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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 253 records · Page 14Linked to original sources

The effect of clindamycin on the microbiota associated with refractory periodontitis.

The purpose of this investigation was to determine the effect of clindamycin hydrochloride, as an adjunct to scaling, on the microbiota associated with refractory periodontitis and to elucidate the probable causative bacteria associated with the disease. Microbial samples were collected from a subset of 9 patients with severe adult periodontitis who had not responded to conventional treatment modalities including the use of tetracycline and other antibiotics. Microbial samples were collected from a relatively deep site determined to be actively losing attachment and a comparably deep, but quiescent, control site in each patient prior to clindamycin therapy. Samples continued to be collected from the same sites for up to 1 year post-therapy. The microbial flora of each sample were enumerated by darkfield microscopy and predominant cultivable methods. Prior to clindamycin therapy, both active and control sites consisted on average of approximately 50% spirochetes and motile rods and 40% Gram-negative anaerobic rods. Bacteroides intermedius and Porphyromonas gingivalis (formerly B. gingivalis) were elevated in the active, as compared to control, sites and accounted for approximately 20% of the cultured microbiota in the former. Following treatment with clindamycin, the Gram-negative components of the microbiota were either eliminated or severely suppressed. At 1 year post-therapy, spirochetes and motile rods together accounted for about 15% of the microscopic flora. Total Gram-negative anaerobic rods accounted for approximately 20%, and B. intermedius and P. gingivalis combined accounted for less than 2% of the cultured microbiota from historical active sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗

Clinical efficacy of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride during 6 months of use.

The efficacy of combined use of toothpaste and oral rinse containing sanguinaria extract and zinc chloride was compared to placebo products in a 6-month clinical trial. Sixty subjects with moderate levels of plaque and gingivitis were randomly assigned to active and placebo groups. Noninvasive measures of plaque and gingivitis were assessed at baseline and at 2, 6, 8, 14, 20, and 28 weeks. Bleeding on probing was measured at baseline and 6, 14, and 28 weeks. Active group scores were significantly lower (P less than .0001) than placebo scores at each post-baseline time point for all indices, with the exception of plaque at 2 weeks. The 28 week active group scores were 21% lower than the placebo group for plaque, 25% lower for gingivitis, and 43% lower for bleeding on probing. No dental staining or taste alteration was reported in the active group. Three of 30 active group subjects exhibited minor soft tissue irritations that resolved spontaneously without discontinuation of product use. Results indicate that the test products showed good levels of safety and efficacy when administered in a combined use regimen for 6 months.

Adult↗

Effect of 6 months use of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride upon the microflora of the dental plaque and oral soft tissues.

This study documented the effect upon the oral flora of twice daily brushing with a dentifrice containing 0.075% sanguinaria extract and 2% zinc chloride, followed by use of a mouthrinse containing 0.03% sanguinaria extract and 0.2% zinc chloride. Sixty subjects were randomly assigned to treatment or placebo groups and monitored in a 6-month double-blind clinical trial. Bacteriological samples from the tongue, buccal mucosa, and supra- and subgingival plaque were characterized at 0, 14, and 28 weeks. Microbiological monitoring showed no increases in populations of yeast, staphylococci, coliform organisms, or Pseudomonas. Total Gram-negative counts in supragingival plaque samples decreased 83% in the active group compared to a 232% increase for the control group. Populations of B. intermedius in supragingival plaque were significantly lower in the active group at 3 months and significantly lower counts of Fusobacterium sp. were observed at 3 and 6 months. Results indicate that use of the test products did not promote opportunistic overgrowth of pathogens in the oral flora. Additionally, the alterations in organisms associated with gingivitis may account for reductions in gingivitis seen in the active group.

Adult↗

Response times to speech stimuli as measures of benefit from amplification.

The benefits of management of hearing disability, in particular by provision of a hearing aid, are traditionally assessed by the percentage improvement in performance on a speech identification task. To provide precise and stable results, such procedures require more time than is available in most clinical settings. In any stressed performance, e.g. an impaired individual trying to listen in noise, there is a trading relationship between accuracy and effort (the cost at which accuracy is achieved). If the control of performance naturally spends effort to stabilize high performance, then benefit from amplification may essentially comprise and be measurable as reduction in effort rather than improvement in accuracy. Certainly complaints of hearing disability emphasize fatigue from careful listening. Hence a hearing aid may not only enable hearing impaired persons to hear more of speech but may enable them to hear it more easily, thus reflecting a second dimension to disability and benefit. Ease of listening was investigated using auditory response times to speech stimuli of two levels of structure: single words and sentences. The speech material was presented to 44 experienced hearing aid users (mild to moderate sensorineural hearing impairment). The speech was presented both unaided and aided at presentation levels of 60, 70 and 80 dB SPL and signal-to-noise ratios of quiet and + 5 dB. Response times were taken to the tokens within each list that were correctly identified. Benefit is defined as the decrease in response time from the unaided to the aided condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines.

In an attempt to gain some insight into the many factors influencing antibody gene expression in human B cell lines, we have examined in detail the relationship between cell surface phenotype, cytokines, and the growth and antibody-producing capacity of a panel of immortalized human B cell lines. The cell panel comprised lines secreting either high or low titers of antibodies against Rhesus D, hepatitis B surface, and tetanus toxoid antigens. All the transformed cell lines exhibited a cell surface phenotype characteristic of well-differentiated peripheral blood cells strongly expressing CD23 and CD38 while weakly expressing CD10 and CD21. There was no obvious relationship between the antibody-body-secreting and proliferative capacity of the cell lines and their cell surface phenotype. Antibody secretion by the cells was rarely improved by the addition of a wide range of doses of recombinant IL-2, IL-4, or IL-6. In addition, such treatment frequently inhibited proliferation. Supernatants from some of the cell lines promoted the growth of unrelated cell lines but failed to influence antibody production. Such supernatants contained the highest concentration of IL-1, TNF beta, TGF beta, and soluble CD23. In contrast, the heterohybrid supernatant which inhibited cell growth secreted low levels of these cytokines. None of the cell lines secreted detectable amounts of IL-2, IL-4, INF gamma, or GCSF. There was no obvious relationship between cytokine production and antibody secretion. Finally, LPS had a slight but variable effect on antibody secretion but failed to influence cell growth.

Antibody Formation↗

Immunoglobulin isotype production by cycling human B lymphocytes in response to recombinant cytokines and anti-IgM.

Actively cycling populations of purified human tonsilar B lymphocytes were examined for their capacity to secrete IgM, IgA, IgE and IgG of all four subclasses in direct response to recombinant cytokines; in some experiments, monoclonal antibody to IgM (anti-mu) was included in order to explore the influence of antigen receptor ligation on immunoglobulin (Ig) production. Enhanced IgM release was seen on culture of the cycling cells with either interleukin-2 (IL-2), IL-4 or interferon-alpha (IFN-alpha). IL-2 and IFN-alpha also augmented IgA production, whereas IL-4 had no effect on this isotype. IL-4 did, however, encourage the production of the IgG subclasses IgG1, IgG2 and IgG3, while IL-2 augmented IgG1 and IgG3 release and IFN-alpha increased IgG1 levels. IgG4 production, and that of IgE, failed to be perturbed by any of the cytokines assayed. Neither IL-1 alpha, IL-1 beta, IL-5 nor IFN-gamma significantly altered the profile of Ig isotype release. When confronted with anti-mu, cycling B cells demonstrated a marked suppression in IgM production. Suppression could not be overcome by the addition to culture of the normally IgM-promoting IL-4. Concomitant with the reduction in IgM levels, an increase in IgG release was observed. This was comprised of elevations in IgG1 and IgG3. Although not influencing IgA release directly, anti-mu was found to promote increased IgA production in co-culture with either IL-2 or IFN-alpha. The findings are discussed in the context of recent findings on Ig isotype control in both human and murine systems.

Antibodies, Anti-Idiotypic↗

Induction of an immune response to keyhole-limpet hemocyanin in surgical patients with anergy.

Groups of surgical patients, classified as reactive or anergic on the basis of delayed type hypersensitivity skin testing with five recall antigens, were immunized with keyhole-limpet hemocyanin (KLH) alone or KLH together with mediators derived from leukocytes of a KLH immune donor cultured with antigen. Patients with anergy injected with KLH alone did not generate an immune response as judged by a T cell proliferative reaction performed 14 days after immunization. In contrast, leukocytes of patients with anergy immunized with KLH together with the mediators reacted to KLH in vitro in similar numbers and with a magnitude comparable to that given by reactive, hospitalized patients without anergy immunized with KLH alone. These results confirm and extend our previous observations showing that anergy defined as a lack of cell-mediated immunity to recall antigens such as purified protein derivative extends to the generation of a systemic immune response to a neoantigen such as KLH and mediators that could restore a state of delayed hypersensitivity to purified protein derivative could also be instrumental in inducing cell-mediated immunity de novo when injected together with the antigen.

Antibody Formation↗

The influence of inborn athletic potential on choice of profession and exercise habits of paramedical students.

Twenty physiotherapy and 15 pharmacology students from the 2nd-year paramedical class were studied to determine whether inborn athletic potential had influenced their choice of profession. Each subject completed a questionnaire and performed a graded treadmill test to exhaustion to determine maximum oxygen consumption (VO2max), peak treadmill running velocity and ventilation threshold (VT). No difference was found between physiotherapy and pharmacy students in body mass, VO2max or running speed at VT, but physiotherapy students reached a higher peak treadmill velocity (P less than 0.01). Fewer pharmacy students participated in sport at university. To determine factors influencing participation in sport, students from both groups who exercised were compared with non-exercisers. Students who exercised had significantly higher VO2max, peak treadmill running velocity and VT, but differences were less than could be explained purely on the basis of superior genetic endowment. It is concluded: (i) that physiotherapy students do not have greater inborn athletic potential than pharmacy students; (ii) that exercising students show physiological adaptations compatible with a higher level of 'fitness', and (iii) that whereas lack of inborn athletic potential is not the reason why some students do not exercise regularly at university, inborn athletic potential may determine those who will exercise competitively.

Attitude↗

Mitogen-induced phosphorylation of human B-lymphocyte proteins. Relationship to protein kinase C activation.

We have investigated the rapid phosphorylation of proteins in B-lymphocytes incubated with the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), anti-Ig and combinations of TPA and the Ca2+ ionophore ionomycin. Two-dimensional electrophoretic analysis was used to identify the proteins phosphorylated in cells preincubated with [32P]Pi. TPA induced a characteristic pattern of labelled proteins, four of which (pp85, pp76, pp66 and pp63) showed a dose-dependent incorporation of 32P on serine residues. The phosphorylation of pp63 and pp66, in particular, correlated with the mitogenic dose-response curve. Addition of the Ca2+ ionophore ionomycin to B-cells also stimulated a characteristic incorporation of 32P into proteins, which included pp63 and pp66. With combined doses of TPA and ionomycin, these two proteins show an enhanced phosphorylation, which correlated well with the synergistic enhancement of proliferation shown by this combination of agents. Protein kinase C (PKC) was partially purified from B-cells and separated into alpha and beta subtypes. The activation of both PKCs was assessed with increasing doses of TPA and concentrations of Ca2+ of 0.1 microM and 2 microM. For both forms of PKC, in particular the beta form, higher concentrations of Ca2+ shifted the dose-response curve for TPA to the left and increased the maximum activation. Anti-Ig, which stimulated B-cells by cross-linking surface immunoglobulin and causing hydrolysis of PtdIns(4,5)P2, also caused increased phosphorylation of several proteins, which again included pp63 and pp66. These data suggest that PKC, particularly the beta form, is involved in the early part of the proliferation cascade for human B-lymphocytes. It is most probably activated in a synergistic manner by the increased Ca2+ and diacylglycerol levels which result from the earlier hydrolysis of PtdIns(4,5)P2.

Animals↗

Lovastatin therapy for hypercholesterolemia in cardiac transplant recipients.

Hypercholesterolemia (type II hyperlipidemia) after cardiac transplantation is common and may play a role in the accelerated rate of coronary atherosclerosis seen following the procedure. However, conventional cholesterol-lowering drugs are either ineffective or contraindicated for use in transplant recipients. The presence of type II hyperlipidemia was identified in 11 cardiac transplant recipients during a mean follow-up period of 15 months (range 3 to 41) after transplantation. Lovastatin, at an initial dosage of 20 mg/day, was administered for a period of 1 year. The maximal dosage of lovastatin was 60 mg/day. All patients received maintenance dosages of immunosuppressive agents, including cyclosporine-A, prednisone and, in some instances, azathioprine. Lipid profiles, hepatic transaminases, serum creatinine, creatine kinase and cyclosporine-A serum trough levels were measured quarterly. Total cholesterol decreased by 27% (354 +/- 50 vs 258 +/- 36 mg/dl, p less than 0.01) after 3 months and remained stable thereafter. Similarly, low density lipoprotein cholesterol decreased by 34% (221 +/- 51 vs 146 +/- 40 mg/dl, p less than 0.01) after 3 months and remained constant. Triglycerides, high density lipoprotein, hepatic transaminases, creatinine, creatine kinase and trough cyclosporine-A levels remained stable during the 1-year follow-up period. Lovastatin was uniformly well tolerated in this study group. When given in modest dosages, lovastatin appears to be a safe, effective and well-tolerated therapy for hypercholesterolemia in cardiac transplant recipients.

Adult↗

Epstein-Barr virus and a tumour-promoting phorbol ester use similar mechanisms in the stimulation of human B-cell proliferation.

In marked contrast to ligands which activate B cells via their physiological receptors for antigen, transforming Epstein-Barr virus (EBV) was found to be mitogenic for human B lymphocytes without increasing inositol phospholipid hydrolysis. B-cell stimulation by EBV showed similar characteristics to those achieved by the tumour-promoting phorbol ester TPA, in terms of the temporal appearance of surface activation antigens, the induction of RNA and DNA synthesis and the lower requirement for medium Ca++ in comparison to agonists that lead to an increase in inositol phospholipid hydrolysis. The calcium- and phospholipid-dependent kinase, protein kinase C (PKC), is activated by TPA and a proteolytically cleaved fragment (PKM) results. EBV induced the appearance of a calcium- and phospholipid-independent activity that was chromatographically inseparable from PKM and this activity was capable of phosphorylating vimentin, a cell component that is thought to participate in the signal transduction cascade. These findings are discussed with special reference to the biochemical signalling pathways on which EBV might impinge to usurp growth control in B lymphocytes.

Antigens, Surface↗