Biomedical subjects

S Joseph

Publications and source records attributed to S Joseph.

At least 19 recordsLinked to original sources

PubMed1999

Site-directed hydroxyl radical probing of 30S ribosomal subunits by using Fe(II) tethered to an interruption in the 16S rRNA chain.

Two in vitro transcripts, one corresponding to the 5' and central domains (residues 1-920) of 16S rRNA and the other corresponding to its 3' domain (residues 922-1542), assemble efficiently in trans with 30S ribosomal proteins to form a compact ribonucleoprotein particle that cosediments with natural 30S subunits. Isolated particles are similar in appearance to natural 30S subunits with electron microscopy and contain a full complement of the small subunit ribosomal proteins. The particles have a reduced ability to bind tRNA (attributable to the location of the discontinuity in a conserved region of the rRNA) near features that have been implicated in tRNA binding. Association of these two halves of 16S rRNA in trans must be stabilized by either previously unidentified RNA-RNA contacts or interactions mediated by ribosomal proteins because there are no known direct interactions between them. The trans construct was used to probe the three-dimensional RNA neighborhood around position 922 of 16S rRNA by generating hydroxyl radicals from Fe(II) tethered to the 5' end of the 3' transcript. Hydroxyl radical-induced cuts in the 16S rRNA chain were localized by primer extension to nucleotides 923-929 and 1192-1198, providing evidence for the mutual proximity of the 920 and 1192 regions.

Centrifugation, Density Gradient↗

PubMed1999

The lymphopenia mutation of the BB rat causes inappropriate apoptosis of mature thymocytes.

BB rats develop autoimmune diabetes mellitus at a high frequency. A key factor in the development of the disease is an autosomal recessive mutation determining peripheral T cell lymphocytopenia. Previous studies have suggested that the lymphopenia could be caused by increased cell death. Here we demonstrate that the lyp mutation dramatically reduces the in vitro lifespan of the TCRhi single-positive thymocytes and peripheral T cells, without abolishing their capacity to proliferate. The reduced lifespan is due to an increased rate of apoptosis, and is detected in single-positive thymocytes displaying characteristics of cells which have undergone positive selection. The cell death defect does not affect the in vitro lifespan of peripheral B cells. Interestingly, stimulation can rescue peripheral lyp/lyp T cells from immediate cell death. We propose that the lymphopenia mutation prevents the accumulation of a normal T cell pool, including regulatory subsets, without preventing the activation and proliferation of reactive T cells, thereby creating conditions appropriate for the development of uncontrolled autoimmune responses.

Animals↗

PubMed1999

Posttraumatic stress disorder and traumatic brain injury: are they mutually exclusive?

It has been suggested that posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) must be mutually incompatible disorders. However, growing empirical evidence has begun to question this. Evidence suggests that although PTSD may be relatively rare among the TBI population, some TBI patients seem to develop PTSD. We suggest two theoretical routes through which PTSD might develop in TBI patients: through nonconscious processes in individuals who are subsequently amnesic, but who were conscious at the time of the traumatic episode and through subsequent appraisal processes in individuals who were unconscious during the traumatic episode.

Adaptation, Psychological↗

PubMed1999

Mouse adenovirus (MAV-1) expression in primary human endothelial cells and generation of a full-length infectious plasmid.

Using RT-PCR, we show that mouse adenovirus type I (MAV-1) is capable of infecting and expressing in various cell types, specifically human endothelial cells. The capability of MAV-1 to infect and express in human endothelial cells makes it a potentially useful alternative to the use of human adenoviruses type 2/5 (Ad2/5) in virus-based gene therapy, although presently MAV-1 can only be produced at lower titers than Ad2/5. In this report, we present methods for the purification of MAV-1 DNA and use of this DNA along with a modified bacteria-based homologous recombination protocol to generate a full-length plasmid clone of MAV-1 DNA. Using various transfection procedures, we show that this plasmid MAV-1 DNA can generate plaques of MAV-1 virus, albeit at low efficiencies (about 0. 2 p.f.u./microg DNA). Furthermore, the construction of an MAV-1 plasmid along with its capability to express in human cells justifies the full development of MAV-1 into a system of gene therapy.

Adenoviridae↗

PubMed1999

Neuropsychological factors associated with borderline pathology in children.

OBJECTIVE: To determine whether children with borderline pathology have a specific pattern of neuropsychological risk factors. METHOD: The subjects were 94 school-age children in day treatment, divided into borderline (n = 41) and nonborderline (n = 53) groups according to results of the Child version of the Diagnostic Interview for Borderlines. All children were assessed with the Child Behavior Checklist, the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and a neuropsychological battery. RESULTS: Children with borderline pathology had abnormal scores on the Wisconsin Card Sorting Test and on the Continuous Performance Test, both of which suggested problems with executive function. Although borderline pathology was highly comorbid with conduct disorder, most results were independent of this comorbidity. CONCLUSIONS: Borderline pathology in children has a unique pattern of neuropsychological risk factors that may reflect a diathesis for this syndrome.

Analysis of Variance↗

PubMed1998

Drug metabolism biosensors: electrochemical reactivities of cytochrome P450cam immobilised in synthetic vesicular systems.

Biosensors containing cytochrome P450cam in a didodecyldimethylammonium bromide vesicular system were prepared by cross-linking onto a glassy carbon electrode (GCE) with glutaraldehyde in the presence of bovine serum albumin. Cyclic voltammetric responses of the sensor in air-free buffer solution showed that the sensor exhibited reversible electrochemistry due to direct electron exchange between the haem Fe(3+/2+) redox system and the GCE surface. In air-saturated solution containing camphor, the biosensor gave an irreversible electrocatalytic current which is compatible with the monooxygenation of the substrate. Steady state amperometric experiments with camphor, adamantanone and fenchone were performed with a biosensor prepared by cross-linking P450cam with glutaraldehyde onto a Pt disc electrode. The sensor was characterised by fast amperometric responses, attaining steady-state in about 20 s in a cobalt sepulchrate mediated electrochemical system. The kinetic parameters of the biosensor were analysed using the electrochemical Michaelis Menten equation. The estimated apparent Michaelis-Menten constant, Km, values for the biosensors were in the range of 1.41-3.9 mM.

Animals↗

PubMed1998

EF-G-catalyzed translocation of anticodon stem-loop analogs of transfer RNA in the ribosome.

Translocation, catalyzed by elongation factor EF-G, is the precise movement of the tRNA-mRNA complex within the ribosome following peptide bond formation. Here we examine the structural requirement for A- and P-site tRNAs in EF-G-catalyzed translocation by substituting anticodon stem-loop (ASL) analogs for the respective tRNAs. Translocation of mRNA and tRNA was monitored independently; mRNA movement was assayed by toeprinting, while tRNA and ASL movement was monitored by hydroxyl radical probing by Fe(II) tethered to the ASLs and by chemical footprinting. Translocation depends on occupancy of both A and P sites by tRNA bound in a mRNA-dependent fashion. The requirement for an A-site tRNA can be satisfied by a 15 nucleotide ASL analog comprising only a 4 base pair (bp) stem and a 7 nucleotide anticodon loop. Translocation of the ASL is both EF-G- and GTP-dependent, and is inhibited by the translocational inhibitor thiostrepton. These findings show that the D, T and acceptor stem regions of A-site tRNA are not essential for EF-G-dependent translocation. In contrast, no translocation occurs if the P-site tRNA is substituted with an ASL, indicating that other elements of P-site tRNA structure are required for translocation. We also tested the effect of increasing the A-site ASL stem length from 4 to 33 bp on translocation from A to P site. Translocation efficiency decreases as the ASL stem extends beyond 22 bp, corresponding approximately to the maximum dimension of tRNA along the anticodon-D arm axis. This result suggests that a structural feature of the ribosome between the A and P sites, interferes with movement of tRNA analogs that exceed the normal dimensions of the coaxial tRNA anticodon-D arm.

Anticodon↗

PubMed1998

Cardiac troponins.

Explore the source record for details and available documents.

Angina, Unstable↗

PubMed1998

The Depression-Happiness Scale: reliability and validity of a bipolar self-report scale.

This article reports two studies aimed at validating the 25-item self-report McGreal and Joseph (1993) Depression-Happiness Scale (D-H S). In the first study, principal component data are reported on the D-H S with 194 respondents. A forced 1-factor solution confirmed the unidimensionality of the scale (item loadings ranged from .38 to .77) and thus the feasibility of a statistically bipolar measure. In the second study, data on the convergent validity of the D-H S with the Beck Depression Inventory (r=-.75) and the Oxford Happiness Inventory (r=.59) with 100 respondents are reported confirming the construct validity of the scale. Implications for research in social and clinical psychology are discussed along with the possible uses of the D-H S in a clinical setting.

Adolescent↗

PubMed1998

Synergistic effect of flunarizine and sodium valproate on seizure thresholds elicited by cortical stimulation in conscious rats.

The effect of flunarizine (FLU) and sodium valproate (SV) alone and in combination were examined for their effects on seizure thresholds elicited by cortical stimulation in conscious rats. Two different pharmacodynamic parameters could be distinguished viz, the threshold for localised seizures (TLS) defined as the current (mu A) required to elicit forelimb clonus and the threshold for generalised seizure (TGS), defined as the current (mu A) required to elicit vigorous clonic activity without a tonic component. In preliminary neuro-behavioral studies on rats, the most favourable combination was FLU 10 mg/kg i.p. and SV 200 mg/kg i.p., which produced anticonvulsant efficacy with minimal neurotoxicity. With FLU alone, SV alone and the combination of FLU and SV, the mean % change +/- SEM from baseline values over a period of 6 h were for TLS: 3.8 +/- 0.8, 23.9 +/- 3.7, and 29.8 +/- 2.1; and for TGS 5.5 +/- 0.7, 15.6 +/- 2.7 and 190.9 +/- 22.7 respectively, indicating that FLU alone had no effect on TLS or TGS, SV significantly elevated TLS but had no effect on TGS and the combination of FLU plus SV produced a synergistic elevation of both TLS and TGS-the intensity of effect being more on TGS than on TLS. This model provides a new dimension to the profiling of two anticonvulsant agents with different mechanisms of anticonvulsant activity and offers predictive criteria for protective effects on clinical manifestations of partial or generalised tonic clonic seizure.

Animals↗

PubMed1998

Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice.

The efficacy of Flunarizine (FLU), a calcium channel blocker, in combination with conventional antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), and ethosuximide (ESM), at ED50 doses, were examined for protective effects against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures in mice. In both models, only VPA and FLU showed significantly enhanced protection, which was additive ie. 100% protection. In the MES test, though FLU combined with PHT did show a slightly enhanced protection (66.6%), with CBZ there was no enhancement as compared to either drug alone. In the PTZ test, FLU with ESM showed 83% protection this however was not statistically significant. The findings of this study in mice suggest that FLU would be a suitable candidate for add-on therapy with VPA for clinical epilepsy.

Animals↗

PubMed1997

Mapping the inside of the ribosome with an RNA helical ruler.

The structure of ribosomal RNA (rRNA) in the ribosome was probed with hydroxyl radicals generated locally from iron(II) tethered to the 5' ends of anticodon stem-loop analogs (ASLs) of transfer RNA. The ASLs, ranging in length from 4 to 33 base pairs, bound to the ribosome in a messenger RNA-dependent manner and directed cleavage to specific regions of the 16S, 23S, and 5S rRNA chains. The positions and intensities of cleavage depended on whether the ASLs were bound to the ribosomal A or P site, and on the lengths of their stems. These data predict the three-dimensional locations of the rRNA targets relative to the positions of A- and P- site transfer RNAs inside the ribosome.

Anticodon↗

PubMed1997

Religiosity and sphere-specific just world beliefs in 16- to 18-year-olds.

One hundred forty-three (31 female and 112 male) English school pupils, 16 to 18 years old, completed the Francis Scale of Attitudes towards Christianity (FSAC; Francis & Stubbs, 1987), the Global Belief in a Just World Scale (GBJWS; Lipkus, 1991), and the Multidimensional Belief in a Just World Scale (MBJWS; Furnham & Procter, 1992). The MBJWS yields three subscale scores: Sociopolitical Just World Beliefs (SJW), Interpersonal Just World Beliefs (IJW), and Personal Just World Beliefs (PJW). Scores on the FSAC were not associated with scores on the GBJWS, the SJW, or the IJW, but they were positively associated, albeit weakly, with scores on the PJW.

Adolescent↗

PubMed1997

Rifampin-monoresistant tuberculosis in New York City, 1993-1994.

All New York City patients whose cultures yielded Mycobacterium tuberculosis with isolated resistance to rifampin in 1993 and 1994 were included in this study. Of the 96 patients, 48 (50%) had primary resistance, 32 (33%) had acquired resistance, and 16 (17%) had unclassified resistance; 66% had histories of illicit drug use, and 79% were infected with human immunodeficiency virus (HIV). The median time to emergence of resistance was 40 weeks among the 32 patients with acquired resistance. Each of the HIV-infected patients with acquired resistance (cases, n = 29) was matched to two HIV-infected patients who had disease due to fully susceptible M. tuberculosis (controls, n = 58). In multivariate analysis, factors associated with the emergence of rifampin resistance were as follows: a sputum smear positive for acid-fast bacilli, advanced immunosuppression, and nonadherence to therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Lack of HLA-DR2-associated DRB1 gene in a family.

HLA-DR51 haplotypes co-express one DRB1 (B1*15 or B1*16) gene and one DRB5 gene. These haplotypes also carry two pseudogenes (DRB6 and DRB9) During routine HLA typing for transplantation, we observed an unexpected DR51 haplotype in two subjects (mother and daughter) in a family. Serological typing showed that these subjects are positive for DR51 and DQ6 but negative for DR15 and DR16. Investigations of genomic DNA by molecular techniques showed that these individuals carry DRB5*0101, DRB6*02 and DQB1*0602 genes, whereas the DRB1 gene associated with either DR15 (B1*1501 to B1*1504) or DR16 (B1*1601 to B1*1606) was not detected in the mother and daughter. It is possible that the new haplotype, DQB1*0602, DRB6*02, DRB5*0101, arose by deletion of DR2-associated DRB1 gene.

Female↗

PubMed1997

Limited utility of ICD-10 and DSM-IV classification of dissociative and conversion disorders in India.

Studies of psychiatric out-patients from India have found that diagnosis of some of the subcategories of the dissociative and conversion disorders of the ICD and DSM classificatory systems are rarely made in this setting. Moreover, it was found that a significant percentage of patients seen in psychiatric practice may not fit into the defined subcategories of dissociative (conversion) disorders of these systems of classification. We studied the prevalence of various ICD-10 and DSM-IV categories of dissociative (conversion) disorders and our own proposed category of 'brief dissociative stupor' (BDS), among all the in-patients of a psychiatric unit in a general teaching hospital, over a 2-year period. There were 18 patients who fulfilled our criteria for BDS and 18 patients in the second group which included all of the remaining subjects with a diagnosis of any other subcategory of dissociative disorder according to ICD-10. Our analysis revealed that there were no patients with a diagnosis of dissociative amnesia, fugue, stupor, trance and possession disorders or identity disorders. There were significantly more female patients in the BDS group, and they also had significantly more comorbid Axis-I diagnoses and panic attacks. Since 50% of our patients fulfilled the criteria for BDS, there is clearly a need for further studies to establish the prevalence of this subcategory in patients from other centres. The classification of these patients with this phenomenology is problematic. Inclusion of a subcategory of dissociative non-epileptic seizures, instead of dissociative convulsions, should improve the classification of dissociative (conversion) disorders.

Adolescent↗

PubMed1997

Attitudes towards emotional expression and post-traumatic stress in survivors of the Herald of Free Enterprise disaster.

The relationship between self-reported attitudes towards emotional expression, assessed at three years after the accident, and post-traumatic symptoms, assessed at five years after the accident, was investigated in 37 survivors of the Herald of Free Enterprise disaster. It was found that lower scores on the attitudes towards emotional expression scale, indicating more negative attitudes (e.g. 'I think getting emotional is a sign of weakness') were associated with higher symptom scores. This association remained even when retrospectively assessed perceptions of helplessness during the disaster and symptoms assessed at three years were partialled out. Implications for therapeutic intervention are discussed.

Accidents, Traffic↗

PubMed1997

Schizotypal traits and dimensions of religiosity.

In the present study the association between religiosity and schizotypal traits was investigated. Two hundred and one respondents completed self-report measures of schizotypal traits as well as measures of religiosity developed, on the basis of theoretical work on the nature of delusional thinking, to tap the dimensions of preoccupation, guidance, conviction, and emotional involvement. For women, no associations were found between scores on the religiosity and schizotypy scales. For men, however, higher scores on religious preoccupation were associated with higher scores on magical ideation. It would seem that religiosity is not clearly associated with schizotypal traits.

Adolescent↗