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Biomedical subjects

A Peter

Publications and source records attributed to A Peter.

At least 37 records · Page 2Linked to original sources

Personality traits and personality disorders.

The structure of personality disorder traits was examined in a sample of 400 undergraduates who completed the personality disorder questionnaire from the Structured Clinical Interview for DSM-III-R (SCID-II). The relations between personality disorder and normal personality traits indexed by the Eysenck Personality Questionnaire-Revised (EPQ-R) were examined. The three-cluster model of personality traits--as described in the DSM scheme--found equivocal support. Exploratory principal components analysis and confirmatory factor analysis found four broad factors of personality disorder that overlapped with normal personality traits: an asthenic factor related to neuroticism; an antisocial factor associated with psychoticism; an asocial factor linked to introversion-extraversion; and an anankastic (obsessive-compulsive) factor. There is growing agreement about the number and type of broad personality disorder dimensions; similar dimensions may be found in clinical and non-clinical samples, suggesting that those people with personality disorders differ quantitatively rather than qualitatively from others; and there is substantial overlap between normal and abnormal personality dimensions.

Adult↗

Chemical characterization of the predominant proteins secreted by mouse seminal vesicles.

Mouse seminal vesicles secrete four major protein components with estimated molecular masses of 95, 38, 17, and 16 kDa. Amino acid sequencing revealed that the 95-kDa component represents a protein with an unknown structure, while the 38-kDa component was identified as semenoclotin, the 17-kDa component as seminal-vesicle-secreted protein IV, and the 16-kDa component as seminal-vesicle-secreted protein V. Semenoclotin and the 95-kDa component were readily cross-linked by transglutaminase, suggesting that the two proteins are involved in the formation of the mouse copulatory plug. Treatment of mouse seminal vesicle fluid with human prostate-specific antigen rapidly degraded semenoclotin, indicating a structural resemblance of this protein to human semenogelins, despite the vast difference in primary structure. As previously reported for other seminal-vesicle-secreted proteins, the semenoclotin transcripts are shown to be under androgen control.

Amino Acid Sequence↗

Apoptosis induced by gamma-irradiation, but not CD4 ligation, of peripheral T lymphocytes in vivo is p53-dependent.

Mice generated by homologous recombination which carry a large deletion of the p53 tumour suppressor gene have a high incidence of spontaneous Thy1-positive thymic lymphoma. Extra-thymic lymphomas are rare. Apoptosis following gamma-irradiation in thymocytes from these animals in vitro is p53-dependent and there is a marked gene dose effect: heterozygotes show partial resistance to irradiation-induced cell death. Apoptosis in the T-cell zones of lymph nodes following in vivo gamma-irradiation was p53-dependent, but the gene dosage effect was less marked than that noted for thymocytes. Apoptosis was induced in vivo by ligation of CD4 on the cell surface following intravenous injection of anti-CD4 monoclonal antibody. Apoptosis was counted in lymph node sections using a semi-automated morphometric system. This showed no evidence of p53 dependency. In contrast to a previous report, which used a different line of p53-deficient mice, splenocytes from p53-null mice did not differ significantly from wild-type cells with respect to in vitro proliferative activity and response to mitogenic stimulation by concanavalin A. This may be due to strain differences. Therefore, whilst p53 has a role in the deletion of lymphocytes which have acquired pathological DNA strand breaks which may lead to mutations, the results of this study imply that p53 is not involved in the control of apoptosis following engagement of surface receptors, nor in response to physiological DNA breaks and normal recombination events during T-cell ontogeny.

Animals↗

T cell receptor alpha-chain tail is required for protein kinase C-mediated down-regulation, but not for signaling.

Antigen stimulation through the T cell receptor (TCR) induces phosphorylation of the associated CD3 gamma delta epsilon- and zeta-chain cytoplasmic tails. These events lead to the induction of the intracellular signaling pathways with concomitant receptor down-regulation. The TCR is down-regulated from the cell surface by the activation of protein kinase, C (PKC) and subsequent serine phosphorylation of the CD3 gamma-chain. We report here that the TCR alpha-chain cytoplasmic tail is also necessary for PKC-mediated internalization of the TCR complex. The requirement for the TCR alpha-chain cytoplasmic tail is specific for internalization of the TCR complex, since down-regulation of CD4 is still intact in hybridoma cells expressing a tailless TCR alpha-chain. The absence of TCR internalization directly correlates with defective PKC-mediated phosphorylation of the CD3 gamma-chain. Despite deficient PKC-mediated TCR down-regulation, the tailless alpha beta TCR still transduces antigenic signals resulting in the production of interleukin-2. Although the TCR tails are not obviously required for signal transduction, the TCR alpha-tail may serve as a targeting domain for PKC-mediated down-regulation of the TCR complex.

Amino Acid Sequence↗

[Lacrimal duct surgery in childhood. Retrospective study at the Munster University Ophthalmology Clinic].

UNLABELLED: Surgery on the lacrimal system in 296 children was performed at the Münster University Eye Hospital from 1987 to 1992. PATIENTS AND METHODS: The age of the patients, etiology of the obstruction and surgical strategy were analyzed retrospetively. A questionnaire was sent to the parents to allow evaluation of the results and subjective satisfaction. RESULTS: A total of 181 questionnaires was sent back to our hospital (results of 210 operations, including 24 preoperations). Of the 124 children were up to 3 years old. 197 obstructions were congenital, 7 traumatic, 4 results of inflammation, and 2 iatrogenic. In 184 patients we performed intubation with silicon tubing. Seven patients had canalicular surgery, and 19 patients had dacryocystorhinostomy (DCR). After intubation 87.5% of patients were practically without complaints, after canalicular surgery 85.7% and after DCR 78.9%. Five patients suffered from severe problems and had to be reoperated.

Child, Preschool↗

Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA.

Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both in F-PSA and in the PSA-ACT complex, while one antigenic domain was specific for F-PSA. The different domains contained both continuous and discontinuous epitopes. The combination of antibodies recognizing antigenic domains exposed both in F-PSA and PSA-ACT made it possible to develop several highly sensitive sandwich immunoassays for determination of total PSA, i.e. F-PSA + PSA-ACT, with the same molar response for F-PSA and PSA-ACT. Assays specific for F-PSA (cross-reactivity between F-PSA and PSA-ACT < 1%) were developed by the combination of antibodies recognizing epitopes exposed only in F-PSA and antibodies recognizing epitopes exposed both in F-PSA and PSA-ACT.

Animals↗

Film thickness of various dentine bonding agents.

Curing dentine bonding agents create a film thickness on the surface of teeth which are prepared for all-ceramic crowns. The aim of this study was to investigate if the film thickness of dentine bonding agents (DBAs) is acceptable with the fit of definitive restorations of 50-100 microm. AllBond 2, Syntac, ART Bond, P-Bond (an experimental DBA), and the Primer of AllBond 2 were applied onto teeth which were prepared with standardized all-ceramic crown preparations. The DBAs were applied onto the prepared tooth surfaces according to manufacturers' instructions and under a standardized simulation of intrapulpal pressure. After curing the DBAs, the teeth were cut mesiodistally and orolingually and the film thickness was measured under a light microscope. Only the film thicknesses of AllBond 2 and P-Bond were low enough and, therefore, would enable curing to take place immediately after their application.

Acid Etching, Dental↗

A menopause-specific quality of life questionnaire: development and psychometric properties.

OBJECTIVE: To develop a condition-specific quality of life questionnaire for the menopause with documented psychometric properties, based on women's experience. METHODS SUBJECTS: Women 2-7 years post-menopause with a uterus and not currently on hormone replacement therapy. Questionnaire development: A list of 106 menopause symptoms was reduced using the importance score method. Replies to the item-reduction questionnaire from 88 women resulted in a 30-item questionnaire with four domains, vasomotor, physical, psychosocial and sexual, and a global quality of life question. Psychometric properties: A separate sample of 20 women was used to determine face validity, and a panel of experts was used to confirm content validity. Reliability, responsiveness and construct validity were determined within the context of a randomized controlled trial. Construct validation involved comparison with the Neugarten and Kraines'Somatic, Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General Well-Being Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index, and the Life Satisfaction Index. RESULTS: The face validity score was 4.7 out of a possible 5. Content validity was confirmed. Test-retest reliability measures, using intraclass correlation coefficients were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The intraclass correlation coefficient for the vasomotor domain was 0.37 but there is evidence of systematic change. Discriminative construct validity showed correlation coefficients of 0.69 for the physical domain, 0.66 and 0.40 for the vasomotor domain, 0.65 and -0.71 for the psychosocial domain, 0.48 and 0.38 for the sexual domain, and 0.57 for the quality of life question. Evaluative construct validity showed correlation coefficients of 0.60 for the physical domain, 0.28 for the vasomotor domain, 0.55 and -0.54 for the psychosocial domain, 0.54 and 0.32 for the sexual domain, and 0.12 for the quality of life question. Responsiveness scores ranged from 0.78 to 1.34. CONCLUSIONS: The MENQOL (Menopause-Specific Quality of Life) questionnaire is a self-administered instrument which functions well in differentiating between women according to their quality of life and in measuring changes in their quality of life.

Attitude to Health↗

A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17 beta combined with an oral progestin on quality of life in postmenopausal women.

OBJECTIVE: To compare the effect of transdermal estradiol-17 beta and oral conjugated equine estrogen when combined with an oral progestin on quality of life in post-menopausal women. DESIGN: Randomized controlled double-blind trial. A randomization error lead to the exclusion of six subjects but the soundness of the remaining randomization was confirmed. SETTING: Large urban community. PATIENTS: Women 2-7 years after menopause with a uterus and ovaries, and not currently using hormone replacement therapy. Seventy-four women completed the trial. INTERVENTIONS: After baseline measures of quality of life, subjects were randomly assigned to either continuous oral conjugated equine estrogen 0.625 mg daily or continuous transdermal estradiol-17 beta 50 mcg twice weekly, for four 4-week cycles. Medroxyprogesterone acetate 10 mg oral tablets was administered to both groups for the last 12 days of each cycle. OUTCOMES MEASURED: Quality of life was determined using the Menopause-Specific Quality of Life Questionnaire. Tolerability was determined by a specifically designed list of adverse effects. Both measures were recorded at base-line and in mid-cycle during the second, third and fourth cycles of treatment. RESULTS: There were no statistically significant differences in any of the domains at baseline between the oral and transdermal treatment groups. In the vasomotor domain-scores for the oral and transdermal groups improved from baseline levels of 3.14 and 3.09, respectively, to 1.32 and 1.23; physical domain scores improved from 2.45 and 2.73 to 2.04 and 1.78; psychosocial domain scores improved from 2.72 and 3.04 to 2.21 and 1.94; sexual domain scores improved from 2.32 and 2.16 to 1.64 and 1.30. There were no statistically significant group differences or time/group interactions. Both forms of therapy were equally well tolerated. CONCLUSIONS: Improvement in all domains, measured by the Menopause-Specific Quality of Life Questionnaire, was observed in both the oral and transdermal groups. In the absence of a placebo control group, the improvements observed cannot be attributed solely to the therapy. Neither form of therapy offered an advantage over the other in respect to improvement in quality of life.

Administration, Cutaneous↗

A motif within the T cell receptor alpha chain constant region connecting peptide domain controls antigen responsiveness.

Mutant alphabeta TCRs were generated by replacing domains of the alpha and beta chain constant regions with homologous domains from TCR delta and gamma chains, respectively. Chimeric TCRs in which the alpha chain contains TCR delta chain sequences within the connecting peptide domain are unresponsive to alloantigens and superantigens, and have defective interactions with the CD3/zeta complex. Although these antigen-unresponsive TCRs undergo zeta chain phosphorylation upon stimulation with superantigen, they do not generate a full signal capable of producing IL-2. Mutant TCRs acquire signaling activity with a combination of superantigen and calcium ionophore, indicating a defect in calcium-mediated signaling. Finally, a conserved motif, FETDxNLN, present in the alpha chain connecting peptide domain, is disrupted in all signaling-defective TCRs. This conserved alpha chain connecting peptide motif might mediate the transfer of signals from the alphabeta heterodimer to the CD3/zeta complex.

Amino Acid Sequence↗

Surgery in ovarian cancer: the concept of cytoreductive surgery.

Critical analysis of the collected evidence on cytoreductive surgery suggests a median survival benefit of 9-12 months in combination with platinum-based chemotherapy. Recently, a randomized study on the value of secondary cytoreduction showed a median survival benefit of 6 months for those with small residual disease after the second operation. Primary cytoreduction is feasible in approximately 70% of patients, with an acceptable level of morbidity. The reported evidence justifies a serious attempt at cytoreductive surgery at the first operation by an experienced gynaecological oncologist.

Carcinoma↗

Lethal Waterhouse-Friderichsen syndrome in posttraumatic asplenia.

We herein report a case of fulminant lethal Waterhouse-Friderichsen syndrome in an elderly female patient seven years after posttraumatic splenectomy. In contrast to various reports, this patient had not been vaccinated against Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae, respectively, although infections with these microorganisms are known to cause the main lethal diseases in asplenic patients. Again, we recommend obligatory vaccinations against the mentioned bacteria for it is known that this decreases the risk of fatal septic events in these patients. To optimize prevention, it is imperative to vaccinate patients undergoing splenectomy before discharge from hospital.

Blood Coagulation Tests↗

The role of volume-sensitive Cl- channels in the stimulation of chloride absorption by short-chain fatty acids in the rat colon.

The short-chain fatty acids acetate, propionate and butyrate induced a concentration-dependent decrease in short-circuit current (Isc) of the rat colon in vitro. The decrease in Isc, being more pronounced in the distal than in the proximal colon, was dependent on the presence of Cl- ions and partly on the presence of HCO3-. In the distal colon, the fall in Isc could be inhibited by amiloride, indicating that the activity of the Na+/H+ exchanger is necessary for the induction of this response. The decrease in Isc was diminished by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate, and the lipoxygenase inhibitor, nordihydroguaiaretic acid. In contrast, inhibitors of the leukotriene pathway or a Cl- channel blocker did not affect the Isc response in the proximal colon. Measurements of unidirectional fluxes revealed that butyrate caused a stimulation of the mucosa to serosa fluxes (Fms) of Na+ and Cl- in the distal, but only of FNams in the proximal colon. Unidirectional Rb+ fluxes were not altered. The stimulation of Fclms correlated with the degree of metabolism of the short-chain fatty acid. The increase in FClms was most pronounced for butyrate, smaller for acetate and not observed with the poorly metabolizable short-chain fatty acid, isobutyrate. Consequently, two factors seem to be responsible for the stimulation of Cl- absorption by short-chain fatty acids in the distal colon: (1) the intracellular production of HCO3- during the oxidation of short-chain fatty acids as substrate for the apical Cl-/HCO3- exchanger, and (2) the activation of volume-sensitive basolateral Cl- channels.

Animals↗

Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene.

In human tumourigenesis the tumour suppressor gene most commonly affected by mutation, inactivation or allele loss is p53. Loss of p53 function is associated both with failure to maintain a normal diploid status and inability to delete cells by apoptosis following DNA damage. To investigate further the role of p53 we have generated mice carrying a large deletion within the gene. All animals homozygous for this deletion develop spontaneous tumours, predominantly lymphomas, by the age of 6 months. 10% of heterozygotes develop a range of neoplasms, with a lower predisposition towards lymphoma, by 9 months. Both tumour incidence and spectrum in heterozygotes differ from those previously reported in another p53 mutant stock, suggesting either difference in exposure to carcinogens between the two stocks, or a role for modulating genes within different genetic backgrounds. Tumours showed frequent loss of diploid status, and the majority of those arising in heterozygotes showed loss of the wild type allele. These findings are consistent with the concept that p53 acts as a tumour suppressor by preventing the propagation of DNA damage to daughter cells.

Alleles↗

[The patient with chronic low back pain in a thermal spa].

We have made our study over a period of five months. Out of 553 patients admitted to the Thermal Clinic at Lavey-les-Bains, we observed 111 patients suffering from chronic low-back pain, noting the changes, both subjective and objective, during their three-week stay at the clinic. From the physical aspect, they were encouraged to increase lumbothoracic mobility. From the subjective aspect, an evaluation of pain and handicap level, was made using a visual comparison scale and the completion of a questionnaire. We concluded that, in the short term, thermal treatment resulted in an appreciable relief of pain for these patients. In the long term, however, in view of the changing developments in clinical measuring techniques it is not possible to estimate in advance the functional effectiveness of treatment.

Adult↗

New simplified molecular design for functional T cell receptor.

We have produced a chimeric single-chain T cell receptor (TcR) that combines the specific antibody recognition function and TcR/CD3 signaling properties within the same polypeptide chain. This hybrid molecule consisted of a single-chain antibody combining site that was connected over a short spacer to the transmembrane and cytoplasmic region of CD3 zeta. When expressed on TcR- or TcR+ T cell hybridomas it could mediate recognition of relevant target cells and subsequent production of lymphokines; i.e. it could functionally replace the TcR/CD3 complex. Therefore, the single-chain TcR model presented here represents an interesting and useful means for the creation of T cells with new specificities.

Base Sequence↗

Promoter, enhancer and silencer elements regulate rearrangement of an immunoglobulin transgene.

The chicken Ig lambda light chain locus is composed of a single V gene closely linked (1.8 kb) to a single J-C unit in its natural configuration. In mice transgenic for this locus, the transgene becomes rearranged in B cells and to a much lesser extent in T cells. Modifications were introduced in the transgene in order to characterize elements which target the recombinase to the Ig loci. In the absence of either the promoter or the enhancer located 3' of C lambda, rearrangement of the transgene is reduced 20- to 100-fold. Moreover, rearrangement is increased 5-fold when the DNA segment between V lambda and J lambda ('Uo segment'), which is deleted during the joining process, is replaced by a neutral DNA segment of equal length. The Uo segment behaved as a strong transcriptional silencer when tested in a CAT assay in vitro. Control transgenic mice harbouring only the two 3 bp mutations that introduced restriction sites at both ends of the Uo segment to allow for its replacement were also analysed. Rearrangement was reduced 10- to 100-fold in B cells from such transgenic lines. A model is proposed whereby the sites of these two mutations would function by counteracting transiently the repressing effect of the silencer, thus giving access of the chicken light chain locus to the recombinase.

Animals↗

Practice nursing in Glasgow after the new general practitioner contract.

Six months after the implementation of the new general practitioner contract in April 1990, practice nurses employed in greater Glasgow were surveyed using a self completed postal questionnaire. Of the 165 practice nurses employed in greater Glasgow 153 (93%) were identified and surveyed. Of these, 131 responded to the questionnaire (86%). The practice nurses were well qualified and experienced. Sixty per cent were under 40 years of age, 68% had been recruited within the previous year and 70% were employed for five sessions or more per week. Many carried out extended nursing duties, including health promotion activities. Many described inadequacies of their employment contract, practice facilities and the functioning of the primary health care team. If service quality is to be assured in practice nursing and practice nurses are to function as key primary health care team workers, then it is important that their role, professional skills, and working facilities are defined, supported and monitored. This should be addressed by general practitioners, practice nurses, and their professional bodies, in collaboration with the health board.

Adult↗