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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 325 records · Page 18Linked to original sources
PubMed1995

Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate.

Neisseria gonorrhoeae attaches to host epithelial cells via pili and opacity-associated (Opa) outer membrane proteins. Pilus- gonococci (Gc) of strain MS11 adhere to both human and nonhuman cells, but only when particular Opa proteins are expressed; OpaA+ variants adhere best, OpaC+ variants are next best, and the seven other Opa+ variants adhere poorly or not at all. The adherence of OpaA+ Gc to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate (HS), but not by chondroitin sulfate. OpaA+ Gc do not adhere to CHO cells devoid of HS proteoglycans; low concentrations of heparin restore OpaA+ Gc adherence to these HS-deficient CHO cells and high concentrations inhibit it. 3H-heparin binding to whole Gc parallels their adherence abilities (OpaA+ > OpaC+ > OpaH+ >> Opas B, D, E, F, G, I = Opa- = 0). Opa proteins separated by SDS-PAGE also bind 3H-heparin. These data suggest that adherence of pilus-, Opa+ Gc involves HS-proteoglycan of eukaryotic cells.

Animals↗
PubMed1995

Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes.

Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.

B-Lymphocytes↗
PubMed1995

Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood.

Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

Adolescent↗
PubMed1995

Rabbit medial collateral ligament scar weakness is associated with decreased collagen pyridinoline crosslink density.

This study was carried out to quantify the potential associations between material strength and both collagen concentration and pyridinoline collagen crosslink density in the healing medial collateral ligament of the rabbit and to compare these parameters with those of normal ligaments. The right hindlimbs of 24 skeletally mature (12-month-old) New Zealand White rabbits were subjected to a standardized 4 mm midsubstance "gap" injury to the medial collateral ligament. The animals were killed in groups of six at postoperative intervals of 3, 6, 14, or 40 weeks, and the femur-medial collateral ligament-tibia complexes were mechanically tested in tension to failure. Subsequent to mechanical testing, the failure sites of the ligaments were assessed for concentrations of hydroxyproline and hydroxylysyl pyridinoline. Nine additional rabbits served as age-matched normal controls. In healing ligaments, normal collagen concentrations were reached in less than 14 weeks, but the hydroxylysyl pyridinoline crosslink densities remained low and were only 45% of the control values after 40 weeks of healing. Similarly, mechanical values remained much less than the controls. Linear regression analysis of data on scar tissue alone showed a moderately strong positive correlation between hydroxyproline concentration and material strength (r2 = 0.51, p = 0.0001) but no correlation between crosslink density and strength of scar tissue. A similar pattern of correlation was obtained between the elastic modulus of the scar tissue and the biochemical variables, but the r2 values were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

Soft-tissue "flaws" are associated with the material properties of the healing rabbit medial collateral ligament.

This study evaluated microscopic flaws in the healing rabbit medial collateral ligament and their significance in terms of the material properties of this ligament during healing. A gap injury was created in the midsubstance of the medial collateral ligament in the right hindlimb of 15 skeletally mature (12 months old) New Zealand White rabbits. At postoperative intervals of 3, 6, or 14 weeks, histomorphometric analysis of the flaws was carried out in subgroups of animals. The medial collateral ligaments from four of the left hindlimbs (randomly selected) were used as uninjured contralateral controls. In one histologic section of each area of scar tissue and the analogous area in the controls, specified tissue flaws (blood vessels, fat cells, hypercellular areas, loose matrix, disorganized matrix, or a combination of these) were measured by four independent and blinded observers. The results showed that the mean total area of the flaws, as a percentage of the total section, and the mean area of the largest flaw decreased with healing time in each healing group but did not achieve control values by 14 weeks. Because it was not possible to test the healing medial collateral ligaments mechanically prior to measurement of the flaws (due to the destructive nature of failure testing), the data on the flaws were compared with the material strength and stiffness of a separate series of similarly injured and mechanically tested medial collateral ligaments (data published previously). A maximum likelihood statistical analysis showed a very strong functional association between the mean area of the largest flaw and the stress at failure (p < 0.004) and between the mean flaw area as a percentage of the total section area and the elastic modulus (p < 0.001). This study therefore demonstrates that it is possible to quantify material flaws in scar tissue in rabbit medial collateral ligaments, that these flaws become smaller with healing time as the scar remodels, and that flaws are functionally associated with the material properties of the ligament in this model (larger flaws with less tensile strength and more flaws with less stiffness).

Analysis of Variance↗
PubMed1995

Resection of a massive sacrococcygeal teratoma using hypothermic hypoperfusion: a novel use of extracorporeal membrane oxygenation.

A 33-week-gestation infant with a massive sacrococcygeal teratoma weighted 4,000 g, but the actual weight of the infant was approximately 1,500 g. With the potential for massive blood loss and impaired lung compliance during resection, some type of cardiopulmonary support was necessary. Resection was undertaken with the assistance of venoarterial extracorporeal membrane oxygenation (ECMO) and hypothermic hypoperfusion. Immediately after removal of the tumor, which weighted 2,420 g, the infant was decannulated from ECMO, and the carotid artery was primarily reconstructed end-to-end. The amount of intraoperative blood loss was 550 mL Postoperatively, the child weighted 1,580 g. Follow-up head ultrasound results were normal, and the patient has done well. This is the first reported case in which ECMO with hypothermic hypoperfusion was used for resection of a massive tumor. This experience shows that ECMO is both useful and safe as a means of temporary cardiopulmonary support for resection of massive tumors in infants.

Coccyx↗
PubMed1995

Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis.

The characteristics of antigen-specific IgG in patients with multiple sclerosis and patients with encephalitis have been compared. Both groups of patients showed antigen-specific oligoclonal bands locally synthesised in the CSF. When the affinity distribution of the antigen-specific IgG was measured there was a marked difference between the two groups. Encephalitis patients had high affinity antibody against the causative antigen. This was consistent with the antibody undergoing affinity maturation as a result of the immune system fighting a primary infection. Multiple sclerosis patients lacked high affinity response. This lack of high affinity antibody was also seen in those encephalitis patients when antigens other than the causative antigen were studied.

Adolescent↗
PubMed1995

A survey of health professionals' views on possible changes in the provision and organisation of antenatal care.

OBJECTIVE: To ascertain the views of midwives, obstetricians and general practitioners (GPs) on possible changes in the provision of antenatal care, and to describe any differences in attitude between the three professional groups. DESIGN: survey using postal questionnaire. SETTING: Three hospitals in south-east London. PARTICIPANTS: The questionnaire was sent to 251 midwives, 50 obstetricians, and 438 GPs. The overall response rate was 70%. MEASUREMENTS: A questionnaire asking whether the health professionals would like to see, were undecided, or would not like to see, 12 possible changes in the provision of antenatal care. FINDINGS: The changes that most health professionals wanted to see were individualised visit schedules and an increase in continuity of care-giver. There were significant differences between the three professional groups for 11 of the 12 possible changes, with midwives being the group most keen, and GPs tending to be the least keen, to see change. KEY CONCLUSIONS: It is important to recognise and address the different views of midwives, obstetricians and general practitioners at this time when major changes in the organisation of antenatal care are being planned or implemented. IMPLICATIONS FOR PRACTICE: Differences in attitudes between health professionals need to be addressed when planning changes in the provision of antenatal care.

Attitude of Health Personnel↗
PubMed1995

Regular smokers, lifetime very light smokers, and reduced smokers: comparison of psychosocial and smoking characteristics in women.

This study compared stable very light smokers (VLS; less than 6 cigarettes a day) with regular smokers (RS; greater than 14 cigarettes a day) in a cohort of women followed up for 1 year. The VLS showed evidence of inhaling the cigarette smoke. They were not novice smokers, nor were they under particular pressure to limit their smoking. Among the 61 VLS, 34 had at one time smoked more than 10 cigarettes per day. These "reduced smokers" were broadly similar to the lifetime VLS, who differed from RS in several important respects. In a multiple logistic regression, education and smoking patterns in relatives were independently associated with very light versus regular smoking. Familial factors and personal resources may protect against dependence among those who use tobacco.

Adult↗
PubMed1995

Heparin protects Opa+ Neisseria gonorrhoeae from the bactericidal action of normal human serum.

The pathobiological significance of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) changes in gonorrheal disease are poorly understood. We assessed variants of strain MS11mk with different LOS and Opa phenotypes for their liability to killing by normal human sera. LOS differences correlated with strikingly disparate susceptibilities to serum killing; LOSa variants were serum resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants enhanced their survival (as reported previously). Opa phenotype had little influence on the killing of serum-sensitive LOSb cells that were incubated directly in normal human sera, but preincubation of Opa+ LOSb variants in heparin increased their serum resistance whereas Opa- LOSb variants showed no change. Some Opa proteins conferred slightly higher resistance than others, but heparin preincubation increased serum resistance for variants expressing each of seven Opa proteins. These in vitro phenomena may relate to conditions within the male urethra where sulfate-containing proteoglycans are abundant and where antibody and complement may transude from blood plasma. The results suggest that the selective advantage for Opa+ Neisseria gonorrhoeae bacteria observed in vivo may reflect their ability to utilize host cell components to resist killing by host defenses.

Antigens, Bacterial↗
PubMed1995

Determination of body composition from skinfold thickness: a validation study.

Measurement of body composition is proving increasingly important in clinical nutrition and research. Skinfold thickness is a simple means of estimating body composition which is widely used in children, but there is little information on its validity. There has been a proliferation of equations for estimation of body composition from skinfolds, but some doubt as to their general applicability. The aim of the present study was to validate five currently used equations for this purpose in a sample of 98 healthy prepubertal children (64 boys, 34 girls), mean (SD) age 9.1 (1.7) years by comparison of estimates from each equation with measurements of fatness derived from hydrodensitometry. Differences between methods were determined by calculation of biases and limits of agreement. Limits of agreement between predicted and measured fatness were wide, particularly in the girls, and some distinct biases were apparent. Choice of prediction equation therefore has a substantial influence on the estimate of fatness obtained when using skinfolds in children. The existing published equations are associated with large random errors or significant systematic errors. For the time being skinfolds might best be regarded as indices (rather than measures) of body fatness in individuals, or means of estimating body fatness of groups. Estimating the total body fatness of individual prepubertal children using skinfolds, on the basis of this evidence, is not advisable at present.

Adipose Tissue↗
PubMed1995

A comparison of methods of predicting maximum oxygen uptake.

The aim of this study was to compare the results from a Cooper walk run test, a multistage shuttle run test, and a submaximal cycle test with the direct measurement of maximum oxygen uptake on a treadmill. Three predictive tests of maximum oxygen uptake--linear extrapolation of heart rate of VO2 collected from a submaximal cycle ergometer test (predicted L/E), the Cooper 12 min walk, run test, and a multi-stage progressive shuttle run test (MST)--were performed by 22 young healthy males (mean(s.d.) age 22.1 (2.4) years; body mass 72.4(8.9kg)) and the values compared to those obtained by direct measurement on a maximal treadmill test. All of the subjects were regular exercisers. The mean(s.d.) from the various tests in ml.kg-1.min-1 were as follows: treadmill 60.1(8.0), Cooper 60.6(10.3), MST 55.6(8.0), and predictedL/E 52.0(8.4). The Cooper test had a correlation with the treadmill test of 0.92, while the MST and the predictedL/E had correlations of 0.86 and 0.76 respectively. Both the MST and predictedL/E showed systematic underprediction of the treadmill value. On average, the MST was 4.5 ml.kg-1.min-1 (s.e. 0.9) lower than the treadmill VO2max while the predictedL/E was 7.8 ml.kg-1. min-1 (s.e. 1.4) lower than the treadmill VO2max. These findings indicate that, for the population assessed, the Cooper walk run test is the best predictor of VO2max among the three tests.

Adult↗
PubMed1995

Normalization of raised sodium absorption and raised calcium-mediated chloride secretion by adenovirus-mediated expression of cystic fibrosis transmembrane conductance regulator in primary human cystic fibrosis airway epithelial cells.

Cystic fibrosis airway epithelia exhibit a spectrum of ion transport properties that differ from normal, including not only defective cAMP-mediated Cl- secretion, but also increased Na+ absorption and increased Ca(2+)-mediated Cl- secretion. In the present study, we examined whether adenovirus-mediated (Ad5) transduction of CFTR can correct all of these CF ion transport abnormalities. Polarized primary cultures of human CF and normal nasal epithelial cells were infected with Ad5-CBCFTR at an moi (10(4)) which transduced virtually all cells or Ad5-CMV lacZ as a control. Consistent with previous reports, Ad5-CBCFTR, but not Ad5-CMV lacZ, corrected defective CF cAMP-mediated Cl- secretion. Basal Na+ transport rates (basal Ieq) in CF airway epithelial sheets (-78.5 +/- 9.8 microA/cm2) were reduced to levels measured in normal epithelial sheets (-30.0 +/- 2.0 microA/cm2) by Ad5-CBCFTR (-36.9 +/- 4.8 microA/cm2), but not Ad5-CMV lacZ (-65.8 +/- 6.1 microA/cm2). Surprisingly, a significant reduction in delta Ieq in response to ionomycin, a measure of Ca(2+)-mediated Cl- secretion, was observed in CFTR-expressing (corrected) CF epithelial sheets (-6.9 +/- 11.8 microA/cm2) when compared to uninfected CF epithelial sheets (-76.2 +/- 15.1 microA/cm2). Dose response effects of Ad5-CBCFTR on basal Na+ transport rates and Ca(2+)-mediated Cl- secretion suggest that the mechanism of regulation of these two ion transport functions by CFTR may be different. In conclusion, efficient transduction of CFTR corrects hyperabsorption of Na+ in primary CF airway epithelial cells and restores Ca(2+)-mediated Cl- secretion to levels observed in normal airway epithelial cells. Moreover, assessment of these ion transport abnormalities may represent important endpoints for testing the efficacy of gene therapy for cystic fibrosis.

Adenoviridae↗
PubMed1995

HFA-134a (1,1,1,2-tetrafluoroethane); lack of oncogenicity in rodents after inhalation.

1. Groups of 60 male and 60 female B6C3F1 mice or HanIbm Wistar rats were exposed to HFA-134a using snout-only inhalation exposure techniques for periods of one hour daily for at least 104 weeks. HFA-134a was delivered directly from cylinders at vapour concentrations of 2500, 15,000 and 75,000ppm for mice and from metered-dose inhalers at vapour concentrations of 2500, 10,000 and 50,000ppm for rats. 2. Intended dosages were achieved. 3. Evidence of absorption was found at each dose level and was dose related. 4. Neither species suffered treatment related effects on survival, clinical signs, body weights, haematology nor on the type, incidence, site or severity of gross lesions. 5. There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats. 6. There were no non-neoplastic findings related to treatment in mice. 7. HFA-134a was considered not to be oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.

Absorption↗
PubMed1995

The chemistry of pseudomonic acid. Part 14. Synthesis and in vivo biological activity of heterocyclyl substituted oxazole derivatives.

Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.

Animals↗