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Biomedical subjects

M Schmid

Publications and source records attributed to M Schmid.

At least 379 records · Page 21Linked to original sources

Human interleukin-7 induces proliferation of neoplastic cells from chronic lymphocytic leukemia and acute leukemias.

The biologic effects of interleukin-7 (IL-7) and the expression of specific IL-7 membrane receptors on isolated neoplastic cells from previously untreated patients with chronic lymphocytic leukemia as well as acute leukemias were investigated in vitro. Leukemic cells were incubated for up to 6 days with various concentrations of IL-7 (0.01 to 2,000 U/mL). Neoplastic cells of the T- or B-phenotype from chronic as well as from acute leukemias proliferated in a dose-dependent manner. Cells from acute myeloid leukemias also proliferated in response to IL-7. An optimal proliferative effect was achieved between 96 and 120 hours with 200 U/mL IL-7. Combinations of IL-7 with IL-2 and tumor necrosis factor-alpha showed an additive effect on [3H]TdR incorporation. IL-7 binding assays gave a value of approximately 33 to 180 high-affinity (kd approximately 20 pmol/L) binding sites/cell and approximately 241 to 3,280 low-affinity (kd approximately 600 pmol/L) binding sites/cell. Receptor expression correlated with the proliferation in response to IL-7. These data indicate that IL-7 can induce proliferation of relatively mature tumor cells, and that this effect is not restricted to the lymphoid lineage.

Adult↗

[Hepatitis C antibodies in acute Non-A, Non-B hepatitis].

Stored serum samples of 20 patients with clinically and bioptically proven non-A, non-B hepatitis (NANBH) in the acute stage were tested for the presence of antibodies to hepatitis C virus (anti-HCV) by means of the Ortho ELISA system. After a mean period of 8 weeks from onset of the disease, 8 of 20 patients (40%) had anti-HCV. Our follow-up study included 14 patients. Of 9 primarily anti-HCV-negative patients, 2 became positive after 2 and 7 months respectively, whereas 7 patients remained anti-HCV-negative up to 52 months (range 1-128) after the onset of hepatitis. The prevalence of anti-HCV was 71% in 7 patients with parenteral hepatitis related to transfusions (n = 2) or drug abuse (n = 5), and 38% in 13 patients with sporadic NANBH. Of the 8 anti-HCV-negative patients with sporadic NANBH, 5 had stayed in one of the countries where enterically transmitted NANBH is endemic 3 to 6 weeks before the onset of their disease. Our results show that at present the anti-HCV-test supplies an etiologic basis for approximately half of all cases of NANBH in acute stage. Nevertheless, in most cases the acute NANBH remains a diagnosis of exclusion.

Adolescent↗

Non-isotopic detection of chromosome 1 in human meiosis and demonstration of disomic sperm nuclei.

Nonradioactive in situ hybridization with the biotin-labeled chromosome 1-specific probe pUC1.77 was performed on human mitotic and meiotic chromosomes, and on sperm nuclei. The streptavidine-horseradish-peroxidase and diaminobenzidine detection system demonstrated heteromorphisms in the 1q12 heterochromatic region, not only in mitotic cells but also in mature sperm heads. The localization of chromosome 1 could be traced through all meiotic stages and in the sperm nuclei. The frequency of chromosome 1 disomy in human sperm, as indicated by two distinct hybridization signals, was calculated to be 0.41%.

Adult↗

Cytogenetic and molecular characterization of a small ring chromosome in the complex karyotype of a girl with Turner syndrome.

Blood samples of an 8-year-old girl with Turner syndrome were examined using cytogenetic and molecular methods. Chromosomal analyses revealed a mosaic karyotype consisting of 25% 47,X,der(X), +r(X) and 75% 46,X,der(X) cells. Southern blot hybridizations with Y-specific DNA probes excluded a Y chromosomal origin of the small ring chromosome. In situ hybridization using DNA probe pXBR showed it to be X-derived. Examination of C-, Q-, and R-banding patterns indicated that the der(X) chromosome probably arose by a translocation event.

Blotting, Southern↗

Chromosome banding in Amphibia. XVI. High-resolution replication banding patterns in Xenopus laevis.

High-resolution replication banding patterns were induced in prometaphase and prophase chromosomes of Xenopus laevis by treating kidney cell lines with 5-bromodeoxyuridine (BrdU) and deoxythymidine (dT) in succession. Up to 650 early and late replicating bands per haploid karyotype were demonstrated in the very long prophase chromosomes. This permits an exact identification of all chromosome pairs of X. laevis. Late replicating heterochromatin was located by analysing the time sequence of replication throughout the second half of S-phase. Neither heteromorphic sex chromosomes nor sex chromosome-specific replication bands were demonstrated in the heterogametic ZW females of X. laevis. A detailed examination of the BrdU/dT-labelled prometaphases and prophases revealed that the X. laevis chromosomes can be arranged in groups of four (quartets), most of which show conspicuous similarities in length, centromere position, and replication pattern. This is interpreted as further evidence for an ancient allotetraploid origin of X. laevis.

Animals↗

Prednimustine combined with mitoxantrone and 5-fluorouracil for first and second-line chemotherapy in advanced breast cancer.

A total of 60 patients with advanced breast cancer were treated with a combination of prednimustine (P: 110 mg/m2, days 1-5), mitoxantrone (M: 12 mg/m2, day 1) and 5-fluorouracil (F: 500 mg/m2, day 1) (PMF). Treatment was repeated every 3 weeks. In all 53 patients were evaluable for response. A total of 12 subjects had failed prior chemotherapy for metastatic disease. In response to PMF treatment we observed 21 partial remissions and 3 complete remissions, amounting to a total response rate of 45%. The median duration of response was 39 weeks, and median survival was 56 weeks. Dose-limiting side effects were leukopenia (40 cases) and thrombocytopenia (11 patients). Nausea and vomiting was experienced by 93% of subjects; in 56% of cases it reached WHO stage II-III. Alopecia occurred in 18% of our patients. Our results suggest that PMF represents an active regimen in the treatment of advanced breast cancer and yields a response rate of 45%. Considering that the majority of our patients had not received prior chemotherapy, the question remains open as to whether a 45% response rate outweighs the observed toxicity.

Adult↗

Chromosome topology in mammalian interphase nuclei.

Since 1968, when Comings published the pioneering paper on "the rationale for an ordered arrangement of chromatin in the interphase nucleus," technical methods have progressed tremendously and improved our understanding of interphase organization. The existence of highly ordered organizational patterns of the cell nucleus appears to be beyond any doubt and it is difficult to escape the conclusion that interphase chromosome topology is important for the complex regulation of the many varied and interrelated nuclear processes. However, it is worth emphasizing that a universally valid principle of chromosome arrangement does not exist and, therefore, any generalization of interphase patterns can be misleading. The factors of order according to which the chromosomes are arranged inside the nucleus are manifold: (1) Individual chromosomes remain in spatially separated domains throughout interphase, preventing an intermingling of the decondensed euchromatin. (2) Chromosome regions that contain constitutive heterochromatin associate into larger chromocenters. (3) In most cell types direct associations between interphase domains of homologous chromosomes are not observed. In others homologous heterochromatic regions tend to be paired preferentially. (4) Interphase chromosomes do not float freely in the nucleoplasm; they are associated to varying degrees with the nuclear membrane and other components of the nuclear scaffold. The number of attachment sites for each chromosome to the nuclear membrane is relatively low. (5) The positions of centromeres (and pericentromeric heterochromatin) are nonrandom and characteristic of each cell type. Specific centromere movements occur during the cell cycle, during differentiation, and under certain pathophysiological conditions. (6) The telomeric chromosome ends are particularly prone to associate in certain somatic cell types and in meiotic prophase cells. (7) The arrangement of repetitive DNA families appears to determine a structural framework of the interphase nucleus. Different cell types of one organism can exhibit marked differences in their repetitive DNA framework, whereas cells that are in an identical differentiated state or an identical phase of the cell cycle often show comparable interphase patterns even in evolutionarily distant species. (8) The various steps of ribosome biogenesis take place in a precise fashion within a separate nuclear domain, the nucleolus. The topologically well-defined nucleolar substructures are required for rDNA transcription and pre-rRNA processing. (9) A compartmentalization of transcriptional and processing events is also evident in the rest of the nucleus. However, it is not yet known if the in situ sites of transcription and RNA processing for a particular (nonribosomal) gene or gene family are actually adjacent. (10) DNA replication is precisely spatiotemporally regulated within the nucleus. The replication domains are immobilized on the nuclear matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Quantitative determination of rDNA transcription units in vertebrate cells.

The adenosine analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) unravels the compact nucleoli to necklace-like structures when applied to living cells. The nucleolar beads contain RNA polymerase I (RPI) and argyrophilic proteins, both properties considered to be characteristic of ribosomal gene activity. Each granule is supposed to represent a single transcription unit consisting of an actively transcribing gene and its RPI complex. Indirect immunofluorescence with anti-RPI antibodies was used to determine the number of transcription units in DRB-treated cells of some representative mammals, marsupials, birds, and amphibians. We estimate that 45 to 145 rRNA genes are transcriptionally active in vertebrate fibroblasts, depending on the species. Nucleolar transcriptional activity does not correlate with the total number of rRNA genes. During in vitro aging of fibroblasts, the number of transcription units appears to remain unchanged. Different cell types of one same organism show varying numbers of transcription units, reflecting their differential metabolic activity. A particular situation exists in phytohemagglutinin-stimulated lymphocytes. In the course of nucleolar activation, the number of transcription units is increased considerably, implying that formerly inactive rRNA genes are recruited for transcription. The opposite phenomenon is observed during spermatogenesis. With the diploid spermatocytes developing into haploid spermatids, the transcriptionally active rRNA genes decrease in number until rRNA synthesis is completely blocked.

Animals↗

Ring chromosome 4 in a child with mild dysmorphic signs.

We report on an 8-year-old boy exhibiting microcephaly, clinodactyly and growth retardation. Chromosome analysis showed a ring chromosome 4 in 97% of the cells and a high number of hyperploid cells with various ring formations. The breakpoints are presumed to be close to or in the telomeric regions of both arms. The patients reported with ring chromosome 4 and breakpoints close to the telomeres of both arms showed unspecific, mild clinical findings with normal or retarded mental development. These signs are probably related to the continuous generation of aneuploid cells.

Abnormalities, Multiple↗

[Coincidence of sigmoid cancer and sigmoid diverticulitis].

From 1985 to 1989 265 patients with a carcinoma of the sigmoid or sigmoid diverticulitis have been operated in our clinic. 23 of the treated patients synchronously had a carcinoma and a diverticulitis. The carcinoma in these cases was found to be significantly more frequent in a stage T1 or T2. We also found a significantly higher rate of perforations in this group of patients.

Adenocarcinoma, Mucinous↗

[Texture formation of the dental ceramic core material In-Ceram and thermal expansion of its individual components].

Electron microscopic investigations of the core material In-Ceram show how its texture is formed. While these are processed the Al2O3 crystallites turn idiomorphic. Etching the material with sulphuric acid selectively dissolves the glassy phase and reveals the crystallites. The chemical composition of the two components of the core material is determined by microprobe analysis. While the crystallites are pure Al2O3, the glass consists of La2O3, SiO2, Al2O3 and CaO. Measurements of the thermal expansions of the glass and the Al2O3 frame show the value for the glass to be 5.1% lower than that of the Al2O3 frame. This results in internal pressure and contributes to the high strength of the material.

Aluminum Oxide↗

In vitro differentiation from a pluripotent human CD4+CD8+ thymic cloned cell into four phenotypically distinct subsets.

Human thymic cell differentiation is almost totally unknown. In the present study we developed an in vitro system using human thymic cloned cells to analyze precursor-progeny relationship. We obtained several CD4+CD8+ double positive thymic clones that could give rise after several weeks in culture only to either CD4 or CD8 single positive clones. By contrast we isolated a unique pluripotent thymic double positive clone, termed B12, which differentiated into four phenotypically distinct T cell clones, namely double-positive CD4+CD8+, double-negative CD4-CD8- or either single-positive phenotype. We derived stable subclones representative of each phenotype and we showed by molecular analysis that they expressed the same TCR. Utilization of either CD3 or anticlonotypic mAb revealed that this TCR expressed by the four subclones was functional.

Antigens, CD↗

Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo.

Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors. After 1 day of incubation in culture medium, TNF receptors were detectable in the range of 540 to 1,500/cell. Kinetic experiments revealed that receptor expression was half-maximal after 3 hours of culturing and required de novo protein synthesis. The Scatchard plots of TNF-alpha binding indicated a single set of high-affinity TNF receptors with a dissociation constant of 70 pmol/L. TNF receptor expression in vitro was found in all examined cases. All cytokines tested, with the exception of IL-2, did not influence the expression of TNF receptors. The TNF receptor expression is enhanced in B-CLL cells cultured in the presence of interleukin-2 when compared with the receptor expression of cells cultured in medium alone. Our data suggest that neoplastic B-CLL cells in patients with stable disease do not express TNF receptors in vivo and that an unknown mechanism suppressing TNF receptor expression in vivo may play a role in growth regulation of neoplastic B cells.

B-Lymphocytes↗

Undulin, an extracellular matrix glycoprotein associated with collagen fibrils.

Undulin, a novel noncollagenous extracellular matrix protein, was isolated from skin and placenta. In polyacrylamide gels most of the unreduced protein migrates with Mr above 1,000,000 yielding bands A (Mr 270,000), B1 (Mr 190,000), and B2 (Mr 180,000) after reduction. Undulin is biochemically and immunochemically distinct from other previously characterized large matrix glycoproteins. Immunoblotting using monoclonal antibodies suggests that bands A and B are closely related. Electron microscopy reveals undulin as structures consisting of an approximately 80-nm-long-tail with a nodule on one end and with one or two shorter arms on the other. Ultrastructurally immunolabeled undulin is found mainly between densely packed mature collagen fibrils. Indirect immunofluorescence shows bundles of uniform wavy fibers in dense connective tissues superimposable on a subpopulation of type I collagen structures. This suggests that undulin serves a specific yet unknown function in the supramolecular organization of collagen fibrils in soft tissues.

Amino Acids↗

Karyotype and chromosome banding in the reed frog Hyperolius viridiflavus ommatostictus (Amphibia, Anura, Hyperoliidae).

C-banding and mithramycin staining were used to characterize the karyotypes of 10 specimens of the African reed frog Hyperolius viridiflavus ommatostictus from Tanzania. The diploid chromosome number is 2n = 24. Although no heteromorphic sex chromosomes were present in the mitotic karyotypes, in many diakineses of male meiosis one or two bivalents exhibited an end-to-end arrangement. In the laboratory 7 out of 24 females changed sex spontaneously. This indicates that an XY/XX system of sex determination operates in H. viridiflavus ommatostictus.

Animals↗

[Virostatic treatment of chronic hepatitis].

Immunosuppressive therapy of viral borne chronic active hepatitis is obsolete, and virostatic therapy with alpha-interferon is under worldwide investigation. The mechanism of and indications for interferon therapy are discussed. Combined therapy may be more effective than monotherapy with interferon, and combined therapy with corticosteroids is now being attempted. Corticosteroids are given as induction therapy, with sudden interruption followed by longterm interferon therapy. The results of several studies of interferon monotherapy in various countries show seroconversion from HBe in 30-50% and conversion from HBs to anti-HBS in 10%. Preliminary results of a pilot study of interferon in chronic active non-A non-B hepatitis show an immediate therapeutic effect and often, regrettably, an equally prompt rebound after interruption of therapy. Controlled therapeutic studies are needed and in progress.

Adolescent↗