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Biomedical subjects

S John

Publications and source records attributed to S John.

At least 127 records · Page 7Linked to original sources

Erotomania in a brain-damaged male.

A 31-year-old male presented to a neuropsychiatric service for the first time with an erotomatic delusion among other symptoms. He had suffered significant brain damage several times in the past and experienced a recent loss. After extensive evaluation, a trial of haloperidol resulted in some improvement. However, the erotomanic delusion remained unchanged.

Adult↗

Nucleosome positioning on the MMTV LTR results from the frequency-biased occupancy of multiple frames.

The translational positions of nucleosomes in the promoter region of the mouse mammary tumor virus (MMTV) were defined at high resolution. Nucleosome boundaries were determined in primer extension assays using full-length single-stranded mononucleosomal DNA prepared from cells treated with formaldehyde, a reversible protein-DNA cross-linking agent. Multiple boundaries were observed in both the nucleosome A (Nuc-A) and Nuc-B region of the promoter, indicating multiple nucleosome translational frames. The different nucleosome frames in both the Nuc-A and Nuc-B regions were occupied unequally. The most frequently occupied frames were found clustered within 50-60 bases of each other, resulting in a distribution centered in the positions defined previously at low resolution for Nuc-A and Nuc-B. The most abundant 5' ends of the frames in the B region were found between -235 and -187, and the 3' ends between -86 and -36, whereas in the A region the most abundant 5' ends were between -22 and +42, and the 3' ends between +121 and +186. Although frames in the Nuc-B region of the LTR extend at a low frequency in the 5' direction toward the Nuc-C region, there is a sharp discontinuity in the 3' direction toward Nuc-A, suggesting the presence of a boundary constraint in the A-B linker. The positions and relative occupancies of nucleosome frames, in either the B or the A region, did not change when the promoter was activated with dexamethasone.

Animals↗

The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15.

To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein.

Amino Acid Sequence↗

Retinitis pigmentosa in India: a genetic and segregation analysis.

Seventy-eight families with retinitis pigmentosa, presenting at the genetic clinic of Sankara Nethralaya, Madras, over a period of 6 months (from April to September 1993), were assessed to determine the different genetic types: 9% were autosomal dominant; 36%, autosomal recessive; 3%, X-linked recessive; 44%, isolated cases and 8%, undetermined genetic type. A high incidence of consanguinity was observed in autosomal recessive (57%) and isolated cases (37%). Segregation analysis showed good agreement in autosomal dominant (chi 2 = 0.864) and recessive families (p = 0.222). The high proportion of autosomal recessive and isolated cases in this study, when compared with other similar studies, is due to the high incidence of consanguineous marriages in the Indian subcontinent.

Consanguinity↗

Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins.

The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins.

Animals↗

Oguchi disease: suggestion of linkage to markers on chromosome 2q.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness. The condition is associated with fundus discolouration and abnormally slow dark adaptation. Earlier studies suggested that the 48 kD protein S antigen may be involved in the recovery phase of light transduction. Previous cytogenetic and linkage studies have localised the S antigen gene (SAG) to chromosome 2q37.1. In the present study markers which map to distal chromosome 2q were typed in an inbred Oguchi pedigree. The segregation data obtained suggested that the affected subjects are homozygous by descent for a region between D2S172 and D2S345. An intragenic SAG polymorphism was homozygous in all affected people and a recombination event suggested that SAG maps proximal to D2S345. Collectively, these findings support the hypothesis that a defect in S antigen may be responsible for Oguchi disease.

Antigens↗

A prospective study of cortical scarring in acute febrile pyelonephritis in adults: clinical and bacteriological characteristics.

Previous reports have demonstrated lesions on computerized axial tomography (CT), and nuclear scintigraphy (DMSA) in acute pyelonephritis (PN). We undertook a prospective study of all patients presenting to our hospital with PN over 40 months. Patients who fulfilled diagnostic criteria, were treated with intravenous antibiotics. Excluding two who were pregnant, all patients had imaging by intravenous urography (IVU), CT and DMSA during their admission. Urine samples were collected prior to treatment. Patients without IVU evidence of cortical scarring but with parenchymal defects on CT and/or DMSA underwent a repeat DMSA three or more months after the acute episode. Of the 164 patients, 142 were female. E. coli was found in 116 patients. Forty-six patients had an abnormality on IVU. Of the 106 patients without IVU evidence of cortical scarring, 59 had a defect on CT and/or DMSA. Late DMSA scans in 35 of these 59 patients showed a persistent abnormality in 77%. E. coli characteristics such as P-fimbriae and Type 1 fimbriae were not predictive of acute imaging abnormalities. Inhibition of E. coli growth by the addition of EDTA was highly predictive of acute CT and DMSA abnormalities with a sensitivity of 83.3% and a specificity of 82.8%. Acute pyelonephritis is often associated with acute CT and/or DMSA abnormalities which may evolve into renal cortical scars. Acute scan abnormalities can be predicted by the presence of E. coli which were susceptible to EDTA in culture. Late scarring could not be predicted by clinical features, response to treatment or antibiotic used.

Acute Disease↗

The 5' enhancer of the mouse mammary tumor virus long terminal repeat contains a functional AP-2 element.

The mouse mammary tumor virus (MMTV) retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV long terminal repeat (LTR) has been implicated in tissue-specific activation of these genes. In this study, we characterize an enhancer element (Ban2; -1075 to -978) at the 5' end of the MMTV LTR. We show that this enhancer is 5-fold more active in a murine mammary carcinoma cell line (34i) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity. DNA-binding proteins that interact with each of the four elements have been identified. One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2. The mp5/AP-2 DNA binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies. We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells, and requires an intact mp5-binding site.

Animals↗

Endocrine profile of women with amenorrhea and oligomenorrhea.

OBJECTIVES: To find out the common causes of amenorrhea and oligomenorrhea in south Indian women and to draw up a protocol for evaluation of women with these problems. METHODS: A retrospective study of 426 women with amenorrhea and oligomenorrhea was carried out. RESULTS: Forty-one patients had primary amenorrhea, 132 had secondary amenorrhea and 289 women presented with oligomenorrhea. Hypergonadotropic amenorrhea and congenital absence of the uterus and vagina accounted for 60% of primary amenorrhea. Chronic anovulatory disorders and premature ovarian failure were found in 72% of women with secondary amenorrhea but weight loss related amenorrhea was uncommon. CONCLUSIONS: On the basis of the observations made, a protocol for evaluation and management of women with amenorrhea and oligomenorrhea was evolved.

Adult↗