Biomedical subjects

C Vincent

Publications and source records attributed to C Vincent.

At least 181 records · Page 10Linked to original sources

PubMed1994

Mental and physical health status in a community sample of New Zealand Vietnam War veterans.

The data presented in this paper were obtained by a survey involving 573 New Zealand Vietnam veterans. It represents the first comprehensive report on the mental and physical health of a community sample of these ex-service personnel. Although most of these veterans were reasonably healthy for their age, a small proportion was substantially worse off than their Vietnam veteran peers, reporting relatively low levels of psychological wellbeing, relatively high levels of psychological distress and post-traumatic stress disorder, a greater number and severity of physical health symptoms, lower self-rated health status, and making more frequent contacts with health care providers.

Australia↗

PubMed1994

Immunoblotting detection of so-called 'antikeratin antibodies': a new assay for the diagnosis of rheumatoid arthritis.

OBJECTIVES: To assess the diagnostic value for rheumatoid arthritis (RA), of an immunoblotting assay based on the rat oesophagus epithelium antigens recognised by the so-called 'antikeratin antibodies' ('AKA'), antigens that have been identified as three non-cytokeratin proteins (referred to as A, B and C proteins). METHODS: After polyacrylamide gel electrophoresis in non-denaturing conditions and electrotransfer of an epithelial extract, the immunoreactivities to the A, B and C proteins of a series of serum samples from 88 patients with RA and 100 patients with non-rheumatoid rheumatic diseases, were semiquantitatively evaluated. RESULTS: A total of 81.8% of RA serum samples recognised the three proteins, while 91% of non-RA serum samples only weakly recognised the A and B proteins but not the C protein. Only in the group of RA patients, were the titres of the antibodies to the A, B and C proteins found to be significantly correlated with each other and with the titres of 'AKA' detected by the standard indirect immunofluorescence (IIF) method. For a diagnostic specificity of 99%, the diagnostic sensitivities of the detection of the A and B proteins were 50% and 43.2%, respectively, when those of the detection of 'AKA' by IIF and of IgM-rheumatoid factor by enzyme-linked immunosorbent assay were 42% and 54%, respectively. In contrast, at a same specificity of 99%, the diagnostic sensitivity of the detection of the C protein was significantly higher with a value of 70.5%. CONCLUSION: This immunoblotting assay which is the first immunochemical method proposed for the detection of 'AKA, should be validated on larger series of patients but can already be considered as a very powerful test for the serological diagnosis of RA.

Arthritis, Rheumatoid↗

PubMed1994

Clinical complaints: a means of improving quality of care.

OBJECTIVES: To establish the reasons for clinical complaints, complainants' feelings about the original incident, and their motivation in complaining. DESIGN: Postal questionnaire survey. SETTING: 24 hospitals in North West Thames region. SUBJECTS: 1007 complainants who had written to 20 hospitals between 1 January 1992 and 30 June 1993 about a complaint involving a clinical incident. MAIN MEASURES: Personal details, the nature of the complaint, the complainant's reaction to the original incident, the quality of the explanation at the time of the incident, the reasons for making a complaint, and what would have prevented the incident. RESULTS: 491 completed questionnaires were received (response rate 49%). Complaints arose from serious incidents, generally a clinical problem combined with staff insensitivity and poor communication. Clinical complaints were seldom about a clinical incident alone (54; 11%); most (353; 72%) included a clinical component and dissatisfaction with personal treatment of the patient or care. In all, 242(49%) complainants reported a need for additional medical treatment, 206(42%) reported that the patient's condition had worsened as a result of treatment, and 175(36%) that side effects had been experienced. In 26(5%) cases the patient had died. Complainants' primary motive was to prevent recurrence of a similar incident. Lack of detailed information and staff attitude were identified as important criticisms. CONCLUSIONS: The emphasis must be on obtaining a better response to complaints at the clinical level by the staff involved in the original incident, not simply on adjusting the complaints procedure. Staff training in responding to distressed and dissatisfied patients is essential, and monitoring complaints must form part of a more general risk management programme.

Attitude of Health Personnel↗

PubMed1994

[Social reintegration: a dynamic program to help psychiatric patients acquire functional and interpersonal skills].

Since new mental health policies have been developed, government and community-based organizations appear to be working closer toward facilitating the social reintegration process regarding persons experiencing psychiatric problems. This article describes a project which fosters the development of a patient's functional and interpersonal skills in a para-hospital environment: supervised apartments. The program's objective is to encourage awareness of an individual's situation and especially to allow him or her to acquire and experiment a certain number of skills for the ultimate purpose of reintegrating the community. This project is carried out by the psychiatry department of Notre-Dame Hospital in collaboration with the Maison l'Echelon Inc., a non-profit organization that manages a group of supervised apartments for psychiatric patients.

Adolescent↗

PubMed1993

Internalization and degradation of anti-CD4 monoclonal antibodies bound to human peripheral blood lymphocytes.

Treatment of patients with anti-CD4 mAbs induces both functional alterations of CD4+ cells and depletion of circulating CD4+ lymphocytes. Some of these effects depend on the amount of mAb molecules bound per CD4+ cell and on the properties of the Fc part of the mAb (isotype specificity). We have investigated the fate of anti-CD4 monoclonal antibodies (mAbs) after their interaction with CD4 protein on the surface of peripheral blood lymphocytes (PBL). We used seven anti-CD4 mAbs whose epitope specificity, equilibrium constant and kinetics of binding are reported. Lymphocytes were saturated with anti-CD4 mAbs either at +4 degrees C or 37 degrees C then washed and incubated in antibody-free medium. At different time intervals cells were processed for analysis. By indirect immunofluorescence, it was shown that the amount of surface-bound mAb decreased rapidly when cells were incubated at 37 degrees C, but not at 4 degrees C. With 125I-mAbs, we demonstrate that there was a rapid internalization of the molecules followed by the re-expression on the cell surface of a part of initially bound mAbs and by the release of partially degraded antibody in the cell supernatant. In the presence of sodium azide (10 mM) only a slow dissociation of intact antibody occurred, without internalization. The radioactive material eluted in the 100-200 kDa zone from supernatants was only partly adsorbed on protein A and hardly on CD4+ cells, indicating that alterations of the Fc region and loss of antigen binding activity, possibly by formation of CD4-anti-CD4 complexes, had occurred during the process of internalization and release into the extracellular medium. These data may be important to consider for adjusting the dosage of anti-CD4 mAbs to be administered.

Antibodies, Monoclonal↗

PubMed1993

Characterisation of the rat oesophagus epithelium antigens defined by the so-called 'antikeratin antibodies', specific for rheumatoid arthritis.

OBJECTIVES: An attempt was made to characterise the antigens recognised by serum IgG antibodies directed to the stratum corneum of rat oesophagus epithelium, the so-called 'antikeratin antibodies', which were shown to be highly specific for rheumatoid arthritis (RA) and thus to have an actual diagnostic value. METHODS: Immunoblotting was performed with RA serum samples on different extracts of rat oesophagus epithelium separated by various monodimensional and two dimensional electrophoreses. RESULTS: Three low-salt-soluble antigens sensitive to proteinase K and, therefore, of protein nature were identified. Two proteins, with apparent molecular masses of 210 and 120-90 kilodaltons, shared isoelectric points ranging from 5.8 to 8.5; the third protein exhibited isoelectric points from 4.5 to 7.2 while its molecular mass ranged from 130 to 60 kilodaltons. Immunoadsorption of RA serum samples onto cytokeratins extracted from the stratum corneum of rat oesophagus epithelium did not change their immunoreactivity towards the three antigenic proteins. Widely used deglycosylation and dephosphorylation methods failed to modify either the electrophoretic migration of the proteins or their immunoreactivity with RA serum samples. CONCLUSION: The so-called 'antikeratin antibodies' do not react with cytokeratins. They specifically recognise three late epithelial differentiation proteins which had not been previously described. These proteins may be related to (pro)filaggrin.

Animals↗

PubMed1993

The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," autoantibodies specific for rheumatoid arthritis.

In rheumatoid arthritis (RA), the high diagnostic value of serum antibodies to the stratum corneum of rat esophagus epithelium has been widely reported. These so-called "antikeratin antibodies," detected by indirect immunofluorescence, were found to be autoantibodies since they also labeled human epidermis. Despite their name, the actual target of these autoantibodies was not known. In this study, a 40-kD protein (designated as 40K), extracted from human epidermis and specifically immunodetected by 75% of RA sera, was purified and identified as a neutral/acidic isoform of basic filaggrin, a cytokeratin filament-aggregating protein, by peptide mapping studies and by the following evidences: (a) mAbs specific for filaggrin reacted with the 40K protein; (b) the autoantibodies, affinity-purified from RA sera on the 40K protein, immunodetected purified filaggrin; (c) the reactivity of RA sera to the 40K protein was abolished after immunoadsorption with purified filaggrin; (d) the 40K protein and filaggrin had similar amino acid compositions. Furthermore, autoantibodies against the 40K protein and the so-called "antikeratin antibodies" were shown, by immunoadsorption experiments, to be largely the same. The identification of filaggrin as a RA-specific autoantigen could contribute to the understanding of the pathogenesis of this disease and, ultimately, to the development of methods for preventing the autoimmune response.

Amino Acids↗

PubMed1993

Fertilisation and thimerosal stimulate similar calcium spiking patterns in mouse oocytes but by separate mechanisms.

Exposure of freshly ovulated mouse oocytes to a fertilising spermatozoon, thimerosal, Sr2+ or acetylcholine induced similar Ca2+ spiking responses. We propose that each of the four agents reduces the threshold for Ca2+ release from internal stores, but by different mechanisms. All agents except thimerosal stimulated oocyte activation, but thimerosal caused dissassembly of the meiotic spindle and thus prevented progress into interphase. Dithiothreitol (DTT) completely blocked and reversed the spiking responses induced by thimerosal, but facilitated and accelerated those induced by spermatozoa, Sr2+ and acetylcholine. The stimulatory effect of DTT was not simply a consequence of progress into interphase, but was attributable, at least in part, to an enhancement of divalent cation entry, as measured by Mn2+ quench analysis of fura-2 in both fertilised and unfertilised oocytes. Possible mechanisms by which DTT might achieve its effects are discussed.

Animals↗

PubMed1993

Beta 2-microglobulin metabolism in uremic patients who are undergoing dialysis.

Plasma beta 2-microglobulin (beta 2m) is increased in chronically hemodialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We undertook metabolic studies to define whether plasma beta 2m is regulated by extrarenal proteolysis of the protein or by storage in a captation pool, a condition which may precede beta 2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy controls were enrolled into the 6 to 10 day study. Using trace amounts of 131I-beta 2m and total body counting, half-life was between 2.4 and 8 days. 125I-beta 2m plasma kinetics was more suitable to calculate fractional catabolic rate and synthetic rate. A three compartment model was chosen to calculate turnover parameters in dialysis patients, whereas the regular two compartment model fitted best for healthy controls. beta 2m synthesis rate was increased in uremic patients when compared with controls (4.49 +/- 2.60 vs. 3.68 +/- 1.43 mg/kg/day, NS). The three compartment model did not integrate all the experimental data, since it was possible to calculate a captation compartment which accumulated beta 2m without fast proteolysis. The captation pool was positively correlated with plasma beta 2m concentration and comprised between 23% and 59% of the amount of the beta 2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta 2m indicate a slight increase in beta 2m synthesis rate in uremic patients on supportive therapy, irrespective of the technique in use. Kinetic analysis requires a model taking into account a storage compartment which is more complex than the three compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1992

The health and mental health of New Zealand Vietnam war veterans with posttraumatic stress disorder.

AIM: To examine the extent of posttraumatic stress disorder (PTSD) in a sample of New Zealand Vietnam veterans and to compare the pattern of health and mental health between veterans classified as posttraumatic stress disorder cases and non-cases. METHOD: Five hundred and seventy-three randomly selected male Vietnam veterans participated in a mailed survey. The questionnaire assessed several mental health dimensions and a number of components of physical health. Demographic and military service details were also gathered. RESULTS: The study classified 12% of the sample of veterans as suffering from posttraumatic stress disorder. The posttraumatic stress disorder group differed from the non-posttraumatic stress disorder group on all measures of physical and mental health. They reported higher symptom scores, more disability days, lower self rated health and made more frequent contacts with health care providers. They also experienced greater anxiety, depression and loss of control, and lower wellbeing. Significant differences on some demographic and military service measures were also found between the groups. CONCLUSIONS: A number of New Zealand Vietnam veterans may be classified as exhibiting the symptoms of posttraumatic stress disorder, with the proportion being comparable to rates found in US studies. Veterans with posttraumatic stress disorder experience significantly poorer physical and mental health. Combat experience in Vietnam appears to contribute to posttraumatic stress disorder level. It is suggested that posttraumatic stress disorder may be under-utilised as a diagnostic category because it may coexist with depression or anxiety states and that physicians should be attentive to military service as an indicator of posttraumatic stress disorder.

Adult↗

PubMed1992

Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)-infected patients.

Infection by the human immunodeficiency virus is associated with polyclonal B cell activation and increased levels of serum IgA. In order to characterize the molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in sera from 60 HIV-1-infected patients and 40 healthy controls. In addition, secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory component (SC), and the distribution of monomeric and polymeric IgA were determined. The data confirm the elevation of total serum IgA levels in HIV-1-infected patients, and both IgA1 and IgA2 concentrations are elevated. Furthermore, the data show a substantial increase in serum levels of both monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in CDC group II patients versus controls and more frequently elevated in CDC group IV patients. The highest S-IgA levels were found among patients with the lowest blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in HIV-1-infected patients and positively correlated with serum S-IgA levels. Conversely, serum levels of free SC were not altered. An increase in serum S-IgA was not related to human hepatitis B virus infection and/or to hepatic dysfunction or to diarrhea or overt intestinal infection. The data indicate that secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites, increase in the serum of HIV-1-infected patients.

Adult↗

PubMed1992

Monocyte-independent T-cell activation by polyclonal antithymocyte globulins.

The in vitro mitogenic properties of polyclonal antithymocyte and antilymphocyte globulins (ATG) on peripheral blood mononuclear cells were investigated. The ATG were mitogenic in a dose-dependent manner with maximal proliferation observed at 250 or 500 micrograms/ml. ATG activated blastogenesis of CD4+, CD8+, and CD57+ (NK cells) lymphocytes. The ATG induced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression and lymphokine secretion in cell culture supernatant and IL-2 receptor (CD25) expression. At submitogenic concentrations ATG potentialized the effect of phorbol esters on T cell proliferation, but not that of calcium ionophore. The mitogenic effect of ATG was not abrogated by monocyte depletion indicating that like CD2 monoclonal antibodies (mAbs) ATG activate T cells via a monocyte-independent pathway. CD3 and CD2 mAbs which activate T cells without binding to B surface determinants stimulated the proliferation of B cells and their differentiation into immunoglobulin (Ig)-secreting cells. In contrast, ATG induced only a transient B cell activation, but failed to support B cell differentiation into Ig-secreting cells despite the secretion of IL-2. These properties shared by ATG obtained in horses or rabbits by immunization with different cell types appear to differ from those of other T cell mitogens.

Antibody Formation↗

PubMed1992

Down-regulation of cell surface CD4 molecule expression induced by anti-CD4 antibodies in human T lymphocytes.

Antigenic modulation was defined as the down-regulation of a cell surface antigen expression induced by exposure to specific antibody. We investigated the modulation of CD4 surface expression in human peripheral blood lymphocytes incubated in vitro with anti-CD4 monoclonal antibodies (mAbs). Modulation of surface CD4 was achieved at 37 degrees C, but not at 4 degrees C, with five different murine anti-CD4 mAbs of IgG1 and IgG2a subclasses, with different epitope specificities. Modulation was dose dependent with a maximum at nonsaturating mAb concentration. It was reversible upon culture in mAb-free medium. It was accelerated and amplified in the presence of monocytes or after cross-linking of anti-CD4 mAbs. It could be induced with solid phase anti-CD4 mAbs, but not with soluble F(ab')2 fragments. Its magnitude was identical on all CD4+ lymphocytes. It was associated with a moderate down-regulation of CD2 and CD3 but not of CD8 and HLA class I surface expression. Modulation was slightly augmented by addition of inhibitors of the endosome/lysosome pathway but not by protein synthesis inhibitors. The anti-CD4 mAb initially bound to cell surface was no longer detectable after 24 hr of culture. Most of surface CD4 proteins complexed with antibody were rapidly internalized and transiently replaced by CD4 from an intracytoplasmic pool and then no longer were expressed. CD4 mRNA was moderately decreased in cells incubated with anti-CD4 mAb while beta-actin and beta 2-microglobulin mRNAs remained at stable levels. It was concluded that down-regulation of CD4 surface expression induced by anti-CD4 mAb concerned only a part of CD4 molecules and was associated with a decreased synthesis. The delay required to achieve maximal modulation is likely to reflect exhaustion of the intracytoplasmic recycling pool of CD4 molecules.

Animals↗

PubMed1992

Kinetics of 125I-beta 2-microglobulin turnover in dialyzed patients.

The kinetics of beta 2-microglobulin (beta 2m) were studied in 17 anephric or functionally anephric hemodialyzed patients and five healthy subjects as controls. Highly purified beta 2m was radiolabeled with 125I and infused into patients. The radioactivity in plasma and dialysis fluids was measured during a week including two or three dialysis sessions. Patients were classified in four groups according to treatment: hemodialysis on Cuprophan (N = 5) or on AN69 membranes (N = 5), hemofiltration (N = 4) and CAPD (N = 3). Plasma activity was fitted to a three compartment model. In controls almost 100% of the radioactivity was recovered in urine within 96 hours and there was no extrarenal catabolism. In patients the fractional catabolic rate ranged from 0.0008 to 0.0022 min-1 versus 0.026 to 0.047 min-1 in controls. The synthetic rate was within the range of values from controls in 10 patients but higher in the seven others. It was correlated with plasma beta 2m concentration. Kinetic data indicate a retention of intact beta 2m. The original model was therefore modified with an additional compartment representing beta 2m captation. The amount of capted beta 2m was more elevated in hemodialyzed patients than in patients treated by hemofiltration or CAPD, in whom it could reach 5 mg/kg/day. Hemofiltration or CAPD may eliminate about 30 to 100% of beta 2m produced and therefore contribute to the low captation amount of these patients, as compared with that of patients treated by hemodialysis.

Adult↗

PubMed1992

Use of fetal bovine serum to protect against zona hardening during preparation of mouse oocytes for cryopreservation.

Addition of 20% fetal bovine serum (FBS) to media used for cryopreservation does not reduce the premature release of cortical granules but does prevent their action on the zona pellucida and thereby prevents zona hardening. In this paper, it is shown that the washing period required for removal of FBS is less than 12 min for cumulus-free oocytes and between 150 and 170 min for cumulus-intact oocytes. When these washing periods are observed after exposure of oocytes to the cryoprotectant dimethylsulphoxide (DMSO; 1.5 M) in the presence of 20% FBS, a subsequent exposure to calcium ionophore A23187 or a second exposure to 1.5 M DMSO both lead to zona hardening. This result suggests that sufficient cortical granules remain to elicit a block to polyspermy at fertilization. Oocytes, which had been exposed to DMSO and FBS and then washed free of both, were fertilized in vitro; the incidence of polyspermy was not found to be elevated over the level found in controls.

Animals↗

PubMed1992

Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae.

The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp-MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives.

Cells, Cultured↗

PubMed1992

The expression of desmosomal and corneodesmosomal antigens shows specific variations during the terminal differentiation of epidermis and hair follicle epithelia.

Using five monoclonal antibodies (MAb), we studied by indirect immunofluorescence the desmosomes and a junctional structure specific to cornified layers, the corneodesmosome, in normal and plantar epidermis and in the various sheaths of the anagen hair follicle. The monoclonal antibodies DP1&2.2-15, PG5.1, and DG3.10, specific for desmoplakins I/II, plakoglobin, and desmoglein I, respectively, were used to study the desmosome antigens, and G36-19 and G20-21 to study the corneodesmosome antigens. The distribution and sequence of expression of the five antigens allowed the nine epithelial differentiation pathways studied to be merged into four distinct families: non-plantar epidermis, characterized by the absence of desmosome and corneodesmosome antigens in the stratum corneum; the outer root sheath of the hair follicle, which behaves like the viable layers of the epidermis with regard to the desmosome antigens but does not express the corneodesmosome antigens; plantar epidermis and the three components of the inner root sheath in which the corneodesmosome antigens are present up to the desquamating layer; and the three components of the hair shaft, which are characterized by the absence of expression of both the desmosome and the corneodesmosome antigens in its mature portion.

Antibodies, Monoclonal↗

PubMed1992

Cell cycle progression of parthenogenetically activated mouse oocytes to interphase is dependent on the level of internal calcium.

Nuclear maturation of the mouse oocyte becomes arrested in metaphase of the second meiotic division (MII). Fertilization or parthenogenetic activation induces meiotic completion, chromosomal decondensation and formation of a pronucleus. This completion of meiosis is probably triggered by a transient increase in cytosolic calcium ions. When activated just after ovulation by a low concentration of the calcium ionophore A23187, the majority of the mouse oocytes go through a metaphase to anaphase transition and extrude their second polar body but they do not proceed into interphase; instead their chromatids remain condensed and a microtubular metaphase spindle reforms (metaphase III). However, a high percentage of these oocytes will undergo a true parthenogenetic activation assessed by the formation of a pronucleus, when exposed to a higher concentration of the calcium ionophore. The capacity of the mouse oocyte to pass into metaphase III is lost with increasing time post-ovulation. Direct measurement of intracellular calcium with Fura-2 reveals higher levels of cytosolic calcium in aged oocytes and/or using higher concentrations of calcium ionophore for activation. It is concluded that the internal free calcium level determines the transition to interphase.

Animals↗