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Biomedical subjects

M Curry

Publications and source records attributed to M Curry.

At least 19 recordsLinked to original sources
PubMed2003

Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care.

OBJECTIVE: To examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care. METHODS: The first 460 homosexually active men enrolling in an Australian integrated primary care programme were screened for current depressive disorders using the Primary Care Evaluation of Mental Disorders (PRIME-MD) and completed questionnaires on their sexual behaviour in the prior 6 months. One hundred and sixty-two (35%) were HIV positive, 283 (62%) were HIV negative and 15 (3%) were untested. RESULTS: The prevalence of major depressive episode (MDE), as measured by the PRIME-MD, on enrollment was 28% (129/460), while the prevalence of dysthymic disorder (DD) was 26% (121/460). These include 84 men (18%) who met the criteria for both disorders ('double depression'). Neither disorder was associated with HIV status. Men with MDE were less likely to have been sexually active than the remainder of the cohort (90/129 [70%] vs. 291/331 [88%]; OR: 0.32 [95% CI: 0.19-0.52]; P<0.0001). Men with DD alone, however, were significantly more likely than men with neither disorder to report having had unprotected anal intercourse with a casual partner (11/38 [29%] vs. 43/292 [15%]; OR: 2.36 [95%CI: 1.09-5.10]; P=0.035). CONCLUSIONS: Depressive disorders were highly prevalent in this cohort and independent of HIV status. MDE was associated with reduced sexual activity. Among men without MDE, the presence of DD was independently associated with an increased likelihood of reporting unsafe anal sex with a casual partner in the prior 6 months.

Adult↗
PubMed2000

The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C.

BACKGROUND & AIMS: In hepatitis C infection, several studies have examined the role of the major histocompatibility complex (MHC) in determining outcome, with variable results. To clarify the importance of MHC, we examined class II DR and DQ antigens in a homogenous cohort of women exposed to hepatitis C genotype 1b from a single inoculum. METHODS: Of 243 participants, 95 had spontaneous viral clearance and 148 are chronically infected. The frequencies of HLA class II DR and DQ antigens were compared between the 2 groups and between liver biopsy findings of 145 chronically infected subjects. RESULTS: DRB1*0101 and DQB1*0501 alleles were more frequent in subjects who sustained viral clearance than in chronically infected subjects (32.3% and 36.8% vs. 8.8% and 14.2%, respectively; P = 0.002). DRB1*03011 and DQB1*0201 occurred more frequently in chronically infected subjects than in those who cleared the virus (41.5% and 42.6% vs. 16.7% and 15.8%, respectively; P = 0.001). Both DRB1*03011 and DQB1*0201 were significantly less frequent in those with higher inflammatory scores on liver biopsy. CONCLUSIONS: We show that in a homogenous cohort of women infected with the same hepatitis C virus, several HLA antigens are associated with either viral clearance or persistence. This suggests a strong role for host immunogenetic factors in determining outcome in hepatitis C infection.

Adult↗
PubMed1999

Nutraceuticals.

Explore the source record for details and available documents.

Dietary Supplements↗
PubMed1999

Non-peptide corticotropin-releasing hormone antagonists: syntheses and structure-activity relationships of 2-anilinopyrimidines and -triazines.

Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [125I]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (Ki = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than alpha-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH1 receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH1 receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH1 Ki = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

Animals↗
PubMed1999

Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines.

The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course.

Administration, Oral↗
PubMed1998

A two-year follow-up survey of antibody to Cryptosporidium in Jackson County, Oregon following an outbreak of waterborne disease.

To estimate the duration of Cryptosporidium-specific antibody, a Western blot assay measured antibody in paired sera from 124 residents of Jackson County, Oregon collected 0.5 and 2.5 years after the end of an outbreak in Talent, Jackson County. The outcome measure was the intensity of antibody responses, (which may approximate to a titre), to 27-kDa and 15/17-kDa antigens. Intensity of response to the 27-kDa antigen(s) declined to 54% of the 1992 value while responses to a 15/17-kDa antigen(s) remained close to the initial values. Increasing age of the donor predicted higher intensity of antibody to the 15/17-kDa antigen(s) in both the initial (P = 0.004) and follow-up (P = 0.038) surveys. No relationship was observed between age and antibody intensity for the 27-kDa antigen(s) during either survey (P > 0.10). Both the initial and follow-up surveys showed significant elevations in antibody intensity for Talent residents, possibly indicating a high endemic rate of infection/re-infection or high levels of chronic infection.

Animals↗
PubMed1998

Comparisons of ELISA and Western blot assays for detection of Cryptosporidium antibody.

A seroprevalence survey was conducted using ELISA and Western blot (WB) assays for antibody to three Cryptosporidium antigens on 380 blood donors in Jackson County, Oregon. The purpose was to determine if either assay could detect serological evidence of an outbreak which occurred in Talent, Oregon 6 months earlier. The ELISA, which tested for combined IgG, IgA and IgM, and the WB, which tested separately for IgG and IgA, detected an almost twofold increase in serological response for persons who consumed Talent drinking water during the previous 11 months. The increases, however, were statistically significant (P < 0.05) only for the WB. The identification of serological evidence of infection, using sera collected 6 months after the end of the outbreak in a population not selected because of cryptosporidiosis-like illness, suggests that assays of Cryptosporidium-specific IgG and IgA may assist in estimating the magnitude of asymptomatic infections in the population.

Adolescent↗
PubMed1997

Delayed correction of portal hypertension after portal vein conduit arterialization in liver transplantation.

A 55-year-old woman underwent orthotopic liver transplantation for autoimmune chronic active hepatitis. Extensive portal and superior mesenteric venous thrombosis precluded standard portal venous reconstruction and necessitated use of a venous conduit from the recipient splenic vein of the donor liver. Flow through this conduit was poor, however, and to prevent subsequent portal venous thrombosis and graft loss, the conduit was arterialized by end-to-side anastomosis with the recipient hepatic artery. This ensured graft survival but resulted in prehepatic portal hypertension, which required ligation of the arterioportal fistula for 4 months. The patient had a satisfactory outcome.

Anastomosis, Surgical↗
PubMed1994

Responses of salivary acinar cells to intracellular alkalinization.

Responses of rat submandibular acini to intracellular alkalinization were investigated. Intracellular alkalinization was induced by addition of NH4Cl or methyl amines, or by prepulse with Na butyrate. Only partial recovery occurred following Na butyrate prepulse or methylated amine addition, but full recovery was observed following addition of NH4Cl. The latter recovery was DIDS and dimethylamiloride-insensitive but was inhibited by bumetanide or high [K+] and stimulated in Na(+)-free buffer and by ouabain. Acetylcholine stimulated recovery from NH4Cl- or Na butyrate pre-pulse-induced alkalinization and reduced the extent of alkalinization induced by methylated amines. Acetylcholine-stimulated recovery from NH4Cl-induced alkalinization was mimicked by substance P or ionomycin and was partially Ca(2+)-dependent. This stimulated recovery was bumetanide-insensitive but was partially sensitive to charybdotoxin. Taken together, these data indicate that in unstimulated cells, recovery from alkalinization induced by NH4Cl occurs by bumetanide-sensitive transport of the NH4+ ion, that DIDS-inhibitable anion transport contributes little to this recovery, and that acetylcholine and other Ca(2+)-elevating agents accelerate recovery from NH4Cl-induced alkaline challenge by a mechanism insensitive to bumetanide, DIDS, ouabain, and dimethylamiloride but sensitive to extracellular Ca2+ and to charybdotoxin. Partial recovery from alkaline challenge can also occur in the absence of NH4+ ions, and acetylcholine also stimulates this mode of recovery. Together, these data suggest that these cells have little intrinsic ability to recover from intracellular alkalinization and that the NH4+ ion may be a surrogate for K+ in at least two ion transport pathways.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Reproducibility of computer-aided semen analysis: comparison of five different systems used in a practical workshop.

STUDY OBJECTIVES: To assess a single (donor) sample by the use of five computer-assisted semen analysis (CASA) systems. SETTING: British Andrology Society advanced course on computer-assisted semen analysis techniques, September 1992. PARTICIPANTS: Clinical, technical and scientific personnel with mixed experience of CASA techniques, but all interested in semen assessment technology. RESULTS: 22 sets of data, comprising 6 commonly derived parameters, from the same sample were obtained using five CASA systems. The coefficients of variation for sperm concentration (29%) and proportion motile (24%) were comparable to those previously reported for manual assessments. For all parameters, "within system" variability was considerably greater than "between system," indicating that differences in sample handling and operator expertise were more significant sources of variation than the CASA systems themselves. CONCLUSIONS: Emphasis on operator training and standardization of sample handling techniques would enhance the reproducibility of CASA measurements more than improvements in the CASA systems themselves. There was evidence, however, that the CASA measurements were more consistent than equivalent manual measures, and also provide information about the quality of sperm motility which cannot be obtained by alternative techniques.

Education, Medical, Continuing↗
PubMed1992

Intracellular pH changes induced by exposure to weak acids and bases in submandibular cells of early postnatal rats.

The intracellular pH of submandibular cells of adult, 1-day-old and 1-week-old rats was measured with the pH sensitive fluorimetric indicator SNARF-1, following shifts induced by exposure to a weak acid (sodium butyrate) or a weak base (NH4Cl). The effects of several ion transport inhibitors and agonists on both the pH change and the rate of recovery were examined. The results indicate that, in most respects, the processes involved in pH regulation were similar in the neonatal and mature cells. However, cholinergic and peptidergic stimulation accelerated recovery from sodium butyrate-induced acidification more, and from NH4Cl-induced alkalinization less, in cell preparations from 1-day-old animals.

Acetylcholine↗
PubMed1992

The effect of NH4Cl on Rb+ fluxes in resting and stimulated rat submandibular acinar cells.

Dispersed salivary acini isolated from the rat submandibular gland were incubated in a HEPES-buffered Krebs-Ringer solution or in the same buffer containing 20 mM NH4Cl and the accumulation and efflux of K+ were measured with the radiotracer 86Rb+, in the presence and absence of acetylcholine and of transport inhibitors. Exposure to NH4Cl caused a significant (greater than 50%) reduction in tracer accumulation. This effect was blocked by 0.1 mM bumetanide, but not by 1 mM ouabain. The effect of NH4Cl was, on the other hand, nearly additive with that of 1 microM acetylcholine. In cells preincubated with tracer, acute addition of NH4Cl caused a significant net efflux of isotope, so that the tracer content fell to 45% of the control value within 10 min. Bumetanide added to preloaded cells in the same fashion had no effect on tracer content and did not modify the efflux of 86Rb+ induced by 1 microM acetylcholine. However, this inhibitor essentially abolished the NH4Cl-induced tracer efflux. Exposure to NH4Cl during tracer loading did not appear to affect subsequent agonist-stimulated tracer efflux. These results suggest that: (1) the inhibition of K+ entry by NH4Cl is due to an effective competition by the NH4+ ion with Rb+ (and K+) for uptake via a bumetanide-sensitive Na+/K+/2Cl- contransporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Effects of NH4Cl and dimethylamine on Cl- fluxes in resting and stimulated rat submandibular acinar cells.

Transmembrane movements of K+ and Cl- in salivary acinar cells are important in the formation of saliva, and may be affected by changes in intracellular pH (pHi). Exposure to NH4Cl increases pHi transiently, but NH4+ may have effects independent of pHi. To investigate how Cl- transport may be altered under these conditions, rat submandibular acini were exposed to NH4Cl, and transmembrane Cl- transport was studied with 36Cl-. NH4Cl increased intracellular Cl- in these cells. The initial phase of this increase was partially HCO(3-)-dependent and was inhibited by 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), while the sustained phase was inhibited by 0.1 mM bumetanide. NH4Cl also inhibited acetylcholine-induced Cl- efflux from tracer preloaded cells. Changes in pH did not always correlate in time or extent with those of Cl- transport. We conclude that 1) exposure to NH4Cl increases Cl-uptake primarily by a bumetanide-sensitive transport system that did not reach steady state during the experiment, 2) exposure to NH4Cl also stimulates Cl- uptake by a DIDS-sensitive mechanism, and 3) only the latter is pHi sensitive.

Acetylcholine↗