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Biomedical subjects

B M Jones

Publications and source records attributed to B M Jones.

At least 37 records · Page 2Linked to original sources
PubMed2000

Changes in cytokine production during pregnancy in patients with Graves' disease.

In order to investigate the role of type 1 and type 2 cytokines in the remission of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests were performed in the first, second, and third trimesters of pregnancy and 10-17 weeks after delivery. IL-4 production was not affected greatly by normal or GD pregnancy, whereas IFN-gamma production was suppressed throughout pregnancy but returned to normal levels after delivery in both controls and patients. IL-6 and TNF-alpha tended to be higher in GD pregnancy than normal pregnancy, especially in the second and third trimesters. Controls had raised IL-10 in the first trimester with a return to normal levels by the third trimester, whereas patients had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater extent in control than Graves' pregnancy, especially during the second and third trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL-12 may be deficient in GD.

Adult↗
PubMed2000

Inhibition of chemotaxis by organic acids from anaerobes may prevent a purulent response in bacterial vaginosis.

It has been postulated that certain organic acids produced by the anaerobes associated with bacterial vaginosis (BV) could prevent a purulent response in this infection. Varying concentrations of pure succinic, acetic and lactic acids were incubated in vitro with a monocytic cell line (MonoMac 6). High inhibition of chemotaxis was produced by succinic acid; lower inhibition and no inhibition was shown by acetic acid and lactic acid respectively. Succinic and acetic acids were detected in high concentrations in the vaginal fluid of women with BV and in culture supernates of Prevotella and Mobiluncus spp.; these acids impaired chemotaxis of MonoMac 6 cells in vitro. The vaginal fluids of normal women and the culture supernates of Lactobacillus spp. had no effect on chemotaxis.

Bacteria, Anaerobic↗
PubMed1999

Markers of lymphocyte homing distinguish CD4 T cell subsets that turn over in response to HIV-1 infection in humans.

In HIV-1 infection, the abrupt rise in CD4 T cells after effective antiretroviral therapy has been viewed as a measure of HIV-1-related CD4 T cell turnover in the steady state. The early (2-4 wk) response is reportedly dominated by CD4 T cells with a memory (CD45RO) phenotype. It is controversial whether the measurement of steady-state kinetics identifies cells that otherwise would have been recruited into a short-lived, virus-producing pool or reflects lymphoid redistribution/sequestration. We performed detailed phenotypic and kinetic analysis of CD4 T cell subsets in 14 patients. Turnover occurs in memory (CD45RO) as well as naive (CD45RA) cells, if the latter are present at baseline. Most of the turnover occurs in those memory (CD45RO) and naive (CD45RA) cells that are programmed for recirculation through lymphoid organs (CD62L+ and CD44low), whereas very little turnover occurs in memory cells (CD45RO) destined for recirculation from blood to tissue (CD62L- and CD44high). Turnover occurs in both activated (CD25+ and HLA-DR+) and nonactivated populations, although it is restricted to CD38-positive cells, indicating that turnover does not measure cells that are already infected. More likely, turnover occurs in cells that replace infected cells or are on their way to becoming infected. Taken together, markers of lymphocyte trafficking better describe cell turnover related to virus replication than do naive and memory markers per se, and lymph organs, not tissue-destined cells or peripheral blood cells, appear to be the important site of virus replication and CD4 T cell turnover, destruction, and redistribution.

ADP-ribosyl Cyclase↗
PubMed1999

Lymphocyte kinetics and precursor frequency-dependent recovery of CD4(+)CD45RA(+)CD62L(+) naive T cells following triple-drug therapy for HIV type 1 infection.

New therapeutic regimens have dramatically altered morbidity and mortality attributed to HIV-1 infection. Changes in lymphocyte subsets after treatment may mirror salutary clinical changes. Over 4 months we analyzed lymphocyte subsets in 20 patients starting new HIV-1 therapy. Absolute numbers of lymphocytes, CD4+ T cells, CD8+ T cells, and B cells increased significantly by 4 months, but CD8+ T cell and B cell increases were restricted to late-stage patients. Subset analysis revealed that the magnitude of recovering naive-phenotype CD4+ T cells (slope) correlated with the number of these cells present at baseline, equaling or exceeding the memory-phenotype slope within days if these naive cells were abundant at baseline. Five of 10 patients in whom naive-phenotype CD4+ T cells were absent at baseline partially repopulated these cells by 4 months. These findings have important implications for the origin and mechanisms of renewal of naive-phenotype CD4+ T cells following effective treatment for HIV-1 infection.

Adult↗
PubMed1999

Acromelic frontonasal dysostosis.

We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.

Abnormalities, Multiple↗
PubMed1999

Antimicrobial activity of extracts from the cell cultures of some Turkish medicinal plants.

Twenty-four callus, and eleven cell suspension, cultures were established from Turkish medicinal plants, and crude extracts prepared from them tested against microorganisms to assess their antimicrobial activities in vitro. Of the extracts tested, those belonging to the cell cultures of five of the plant species showed antibacterial activity against mainly three bacteria and a yeast. No activity was observed against herpes simplex viruses, HSV-I and II, but an extract from Hypericum capitatum showed a slight anti-retroviral activity against HIV-I.

Animals↗
PubMed1999

Impaired production of IL-12 in systemic lupus erythematosus. III: deficient IL-12 p40 gene expression and cross-regulation of IL-12, IL-10 and IFN-gamma gene expression.

Interleukin 12 (IL-12) is a heterodimer comprising p35 and p40 subunits which are encoded and regulated separately. The authors previously demonstrated deficient IL-12 production in SLE which correlates negatively with disease activity. The present study was designed to determine whether deficiency of IL-12 and excess production of IL-10 and IL-6 in systemic lupus erythematosus (SLE) are due to aberrant regulation at the gene level. Using semiquantitative RT-PCR assay, it was shown that constitutive expression of IL-12 p35 gene is somewhat impaired in SLE compared with controls and that IL-12 p40 mRNA, which was present at low levels in controls, was undetectable in unstimulated SLE peripheral blood mononuclear cells (PBMC). Gene expression of IL-12 p35 and p40 was significantly increased in response to SAC, with significantly lower SAC-induced expression of p40 in SLE patients than controls. SAC-stimulated IL-12 p35 and p40 mRNAs were significantly augmented by interferon gamma (IFN-gamma). Exogenous IL-12 or IFN-gamma significantly inhibited IL-10 gene expression, without affecting IL-6 mRNA or other proinflammatory cytokine mRNA levels. These observations were further confirmed by studies of protein production at the single cell level using ELISPOT assay. Downregulation of IL-12 p40 expression appears to be the cause of IL12 p70 deficiency in SLE. If this defect could be repaired, normalization of IL-12 and IFN-gamma production should reduce excessive IL-10 and prevent pathology.

Cells, Cultured↗
PubMed1999

The in vitro antibacterial activity of Turkish medicinal plants.

A total of 76 extracts from 35 plants available in the Turkish flora were assayed for their in vitro antibacterial activities against five pathogenic bacteria and a yeast. Sixteen crude extracts from eight plant species were found to possess an activity against at least one or more test microorganisms. Bioassay-guided fractionation of the most active crude extracts was also carried out with the most active extracts. Activity against Staphylococcus aureus, Bacillus cereus, Branhamella catarrhalis, Escherichia coli, Clostridium perfringens and Candida albicans (yeast) is discussed.

Anti-Bacterial Agents↗
PubMed1999

Effect of radioactive iodine therapy on cytokine production in Graves' disease: transient increases in interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor-alpha, with longer term increases in interferon-gamma production.

Spontaneous and mitogen-stimulated production of interleukin-4 (IL-4), IL-6, IL-10, IL-12, interferon-gamma (IFNgamma), and tumor necrosis factor-alpha were evaluated by enzyme-linked immunospot assay of peripheral blood mononuclear cells from patients with Graves' disease immediately before and at 4, 17, and 59 days after treatment with radioactive iodine. Patients had significantly reduced IL-4 and IFNgamma production before treatment compared with healthy controls. Both cytokines were increased to normal levels by day 17 after treatment, and IFNgamma remained at normal levels on day 59, whereas IL-4 returned to subnormal levels at this time. IL-12 production was initially normal and was not significantly altered by therapy. IL-6, IL-10, and tumor necrosis factor-alpha were also normal before radiotherapy, but increased significantly on day 17, returning to pretreatment levels by day 59. Thus, radioiodine treatment induced a transient increase in both proinflammatory and antiinflammatory cytokines and a more prolonged increase in IFNgamma production, the latter representing a definite shift toward a type 1 cytokine profile.

Adult↗
PubMed1999

Reduced in vitro production of interferon-gamma, interleukin-4 and interleukin-12 and increased production of interleukin-6, interleukin-10 and tumour necrosis factor-alpha in systemic lupus erythematosus. Weak correlations of cytokine production with disease activity.

Production of cytokines in unstimulated and mitogen-stimulated cultures were evaluated by ELISPOT in 34 SLE patients with low to moderate disease activity and 23 healthy controls. Significantly reduced production of IFN gamma, IL4 and IL12 and significantly increased production of IL6, IL10 and TNF alpha were found in patients with SLE. Regression analysis revealed that production of all six cytokines tended to decrease with increasing disease activity, but negative correlation with SLEDAI was significant (p < 0.05) only for PHA-stimulated IL4, unstimulated and PHA-stimulated IL10 and SAC-stimulated IL6. Negative correlation of stimulated and unstimulated IL6 and TNF alpha production with anti-DNA antibody levels were also significant.

Adolescent↗
PubMed1998

Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes.

Interleukin 12 (IL-12) plays a crucial role in defensive immune responses, modulation of cytokine production and is involved in the pathogenesis of some autoimmune diseases. The authors investigated whether decreased in vitro production of IL-12 occurs in systemic lupus erythematosus (SLE), in which the cytokine secreting pattern is predominantly type 2. IL-12 production by SLE peripheral blood mononuclear cells (PBMC) was significantly impaired compared with normal PBMC, and this was not due to decreased numbers of monocytes. After depletion of non-adherent cells from PBMC, monocytes of SLE patients produced significantly less IL-12 than those of controls, but IL-12 levels in SLE and control non-adherent cells supernatants were not significantly different. Exogenous recombinant (r)IL-10 strongly inhibited IL-12 production by both SLE and normal PBMC and anti-IL-10 neutralizing antibody significantly reversed the IL-12 deficiency of SLE PBMC and SLE monocytes, while not affecting normal PBMC. Recombinant interferon gamma (rIFN-gamma) considerably enhanced IL-12 production in both SLE and normal PBMC, but it did not significantly reverse the inhibitory effect of rIL-10 on IL-12 production. IL-12 production was significantly lower in patients with active SLE than those in remission. These results suggest that SLE monocytes may be deficient in IL-12 production and that this is secondary to abnormal production of various cytokines, especially excessive production of IL-10.

B-Lymphocytes↗
PubMed1998

Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production in vitro is correlated negatively with serum IL-10, positively with serum IFN-gamma and negatively with disease activity in SLE.

Interleukin 12 (IL-12) is a key cytokine in regulating type 1 or type 2 cytokine production and in determining the nature of immune responses. Our previous studies demonstrated that its production was significantly impaired in systemic lupus erythematosus (SLE) patients and this deficient IL-12 production was mainly mediated by excessive endogenous IL-10. The present study was designed to further reveal the relationships of in vitro IL-12 production with abnormalities of in vivo cytokine synthesis and disease activity in SLE. Experimental results showed that IL-12 production in vitro was inversely correlated with serum IL-10 level, anti-ds DNA antibody level and SLE disease activity index (DAI), but positively correlated with serum interferon gamma (IFN-gamma) level, with which serum IL-10 correlated negatively. Data also showed that serum IL-10 was significantly higher than that of controls and closely correlated with anti-ds DNA antibody level and SLEDAI. The study confirms that deficient IL-12 production in SLE patients is associated with in vivo abnormalities of cytokine production, especially with increased IL-10 production.

Adult↗
PubMed1998

Maxillary distraction osteogenesis in Pfeiffer's syndrome: urgent ocular protection by gradual midfacial skeletal advancement.

Distraction osteogenesis is increasingly recognised as a potentially useful technique to achieve the co-ordinated augmentation of craniofacial skeletal and soft tissue. A case is presented where bilateral maxillary distraction was successfully used to advance the midface in the treatment of recurrent ocular dislocation, in a 10-month-old boy with Pfeiffer's syndrome.

Acrocephalosyndactylia↗
PubMed1998

A study of the prevalence of hydrogen peroxide generating Lactobacilli in bacterial vaginosis: the determination of H2O2 concentrations generated, in vitro , by isolated strains and the levels found in vaginal secretions of women with and without infection.

The concentration of hydrogen peroxide in the vaginal secretions of normal women were compared with levels found in women infected with bacterial vaginosis (BV). The mean concentration found in 90 normal samples was 0.171 microg per ml, whereas in women with BV, the mean level was 0.04 microg per ml (P < 0.001). In vitro culture experiments using TMB agar showed that in normal women, 75% of Lactobacillus strains produced H2O2 and 25% did not, whereas in women 'infected' with BV. 14% of the isolates produced H2O2 and 86% did not (P < 0.001). Quantitative culture tests showed that both anaerobic and facultative strains of Lactobacilli isolated from normal women generated significantly higher levels of H2O2 than strains cultured from women with BV. Anaerobic strains isolated from normal women produced a mean level of 6.8 microg per ml, compared with the mean level of 1.4 microg per ml from women with BV. Facultative strains from normal women produced mean levels of 18.3 microg per ml compared with 2.4 microg per ml produced by strains from BV-infected women, which had been incubated under the same conditions (P < 0.001). There results indicate that Lactobacilli which produce H2O2 probably have a significant role in protecting the vaginal ecosystem from BV infection.

Journal Article↗
PubMed1998

The feet in Pfeiffer's syndrome.

Broad toes are the classic clinical finding occurring in the feet in Pfeiffer's syndrome patients, but few cases undergo formal radiological assessment. However, the feet in other craniosynostosis syndromes resulting from mutations of the fibroblast growth factor receptor 2 gene have anomalies at many other sites within the feet, which raised the possibility that there may also be a wider range of anomalies other than broad big toes in the feet of those with Pfeiffer's syndrome. The object of this study was to assess prospectively the incidence and pattern of clinical and radiographic anomalies of the feet of patients with a confirmed diagnosis of Pfeiffer's syndrome. Twenty-two Pfeiffer's syndrome patients were examined both clinically and radiologically for anomalies of the feet. Clinical examination revealed broad big toes in 12 patients and syndactyly in 2. Radiographs of the feet were evaluated by a radiologist with an interest in skeletal dysplasia as well as by members of the Craniofacial team. A wider range of radiological than clinical anomalies involving the phalanges, metatarsals, and tarsals was seen. The severity of the anomalies observed ranged from normal to those resembling the feet of Apert's syndrome patients. Only 4 patients had radiologically normal feet. These radiographic findings suggest that there is a range of foot anomalies more extensive than the broad big toes, which are classically associated with Pfeiffer's syndrome.

Acrocephalosyndactylia↗
PubMed1998

The elbow in syndromic craniosynostosis.

Craniosynostosis may occur in conjunction with limb and visceral anomalies in more than 100 syndromes and may include anomalies of the elbow. Apert's, Pfeiffer's, Crouzon's, and Saethre-Chotzen syndrome have been linked with anomalies of the elbow, but the incidence and severity of such anomalies is unknown. A prospective radiographic study was undertaken to establish the types, incidence, and severity of elbow anomalies in patients with either Apert's, Pfeiffer's, Crouzon's, or Saethre-Chotzen syndrome attending the Craniofacial Centre at Great Ormond Street Hospital during a 12-month period. This study showed that elbow anomalies were very common in Apert's and Pfeiffer's syndrome, but less so in Crouzon's syndrome. The elbows in all patients with Saethre-Chotzen syndrome were normal. A range of anomalies was seen, with overlap between the syndromes. The severest anomaly seen in children with Crouzon's, Pfeiffer's, and Apert's syndrome was complete synostosis, which may require surgical intervention in due course. The results of this study suggest that the incidence of elbow anomalies in Apert's, Pfeiffer's, and Crouzon's syndrome is higher than the current literature suggests. Synostosis can be so severe that orthopedic review as part of the management of these children may be beneficial and may become increasingly important as more of these children survive into adulthood.

Acrocephalosyndactylia↗
PubMed1998

A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy.

Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 +/- 9% to 43 +/- 16% (mean +/- SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.

Antibodies, Blocking↗