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Biomedical subjects

P Soni

Publications and source records attributed to P Soni.

10 recordsLinked to original sources

Spatial-temporal analysis of non-stationary fMEG data.

Magnetoencephalography (MEG) is a technique used to non-invasively record neuromagnetic fields generated by the human brain. Our new SARA (SQUID Array for Reproductive Assessment) is a unique MEG device designed specifically for the study of the fetal neurophysiology. During the acquistion of fetal magnetoencephalography (fMEG), many other interfering bio-magnetic signals are collected as well. Examples include the movement of fetus or muscle contraction of the mother. As a result, the recorded signals may show unexpected patterns, other than the target signal of interest. These interventions makes it difficult for a physician to assess the exact fetal condition, including its response to various stimuli. We propose using intervention analysis and spatial-temporal autoregressive moving average (STARMA) modeling to address the problem. STARMA is a statistical method that examines the relationship between the current observations as a linear combination of past observations, as well as observations at neighboring sites. Through intervention analysis, the change in pattern due to interfering signals can be well accounted for. When these interferences are removed, the end product is a template time series, or a typical signal from the target of interest thus providing a more reliable means to monitor the actual signals generated by the fetal brain and other organs of interest.

Female↗

GB virus C/hepatitis G virus (GBV-C/HGV): still looking for a disease.

GB Virus C and Hepatitis G Virus (GBV-C/HGV) are positive, single-stranded flaviviruses. GBV-C and HGV are independent isolates of the same virus. Transmission via the blood-borne route is the commonest mode, although vertical and sexual transmission is well documented. GBV-C/HGV is distributed globally; its prevalence in the general population is 10 fold higher in African countries than in non-African countries. High prevalences of GBV-C/HGV have been found in subjects with frequent parenteral exposure and in groups at high risk of exposure to blood and blood products. The clinical significance of human infection with GBV-C/HGV is currently unclear. The virus can establish both acute and chronic infection and appears to be sensitive to interferon. Only some 12-15% of chronic Non-A, B, C hepatitis cases are infected with GBV-C/HGV. A direct association with liver pathology is still lacking and it is not yet clear as to whether GBV-C/HGV is indeed a hepatotropic virus. Current evidence suggests that the spectrum of association of GBV-C/HGV infection with extrahepatic diseases ranges from haematalogical diseases, aplastic anaemia, human immunodeficiency virus (HIV)-positive idiopathic thrombocytopenia and thalassemia, through to common variable immune deficiency and cryoglobunemia.

Carcinoma, Hepatocellular↗

The differential effects of pp120 (Ceacam 1) on the mitogenic action of insulin and insulin-like growth factor 1 are regulated by the nonconserved tyrosine 1316 in the insulin receptor.

pp120 (Ceacam 1) undergoes ligand-stimulated phosphorylation by the insulin receptor, but not by the insulin-like growth factor 1 receptor (IGF-1R). This differential phosphorylation is regulated by the C terminus of the beta-subunit of the insulin receptor, the least conserved domain of the two receptors. In the present studies, deletion and site-directed mutagenesis in stably transfected hepatocytes derived from insulin receptor knockout mice (IR(-/-)) revealed that Tyr(1316), which is replaced by the nonphosphorylatable phenylalanine in IGF-1R, regulated the differential phosphorylation of pp120 by the insulin receptor. Similarly, the nonconserved Tyr(1316) residue also regulated the differential effect of pp120 on IGF-1 and insulin mitogenesis, with pp120 downregulating the growth-promoting action of insulin, but not that of IGF-1. Thus, it appears that pp120 phosphorylation by the insulin receptor is required and sufficient to mediate its downregulatory effect on the mitogenic action of insulin. Furthermore, the current studies revealed that the C terminus of the beta-subunit of the insulin receptor contains elements that suppress the mitogenic action of insulin. Because IR(-/-) hepatocytes are derived from liver, an insulin-targeted tissue, our observations have finally resolved the controversy about the role of the least-conserved domain of insulin and IGF-1Rs in mediating the difference in the mitogenic action of their ligands, with IGF-1 being more mitogenic than insulin.

Animals↗

Cell adhesion properties and effects on receptor-mediated insulin endocytosis are independent properties of pp120, a substrate of the insulin receptor tyrosine kinase.

pp120 undergoes phosphorylation by the tyrosine kinase of the insulin, not the insulin-like growth factor 1 (IGF-1), receptor. Moreover, pp120 stimulates receptor-mediated insulin, but not IGF-1, endocytosis, suggesting that pp120 phosphorylation underlies its effect on insulin endocytosis. pp120 phosphorylation also underlies its bile acid transport and tumor suppression functions. In addition to depending on the intracellular tail, the cell adhesion property of pp120 depends on Arg98 in the N-terminal IgV-like ectoplasmic domain. To investigate whether this domain mediates the effect of pp120 on insulin endocytosis, we mutated Arg98 to Ala and examined whether this mutation altered pp120 phosphorylation and its effect on ligand endocytosis in transfected NIH 3T3 cells. This mutation did not modify either pp120 phosphorylation or its effect on receptor-mediated ligand endocytosis. These findings support the hypothesis that stimulation of insulin endocytosis by pp120 is not mediated by Arg98 in the N-terminal IgV-like ectoplasmic domain of pp120.

3T3 Cells↗

Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the juxtamembrane domain of the insulin receptor.

pp120, a substrate of the insulin receptor tyrosine kinase, does not undergo ligand-stimulated phosphorylation by the insulin-like growth factor-1 (IGF-1) receptor. However, replacement of the C-terminal domain of the IGF-1 receptor beta-subunit with the corresponding segment of the insulin receptor restored pp120 phosphorylation by the chimeric receptor. Since pp120 stimulates receptor-mediated insulin endocytosis when it is phosphorylated, we examined whether pp120 regulates IGF-1 receptor endocytosis in transfected NIH 3T3 cells. pp120 failed to alter IGF-1 receptor endocytosis via either wild-type or chimeric IGF-1 receptors. Thus, the effect of pp120 on hormone endocytosis is specific to insulin, and the C-terminal domain of the beta-subunit of the insulin receptor does not regulate the effect of pp120 on insulin endocytosis. Mutation of Tyr960 in the juxtamembrane domain of the insulin receptor abolished the effect of pp120 to stimulate receptor endocytosis, without affecting pp120 phosphorylation by the insulin receptor. These findings suggest that pp120 interacts with two separate domains of the insulin receptor as follows: a C-terminal domain required for pp120 phosphorylation and a juxtamembrane domain required for internalization. We propose that the interaction of pp120 with the juxtamembrane domain is indirect and requires one or more substrates that bind to Tyr960 in the insulin receptor.

3T3 Cells↗

Thioridazine interferences with imipramine metabolism and measurement.

A case is presented in which toxic concentrations of imipramine (Tofranil) resulted from the co-administration of low-dose thioridazine (Mellaril). This probably occurred in an individual with genetically reduced capacity for oxidative drug metabolism, specifically via thioridazine's interference with the hepatic cytochrome P450IID6 isoenzyme (CYP2D6). In addition, coelution of thioridazine and its metabolites resulted in false elevations of imipramine and desipramine as measured by a common high-performance liquid chromatography (HPLC) method (cyanopropyl column). In contrast, an enzyme immunoassay (Abbott TDxFLx) and a second reference HPLC method (silica column) accurately resolved the analytes. This combination of psychiatric drugs is not uncommon in the pediatric population and is one of which both clinicians and laboratorians need to be aware. To the author's knowledge, this is the first report of interferences of thioridazine with both the metabolism and measurement of imipramine in a pediatric patient.

Antidepressive Agents, Tricyclic↗

Buspirone-associated mental status changes.

The pharmacological management of anxiety in children primarily has used antidepressants, such as imipramine. Buspirone, an atypical anxiolytic, has been shown to be of benefit in both adults and children. It has relatively few side effects and is generally well tolerated. Two cases are reported here involving children treated for anxiety with buspirone who subsequently suffered a possible psychotic deterioration.

Anxiety Disorders↗

Bacteriological study of meningococcal meningitis.

One hundred and thirty samples of cerebro spinal fluid were collected from patients admitted with suspected signs and symptoms of meningococcal meningitis (M. meningitis) during the period from January 1986 to April 1989 and were processed for gram's staining, cultivation and latex agglutination tests for detection of polysaccharide antigen in the CSF. Totally 41.5% of turbid and hazy spinal fluid were positive for N. meningitidis by smear examination. Only 24.6% were positive by culture but 61.5% of sample were positive by latex agglutination tests. All the strains were sensitive to all antibiotics except one strain which was resistant to penicillin but it was sensitive to rifampicin.

Adolescent↗