Search PubMed⌕ Search

Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 145 records · Page 8Linked to original sources
PubMed1997

Brain-infiltrating cytolytic T lymphocytes specific for Theiler's virus recognize H2Db molecules complexed with a viral VP2 peptide lacking a consensus anchor residue.

Mice expressing the H2b haplotype are resistant to infection with Theiler's murine encephalomyelitis virus (TMEV), which causes chronic demyelination in susceptible mice. The prominent cytolytic T-lymphocyte (CTL) response to the VP2 antigen encoded by TMEV led us to the identification of a class I-binding peptide derived from the VP2 antigen. Escherichia coli transformants overexpressing a series of 11 overlapping VP2 protein fragments were subjected to lysis and alkali digestion, and the resultant peptide pools were tested for their abilities to sensitize RMA-S targets for lysis by CTLs. The source of effector CD8+ T cells for the assays was either freshly harvested central nervous system-infiltrating lymphocytes (CNS-IL) or CNS-IL-derived VP2-specific CTL clones and lines. A 10-residue peptide at VP2 positions 121 to 130 (VP2(121-130)) (FHAGSLLVFM) was identified that sensitized targets for lysis and formed stable complexes with H2Db class I molecules. The VP2(121-130) peptide sensitized target cells for lysis by freshly harvested CNS-IL CTLs at femtomolar concentrations. Despite its relative high level of biological activity, the VP2(121-130) peptide is distinguished from other Db-binding peptides by its lack of an asparagine residue at position five, which had been previously proposed to be a requirement for Db-peptide complexing.

Amino Acid Sequence↗
PubMed1997

Drug-induced linear IgA disease: target antigens are heterogeneous.

No information is available concerning the target antigen(s) in drug-induced linear IgA disease. The purpose of this study was to define better drug-induced linear IgA disease by studying its immunopathological, immunoultrastructural and immunochemical characteristics in three patients. In the first patient, IgA deposits were seen in the lamina lucida. In the second and the third patients, IgA deposits were seen on each side of the lamina densa. Immunoblotting of the first patient's serum showed that IgA reacted with a protein of 230 kDa similar to the bullous pemphigoid-associated antigen 1 (BPAG 1). The second patient's serum did not react with specific bands. In the third patient IgA antibodies reacted with a protein of 97 kDa on epidermal extracts. Our findings suggest that, as in idiopathic forms, the target antigen is not unique in drug-induced linear IgA disease. In some patients, drug-induced linear IgA disease may represent an IgA class response to the BPAG 1.

Adult↗
PubMed1997

High level aminoglycoside resistance in enterococci isolated from hospitalized patients.

Drug resistance in enterococci isolated from hospitalized patients is reported. Out of 421 strains tested, 45 (10.7%) showed high level aminoglycoside resistance (HLAR). At the species level, 8.2 per cent of Enterococcus faecalis and 33.3 per cent of E. faecium were HLAR. While all the strains of E. faecalis were sensitive to vancomycin, one strain of E. faecium was vancomycin resistant.

Anti-Bacterial Agents↗
PubMed1997

MK-801 limits neurovascular dysfunction during experimental allergic encephalomyelitis.

Increased permeability of the blood-brain barrier (BBB) is a characteristic of the demyelinating disease multiple sclerosis and the animal counterpart experimental allergic encephalomyelitis (EAE). In physically traumatized cerebral tissue neurovascular damage, linked with activation of the cerebroendothelial-bound N-methyl-D-aspartate receptor, can be treated with the antagonist MK-801. We have examined the ability of MK-801 to modify BBB leakage and the development of disease during EAE. Prophylactic MK-801, at 0.15 mg kg(-1) body weight suppressed neurovascular breakdown, measured by a dual radioisotope technique, and significantly reduced neurological deficits (P < .05), but not perivascular lesions. A 2-fold increase in administered MK-801 completely prevented abnormal extravasation in cerebella (P < .01) and significantly inhibited BBB disruption in medulla-pons (P < .05) and cervical spinal tissues (P < .01). High-dose treatment also restricted disease development (P < .01) and lesion formation (P < .05). Therapeutic MK-801, at 0.30 mg kg(-1) body weight, completely counteracted neuroendothelial leakage in cerebella (P < .05) and inhibited BBB dysfunction in remaining tissues without restricting inflammatory cell invasion. However, doubling the dose did not further enhance suppression of neurovascular breakdown. Our use of MK-801 to control major features of EAE strongly implicates N-methyl-D-aspartate receptor-dependent mechanisms in disease development and prompts consideration of a role for the receptor in the pathogenesis of human demyelinating conditions.

Animals↗
PubMed1997

Epstein-Barr virus-associated lymphoproliferative disease during methotrexate therapy for psoriasis.

BACKGROUND: Epstein-Barr virus (EBV)-associated lymphoproliferative disorders have recently been observed during treatment of rheumatoid arthritis and dermatomyositis with low-dose methotrexate. OBSERVATION: A patient with psoriasis developed a B-cell lymphoproliferative disorder during long-term treatment with low-dose methotrexate. The lymphoid cells expressed EBV latent membrane protein 1, and the EBV viral genome was present as demonstrated by in situ hybridization. Evaluation for EBV clonality showed that the lymph node contained clonal EBV DNA. Polymerase chain reaction studies confirmed that the B-cell lymphoproliferative disorder was mainly monoclonal, suggesting that the disorder arose from a single EBV-infected B-cell clone. CONCLUSIONS: Lymphoproliferative disorders associated with Epstein-Barr virus in which the clinicopathological presentation is similar to those occurring in patients after transplantation may be observed in patients with psoriasis treated with methotrexate. While it is impossible to rule out a fortuitous occurrence of an EBV-associated lymphoproliferative disorder and psoriasis treated with methotrexate in the same patient, EBV appears to be critical in the pathogenesis of the lymphoproliferative disorder in this patient.

Antigens, Viral↗
PubMed1997

[BCG-induced mycobacterium infection induced by alternative medicine].

INTRODUCTION: Mesotherapy is an alternative medical process defined by the intradermal injection of small amounts of pharmacological substances. It has been associated with the development of mycobacterial infections. CASE REPORT: A 80-year-old woman presented with a Mycobacterium bovis infection of the face following mesotherapy. Genome analysis of the mycobacterial strain isolated from a skin lesion using pulse-field gel electrophoresis demonstrated the presence of a vaccinal strain identical to the one employed by the same physician to vaccinate a child two hours before. DISCUSSION: Given the severity of mycobacterial infections following mesotherapy and given the lack of evidence about its efficacy, mesotherapy should not be performed on the face. Standardisation of aseptic measures in the daily medical practice could prevent such infectious complications.

Aged↗
PubMed1996

The lifetime occurrence of sexually transmitted diseases among a cohort aged 21.

AIMS: To determine the lifetime occurrence of sexually transmitted diseases (STDs) among a cohort aged 21. METHODS: Participants were interviewed at aged 21 as part of a multidisciplinary health and development study. Questions on STDs and sexual behaviour were presented by computer. RESULTS: Of the cohort members known to be alive, 92% responded. Among the sexually experienced 8.6% of the men and 17.3% of the women reported ever having had an STD. Genital warts and chlamydial infection were the commonest STDs among the men, and chlamydial infection, genital warts, and genital herpes among the women. General practice was the commonest place for treatment, and only a minority of people were treated at sexual health clinics. The risk of having an STD increased steeply with the lifetime number of sexual partners. CONCLUSIONS: STDs are common problems among young New Zealanders, especially women. The rate was as high as the US. Prevention should be directed at increasing the use of condoms, but education aimed at reducing the number of sexual partners and delaying the onset of sexual involvement should be considered seriously. A more coordinated approach to treatment is required to take into account the diversity of settings where STDs are treated. Surveillance of STDs needs to be extended, as currently the only data are from sexual health clinics.

Adult↗
PubMed1996

Evidence for phosphorylation of CTP:phosphocholine cytidylyltransferase by multiple proline-directed protein kinases.

Reversible phosphorylation of CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of phosphatidylcholine biosynthesis, is thought to play a role in regulating its activity. In the present study, the hypothesis that proline-directed kinases play a major role in phosphorylating cytidylyltransferase is substantiated using a c-Ha-ras-transfected clone of the human keratinocyte cell line HaCaT. Cellular extracts from epidermal growth factor-stimulated HaCaT cells and from ras-transfected HaCaT cells phosphorylated cytidylyltransferase much stronger as compared with extracts from quiescent HaCaT cells. The tryptic phosphopeptide pattern of cytidylyltransferase phosphorylated by cell-free extracts from ras-transfected HaCaT cells was similar compared with the patterns of cytidylyltransferase phosphorylated by p44mpkmitogen-activated protein kinase and p34cdc2 kinase in vitro, whereas in the case of casein kinase II the pattern was different. Furthermore, in c-Ha-ras-transfected HaCaT cells the in vivo phosphorylation state of cytidylyltransferase was 2-fold higher as compared with untransfected HaCaT cells. This higher phosphorylation of cytidylyltransferase in the ras-transfected clone was reduced to a level below the phosphorylation of cytidylyltransferase in untransfected cells, using olomoucine, a specific inhibitor of proline-directed kinases. The reduced phosphorylation of cytidylyltransferase in olomoucine-treated cells correlated with an enhanced stimulation of enzyme activity by oleic acid.

CDC2 Protein Kinase↗
PubMed1996

Regulation of expression of the rat serine protease inhibitor 2.3 gene by glucocorticoids and interleukin-6. A complex and unusual interplay between positive and negative cis-acting elements.

The rat serine protease inhibitor 2.3 gene (spi 2.3) is almost completely silent in normal animals and is transiently expressed during acute inflammation. It encodes a potential anti-elastase which is likely to play a major physiological role for the host defense. Two well-known inflammatory mediators, glucocorticoids and interleukin-6 (IL-6) activate the spi 2.3 promoter and increase steady-state levels of mRNA in cultured hepatocytes. GC activation is mediated by a single glucocorticoid-response element which seems to act autonomously. A unique array of four functional IL-6-response sites was identified in the spi 2.3 promoter. Three of them (C-II--IV) bear structural identity to the CCAAT/enhancer-binding-protein-binding site consensus sequence, whereas the fourth closely resembles the consensus kappa B nuclear factor recognition motif. The C-IV element, which is the most active, contains the motif 5'-CTGGGA and binds the IL-6-inducible acute-phase response factor present in liver nuclear extracts from inflamed rats. Both basal and IL-6-dependent activities of each individual cytokine-response element tested separately are strongly down regulated by a recently identified regulatory sequence, located in the 3' untranslated region of the spi 2.3 gene. However, this repressor element does not significantly affect overall IL-6-dependent spi 2.3 promoter activity. This suggests that, in the context of the active gene in vivo, all four IL-6-response sites, which are largely redundant, cooperate to overcome the strong repressive effect of the 3' untranslated region silencer and are needed to bring about a maximal IL-6 response. These data reveal a novel type of regulation of an acute-phase gene involving different classes of IL-6-response elements controlled by a repressor and acting in conjunction with a glucocorticoid-response element.

Animals↗
PubMed1996

Progestogen-only oral contraceptives and risk of breast cancer in New Zealand.

Little is known about the influence of progestogen-only oral contraceptives on a woman's risk of breast cancer. This issue was examined in a national population-based case-control study in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. Use of progestogen-only pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who had ever used progestogen-only pills was estimated to be 1.1 (95 percent confidence interval [CI] = 0.73-1.5). In women aged 25 to 34 years, the RR was 2.3 (CI = 1.2-4.3). Women who had started using progestogen-only pills within the last 10 years were at increased risk of breast cancer (RR = 1.6, CI = 1.0-2.4), whereas those who had first used them earlier were at significantly reduced risk (RR = 0.44, CI = 0.22-0.90). These findings are similar to results for depot medroxyprogesterone acetate, and a possible analogy with the influence of pregnancy is also suggested.

Adult↗
PubMed1996

Reversible modification of thiol-containing polypeptides with poly (ethylene glycol) through formation of mixed disulfide bonds. The case of papaya proteinase III.

Papaya proteinase III (PPIII) was purified, as the S-methylthio derivative from the latex of Carica papaya L., by ion-exchange chromatography. Separation of reactivable PPIII from the irreversibly oxidized molecular species of this enzyme was readily achieved after a selective conversion of the reactivated proteinase into the S-monomethoxypoly(ethylene glycol)thio derivative (S-mPEG thio PPIII). From this derivative, a PPIII preparation titrating 1 mol of thiol/mol of enzyme was regenerated. From the physicochemical properties of S-mPEG thio PPIII that were investigated, it is concluded that interactions between the mPEG and the PPIII chains occur only to a limited extent. In addition to its usefulness for purifying thiol-containing enzymes, the mPEG modification resulting from mixed disulfide bond formation may find other practical applications.

Circular Dichroism↗
PubMed1996

Comparison of idarubicin and daunorubicin and their main metabolites regarding intracellular uptake and effect on sensitive and multidrug-resistant HL60 cells.

To study the effect of the main metabolites on the cytotoxic effect of daunorubicin and idarubicin in human HL-60 cells, drug-sensitive and multidrug-resistant HL60 cells were incubated with idarubicin and daunorubicin and their metabolites idarubicinol and daunorubicinol over a wide range of concentrations. The intracellular uptake of the drugs was determined by photofluorometry, and the cytotoxic effect in vitro was determined by a bioluminescence assay of intracellular adenosine triphosphate (ATP) after 4 days of culture in liquid medium. The effect of intracellular drugs was calculated from the incubation-concentration versus intracellular-uptake and cytotoxic-effect curves. The intracellular uptake of idarubicin was 6 times that of daunorubicin in drug-sensitive cells and 25 times higher in resistant cells. For idarubicinol as compared with daunorubicinol the corresponding factors were 25 and 7, respectively. As compared with the parent substances, the uptake of idarubicinol and daunorubicinol was 16% and 4%, respectively, in sensitive cells and 40% and > 100%, respectively, in resistant cells. An intracellular concentration of 0.5 nmol/mg protein of both parent substances caused a 50% growth inhibition in drug-sensitive cells as compared with 10 nmol/mg protein for drug-resistant cells. For the metabolites an intracellular concentration of 0.4 nmol/mg protein of idarubicinol and 2.0 nmol/mg protein of daunorubicinol was required to inhibit cells' growth by 50% in drug-sensitive HL60 cells. In the resistant HL60 cells the corresponding values were 30 nmol/mg protein for idarubicinol and 40 nmol/mg protein for daunorubicinol. These results confirm that idarubicinol may significantly contribute to the clinical effect of idarubicin. However, in combination with previous results that have shown low intracellular concentrations of the metabolites in vivo, it appears that the pharmacokinetic properties of the mother substances provide the major explanation for the clinical effect of idarubicin.

Antibiotics, Antineoplastic↗
PubMed1996

HIV/AIDS in New Zealand: an epidemic in decline?

OBJECTIVE: To describe the AIDS epidemic in New Zealand, and to discuss the reasons for an apparent decline in incidence. METHODS: The AIDS Epidemiology Group collects information on persons diagnosed with AIDS through a compulsory notification system. Data were presented on people diagnosed to the end of 1994, and reported by the end of September 1995. RESULTS: The cumulative incidence of AIDS in New Zealand was similar to that in some other Western countries, such as the United Kingdom, Germany and Sweden, before 1989, but has been declining since 1989. The epidemic is concentrated among men who have sex with men (89%). The median survival after diagnosis with AIDS is 13 months. CONCLUSIONS: The observed decline is not likely to be due to reporting delays or changes in reporting or diagnostic practices. The major factor was probably a rapid decline in HIV incidence among homosexual men a decade ago, and the effective prevention of epidemics in other subgroups. The epidemic in New Zealand started later than in other countries, enabling an earlier response, and there is evidence of behaviour change in high risk groups. Preventive efforts and monitoring must be maintained in order to ensure there is no reversal of this decline.

Acquired Immunodeficiency Syndrome↗