerstitial nephropathy that leads to salt wasting and end-stage renal failure. A gene locus (MCKD1) has been mapped on chromosome 1q21. Here we report on a large MCKD1 family of British origin linked to the MCKD1 locus. Haplotype analysis performed with markers spanning the previously reported critical MCKD1 region allowed for the refinement of this interval to 4 cM by definition of D1S305 as a new proximal flanking marker. Furthermore, we constructed a yeast artificial chromosome, P1-related artificial chromosome, and bacterial artificial chromosome contig of this region, which is only sparsely covered by the Human Genome Sequencing Project. This enabled us to map numerous expressed sequence tags within the critical interval. This physical and partial transcriptional map of the MCKD1 region is a powerful tool for the identification of positional and functional candidate genes for MCKD1 and will help to identify the disease-causing gene.

Chromosomes, Human, Pair 1↗
PubMed2000

Evidence of further genetic heterogeneity in autosomal dominant medullary cystic kidney disease.

BACKGROUND: Autosomal dominant medullary cystic kidney disease is a genetically heterogeneous nephropathy with clinical and morphological features similar to recessively inherited juvenile nephronophthisis. Recently, a second gene locus on chromosome 16p12, MCKD2 has been mapped [1] in addition to the known locus on chromosome 1q21 (MCKD1) [2]. In a previous study we have excluded linkage for three caucasian families to the MCKD1 locus [3]. METHODS: Haplotype analysis was performed on 72 individuals (including 24 affected subjects), using a set of seven microsatellite markers spanning the critical region on chromosome 16p12-p13 of about 10.5 cM. RESULTS: We report on haplotype analysis of closely linked markers to the MCKD2 locus in the previously studied families and two additional families. CONCLUSION: In all five families the association of MCKD2 with the disease was excluded by a multipoint LOD score <-2, thus suggesting the involvement of a third MCKD locus.

Chromosome Mapping↗
PubMed1998

Autosomal dominant medullary cystic kidney disease: evidence of gene locus heterogeneity.

Autosomal dominant medullary cystic kidney disease (ADMCKD; synonym: medullary cystic disease, MCD) is an autosomal dominant kidney disorder, sharing morphological and clinical features with recessive juvenile nephronophthisis (NPH), such as reduced urinary concentration ability and multiple renal cysts at the corticomedullary junction. While in NPH end-stage renal disease (ESRD) occurs in adolescence, ADMCKD leads to ESRD in adulthood. Recently a gene locus for ADMCKD has been localized to chromosome 1q21 in two large Cypriot families. This prompted us to examine linkage in three ADMCKD-families, using the same set of polymorphic microsatellite markers spanning the critical region on chromosome 1q21. Haplotype analysis revealed that none of the three families showed linkage to this locus, thus demonstrating evidence for genetic locus heterogeneity. Additional linkage analysis studies need to be performed in order to identify further gene loci cosegregating with this autosomal dominant kidney disorder.

Adult↗
PubMed1996

Application of attributed graphs in diagnostic pathology.

OBJECTIVE: To compute attributed graphs based upon calculation of the minimum spanning tree (MST) for various applications in diagnostic lung pathology. STUDY DESIGN: The study design included assistance in histologic diagnosis, confirmation of the diagnosis in single cases, measurement of texture alterations after induction chemotherapy, estimation of prognosis of operated-on lung cancer patients and analysis of lung cancer cells in association with differentiation markers. The histologic slides were Feulgen stained, and features of the integrated optical density (IOD) were associated with the nodes of the MST. The same procedure was applied to immunohistochemically and ligand histochemically stained slides by calculation of the mean staining intensity of the cytoplasm of tumor cells. A measure for structural entropy was introduced by computing the relative differences in distance and IOD between neighboring tumor cells in a 1/r2 field of force. In addition, the current of entropy was computed. RESULTS: Structural entropy reflects alterations in regular textures; the current of entropy is an especially good prognostic parameter in lung cancer. In immunochemistry and ligand histochemistry, construction of the attributed MST permits detailed insight into locally different staining behavior of tumor cells and immunocompetent cells. CONCLUSION: Attributed graphs contain important information that can be used for the estimation of survival or for confirmation of diagnostic entities, such as tumor cell types.

Adolescent↗
PubMed1993

Immortalization with herpesvirus saimiri modulates the cytokine secretion profile of established Th1 and Th2 human T cell clones.

T blasts of six established human CD4+ T cell clones with defined Ag specificity and cytokine secretion profile (3 Th1 and 3 Th2) were immortalized with Herpesvirus saimiri (HVS) and compared with their uninfected counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones neither substantially changed their original surface markers nor lose their ability to proliferate in response to their specific Ag but did acquire the ability to proliferate in response to contact signals delivered by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activity. HVS-transformed Th1 clones but not their uninfected counterparts spontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gamma, and TNF-beta) and such a production was further enhanced by stimulation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but not uninfected Th2 clones constitutively expressed both IL-4 and IL-2 mRNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb induced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 but not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL-2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up-regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clones. The ongoing proliferation of HVS-transformed clones was partially inhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abolished by the combined addition of the two anticytokine antibodies, suggesting that both IL-2 and IL-3 can function as autocrine growth factors for HVS-transformed Th1 and Th2 clones.

Cell Transformation, Viral↗
PubMed1993

Involvement of the high-affinity receptor for IgG (Fc gamma RI; CD64) in enhanced tumor cell cytotoxicity of neutrophils during granulocyte colony-stimulating factor therapy.

Three different classes of Fc receptors for IgG (Fc gamma R) are currently distinguished in humans, of which polymorphonuclear phagocytes (PMN) normally express both low-affinity receptor classes--Fc gamma RII (CD32) and Fc gamma RIII (CD16). During therapy with granulocyte colony-stimulating factor (G-CSF), neutrophils from patients with various malignancies and different hematologic disorders were found to additionally express high levels of the receptor with high affinity for IgG (Fc gamma RI; CD64). For these patients, the relative fluorescence intensity (rFI) for Fc gamma RI was 5.3 (range, 1.7 to 10.3; n = 19), compared with 1.0 (range, 1.0 to 1.1; n = 8) for healthy donors. The expression of Fc gamma RI during G-CSF therapy could be confirmed by using a panel of six CD64-specific antibodies, and by showing mRNA for Fc gamma RI. So far, three genes for Fc gamma RI have been identified, encoding four distinct transcription products. By reverse transcriptase-polymerase chain reaction technology, transcripts for both membrane-associated isoforms (hFc gamma RIa and hFc gamma RIb2) could be detected. The functional activity of Fc gamma RI on PMN during G-CSF therapy was shown by measuring binding of monomeric human IgG and antibody-dependent cellular cytotoxicity (ADCC). Thus, Fc gamma RI-positive neutrophils displayed enhanced ADCC activity to glioma (A1207), squamous cell (A431), and ovarian (SK-ov3) carcinoma cell lines. The involvement of Fc gamma RI in this increased cytotoxic activity was shown by blocking Fc gamma receptors with monoclonal antibodies, and by using F(ab')2 x F(ab')2-bispecific antibodies with specificities against tumor-related antigens and Fc gamma RI, resulting in solely Fc gamma RI-mediated cytotoxicity. Therapeutically, this additional Fc receptor on PMN may increase the efficacy of experimental antibody therapy.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1991

Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines.

Herpesvirus (h.) saimiri, an infectious agent of squirrel monkeys, is capable of persisting in T lymphocytes of various primate species. It has been used as a vector for the functional analysis of regulatory genes in primary human T lymphocytes. As it is not yet known whether other cell types are capable of supporting viral persistence, various human cell lines were investigated using selectable h. saimiri recombinants. The lines chosen represent cells from the epithelium and connective tissue as well as from all haematopoietic lineages, i.e. cells of B and T lymphoid origin as well as myeloid-, fibroblast- and carcinoma-derived cultures converted to Geneticin or hygromycin B resistance, and harbouring episomal DNA of the selectable recombinants. The Burkitt's lymphoma-derived cell line Raji also contained simultaneously persisting episomes of the Epstein-Barr virus. Most of the cell cultures except a pancreatic carcinoma line and foreskin fibroblasts did not produce infectious virus. These observations show that a herpesvirus genome can persist episomally in a broad range of cultured cell types. The variety of infectable cell types and species suggests the presence of a widely distributed and well conserved virus receptor for h. saimiri. Thus the h. saimiri genome could be applied more generally as a vector.

Blotting, Northern↗
PubMed1979

[Acute hemorrhagic pancreatitis--extended abdominal drainage and perirenal drainage links].

Acute haemorrhagic pancreatitis, when mainly situated in the body and tail of the pancreas, may be associated with abscess formation in the left perirenal region through the radix mesosoli transversi. Next to the extensive drainage of the abdomen and pancreas, we advise supplementary primary left perirenal-retroperitoneal drainage, considering how difficult it can be to loalize a secondary postoperative pancreatic abscess, especially when a computer-assisted tomography (CAT) is unavailable. In those cases in which the transverse colon had suffered circulatory damage from the acute pancreatitis, good results have been obtained with temporary coecostomy.

Adult↗
PubMed1976

[Changes in serum lipids and lipoproteins in acute hepatitis].

In 50 patients with acute hepatitis serum lipide and lipoproteins were determined at regular intervals and the results were compared with the usual liver function tests. Australia-antigen was established in 26 patients. During the first three weeks of the disease the most striking finding was a significant increase in the triglycerides, which was most pronounced at the end of the second week. Triglyceride levels usually returned to normal during the fourth week. In the course of the disease, lipoprotein electrophoresis showed marked decrease or absence of alpha- and pre-beta-lipoproteins during the first two weeks. During the third week faint alpha and pre-beta bands recurred in most patients. By the end of the fourth week lipoprotein electrophoretic findings were back to normal. There was general correlation between routine tests of liver function and results of lipid analyses throughout the course of the disease. This typical pattern of serum lipid and lipoprotein changes was found with near-consistency in patients with HAA-positive hepatitis. It was also present in the majority of HAA-negative patients, though in these the characteristic discrepancy between hypertriglyceridemia and simultaneous decrease of the pre-beta-lipoprotein band in eletrophoresis was, on the average, absent.

Acute Disease↗
PubMed1975

[Lipoprotein X in hepatobiliary diseases].

The diagnostic and prognostic reliability of lipoprotein-X (Lp-X) in demonstrating or ruling out cholestasis has been evaluated in a group of 80 patients with diseases of the liver and/or the biliary tracts, and in 103 subjects with various other diseases. The results of Lp-X detection were compared with the so-called "enzymes indicating cholestasis": alkaline phosphatase, leucine arylamidase, and gamma-glutamyltranspeptidase. Where possible a histologic specimen of the liver was obtained. The correlation between Lp-X and "enzymes indicating cholestasis" was satisfactory in more than 90% of cases. When compared with the histologic findings, Lp-X proved to be more reliable than the enzymes. Despite this fact, Lp-X did not show absolute specifity in the detection of cholestasis as there were several negative results in cases with histologically proven cholestasis. Furthermore, the differentiation of intra- and extrahepatic cholestasis was not possible on the basis of Lp-X. In the control group of 103 patients with other than hepatobiliary diseases, a positive Lp-X result was found in 3 cases. Further investigations in these three patients revealed that primarily unsuspected hepatobiliary disease could not be ruled out. In the follow-up of a hepatobiliary disease the transition of Lp-X to negative indicates a trend towards improvement of cholestasis 1-2 weeks earlier than the enzymes mentioned above.

Alkaline Phosphatase↗