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Biomedical subjects

J Mendel

Publications and source records attributed to J Mendel.

At least 19 recordsLinked to original sources

Role of hydrogen peroxide in sperm capacitation and acrosome reaction.

The generation of reactive oxygen species (ROS) has been implicated in the regulation of sperm capacitation and acrosome reaction; however, the mechanisms underlying this regulation remain unclear. To examine the cellular processes involved, we studied the effect of different concentrations of hydrogen peroxide (H(2)O(2)) on protein tyrosine phosphorylation under various conditions. Treatment of spermatozoa with H(2)O(2) in medium without heparin caused a time- and dose-dependent increase in protein tyrosine phosphorylation of at least six proteins in which maximal effect was seen after 2 h of incubation with 50 microM H(2)O(2). At much higher concentrations of H(2)O(2) (0.5 mM), there is significant reduction in the phosphorylation level, and no protein tyrosine phosphorylation is observed at 5 mM H(2)O(2) after 4 h of incubation. Exogenous NADPH enhanced protein tyrosine phosphorylation similarly to H(2)O(2). These two agents, but not heparin, induced Ca(2+)-dependent tyrosine phosphorylation of an 80-kDa protein. Treatment with H(2)O(2) (50 microM) caused approximately a twofold increase in cAMP, which is comparable to the effect of bicarbonate, a known activator of soluble adenylyl cyclase in sperm. This report suggests that relatively low concentrations of H(2)O(2) are beneficial for sperm capacitation, but that too high a concentration inhibits this process. We also conclude that H(2)O(2) activates adenylyl cyclase to produce cAMP, leading to protein kinase A-dependent protein tyrosine phosphorylation.

Acrosome Reaction↗

A low-cost, full-function picture archiving and communication system using standard PC hardware and the traditional 4-over-4 display format.

OBJECTIVE: With a 12-year background of our completely digital nuclear medicine picture archiving and communication system (PACS), we have recently implemented a novel PACS, OpenPACS, which can be used for interpretation and display of CT, MR imaging, sonography, nuclear medicine, and computed and digital radiography studies. OpenPACS uses low-cost standard PC hardware and software that is widely available and is readily serviced and maintained. The OpenPACS application program is available over the Internet. CT or MR imaging slices from one or multiple studies can be presented simultaneously or in cine mode on a wall-sized multimonitor display. The assembly, with a total resolution of 6400 x 4800 pixels, resembles a traditional array of eight standard X-ray viewboxes. A wireless mouse is used to vary attenuation and other display parameters. Multiple backup and redundancy are provided. Currently, six CT and six MR imaging scanners of different vendors are networked to OpenPACS, which is also networked to our nuclear medicine PACS. CONCLUSION: After only a brief introduction, radiologists rapidly become familiar with the system because it is based on the use of standard Windows icons and procedures and offers a display that resembles a standard X-ray film presentation.

Data Display↗

Clinical trial of remote radiologist services for a military installation.

It is often difficult to provide continuity of professional radiological services at U.S. military facilities located at a distance from major metropolitan areas. To address this problem, we have designed and evaluated a program to send x-ray films from a U.S. Army hospital to a remote site for expert radiological interpretation. Nine hundred and forty-two x-ray studies were sent by U.S. Express Mail from the Radiology Department of a U.S. Army Hospital over a 2-month period. The typed reports were sent back to the hospital through the use of a computer-to-computer telephone link within 72 hours of film transport. No studies were lost and security of all studies was maintained. This program offers a cost-effective, otherwise unavailable means to provide high quality professional radiological services to U.S. military facilities both inside the United States and in foreign countries.

Computer Communication Networks↗

High local carcinogenic activity of 1,3-dimethyl-3-phenyl-1-nitrosourea and its inactivation by intravenous application in rats: comparison of in vivo findings with the in vitro direct and a combined in vivo/in vitro sister chromatid exchange assay in V79-E cells.

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) is a very potent local carcinogen in rats and induces a 100% frequency of forestomach carcinomas when applied i.g. in two different dosages (10 applications of 0.3 or 0.03 mmol/kg body wt, respectively, at 14-day intervals), but it is inactive upon i.v. administration (10 applications of 0.03 mmol/kg body wt at 14-day intervals). By means of the direct sister chromatid exchange (SCE) assay in V79-E cells in the presence of rat blood, serum or plasma, respectively, as well as by a 'host-mediated' SCE assay (in which the agent was given i.v. to rats, and blood taken from the animal was checked for the recovery of genotoxic activity in cell cultures), we tried to elucidate the unexpected lack of carcinogenic activity of i.v. DMPNU. The direct SCE assay revealed a drastic reduction of DMPNU genotoxicity by rat blood, serum or plasma, respectively, which is abolished by the esterase inhibitor diisopropylfluorophosphate. In the 'host-mediated' SCE assay a genotoxic activity of DMPNU was only recoverable after a very high i.v. dose and when the blood added to the cell cultures had been taken from the rat heart within 1 min after DMPNU administration in vivo. 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-phenyl-1-nitrosourea (MPNU) were used as positive controls in these experiments and also gave a lower response than theoretically expected, but the relative loss of activity with the latter compounds was much lower than with DMPNU. It is assumed that an esterase in rat blood effectively decomposes this trisubstituted nitrosourea. Problems of the novel 'host-mediated' SCE assay are discussed.

Animals↗

Carcinogenicity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea and its 1-methyl trideuterated derivative in rats.

The carcinogenic activity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea (Cl-MPNU) and its 1-methyl trideuterated analog (Cl-MPNU-d3) was compared by intragastric administration to hooded rats of equimolar doses of both compounds. A 100% frequency of forestomach tumors was observed in both groups. However, the mean latency period of the animals treated with Cl-MPNU-d3 was significantly longer (P less than 0.01). The results suggest the occurrence of a deuterium isotope effect in nitrosoureas but not as distinct as in nitrosamines.

Animals↗

Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells.

The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid.

Animals↗

Studies by means of the SCE assay in V79-E Chinese hamster cells on the mode of action of tri-substituted nitrosoureas.

The genotoxic activity of 3,3-diethyl-1-methyl-1-nitrosourea ( DEMNU ), 1,3-dimethyl-3-phenyl-1-nitrosourea ( DMPNU ) and 1-chloroethyl-3-methyl-3-phenyl-1-nitrosourea ( CEMPNU ) was studied in the SCE assay in V79-E cells in vitro. These compounds are very stable in aqueous solutions, but are directly acting genotoxins . The SCE rates increase linearly with the length of the incubation period. This direct activity is presumably due to an intracellular catalytic decomposition. Whereas the SCE-inducing effect of DMPNU and CEMPNU is not influenced by addition of S9 mix, that of DEMNU is strongly potentiated by rat and Syrian hamster S9 mix. This DEMNU activation is an NADPH-dependent enzymatic reaction and is inducible by phenobarbital. The absence of a direct mutagenic effect of DEMNU in the Ames test, as reported by other authors, is probably caused by a striking insensitivity to tri-substituted nitrosoureas of the Salmonella assay. This assumption was substantiated by long-term application of very low DMPNU doses to V79-E. Long-term simultaneous treatment with DMPNU and bromodeoxyuridine (BUdR) significantly diminished the rate of SCE induction.

Animals↗

Genetic and cytogenetic effects of 1,3-dimethyl-3-phenyl-1-nitrosourea in Salmonella typhimurium and Chinese hamster V79 cells.

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) shows no spontaneous decomposition in aqueous buffered solution (pH 7.0) at 37 degrees C over a measuring period of 10 days, but it is directly genotoxic in all assays applied. This compound induces base substitutions in Salmonella typhimurium (especially in the plasmid harbouring strain TA 100), gene mutations at the HGPRT+ locus of Chinese hamster V79 cells, and is a very potent inducer of clastogenic damage and sister chromatid exchanges in V79 cells. Data on gene mutation induction by 1-methyl-1-nitrosourea are included for comparison. The findings on DMPNU are discussed in comparison with trialkylnitrosoureas. In contrast to these latter compounds, DMPNU is active without addition of S9 mix in vitro. It is assumed that its genotoxic activity is due to an intracellular catalytic degradation favoured by the electron-withdrawing effect of the phenyl group.

Animals↗

The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

Administration, Oral↗

Patulin, a further clastogenic mycotoxin, is negative in the SCE assay in Chinese hamster V79-E cells in vitro.

Patulin is a potent inducer of chromatid-type aberrations in Chinese hamster V79-E cells, but loses its activity when 9000 g supernatant of rat-liver homogenate is added. The narrow dose range of patulin clastogenicity shows a quantitative relationship between absolute amount of mycotoxin applied and the number of indicator cells treated. Within a dose range permitting survival of V79-E, patulin does not induce an increase of the SCE rate. It is suggested that patulin clastogenicity is caused by interaction with chromosomal proteins and that DNA is not the virtual target of this mycotoxin.

Animals↗