Biomedical subjects
Publications and source records attributed to A C Ghosh.
A rapid, convenient TLC method is described for detection of cyclochlorotine, a carcinogen produced by the commonly found storage mold Penicillium islandicum Sopp. This method has also led to the isolation of a new toxic metabolite, simatoxin.
In a survey designed to determine the prevalence of Bacillus cereus in the faeces of healthy persons, the organism was found in low numbers in 100 (14%) of single faecal specimens from 711 adults in the general population. In addition, in an attempt at assessing the changes in the B. cereus distribution within the faecal flora of the individual, weekly faecal specimens were submitted over a seven-week period by 18 members of staff of two laboratories. The total isolation rate was again 14%, with 15 serotypes represented. In four individuals B. cereus was isolated in two consecutive weeks and in all cases the isolates were of different serotypes. Excretion was never recorded for more than two consecutive weeks. These findings probably reflect the intake of B. cereus in the individual's diet.
Production of luteoskyrin, a hepatotoxin synthesized by Penicillium islandicum Sopp., was studied with various fermentation methods. Best results were obtained in static fermentations on glutinous rice at 30 degrees C. The isolated yield of pure luteoskyrin was approximately 400 mg per kg of rice. Also produced were skyrin, islandicin, iridoskyrin, rubroskyrin, chrysophanol, mannitol, and erythritol. A new metabolite, which we call pibasterol, was also isolated.
Production of the hepatotoxin cyclochlorotine by Penicillium islandicum was studied under a variety of fermentation conditions. The best system for production was agitated red wheat. A thin-layer chromatographic method was developed for the detection of this cyclic polypeptide. These experiments have resulted in the isolation of a new toxic metabolite, which we call simatoxin.
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The ability of certain strains of Bacillus cereus consistently to elaborate a filterable non-dialysable toxin capable of causing severe disruption and necrosis of the intestinal mucosa and submucosa is confirmed. This property is not universal to all B. cereus strains and different degrees of production of this toxin are exhibited by the different strains which produce it. The necrotic effect is produced by whole-cell cultures of the toxin producing strains in broth and in boiled rice. Some characteristics of this necrotic toxin are described and its relationship with the diarrhoeal and other known B. cereus toxins is discussed.
Escherichia coli O 27 H 7 was found in 16 stool samples submitted during a Caribbean cruise (Cruise Z) by 29 patients reporting with diarrhoea. A retrospective search revealed E. coli O 27 H 7 in 11 of 20 and 2 of 14 stool cultures from patients on two previous cruises (Y and X respectively) and in a culture from fresh cream (Cruise Y). The repeated occurrence of E. coli O 27 H 7 in the absence of any other apparent cause suggested that this serotype may have been responsible for the diarrhoea. The results of pathogenicity tests suggested that this strain elaborated heat-stable (ST) enterotoxin. The possibility that food may have been the vector is discussed.
4-Amino-4-norpyridoxol, a new key intermediate for the modification of the 4 position of vitamin B6, has been obtained by an unusual photochemical rearrangement of pyridoxal oxime. It has also been synthesized starting from 3,-alpha5-O-dibenzylpyridoxal, which was converted to 3,alpha5-O-dibenzylpyridoxamide. The latter, on Hoffman reaction, gave the desired 3,5-blocked 4-amino derivative. Several derivatives of this analogue have been prepared, and its existence in the amino tautomeric form has been established by NMR spectroscopy. A modified Sandmeyer reaction on 4-amino-4-norpyridoxol gave the 4-bromo analogue, which was found to be moderately active as an inhibitor of mouse mammary adenocarcinoma cells grown in cell culture, whereas the 4-amino analogue was not active at 10(-4)M. Other analogues containing electron-withdrawing and electron-donating substituents in the 4 position of pyridoxine were also tested.
A group of amides of 6-cyano-6-norlysergic acid was prepared from their corresponding lysergamides. None of these N-cyano derivatives showed anticancer activity against lymphoid leukemia L1210 in mice. This is in contrast to the reported in vitro anticancer activity (P-815 mastocytoma) of 6-cyano-6-norlysergic acid diethylamide.
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Salmonella infection on two pig farms and its relation to infection in pigs at slaughter was studied. On the first farm feed ingredients were mixed on the farm, and these included fish meal which was found to be contaminated with salmonellas. The feed was pumped to pigs in liquid form. There was a high salmonella isolation rate at slaughter when the contaminated fish meal was fed in liquid feed, but it was significantly lower when no fish meal was fed to the pigs examined at slaughter. In some instances the same serotypes were found in fish meal and pig excreta on the farm and in caecal contents of the pigs at slaughter. No serotype was repeatedly isolated from any source and it appeared that the serotypes were not able to establish themselves in the pigs. It is concluded that infection found at slaughter originated on the farm where fish meal introduced and maintained infection. There was an opportunity for salmonellas to have multiplied in the liquid feed for several hours each day.On a second farm environmental conditions were similar, but feed was given in the form of ready-made pellets and nuts. Salmonellas were not isolated from the feed. At slaughter there was a significantly lower isolation rate than on the first farm.
The incidence of salmonellas in pigs was studied in five farms and a bacon factory.Persistence and spread of salmonella excretion in pigs in a breeding establishment is described. Salmonella excretor boars and sows were responsible for the spread and perpetuation of infection in the farm. The possibility of spreading salmonella infection between farms through the distribution of excretor pigs was studied. Infection persisted and was related to the initial state of excretion of the pigs while at the farm of origin.The importance of feeding stuffs as a source of salmonella infection in pigs is discussed. Specially prepared heat treated pellets fed to the pigs prevented the introduction of salmonellas.
Twelve mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum in solid-state fermentation on grains were purified and tested for mutagenicity and antibacterial activity in Salmonella/mammalian microsome assays. The mutations studied were reversions of histidine auxotrophs to prototrophy in strains TA98 and TA100 and forward mutations to 8-azaguanine resistance (8AGR) in strain TM677. Rubroskyrin, (+)rugulosin, lumiluteoskyrin [a photoproduct of (-)luteoskyrin], and simatoxin [a new water-soluble metabolite of unknown structure] induced 8AGR mutations in strain TM677 but not histidine reversions in strains TA98 and TA100. Mutagenic potency was reduced by rat-liver microsomes. The carcinogens (-)luteoskyrin and cyclochlorotine were antibacterial but not mutagenic. (+)Rugulosin, rubroskyrin, lumiluteoskyrin, and high concentrations of simotoxin were also antibacterial. Antibacterial activity but not mutagenicity was observed with pibasterol and skyrin. Chrysophanol, islandicin, iridoskyrin, and emodin were inactive as mutagens or as antibacterial agents.