Clinical presentation of shigellosis during the 1984 epidemic of bacillary dysentery in West Bengal.
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Biomedical subjects
Publications and source records attributed to D Sen.
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We have used photochemically detected linear dichroism to measure the separate average angular orientations of nucleosomes and linker DNA in 30-nm chromatin fibers of varying linker size (20-80 base pairs). Our results indicate that the average tilt angles vary with linker size, but not in a monotonic manner, suggesting that the constancy of geometry of the 30-nm fiber is maintained by compensatory changes of nucleosomal tilt which accommodate packing of variable lengths of linker DNA. We discuss the compatibility of our results with the various classes of models that have been proposed for the 30-nm fiber, including the continuous solenoid model and models built from the basic unit of the zig-zag ribbon. Many models can be eliminated, and all have to be modified to fit our results for chromatins with very long linkers.
We have used electric dichroism to investigate the influence of multivalent cations upon the compaction of chicken erythrocyte chromatin from the unfolded, 10-nm fiber to the 30-nm solenoid and subsequent aggregation. The pattern of condensation, which consists of compaction plus aggregation, is found to be strikingly similar for a variety of cations of differing charge, including the physiologically important polyamines spermine and spermidine. With a few exceptions such as Cu2+ and Gd3+, an optimally compacted fiber with reproducible hydrodynamic properties is produced prior to the onset of aggregation. We report the concentrations of di-, tri-, and tetravalent cations required for optimal condensation; in addition, for tri- and tetravalent cations, we were able to estimate the extent of charge neutralization produced by their binding to the optimally compacted fiber. The results show that the multivalent ion concentration required for optimal compaction decreases as cationic charge increases. In addition, the effect of a mixture of dilute mono- and multivalent cations on chromatin condensation is synergistic, rather than competitive as has been found for the multivalent cation induced condensation of DNA or the B----Z conformational transition. A simple calculation indicates that the entropy of ion uptake in chromatin condensation is surprisingly constant for a range of ionic conditions; this factor may be a dominant one in determining the folding equilibrium.
We have used transient electric dichroism to study the ability of DNA-binding drugs to affect the folding of chromatin from the 10- to the 30-nm fiber, either by themselves or in conjunction with multivalent cations. Variables considered include the cationic charge of the drug, the comparative influence of intercalation and groove binding as modes of interaction, and the effect of bis-intercalation compared to mono-intercalation. In parallel with our findings with other cations, we observe that a drug must have a charge of 3+ or greater in order to condense chromatin at concentrations substantially lower than the concentration of chromatin, measured in base pairs. Drugs of low charge, whether groove binders or mono-or bis-intercalators, are unable to condense chromatin on their own. Bis-intercalators of high charge, however, are extremely efficient condensers, being able to cross-link chromatin with greater efficiency than polyamines of corresponding charge. When Mg2+ is used in combination with bis-intercalators of high charge, the order of addition of the two determines whether compaction or cross-linking is favored. Finally, the antibiotics actinomycin D, daunomycin, and distamycin, despite varied modes of binding to DNA, all inhibit the compaction of chromatin beyond a critical point in a remarkably similar manner.
A recent epidemic of acute Shigella dysentery in West Bengal (India) provided us with an opportunity to examine the rectal mucosal abnormalities seen in this condition. One hundred two patients were investigated using sigmoidoscopy, rectal biopsy, and rectal swab for culture. Pure culture of Shigella was obtained in 37 cases, and the rectal biopsy specimens from these patients were assessed in detail. The mean (+/- SD) duration of illness was 47.8 +/- 27.4 h (range 8-120 h), and most patients (31 of 37, 84%) had diarrhea with blood and mucus in the stools. Significant findings at histology were as follows. (a) Cellular infiltrate was predominantly round cell or mixed round cell and neutrophilic in the majority of patients (27, 73%). (b) Disorganization of crypts was seen in as many as 31 patients (84%); in most subjects the distorted architecture was mild, but in a few the defect was severe with crypt branching and dilatation. (c) In the majority of patients the inflammatory process extended to the muscularis mucosae and submucosa; edema with or without increased cellular infiltrate was seen in the muscularis mucosae in 92% and in the submucosa in 80%. (d) There was no difference in the rectal histology of patients with a short history of disease (less than 48 h) compared with those with a longer history, except for goblet cell depletion which was more in those with diarrhea for more than 48 h. (e) The mucosal abnormalities in patients with watery diarrhea were, in general, milder than in those with dysentery, although the difference was statistically not significant; 2 of 6 patients with watery diarrhea had severe colitis. (f) The mucosal abnormalities were more severe in patients with Shigella dysenteriae infection compared with Shigella flexneri.
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Sickle cell nephropathy characterized by proteinuria and predominantly glomerular lesions has not been studied as extensively as renal tubular alterations in sickle cell disease. We reviewed our experience with this entity over a 14-year period. Of 13 children with either proteinuria or the nephrotic syndrome, 8 showed focal and segmental glomerulosclerosis, and 5 had mesangial proliferation. Children with focal and segmental glomerulosclerosis were older at onset of nephropathy and presented with the nephrotic syndrome more frequently than those with mesangial proliferation (p less than 0.05). All patients with mesangial proliferation and half of the focal and segmental glomerulosclerosis patients had supranormal renal clearances at onset of nephropathy suggesting hyperfiltration. Hyperfiltration seen in animals with reduced renal mass, and in human diabetic nephropathy before reduction in nephron units leads to mesangial proliferation and sclerosis. Our study suggests that sickle cell disease produces similar lesions in patients with sickle cell nephropathy.
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Of the 245 acute paediatric diarrhoea cases admitted to the Infectious Diseases Hospital, Calcutta between July, 1979 and June, 1981, rotavirus was detected in the faeces of 55 (22.4%) patients either as the sole aetiological agent or in association with other enteropathogens. Children aged six months to two years were most commonly infected. The virus was detected throughout the year with higher incidence during the winter months of both years. The frequency of detection of major enteropathogens other than rotavirus was Vibrio cholerae biotype El Tor (31.0%), enteropathogenic Escherichia coli (8.2%) and enterotoxigenic E. coli (6.5%).
The prevalence of different types of diarrhoea-producing Escherichia coli among 240 patients with acute diarrhoea in hospital was investigated. The 25 patients (10.4% of the total) from whose faeces we isolated enteropathogenic E. coli (EPEC) were all less than 5 years old but the 29 (12.1%) from whom we isolated enterotoxigenic E. coli (ETEC) were of various ages, most of them greater than 12 years old. No enteroinvasive E. coli (EIEC) strains were isolated. ETEC strains that produced heat-labile toxin (LT) were encountered more often than those that produced either heat-stable toxin (ST) alone or both LT and ST. The ETEC isolates were distributed among eight different serotypes, the commonest being O148:H28 (38%). Correlations between enterotoxin production, serotype pattern and possession of colonisation factor antigens I and II were observed.
Three simple immunological tests, the modified Elek (Biken) test, the modified staphylococcal coagglutination test, and the rapid GM1-horseradish peroxidase-enzyme-linked immunosorbent assay have been evaluated for detection of heat-labile enterotoxin of enterotoxigenic Escherichia coli. Of the 100 coded E. coli strains tested, 94 gave consistent results with all the three immunological tests; a discrepancy was observed in only 6 strains. Identical results were obtained when the Biken test was conducted with complete and incomplete Biken kits (Meguro Institute Ltd., Osaka, Japan). All three immunological tests evaluated in this study were found to be sensitive and simple and can be easily adopted by any laboratory for detection of heat-labile enterotoxins of enterotoxigenic E. coli strains.
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Bacterial enteropathogens and rotavirus were sought in 356 cases with acute diarrhoea admitted to the Infectious Diseases Hospital, Calcutta. One or more pathogens were isolated from 74.7% of the cases. Single enteropathogens could be detected from 66% and multiple enteropathogens from 8.7% of the patients. Vibrio cholerae biotype El Tor, rotavirus, V. parahaemolyticus, and enteropathogenic and enterotoxigenic Escherichia coli were the major pathogens detected. Rotavirus was detected from 7.6% of the cases. A higher rate of detection of rotavirus was seen in children younger than two years. Campylobacter jejuni could be isolated from the faeces of six (15%) of 40 cases either as a single pathogen or in association with V. cholerae biotype El Tor.