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Biomedical subjects

W Troll

Publications and source records attributed to W Troll.

At least 73 records · Page 4Linked to original sources
PubMed1978

Prevention of normal mouse uterine maturation by antipain and elastatinal: suppression of peroxidase activity.

We had shown previously that the serine protease inhibitors, antipain and leupeptin, restrict uterine DNA snythesis and function in adult mice. The present study is an extension, focusing on the perimaturation period. The protease inhibitors, antipain and elastatinal were tested and the end points were uterine development and peroxidase activity in the uterus. Four week old mice were treated with eigher antipain (3 mg), elastatinal (5 mg) or vehicle (control) twice daily for 3 weeks. The uteri were excised, weighed and homogenized. Subcellular fractions were prepared by differential centrifugation. Each fraction was analyzed for peroxidase activity. The weights and protein content of uteri from control mice averaged greater than twice those in either antipain or elastatinal treated mice (p less than 0.001). Peroxidase activity was sharply curtailed by both inhibitors, antipain being more active than elastatinal. Mechanistically, antipain and elastatinal may act directly on the uterus either by inhibiting key enzymes or by preventing the formation of macromolecules crucial to normal function. Alternatively, the protease inhibitors may interfere with ovarian function, thereby restricting normal uterine development.

Animals↗
PubMed1978

Effect of phorbol myristate acetate on cyclic nucleotide levels in mouse epidermis.

Basal levels of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate were determined in mouse epidermis in vivo after a single topical treatment with the tumor promoter phorbol myristate acetate. No changes in cyclic adenosine 3':5'-monophosphate levels were found from 0 to 72 hr after treatment. A twofold increase in cyclic guanosine 3':5'-monophosphate was found 36 hr after treatment. This increase had subsided by 72 hr. The effect of phorbol myristate acetate on DNA, RNA, and protein synthesis in the epidermis of Ha/ICR mice was also measured.

Animals↗
PubMed1977

Production paroxysmal nocturnal hemoglobinuria-like red blood cells by tea.

Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria-like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement-dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement-dependent hemolysis in teaincubated red cells was inhibited by antisera to C3 and C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement-dependent hemolysis of red cells incubated with tea. Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.

Acetylcholinesterase↗
PubMed1977

A protease inhibitor blocks SOS functions in Escherichia coli: antipain prevents lambda repressor inactivation, ultraviolet mutagenesis, and filamentous growth.

Inhibition of DNA synthesis in E. coli by treatment with carcinogenic and mutagenic agents results in the coordinate expression of a group of diverse functions (SOS functions) including lambda prophage induction, filamentous growth, and an error-prone DNA repair activity (SOS repair) believed to be responsible for ultraviolet mutagenesis. It has been proposed that this SOS induction proceeds via irreversible proteolytic inactivation of repressor(s) for SOS functions. To test this hypothesis, we investigated the effect of a protease inhibitor, antipain [(1-carboxy-2-phenylethyl)carbamoyl-L-arginyl-L-valylargininal], on SOS induction. We found that 0.5 mM antipain (which has no effect on cell growth, overall RNA and protein synthesis, or induction of beta-galactosidase) drastically decreases mutagenesis. Antipain also blocks expression of thermally induced mutator activity (another manifestation of SOS repair) and filamentous growth in a tif-1 mutant that expresses SOS functions at 42 degrees without inhibition of DNA synthesis or detectable DNA damage. Furthermore, antipain inhibits thermal induction of lambda prophage in the tif-1 mutant without affecting the kinetics of thermal induction of lambdacI857 prophage. This lambda mutant codes a temperature-sensitive repressor that is directly destroyed by heat and does not require the SOS induction pathway for inactivation at 42 degrees. From our results we conclude that antipain inhibits lambda prophage induction by blocking proteolytic inactivation of lambda repressor and that it inhibits the induction or expression of SOS repair and filamentous growth. Our results suggest a role for proteolytic cleavage in the regulation of SOS functions.

Carbamates↗
PubMed1977

Antipain and leupeptin restrict uterine DNA synthesis and function in mice.

As in rats, administration of estradiol to ovariectomized mice results in a trypsin-like proteolytic activity in the uterus. After fractionation of uteri from estradiol-treated ovariectomized mice the protease activity was found in the 12,000 times g pellet and the nucleus, appearing first in the former. Further fractionation of the pellet by discontinuous sucrose gradient centrigugation resulted in sedimentation of the protease with 5'-nucleotidase, a marker enzyme for plasma membrane and separate from mitochondrial and lysosomal enzyme markers. Solubilization was best accomplished by lysis at 37 degrees. The soluble enzyme from mouse uterus had optimal activity at about 43 degrees and pH 8.3 and was inhibited by diisopropylfluorophosphate, tosylarginine methyl ester, antipain, and leupeptin, but not by soybean trypsin inhibitor. Inhibition in vitro by antipain and leupeptin, two low molecular weight peptides, prompted the study of their effect in vivo on the mouse uterus. After intact, cycling female mice received subcutaneous injections of antipain and leupeptin for 16 days, their uteri showed significant diminution in weight and total DNA when compared to untreated controls. Fertility rates were also diminished. Trypsin-like protease activity may be essential to normal uterine metabolism and function.

Animals↗
PubMed1977

Effects of arsenite on DNA repair in Escherichia coli.

Since environmental exposure to arsenicals has been correlated with a high skin cancer risk among populations exposed to sunlight, it is possible that arsenicals might interfere with the repair of damage to DNA (mostly thymine dimers) resulting from the ultraviolet rays in sunlight. To test this hypothesis, strains of E. coli, differing from each other only in one or more repair functions, were exposed to UV light and then plated in the presence or absence of sodium arsenite. Survival after irradiation of wild type E. coli (WP(2)) was significantly decreased by 0.5mM arsenite. This effect was also seen in strains which are unable to carry out excision repair, suggesting that arsenite inhibits one or more steps in the post-replication repair pathways. This is confirmed by the finding that arsenite has no effect on the post-irradiation survival of a recA mutant, which does not carry out post-replication repair. Mutagenesis after ultraviolet irradiation depends on the rec(+) and lex(+) genes. Arsenite decreases mutagenesis in strains containing these genes. In order to determine its mechanism of action, dose-response relationships of arsenite on a number of cellular functions were carried out. The most sensitive cellular functions found were the induction of beta-galactosidase and the synthesis of RNA. Since error-prone repair in E. coli is an inducible process, the inhibition of mutagenesis after UV irradiation may be the result of inhibition of messenger RNA synthesis.

Animals↗
PubMed1977

High turnover rate of transfer RNA in tumor tissue.

Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g., N2,N2-dimethylguanosine, can originate only from transfer RNA (tRNA). Until recently, it could not be ascertained whether the high level of excretion of such compounds is due to cell death or specific tRNA turnover. However, an approach to this problem became feasible, with beta-aminoisobutyric acid as a probe. This compound is a terminal degradation product of thymine which is present in both DNA and tRNA. Since the pathway of synthesis of thymine is different in the two macromolecules, it and its end product, beta-aminoisobutyric acid can be differentially labeled with [14C]formate and [3H3]methylmethionine as precursors. Therefore the ratio of the two labels in the excreted beta-aminoisobutyric acid is a measure of the macromolecular origin of the degradation product. We have found from such analysis that tRNA's are not homogeneous in their turnover rate. There is a subpopulation that turns over much faster than the rest. The turnover rate of a subpopulation of tRNA's in tumor tissue exceeds the turnover rate of tRNA's in normal tissue. Such rapid degradation of tRNA's must be the source of the massive excretion of modified nucleosides by cancer patients which can be 10-fold higher than in normal subjects.

Aminoisobutyric Acids↗
PubMed1975

Metabolic reduction of benzidine azo dyes to benzidine in the rhesus monkey.

Rhesus monkeys were fed azo dyes derived from benzidine (a known human bladder carcinogen). The urinary excretion of free benzidine was assayed and compared to the amount excreted when benzidine itself was fed. A substantial amount of the dye fed was converted to free benzidine. Results indicate that the simple precaution in the use of only azo dyes manufactured from noncarcinogenic aromatic amines, e.g., aniline, for all consumer products appears prudent.

Aminobiphenyl Compounds↗
PubMed1975

Effects of sodium arsenite on the survival of UV-irradiated Escherichia coli: inhibition of a recA-dependent function.

Epidemiological studies and clinical observation suggesting potential hazards of arsenic compounds in increasing the incidence of cancer have been in complete contradiction with experimental findings in animals. Because of the predominance of skin cancers in the epidemiological reports, we decided to investigate the possibility that arsenic compounds might interfere with DNA repair. Using Escherichia coli as a test system, we show that this is indeed the case. Sodium arsenite, at concentrations of 0.1 mM and higher, decreases the survival of ultraviolet-irradiated E. coli WP2, a strain which possesses the full complement of repair genes. The effect of the arsenite increases with increasing ultraviolet dose. Similar results were obtained with the excision repair deficient strains WWP2 (uvrA) and WP6 (polA). Sodium arsenite had no effect on the survival of a recA mutant, WP10. Survival of ultraviolet-irradiated WP5 (exrA) was enhanced by sodium ardenite, the effect being greatest at low ultraviolet doses. It is postulated that arsenite inhibits a recA-dependent step in DNA repair. To account for the increased survival of the exrA mutant, we suggest that in the absence of the exr+ gene, the arsenite-sensitive recA-dependent function is deleterious. The ability of arsenite to inhibit DNA repair may account for the clinical and epidemiological reports linking arsenicals with an increased incidence of cancer.

Arsenic↗
PubMed1974

The tumor-promoter phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate), a potent aggregating agent for blood platelets.

The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor-promoting agent, caused irreversible platelet aggregation when more than 0.02 microM was stirred with human citrated or heparinized platelet-rich plasma (PRP). With washed platelets, 1 nM was effective. The alcohol phorbol, which has little tumor-promoting activity, failed to cause platelet aggregation. With all but low concentrations of phorbol ester, aggregation was succeeded by a rapid phase. The latter was prevented or reduced by enzymes which destroy ADP and by aspirin, was associated with a change in platelet shape, and was presumably due to released ADP. At higher concentrations, only a rapid phase was seen, and these inhibitors were not effective. Low concentrations did not aggregate platelets in PRP containing sufficient EDTA or EGTA to chelate ionized calcium or in PRP from thrombasthenic patients; higher concentrations caused slight aggregation. Both the primary, non-ADP-dependent aggregation and the rapid ADP-dependent aggregation were markedly inhibited by substances which increase cyclic AMP, metabolic inhibitors, and the sulfhydryl inhibitor N-ethylmaleimide. Phorbol ester reduced platelet cyclic AMP only when it had been previously elevated by prostaglandin E(1). 1 microM did not release beta-glucuronidase, lactic dehydrogenase, or inflammatory material from platelets in 4-5 min despite marked aggregation, but liberated all three in 30 min. The possibility is discussed that low phorbol ester concentrations cause primary aggregation by a direct action on platelet actomyosin.

Adenosine Diphosphate↗