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H W Rüdiger

Publications and source records attributed to H W Rüdiger.

At least 73 records · Page 4Linked to original sources
PubMed1989

Reduced O6-methylguanine repair in fibroblast cultures from patients with lung cancer.

The activity of O6-methylguanine-DNA methyltransferase was determined in fibroblast cultures from 45 patients with lung cancer, 39 patients with cutaneous malignant melanoma, and 29 healthy controls. This enzyme is a critical parameter for the capacity to repair O6-methylguanine (O6-mGua) adducts in DNA, and a decreased activity might therefore be responsible for an enhanced susceptibility to cancer. The assay was performed with 8 x 10(6) fibroblasts which were homogenized and incubated with a known amount of O6-mGua containing DNA. The remaining substrate was determined fluorimetrically after high performance liquid chromatographic separation. O6-mGua repair was significantly reduced in lung cancer patients [6.64 +/- 4.32 (SD) pmol O6-methylguanine repaired/8 x 10(6) cells] as compared to healthy controls [10.35 +/- 5.42, P less than 0.0022] or patients with cutaneous malignant melanoma [10.83 +/- 6.66]. The lowest mean values were detected in a subgroup of 16 lung cancer patients with a tumor manifestation below 46 years of age (5.06 +/- 3.89). Fibroblasts from 4 patients with lung cancer had no detectable repair. We conclude that a reduced capacity to remove O6-mGua adducts may represent a further mechanism of individually enhanced lung cancer risk.

Adult↗
PubMed1989

A new familial syndrome with impaired function of three related peptide growth factors.

We describe a new familial syndrome in three siblings; it is biochemically characterized by a combined defect of the action of the three related peptides insulin, insulin-like growth factor I (IGF I) and epidermal growth factor (EGF). Clinically, the disease has features of Werner syndrome with lipodystrophy, scleroderma-like alterations of the skin, alterations of the skeleton and contractures of joints. In addition, one of the patients has an insulin-resistant diabetes mellitus. Studies with cultured fibroblasts obtained from skin biopsies show a markedly reduced stimulation of RNA synthesis by the three growth factors and a decreased insulin stimulation of 2-deoxy-D-glucose uptake as compared with normal controls. Receptor binding of the three peptides occurred with normal capacity and affinity. We conclude that the signal transfer of different growth factors has a common denominator at the postreceptor level.

Adult↗
PubMed1989

Increased numbers of spontaneous micronuclei in blood lymphocytes and cultures fibroblasts of individuals with familial cutaneous malignant melanoma.

In vitro detection of micronuclei was used to determine spontaneous chromosomal instability in cultured fibroblasts of 28 healthy normal controls, 28 individuals with nonfamilial cutaneous malignant melanoma (CMM) and 14 people with familial occurrence of CMM. Lymphocytes from 40 healthy controls, 40 CMM patients and 6 individuals with familial CMM were also compared for spontaneous expression of micronuclei in vitro. In the familial cases micronucleus frequency was found to be higher, both in cultured fibroblasts (P less than 0.005) and in lymphocytes (P less than 0.001) as compared to normal controls. There was no significant difference between nonfamilial cases and normal controls. We conclude that chromosomal instability may contribute to a genetic risk for development of cutaneous malignant melanoma.

Adult↗
PubMed1989

Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum.

Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 +/- 1.96 vs. 1.82 +/- 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 +/- 3.49 vs. 9.01 +/- 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients.

Cells, Cultured↗
PubMed1989

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma.

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light.

Adult↗
PubMed1989

[Chromosome instability in patients with malignant melanoma of the skin].

The certainty of a strong genetic predisposition to malignant melanoma was first established over 35 years ago. Since it has been shown that constitutive chromosomal instability is significantly correlated with the familial occurrence of cancer, we have studied spontaneous micronucleus rates in fibroblast cultures from 44 melanoma patients, 44 healthy probands and 78 patients with bronchial carcinoma. Here we report a significantly (p = less than 0.0005) increased spontaneous chromosomal instability in patients with cutaneous malignant melanoma compared to healthy controls and other tumor patients (bronchial carcinoma).

Adolescent↗
PubMed1989

Cell kinetic evidence suggests elevated oxidative stress in cultured cells of Bloom's syndrome.

Bromodeoxyuridine/Hoechst flow cytometry was used to analyse disturbed cell proliferation of fibroblasts and lymphoblastoid cells from Bloom's syndrome (BS). Fibroblasts show poor activation, arrest in the G2 phase of the cell cycle along with a prolongation of the G1 phase. This pattern of perturbed cells proliferation is akin to that elicited in normal fibroblasts by 4-hydroxy-nonenal, a breakdown product of lipid peroxides. Treatment with vitamin E improved growth of BS fibroblasts more strongly than growth of normal fibroblasts. Lymphoblastoid cells from BS, to the contrary, experience only a minor arrest in the G2 phase after one round of bromodeoxyuridine incorporation, but are strongly inhibited during and after the second S phase. Thus, their cell cycle arrest is dependent upon BrdU incorporation, as has been found previously in normal cells exposed to elevated concentrations of oxygen or paraquat, a superoxide generating compound. These results suggest that BS cells may suffer from an elevated, endogenous generation of oxygen free radicals.

Bisbenzimidazole↗
PubMed1989

[Childhood obesity as a symptom of genetic syndromes].

The authors describe on examples from the practice of a genetic clinic seven different genetic syndromes associated with obesity: Laurence-Moon-Biedl, Alström, Weiss, Cohen, Carpenter, Prader-Willi and syndrome of insulin resistance. The autosomal recessive determination of the majority of these syndromes emphasizes their genetic impact with a high risk of repeated occurrence in the family. Visual and hearing defects increase clinical and social importance of these syndromes. When evaluating the genetic prognosis of risk families, the authors consider the possibility of prenatal diagnosis and its forms and the risk of implementation of a preventive method. In some instances obesity is a manifestation of a disorder of insulin receptors.

Abnormalities, Multiple↗
PubMed1988

Formation of DNA adducts and water-soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled.

Formation of DNA adducts and of water-soluble metabolites was studied in monocytes of 86 first-degree relatives of 15 families. Tests were performed with blood monocytes using (G-3H)-benzo[a]pyrene as a model pro-carcinogen. Variance analysis revealed significantly higher inter-familial than intra-familial variations. From these data we conclude that the formation of DNA adducts is genetically controlled. Therefore the enhanced formation of benzo[a]pyrene DNA adducts in lung cancer patients found in earlier studies may reflect a genetic predisposition for lung cancer in some patients.

Adolescent↗
PubMed1986

Prolonged plasma half-life of insulin in patients with a genetic defect of high affinity binding sites.

Plasma clearance of endogenous and intravenously administered insulin was studied in three sibs with severe insulin resistance secondary to an affinity defect of their insulin receptors, and in five healthy controls. Intravenous infusion of somatostatin was used to inhibit the insulin secretion. 0.3 U of insulin/kg body weight was administered as an intravenous bolus. Plasma glucose, immunoreactive insulin and C-peptide were determined subsequently at constant intervals. We found a prolonged plasma half-life of insulin in the three patients, being 33.5 +/- 11.8 min vs 8.2 +/- 2.2 min in controls, P less than 0.002, but a normal half-life of C-peptide. The result indicates, that the plasma insulin clearance is predominantly mediated by intact insulin receptors. We conclude, that insulin has a prolonged half-life in all patients with insulin resistance secondary to an impaired receptor function.

Adult↗
PubMed1985

Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor.

The stimulation of glucose uptake and RNA synthesis by insulin was studied in cultured fibroblasts from patients with an inherited affinity defect of the insulin receptor. Additional cell cultures were set up of two patients with Alstrøm syndrome, a genetic disease with insulin resistance but normal insulin receptor, and of eight healthy individuals. In receptor-defective patients we found a corresponding defect of the insulin-mediated stimulation of RNA synthesis but a normal stimulation of glucose uptake. We conclude that both postreceptor effects are controlled by different insulin-directed mechanisms.

Cells, Cultured↗