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Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 73 records · Page 4Linked to original sources
PubMed2001

Rising incidence and prevalence of herpes simplex type 2 infection in a cohort of 26 year old New Zealanders.

OBJECTIVES: To examine changes in the incidence and prevalence of herpes simplex type 2 (HSV-2) infection in a birth cohort of 26 year old New Zealanders in whom seroprevalence had been measured at 3.4% at age 21. METHODS: Sera from 869 cohort members were tested using an indirect IgG enzyme linked immunoassay specific to the HSV-2 glycoprotein G. Serological results were compared with detailed sexual histories. RESULTS: In all, 96 participants (11%) were seropositive for HSV-2, including at least 56 who seroconverted after their 21st birthday. Among those known to be seronegative at age 21, the annual seroconversion rate was 13.5 cases per 1000 per year, compared with 8.1 cases per 1000 per sexually active year before age 21. New infections were associated with female sex and an early age of first intercourse. The average rate of partner change was lower in the cohort after age 21, and was only modestly increased among those who acquired new HSV-2 infections between ages 21 and 26. CONCLUSIONS: HSV-2 seroprevalence has risen sharply in this sexually active cohort, despite a reduction in the overall level of partner change. Increased rates of HSV-2 acquisition after age 21 may be due to a higher prevalence of infection in the pool of potential partners encountered during the third decade of life. Factors related to partner choice may have more influence on the risk of HSV-2 infection than the number of sexual partners alone.

Adult↗
PubMed2001

Hsp27 protects mitochondria of thermotolerant cells against apoptotic stimuli.

Enhanced cell survival and resistance to apoptosis during thermotolerance correlates with an increased expression of heat shock proteins (Hsps). Here we present additional evidence in support of the hypothesis that the induction of Hsp27 and Hsp72 during acquired thermotolerance in Jurkat T-lymphocytes prevents apoptosis. In thermotolerant cells, Hsp27 was shown to associate with the mitochondrial fraction, and inhibition of Hsp27 induction during thermotolerance in cells transfected with hsp27 antisense potentiated mitochondrial cytochrome c release after exposure to various apoptotic stimuli, despite the presence of elevated levels of Hsp72. Caspase activation and apoptosis were inhibited under these conditions. In vitro studies revealed that recombinant Hsp72 more efficiently blocked cytochrome c-mediated caspase activation than did recombinant Hsp27. A model is presented for the inhibition of apoptosis during thermotolerance in which Hsp27 preferentially blocks mitochondrial cytochrome c release, whereas Hsp72 interferes with apoptosomal caspase activation.

Apoptosis↗
PubMed2001

Interactions between P-glycoprotein and drugs used in the supportive care of acute myeloid leukemia patients.

Multidrug resistance due to overexpression of P-glycoprotein (Pgp) leads to reduced intracellular drug accumulation and makes the cells resistant to chemotherapy. In this study we focused on how drugs used in the supportive care of acute myeloid leukemia (AML) patients interfere with Pgp. The effect on intracellular accumulation of the fluorescent dye Rhodamine 123 (Rh 123) was studied in the human promyelocytic leukemia cell line HL-60 and two anthracycline resistant, Pgp expressing, sublines. Each drug was used at two different concentrations: plasma peak concentration and half the plasma peak concentration. Drugs which increased the Rh 123 uptake by > 10% were included in the second part of the study where the cytotoxic effect was tested in combination with daunorubicin. In the Rhodamine assay none of the tested drugs had any significant effect on the Rh 123 efflux in the resistant cell lines. Amphotericin B, cefuroxime, erythromycin and dixyrazin had minor effects on Rh 123 uptake but showed a significant additive effect to the toxicity of daunorubicin suggesting other mechanisms of action than reversal of Pgp. In conclusion this in vitro model where Rh 123 uptake was studied in an anthracycline resistant leukemia cell line could not demonstrate any significant interactions with Pgp for the tested drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Retinoid receptor expression and its correlation to retinoid sensitivity in non-M3 acute myeloid leukemia blast cells.

All-trans-retinoic acid (ATRA) has significantly improved the treatment results in acute promyelocytic leukemia (M3). In non-M3 acute myeloid leukemia (AML), the effects are less clear, and there is a pronounced heterogeneity in the sensitivity to the growth-inhibitory effects of retinoids in leukemic cells from different non-M3 AML patients. Retinoids exert their effects through a number of nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)]. In this study, we determined the expression of RAR alpha, RAR beta, RAR gamma, and RXR alpha by real-time PCR in four cell lines and in blast cells from patients with non-M3 AML before and after ATRA incubation. All four receptors were expressed in cells from all 18 tested patient samples and in four myeloid cell lines. In the majority of the patient samples as well as in the cell lines, there was a pattern of high expression of RAR alpha and RXR alpha and low expression of RAR beta and RAR gamma. There was no correlation between the basal expression of any of the retinoid receptors and sensitivity to ATRA. A 24-h exposure to ATRA increased the expression of RAR alpha, RAR beta, RAR gamma, and RXR alpha in 46%, 77%, 30%, and 38% of the samples, respectively. The mean increase in receptor expression was most pronounced for RAR beta and RXR alpha. There was a significant correlation between an increase in RAR beta expression in response to ATRA and sensitivity to ATRA (P < 0.014). No such correlations were found for RAR alpha, RAR gamma, and RXR alpha. The expression of the monocytoid marker CD14 was significantly correlated with increased expression of RAR alpha (P = 0.03). We conclude that RAR alpha, RAR beta, RAR gamma, and RXR alpha are expressed in non-M3 AML blast cells and that ATRA-induced expression of RAR beta may be a marker for retinoid sensitivity.

Adult↗
PubMed2001

Once daily treatment with terbinafine 1% cream (Lamisil) for one week is effective in the treatment of tinea corporis and cruris. A placebo-controlled study.

Duration of therapy is an important factor in determining patients' compliance in dermatomycosis. Terbinafine (Lamisil) is an allylamine antifungal agent. Its fungicidal properties against dermatophytes should allow physicians to reduce treatment duration without affecting the cure rate. This study was carried out to determine the efficacy and tolerability of terbinafine 1% cream, applied once daily for 7 days, in adult patients with tinea corporis/cruris. In a multicentre, randomized, double-blind, parallel-group study, patients with a clinical diagnosis of tinea corporis/cruris confirmed by microscopy and culture received treatment with either terbinafine 1% cream (n = 57) or placebo cream (n = 60). The patients applied the cream once daily for 7 days, and were then observed for a further 7 weeks. The efficacy was assessed at the end of the study by comparing the rates of mycological cure in the two treatment groups. Total clinical signs and symptoms scores, clinical response, and overall treatment efficacy were also measured and compared between the two groups. A 7-day once-daily course of terbinafine was significantly more effective than placebo in achieving and maintaining mycological cure (84.2 versus 23.3%, P< 0.001). Terbinafine was also significantly more effective than placebo in terms of clinical response, reduction in signs and symptoms scores, and overall efficacy. The short treatment regimen and the sustained high cure rate should contribute to making terbinafine a valuable treatment option in tinea corporis/cruris.

Administration, Cutaneous↗
PubMed2000

Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo.

HSP27 form oligomeric structures up to 800 Kda. In cultured cells, the equilibrium between small and large oligomers shifted towards smaller oligomers when phosphorylated on serine residues. To further explore HSP27 structural organization and its repercussion in HSP27 antiapoptotic and tumorigenic properties, we transfected colon cancer REG cells with wild type HSP27 and two mutants in which the phosphorylatable serine residues have been replaced by alanine (to mimic the non phosphorylated protein) or aspartate (to mimic the phosphorylated protein). In growing cells, wild type and alanine mutant formed small and large oligomers and demonstrated antiapoptotic activity while aspartate mutant only formed small multimers and had no antiapoptotic activity. In a cell-free system, only large oligomeric structures interfered with cytochrome c-induced caspase activation, thereby inhibiting apoptosis. The inability of the aspartate mutant to form large oligomers and to protect tumor cells from apoptosis was overcome by growing the cells in vivo, either in syngeneic animals or nude mice. These observations were reproduced by culturing the cells at confluence in vitro. In conclusion (1) large oligomers are the structural organization of HSP27 required for its antiapoptotic activity and (2) cell-cell contacts induce the formation of large oligomers, whatever the status of phosphorylatable serines, thereby increasing cell tumorigenicity.

Amino Acid Substitution↗
PubMed2000

Enhanced surveillance of HIV infections in New Zealand, 1996-1998.

AIM: To improve understanding of the HIV epidemic in New Zealand through use of an enhanced voluntary reporting system for new diagnoses of HIV. METHODS: Routine reporting of new HIV diagnoses by the two laboratories that perform confirmatory HIV antibody testing, to the Department of Health and later to the AIDS Epidemiology Group, has been in place since 1985. From January 1996, this was supplemented by a questionnaire about demographic characteristics and circumstances of HIV exposure sent to clinicians requesting the HIV test. RESULTS: From January 1996 to December 1998, 260 new diagnoses of HIV were reported (205 males, 55 females) and extra information was obtained from clinicians for 253 (97.3%) people. HIV diagnosis rate was highest for 'other' ethnicity and similar for European, Maori and Pacific Island ethnic groups. Sexual intercourse between men was the commonest mode of infection (43.5%), followed by heterosexual intercourse (40.0%) and injecting drug use (2.7%). Places of infection were New Zealand (38.5%), Australia (7.7%), 'other' overseas (45.4%) and unknown (8.5%). Heterosexual infections were acquired through contact with a person in or from a high prevalence area (mainly in Africa or Asia) for 86.7% of males and 68.2% of females. Second generation heterosexual transmission was rare. CONCLUSIONS: Introduction of an enhanced surveillance system has been successful. Results confirm continuing spread of HIV in New Zealand amongst men who have sex with men, and suggest low levels of heterosexual and injecting drug use transmission in New Zealand. Of major importance in the occurrence of heterosexual infection is the role of imported HIV.

Adolescent↗
PubMed2000

Psychiatric disorders and risky sexual behaviour in young adulthood: cross sectional study in birth cohort.

OBJECTIVE: To determine if risky sexual intercourse, sexually transmitted diseases, and sexual intercourse at an early age are associated with psychiatric disorder. DESIGN: Cross sectional study of a birth cohort at age 21 years with assessments presented by computer (for sexual behaviour) and by trained interviewers (for psychiatric disorder). SETTING: New Zealand in 1993-4. PARTICIPANTS: 992 study members (487 women) from the Dunedin multidisciplinary health and development study. Complete data were available on both measures for 930 study members. MAIN OUTCOME MEASURES: Psychiatric disorders (anxiety, depression, eating disorder, substance dependence, antisocial disorder, mania, schizophrenia spectrum) and measures of sexual behaviour. RESULTS: Young people diagnosed with substance dependence, schizophrenia spectrum, and antisocial disorders were more likely to engage in risky sexual intercourse, contract sexually transmitted diseases, and have sexual intercourse at an early age (before 16 years). Unexpectedly, so were young people with depressive disorders. Young people with mania were more likely to report risky sexual intercourse and have sexually transmitted diseases. The likelihood of risky behaviour was increased by psychiatric comorbidity. CONCLUSIONS: There is a clear association between risky sexual behaviour and common psychiatric disorders. Although the temporal relation is uncertain, the results indicate the need to coordinate sexual medicine with mental health services in the treatment of young people.

Adult↗
PubMed2000

pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F.

The retinoblastoma protein pRB is involved in the transcriptional control of genes essential for cell cycle progression and differentiation. pRB interacts with different transcription factors and thereby modulates their activity by sequestration, corepression, or activation. We report that pRB, but not p107 and p130, binds to and facilitates repression by p120(E4F), a ubiquitously expressed GLI-Kruppel-related protein identified as a cellular target of E1A. The interaction involves two distinct regions of p120(E4F) and the C-terminal part of pRB. In vivo pRB-p120(E4F) complexes can only be detected in growth-arrested cells, and accordingly contain the hypophosphorylated form of pRB. Repression of an E4F-responsive promoter is strongly increased by combined expression of p120(E4F) and pRB, which correlates with pRB-dependent enhancement of p120(E4F) binding activity. Elevated levels of p120(E4F) have been shown to block growth of mouse fibroblasts in G(1). We find this requires pRB, because RB(-/-) fibroblasts are significantly less sensitive to excess p120(E4F).

Adenovirus E1A Proteins↗
PubMed2000

Pregnancies among New Zealand teenagers: trends, current status and international comparisons.

AIMS: To examine trends in birth and total pregnancy rates among teenage women in New Zealand, ethnic differences and international comparisons. METHODS: Routinely collected data on births and abortions by age in New Zealand have been used to derive teenage birth rates and estimated total teenage pregnancy rates. RESULTS: The teenage birth rate rose from the end of the Second World War until 1972, then dropped until 1986, since when it has risen slightly. An increase in the proportion of teenage pregnancies aborted since 1986 has prevented a more marked increase in the birth rate. In 1997, the teenage birth rate for Maori was nearly five times, and the Pacific rate over three times, that of European/Pakeha teenagers. Although the abortion rate was slightly higher among Maori than European/Pakeha teenagers, Maori who became pregnant were much less likely to have an abortion. Of the developed OECD countries, only the USA has a higher teenage birth rate than New Zealand. However, the teenage birth rate among European/Pakeha in New Zealand, while higher than in many Western European countries, is similar to the total rate in Australia, and less than that in the UK and Canada. CONCLUSIONS: This analysis shows that using routinely collected data, it is possible to monitor national teenage pregnancy rates. Improvements in monitoring could be made by collecting ethnicity data on abortions and births in a consistent manner, together with the area of residence of women having abortions. The findings indicate the importance of understanding the impact on Maori women who become pregnant as teenagers and on their children.

Abortion, Induced↗
PubMed2000

Oral contraceptives and fatal pulmonary embolism.

In a national case-control study of fatal pulmonary embolism in New Zealand women of childbearing age, we estimated that current users of combined oral contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national distribution data, the absolute risk of death from pulmonary embolism in current users was estimated to be 10.5 per million woman-years.

Adult↗
PubMed2000

Health researchers' views of ethics committee functioning in New Zealand.

AIMS: To find out, from the perspective of researchers, how ethics committees are dealing with matters of ethical concern in research on humans and to seek the views of researchers on their role in thinking through the ethical issues in research. METHODS: A sample of researchers was selected from the Health Research Council database of grant recipients. Information was sought, using a mailed questionnaire, in relation to essential elements of concern to ethics committees according to the 1996 National Standard, types of study undertaken, codes of practice, national application forms, multicentre review, aspects of committee function and the role of researchers. RESULTS: The response rate was 35/40 (87.5%). Approximately half the respondents commented favourably on most aspects of ethics committee functioning. Major criticisms were directed at the assessment of risks and benefits, scientific validity and handling of consent procedures. Consistent weaknesses in multicentre review, quality of advice and the composition of committees were noted. Positive aspects were: availability of chairpersons for discussion, the protection of vulnerable participants, the handling of the Health Information Privacy Code and the introduction of a national application form. Most researchers expected to take a major role in thinking through the ethical issues in their work. Half reported occasions where ethics committees had unnecessarily impeded research. CONCLUSIONS: The high level of commitment of researchers to ethics should be acknowledged by involving them more in guideline development and education. Perceived deficiencies in the range of expertise on ethics committees, particularly expertise to judge potential harms in experimental research, should be further investigated and addressed. Recommendations to improve the quality of ethical review include reducing the overload on committees by identifying categories of research which might not require full ethics committee review.

Ethics Committees↗
PubMed2000

The detection and quantitation of inflammation in the central nervous system during experimental allergic encephalomyelitis using the radiopharmaceutical 99mTc-RP128.

RP128 is a novel agent which readily chelates 99mTc to form a radiopharmaceutical which binds in vivo to the tuftsin receptor located specifically on neutrophils and monocyte-macrophages, therefore removing the need for in vitro cell labelling prior to intravenous administration. We have assessed the ability of 99mTc-RP128 to detect central nervous system (CNS) inflammation in experimental allergic encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis. The radiopharmaceutical was recorded at significantly increased levels in all EAE diseased CNS tissues, compared to normal and control samples, at 0.5, 1 and 3 h post-injection using a dual radioisotope technique to correct for non-extravasated tracer (P<0.05). Moreover, extravascular accumulation of the agent could be clearly demonstrated in inflammatory tissues with minimal loss of sensitivity when the secondary isotopic correction for blood volume was omitted. In addition, 99mTc-RP128 successfully monitored glucocorticoid suppression of inflammation (P<0.05), recording a typical dose-response to increasing steroid concentration. Clearly, 99mTc-RP128 can quantitatively detect CNS inflammation and assess responses to therapy indicating potential value as an imaging agent both clinically and as a research aid. Furthermore, the rapid in vivo labelling by 99mTc-RP128 of specific inflammatory cells combined with the ability to monitor the progress of anti-inflammatory therapeutics may recommend the agent for use in a variety of inflammatory conditions.

Animals↗
PubMed2000

An evaluation of the National Cervical Screening Programme Otago site.

AIM: To evaluate progress of the Otago Cervical Screening Programme towards achieving its goal of reducing cervical cancer incidence and mortality using data routinely collected by the National Cervical Screening Register (NCSR), and to investigate whether all data required for this task are available from the NCSR. METHOD: Non-identifying data for Otago women aged 20-69 years were obtained from the New Zealand National Cervical Screening Register for the period 1 July 1993 to 30 June 1996. For each five-year age group, proportion screened in three years, short interval re-screening estimates and age-specific reporting rates for squamous atypia of uncertain significance (ASCUS), low-grade intraepithelial lesions (LGIL) and high-grade intraepithelial lesions (HGIL) were calculated. Age-specific reporting rates were also calculated for 20-69 year-old New Zealand women for the same period and compared to the Otago rates. RESULTS: The proportion of eligible women screened was 82.5%, slightly less than the target 85%. Women aged 55 years or more were underscreened, short interval rescreening was more common among younger women, age-specific reporting rates for ASCUS, LGIL and HGIL had increased since 1991/92, and the rate of HGIL was higher than expected in the 20-34 year age group. CONCLUSIONS: In order to maximise the effectiveness and efficiency of the Otago Cervical Screening Programme, it is recommended that participation amongst older women be increased and frequent screening be reduced in the younger age groups. Unexpected elevated rates of HGIL amongst 20-34 year-old women were not adequately explained and require further investigation. Not all data required for an outcome evaluation were available through the NCSR.

Adult↗
PubMed2000

Under proper control, oxidation of proteins with known chemical structure provides an accurate and absolute method for the determination of their molar concentration.

Oxidation at 120 degrees C of inorganic and organic (including amino acids, di- and tripeptides) model compounds by K(2)Cr(2)O(7) in the presence of H(2)SO(4) (mass fraction: 0.572), Ag(2)SO(4) (catalyst), and HgSO(4) results in the quantitative conversion of their C-atoms into CO(2) within 24 h or less. Under these stressed, well-defined conditions, the S-atoms present in cysteine and cystine residues are oxidized into SO(3) while, interestingly, the oxidation states of all the other (including the N-) atoms normally present in a protein do remain quite unchanged. When the chemical structure of a given protein is available, the total number of electrons the protein is able to transfer to K(2)Cr(2)O(7) and thereof, the total number of moles of Cr(3+) ions which the protein is able to generate upon oxidation can be accurately calculated. In such cases, unknown protein molar concentrations can thus be determined through straightforward spectrophotometric measurements of Cr(3+) concentrations. The values of molar absorption coefficients for several well-characterized proteins have been redetermined on this basis and observed to be in excellent agreement with the most precise values reported in the literature, which fully assesses the validity of the method. When applied to highly purified proteins of known chemical structure (more generally of known atomic composition), this method is absolute and accurate (+/-1%). Furthermore, it is well adapted to series measurements since available commercial kits for chemical oxygen demand (COD) measurements can readily be adapted to work under the experimental conditions recommended here for the protein assay.

Amino Acids↗