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Biomedical subjects

M Schwab

Publications and source records attributed to M Schwab.

At least 145 records · Page 8Linked to original sources

Variations in the expression of the adenomatous polyposis coli (APC) tumor suppressor gene in human cancer cell lines of different tissue origin.

The adenomatous polyposis coli (APC) tumor suppressor gene APC is mutated in familial adenomatous polyposis and in most sporadic colorectal tumors. Through its interaction with beta-catenin the APC protein may play a role in a signal transduction pathway regulating cell proliferation. Despite the fact that APC is ubiquitously expressed, mutations leading to truncated proteins are restricted to tumors of the digestive system. To determine further alterations not resulting in protein truncation, but possibly influencing the signaling, we compared the relative expression level of the APC protein and transcripts in 24 human colorectal cancer cell lines and in additional 17 lines of noncolorectal tissue origins, which have not previously been studied. By Western analysis, the highest levels of full-length APC protein were found in a subset of neuroblastoma and retinoblastoma cell lines. In contrast, in five noncolorectal lines it was not detectable. Truncated APC was exclusively found in 18 of the 24 colorectal cancer cell lines, but was never detected in any cell line derived from other tissues. In most colorectal cancer cell lines the protein level of full-length or mutated APC was reduced. By the more sensitive immunoprecipitation analysis, weak expression of full-length APC could be shown even in those noncolorectal cancer cell lines where it was not detectable by Western blotting. In addition, APC transcript expression was found in all cell lines, the level in colorectal cancer cell lines being reduced.

Adenomatous Polyposis Coli↗

HLA class II expression in well differentiated thyroid carcinoma: correlation with clinicopathological features.

Lymphocytic infiltration and aberrant expression of HLA class II antigens on malignant thyroid epithelial cells are assumed to play a relevant role in the immune response against thyroid cancer. Aberrant expression of the HLA class II alpha and beta chains as well as number and distribution of tumor infiltrating lymphocytes were investigated in primary tumors (n = 54) and metastases (n = 4) of well differentiated thyroid carcinomas (follicular carcinoma: n = 26, papillary carcinoma: n = 28). The immunohistochemical findings were correlated with clinicopathological features. An aberrant HLA class II beta chain expression was detected in 9 (28%) papillary carcinomas and 4 (15%) follicular carcinomas. Three HLA class II beta chain positive papillary carcinomas and all follicular carcinomas were negative for the HLA class II alpha chain. All lymph node and distant metastases were negative for both HLA class II alpha and beta chain. Number and distribution of CD45R0+ lymphocytes significantly (p < 0.05, Fisher test) correlated with the aberrant HLA II antigen expression on tumor cells. There was also a significant correlation (p < 0.05, Fisher test) between an aberrant HLA II antigen expression and invasion of the vessels. No correlation was found between aberrant HLA class II expression and the occurrence of lymph nodes or distant metastases. Our findings indicate that the expression of HLA class II antigens on thyroid carcinoma cells is high in the step of invasive growth and that the local immune response towards the HLA class II antigens appears to prevent metastatic spread of HLA II positive tumor cells. There is evidence of different expression of HLA class II chains in follicular and in papillary thyroid carcinomas, which could be a further indicator that in these two subgroups of thyroid carcinomas different changes in the regulatory mechanisms of HLA class II antigen expression occur.

Adult↗

Trocar incision and closure: daily problems in laparoscopic procedures--a new technical aspect.

A mini-laparotomy as described by Hasson was used in a modified way in 1,500 laparoscopic procedures. In comparison with the insertion of a Veress needle, we find the open approach to be a safer and quicker technique to obtain the pneumoperitoneum. A new technique for closure of the trocar incision is described. The technique is recommended due to its easy and safe approach requiring no additional special equipment.

Humans↗

Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells.

To elucidate the contribution of the N-Myc protein to neuroblastomas we have used a synthetic inducible expression system on the basis of the tetracycline repressor of E coli to reversibly express N-myc in a human neuroblastoma cell line in which expression of endogenous N-myc is barely detectable. Like the c-Myc protein, N-Myc up-regulates the expression of both alpha-prothymosin and ornithine decarboxylase. Induction of N-myc increases both the rate of DNA-synthesis and the proliferation rate, and shortens the G1 phase of the cell cycle. A comparison of cell populations in which the presence of N-Myc protein was restricted to different parts of G(zero)/G1 revealed that N-Myc is rate-limiting for cell cycle progression during the first 5 h after serum stimulation of quiescent cells providing direct evidence that Myc-proteins act early after mitogenic stimulation of quiescent cells.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Inhibitory properties coexist with plasticity in the song system of the canary.

The expression of neuronal growth regulating factors (Ni 35/250, GAP-43) were studied immunohistochemically in the plastic telencephalic song system and in the cerebellum of the canary. In the myelinated song nuclei (HVc and RA) growth promoting and inhibiting molecules could be detected, whereas in the white matter tracts of the cerebellum only the neurite growth inhibitor could be detected. The morphodynamic effects of these molecules were assessed by in vitro assays on cryosections. Neurites were formed by 20-30% of the E7 chick cortical neuroblasts cultured in myelinated areas of the vocal control system, neurite outgrowth from the white matter of the cerebellum was completely inhibited.

Animals↗

The DDX1 gene maps within 400 kbp 5' to MYCN and is frequently coamplified in human neuroblastoma.

Human neuroblastoma cells frequently show amplification of the oncogene MYCN, which maps to 2p24. Previous studies have localized the DEAD box motif gene DDX1 to the same chromosome band and demonstrated coamplification of DDX1 and MYCN in two retinoblastoma cell lines. Recently, a high frequency of coamplification of DDX1 and MYCN has been shown in human neuroblastoma cells. We have determined the physical distance between the two genes by pulsed field gel electrophoresis in normal tissue and have found that DDX1 maps to a position at a maximum distance of 400 kbp 5' to MYCN. Two neuroblastoma cell lines with coamplification of DDX1/MYCN showed a similar topographic relationship of the two genes. In contrast, in two cell lines with high copy number, the DDX1 gene was not present in all amplified units recognized by MYCN and had changed its position in the amplified DNA relative to MYCN from 5' to 3', presumably by rearrangement during the amplification process. Our data show that the high frequency of DDX1 coamplification is due to its close physical distance to MYCN. Although amplification has resulted in an elevated expression of DDX1 the significance of overexpression for neuroblastoma remains unclear.

Chromosome Mapping↗

Genomic instability in 1p and human malignancies.

Both cytogenetic and molecular genetic approaches have unveiled non-random genomic alterations in 1p associated with a number of human malignancies. These have been interpreted to suggest the existence of cancer-related genes in 1p. Earlier studies had employed chromosome analysis or used molecular probes mapped by in situ hybridization. Further, studies of the various tumor types often involved different molecular probes that had been mapped by different technical approaches, like linkage analysis, radioactive or fluorescence in situ hybridization, or by employing a panel of mouse x human radiation reduced somatic cell hybrids. The lack of maps fully integrating all loci has complicated the generation of a comparative and coherent picture of 1p damage in human malignancies even among different studies on the same tumor type. Only recently has the availability of genetically mapped, highly polymorphic loci at (CA)n repeats with sufficient linear density made it possible to scan genomic regions in different types of tumors readily by polymerase chain reaction (PCR) with a standard set of molecular probes. This paper aims at presenting an up-to-date picture of the association of 1p alterations with different human cancers and compiles the corresponding literature. From this it will emerge that the pattern of alterations in individual tumor types can be complex and that a stringent molecular and functional definition of the role that Ip alterations might have in tumorigenesis will require a more detailed analysis of the genomic regions involved.

Chromosome Mapping↗

Hyponatraemia and cerebral convulsion due to short term DDAVP therapy for control of enuresis nocturna.

UNLABELLED: Desmopressin (DDAVP) is frequently used in the treatment of primary isolated enuresis nocturna if other approaches have failed. We report a further case of hyponatraemia and cerebral convulsion due to water intoxication after intranasal DDAVP application by a 6 year-old boy with enuresis. CONCLUSION: Although adverse reactions in DDAVP (e.g. hyponatraemia) are rare, it should not be considered as the first choice treatment of enuresis nocturna and only be used with caution.

Child↗

Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer.

To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1 and hPMS2, have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Additionally, defective mismatch repair is thought to account for the observation of microsatellite instability (MIN) in tumors from these patients. The genetic defect responsible for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be clearly delineated. In order to better understand the role of somatic and germline alterations within hMSH2 and hMLH1 in the process of colorectal tumorigenesis, we examined the entire coding regions of both of these genes in seven patients with MIN+ sporadic colorectal cancer, 19 patients with familial colorectal cancer, and 20 patients meeting the strict Amsterdam criteria for HNPCC. Thirteen germline, two somatic, and four neutral alterations were identified. The two somatic mutations occurred in patients having familial cancer, while the germline mutations were distributed among one sporadic (14%), three familial (16%), and nine HNPCC (45%) cases. All patients with identified mutations in the mismatch repair genes, whose tumors were available for analysis, demonstrated MIN. On the other hand, we could not identify mutations in the subset of clinically defined HNPCC patients with MIN negative tumors nor in the majority (6/7) of MIN+ sporadic tumors.

Adaptor Proteins, Signal Transducing↗

A highly amplified mouse gene is homologous to the human interferon-responsive Sp100 gene encoding an autoantigen associated with nuclear dots.

In human cells, three proteins are currently known to colocalize in di screte nuclear domains (designated nuclear dots): Sp100, a transcription-activating protein autoantigenic primarily in patients with primary biliary cirrhosis; PML, a tumor suppressor protein involved in development of acute promyelocytic leukemia; and NDP52, a protein of unknown function. Here we report sequence similarities between the Sp100 protein and a putative protein encoded by a highly amplified mouse gene which is visible as an inherited homogeneously staining region (HSR) on chromosome 1 of some mouse populations. By in situ hybridization, the Sp100 gene was mapped to locus 2q37, the syntenic region of the HSR on mouse chromosome 1. Unlike the highly amplified mouse gene, Sp100 was found to be a single-copy gene and showed no restriction fragment length polymorphisms. Sequence similarities in the promoter regions and similar exon-intron organizations of the two genes were revealed. As for Sp100, steady-state levels of the mRNAs of the HSR-encoded genes could be greatly increased by interferon (IFN) treatment. As in human cells, IFN treatment led to an enlargement in both size and number of nuclear dots in mouse cells as visualized by immunofluorescence staining with autoimmune sera from patients with primary biliary cirrhosis. These data indicate that a gene located in the inherited HSR of mice, designated mSp100, is homologous to the human Sp100 gene, has a similar gene organization, and responds similarly to IFN treatment.

3T3 Cells↗

Vibroacoustic stimulation with a complex signal: effect on behavioral state in fetal sheep.

An ideal vibroacoustic stimulus for testing fetal reactivity has yet to be developed. In the present study in fetal sheep we tested the effect on behavioral state of an amplitude and frequency-modulated signal produced at the abdominal surface of the ewe. The stimulus was presented during periods of fetal non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Evaluation of behavioral state was accomplished by visual observation of strip-chart recordings. Assessed in this manner, vibroacoustic stimulation during NREM sleep consistently resulted in a change to an indeterminate state. However, stimulation during REM sleep failed to have an effect. Additional evaluation applying spectral analysis to the fetal electrocorticogram during stimulation in NREM sleep revealed a marked decrease in delta band power from 100 to 27 +/- 5% and in theta band power from 100 to 40 +/- 4% resulting in a decrease in total power from 100 to 35 +/- 4% (p < 0.05). Stimulation during REM sleep revealed a significant increase in beta band power from 100 to 123 +/- 14%. Vibroacoustic stimulation in both NREM and REM sleep led to an increase in spectral edge frequency, implying central arousal.

Acoustic Stimulation↗

Nitrogen dioxide and respiratory illness in children. Part IV: Effects of housing and meteorologic factors on indoor nitrogen dioxide concentrations.

In a prospective study of infants' exposure to nitrogen dioxide (NO2)* and respiratory illness, NO2 concentrations were measured in more than 1,400 homes in Albequerque, NM, From January 1988 through June 1991 (Health Effects Institute Research Report Number 58, Parts I, II and III). This report characterizes the variability in indoor NO2 concentrations across seasons and years, and identifies factors associated with variation in concentrations between homes and across seasons. In regression analyses of winter data, NO2 levels in the infants' bedrooms were predominately determined by the presence of gas cooking ranges with continuously burning pilot lights, the presence of wall or floor furnaces, the use of the stove for space heating, and the square footage of the living space. These findings are consistent with previously published analysis of data from homes in other U.S. cities. Relatively small differences in seasonal NO2 levels were observed across years. The correlation coefficient (r) of bedroom NO2 levels obtained in the same homes was 0.66 over two winters and 0.48 over two summers. For homes that had gas cooking ranges with continuously burning pilot lights, the NO2 bedroom concentrations differed, on average, less than 5 parts per billion (ppb) across winters. These differences were hypothesized to be caused by differences in the use of indoor NO2 sources, ventilation, and ambient (outdoor) NO2 levels. We were, however, unable to demonstrate an association between year-to-year differences in seasonal indoor NO2 concentrations and reported use of cooking range, furnace, or heater, or ambient NO2 levels, or temperature.

Air Pollution, Indoor↗

[Surgical therapy of pancreatic carcinoma in elderly patients over 70].

Between October 1972 and December 1994, 519 pancreatic resections were performed at the Chirurgische Universitätsklinik Mannheim, 372 for pancreatic carcinoma. Of 328 patients who underwent a partial duodenopancreatectomy for cancer, 45 patients were older than 70 years: only in one case a partial duodenopancreatectomy was performed for chronic pancreatitis. In comparison to all patients the perioperative morbidity increased to 39.1% (21.5% vs. 39.1%). The perioperative mortality of all patients was 1.9%, the mortality of patients older than 70 years was 4.3%. The mean survival time of 28 patients who died subsequently was 30.6 (5-96) months. Despite increased perioperative morbidity and mortality, the patient's age is not considered to be a limiting factor to an attempt at curative resection of pancreatic or periampullary cancer.

Aged↗