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Biomedical subjects

J M Stuart

Publications and source records attributed to J M Stuart.

At least 91 records · Page 5Linked to original sources
PubMed1991

Meningococcal carriage in close contacts of cases.

Between 1 October 1986 and 31 March 1987, 55 cases of meningococcal disease were identified in the South-West of England, an attack rate of 1.54 per 100,000 during the study period. Antibiotics used in the treatment of the disease successfully eliminated nasopharyngeal carriage of meningococci in 13 out of 14 cases without use of rifampicin. The overall meningococcal carriage rate in 384 close contacts was 18.2% and the carriage rate of strains indistinguishable from the associated case strain was 11.1%. The carriage rate of indistinguishable strains in household contacts (16.0%) was higher than the carriage rate in contacts living at other addresses (7.0%, P less than 0.05). A 2-day course of rifampicin successfully eradicated meningococci from 46 (98%) of 47 colonized contacts. In one third of cases groupable meningococci were isolated from at least one household contact; 92% of these isolates were of the same serogroup as the associated case strain. When a meningococcus is not isolated from a deep site in a clinical case of meningococcal disease, culture of serogroup A or C strains from nasopharyngeal swabs of the case or of household contacts is an indication that the close contact group should be offered meningococcal A + C vaccine in addition to chemoprophylaxis. The failure in this and other studies to isolate meningococci from any household contact in the majority of cases may be due either to the relative insensitivity of nasopharyngeal swabbing in detecting meningococcal carriage or to the acquisition of meningococci by most index cases from sources outside the household.

Adolescent↗
PubMed1990

The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis.

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen-induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus-cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chrondrocytes were incubated with various concentrations of interleukin-1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3-fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin-1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin-specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.

Animals↗
PubMed1990

Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate.

The reduction in uterine and fibroid volume associated with the chronic administration of a gonadotropin-releasing hormone agonist (GnRH-a) is thought to be secondary to the analogue induced hypoestrogenic state. Our hypothesis was that the concentration of bioactive estrogen receptors (ER) and progesterone receptors (PR) may be important in the regulation of fibroid growth. The purpose of this study was to determine ER and PR content in fibroids and myometria from women pretreated with GnRH-a compared with controls. Tissue was obtained from 20 premenopausal women with uterine fibroids who were randomized to receive either leuprolide acetate depot, 3.75 mg intramuscularly every 28 days for four injections (n = 10) or placebo (n = 10) before myomectomy. The mean fibroid ER and PR content was significantly greater than the mean myometrial ER and PR content. The mean fibroid ER content for GnRH-a-treated patients was significantly greater than in placebo-treated patients (143.3 +/- 22.8 versus 36.1 +/- 14.3 fmol/mg). The mean fibroid PR and the mean myometrial ER and PR content were not significantly different between treatment groups. Clinically, the significant increase in fibroid ER may be an explanation for the rapid regrowth of fibroids observed after the cessation of GnRH-a therapy.

Antineoplastic Agents↗
PubMed1989

A CD4 cell is capable of transferring suppression of collagen-induced arthritis.

Collagen-induced arthritis can be suppressed by i.v. injection of intact type II collagen (CII) but not type I collagen before immunization. To identify the mechanism mediating this suppression, splenocytes were obtained from mice injected with CII or OVA and administered to recipients that were subsequently immunized with CII. Mice receiving cells from donors injected with CII had a lower incidence of arthritis and lower antibody titers than those receiving cells from OVA-injected donors. Treatment of cells with 3000 rad of gamma-irradiation abrogated the suppression. To determine the phenotype of these donor cells, spleen cells were fractionated by adherence to plates coated with mouse anti-IgG to enrich for Thy-1+ phenotype. Thy-1+ cells injected into naive mice could significantly suppress arthritis. Further depletion of T cell subsets by panning revealed that depletion of CD4+ cells prevented the transfer of suppression whereas removal of CD8+ cells had no effect. Isolated CD4+ cells transferred into naive mice were also suppressive. Recently the Pgp-1 (Ly-24) Ag has been described to identify a unique memory subset of CD4+ cells when present on the cell surface. In CII-tolerized spleen populations, removal of the Pgp-1+ (Ly-24) subset of T cells abrogated suppression and transfer of isolated Pgp-1+ cells suppressed arthritis. These findings indicate that the Pgp-1+ subset of CD4+ cells can suppress collagen-induced arthritis and suggest that a CD4+ memory cell down-regulates autoimmunity. In addition, treatment of donor animals with cyclosporin, which inhibits the development of CD4+ cells, abrogated suppression.

Animals↗
PubMed1989

Identification of an immunosuppressive epitope of type II collagen that confers protection against collagen-induced arthritis.

We have previously reported that collagen-induced arthritis can be suppressed by intravenous injection of native type II (CII) but not type I collagen. We have now identified denatured fragments of CII capable of suppressing collagen-induced arthritis and inducing tolerance. Purified CII was cleaved with cyanogen bromide (CB), and the major resulting peptides were isolated. Female DBA/1 mice were administered OVA, native CII, or one of the CB peptides, intravenously, before immunization with native CII, 6 wk after immunization, mice tolerized with CII and CB11 had a markedly lower incidence of arthritis compared with controls. There was a correlation between the overall antibody response and the incidence of arthritis. In addition, animals tolerized with either CII or CB11 had a decreased antibody response not only to CII, but also to each of the other CB peptides tested. To identify the epitope involved in suppression of arthritis, five synthetic peptides, 21-26 amino acids in length, corresponding to selected regions of CB11, were generated. Each of the peptides was injected intravenously into mice before immunization. Only one of these, CB11 122-147, was capable of suppressing arthritis. In addition, mice given the synthetic peptide CB11 122-147 neonatally were suppressed for arthritis and antibody responsiveness when immunized with CII at 8 wk of age. Thus, we have identified CB11 122-147 as an epitope of CII important in induction of tolerance and suppression of disease. Further experiments narrowing down the pivotal amino acids for the immunogenicity of this epitope and the role this epitope plays in induction and regulation of disease will enhance our understanding of how the immune response to collagen affects autoimmune arthritis.

Animals↗
PubMed1989

Effect of smoking on meningococcal carriage.

A case-control study was done to examine whether certain environmental or medical factors were associated with meningococcal carriage. Questionnaires were posted to 138 meningococcal carriers and their controls, and to 52 carriers of Neisseria lactamica and their controls. Carriers were matched to controls by age, sex, and area of residence. The overall response rate was 89%. There were no differences in environmental or medical factors between N lactamica carriers and their controls, nor in household crowding, housing conditions, frequency of physical exercise, or upper respiratory disorders between meningococcal carriers and their controls. Active smoking and the presence of other smokers in the household were independently associated with meningococcal carriage; the risk of carriage increased significantly with heavier smoking.

Adolescent↗
PubMed1989

Systemic administration of TIMP in the treatment of collagen-induced arthritis in mice.

The type II collagen induced arthritis model was used to evaluate the efficacy of tissue inhibitor of metalloproteases (TIMP) in suppressing the disease in DBA/1 mice. Treatment began following the first clinical manifestations of the disease state. Clinical observations, histological and radiographic findings show a decreased incidence of joint erosion in the treated population relative to the controls. It is concluded that systemic administration of recombinant human TIMP suppresses the pathology of type II collagen induced arthritis.

Animals↗
PubMed1989

The Stonehouse study: secretor status and carriage of Neisseria species.

The genetically determined inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens into saliva and other body fluids is a recognized risk factor for meningococcal disease. During a community-wide investigation of a prolonged outbreak of disease due to a B15:P1.16 sulphonamide-resistant strain of Neisseria meningitidis in Stonehouse, Gloucestershire (the Stonehouse survey), the ABO blood group and secretor status of almost 5000 residents was determined. The proportion of non-secretors in the Stonehouse population was significantly higher than the proportion of non-secretors among blood donors in the South West Region and in England generally. Seven of 13 Stonehouse residents with meningococcal disease who were tested were found to be non-secretors, a high proportion. The outbreak in Stonehouse cannot be explained solely in terms of the increased proportion of non-secretors. There was no clear correlation between the proportions of non-secretors in different areas within the town and the incidence of cases of meningococcal disease. Carriers of meningococci, whether outbreak or other strains, were not more likely to be non-secretors. The reasons why non-secretors are more susceptible to meningococcal disease remain to be determined, but they do not appear to be related to carriage of meningococci.

ABO Blood-Group System↗
PubMed1989

Symphysis-fundus measurements in screening for small-for-dates infants: a community based study in Gloucestershire.

Symphysis-fundus charts were introduced into 50 general practitioner antenatal clinics and the hospital antenatal clinics of two obstetricians in Gloucestershire in February 1985 for a 12-month period. Of the 1139 charts analysed, the sensitivity of one or more low fundal height measurements in predicting birthweight below the tenth centile for gestational age was 51% with a specificity of 88%. In the 319 charts with four or more measurements after 26 weeks gestation a sensitivity of 65% was recorded in predicting birthweight below the tenth centile, rising to 91% in the prediction of birthweight below the fifth centile; the specificity was correspondingly 81% and 80%. The sensitivity of the test varied inversely with maternal body mass index. The mean absolute difference in pairs of observations between general practitioners, midwives and an observer was 1.5 cm. Measurement of symphysis-fundus distance is not a precise diagnostic tool but it does provide an improvement on abdominal palpation in the prediction of small-for-dates infants. The findings of this study support the use of serial symphysis-fundus measurements in community antenatal clinics. Referral for ultrasound investigation is recommended when the measurement is low.

Anthropometry↗
PubMed1988

Induction of arthritis in monkeys by immunization with type II collagen.

Immunization of two cynomolugus and three rhesus monkeys with purified type II collagen resulted in the development of polyarthritis. Arthritis first became clinically apparent 7 wk after primary immunization and persisted for 16 mo. Radiologic examination of the limbs demonstrated soft tissue swelling with severe joint destruction including loss of cartilage and bone. Involved joints eventually became ankylosed with permanent loss of some motion. All of the monkeys developed a response to the immunizing collagen as determined by ELISA of serum for antibodies. Arthritis was associated with weight loss and constitutional symptoms, including lethargy and refusal to eat. One monkey became so debilitated that it was necessary to euthanize it. Histologic examination of the joints showed synovial hypertrophy with pannus formation. A control monkey immunized with type I collagen suffered no apparent ill effects.

Animals↗
PubMed1988

Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice.

Arthritis was induced by immunization of type II collagen in adjuvant in mice from H-2q-bearing crosses between SWR (H-2q/q) and B10 (H-2b/b mice), two strains known to be resistant to collagen-induced arthritis (CIA). The resistance of B10 is known to be due to its MHC haplotype, but it was postulated that the resistance of SWR mice which expresses the susceptible MHC haplotype could be due to the deletion of close to 50% of the V beta genes of the T cell receptor (TCR) in them. 17% of the F1 hybrids, 33% of the SWR backcrosses, 68% of the B10 backcrosses, and 52% of the F2 hybrids developed arthritis on follow-up to 5 mo after primary immunization with collagen. There was no significant difference in anti-type II collagen antibody titers between the arthritic and nonarthritic mice in each of these crosses. The segregation of the TCR genes with arthritis was determined in the F2 population by typing with F23.1 mAb that reacts with T cells using V beta 8 subfamily genes in their TCRs. SWR mice are F23.1- as V beta 8 genes are deleted in them. All six of arthritic mice homozygous for H-2q, and thus with an H-2 haplotype similar to SWR mice, expressed the F23.1 marker. These studies indicate that for complete susceptibility to collagen-induced arthritis, not only is a susceptible MHC haplotype (H-2q) important, but possibly also the presence of a subset of T cells using certain specific V beta genes in their TCRs. Other background genes may, however, modulate the severity of arthritis.

Animals↗
PubMed1988

Collagen autoimmunity and arthritis.

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen-induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.

Animals↗
PubMed1988

The immune response of guinea-pigs to type II collagen: poor cross-reactivity with homologous type II collagen accounts for resistance to collagen-induced arthritis.

In order to determine the susceptibility of guinea-pigs to collagen-induced arthritis (CIA), Hartley and Strain 13 guinea-pigs were immunized with heterologous or homologous type II collagen. None of the animals developed CIA. Because immunity to type II collagen plays a critical role in CIA, we characterized the guinea-pig's immune response to determine the basis for this resistance. Guinea-pigs develop cellular and humoral reactivity to heterologous type II collagen similar to that of CIA-susceptible rats. The reactions distinguish type I from type II collagen but not among several heterologous type II collagens. The cell-mediated immune (CMI) response was specific for determinants on the primary amino acid structure of collagen, whether native or denatured collagen was used for immunization; however, the humoral response was specific for the form of the molecule used for immunization. Guinea-pigs differ from CIA-susceptible rats in that immunization with homologous or heterologous type II collagen fails to induce significant cross-reactive immunity with the homologous antigen. A transient arthritis could be induced in animals immunized with heterologous type II collagen by injecting them intra-articularly with heterologous but not with homologous type II collagen. Our results show that the disparity between immunity to type II collagen and the susceptibility to develop CIA in guinea-pigs is due to their poor cross-reactive immune response to autologous type II collagen.

Animals↗
PubMed1987

An outbreak of meningococcal disease in Stonehouse: planning and execution of a large-scale survey.

In November 1986 a large-scale survey was undertaken in the Gloucestershire town of Stonehouse during an outbreak of meningococcal disease due to group B type 15 subtype P1.16 sulphonamide-resistant strains. There were 15 cases in Stonehouse residents during the 4 years from April 1983, an annual attack rate of 56.5 per 100,000. Four secondary cases occurred despite rifampicin prophylaxis. The objectives of this community survey were to investigate patterns of meningococcal carriage, transmission and immunity and to determine the proportion of non-secretors of blood group antigens in the Stonehouse population and amongst meningococcal carriers. A total of 6237 subjects participated including 75% of the 6635 Stonehouse residents. Over 97% of the participants provided all three of the requested specimens-nasopharyngeal swabs, saliva and blood samples. The co-operation between the many organizations involved in the detailed preliminary planning was instrumental in the success of the survey; in particular the value of effective collaboration between Departments of Community Medicine and Microbiology and of the Public Health Laboratory Service network of laboratories in undertaking investigations of this size and type was clearly demonstrated.

Adolescent↗
PubMed1987

The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica.

A total of 6234 nasopharyngeal swabs was collected during a survey of the population of Stonehouse, Gloucestershire in November 1986 as part of an investigation into an outbreak of meningococcal disease. The overall meningococcal carriage rate was 10.9%. The carriage rate rose with age from 2.1% in the 0- to 4-year-olds to a peak of 24.5% in the 15- to 19-year-olds, and thereafter declined steadily with age. Male carriers outnumbered female carriers of meningococci by 3:2. Group B (or non-groupable) type 15 sulphonamide-resistant strains which had caused the outbreak were isolated from 1.4% of subjects. The age distribution of carriers of these strains was similar to that of other meningococci apart from an additional peak in the 5-9-year age group and a more rapid decline in carriage with increasing age. Variations in the carriage rates of the outbreak strain were seen in children attending different schools and in the residents of different areas of the town. The low carriage rate of these strains in a community during a prolonged outbreak supports the hypothesis that these organisms are less transmissible but more virulent than other strains of pathogenic meningococci. Carriage of Neisseria lactamica, which is thought to be important in the development of meningococcal immunity, was most frequent in children under the age of 5 years and was six times commoner in this age group than carriage of Neisseria meningitidis. In older children and adults female carriers of N. lactamica increasingly outnumbered males in contrast to the male preponderance observed with meningococcal carriage.

Adolescent↗