Search PubMed⌕ Search

Biomedical subjects

P Ray

Publications and source records attributed to P Ray.

At least 145 records · Page 8Linked to original sources

Comparative behavioral epidemiology of gonococcal and chlamydial infections among patients attending a Baltimore, Maryland, sexually transmitted disease clinic.

Between April 1988 and May 1989, 400 males and 400 females attending a Baltimore, Maryland, sexually transmitted disease clinic were enrolled in a study evaluating and comparing behaviors associated with culture-proven gonococcal or chlamydial infection. The subjects were enrolled consecutively, and were all seen by the same clinician. Among participants of each sex, gonorrhea but not chlamydia was associated with increasing numbers of recent (the past 30 days) sexual partners. Compared with males with neither infection, factors independently associated with increased risk of gonorrhea included age less than 20 years (odds ratio (OR) = 1.93), the presence of genitourinary symptoms (OR = 8.07), and recent exposure to a new sexual partner (OR = 2.78); risk for chlamydial infection in males was associated with genitourinary symptoms (OR = 2.83) and was significantly reduced in those reporting multiple recent (OR = 0.19) or new (OR = 0.07) sexual partners. Among females, age less than 20 years was independently associated with gonococcal (OR = 1.86) and chlamydial (OR = 7.79) infections in comparison with females with neither infection. No other behavioral factors were associated with chlamydial infection for females in this study; however, having a regular sexual partner was associated with significantly elevated risk of gonorrhea (OR = 3.85), while the presence of genital tract symptoms was associated with diminished risk (OR = 0.29) for gonorrhea. These data suggest that there are differences in the behaviors associated with gonorrheal and chlamydial infections and that different strategies may be useful in efforts to control these infections.

Adolescent↗

Molecular cloning and serological characterization of a new Plasmodium vivax recombinant antigen which contains apolipoprotein B-100 like sequences.

We have isolated a new recombinant antigen 'PV12' of Plasmodium vivax by immunological screening of the genomic library. The antigen shows a sequence homology with human apolipoprotein B-100. A large number of P. vivax infected individuals (79%) were seropositive against this antigen. The probable function of this antigen could be to evade the host defence system (i) by inactivating the perforin of natural killer cells and (ii) by engaging the host immune system to produce antibodies against this decoy antigen.

Amino Acid Sequence↗

Microsurgical approach to the abdominal thoracic duct in the rat: considerations in the collection of lymphocytes.

In experiments involving the collection of thoracic duct lymphocytes the anatomy of the abdominal thoracic duct in the rat has been further defined. In general, the abdominal thoracic duct lies posterior and to the left of the aorta between the renal arteries and the diaphragm. There are variations in the microsurgical approach to the classically described location of this organ that should be noted by investigators attempting to identify and dissect this structure.

Animal Welfare↗

Cytopathology of PC12 cells infected with Japanese encephalitis virus.

Infection of a clonal rat pheochromocytoma cell line, PC12, with Japanese encephalitis (JE) virus produced successively higher titers of virus in the culture fluid during the 72-h experimental period. In electron microscopical observation, JE virus entered PC12 cells by direct penetration through the plasma membrane at 2 min postinoculation (p.i.) and caused marked cellular hypertrophy and extensive proliferation of the cellular secretory system including rough endoplasmic reticulum (RER) and Golgi complexes starting 24 h p.i. The proliferating RER of the virally infected cells contained progeny virions and characteristic endoplasmic reticulum vesicles in its cisternae, and the proliferating Golgi complexes contained virions in their saccules. These findings indicated that the proliferation of the cellular secretory system occurred in association with viral replication and maturation in the system. Seventy-two hours p.i., the cellular secretory system of infected PC12 cells showed degenerative changes with vesiculation, disorganization, and dispersion of the Golgi complexes and fragmentation, focal cystic dilation, and dissolution of the RER in the same manner as those seen in the secretory system of JE-virus-infected neurons in the mouse brain. Thus, JE-virus-infected PC12 cells seem to be a suitable neurogenic cell line for the study of the pathogenic mechanism of JE virus. At the same time, the virally infected cells seem to offer an interesting cell model for the study of the morphogenesis of the cellular secretory system.

Animals↗

Immunomodulatory effect of cyclophosphamide on host humoral immunity in Dunning's R-3327 adenocarcinoma of the prostate.

The object of the present investigations was delineation of the exclusive effects of cyclophosphamide (Cytoxan) on host humoral response to tumor, as evaluated by the level of circulating antigen/antibody complexes (AACs), which may reflect the chemo-responsiveness of hosts and provide a rationale for new therapeutic strategies. Our data, recorded in Copenhagen X Fischer rats bearing Dunning's R-3327 Mat Ly-Lu adenocarcinoma of the prostate, show no modulatory effect of cyclophosphamide at 10 mg/kg, a nonspecific immunosuppressive effect at 30 mg/kg, and a definite immunostimulatory effect on host humoral immunity at 100 mg/kg. Sequential determination of AAC levels at different stages of tumor growth, i.e. from the primary to the metastatic stage, performed with the original purpose of demonstrating that any disturbance in the immunoregulatory mechanism of the host was due to cyclophosphamide rather than to changes in tumor load, revealed that levels of AACs parallel disease progression in the initial stages of primary tumor growth but rapidly decrease to near-normal levels in the presence of heavy tumor burden.

Adenocarcinoma↗

Bayesian estimation of doxorubicin pharmacokinetic parameters.

Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.

Bayes Theorem↗

Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line.

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.

Adenosine Triphosphate↗

Measurement of regional cerebrovascular haemoglobin oxygen saturation in cats using optical spectroscopy.

We describe the use of optical spectroscopy in the near infra-red light range to non-invasively measure regional cerebral haemoglobin oxygen saturation (rSHbO2) in cats during progressive cerebral hypoxia. This technique differs from spectroscopic techniques previously described in that the concentration ratio--percentage haemoglobin: oxygen saturation--is quantified. This saturation is the weighted summation of saturation in the cerebrovascular system: arterial, venous, and capillary beds. In a cat model of progressive cerebral hypoxia, a positive linear correlation between this regional measurement of cerebral saturation and actual saturation, calculated from cerebral arterial and mixed venous blood, was noted (n = 20, r = 0.88, p less than 0.01). The spectroscopic measurement rSHbO2 is also used to index cerebral oxygen extraction. During hypoxia spectroscopic indexed oxygen extraction (iOE) and cerebral arterial-venous difference in oxygen content were simultaneously measured. A least-squares positive linear correlation between these two parameters was noted [AVDO2 = iOE (0.05) + 4.4] (n = 40, r = 0.6, s = 1.2). Objective measurement of 'regional cerebrovascular haemoglobin saturation' and an index of cerebral oxygen extraction are possible using optical spectroscopy.

Algorithms↗

Ectopic expression of a c-kitW42 minigene in transgenic mice: recapitulation of W phenotypes and evidence for c-kit function in melanoblast progenitors.

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor that is allelic with the murine white-spotting locus (W). W mutations affect melanogenesis, gametogenesis, and hematopoiesis during development and adult life, and they result from the partial or complete loss of c-kit function. The W42 allele is a W mutation with severe effects in both the homozygous and the heterozygous states. Previous analysis of the W42 allele identified a missense mutation in an essential amino acid of the c-kitW42 kinase domain that abolishes the in vitro kinase activity of the c-kitW42 protein but does not affect its normal expression. These results suggested that the c-kitW42 allele was a dominant negative mutation within the context of c-kit-mediated signal transduction. To further explore the dominant negative characteristics of the W42 mutation, we have generated transgenic mice in which ectopic expression is driven by the human beta-actin promoter (hAP). Two mouse lines carrying the hAP-c-kitW42 transgene show an effect on pigmentation and the number of tissue mast cells. The patchy coat color pattern of the line 695 mice may reflect variable expression of the transgene in melanoblast progenitors and their descendants and, consequently, is indicative of a function for c-kit in early melanoblasts. Germ cell development and erythropoiesis, however, do not appear to be affected by the transgene. Mice expressing the c-kitW42 transgene therefore recapitulate some of the phenotypes of mice with W mutations. These results are therefore in agreement with the molecular basis of the W42 mutation and the dominant-negative characteristics of the c-kitW42 protein product.

Alleles↗

Isolation and serological characterization of a Plasmodium vivax recombinant antigen.

A genomic library for Plasmodium vivax was constructed in lambda gt11 and immunologically screened with pooled serum samples from vivax patients. Six seroreactive clones were isolated, and one clone, denoted PV9, was studied further. This clone has an unusual base composition (65% G + C), does not share any homology with P. falciparum, and codes for an entirely new antigenic determinant. Antibodies (immunoglobulin G type) against the PV9-encoded polypeptide were produced in all vivax patients older than 15 years. This seroreactivity was lower among patients younger than 15 years (53%). The antigenic epitope(s) of the PV9-encoded polypeptide was recognized at a similar rate by serum samples from P. vivax patients who were living 350 to 973 km apart. Fifty percent of uninfected Indian adults were also seropositive, whereas all European and American (United States) sera tested were negative, suggesting that anti-PV9 antibodies persist after infection. The seroreactivity pattern of this antigen is similar to that of the immunity developed in malaria after repeated infections.

Adolescent↗

Presence of pancreatic trypsin inhibitor in adrenal medullary chromaffin cells.

A bovine pancreatic trypsin inhibitor was isolated from bovine adrenal medullary chromaffin granules. Its N-terminal sequence is: arg-pro-asp-phe-cys-leu-glu-pro-pro-tyr-thr-gly-pro-cys-lys-ala-arg-ile- arg-tyr- phe-tyr-asn-ala-lys-ala-gly-leu-cys-gln-thr-phe-val-tyr-gly-gly-cys-arg- ala-lys-arg-asn-asn-phe-lys- which corresponds precisely with the N-terminus of Bovine Pancreatic Trypsin inhibitor. The presence of this inhibitor in these granules suggests another method of regulating the prohormone proteases present there.

Adrenal Medulla↗

The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase.

The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction.

Amino Acid Sequence↗