Epidemic shigellosis due to Shigella dysenteriae type 1 in south Asia.
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Biomedical subjects
Publications and source records attributed to D Sen.
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Patients below 5 yr of age, hospitalised for shigellosis over a period of four years (1984-87), were studied. During the epidemic of bacillary dysentery (1984) isolation of different Shigella spp. as well as Shigella dysenteriae type 1 was high. Decreased isolation of Sh. dysenteriae type 1 and increased isolation of Sh. flexneri was observed during post-epidemic years (1985-87). Isolation of different Shigella spp. was always above 25 per cent from patients with dysentery and greater than 7 per cent from those with watery diarrhoea during the post-epidemic years. Higher incidence of shigellosis was observed amongst older children (greater than 3 yr). Most of the shigellosis patients complained of blood and mucus in stools. Vomiting was common among shigellosis patients presenting with watery diarrhoea whereas fever was commonly seen in patients with both dysentery and watery diarrhoea. Most patients of shigellosis presenting with blood and mucus in stools had no dehydration.
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We have discovered that single-stranded DNA containing short guanine-rich motifs will self-associate at physiological salt concentrations to make four-stranded structures in which the strands run in parallel fashion. We believe these complexes are held together by guanines bonded to each other by Hoogsteen pairing. Such guanine-rich sequences occur in immunoglobulin switch regions, in gene promoters, and in chromosomal telomeres. We speculate that this self-recognition of guanine-rich motifs of DNA serves to bring together, and to zipper up in register, the four homologous chromatids during meiosis.
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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.