Unlicensed drugs in neonatalogy: dilemma for doctors.
Explore the source record for details and available documents.
Decision Making↗
Biomedical subjects
S Sinha
Publications and source records attributed to S Sinha.
Thalamic epidermoid cyst. A case report.
A case of thalamic epidermoid cyst is reported. Its clinical presentation, radiological, operative findings and histological findings are discussed. Intraparenchymal epidermoids are uncommon and to our knowledge only one case of thalamic epidermoid has been reported earlier. The literature is reviewed in regard to incidence, location and etiology of Intracerebral epidermoid tumor cysts.
Adult↗
A statistical method for finding transcription factor binding sites.
Understanding the mechanisms that determine the regulation of gene expression is an important and challenging problem. A fundamental subproblem is to identify DNA-binding sites for unknown regulatory factors, given a collection of genes believed to be coregulated, and given the noncoding DNA sequences near those genes. We present an enumerative statistical method for identifying good candidates for such transcription factor binding sites. Unlike local search techniques such as Expectation Maximization and Gibbs samplers that may not reach a global optimum, the method proposed here is guaranteed to produce the motifs with greatest z-scores. We discuss the results of experiments in which this algorithm was used to locate candidate binding sites in several well studied pathways of S. cerevisiae, as well as gene clusters from some of the hybridization microarray experiments.
Algorithms↗
Distribution of HLA-DQA1, polymarker, CSF1PO, vWA, TH01, TPOX, D16S539, D7S820, D13S317, and D5S818 alleles in East Bengali and West Punjabi populations from Indo-Pak Subcontinent.
Blood samples were collected from 115 individuals residing in the Pakistani state of West Punjab and 81 Bengali individuals residing in the state of East Bengal, India. These samples were analyzed for the loci HLA-DQA1, PM (LDLR, GYPA, HBGG, D7S8, and GC) and eight short tandem repeats: CSF1PO, TPOX, THO1, vWA, D16S539, D7S820, D13S317, and D5S818. Departures from Hardy-Weinberg (HWE) were observed in Punjabi population at LDLR, THO1, D13S317, D5S818, and D16S539 and at CSF1PO and THO1 in Bengali population.
Alleles↗
Combined pars plana lensectomy-vitrectomy with open-loop flexible anterior chamber intraocular lens (AC IOL) implantation for subluxated lenses.
OBJECTIVES: To review our experience with combined pars plana lensectomy-vitrectomy and open-loop flexible anterior chamber intraocular lens (AC IOL) implantation for managing subluxated crystalline lenses. METHODS: Retrospective review of 36 consecutive eyes (28 patients), all of which had subluxated crystalline lenses, managed by pars plana lensectomy-vitrectomy with insertion of an open-loop flexible AC IOL. The study was performed at the Medical College of Wisconsin, Milwaukee, over an 8-year period. RESULTS: An average preoperative visual acuity of 20/163 (range, 20/25 to hand motions) improved to 20/36 (range, 20/20 to 4/200) with surgery after a mean follow-up of 14 months (range, 1 to 59 months) (P < .001, Student's paired t test). Final visual acuity of 20/40 or better was achieved in 75% of eyes (27/36). Complications included cystoid macular edema (8% [3/36]), pupillary block (6% [2/36]), retinal detachment (3% [1/36]), hyphema (3% [1/36]), wound leak (3% [1/36]), and transient vitreous hemorrhage (3% [1/36]). No persistent ocular hypertension was seen, nor did angle abnormalities or corneal decompensation develop. CONCLUSIONS: Pars plana lensectomy-vitrectomy with AC IOL implantation appears to be an excellent technique for managing subluxated crystalline lenses. It is associated with a significant improvement in visual acuity (P < .001) and avoids many of the complications seen with extraction of a subluxated lens through a limbal wound. Additionally, use of an AC IOL offers a simplified alternative to placement of a ciliary sulcus sutured posterior chamber intraocular lens (PC IOL).
Adolescent↗
Studies on antidiarrhoeal activity of Punica granatum seed extract in rats.
Methanol extract of Punica granatum seed was evaluated for antidiarrhoeal activity against different experimental models of diarrhoea in rats. P. granatum seed extract treated animals showed significant inhibitory activity against castrol-oil induced diarrhoea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastro-intestinal motility in charcoal meal test in rats. The results obtained established the efficacy of P. granatum seed extract as an antidiarrhoeal agent.
Animals↗
Purification and cloning of amyloid precursor protein beta-secretase from human brain.
Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase.
Amino Acid Sequence↗
Effect of a herbal protein, CI-1, isolated from Cajanus indicus on immune response of control and stressed mice.
The effect of a herbal protein, CI-1, purified from the leaves of Cajanus indicus was evaluated as a probable immunomodulator on immune response in control and stressed mice. In mice, sensitized with sheep red blood cells (SRBC), CI-1 enhanced IgG level by 28% over control (P < 0.05). Primary and secondary antibody response to SRBC and bovine serum albumin (BSA) were significantly increased in CI-1 treated group. Furthermore CI-1 facilitated the delayed type of hypersensitivity (DTH) response to SRBC in sensitized mice and also enhanced leucocyte and macrophage migration inhibition response in immunized mice. A fewer mice displayed symptoms of anaphylactic shock after CI-1 administration at a dose of 6.0 mg/kg body wt. in BSA sensitized mice. The immediate effect of CI-1 on anaphylactic shock was not seen when 150 microg of CI-1 was injected in combination with BSA in the shocking injection. These results suggest that CI-1 influences both humoral and cell-mediated immune response.
Adjuvants, Immunologic↗
Crystal structure of Bacillus subtilis YabJ, a purine regulatory protein and member of the highly conserved YjgF family.
The yabJ gene in Bacillus subtilis is required for adenine-mediated repression of purine biosynthetic genes in vivo and codes for an acid-soluble, 14-kDa protein. The molecular mechanism of YabJ is unknown. YabJ is a member of a large, widely distributed family of proteins of unknown biochemical function. The 1.7-A crystal structure of YabJ reveals a trimeric organization with extensive buried hydrophobic surface and an internal water-filled cavity. The most important finding in the structure is a deep, narrow cleft between subunits lined with nine side chains that are invariant among the 25 most similar homologs. This conserved site is proposed to be a binding or catalytic site for a ligand or substrate that is common to YabJ and other members of the YER057c/YjgF/UK114 family of proteins.
Amino Acid Sequence↗
Typing of eight short tandem repeat (STR) loci in a Saudi Arabian population.
Allele frequency data for eight short tandem repeat (STR) loci, HUMF13A01, HUMFESFPS, HUMF13B, HUMLPL, HUMCSF1PO, HUMTPOX, HUMTHO1 and HUMvWA, were obtained for unrelated individuals in a Saudi Arabian population. All loci, except F13B (P = 0.037) and LPL (P = 0.035), meet Hardy-Weinberg expectations, based on the exact test. The most informative locus is HUMvWA (PD = 0.936) and the least discriminating is the HUMTPOX locus (PD = 0.820). There was only one observation of a departure from expectation from pairwise locus comparisons. These data can be used for estimating the frequency of STR profiles in a Saudi Arabian population.
Alleles↗
Cellular mechanisms of beta-amyloid production and secretion.
The major constituent of senile plaques in Alzheimer's disease is a 42-aa peptide, referred to as beta-amyloid (Abeta). Abeta is generated from a family of differentially spliced, type-1 transmembrane domain (TM)-containing proteins, called APP, by endoproteolytic processing. The major, relatively ubiquitous pathway of APP metabolism in cell culture involves cleavage by alpha-secretase, which cleaves within the Abeta sequence, thus precluding Abeta formation and deposition. An alternate secretory pathway, enriched in neurons and brain, leads to cleavage of APP at the N terminus of the Abeta peptide by beta-secretase, thus generating a cell-associated beta-C-terminal fragment (beta-CTF). A pathogenic mutation at codons 670/671 in APP (APP "Swedish") leads to enhanced cleavage at the beta-secretase scissile bond and increased Abeta formation. An inhibitor of vacuolar ATPases, bafilomycin, selectively inhibits the action of beta-secretase in cell culture, suggesting a requirement for an acidic intracellular compartment for effective beta-secretase cleavage of APP. beta-CTF is cleaved in the TM domain by gamma-secretase(s), generating both Abeta 1-40 (90%) and Abeta 1-42 (10%). Pathogenic mutations in APP at codon 717 (APP "London") lead to an increased proportion of Abeta 1-42 being produced and secreted. Missense mutations in PS-1, localized to chromosome 14, are pathogenic in the majority of familial Alzheimer's pedigrees. These mutations also lead to increased production of Abeta 1-42 over Abeta 1-40. Knockout of PS-1 in transgenic animals leads to significant inhibition of production of both Abeta 1-40 and Abeta 1-42 in primary cultures, indicating that PS-1 expression is important for gamma-secretase cleavages. Peptide aldehyde inhibitors that block Abeta production by inhibiting gamma-secretase cleavage of beta-CTF have been discovered.
Aldehydes↗
Mutations associated with in vivo aflatoxin B1-induced carcinogenesis need not be present in the in vitro transformations by this toxin.
Ingestion of aflatoxin B1 is implicated in the high incidence of human liver cancers in several developing countries. An association has been detected between human exposure to aflatoxins, and mutations in the third base of codon 249 of the p53 gene in hepatomas. In vitro experiments using human cell line cells and aflatoxin B1 have demonstrated the induction of p53 mutations in codon 249 and adjacent codons. It was therefore of interest to see if this correlation between the in vivo and in vitro situations held for other species. The present study examined a rat liver-derived cell line, transformed in vitro with aflatoxin B1, for the presence of mutations associated with in vivo aflatoxin-induced hepatocarcinogenesis. In an in vivo rodent model systems using the aflatoxin B1-sensitive male F344 rat, previous studies have shown that hepatocarcinogenesis is accompanied by significant incidences of codon 12 mutations in K-ras and codon 13 mutations in N-ras genes, but in contrast to the human, apparently not by mutations in codon 243 of the p53 gene (which corresponds to codon 249 in the human gene). In contrast to the situation in humans, mutation in the third base of codon 243 in the rat would not result in any changes in amino acid sequence, but mutations in codon 250, as seen in in vitro human systems, would be expressed in the rat p53 protein. In the present study, an immortalised, non-transformed liver epithelial cell line derived from a male F344 rat was transformed in vitro by aflatoxin B1 as demonstrated by tumour formation in nude mice. The transformation was dependent on metabolic activation of the aflatoxin B1. Transfection of DNA, extracted from these tumours, into NIH 3T3 fibroblasts conferred a stable, malignant transforming capacity. However, no mutations in codon 12 of the K-ras or codon 13 of the N-ras genes were detected in any of these tumours. These results indicate that in vitro transformation does not necessarily involve the same mutations, as those observed in vivo. Also, no mutations in codon 243 or adjacent codons of the p53 gene, paralleling those observed in the human cell line treated with aflatoxin B1, were detected. The results serve to emphasise the in vivo and in vitro variation in the oncogene activation in the same target organ or cell lines derived from that organ, even when using a single carcinogen activated by a known metabolic pathway.
3T3 Cells↗
Hepatoprotective activity of a herbal protein CI-1, purified from Cajanus indicus against beta-galactosamine HCl toxicity in isolated rat hepatocytes.
A herbal protein, CI-1 purified from a leguminous plant Cajanus indicus, showed dose dependent-(1.5-6.0 mg/kg x 7 days) protective activity on isolated hepatocytes (ex vivo) against beta-galactosamine-HCl induced hepatic damage in rats. It enhanced the percent viability of the hepatocytes following beta--galactosamine treatment. CI-1 was also effective in counteracting the toxic effects of beta-galactosamine, as shown by reversed levels of the altered enzymes, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transminase (GPT) and alkaline phosphatase (ALP) both in isolated hepatic cells as well as in serum. In comparison silymarin, a known hepatoprotective agent, produced dose related protection at-relatively much higher doses than CI-1.
Alanine Transaminase↗
Lectin like properties and differential sugar binding characteristics of C-reactive proteins purified from sera of normal and pollutant induced Labeo rohita.
Different forms of C-reactive proteins (CRPs) have been purified to electrophoretic homogeneity from the sera of Labeo rohita confined in freshwater (CRP(N)) and water polluted with nonlethal doses of cadmium (CRP(Cd)) or mercury (CRP(Hg)). CRP(N), CRP(Cd), and CRP(Hg) show remarkable differences in their electrophoretic mobility but exhibit strong immunological cross reactivity. All these CRPs exhibit variable agglutination properties with erythrocytes from diverse sources in presence of Ca+2, which could be inhibited by a variety of sugars showing specificity for galactose. Inhibition results show that the potency of galactose as an inhibitor increases about 4 fold in the process of transformation of CRP(N) to CRP(Cd) and CRP(Hg). In case of CRP(N), Gal beta(1 --> 1) Gal and oNO2 phenyl beta-Gal show highest inhibitory potency while oNO2-phenyl beta-Gal is the most potent inhibitor for CRP(Cd) and CRP(Hg) but the potency of Gal beta(1 --> 1) Gal reduced drastically. 6-phosphate D-Gal and stachyose are 20 times weaker inhibitors than D-Gal for induced CRP mediated agglutination, in contrast, these sugars are only 6 times weaker for CRP(N). Dissociation constants of the binding of CRP(N) with phosphoryl choline (PC) and galactose are about 9 mM and PC binding causes a change in the alpha and beta conformations of these CRPs.
Agglutination Tests↗
Effect of training on the incidence of nerve damage in thyroid surgery.
Explore the source record for details and available documents.
General Surgery↗
Antigenic definition of plasma membrane proteins of Bacillus Calmette-Guérin: predominant activation of human T cells by low-molecular-mass integral proteins.
Mycobacterial plasma membrane proteins, in particular the detergent-soluble or 'integral' ones, comprise a class of mostly unexplored antigens capable of inducing potent activation of human T cells. Plasma membrane isolated from culture-grown Bacillus Calmette-Guérin (BCG; Indian vaccine; Danish strain) was subjected to a Triton X-114-based biphasic extraction procedure for isolation of peripheral (water-soluble) and integral proteins (PMP and IMP). A distinction between the two protein pools was evident from results of SDS-PAGE and immunoblotting using antisera raised in rabbits. An enzyme-linked immunosorbant assay with a panel of WHO-IMMYC monoclonal antibodies against various mycobacterial antigens revealed that three well-known antigens, 19 kDa, 33/36 kDa (proline rich) and 38 kDa (PstS homologue), were part of the IMP pool; and another such antigen, 14/16 kDa alpha-crystallin homologue, partly constituted the PMP pool. Apparently, antigenically distinct species of the immunomodulatory moiety lipoarabinomannan partitioned in aqueous and detergent phases. Human T-cell proliferation assays in donors comprising tuberculoid leprosy and pulmonary tuberculosis patients and healthy BCG vaccinees showed significantly greater potency of IMP over PMP and this immunodominance appeared to be directed towards CD4+ cells. IMP of < 56 kDa were resolved by 'continuous elution SDS-PAGE' into 15 fractions which, after extraction of SDS, were used in T-cell proliferation assays for the identification of immunodominant constituents. Proteins falling within three low-molecular-mass zones (all < 35 kDa) performed better than the rest, particularly a approximately 22 kDa fraction, which strongly stimulated T cells from all five donors. Partial overlap between IMP and secreted proteins, as noticed in this study, could provide clues to immunodominance of the latter. The apparent uniqueness and a high T-cell activating potency make mycobacterial IMP attractive candidates for designing future vaccines or immunotherapeutic agents.
Antibodies, Monoclonal↗
Simultaneous alterations of retinoblastoma and p53 protein expression in astrocytic tumors.
The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpression is thought to indicate defective tumor suppression and subsequently more aggressive tumors. Therefore, to assess the alterations in the conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded sections, 64 astrocytic tumors were studied (16 astrocytomas,7 gemistocytic astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be positive for p53 protein. Seventeen of these showed aberrant heterogenous staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors, simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases. This was more commonly observed among glioblastoma cases (7/22). No statistical difference was found between the survival rate of heterogenous pRb and p53 positivity in different grades of tumors. In glioblastomas, the survival rate appeared to be less in patients expressing heterogenous pRb, but this was not statistically significant. These results lead us to suspect that p53 and pRb pathways are inactivated, either through mutation or as part of the neoplastic process in astrocytic tumors.
Adolescent↗
Periosteal chondroma of the distal radius.
We report a case of periosteal chondroma in an unusual location at the distal end of the radius.
Adult↗