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H W Rüdiger

Publications and source records attributed to H W Rüdiger.

At least 91 records · Page 5Linked to original sources
PubMed1985

Three different classes of oral antidiabetic drugs do not increase insulin binding and insulin-induced RNA synthesis in human fibroblast cultures.

We describe insulin binding and insulin-mediated RNA synthesis on seven human fibroblasts strains in culture initiated from skin biopsies in the presence of three oral antidiabetic agents, Metformin, Gliquidone, and a non-sulfonylurea antidiabetic drug (B X DF 591 ZW), which belong to different chemical classes. At least at a nontoxic pharmacologic concentration of 1 microgram/ml these drugs did not influence the number and affinity of insulin receptors, nor did they increase the insulin-mediated RNA synthesis. We conclude that cultured fibroblasts do not represent the proper target for an evaluation of an extrapancreatic action of oral antidiabetic drugs.

Cells, Cultured↗
PubMed1985

Enhanced formation of benzo(a)pyrene:DNA adducts in monocytes of patients with a presumed predisposition to lung cancer.

Blood monocytes from 45 selected patients with lung cancer and 30 healthy controls were incubated with [G-3H]-benzo(a)pyrene for 30 h, and the formation of covalently bound DNA adducts was determined. The lung cancer patients were either relatively young (below 46 yr), nonsmokers, or had at least one first degree relative with lung cancer. Therefore, they might be considered cancer prone. The DNA adducts were significantly elevated in 22 patients with early age cancer (4.34 fmol/micrograms of DNA; P less than 0.04). In 12 familial cases, the slight elevation (2.77 fmol/micrograms of DNA) was not statistically significant in comparison to healthy controls. Benzo(a)pyrene:DNA adduct levels did not differ significantly between smokers and nonsmokers. Eight of 9 lung cancer patients with DNA adducts equal or above 4.5 fmol/micrograms of DNA but only 16 of 36 with adducts below this value had either oat cell or squamous cell cancer (P less than 0.05). The observed enhanced formation of covalent DNA adducts in blood monocytes exposed to a carcinogenic polycyclic hydrocarbon may be genetically determined and could play a role in the development of lung cancer at an early age.

Adult↗
PubMed1984

Heterozygous carriers for Bloom syndrome exhibit a spontaneously increased micronucleus formation in cultured fibroblasts.

Cultured fibroblasts of homozygotes and heterozygotes for Bloom syndrome exhibit an enhanced formation of micronuclei. The number of spontaneously occurring micronuclei permit clear separation of heterozygotes from either normal controls or homozygous patients without overlap between these groups. The observed differences could not be enhanced further by the addition of various mutagens. We conclude from the increased chromosomal damage that heterozygotes for Bloom syndrome may have a higher risk for malignant diseases.

Bloom Syndrome↗
PubMed1983

Pathogenetic mechanisms of hereditary diabetes mellitus.

Novel laboratory techniques such as the determination of proinsulin, insulin, C-peptide and insulin receptors have allowed further subclassification of diabetes mellitus today as representing a symptom rather than a disease. Numerous pathogenetic mechanisms of diabetes have been identified, many of these being genetically determined and this may extend possibilities for genetic counselling. As a geneticist's view, the pathogenetic concept of diabetes presented here is mostly confined to genetic mechanisms, leaving aside other influences on the development of diabetes such as hormones, viruses, nutrition and drugs. Mendelian inherited diabetic disorders are related to different pathogenetic principles where possible, being speculative in some cases.

Diabetes Mellitus↗
PubMed1983

Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.

We describe three siblings with a mild diabetes mellitus in combination with acanthosis nigricans and multiple minor physical abnormalities. Fasting plasma insulin was elevated up to 100-fold as compared with normal values, and the diabetes was classified as insulin resistant. Insulin-binding studies on erythrocytes, monocytes, and cultured fibroblasts disclosed an abnormally reduced binding capacity, as compared with that of healthy controls, which was most prominent at low concentrations of insulin. Scatchard analysis on erythrocytes of the three patients revealed a normal number of total insulin-binding sites per cell, but a complete lack of insulin binding to the high-affinity receptor component. The findings are consistent with the assumption of two genetically distinct types of insulin receptors.

Acanthosis Nigricans↗
PubMed1983

Familial cancer or cancer family syndrome. Report on a cancer family and consideration of genetic mechanisms.

We present a family with an unusually high incidence of cancer in four generations. Complete information could be obtained for the first three generations with 73 persons. Tumor incidence was 2/8 in the first generation, 14/22 in the second, and 11/44 in the third generation. A formal analysis, however, according to the four criteria of cancer family syndrome: increased frequency of adenocarcinomas of multiple anatomical sites, multiple primary malignant neoplasms, early age of onset, and autosomal dominant mode of inheritance, revealed that in this family multiple primaries are virtually absent and that tumors do not occur at a particularly early age. We therefore consider this family shows that familial clustering of tumors may follow an autosomal dominant pattern of inheritance even when the strict criteria of cancer family syndrome are not fulfilled. We conclude that the phenomenon of cancer families is not confined to one or two distinct clinical types.

Adenocarcinoma↗
PubMed1983

An investigation into the frequency of mitral valve prolapse in von Willebrand disease.

The reported extremely high incidence of mitral valve prolapse in von Willebrand patients (60%) in combination with multiple signs of mesenchymal dysplasia points to a hitherto unknown pleiotropic effect of the von Willebrand gene and needs further confirmation. Therefore, we looked for the presence of mitral valve prolapse in 19 patients with classical von Willebrand disease. While 58% of these patients had one or more physical findings which could be interpreted as symptoms of mesenchymal dysplasia, we found only one patient with a mitral valve prolapse (5.3%), comparable to the 6% incidence in the normal population. Therefore, we must conclude that there is no association between mitral valve prolapse and von Willebrand disease.

Adolescent↗
PubMed1982

The syndrome of diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities (DIDMOAD-syndrome). Two affected sibs and a short review of the literature (98 cases).

We describe two sibs with DIDMOAD-Syndrome, a 19-year-old girl with diabetes mellitus (type I), optic atrophy, inner-ear deafness, and atonia of the urinary tract, and her 5-year-old brother with diabetes mellitus (type I) and optic atrophy. Studies of red blood cell insulin receptors revealed a normal number of receptors per cell and normal affinity to insulin. The syndrome represents an autosomal recessively inherited type of diabetes mellitus, which remains often undiagnozed since most of the symptoms except diabetes mellitus and optic atrophy occur with varying expressivity. An atonia of the efferent urinary tract often with fatal complications is present in 46% of all patients with this syndrome reported in the literature and is unfortunately not included in the acronym DIDMOAD.

Adult↗
PubMed1982

Cytogenetic demonstration of a corrective factor in Bloom's syndrome.

Patients with Bloom's syndrome, an autosomal recessively inherited disorder, have a highly increased risk of developing early malignancies of various types. The chromosomes of such patients exhibit an enhanced rate of spontaneous sister chromatid exchange. Cocultivation of patients' fibroblasts (as responder cells) with fibroblasts from healthy donors or from patients with xeroderma pigmentosum or Fanconi's anaemia (as effector cells) produces a dose-dependent reduction in Bloom-specific sister chromatid exchange; however, Bloom heterozygotes exhibit a reduced corrective capacity. The reduction in Bloom-specific sister chromatid exchange is related to the presence of a soluble factor (m.w. 10 000-20 000) which is produced in culture by normal proliferating fibroblasts. This corrective factor might represent a cancer-protective principle that is defective in patients with Bloom's syndrome.

Bloom Syndrome↗
PubMed1981

Mutagen-induced sister chromatid exchange rate in Bloom syndrome remains unaltered in the presence of Bloom corrective factor.

Fibroblasts of a patient with Bloom syndrome (GM-1492) were cultured in the presence of either mitomycin C, ethylmethanesulfonate, or 4-nitroquinoline-1-oxide, (4-NQ1-O) and sister chromatid exchange was determined. The mutagens enhanced the sister chromatid exchange rate to different degrees, 4-NQ1-O being the most potent substance. Bloom corrective factor, which is present in normal cell-conditioned culture medium, reduced the spontaneously increased SCE in Bloom syndrome cells by about 20 SCE per metaphase but failed to reduce the additional mutagen-induced SCE increase. These findings indicate that only spontaneously, but not mutagen-induced, SCE in Bloom syndrome fibroblasts can be decreased by the Bloom corrective factor.

4-Nitroquinoline-1-oxide↗
PubMed1981

Decreased rate of benzo(a)pyrene-induced sister chromatid exchange in fibroblast cultures from patients with lung cancer.

Fibroblast cultures from 29 lung cancer patients including eight familial cases and from 25 healthy controls were investigated. We studied the benzprene-induced sister chromatid exchange (SCE) following incubation in the presence of 150 nM benzo(a)pyrene and found spontaneously increased SCE values in the patients' cells but a reduced response to benzprene as compared to the control cultures. The benzpyrene-induced SCE was positively correlated with both benzpyrene metabolism and DNA adducts in normal control cells but not in the patients' cells. The ratio of benzypyrene DNA adducts and benzpyrene-induced rate of SCE calculated for the individual cell strains exhibited a bimodal distribution with patients' cells, but not with control cells. We speculate that the described differences between patients' and control fibroblasts might reflect a genetic predisposition to the development of lung cancer in about one half of the patients tested.

Benzopyrenes↗
PubMed1981

Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect.

The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied. Cells of Fanconi anemia and xeroderma origin reduced the rate of SCEs in Bloom cells by about 45%-50%, just as control cells do. In contrast, heterozygous Bloom cells reduced the rate of SCEs by only 16%-28%. In absolute figures, Fanconi cells reduced the mean rate of SCE in Bloom cells from 55.7 +/- 5.50- to 27.7 +/- 6.44, xeroderma cells to 30.5 +/- 5.73, and control cells to 28.3 +/- 5.35. Three different cell strains from Bloom syndrome heterozygotes reduced the rate to 40.1 +/- 8.81, 47.0 +/= 6.94, and 47.5 +/- 8.32. There was no effect on any of these cell strains by Bloom syndrome fibroblasts. We interpret the functional deficiency of heterozygous Bloom syndrome fibroblasts as a gene dosis effect. It probably represents a specific manifestation of the yet unknown primary defect, because it suggests the existence of a "corrective factor" that is inactive or absent in homozygous Bloom cells and reduced in heterozygotes. It may be identical with or closely related to the normal gene product at the Bloom locus.

Bloom Syndrome↗