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Biomedical subjects

C Vincent

Publications and source records attributed to C Vincent.

At least 163 records · Page 9Linked to original sources
PubMed1995

Risk factors for nosocomial colonization with multiresistant Acinetobacter baumannii.

A six-month prospective survey was carried out in a university hospital to assess the incidence of Acinetobacter baumannii cross-contamination and to identify risk factors for colonization. Clinical isolates obtained during the study period were biotyped and genotyped by pulsed-field gel electrophoresis after ApaI macrorestriction of total DNA. Case-control univariate and multivariate analyses were performed to identify risk factors for Acinetobacter baumannii colonization. One hundred forty-seven patients hospitalized in 36 units were colonized or infected, of whom 52 were in three intensive care units. The urinary (29%) and bronchopulmonary tracts (26%) were the most frequently colonized sites. Nine major restriction patterns were identified: two were exhibited by epidemic multi-resistant strains of biotype 9 which were isolated from 65 patients hospitalized in ten units. Multivariate analysis showed that case-patients were (a) more likely than non-infected controls to be male, to have been previously hospitalized in another unit and to have had longer stays in the unit before colonization and hyperalimentation; and (b) more likely than controls colonized with other gram-negative bacilli to be male, to have had longer hospitalization, to have received treatment with third-generation cephalosporins and to have had a urinary catheter. The high incidence of colonization with Acinetobacter baumannii can thus be attributed to frequent cross-contamination and the use of broad-spectrum antibiotics. Colonized patients appear to be the major source of cross-contamination as epidemic strains spread throughout the hospital.

Acinetobacter Infections↗
PubMed1995

The developmental relationships of the neural tube and the notochord: short and long term effects of the notochord on the dorsal spinal cord.

Patterning of the ventral half of the neural tube results from the inductive influence of the notochord and of the floor plate. We have studied here the effect of an ectopically grafted notochord on the development of the dorsalmost part of the neural tube i.e. roof plate and alar plates. We show that at their early stages, dorsal genes are repressed by the dorsal graft of a notochord, as shown previously in other studies. We found also that when the notochord is implanted in a mediodorsal position on top of the roof plate (and not laterally as previously performed in other studies) the genes specifics of the floor plate are not induced, and motoneurons do not differentiate. The notochord prevents the formation of the medial septum from roof plate cells and induces their active proliferation between E5 and E7. Roof and dorsal alar plates derived cells start to die from E7 onward leaving a dorsally truncated spinal cord. If the notochord is grafted at 20 degrees-30 degrees from the sagittal plane ventral genes and structures are induced and the roof plate differentiates normally. We conclude that roof plate cells exhibit a specific response to notochord signals, the short range effect of which is thus strikingly demonstrated.

Animals↗
PubMed1995

Capacity of mouse oocytes to become activated depends on completion of cytoplasmic but not nuclear meiotic maturation.

The ability of mouse oocytes to become activated after exposure to the calcium ionophore A23187 has been investigated at different stages of meiotic maturation. The potential to respond to ionophore has been studied in relation to the time since resumption of meiotic maturation, the chromosomal conformation of the DNA within each cell and the protein synthetic profile of the maturing oocyte. Our studies demonstrate that when maturing oocytes from an MF1 strain of mice were treated with A23187 activation occurred only in oocytes which had reached second meiotic metaphase (MII). However, development of the ability to respond to ionophore was not dependent on an orderly progression through normal chromosomal rearrangements such as separation at metaphase I (MI) and subsequent polar body extrusion, since these processes could be prevented and the capacity to be activated became apparent in such oocytes at a time when control cells had reached MII. These data suggest that the ability to respond to ionophore depends on the development of a cytoplasmic component or complex capable of monitoring the time since initiation of germinal vesicle breakdown. Metabolic radiolabelling of oocytes which were able to respond to calcium ionophore, even though they had been prevented from undergoing normal chromosomal rearrangements, showed them to be synthesising a group of proteins known as the 35 kDa complex.

Animals↗
PubMed1995

The health beliefs and behaviors of three groups of complementary medicine and a general practice group of patients.

Patients (n = 256), consulting either a general practitioner (GP) or one of three complementary practitioners (osteopath, homeopath, or acupuncturist), completed a seven-part questionnaire that looked at demographic data, medical history, familiarization with complementary therapies, health beliefs and life-style, health locus of control, scientific health beliefs, and their perceptions of the consultation style of general and complementary practitioners. The four subject groups did not differ significantly on the demographic variables of sex, years of schooling, whether or not they had a degree, marital status, or income, but did differ on age and number of children. The effects of both the significant demographic variables and some aspects of patients medical history were controlled for in subsequent analyses. Acupuncture patients stood out as having the most different chronic medical history. They were also least satisfied with their GP, had least confidence in prescribed drugs, and were most concerned with leading a healthy life-style. The acupuncture patients were most skeptical about orthodox medicine. The main finding was that patients of complementary practitioners are not a homogeneous group, but do differ in their views on satisfaction with GPs, healthy life-style, global environmental issues, confidence in prescribed drugs, faith in medical science, importance of a "healthy mind," harmful effects of medical science, and scientific methodology. The results imply that patients consult different practitioners, general or alternative, on the basis of a combination of their level of skepticism about orthodox medicine, their life-style, and other health beliefs. To talk of patients of complementary practitioners as a homogeneous group is fundamentally wrong.

Acupuncture Therapy↗
PubMed1995

The perceived efficacy of complementary and orthodox medicine in complementary and general practice patients.

A total of 216 patients attending either the British School of Osteopathy, a large acupuncture centre (City Health Centre), the Royal Homeopathic Hospital or a large general practice in South London completed a questionnaire on the perceived efficacy of orthodox and complementary medicine. The questionnaire covered 1) demographic information and experience of complementary medicine; 2) the Health Locus of Control scale; (3) attitudinal variables: belief in the importance of a scientific base to medicine, the importance of psychological factors in illness and the possible side effects of modern medicine; and 4) ratings of the perceived efficacy of acupuncture, osteopathy, homeopathy, herbalism and orthodox medicine for 16 illnesses, divided into four categories: major, minor, chronic and psychological. Whilst there was no difference between the four groups, health locus of control beliefs showed the acupuncture patients believed less in the scientific basis of orthodox medicine and more in its harmful effects compared with all other groups. Again, acupuncture patients more than any other group tended to believe in the efficacy of that therapy to 'cure' major, minor, chronic and psychological problems. Beliefs in the efficacy of complementary therapies were associated with a belief in importance of psychological factors in illness and concerns about the harmful effects of orthodox medicine. Results are discussed in terms of three things: differences between lay and professional medical beliefs; the health education implications for this research, and the role of complementary therapies in general practice and health promotion.

Acupuncture Therapy↗
PubMed1995

Control of flower development and phyllotaxy by meristem identity genes in antirrhinum.

The flower meristem identity genes floricaula (flo) and squamosa (squa) promote a change in phyllotaxy from spiral to whorled in Antirrhinum. To determine how this might be achieved, we have performed a combination of morphological, genetic, and expression analyses. Comparison of the phenotypes and RNA expression patterns of single and double mutants with the wild type showed that flo and squa act together to promote flower development but that flo is epistatic to squa with respect to early effects on phyllotaxy. We propose that a common process underlies the phyllotaxy of wildtype, flo, and squa meristem development but that the relative timing of primordium initiation or growth is altered. This process depends on two separable events: setting aside zones for potential primordium initiation and partitioning these zones into discrete primordia. Failure of the second event can lead to the formation of continuous double spirals, which are occasionally seen in flo mutants.

Base Sequence↗
PubMed1995

Monoclonal antibodies to human epidermal filaggrin, some not recognizing profilaggrin.

To improve understanding of human profilaggrin processing to filaggrin, we produced seven monoclonal antibodies against epidermal filaggrin (AHF1-7). They were characterized on human epidermis by indirect immunofluorescence, immunogold labeling, and immunoblotting and found to be directed against seven different epitopes of (pro)filaggrin. AHF1-5 labeled the keratohyalin granules and the fibrous matrix of the lower corneocytes, and recognized filaggrin and profilaggrin. AHF6 also labeled the keratohyalin granules and the corneocyte matrix, but only recognized filaggrin. In addition to this reactivity within the upper epidermis, AHF4-6 stained the cytoplasm of the basal cells, and cross-reactivity of AHF5 and AHF6 with cytokeratin K14 was revealed on immunoblots. It is interesting that AHF7 recognized filaggrin, but not profilaggrin, and labeled only the corneocyte matrix and not the keratohyalin granules. This indicates that filaggrin and cytokeratins share several antigenic determinants and that filaggrin bears at least one epitope absent from its precursor. The original series of monoclonal antibodies described here appears to be a powerful tool for studying human profilaggrin processing in normal conditions and in the keratinization disorders in which processing is altered.

Antibodies, Monoclonal↗
PubMed1995

The rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix of the cornified cells but not the profilaggrin-containing keratohyalin granules in human epidermis.

Since they were first described, serum IgG antibodies to the stratum corneum of rat oesophagus epithelium, highly specific for rheumatoid arthritis (RA), have been consensually called antikeratin antibodies (AKA). However, we recently demonstrated that they actually recognize three new proteins of rat oesophagus epithelium distinct from cytokeratins, and also human epidermal filaggrin. In this work we provided further evidence that AKA and RA-associated anti-filaggrin autoantibodies are the same antibodies. Moreover, analysing by indirect immunofluorescence on human skin a large series of 212 well characterized RA sera and anti-filaggrin autoantibodies purified from RA sera by affinity chromatography, we demonstrated the specific binding of AKA to the stratum corneum of human epidermis and the absence of any staining of the granular keratinocytes. This binding was confirmed and the AKA antigen precisely localized in human epidermis by immunoelectron microscopy. The antigen was found to be restricted to the filaggrin-containing intracellular fibrous matrix of the corneocytes, up to the desquamating cells. In contrast, MoAbs directed to human filaggrin and to profilaggrin, its precursor, not only stained the intracellular matrix of the lower corneocytes but also the keratohyalin granules of the granular cells, where profilaggrin is stored. These results reinforced by the absence of immunoblotting reactivity of RA sera to profilaggrin suggest that the epitopes recognized by AKA are absent from profilaggrin. Their identification may provide more insight into the pathogenesis of RA.

Adult↗
PubMed1995

The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.

The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.

Antibodies, Antinuclear↗
PubMed1995

Placebo controls for acupuncture studies.

Many studies of acupuncture treatment are seriously flawed by methodological problems. Poor design, inadequate measures and statistical analysis, lack of follow-up data and sub-standard treatment are all too common. However, the major problem, which many investigators consider to be still unresolved, is the definition of an appropriate placebo control. The use of inappropriate placebo controls has bedeviled acupuncture research and led to serious misinterpretation of the results of clinical trials. While a number of different solutions have been proposed there is, as yet, no agreed way of assessing the adequacy of control conditions or of deciding which placebo to use in a particular trial. We propose that assessing the credibility of treatments and control conditions may provide a way forward to a more rigorous, consensus approach.

Acupuncture Therapy↗
PubMed1994

Seryl-tRNA synthetase from Escherichia coli: implication of its N-terminal domain in aminoacylation activity and specificity.

Escherichia coli seryl-tRNA synthetase (SerRS) a dimeric class II aminoacyl-tRNA synthetase with two structural domains charges specifically the five iso-acceptor tRNA(ser) as well as the tRNA(sec) (selC product) of E. coli. The N-terminal domain is a 60 A long arm-like coiled coil structure built of 2 long antiparallel a-h helices, whereas the C-terminal domain is a alpha-beta structure. A deletion of the N-terminal arm of the enzyme does not affect the amino acid activation step of the reaction, but reduces dramatically amino-acylation activity. The Kcat/Km value for the mutant enzyme is reduced by more than 4 orders of magnitude, with a nearly 30 fold increased Km value for tRNA(ser). An only slightly truncated mutant form (16 amino acids of the tip of the arm replaced by a glycine) has an intermediate aminoacylation activity. Both mutant synthetases have lost their specificity for tRNA(ser) and charge also non-cognate type 1 tRNA(s). Our results support the hypothesis that class II synthetases have evolved from an ancestral catalytic core enzyme by adding non-catalytic N-terminal or C-terminal tRNA binding (specificity) domains which act as determinants for cognate and anti-determinants for non-cognate tRNAs.

Acylation↗
PubMed1994

Why do people sue doctors? A study of patients and relatives taking legal action.

To examine the reasons patients and their relatives take legal action, we surveyed 227 patients and relatives who were taking legal action through five firms of plaintiff medical negligence solicitors. Over 70% of respondents were seriously affected by incidents that gave rise to litigation with long-term effects on work, social life, and family relationships. Intense emotions were aroused and continued to be felt for a long time. The decision to take legal action was determined not only by the original injury, but also by insensitive handling and poor communication after the original incident. Where explanations were given, less than 15% were considered satisfactory. Four main themes emerged from the analysis of reasons for litigation: concern with standards of care--both patients and relatives wanted to prevent similar incidents in the future; the need for an explanation--to know how the injury happened and why; compensation--for actual losses, pain and suffering or to provide care in the future for an injured person; and accountability--a belief that the staff or organisation should have to account for their actions. Patients taking legal action wanted greater honesty, an appreciation of the severity of the trauma they had suffered, and assurances that lessons had been learnt from their experiences. A no-fault compensation system, however well intended, would not address all patients' concerns. If litigation is viewed solely as a legal and financial problem, many fundamental issues will not be addressed or resolved.

Adolescent↗
PubMed1994

Molecular variants of beta 2-microglobulin in renal insufficiency.

Many patients with renal insufficiency treated by dialysis for more than 10 years have tissue deposits of amyloid material containing polymerized beta 2-microglobulin (beta 2m). The mechanisms of beta 2m polymerization and degradation remain unknown. In biological fluids (serum and urine) from haemodialysis patients and in dialysis fluids from patients treated by chronic ambulatory peritoneal dialysis (CAPD), we have characterized different molecular forms of beta 2m, including proteolytic split products. beta 2m isoforms of pI 5.7, 5.3 and 4.5-5.0 were isolated from urine and CAPD fluid. The pI 5.3 beta 2m, but not the other forms, was recovered both as monomers and as dimers. Such dimers were also detected in serum from patients but not from healthy controls. pI 5.3 and 5.7 beta 2m isoforms were found to be nearly identical by mass spectrometry and by their amino acid sequences. The amino acid sequence of the 43 N-terminal amino acids of beta 2m of pI 5.0 showed identity with the corresponding region of pI 5.7 beta 2m. Fragments recovered from CAPD fluid were similar to proteolytic fragments generated from pure pI 5.7 beta 2m by incubation in mouse ascitic fluid at acidic pH. Furthermore, pure pI 5.7 beta 2m was converted into more acidic forms of 12 kDa upon incubation in mouse ascitic fluid at acid pH. beta 2m dimers found in serum may represent a precursor of amyloid fibrils.

Amino Acid Sequence↗
PubMed1994

Effect of the Gulf War on reactivation of adverse combat-related memories in Vietnam veterans.

Symptoms of combat related posttraumatic stress disorder (PTSD) have been reported extensively in Vietnam veterans. A few of these studies have reported situations in which PTSD has been reactivated in veterans with a history of PTSD. The present study reports the effects of media coverage of the Gulf War on a community sample of New Zealand Vietnam veterans. Levels of PTSD, distress, and well-being were assessed before and after the outbreak of hostilities. Most veterans closely followed the media presentation of the war and reported revived memories of Vietnam. Increased memories of Vietnam were associated with higher levels of PTSD and distress. It is suggested that veterans have heightened susceptibility to combat related stimuli because of their previous combat experience and that these stimuli can reactivate PTSD symptoms and distress. Implications of this finding for other groups in the community who harbour residual PTSD effects are discussed.

Adult↗
PubMed1994

Plasma 5-fluorouracil and alpha-fluoro-beta-alanin accumulation in lung cancer patients treated with continuous infusion of cisplatin and 5-fluorouracil.

This study was undertaken to investigate the day-to-day pharmacokinetic variability of 5-fluorouracil (5FU) given as a continuous i.v. infusion concomitantly with cisplatin. Ten lung cancer patients were investigated during the first course of chemotherapy. All patients had advanced, previously untreated, inoperable non-small-cell lung cancer. They received continuous infusions of cisplatin given at 100 mg/m2 over 5 days and of 5FU given at 1 g/m2 daily from day 2 to day 5. Both drugs were infused i.v. for 24 h/day at a constant rate with a volumetric pump. Blood samples were drawn from day 2 to day 5, every 4 h from 8 a.m. to 8 p.m. and every 2 h during the night (8 p.m. to 8 a.m.). Plasma 5FU and FBAL concentrations were determined simultaneously by gas chromatography-mass spectrometry. Plasma 5FU concentrations varied widely over the 4-day treatment course for each patient. Despite continuous constant-rate 5FU administration, plasma 5FU concentrations were significantly lower between 8 a.m. and 8 p.m. than during the night. Mean plasma concentrations of 5FU and FBAL increased significantly from the 1st day (0.42 and 1.19 micrograms/ml for 5FU and FBAL, respectively) to the 4th day of 5FU infusion (0.67 and 1.78 micrograms/ml for 5FU and FBAL, respectively). Further study is warranted to elucidate the mechanisms of the observed increase in plasma 5FU concentrations as well as its relationship with cisplatin coadministration and to assess the clinical relevance of this plasma 5FU accumulation.

Aged↗
PubMed1994

A proposed new contiguous gene syndrome on 8q consists of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, a dominant form of hydrocephalus and trapeze aplasia; implications for the mapping of the BOR gene.

The analysis of a de novo 8q12.2-q21.2 deletion led to the identification of a proposed previously undescribed contiguous gene syndrome consisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydrocephalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hydrocephalus. In contrast, we report a new localization for the gene responsible for BOR syndrome which is more telomeric to an initial placement. Linkage analysis of affected families consistently mapped the gene responsible for BOR and Branchio-Oto (BO) syndromes to within the deletion. Using new algorithms, a YAC contig was constructed and used to localize the breakpoint of another chromosomal rearrangement associated with BO syndrome to a 500 kb interval within the deletion. The 8q12.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.

Base Sequence↗