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Biomedical subjects

H Ernst

Publications and source records attributed to H Ernst.

At least 109 records · Page 6Linked to original sources
PubMed1988

Synthesis of the major inner capsid protein VP6 of the human rotavirus Wa in Escherichia coli.

The gene for the major inner capsid protein VP6 of human rotavirus strain Wa has been cloned and placed into a bacterial expression vector under the control of the inducible hybrid trp-lac (tac) promoter. Recombinant VP6 was produced at low levels in a cell-free Escherichia coli transcription-translation system programmed with this expression plasmid. The yield of VP6 synthesized in the extract could be increased several-fold by introduction of point mutations upstream and downstream from the start codon. Upon induction with IPTG, E. coli JM105 cells harboring the mutated expression plasmid produced VP6 as shown by immunoblotting of proteins from bacterial lysates with anti-Wa antiserum. Recombinant VP6 appeared to inhibit the growth of E. coli and did not accumulate in the cells to high levels. Conformational analysis with a monoclonal antibody suggested that bacterially produced VP6 adopted an oligomeric structure characteristic for native VP6.

Amino Acid Sequence↗
PubMed1988

Myocardial effects of calcium cyclamate in the BIO F1D Alexander Syrian golden hamster.

In a subchronic 90-day oral toxicity study, 5 groups (20 males, 20 females each) of F2-descendants of BIO F1D Alexander hamsters received 0, 275, 550, 1,100 and 2,200 mg/kg b.w./day doses, respectively, of calcium cyclamate in the drinking water. These doses caused no adverse health effects in any treated animal and the multifocal myocardial calcifications, detectable at a 100% incidence in the male and female control hamsters (20 males, 20 females), were not exacerbated by the sweetener. Instead, the myocardial lesions exhibited a striking negative dose-response relationship with a 0% incidence in the males and a 5% incidence in the female hamsters of the highest dose group.

Animals↗
PubMed1988

A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus.

Two skeletal myosin light chains, MLC1 and MLC3, are generated from a single gene by transcription from two different promoters and alternate splicing of the pre-mRNAs. To define DNA sequences involved in MLC transcriptional control, we constructed a series of plasmid vectors in which segments of the rat MLC locus were linked to a CAT gene and assayed for expression in muscle and nonmuscle cells. Whereas sequences proximal to the two MLC promoters do not appear to contain tissue-specific regulatory elements, a 0.9-kb DNA segment, located greater than 24 kb downstream of the MLC1 promoter, dramatically increases CAT gene expression in differentiated myotubes but not in undifferentiated myoblasts or nonmuscle cells. The ability of this segment to activate gene expression to high levels, in a distance-, promoter-, position-, and orientation-independent way, defines it as a strong muscle-specific enhancer element.

Animals↗
PubMed1987

Contribution of polycyclic aromatic hydrocarbons and nitro-derivatives to the carcinogenic impact of diesel engine exhaust condensate evaluated by implantation into the lungs of rats.

Diesel exhaust condensate was separated by a liquid-liquid distribution into a hydrophilic (I; about 25% by weight of the total condensate) and a hydrophobic part (II; about 75%-wt.). To evaluate the carcinogenicity, the proportionately dosed fractions have been implanted into the lungs of Osborne Mendel rats and compared with several doses of benzo[a]pyrene and the vehicle, a mixture of trioctanoin plus beeswax. Only the hydrophobic part which contained polycyclic aromatic compounds (PAC) resulted in 5 malignant tumors in a group of 35 animals. In addition, the hydrophobic part was separated by column chromatography on Sephadex LH 20 and subsequently on silica gel into several fractions, such as non-aromatic compounds plus PAC with 2 and 3 rings (IIa; 72%-wt of the total condensate), polycyclic aromatic compounds (PAH) with 4 and more rings (IIb; 0.8%-wt), polar PAC (IIc; 1.1%-wt) and nitro-PAH (IId; 0.7%-wt). PAH consisting of 4 and more rings (IIb) were found to be the most potent subfraction and provoked when proportionately dosed 6 carcinomas in a group of 35 rats. Only a low contribution to the carcinogenicity was observed by the subfraction of nitro-PAH (IId) which produced 1 carcinoma/35 rats. The polar PAC (IIc) and the fraction of non-aromatics plus PAC with 2 and 3 rings (IIa), although the main subfraction (72%-wt of the total condensate) did not provoke any tumors. The reconstitution of all hydrophobic subfractions (IIa-d) resulted in the same carcinogenic potency as the unfractionated hydrophobics (II), provoking 7 carcinoma in 35 rats. It may be concluded from these findings that most of the carcinogenicity of diesel exhaust originates from the PAH consisting of 4 or more rings.

Animals↗
PubMed1987

Failure to transmit diethylnitrosamine tumorigenicity from transplacentally exposed F1 generation Syrian hamsters to the respiratory tract of F2 and F3 generations.

A multigeneration study with four successive generations of Syrian hamsters was conducted to determine whether a single s.c. injection of different doses of diethylnitrosamine (DEN) (1.25, 2.5, 5, 10, and 20 mg/kg body weight) on day 15 of pregnancy induces respiratory tract tumors not only in the treated P generation mothers and their F1 progeny but also in F2 and F3 generations. In this study, the P generation mothers only were given a single injection of DEN during the period of gestation. Fifty-six % of the 36 DEN-treated mothers and 52% of their F1 generation offspring (total, 233 animals) developed neoplasms in the respiratory tract. A single respiratory tract tumor was found in one DEN-unexposed F1 generation control hamster as well as in one F2 generation animal (total, 209 animals) descended from DEN-exposed P generation. Both tumors were considered to have arisen spontaneously. No respiratory tract tumors were observed in the F3 generation (total, 160 animals) descended from a DEN-exposed P generation. Thus our results indicate that the vertical transmission of the tumorigenic effect of DEN in Syrian hamsters is limited to one generation and does not persist in the F2 and F3 generations.

Animals↗
PubMed1987

Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA.

A clone encoding the alpha-subunit of eukaryotic initiation factor 2 (eIF-2 alpha) was isolated from a lambda gt11 expression library of rat brain cDNAs. The fusion protein expressed by the recombinant phage reacts with eIF-2 alpha antiserum except when the serum is preadsorbed with pure eIF-2. The translation of hybrid-selected HeLa cell mRNA produces two proteins which are indistinguishable from authentic HeLa eIF-2 alpha and its phosphorylated form when analyzed by electrophoresis in two-dimensional isoelectrofocusing/sodium dodecyl sulfate-polyacrylamide gels and by partial protease digestion. HeLa cell eIF-2 alpha mRNA migrates as a single band of about 1600 nucleotides. The rat cDNA insert was sequenced, and the region coding for eIF-2 alpha was identified. A human cDNA clone was obtained by hybridization screening with the rat cDNA, and its sequence was determined also. Both rat and human eIF-2 alpha proteins comprise 315 amino acids (36.1 kDa) and differ by only three amino acids. The eIF-2 alpha mRNA is found exclusively in polysomes containing 10 or more ribosomes in exponentially growing HeLa cells. In serum-depleted cells which synthesize eIF-2 and bulk protein more slowly than exponential cells, the level of eIF-2 alpha mRNA is not changed, the average polysome size is reduced to 7, and little or no eIF-2 alpha mRNA is detected in the ribonucleoprotein fraction. These results are consistent with the view that eIF-2 alpha mRNA translation is very efficient compared to other mRNAs in the cell.

Amino Acid Sequence↗
PubMed1987

Chemotherapy of thyroid carcinoma.

On the basis of 8 patients of our own and a survey of the literature, the present state of chemotherapy of thyroid carcinoma is discussed. Chemotherapy is only indicated in cases of progressing disease after exhaustion of all conventional therapies. Only in cases of undifferentiated giant- or spindle-cell thyroid carcinomas can chemotherapy following conventional treatment be approved right from the beginning. The three most widely applied cytostatics are adriamycin, bleomycin and cis-platinum, and it seems that adriamycin monotherapy, is superior to all other therapies, even combinations, except probably for the undifferentiated thyroid carcinoma. In addition to the patient's general condition, a sufficiently high single dose of adriamycin, which should be increased in case of nonresponse, appears to be essential for the therapeutical effect. Due to its low toxicity, especially cardiotoxicity, 4'-epi-adriamycin, which, while being almost as effective, can be applied at higher doses and over longer periods, seems to be promising. Approximately 1/3 of thyroid carcinomas respond to adriamycin monotherapy, the response rate probably being highest for medullary types and lowest for undifferentiated thyroid carcinomas. The highest response is observed in the case of pulmonary metastases, followed by bone metastases and local tumor growth. If thyroid carcinomas respond to chemotherapy--even by no-change behavior only--a prolongation of median survival rates from 3-5 months (nonresponders) to 15-20 months (responders) can be achieved.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Induction of malignant peripheral nerve sheath tumors in European hamsters with 1,1-dimethylhydrazine (UDMH).

A rate of up to 43% of malignant peripheral nerve sheath tumors (PNST) was induced in European hamsters (EH) after weekly s.c. administration of 1,1-dimethylhydrazine (UDMH). The overall neoplastic response in the treated EH was also elevated as compared to the untreated controls. Histologically, the malignant PNST were neurofibrosarcomas and melanotic as well as unpigmented schwannomas. The occurrence of melanotic schwannomas is briefly discussed with regard to the histogenesis of this rare tumor type.

Animals↗
PubMed1987

Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats.

About 50 dusts were examined on their carcinogenicity in rats mainly after intraperitoneal injection and some after intratracheal instillation. In the i.p. test, very low doses between 0.05 and 0.5 mg asbestos led to tumour incidences of about 20 to 80%. Polyvinyl-pyridine-N-oxide prolonged the tumour latency after injection of actinolite. 60 mg attapulgite from three sources with short fibre lengths were not shown to be carcinogenic but an attapulgite sample with longer fibres had a moderate effect. Relatively thick rock and ceramic fibres (median greater than 1 micron) induced tumours, but slag and wollastonite fibres did not, probably because of their better solubility. Intratracheal instillations of glass microfibres (20 X 0.5 mg) led to lung tumours in 5 of 34 rats (0 in control). The carcinogenic potency of an inorganic fibre depends on its size and persistency, and possibly also on other properties, especially on the surface. Nickel powder, nickel oxide, nickel subsulfide and cadmium sulfide were all found to be carcinogenic in the two tests. Cadmium chloride and cadmium oxide could only be administered in very low doses because of their high acute toxicity. A high amount of magnetite (15 X 15 mg i.tr.) led to an unexpected lung tumour incidence of 69%. The i.p. test in rats proved to be very sensitive for detecting the carcinogenic potency of non-acute toxic natural and man-made mineral dusts as well as metal compounds. This means that, if a high dose of one of these dusts does not induce tumours in this test, no suspicion of carcinogenic potency can be substantiated.

Animals↗
PubMed1987

Tumorigenicity study in Syrian hamsters fed areca nut together with nitrite.

In order to evaluate the effect of concurrent administration of areca nut and sodium nitrite, a long-term feeding study was conducted with 120 Syrian hamsters. The animals were divided into four treatment groups, each consisting of 15 males and 15 females, and received 2 g/kg diet of sodium nitrite (group I), 20 g/kg diet of powdered areca nut (group II), 2 g/kg diet of sodium nitrite plus 20 g/kg diet of areca nut (group III) or powdered diet only (group IV) throughout their lifetime. Urine samples from all groups were analysed for N-nitrosonipecotic acid (NNIP), a major urinary metabolite of areca-nut-derived nitrosamines. NNIP was only detected in the urine of hamsters fed nitrite plus areca nut (concentration: 1.9 +/- 0.9 ng/ml urine), indicating that areca nut alkaloids underwent in vivo nitrosation to form areca-nut-specific nitrosamines. The total tumour response was not significantly elevated in groups II and III. Hamsters of group III had a markedly, but also insignificantly higher frequency of malignant tumours than those of the other groups, with a statistically significant increase in malignant lymphomas in the males. Although limited by the low number of animals per group, these results indicate that exposure to nitrite together with areca nut constituents appears to enhance the risk of developing malignancies.

Animals↗
PubMed1986

Chronic effects on the respiratory tract of hamsters, mice and rats after long-term inhalation of high concentrations of filtered and unfiltered diesel engine emissions.

A long-term exposure study with hamsters, mice and rats inhaling filtered and unfiltered diesel engine exhaust was carried out to investigate effects of chronic toxicity and, predominantly, carcinogenicity in the respiratory tract. The level of diesel exhaust in the exposure chambers corresponded to a concentration close to 4 mg m-3 in the unfiltered diesel exhaust. Satellite groups of animals were additionally treated with BaP, DBahA or nitrosamines in order to check for syncarcinogenic effects. In hamsters and rats, alveolar lung clearance and mechanical lung function tests as well as biochemical and cytological measurements in lung lavage fluids showed significant changes only after exposure to unfiltered diesel exhaust and, predominantly, in rats. No lung tumors were found in hamsters. Spontaneous tumor rates occurred in mice and both types of diesel exhaust increased the incidence of adenocarcinomas in the lungs. In rats, only the unfiltered diesel exhaust caused a lung tumor incidence. It amounted to 16% with no tumors in the controls. The heavy load of particulate matter in the lungs of rats was caused by an exposure-related impairment of the alveolar lung clearance and may have been instrumental in the induction of squamous cell tumors. However, an effect of particle-associated PAH cannot be excluded. Syncarcinogenic effects of diesel exhaust after initial carcinogen treatment were found only in the respiratory tract of rats.

Animals↗
PubMed1986

Tuberous sclerosis with angiomyolipoma and metastasized hypernephroma.

This is a case report of a patient with angiomyolipomas in both kidneys which was confirmed in one kidney by open biopsy and histologic examination. Two years after diagnosis of the angiomyolipomatosis, the patient died of metastatic hypernephromas of both kidneys. The tumors had affected the kidneys almost totally; only in the right kidney were remnants of the angiomyolipoma still recognizable. A review of the literature shows how rare is the simultaneous occurrence of angiomyolipomas and hypernephroma.

Adult↗