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Biomedical subjects

U Mohr

Publications and source records attributed to U Mohr.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sarcocystis muris--a rare case in laboratory mice.

In a lifespan transgeneration study under standard laboratory conditions using a total of 4682 CBA/J mice, unusual intramuscular inclusions were found in the diaphragm, heart and skeletal muscle of one mouse using light microscopy. Located within the myocytes, they caused no visible tissue reaction. Cross-sections of these spherical and cystic lesions showed numerous banana-shaped structures, identified as permanent parasitic bradyzoites, which permitted these infections to be diagnosed microscopically as sarcocystosis.

Animals↗
PubMed1998

Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction.

Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, has been implicated as an etiologic agent in the Balkan endemic nephropathy (BEN), a chronic disease affecting populations in the Balkans. Compared with unaffected individuals, patients suffering from BEN and/or urinary tract tumors were more frequently found to have a capacity for rapid debrisoquine (DB) metabolism, a metabolic reaction related mostly to cytochrome P450 (CYP) 2D in humans. Earlier studies, using female DA and Lewis rats phenotyped as poor or extensive DB metabolizers respectively, revealed a parallelism between DB-4 hydroxylation and OTA-4 hydroxylation. To investigate whether genetic polymorphism modifies tumor induction, we have compared both OTA-induced renal carcinogenicity and DNA adducts in DA and Lewis rats of both sexes. OTA induced renal adenocarcinoma, DA male rats being most responsive, while DA females were resistant. Lewis rats showed an intermediate renal tumor response. OTA also induced malignant transitional cell carcinomas of the bladder in DA male rats only. DNA adducts in the kidney, as judged by the nature of spots and prevalence in OTA-treated animals, were significantly correlated with renal carcinogenicity of OTA, being highest in DA males and lowest in DA females. A parallelism between karyomegalies and tumors of the kidney was observed. In conclusion, our results classify OTA as a genotoxic carcinogen in rats, with sex-specific response controlled in part by drug-metabolizing enzymes that convert OTA into reactive intermediates.

Animals↗
PubMed1998

Ki-ras gene mutations and absence of p53 gene mutations in spontaneous and urethane-induced early lung lesions in CBA/J mice.

Ki-ras and p53 genes are involved in human lung carcinogenesis; however, the role of these genes in experimental lung tumors is not well known. In our study, the CBA/J mouse strain was used to investigate the presence of Ki-ras and p53 alterations in lung carcinogenesis of spontaneous tumors and tumors induced with high and low doses of urethane (ethyl carbamate). To study the presence of these alterations in the early stages of lung carcinogenesis and in very small lung tumors, restriction fragment length polymorphism and single-strand conformation polymorphism analyses were performed on polymerase chain reaction-amplified DNA from microdissected tumoral and normal lung samples. Ki-ras gene mutations in codons 12 and 61 were detected in all types of lung lesions, even in small and preneoplastic lesions, and their incidence increased with progression from lung hyperplasias (18%) to adenomas (75%) and to carcinomas (80%). Urethane exposure, in both high and low doses, increased the incidence of Ki-ras mutations in lung tumors, especially in adenomas. The presence of Ki-ras gene mutations in very small urethane-induced lung tumors and the absence of hyperplasias among the treated-group lesions may indicate that urethane accelerates tumoral progression. No p53 mutations were detected in exons 5-8 in any of the epithelium-derived lung tumors. Only one p53 mutation in exon 5 was found in a spontaneous lymphoma. Therefore, p53 mutations do not seem to cooperate with Ki-ras gene mutations or represent an alternative molecular pathway in murine carcinogenesis.

Adenoma↗
PubMed1998

Sex- and strain-specific expression of cytochrome P450s in ochratoxin A-induced genotoxicity and carcinogenicity in rats.

Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, is implicated in the etiology of Balkan endemic nephropathy (BEN), a chronic disease affecting populations in the Balkans. Patients suffering from Balkan endemic nephropathy, urinary-tract tumors, or both are more frequently extensive metabolizers of debrisoquine than persons unaffected by these conditions. As shown previously (Castegnaro et al., Int J Cancer, 77:70-75, 1998), OTA induction of renal tumors is markedly sex- and strain-specific in Dark Agouti (DA) and Lewis rats, with DA males being most responsive and DA females being resistant; only DA females were phenotyped as slow debrisoquine metabolizers. Formation of OTA-related DNA adducts in the kidney was closely correlated with renal carcinogenicity. To elucidate the critical biotransformation enzymes involved in OTA genotoxicity and carcinogenicity, the expression of cytochrome P450s (CYPs) 1A, 2A, 2B, 2C, 2D, and 3A in the kidney and liver microsomes of untreated and OTA-treated DA and Lewis rats (both sexes) was determined by western blot analysis. Chronic OTA treatment was found to modify CYP expression in kidney and liver. In the animals most susceptible to renal OTA carcinogenicity and DNA adduct formation, the OTA-toxifying isoforms (CYPs 2C11, 1A2, and 3A) were highly expressed in the liver, and little of the OTA-detoxifying isoforms (CYPs 1A1 and 2A) was detected. CYP2D was not expressed in DA rats and therefore is not involved in these phenomena. Our results confirm that the strain- and sex-specific genotoxic response of OTA is controlled, in part, by CYP-mediated metabolic reactions that convert OTA into DNA-reactive intermediates.

Animals↗
PubMed1997

Formation and persistence of the miscoding DNA alkylation product O6-ethylguanine in male germ cells of the hamster.

The cellular parameters which modulate trans germ-line carcinogenesis by DNA-reactive agents have not yet been studied in detail. Therefore, we have measured in this study the formation and repair kinetics of the miscoding alkylation product O6-ethylguanine (O6-EtGua) in nuclear DNA of spermatogonial cells of the Syrian golden hamster (SGH) after exposure to either of two potent N-nitroso carcinogens, ethylnitrosourea (ENU) or diethylnitrosamine (DEN). Both compounds, the spontaneously decomposing ENU, and DEN, which has to be converted by cellular enzymes to the reactive ethyl diazonium ion, induce the same pattern of alkylation products in nuclear DNA. Adduct analyses were performed at the single-cell level by using a quantitative immunocytological assay and anti-(O6-EtGua) monoclonal antibodies. 1.5 h after intraperitoneal application of ENU (100 microg/g body weight) O6-EtGua levels in the nuclear DNA of spermatogonia were similar to those in other cell types of the same hamster. About 30% of the initially formed DNA adducts were still persistent in spermatogonial cells even 4 days after ENU exposure. The presence of O6-EtGua in DNA after exposure to DEN (100 microg/g body weight) implies the capability of hamster spermatogonial cells to convert nitrosamines into DNA-alkylating metabolites. This capability of male germ cells in combination with their limited repair capacity for a critical DNA adduct and their high rate of proliferation may be considered as a major risk factor for genetic effects including carcinogenesis in subsequent generation(s).

Animals↗
PubMed1997

Subcutaneous soft tissue tumours at the site of implanted microchips in mice.

An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected.

Animal Identification Systems↗
PubMed1997

Cystic squamous cell carcinomas in the lungs of Syrian golden hamsters induced by coal oven flue exhaust mixed with pyrolized tar pitch in combination with benzo(a)pyrene.

Among a variety of induced pulmonary tumours, cystic squamous cell carcinomas were observed in five Syrian hamsters that inhaled a mixture of pyrolized tar pitch with coal oven flue exhaust (PCE) and additionally received intratracheal injections of benzo(a)pyrene. The histological appearance of these particular tumours is described, compared to similar tumour types in rats and the susceptibility of both species to inert particles is discussed.

Animals↗
PubMed1997

Incidence and spectrum of spontaneous neoplasms in Han:NMRI mice of both sexes.

Two hundred Han:NMRI mice of both sexes were kept for their natural life-span to obtain information about the spontaneous tumour spectrum of this strain. Neoplasms were seen in 72% of the males and 64% of the females. Lung tumours, Harderian gland tumours, liver and adrenal gland neoplasms were common in males, while ovary tumours and lung tumours were the most frequent neoplasms in females.

Age Factors↗
PubMed1997

Spontaneous myelofibrosis in castrated and ovariectomized NMRI mice.

The histopathological appearance of myelofibrosis of the bone marrow is described in aged castrated males, ovariectomized females and in male and female control NMRI mice. The highest incidence of the lesion was observed in ovariectomized and female control mice where more than 90% of the animals were affected. The presence of myelofibrosis in the bone marrow of ovariectomized females and castrated males indicates that estrogens may not play a major role in the development of the lesion and other hormonal disturbances must also be considered.

Age Factors↗
PubMed1997

Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles.

Cystic keratinizing squamous cell lesions from three inhalation studies (Study A, B, C) and one intratracheal instillation study (Study D) in rats were reclassified and a certain number of lesions examined immunohistochemically for PCNA (proliferating cell nuclear antigen) as a marker of cellular proliferation. The following classification was used: squamous cell metaplasia with marked keratinization, keratinizing cyst, cystic keratinizing epithelioma, cystic keratinizing squamous cell carcinoma, keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma. In study A (inhalation of coal oven exhaust and subcutaneous injection of a high dose of DB (ah)A) 49.3% of rats developed cystic keratinizing squamous cell carcinomas. Inhalation of coal oven exhaust gas together with intratracheal instillation of crocidolite or subcutaneous injection of a low dose DB(ah)A (dibenz(ah)anthracene) resulted in cystic keratinizing squamous cell carcinomas in 23% to 24% of the rats. High incidences of cystic squamous cell carcinomas in the range of 31.9% to 76.4% were observed in rats of Study B1 after a 10-months exposure to tar/pitch condensation aerosol (different B(a)P (benzo(a)pyrene) concentrations) with added carbon black in some groups. After a 20-months exposure period to the same inhalation atmospheres (Study B2) the incidence of squamous cell carcinomas was increased up to 95.8%. Exposure of rats to various concentrations of unfiltered diesel exhaust (Study C) resulted in incidences of cystic keratinizing epitheliomas ranging from 2.5% (2.5 mg/m3) to 10.7% (7.5 mg/m3). Epitheliomas were also observed in 16.2% of carbon black and 16.0% of titanium dioxide exposed rats. Only a few cystic keratinizing squamous cell carcinomas occurred. In the intratrachel instillation study (Study D) increased incidences of cystic keratinizing epitheliomas occurred in rats exposed to native diesel exhaust particles (16.7%), high dose of extracted diesel exhaust particles (14.6%), extracted printex 90-carbon black particles (18.8%), and extracted printex 90-carbon black particles + B(a)P (18.8%). High indicences of cystic keratinizing squamous cell carcinomas were noted in rats that received 15 mg B(a)P (14.6%) or 30 mg B(a)P (72.7%) intratracheally. Immunohistochemical labeling of nuclei with PCNA demonstrated proliferative activity in one or two (and focally more than two) peripheral cell layers of cystic keratinizing epitheliomas and in more than three peripheral cell layers of cystic keratinizing squamous cell carcinomas and keratinizing squamous cell carcinomas. The wall of keratinizing cysts showed no or a weak reaction.

Administration, Inhalation↗
PubMed1997

Paramagnetic metal scavenging by melanin: MR imaging.

PURPOSE: To quantitate the binding of metals to synthetic melanin in vitro, which is believed to be the reason why melanotic melanomas are hyperintense on T1-weighted magnetic resonance (MR) images, and to test whether such binding by natural melanin can be detected in cultured melanoma cells in vivo with MR imaging. MATERIALS AND METHODS: Seven synthetic metallomelanins were prepared and their metal contents and relaxivities determined. Melanotic PC1A and amelanotic B16 melanoma cells were incubated with increasing concentrations of iron. MR images of synthetic melanin and cell phantoms were obtained. RESULTS: The iron-binding capacities and relaxivities of the different synthetic metallomelanins varied considerably, which reflects the heterogeneous structure of melanin and the complexity of its binding of metals. Nevertheless, the MR signal intensities of the synthetic melanin and cell phantoms show marked increases that scale, respectively, with increasing iron content and iron concentration in the incubation medium. CONCLUSION: Melanotic melanomas are hyperintense on T1-weighted images because of paramagnetic metal scavenging. This observation has implications for the interpretation of MR images, the improved detection of melanomas, and the development of imaging marker genes.

Animals↗
PubMed1996

4-Chloro-m-cresol, a potent and specific activator of the skeletal muscle ryanodine receptor.

The aim of the present study was to determine the effects of 4-chloro-m-cresol (4-CmC), a preservative often added to drugs intravenously administered, on the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor. In heavy SR vesicles obtained from rabbit back muscles, 4-CmC stimulated (Ca2+)-activated [3H]ryanodine binding with an EC50 of about 100 microM. In the same concentration range, 4-CmC directly activated the isolated Ca2+ release channel reconstituted into planar lipid bilayers. The sensitivity to 4-CmC was found to be higher when applied to the luminal side of the channel suggesting binding site(s) different from those of nucleotides and caffeine. In skeletal muscle fibre bundles obtained from biopsies of patients susceptible to malignant hyperthermia, a skeletal muscle disease caused by point mutations in the ryanodine receptor, 4-CmC evoked caffeine-like contractures. Contrary to caffeine which induces contractures in millimolar concentrations, the threshold concentration for 4-CmC was 25 microM compared to 75 microM for non-mutated control fibres. Since these data strongly indicate that 4-CmC specifically activates SR Ca2+ release also in intact cell systems, this substance might become a powerful tool to investigate ryanodine receptor-mediated Ca2+ release in muscle and non-muscle tissue.

Animals↗
PubMed1996

Absence of effect of caffeine on the thyroid in the Syrian golden hamster: results of a 90-day study.

Caffeine in drinking water was offered ad lib. to male and female Syrian golden hamsters (Mesocricetus auratus W) for 90 days. Animals were randomly assigned to three dose groups (91.3, 274 and 822 mg/litre) and one control group (filtered tap water), each consisting of 20 male and 20 female animals. In relation to body weight, mean caffeine consumption was higher in females (low dose: 14.7; medium dose: 50.8; high dose: 104.8 mg/kg body weight/day) than males (low dose: 9.0; medium dose: 24.6; high dose: 65.2 mg/kg body weight/day). Caffeine in plasma was measured after 3 days, 3 wk and 3 months of treatment. As expected from calculation of the caffeine intake, mean values were higher in females (low dose: 0.6; medium dose: 3.6; high dose: 7.2 mg/litre) than in males (low dose: 0.4; medium dose: 0.7; high dose: 2.9 mg/litre). After 3 days of treatment, a transient, non-dose-related increase in mean (SEM) tri-iodothyronine (n=10) was found in the medium and high-dose (751+/-23 and 742+/-25 ng/litre, respectively) groups of males compared with that in the controls (610+/-39 ng/litre)(P<0.05). The values measured at later time points (days 24 and 91) were similar in all groups. No treatment-related changes were found in thyroxine (days 3, 24 and 91) and other clinicochemical analytes (day 91), absolute and relative adrenal weight (day 91), gross pathology and thyroid histopathology (day 91). In conclusion, no signs of thyroid toxicity of caffeine were observed in the Syrian golden hamster.

Administration, Oral↗
PubMed1996

Proteolytic processing of class IV chitinase in the compatible interaction of bean roots with Fusarium solani.

Three chitinase isoenzymes, PvChiE, PvChiF, and PvChiG (molecular masses 29, 28, 27 kD, respectively), were purified from bean (Phaseolus vulgaris L. cv Saxa) roots infected with the fungal pathogen Fusarium solani f. sp. phaseoli, and their amino acid sequence was partially determined. All sequences from all three isoenzymes exactly matched deduced amino acid sequences of the bean class IV chitinase PvChi4, formerly called PR4. The N terminus of PvChif mapped to the hinge region, and the N terminus of PvChiG mapped to the catalytic domain of PvChi4. The N terminus of PvChiE was blocked. The appearance of PvChiE, PvChiF, and PvChiG correlated with an increase in protease activity in infected roots, and they could be generated in vitro by mixing extracts with high protease activity with extracts containing high amounts of PvChi4. Extracts from infected roots prepared in the presence of protease inhibitors also contained the processed forms of PvChi4, indicating that processing occurred in planta and not as an artifact of extraction. Processing of PvChi4 was not detected in incompatible interactions with a nonhost strain of F. solani and in symbiotic interactions with Glomus mosseae, and thus may be important only in compatible interactions with F. solani.

Amino Acid Sequence↗
PubMed1996

[Lymph node diagnosis with imaging methods. An overview with special reference to recent developments in the area of MR contrast media].

The main problem in current lymph node imaging is the lack of reliable criteria for differential diagnosis between benign and malignant nodes, the main criterion being size. To reliably opacify all lymph nodes in the body, an intravenous contrast agent is therefore necessary. Two new contrast agents for MRI seem promising: lymphotropic iron oxides and Gadolinium DTPA-PGM. After intravenous administration these agents accumulate in phagocytic cells of normal lymph nodes but are excluded from nodes in which phagocytic activity is replaced. While iron oxides are already in clinical studies, GD-DTPA-PGM is in preclinical studies. Both agents seem to significantly improve the differential diagnosis between benign and malignant lymph nodes irrespective of size.

Contrast Media↗