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Biomedical subjects

U Mohr

Publications and source records attributed to U Mohr.

At least 19 recordsLinked to original sources
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

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↗
PubMed1995

Increased risk of cancer in the descendants of Syrian hamsters exposed prenatally to diethylnitrosamine (DEN).

Transmission of site-specific tumorigenicity (papillomas in larynx and trachea) of diethylnitrosamine (DEN) to the 2 subsequent generations (F1 and F2) was studied using an outbred strain (Han:AURA) of pregnant Syrian golden hamsters (P generation), which were treated i.p. with 10 mg/kg b.w. of DEN on day 12, 13 or 14 of gestation. Laryngotracheal papillomas were induced by DEN in the P and F1 generations only, while these tumours did not occur in the F2 generation. Spontaneously occurring tumours, including uterine adenocarcinomas, lymphomas, and laryngotracheal neuro-endocrine cell tumours, were observed at higher incidences among the F2 animals derived from the P generation hamsters treated with DEN only on day 13 or 14 of gestation. In the same animals, the ratio of malignant to benign tumours was considerably higher than in controls. In addition, the F2 hamsters derived from the DEN-treated P generation showed more frequent multiple organ involvement in tumorigenesis than the F2 controls. Several uncommon malignant tumours were detected in the F2 offspring, possibly the result of damage caused to germ cells by the prenatal exposure of F1 Syrian hamsters to DEN.

Animals↗
PubMed1995

Phenyl isocyanate-induced asthma in rats following a 2-week exposure period.

This study was conducted to assess the toxic effects of repeated inhalation exposures to phenyl isocyanate vapor in male Wistar rats. Rats were exposed to design concentrations of 0, 1, 4, 7, or 10 mg/m3 phenyl isocyanate air for 2 weeks (6 hr/day, 5 days/week). The rats were assessed for normal toxicologic parameters, and pulmonary function tests, blood gas measurements, and analysis of bronchoalveolar lavage fluid (BALF) parameters were utilized shortly after exposures as well as 2 months postexposure. The results indicated that rats exposed to 7 and 10 mg/m3 experienced decreased body weights, hypoactivity, hypothermia, signs of respiratory tract irritation, delayed onset of mortality, and changes in organ weights. In addition, pulmonary function tests demonstrated decreased forced expiratory flow rates and quasistatic lung compliance. Arterial blood gases showed an arterial hypoxemia and changes consistent with a pronounced venous-admixture-like perfusion, suggesting severe mismatch of the ventilation/perfusion relationship. Delayed onset of mortality appeared to be associated with respiratory acidosis and hypoxemia. Biochemical and cellular components in BALF complemented the results of the functional alterations. Remarkable changes were indicated by increased activities of the BALF parameters, gamma-GPT, protein, and sialic acid. Histopathological findings provided evidence of increased secretory cell activity and a concentration-dependent increase in goblet cell hyperplasia at concentrations of 4 mg/m3 and above. In rats exposed to 7 mg/m3 further findings consisted of intraluminal inflammation of airways, hypertrophia of bronchial smooth muscle, epithelial desquamation, and eosinophilia of the airways. A complete regression of morphological lesions was not found in the animals exposed to 4 mg/m3 and above at the 2-month postexposure time period. In conclusion, the damage to the airways comprise most of the features characteristic of chronic airway inflammation or asthma.

Administration, Inhalation↗
PubMed1995

Chemically induced pulmonary mucoepidermoid carcinoma in a female Wistar rat.

A case of a mucoepidermoid carcinoma, conventionally classified as an adenosquamous carcinoma, is described. The tumour bearing rat was exposed to a mixture of a pyrolized pitch condensate rich in polycyclic aromatic hydrocarbons and carbon black particles by inhalation for 10 months. The neoplasm was examined by conventional histopathologic procedures and by immunohistochemical detection of intermediate filaments. Morphologically, the tumour consisted of two components. The centre of the neoplasm was predominantly of adenocarcinomatous tissue and this was surrounded by keratinized squamous epithelium. The predominantly adenocarcinomatous component had a characteristic structural pattern consisting of one or a few layers of squamous epithelium covered by a continuous layer of mature goblet cells. The flattened cells were recognizable as squamous cells on the light microscopic level only after immunohistochemical staining with cytokeratin antibodies. Goblet cells and extracellular mucin were intensely positive for the PAS-reagent. This mucoepidermoid carcinoma in the rat was morphologically similar to those described in man. It is still unclear whether pulmonary mucoepidermoid carcinomas of humans originate from the bronchial epithelium or bronchial glands. It is most probable that the mucoepidermoid carcinoma of a rat described in this communication occurred by metaplasia in a carcinoma of bronchiolo-alveolar origin.

Animals↗
PubMed1995

Formation of O6-ethylguanine in spermatogonial DNA of adult Syrian golden hamster by intraperitoneal injection of diethylnitrosamine.

17-Week-old Syrian golden hamsters received a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 100 mg/kg body weight. The DNA alkylation product O6-ethylguanine was formed in the spermatogonia. The data demonstrate that DEN can pass the blood-testis barrier and be metabolized in the spermatogonia to yield an alkylating derivative or that externally activated metabolites themselves can pass the barrier.

Animals↗
PubMed1995

A histopathological study on alterations in DMBA-induced mammary carcinogenesis in rats with 50 Hz, 100 muT magnetic field exposure.

Several epidemiological studies have indicated that residential or occupational exposure to 50 or 60 Hz magnetic fields (MF) may increase the risk of breast cancer, possibly by suppression of pineal production of the oncostatic hormone melatonin. In view of the methodological problems of epidemiological studies on MF exposure and cancer risk, laboratory studies are needed to determine whether 50/60 Hz exposure can initiate, promote or copromote mammary cancer. In the present study, 216 female Sprague-Dawley rats were divided into four groups. Two of the groups (with 99 animals each) received oral applications of 7,12-dimethylbenz[a]anthracene (DMBA) and were either sham-exposed or exposed in a 50 Hz, 100 muT MF for 24 h/day 7 days/week for a period of 91 days. The other two groups (nine animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. At the end of the 3 month period of MF exposure, all rats were used for histopathological diagnosis of lesions. At the time of necropsy, significantly more MF-exposed DMBA-treated rats exhibited macroscopically visible mammary tumours than DMBA-treated controls. Furthermore, the size of mammary tumours was significantly larger in MF-exposed rats. Histopathological examination of the mammary gland showed that the number of neoplastic and non-neoplastic lesions did not significantly differ between groups, indicating that MF exposure had not altered the incidence of mammary lesions but had only accelerated tumour growth, consistent with a co-promoting effect. In the MF-exposed group, significantly more rats exhibited malignant mammary tumours than in controls, indicating that MF exposure had affected the progression of DMBA-induced lesions. The number of metastases of mammary tumours or of primary lesions in other organs in response to DMBA was not affected by MF exposure. In rats without DMBA application, no non-neoplastic or neoplastic lesions were determined. The data demonstrate that long-term exposure of DMBA-treated female rats promotes the growth and progression of mammary tumours, while tumour incidence is not affected, at least under the experimental conditions of the present study. The data thus add to the accumulating evidence that MF exposure exerts tumour co-promoting effects.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Neoplastic lung lesions in rat after chronic exposure to crystalline silica.

Groups of 100 SPF Fischer-344 rats were exposed 6 h a day, 5 d a week for 24 months to crystalline silica (1 mg center dot m-3, DQ 12 quartz) or titanium dioxide (5 mg center dot m-3) or air only. The animals were kept without further exposure for an additional 1.5 months. In the group exposed to crystalline silica a significantly increased incidence of 20 primary lung tumors was observed among 19 animals. The distribution of tumor types consisted of 3 adenomas, 11 adenocarcinomas, 4 benign cystic keratinizing squamous-cell tumors, 1 adenosquamous carcinoma, and 1 squamous-cell carcinoma. There were also 13 nodular hyperplasia lesions, which were interpreted to be borderline cases of adenomas. Approximately half of the adenoid tumors and all of the nodular hyperplasia lesions were characterized by moderate central fibrosis. The principal nonneoplastic findings in the silica-exposed group were lipoproteinosis, inflammation, epithelial hyperplasia, and fibrosis. The results can be considered significant due to the increased lung tumor incidence at a relatively low exposure level.

Administration, Inhalation↗
PubMed1994

Assessment of respiratory hypersensitivity in guinea-pigs sensitized to diphenylmethane-4,4'-diisocyanate (MDI) and challenged with MDI, acetylcholine or MDI-albumin conjugate.

Guinea-pigs were sensitized to monomeric diphenylmethane-4,4'-diisocyanate (MDI) by two intradermal injections (1-10% MDI, injection volumes of 50-100 microliters/day, on days 0, 2 and 4) or by a single brief high-concentration inhalation exposure (135 or 360 mg/m3, 15 min). Starting with day 21 following sensitization the animals were subjected to inhalation-challenge exposures (30 min) with non-irritating and irritating concentrations of the hapten (MDI). MDI-challenge concentrations ranged from 3.4 +/- 0.9 to 60 +/- 14.3 mg/m3 air. In some groups guinea-pigs were also challenged with acetylcholine (ACh) aerosol or the MDI-guinea pig serum albumin (GPSA) conjugate. Experimental findings indicated that from intradermally sensitized animals an immediate onset respiratory hypersensitivity response could only be elicited with concentrations exceeding the irritant threshold concentration for MDI, i.e. with concentrations greater than approximately 20 mg/m3 air. Guinea-pigs challenged with the MDI-GPSA conjugate (35.3 +/- 2.8 mg/m3 air) also experienced a weak immediate-type respiratory hypersensitivity response. An increased non-specific airway hyper-responsiveness following ACh-challenge was only observed from animals challenged with approximately 60 mg MDI/m3 air. The histopathological evaluation of lungs and lung-associated lymph nodes revealed an association of the increase in eosinophilic granulocytes and concentration of MDI used for challenge exposures. It appeared, in most instances, that this influx was more pronounced in animals sensitized with MDI as compared with concurrent controls challenged with the same MDI concentration. Guinea-pigs sensitized by a single 15-min inhalation exposure to either 135 or 360 mg MDI/m3 air were challenged sequentially with 12 +/- 2.1 mg MDI/m3 air, ACh and MDI-GPSA conjugate. Following the inhalation-induction, an airway hyper-responsiveness was elicited both after challenge with MDI and with the MDI-GPSA conjugate. The influx of eosinophilic granulocytes was more pronounced from animals sensitized by inhalation when compared with guinea-pigs sensitized intradermally and challenged with the same concentration of MDI. Thus, experimental findings suggest that elicitation of respiratory hypersensitivity is concentration-dependent and that challenge concentrations should slightly exceed the threshold concentration for irritation (approximately 20 mg/m3). Sensitization by inhalation increased the susceptibility to irritant stimuli and thus confounds the selection of the most appropriate concentration for challenge. However, the combined assessment of specific pathologic features such as airway eosinophilia and the evaluation of several breathing parameters during hapten- and ACh-challenge make it easier to distinguish effects caused by irritation and respiratory hypersensitivity.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1994

A single point mutation results in A allele-specific exon skipping in the bovine alpha s1-casein mRNA.

Bovine alpha s1-casein (alpha s1-CN) allele A is found in low allelic frequencies among different cattle breeds and is known to be characterized by the deletion of amino-acid residues 14 to 26 of the mature protein (as defined via the most common allele B), and a corresponding deletion of 39 bp from its cDNA. Based upon the genomic sequence of bovine alpha s1-CN [Koczan et al., Nucleic Acids Res. 19 (1991) 5591-5596], this allelic deviation can be interpreted as an absence of exon 4 from the A allele mRNA and protein product. We demonstrate that this allelic aberration is not caused by a genomic deletion across the exon-4 DNA, but is correlated with a single point mutation at position +6 in the splice donor sequence distal of exon 4, which results in upstream exon skipping during the serial splice reactions of the A allele alpha s1-CN pre-mRNA. The A-allele-specific mutation at position +6 is able to interrupt the perfect complementarity of the intron-4 splice donor signal (positions one to eight) with U1-snRNA, which may then no longer be able to compensate for a rather weak exon-4 upstream splice acceptor sequence in facilitating the initial binding of U2 auxiliary factor/65-kDa (U2AF65) to that polypyrimidine tract. This interpretation of the exon skipping mechanism in alpha s1-CN allele A is in agreement with similar results obtained [Hoffmann and Grabowski, Genes Dev. 6 (1992) 2554-2568] in an analysis of the rat preprotachykinin-encoding gene and in vitro experiments.

Alleles↗
PubMed1994

Spectrum of glandular differentiation in experimental carcinoma of the esophagus induced by 2,6-dimethylnitrosomorpholine under the influence of esophagojejunostomy.

To investigate the influence of reflux esophagitis (RE) on the glandular differentiation of carcinomas of the esophagus induced by 2,6-dimethylnitrosomorpholine (2,6-DMNM), a study was carried out using 4 experimental groups and 2 control groups of 8-week-old Sprague-Dawley rats, each consisting of 20 males and 20 females. An esophagojejunostomy (EJ) with gastric preservation was performed in two groups of animals. Fifteen days thereafter the potent esophagotropic carcinogen 2,6-DMNM was subcutaneously injected, once a week for life, at doses of 1/100 and 1/10 of the 50% lethal dose in each group respectively. The result was a spectrum of carcinomatous tumors mainly developing in the lower half of the esophagus, which were thoroughly investigated by serial sectioning, staining for mucins, and in selected cases by electron microscopy. They were classified as follows: 16 pure squamous cell carcinomas (SCC), 5 SCC with focal mucous or glandular differentiation (FGD), 11 pure adenocarcinomas (ADC), and 12 ADC with areas of squamous cell differentiation (SCD). By contrast, in 2 similar experimental groups in which the previous EJ was not performed, 15 animals showed SCC of the pure type, without evidence of mucous or glandular differentiation. No tumors were observed in the two control groups without carcinogen treatment. Of these, the group that underwent EJ showed reflux esophagitis. In conclusion, the tumors of the esophagus induced by 2,6 DMNM under the influence of EJ are not only pure ADC and pure SCC, as we have previously reported, but also intermediate tumors showing either SCC with focal mucous or glandular differentiation (SCC + FGD) or ADC with areas of squamous cell differentiation (ADC + SCD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗