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Biomedical subjects

A Lane

Publications and source records attributed to A Lane.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effects of pancreatic spasmolytic Polypeptide (PSP) on epithelial cell function.

Trefoil peptides are expressed near endodermal ulcerations and may modulate epithelial repair. The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats. Ion transport was assessed as changes in short-circuit current in rat intestine and adenocarcinoma cells in Ussing chambers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in the presence of extracellular glutathione (GSH). The effect was attenuated by GSH depletion with buthionine sulphoximine, even in GSH-containing media. When GSH-reduced PSP was carboxymethylated with iodoacetic acid, it still depended on extracellular GSH for its growth effect. Intestinal epithelial proliferation in rats was not affected by either intravenous or intraluminal infusion. PSP had no effect on basal or stimulated ion flux in rat jejunum or epithelial monolayers. The peptide did not compete with 125I-labeled epidermal growth factor for its receptor. [14C]Iodoacetamide treatment of PSP, followed by prolonged tryptic digestion yielded predominantly a 14C-labeled tetrapeptide fragment containing Cys1O4, with a lesser quantity of a 14C-labeled 15-amino-acid peptide containing Cys95 (molar ratio 15:1). GSH may predominantly reduce the Cys6-Cys1O4 terminal disulphide bond in PSP. We conclude that some epithelia may exhibit a growth response to PSP if extracellular GSH is present. Reduction of PSP by GSH is not necessary for this response, suggesting that the trefoil receptor or its signal transduction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concentration.

Animals↗
PubMed1996

Factor VII Arg/Gln353 polymorphism determines factor VII coagulant activity in patients with myocardial infarction (MI) and control subjects in Belfast and in France but is not a strong indicator of MI risk in the ECTIM study.

This paper describes the relationship of factor VII coagulant activity (FVIIc), FVII Arg/Gln353 genotype and risk of myocardial infarction (MI) in the ECTIM (Etude Cas Témoin sur l'Infarctus du Myocarde) study, a multi-centre case-control study on MI. FVIIc was significantly higher in controls from all four centres: Belfast, Lille, Strasbourg and Toulouse, perhaps because elevated FVIIc may predispose to fatal rather than non-fatal MI. Major influences on FVIIc were FVII Arg/Gln353 genotype, triglyceride and cholesterol levels. There was no significant effect of genotype on MI risk however there was a non-significant trend towards increased MI risk in FVII Arg353 homozygotes. Confirming previous observations, FVIIc was highest in FVII Arg353 homozygotes, intermediate in heterozygotes and lowest in FVII Gln353 homozygotes (except Toulouse cases) these differences being highly statistically significant (except Strasbourg cases P = 0.1). In Belfast, consistent with previous findings, there was significant interaction between FVII Arg/Gln353 genotype and triglyceride level in determining FVIIc, whilst this was absent in the French centres. In conclusion, FVII Arg/Gln353 genotype strongly determines FVIIc although neither factor has a strong impact on MI risk in the ECTIM study.

Adult↗
PubMed1996

Toxoplasma gondii: appearance of specific markers during the development of tissue cysts in vitro.

Cultures were initiated in Madin-Darby bovine kidney (MDBK) cells from ME49 strain bradyzoites. Specific antibody staining showed that two populations of parasites exist, one being a predominant population of tachyzoites that were positive for the tachyzoite-specific marker SAG1 and negative for the bradyzoite-specific marker P36. All of these parasites expressed the dense granule molecule GRA5, which in larger clusters was seen faintly in the membrane of the parasitophorous vacuole. No rosette formation or monolayer destruction was observed. Also seen was a sub-population of bradyzoites that were positive for P36 and negative for SAG1. Approximately 90% of these parasites expressed the matrix molecule P29. These parasites were also positive for the dense granule molecule GRA5, which was highly concentrated in the wall of the cyst. These bradyzoite clusters contained fewer parasites and were smaller in diameter than those expressing tachyzoite markers.

Animals↗
PubMed1996

Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.

The influence of sociodemographic, clinical and treatment factors on the quality of life of patients with schizophrenia has yet to be fully defined. We evaluated the quality of life of patients with schizophrenia who were attending a catchment area rehabilitation centre, in order to establish its clinical correlates. These patients had a poor to moderate quality of life which was inversely related to negative symptom severity, illness duration, the cumulative length of previous hospitalization and patient age. Patients residing in hostels or group homes had a poorer quality of life than those living independently or with their family. The presence of tardive dyskinesia was associated with a poorer quality of life. This association merits further investigation.

Adolescent↗
PubMed1996

6,7-disubstituted 2,4-diaminopteridines: novel inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.

Four novel, disubstituted diaminopteridines have been identified which antagonize the uptake of a folate precursor (para-aminobenzoic acid) by rat-derived Pneumocystis carinii maintained in short-term axenic culture at concentrations ranging from 4.5 to 26 microM. The compounds were at least 10 to 100 times more active than trimethoprim in this assay. None of these entities exhibited toxicity to mammalian cell lines at < 100 microM. The same structures also caused significant inhibition of Toxoplasma gondii tachyzoite replication within Madin-Darby bovine kidney cells at concentrations ranging from 0.1 to 10 microM. Three of the structures (GR92754, AH10639, and AH2504) were at least an order of magnitude more potent than the standard anti-T. gondii agent, pyrimethamine. All three entities were also significantly more potent and selective than pyrimethamine as inhibitors of T. gondii dihydrofolate reductase (DHFR), with 50% inhibitory concentrations within the range of 0.018 to 0.033 microM. One of these compounds, 6,7-dibutyl-2,4-diaminopteridine (GR92754), was also a potent and selective inhibitor of P. carinii DHFR (50% inhibitory concentration, 0.082 microM). GR92754 is the first DHFR inhibitor described that exhibits greater potency, selectivity, and intracellular activity against both organisms than any of the DHFR agents used clinically, namely, trimethoprim, pyrimethamine, and trimetrexate. This information could provide the starting point for examination of the pharmacokinetic and therapeutic potential of GR92754 and related chemical entities with animal models.

4-Aminobenzoic Acid↗
PubMed1996

Direct costs of osteoporosis for New Zealand women.

The burden of illness of osteoporosis in New Zealand is substantial. Prevalence estimates based on international research suggest that up to 30% of postmenopausal women may have osteoporosis. The projected increase in population of women aged >or= 60 years suggests that the burden of illness associated with osteoporosis will escalate. Currently, cost estimates in New Zealand for specific procedures are severely limited by the absence of a comprehensive, nationwide, case-mix system of costing. In this analysis, first-year total direct costs of hospitalisation, recovery and residential care associated with osteoporotic hip fractures, assuming an annual incidence of 1537.63 such fractures in New Zealand women aged > or = 60 years, were estimated at $NZ41,684,460 [1995 dollars ($NZ1 = $US0.65 in 1995)]. Second-year costs were $NZ24,952,895. The combined total over 2 years post-hip fracture was estimated to be $NZ66,637,355. Annual non-hip fracture costs for women aged > or = 45 years were estimated at $NZ4 401 248. Pharmacotherapy data for the treatment of osteoporosis indicate that the societal costs of treating the diagnosed condition for men and women in New Zealand are $NZ3 385 590 per year (1995 dollars).

Cost of Illness↗
PubMed1996

Low plasma levels of factor VIIc and antigen are more strongly associated with the 10 base pair promoter (-323) insertion than the glutamine 353 variant.

In a group of 705 healthy middle-aged men, we have examined the relationship between plasma levels of Factor VII (FVII) c and Factor VII antigen (FVIIag) and two polymorphisms in the FVII gene. One polymorphism alters arginine at position 353 to glutamine (R/Q), and the other is the result of a 10 base pair (bp) insertion in the promoter region at position -323 from the start of translation (0/10bp). The frequency for the Q allele was 0.105 (95% CI 0.09-0.12) and for the 10bp allele was 0.117 (95% CI 0.10-0.13). Men who were carriers of either of the rare alleles had levels of FVIIc and FVIIag that were approximately 20% lower than non-carriers, and both of these effects were highly statistically significant (p < 0.0001). Strong allelic association was observed between the two polymorphisms, with R and 0 bp being on the same chromosome in 96% of cases, and Q and 10 bp being on the same chromosome in 90% of cases where this could be determined unambiguously (Delta = 0.92, chi 2 = 1206, p < 0.0001). This strong allelic association created three major genotype groups which were found to have significantly different levels of FVIIc (p < 0.001). In the 547 men homozygous for both common alleles (R/R & 0/0), mean (SD) FVIIc was 101 (29) as compared with 85 (30) in the 20 men with the genotype R/R & 0/10 and 81 (23) in the 126 men with the genotype R/Q & 0/10, suggesting a larger lowering effect associated with the 10 bp allele (16%) compared to the Q allele (an additional 4%). The lowering effect on FVII associated with the 10 bp allele remained statistically significant after adjusting for the effect of the Q allele (p = 0.004 for FVIIc and p = 0.06 for FVIIag), but the effect associated with the Q allele was no longer significant after adjusting for the 10 bp allele, suggesting that the strongest effect on levels of FVIIc was associated with the 0/10 bp genotype. In the sample overall, plasma FVIIc was associated positively with serum triglyceride concentration and the slope of this relationship was significantly greater in those with the genotype R/R compared to the other groups combined (0.12 versus 0.02, p = 0.008) with differences of similar size seen in the 0/0 compared to 0/10 + 10/10 groups. However, using the combined genotype, the slope of this relationship in the R/R & 0/10 group was 0.38 and was significantly steeper (p = 0.01) than in the other two groups who did not differ in this respect (slopes 0.11 and 0.08). This effect was seen on four subsequent annual examinations, and was also evident in the relationship between FVIIag and triglyceride concentration (p = 0.003 for difference between groups measured at baseline only). These data suggest that part of the previously described effects on FVIIc levels associated with the R/Q polymorphism may be explained by genetic variation in the promoter region of the FVII gene.

Antigens↗
PubMed1995

Transesophageal dobutamine stress echocardiography in the evaluation of coronary artery disease.

OBJECTIVES: The goal of this study was to determine the feasibility, safety, sensitivity and specificity of transesophageal dobutamine stress echocardiography for the detection of coronary artery disease. BACKGROUND: Dobutamine stress echocardiography has been shown to be an extremely sensitive and specific noninvasive technique for the detection of myocardial ischemia. However, inadequate transthoracic images preclude the use of dobutamine stress echocardiography in a small but significant group of patients. Transesophageal echocardiography provides better resolution than that obtained with routine transthoracic imaging. METHODS: Patients scheduled for routine cardiac catheterization underwent transesophageal dobutamine stress echocardiography. All patients underwent coronary arteriography within 48 h of the study, and lesion severity was determined by quantitative coronary angiography. Significant coronary obstruction was defined as stenosis > 50%. RESULTS: Fifty-one male patients were enrolled in the study; six were excluded for technical reasons. There were no adverse outcomes or complications. Of 27 patients with significant coronary artery disease, 22 had positive study results (sensitivity 82%). Of 13 patients without significant obstructive coronary disease, 1 had a false positive study result (specificity 93%). In patients with a minimal lumen diameter < 1.25 mm, sensitivity was > 80%, and in patients with a minimal lumen diameter > 1.5 mm, sensitivity was < 70%, suggesting that lesions with a minimal lumen diameter < 1.25 mm are more likely to be physiologically significant. CONCLUSIONS: Transesophageal dobutamine stress echocardiography is a feasible, safe and accurate technique for the detection of myocardial ischemia. There are inherent limitations to this technique in that transesophageal echocardiography must be performed. Transesophageal dobutamine stress echocardiography may allow extension of dobutamine stress testing to patients with inadequate transthoracic echocardiographic imaging and may provide an opportunity for further research applications.

Coronary Angiography↗
PubMed1995

Reproductive behaviour in schizophrenia relative to other mental disorders: evidence for increased fertility in men despite decreased marital rate.

Using case register data, the overall marital rate among 5158 patients with mental illness was found to be comparable to the general population. The proportion of those ever married was markedly reduced in the schizophrenic group relative to those with a manic or neurotic illness. Men with schizophrenia had a particularly low rate of marriage. The overall marital fertility of the 3 groups was comparable to each other and appeared to be higher than that in the general population. In the schizophrenic group only, married men, particularly those with a family history of mental disorder, produced more children than married women. Men might represent a more fertile group of schizophrenic patients with some biological advantage of increased fecundity, which may help to compensate for negative selection pressures.

Analysis of Variance↗
PubMed1995

Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator inhibitor 1 gene.

Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their excess risk of cardiovascular disease. We examined the determinants of PAI-1 activity in 146 NIDDM subjects by using specific assays of insulin and intact and des-31,32-proinsulin and measures of insulin resistance, relating these measurements to serum lipids, hypoglycemic therapy, and a common 4G/5G polymorphism in the promoter region of the PAI-1 gene. Subjects were treated with insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In the whole group, PAI-1 activity correlated significantly with serum triglycerides (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in subjects not on insulin (n = 110), with insulin sensitivity (r = -0.42, P < 0.001). There was a significant difference in PAI-1 activity among the three genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1 activity correlated significantly with triglyceride levels (r = 0.65, P < 0.0001). There was no significant difference in PAI-1 activity in the different treatment groups despite a significant difference in concentrations of intact and des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the interaction between PAI-1 4G/5G genotype and triglyceride were the strongest determinants of PAI-1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Antecedents of multidimensional competitive state anxiety and self-confidence in duathletes.

The purpose of this study was to explore the situational antecedents of multidimensional state anxiety among competitors in the sport of duathlon (run/cycle/run). Subjects (N = 122; Age: M = 28.3 yr., SD = 7.8 yr.) completed the Competitive Sport Anxiety Inventory-2 1 hr. before competition. In addition, they completed a 21-item Prerace Questionnaire modified for duathlon on which scores were factor analysed. Six factors accounted for 73.5% of the variance, similar to those identified by Jones, et al. in 1990. Step-wise multiple regression indicated that race goals and perceived readiness were significant predictors of cognitive anxiety, somatic anxiety, and self-confidence. Self-confidence was also predicted by attitude toward previous performance. This finding supports the proposal that these anxiety subcomponents share common antecedents but challenges the notion that cognitive and somatic anxiety also have unique antecedents.

Adolescent↗
PubMed1994

Properties of multiple G.A mismatches in stable oligonucleotide duplexes.

The solution structure of the deoxydecanucleotide [sequence: see text] has been determined by NMR methods. This duplex, which contains six G.A mismatches and four Watson-Crick base pairs, is thermodynamically more stable than a decamer where T.A base pairs are substituted for the G.A mismatches, and is less stable than the duplex that contains G.C base pairs. Circular-dichroism spectroscopy indicates an overall B-like conformation for the decamer, but stronger than usual base stacking. 1H-NMR spectroscopy revealed that the N1H groups of the mismatched guanine residues are not hydrogen bonded, and 31P-NMR showed the presence of BII phosphate conformations for the GpA steps. Detailed analysis of the NMR data showed that all nucleotides have anti glycosidic torsion angles and S type sugar puckers. The G.A mismatches pair in the amino form as originally proposed by Li et al. [Li, Y., Zon, G. & Wilson, W. D. (1991) Proc. Natl Acad. Sci. USA 88, 26-30], which results in extensive base-base stacking between the tandem G.A base pairs and their nearest neighbours. The terminal G.A base pairs are less stable than the central base pairs and show evidence of an equilibrium between two conformations, one involving BII phosphate.

Base Sequence↗
PubMed1994

Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis.

In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF at 75 mg/day or placebo (both groups received supplementary calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional analyses and extended observations are now available on 50 women from the NaF group followed for up to 6 years of treatment. In these women, LS-BMD increased linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because during the 4 year trial the NaF dosage was decreased (because of side effects) in 54 of the 101 women randomized to NaF, dose-response relationships could be evaluated. For the entire study population, serum F level correlated directly with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2. Multivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of several variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increasing LS-BMD except when the higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.

Aged↗
PubMed1994

Variable selectivity of the Hitachi chemistry analyzer chloride ion-selective electrode toward interfering ions.

Chloride measurements by ion-selective electrodes are vulnerable to interference by anions such as iodide, thiocyanate, nitrate, and bromide. We have found that the degree of interference of these anions on the Hitachi chemistry analyzer chloride electrode varies from electrode to electrode and this variation can even occur within the same lot of membrane. This variation is not dependent upon the length of time the cartridge has been in the analyzer because no correlation existed between the usage time and the electrode response to interfering ions. Neither is this variation due to the deterioration of the electrode because all electrodes tested had calibration slopes within the manufacturer's specification. Our study, however, showed that even after repeated exposure to a plasma sample containing 2 mM thiocyanate, the chloride electrode was still able to accurately measure the chloride in plasma without thiocyanate, thus confirming that a carryover effect does not exist from a previous thiocyanate-containing sample.

Anions↗