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Biomedical subjects

F Talbot

Publications and source records attributed to F Talbot.

At least 19 recordsLinked to original sources

Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation.

BACKGROUND/AIMS: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. METHODS: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves. RESULTS: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001). CONCLUSION: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Adult↗

Functional and dysfunctional perfectionists: are they different on compulsive-like behaviors?

Both perfectionism and excessive responsibility have been linked to obsessive compulsive disorder (OCD). Up to now however, a greater number of studies have focused on the role of responsibility. The present study compared compulsive-like behavior of people with different styles of perfectionism. Sixteen functional perfectionists (FP) and 16 dysfunctional perfectionists (DP) were compared on three different tasks in order to explore OC type behavior such as doubting, checking and intrusions. Results show that DP participants, compared to FP participants, scored higher on an OC behavior scale, took significantly more time to complete a precision task and precipitated their decision when confronted with ambiguity. The two groups also tended to differ in their intrusive thoughts following an unsolved problem; FP participants were more preoccupied about solving the problem than about the quality of their performance, contrary to DP subjects. Results are discussed according to theoretical models of OCD.

Adult↗

A review of the relationship between depression and diabetes in adults: is there a link?

OBJECTIVE: To review the support for two hypotheses concerning the interrelationship between depression and diabetes and to identify areas in which more research is needed. RESEARCH DESIGN AND METHODS: A review was conducted using primarily electronic databases. Articles relating to diabetes and depressive symptomatology, depressive disorder, and dysthymic disorder were selected. The study focuses mainly on adults with diabetes. RESULTS: The initial onset of major depressive disorder (MDD) seems to be independent of the onset of type 2 diabetes, but results remain equivocal for type 1 diabetes. However, in both type 1 and type 2 diabetes, diabetes-related psychological and physiological processes may be involved in the higher recurrence and longer duration of MDD and depressive symptomatology CONCLUSIONS: The hypotheses that the initial occurrence of clinically significant depression, MDD, results from either biochemical changes directly due to type 2 diabetes or its treatment or from the psychosocial demands imposed by the illness or its treatment do not seem to be supported. MDD in diabetic individuals represents a multidetermined phenomenon resulting from interactions between biologic and psychosocial factors. This interaction may increase the probability of developing type 2 diabetes in otherwise healthy individuals.

Adult↗

Relations of diabetes intrusiveness and personal control to symptoms of depression among adults with diabetes.

The generalizability of a model linking illness characteristics to psychosocial well-being was tested in a cross-sectional study of 237 adults with type 2 diabetes. It was hypothesized that diabetic complications increase illness intrusiveness, which in turn increases depressive symptomatology either directly or indirectly by reducing personal control over health outcomes. Illness intrusiveness was defined as the result of disruptions of valued activities and interests due to constraints imposed by the illness. An excellent fit of this model to the data was found using structural equation modeling. The model explained 65% of the variance in depressive symptomatology. Assessment of an alternative model excluding personal control suggested that the extent to which diabetes intrudes in life, rather than diabetic complications per se or personal control, is a key factor in relation to depressive symptomatology in individuals with diabetes.

Adult↗

Biochemical and immunological analyses of the flagellin of Clostridium tyrobutyricum ATCC 25755.

The monoclonal antibody 21E7-B12 (IgG3) can be used in a direct method of Clostridium tyrobutyricum detection based on an immunoenzymatic assay. Immunoelectron microscopy demonstrated that the 21E7-B12 antibody recognized the surface-exposed epitopes on the flagellar filaments of C. tyrobutyricum. After flagellar extraction, the purified flagellin showed an apparent molecular mass of 46 kDa with an isoelectric point of 3.6. Sugar staining, mild periodate oxidation and beta-elimination experiments showed that the flagellin was glycosylated and that the 21E7-B12 epitope was located in the sugar moiety. Amino acid composition showed that the flagellar filament protein contained a high percentage of serine and threonine, while proline was absent. The first 23 residues of the N-terminal were determined and sequence homology with other flagellins was found.

Amino Acid Sequence↗

Partial analysis of the flagellar antigenic determinant recognized by a monoclonal antibody to Clostridium tyrobutyricum.

In order to count Clostridium tyrobutyricum spores in milk after membrane filtration, murine 21E7-B12 monoclonal antibody was produced. Elution of the monoclonal antibody from this antigen, the flagellar filament protein, by carbohydrate ligands was used to study the epitope structure. A competitive elution of an anti-dextran monoclonal antibody by carbohydrate ligands served as a control in order to validate the immunological tool applied to flagellin epitope study. The carbohydrate moiety of flagellin contained D-glucose and N-acetyl-glucosamine in a molar ration of 11:1 as determined by gas-liquid chromatography and 2 low-abundancy unidentified compounds. In ELISA, D-glucose and N-acetyl-glucosamine did not dissociate the antibody-flagellin complex contrary to maltose, maltotriose, maltotetraose and maltopentaose. The efficiency of elution increased from the dimer to the pentamer and became nil for maltohexaose and maltoheptaose. The fact that the hexamer and heptamer could not react with the 21E7-B12 monoclonal antibody could be explained by a drastic conformational change. The over-all stretched maltopentaose switch to a helical-shaped maltoheptaose which could not fit the 21E7-B12 monoclonal antibody antigen-combining site. Thus, flagellin epitope may contain alpha (1-->4) linked glucose residues plus either N-actyl-glucosamine or an unidentified compound that maintain it in an extended shape.

Antibodies, Monoclonal↗

Evidence for an heterogeneous glycosylation of the Clostridium tyrobutyricum ATCC 25755 flagellin.

Glycosylation analysis of the flagellin from the Gram-positive species Clostridium tyrobutyricum has been supplemented. Amino acid analysis of the glycopeptides obtained after pronase digestion of flagellin indicated that O-glycosylation which was previously demonstrated after nonreductive beta-elimination, probably occurred via the hydroxyl group of serine. Otherwise, beta-elimination partly deglycosylated flagellin. After this treatment carbohydrates were still linked to protein as shown by a digoxigenin-hydrazide labelling. Therefore, in addition to linkages via serine, alkaline resistant linkages exist on the flagellin and some glycans may be linked to the protein core via the amide nitrogen of asparagine or via the hydroxyl group of tyrosine. Furthermore, according to an immunological analysis, glycans attached to flagellin via alkaline sensitive linkages may be different from those attached via alkaline resistant linkages.

Amino Acids↗

The assessment of diabetes-related cognitive and social factors: the Multidimensional Diabetes Questionnaire.

The purpose of this study was to examine the psychometric properties of the recently developed Multidimensional Diabetes Questionnaire (MDQ). The MDQ, which is theoretically linked to a social learning perspective of diabetes, was designed to provide a comprehensive assessment of diabetes-related cognitive and social factors. It includes 41 items grouped into three sections: (1) perceptions related to diabetes and related social support, (2) positive and misguided reinforcing behaviors related to self-care activities, and (3) self-efficacy and outcome expectancies. Confirmatory factor analyses, conducted on a sample of 249 patients with non-insulin-dependent diabetes mellitus, supported the construct validity of the MDQ. Adequate internal consistency and significant demographic, psychological, behavioral, and disease-related correlates were found. The MDQ may prove valuable in understanding individual differences in adjustment to diabetes.

Adult↗

The development of an empirical psychosocial taxonomy for patients with diabetes.

The main purpose of this study was to develop and to cross-validate an empirically derived psychosocial taxonomy of patients with diabetes. In the first study, 101 patients with Type I or Type II diabetes completed the Multidimensional Diabetes Questionnaire. Cluster analysis identified three clusters, labeled adaptive copers, low support-low involvement, and spousal overinvolvement. In the second study, the taxonomy was cross-validated using an independent sample of 132 patients with long-standing Type II diabetes. The results confirmed that the multivariate classification system was unique and highly accurate. External validation, using general psychological as well as diabetes-specific measures, supported the validity and distinctiveness of the patients' profiles. These findings help establish a multiaxial psychosocial taxonomy of diabetes and may have significant implications for the management of patients with diabetes.

Adaptation, Psychological↗

Pericranial muscle tenderness and exteroceptive suppression of temporalis muscle activity: a blind study of chronic tension-type headache.

The aim of the present study was to examine the ability of pericranial muscle tenderness and the second exteroceptive suppression period to distinguish chronic tension-type headache sufferers, migraine sufferers, and controls in a young adult population utilizing a blind design. The second exteroceptive suppression periods were assessed using the methodology recommended by the European Headache Federation and were scored with an automated computer software program designed in our laboratory to provide reliable, standardized, and precise quantification of exteroceptive suppression periods and eliminate any influence of experimenter bias that may occur with manual scoring. Our sample consisted of 45 subjects diagnosed according to IHS criteria: 25 with chronic tension-type headache and 20 with migraine without aura. Twenty-three headache-free controls were recruited. Consistent with our previous findings, abnormalities in pericranial muscle tenderness, but not in the second exteroceptive suppression period distinguished chronic tension-type headache sufferers from controls. The chronic tension headache sufferers exhibited the highest pericranial muscle tenderness and the control group exhibited the lowest tenderness (P < .001). Pericranial muscle tenderness was quite successful in distinguishing recurrent headache sufferers from controls, but failed to distinguish chronic tension-type headache sufferers from migraineurs. Our findings raise the possibility that pericranial muscle tenderness is present early in the development of chronic tension-type headache and migraine without aura, and thus might contribute to the etiology of headache disorders. Our findings also indicate that a shortened second exteroceptive suppression period is not a reliable marker for chronic tension-type headache in young adults.

Adolescent↗

Behavioral expressions of intolerance of uncertainty in worry. Experimental findings.

Intolerance of uncertainty has been related to increased worry in recent conceptual models of Generalized Anxiety Disorder (GAD). The present study examines the relationship between a measure of intolerance of uncertainty, the Intolerance of Uncertainty scale (IU), and behaviors associated with GAD, such as slowness of execution and amount of evidence required before decision making. A total of 49 individuals participated in the study. Three experimental tasks varying in level of ambiguity and difficulty were used. The analyses show a positive correlation between scores on the IU and number of cues required before responding in a moderately ambiguous inference task. However, scores on the IU were not significantly related to responses in an unambiguous task (regardless of the level of difficulty) or in a highly ambiguous task. The results suggest that high worriers have a lower threshold of tolerance of uncertainty for intermediate levels of ambiguity. The results are discussed in terms of theoretical models of GAD.

Adult↗

Monoclonal antibody detection of Clostridium microcolonies directly on membrane used for milk filtration.

The normal procedure for bacterial colony detection requires a nitrocellulose transfer step after membrane filtration and culture to prevent the development of a high background during the immunodetection. In this paper, we describe a modification of the basic protocol that omits the transfer step and reduces the risk of background. Previous observations indicated that interactions between milk components (principally cream) and membrane are responsible for the high non-specific staining observed. Experiments were performed to remove lipid components or to block the membrane binding sites before milk filtration. Samples of milks of different origin (collected at different times of the year) and different membranes were tested. The results obtained showed that removing lipids did not significantly improve the test but, on the contrary, led to an antigen diffusion. Incubation of the membrane in 0.1% (w/v) of Tween 20 in phosphate-buffered saline before milk filtration prevented non-specific binding, and allowed performance of the detection without any noticeable background.

Animals↗

Is health locus of control a 3-factor or a 2-factor construct?

Although the Multidimensional Health Locus of Control (MHLC) scales are commonly used, uncertainty about their factorial validity still remains. In the present study, confirmatory factor analyses of a French-Canadian adaptation of the Multidimensional Health Locus of Control scales (MHLC) were conducted to compare in a non-clinical group of 224 adults two factor models. Multigroup analyses were also conducted using this group and a clinical group of 132 diabetics to assess the equivalence of the MHLC factor structure across these two groups. A 3-factor model postulating an internal, external, and chance dimension, and accounting for measurement errors provided the best fit to the data. Multigroup analyses failed to support the equivalence of the MHLC factor loadings across the non-clinical and clinical group. These findings suggest that comparisons of MHLC scores across such groups may be problematic.

Adult↗

Assessing the dimensions of pain: a multitrait-multimethod evaluation of seven measures.

A multitrait-multimethod design was used to examine the convergent and discriminant validity of seven pain measures from three widely used self-report instruments designed to assess the sensory, affective and intensity dimensions of pain. The instruments were the McGill Pain Questionnaire, the Pain Perception Profile and Numerical Ratings. Three distinct factor models, each corresponding to a different hypothesis about how these pain measures are related, were tested using confirmatory factor analysis in a sample of 419 headache sufferers. A three-factor model, postulating three correlated factors defined by the three assessment instruments best explained the correlations between the pain measures. Measures of sensory, affective and intensity dimensions from the three instruments failed to exhibit convergent or discriminant validity. Rather, instrument variance obscured the pain qualities the three pain instruments were designed to assess. These findings suggest that greater attention needs to be paid to how formal characteristics of pain assessment instruments influence patients' descriptions of their pain.

Adolescent↗

Production of monoclonal antibodies against the outer cell wall of Clostridium tyrobutyricum.

Several hybridoma cell lines producing murine monoclonal antibodies (mAbs) directed to the Clostridium tyrobutyricum outer cell wall have been established and characterized. Whole bacteria, crude extract of cell wall, and polysaccharide fraction of crude extract have been used as immunogens. The immunizations were performed either in vivo or in vitro after priming in vivo. Amongst the clones obtained, six hybridoma cell lines were selected. Four mAbs recognized only the immunizing strain (ATCC 25755), while two mAbs recognized all the C. tyrobutyricum tested strains. Three mAbs were IgM, one IgG3, and two IgG1 isotypes. The antigens (proteins or polysaccharides) recognized by these mAbs have been characterized by Western Blot. These mAbs could be used for an early detection of C. tyrobutyricum in milk.

Animals↗

Functional analysis of P-glycoprotein mutants identifies predicted transmembrane domain 11 as a putative drug binding site.

The substitution of a single serine to phenylalanine residue within the predicted transmembrane domain 11 of P-glycoproteins (P-gps) encoded by mouse mdr1 (Ser941, 1S;Phe941, 1F) or mdr3 (Ser939, 3S; Phe939, 3F) strongly modulates both the overall activity and substrate specificity of the two P-gps. In cell clones expressing either wild-type (1S, 3S) or mutant P-gps (1F, 3F), we show that the modulating effect of the mutation on the levels of adriamycin (ADM) resistance detected in drug cytotoxicity assays is paralleled by a similar modulation of the intracellular accumulation and extracellular efflux of radiolabeled adriamycin ([14C]ADM) from preloaded cells. Cytofluorescence studies with ADM on live cells produce similar results and demonstrate strong nuclear ADM accumulation only in drug-sensitive LR cells and in the 1F expressing cells, with little if any accumulation in 1S, 3S, or 3F expressing cells. Drug cytotoxicity and drug transport assays carried out in the presence of verapamil or progesterone suggest that the Ser to Phe substitution also reduces the capacity of these two reversal agents to modulate P-gp activity. Labeling experiments with the photoactivatable P-gp ligands iodoarylazidoprazosin and azidopine indicate a strong reduction in binding of these photoactivatable probes to the mutant P-gps (1F, 3F) as compared to their wild-type counterparts (1S,3S). These results indicate that the studied mutations in TM11 reduce drug transport by decreasing initial drug binding to P-gp. This phenotype is opposite to that of a mutation near TM3 in human MDR1 (pst 185), where decreased drug transport is associated with increased drug binding and decreased drug release from P-gp [Safa, A. R., Stern, R. K., Choi, K., Agresti, M., Tamai, I., Metha, N. D., & Roninson, I. B. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7225-7229].

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Lipophilic cations: a group of model substrates for the multidrug-resistance transporter.

The possibility that simple lipophilic cations such as tetraphenylphosphonium (TPA+), triphenylmethylphosphonium (TPMP+), and diphenyldimethylphosphonium (DDP+) are substrates for the multidrug-resistance transport protein, P-glycoprotein, was tested. Hamster cells transfected with and overexpressing mouse mdr1 or mouse mdr3 exhibit high levels of resistance to TPP+ and TPA+ (20-fold) and somewhat lower levels of resistance to TPMP+ and DDP+ (3-12-fold). Transfected cell clones expressing mdr1 or mdr3 mutants with decreased activity against drugs of the MDR spectrum (e.g., Vinca alkaloids and anthracyclines) also show reduced resistance to lipophilic cations. Studies with radiolabeled TPP+ and TPA+ demonstrate that increased resistance to cytotoxic concentrations of these lipophilic cations is correlated quantitatively with a decrease in intracellular accumulation in mdr1- and mdr3-transfected cells. This decreased intracellular accumulation is shown to be strictly dependent on intact intracellular nucleotide triphosphate pools and is reversed by verapamil, a known competitive inhibitor of P-glycoprotein. Taken together, these results demonstrate that lipophilic cations are a new class of substrates for P-glycoprotein and can be used to study its mechanism of action in homologous and heterologous systems.

ATP Binding Cassette Transporter, Subfamily B, Mem↗