Search PubMed⌕ Search

Biomedical subjects

C M Thomas

Publications and source records attributed to C M Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Urinary bladder cancer test: a new urinary tumor marker in the follow-up of superficial bladder cancer.

OBJECTIVES: To study the diagnostic performance of the Urinary Bladder Cancer (UBC) test in patients with superficial bladder carcinoma. METHODS: One hundred one patients in follow-up for superficial bladder cancer (pTa, pT1, carcinoma in situ) were recruited for this study. Each patient underwent cystoscopy and transurethral resection or biopsy, with subsequent histologic confirmation in the case of abnormalities. In addition, specimens were assessed with an immunoenzymometric assay for cytokeratin expression (the UBC test), and the urinary creatinine concentration was determined to correct for different degrees of urinary dilution. Different methods were applied to calculate the diagnostic value of the UBC test. RESULTS: Both noncorrected and corrected median values of the UBC test were comparable between patients with and without a recurrent bladder tumor. The overall sensitivity, specificity, and positive and negative predictive values of the noncorrected UBC test was 20.7%, 84.7%, 35.3%, and 72.6%, respectively. For the corrected UBC test, the corresponding values were 20.7%, 79.2%, 28.6%, and 71.3%. The area under the receiver operating characteristic curve was not significantly different from 0.50, indicating no diagnostic value of the UBC test in this study. CONCLUSIONS: The diagnostic value of this new urinary marker appears insufficient for the follow-up of patients with superficial bladder cancer.

Adult↗
PubMed2000

Genetic complexity of pathogen perception by plants: the example of Rcr3, a tomato gene required specifically by Cf-2.

Genetic analysis of plant-pathogen interactions has demonstrated that resistance to infection is often determined by the interaction of dominant plant resistance (R) genes and dominant pathogen-encoded avirulence (Avr) genes. It was postulated that R genes encode receptors for Avr determinants. A large number of R genes and their cognate Avr genes have now been analyzed at the molecular level. R gene loci are extremely polymorphic, particularly in sequences encoding amino acids of the leucine-rich repeat motif. A major challenge is to determine how Avr perception by R proteins triggers the plant defense response. Mutational analysis has identified several genes required for the function of specific R proteins. Here we report the identification of Rcr3, a tomato gene required specifically for Cf-2-mediated resistance. We propose that Avr products interact with host proteins to promote disease, and that R proteins "guard" these host components and initiate Avr-dependent plant defense responses.

Biological Evolution↗
PubMed2000

The hierarchy of KorB binding at its 12 binding sites on the broad-host-range plasmid RK2 and modulation of this binding by IncC1 protein.

IncC and KorB proteins of broad-host-range plasmid RK2 are members of the ParA-ParB families of proteins needed for stable partitioning of bacterial chromosomes and plasmids. KorB also functions as a global regulator of expression of RK2 genes. It recognises and binds to a palindromic operator, O(B), found 12 times on RK2 DNA (O(B)1-O(B)12). We performed detailed studies on the binding of KorB to the 12 operators and showed that they fall into three groups (A, B, C) based on the binding strength of KorB. The highest affinity site is O(B)10, which occurs in the promoter transcribing genes for replication, trfAp. Purified IncC1 potentiated KorB binding to all O(B) sites except O(B)3, a site involved in partitioning. Using O(B)10 as a test system, we showed that IncC1 increases the stability of the KorB-DNA complex. The 5 bp sequences flanking the 13mer O(B) site were found to affect KorB binding and IncC1 potentiation activity. Study of hybrid operators indicated that flanking sequences on one side only were sufficient to specify the difference between O(B)10 and O(B)3. Replacement of adenine by guanine at positions -8 and -10 from the O(B)10 centre of symmetry was needed to convert it from the highest-affinity group (A) to the medium-affinity group (B) on the basis of KorB binding. These changes also eliminated potentiation by IncC1. The -8 and -10 positions from the centre of O(B)3 symmetry are occupied by guanines and this may provide part of the specificity of IncC1 behaviour on KorB binding. Studies on a series of synthetic operators suggested that KorB contacts O(B) flanking sequences, and that IncC1 may alter the conformation of multimeric KorB so that it is better able to make these contacts, thus stabilising the complexes once formed.

Bacterial Proteins↗
PubMed2000

Cigarette smoking and the risk of male factor subfertility: minor association between cotinine in seminal plasma and semen morphology.

OBJECTIVE: To evaluate the impact of cigarette smoking on male factor subfertility and the semen parameters of sperm count, motility, and morphology by questionnaire and determination of the cotinine concentrations in blood and seminal plasma of fertile and subfertile males. DESIGN: Case-control study of 107 fertile and 103 subfertile males who provided a standardized blood and semen specimen and completed a self-administered questionnaire about their smoking habits. SETTING: Outpatient fertility clinic of the University Medical Centre St. Radboud, Nijmegen, The Netherlands. PATIENT(S): One hundred seven fertile and 103 subfertile males. INTERVENTION(S): Vena puncture and semen collection. MAIN OUTCOME MEASURE(S): Blood and seminal plasma cotinine levels in relation to semen parameters. RESULT(S): A higher frequency of cigarette smoking was observed in subfertile males than in fertile males, with an odds ratio of 1.7 (95% confidence interval, 0.9-3.2). The self-reported number of cigarettes smoked per day correlated with the cotinine concentrations in blood and seminal plasma for both groups. A small but statistically significant correlation was found between cotinine concentrations in seminal plasma and the percentage of abnormal sperm morphology, but not for other semen parameters (r(s) = 0.19). CONCLUSION(S): Although the mechanism of the toxicity of cotinine on sperm morphology is not clear, this study indicates only a minor effect of cigarette smoking on male factor subfertility, which is probably due to compounds in cigarette smoke other than nicotine (cotinine).

Adult↗
PubMed2000

Male factor subfertility: possible causes and the impact of nutritional factors.

OBJECTIVE: To review possible causes for male factor subfertility with emphasis on nutritional factors such as zinc and folate. DESIGN: A literature search was performed on MEDLINE and via bibliographies of published works. RESULT(S): Many causes for male factor subfertility are described in the literature. Both environmental and genetic factors could play a role. However, the pathogenesis of male factor infertility is poorly understood, including the role of specific micronutrients such as zinc and folate. Both zinc and folate are involved in the synthesis of DNA and RNA. Despite the fact that zinc deficiency leads to several clinical symptoms such as decreased spermatogenesis and impaired male fertility, the exact pathophysiology has not been clarified. CONCLUSION(S): Because most causes of male factor subfertility are unknown, more research is needed. Because male factor subfertility due to nutritional deficiencies is in principle amenable to curative and/or preventive action by supplementation, emphasis should be put on studies on the effect of specific nutrients on male fertility.

Age Factors↗
PubMed2000

Homocysteine and folate levels as risk factors for recurrent early pregnancy loss.

OBJECTIVE: To estimate the relative risk of recurrent early pregnancy loss for different total plasma homocysteine and serum folate concentrations. METHODS: In a case-control study, we measured homocysteine (fasting and afterload), folate (serum and red cells), pyridoxal 5'-phosphate, and cobalamin concentrations in 123 women who had at least two consecutive spontaneous early pregnancy losses each and compared concentrations with those of 104 healthy controls. RESULTS: Women with recurrent early pregnancy losses had significantly lower serum folate concentrations than controls, whereas the other measurements were similar to those of controls. Elevated homocysteine, fasting greater than 18.3 micromol/L and afterload greater than 61.5 micromol/L, was a risk factor for recurrent early pregnancy loss, with odds ratios (ORs) and 95% confidence intervals (95% CIs) of 3.6 (1.2, 12.7) and 2.7 (0.9, 8.8) in the group with recurrent miscarriages: 6.4 (1.9, 24.3) and 4.3 (1. 2, 17.3) in primary aborters, and 4.2 (1.3, 15.4) and 3.4 (1.0, 12. 8) in those with three or more miscarriages. The ORs (95% CIs) in the same study populations for serum folate concentrations less than 8.4 nmol/L were 2.1 (0.9, 4.8), 2.7 (1.0, 7.8), and 3.2 (1.3, 8.1), respectively. A significant dose-response relationship between serum folate concentrations and risk of recurrent early pregnancy loss suggested a protective effect by high serum folate concentrations. CONCLUSION: Elevated homocysteine and reduced serum folate concentrations were risk factors for recurrent spontaneous early pregnancy losses. Folic acid supplementation might be beneficial in women with histories of early pregnancy loss.

Abortion, Habitual↗
PubMed2000

Dispersion of the Cf-4 disease resistance gene in Lycopersicon germplasm.

In the past, numerous Cf genes have been reported in tomato (Lycopersicon esculentum Mill.) that confer resistance against leaf mould (Cladosporium fulvum Cke.). We are interested in genetic variation at Cf loci. Therefore, previously uncharacterized Cf genes were further analysed. Recognition of the AVR4 elicitor, DNA gel blot analysis, PCR analysis and sequencing of part of the Cf-4 locus showed that a large proportion of the accessions tested harboured the Cf-4 resistance gene. We concluded that despite differences in nomenclature, all these accessions harbour the same Cf-4 locus, probably introgressed from the same donor. The origin of the Cf-4 locus and the reasons for discrepancies with earlier reports are discussed.

Blotting, Southern↗
PubMed2000

Paradigms of plasmid organization.

Plasmids are extrachromosomal elements built from a selection of generally quite well understood survival and propagation functions, including replication, partitioning, multimer resolution, post-segregational killing and conjugative transfer. Evolution has favoured clustering of these modules to form plasmid cores or backbones. Co-regulation of these core genes can also provide advantages that favour retention of the backbone organization. Tumour-inducing and symbiosis-determining plasmids appear to co-regulate replication and transfer in response to cell density, both being stimulated at high density. Broad-host-range plasmids of the IncP-1 group, on the other hand, have autogenous control circuits, which allow a burst of expression during establishment in a new host, but a minimum of expression during maintenance. The lessons that plasmids have for clustering and co-regulation may explain the logic and organization of many small bacterial genomes currently being investigated.

DNA Replication↗
PubMed2000

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

INTRODUCTION: Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. PATIENTS AND METHODS: In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. RESULTS: In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Homocysteine metabolism and effects of folic acid supplementation in patients affected with spina bifida.

Folic acid supplementation around conception decreases the risk of having offspring with a neural tube defect. However, the aetiology is often still unknown. This study investigated whether spina bifida patients have lower blood folate and higher fasting and post-methionine-load plasma total homocysteine (tHcy) concentrations than control patients. Moreover, the effects of supplementation with 500 microg folic acid/d on folate and tHcy concentrations were determined. Spina bifida patients (n = 12) and disabled control patients (n = 15) received 4 weeks of placebo treatment followed by 4 weeks of intervention with 500 microg folic acid/d. Blood was collected at the start and after 4 and 8 weeks. A methionine-loading test was performed at the start and the end of the study. At baseline, no significant differences occurred between spina bifida and control patients. Folic acid supplementation significantly increased plasma and red blood cell folate concentrations in both groups. Folic acid decreased fasting tHcy concentrations in control patients by 1.6+/-0.5 micromol/l (p<0.01) and in spina bifida patients by 2.2 +/- 1.3 micromol/l (p = 0.10). This study does not show a derangement in homocysteine metabolism in spina bifida compared to control patients. Moreover, folic acid supplementation seems at least as effective in spina bifida patients as in controls.

Administration, Oral↗
PubMed2000

Imprinting effect in premature ovarian failure confined to paternally inherited fragile X premutations.

Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in female carriers. The occurrence of POF and age at menopause in women with a paternally inherited fragile X premutation (PIP) were compared to those in women with a maternally inherited fragile X premutation (MIP). We identified 148 women in whom the parental origin of the premutation could be determined. In 109 of these women we were able to establish whether POF had occurred: 82 women had a PIP, and 27 had a MIP. Twenty-three of the women (28%) with a PIP had POF, versus only 1 (3.7%) with a MIP (two -tailed Fisher's exact test; P=. 007). Kaplan-Meier analysis of all 148 premutations showed that the age at menopause was significantly lower in the women with a PIP than in the woman with a MIP (Breslow test in Kaplan-Meier analysis; P=.003). Our data strongly suggest that, when POF occurs in fragile X premutation carriers, a considerable proportion of the premutations are inherited paternally (parent-of-origin effect). We hypothesize that this may be owing to a paternal genomic imprinting effect.

Adult↗
PubMed2000

Signs of impaired cognitive function in adolescents with marginal cobalamin status.

BACKGROUND: Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. OBJECTIVE: The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. DESIGN: Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status. RESULTS: The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14). CONCLUSION: Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

Adolescent↗
PubMed2000

Comparison of the hypersensitive response induced by the tomato Cf-4 and Cf-9 genes in Nicotiana spp.

We have previously shown that tomato Cf-9 induces an Avr9-dependent hypersensitive response (HR) in Nicotiana tabacum and potato. We show here that Cf-4 also induces an Avr4-dependent HR in two tobacco species (N. tabacum and N. benthamiana). The HR induced by Cf-4 and Cf-9 was compared in stable tobacco transgenics by a seedling lethal assay and resistance to recombinant Potato virus X expressing Avr4 or Avr9. We also compared HR induction with Agrobacterium-mediated transient expression. The Cf-4/Avr4 combination induced a more rapid HR than Cf-9/Avr9. Sensitive assays for Cf-9 and Cf-4 function should prove useful for structure/function analyses of these resistance proteins in tobacco.

Agrobacterium tumefaciens↗
PubMed2000

Bioavailability of folate from processed spinach in humans. Effect of food matrix and interaction with carotenoids.

The effect of the food matrix and dietary fibre on the bioavailability of folate is not known. In a controlled, 3-week dietary intervention study, 28 men and 42 women were divided into six groups to receive either a control diet (n = 10), or the control diet plus 20 g/MJ per day (n = 12 per group) of whole-leaf spinach, minced spinach, liquefied spinach, or liquefied spinach to which dietary fibre (10 g/kg wet weight) was added. The sixth group received the control diet plus a synthetic carotenoid supplement with similar amounts of beta-carotene and lutein as found in spinach. A significantly higher plasma folate response was found for the pooled spinach groups than for the control group. Among the spinach groups no significant differences were detected. However, the plasma folate response of the pooled minced and liquefied spinach groups was greater than that of the whole-leaf spinach group (p = 0.03). Re-addition of dietary fibre to the liquefied spinach to compensate for the fibre broken down during liquefaction did not reduce the plasma folate response. The consumption of the carotenoid supplement did not have an effect on plasma folate concentrations compared with the control group. The food matrix in which the folate is entrapped plays a role in folate bioavailability.

Adolescent↗
PubMed2000

Homocysteine-lowering effect of 500 microg folic acid every other day versus 250 microg/day.

BACKGROUND/AIMS: Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for neural tube defects and vascular diseases. Supplementation with folic acid decreases tHcy. We investigated whether supplementation with 500 microg folic acid every other day is as effective in lowering tHcy as 250 microg folic acid each day. METHODS: In a 4-week intervention study, 22 healthy young women (18-40 years old) took either 500 microg folic acid every other day (500-microg/2d group) or 250 microg folic acid each day (250-microg/d group). Fasting blood was collected on days 0 and 28. RESULTS: Plasma folate concentrations increased by 11.4 nmol/l (6.8-15.9) in the 250-microg/d group and by 9.1 nmol/l (95% CI 1.9-16.3) in the 500-microg/2d group. These increases were not significantly different from each other. THcy concentrations decreased by 1.52 micromol/l (95% CI -2.09 to -0.95; p < 0.001) in the 250-microg/d group and by 0.88 micromol/l (-1.53 to -0.23; p < 0.05) in the 500-microg/2d group. The difference in decrease between the 250-microg/d group and the 500-microg/2d group was 0.64 micromol/l (p = 0.11). CONCLUSION: Although not conclusive, this study suggests that supplying subjects with folic acid each day decreases tHcy more effectively than a double dose every other day.

Adolescent↗
PubMed2000

Subjective burden in young and older African-American caregivers of patients with end stage renal disease awaiting transplant.

The purposes of this study were to identify the level of subjective burden reported by African American caregivers of patients diagnosed with end stage renal disease (ESRD) awaiting transplantation and identify whether subjective burden, personal strain, and role strain varied by caregiver age. An exploratory descriptive survey design was used. The convenience sample consisted of 78 African American family caregivers. Subjects were obtained from a University transplant clinic in the Mid-South. Caregivers completed the 22-item self-administered Burden Interview (BI) and a demographic data form. Data were analyzed using descriptive statistics and the appropriate parametric and nonparametric tests of group differences. Most caregivers, reported little to none or mild to moderate burden. Results also indicated that there was no significant difference in the level of overall burden, personal strain, and role strain reported by young and older caregivers. Additional findings revealed that burden was least in the caregivers of patients who independently performed activities of daily living (ADL) and greatest among the caregivers of patients assisted by someone other than the caregiver with ADL. Findings from this study may help nurses to assist caregivers to identify their level of burden early in the caregiving process. Implementation of early interventions may prevent negative psychological and physical outcomes in these caregivers.

Adult↗
PubMed1999

The mobile loop region of the NAD(H) binding component (dI) of proton-translocating nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum: complete NMR assignment and effects of bound nucleotides.

The dI component of transhydrogenase binds NAD+ and NADH. A mobile loop region of dI plays an important role in the nucleotide binding process, and mutations in this region result in impaired hydride transfer in the complete enzyme. We have previously employed one-dimensional 1H-NMR spectroscopy to study wild-type and mutant dI proteins of Rhodospirillum rubrum and the effects of nucleotide binding. Here, we utilise two- and three-dimensional NMR experiments to assign the signals from virtually all of the backbone and side-chain protons of the loop residues. The mobile loop region encompasses 17 residues: Asp223-Met239. The assignments also provide a much strengthened basis for interpreting the structural changes occurring upon nucleotide binding, when the loop closes down onto the surface of the protein and loses mobility. The role of the mobile loop region in catalysis is discussed with particular reference to a newly-developed model of the dI protein, based on its homology with alanine dehydrogenase.

Amino Acid Sequence↗