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Biomedical subjects

M L Jones

Publications and source records attributed to M L Jones.

At least 127 records · Page 7Linked to original sources

Monocyte chemoattractant protein 1 in a rat model of pulmonary granulomatosis.

Monocyte chemoattractant protein 1 (MCP1), also known as monocyte chemotactic and activating factor, possesses potent chemotactic activity for monocytes and can augment monocyte tumoristatic activity against some tumor cell lines. While these activities suggest a role in inflammatory and immunologic processes, the biologic role of MCP1 has not been studied in vivo. Glucan-induced pulmonary granulomatosis in the rat is an ideal model in which to study the role of MCP1 because the granulomas are monocyte/macrophage rich. Intravenous infusion of particulate yeast cell wall glucan resulted in the synchronous development of angiocentric pulmonary granulomas. Early lesions (6 hours) were characterized by intravascular glucan aggregates surrounded by neutrophils and foci of alveolar hemorrhage while later appearing granulomatous lesions (48 to 96 hours) were dominated by monocytes and macrophages. Granuloma formation was paralleled by a peripheral blood monocytosis. Analysis of bronchoalveolar lavage (BAL) fluid revealed an early, transient rise in tumor necrosis factor activity followed by a marked rise in monocyte-specific chemotactic activity. The rise in BAL fluid monocyte chemotactic activity, which coincided with the development of the monocyte/macrophage-rich granulomas, was preceded by a marked increase in whole lung MCP1 mRNA expression. BAL fluid monocyte chemotactic activity could be nearly completely neutralized with antibody directed against rat MCP1. These studies demonstrate that MCP1 mRNA expression is upregulated in glucan-induced pulmonary granulomatosis and that MCP1 is present in BAL fluid. Intrapulmonary granulomatosis may be important in the pathogenesis of granuloma formation.

Animals↗

Monocyte chemotaxis and activating factor production by keratinocytes in response to IFN-gamma.

Monocytes accumulate in the epidermis and along the dermo-epidermal junction in several different inflammatory skin diseases. To determine whether human epidermal keratinocytes elaborate a specific chemotaxin responsible for the accumulation of monocytes at these anatomic sites, monocyte chemotactic activity in conditioned 16-h cultured keratinocyte supernatants were assayed using human peripheral blood monocytes as the target cell. Dilutional analysis revealed directed monocyte migration in IFN-gamma-treated (100 U/ml) keratinocyte supernatants (80% maximal FMLP response) which was 10-fold more than IFN-gamma itself or untreated keratinocyte activity alone. Gel filtration chromatography revealed that this activity eluted just ahead of a 12.5-kDa molecular mass marker. Blocking studies demonstrated that a rabbit polyclonal antibody to monocyte chemotaxis and activating factor (MCAF) inhibited all monocyte chemotaxis by greater than 80%. Keratinocytes were metabolically labeled with 35S-cysteine/methionine, and after 16 h incubation the supernatants immunoprecipitated with the same anti-MCAF antibody. MCAF was detected as a protein doublet of 12 and 9 kDa only in IFN-gamma-treated (100 U/ml) keratinocyte supernatants. Incubation with IFN-gamma and TNF-alpha (250 U/ml) in combination resulted in increased production of MCAF protein. By Northern blot analysis, MCAF mRNA was constitutively expressed in keratinocytes and upregulated only in the presence of IFN-gamma. TNF-alpha, IL-1 beta, transforming growth factor-beta and phorbol esters had no positive or negative influence on MCAF mRNA. These studies demonstrate that biologically active MCAF is elaborated by human epidermal keratinocytes upon activation by IFN-gamma, a cytokine also required for the induction of adherence between monocytes and keratinocytes. Keratinocyte-derived MCAF is likely to be important in the regulation of cutaneous monocyte trafficking and may also be responsible for the recruitment of Langerhans cells and dermal dendrocytes, which share many phenotypic features with monocytes/macrophages, to their anatomic locations in skin.

Cells, Cultured↗

A stress analysis of the periodontal ligament under various orthodontic loadings.

The accurate modelling of teeth under orthodontic load in the laboratory has many shortcomings in that it has not been possible to integrate methods, such as three-dimensional models, photo-elastic stress analysis, laser holographic interferometry, and animal studies, to give comprehensive and repeatable results. In this study, using a three-dimensional finite element model of a human maxillary canine tooth, the maximum principal stresses in the periodontal ligament produced by various orthodontic forces were determined. 1 Newton tipping forces produced stresses at the cervical margin of the periodontal ligament as high as 0.196 N/mm2 and apical stresses up to -0.034 N/mm2, while rotatory forces of two equal, but opposing forces of 0.5 Newton at the cervical margin of the crown produced cervical margin stresses ranging between -0.035 and 0.051 N/mm2, and apical stresses of between 0.0018 and 0.0027 N/mm2. These stresses are examined and discussed in relation to previous clinical, laboratory, and histological studies.

Computer Simulation↗

Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen.

Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients.

Administration, Topical↗

A comparison of orthodontic treatment changes as measured from study casts and cephalometric radiographs.

Orthodontic treatment change was examined for 106 consecutively referred patients using serial lateral cephalometric radiographs and study cast records. The 2-D and 3-D measurement systems used to assess the changes were compared for five variables common to both sets of records. No statistical differences were found between the study cast and radiographic records for these variables. The 3-D measurement with the Reflex Metrograph showed marginally better precision in the measurement of the treatment changes examined. However, the main advantage was that it allowed a more thorough and accurate assessment of both individual incisor position and measurement error.

Cephalometry↗

Modulation of keratinocyte-derived interleukin-8 which is chemotactic for neutrophils and T lymphocytes.

Interactions between T lymphocytes, neutrophils, and epidermal cells are believed to play a central role in the pathophysiology of psoriasis and other inflammatory cutaneous disorders. Although there is strong evidence that lymphocyte-function-associated antigen-1 (LFA-1) positive T cells are retained in the epidermis via intercellular adhesion molecule-1 (ICAM-1) expression induced on keratinocytes, the molecular basis for the directed migration of T cells or neutrophils towards the epidermis is not known. To investigate whether epidermal keratinocyte-derived products may be important in the migration of T cells and neutrophils into the epidermis, human keratinocytes were cultured in the presence of various cytokines and chemotactic activity of the supernatants were assessed. TNF-alpha stimulation produced directed migrational responses for both neutrophils and T-lymphocytes (both CD4 and CD8), but not B lymphocytes; 69% of T-cell movement and 80% of neutrophil migration induced by the TNF-alpha treated keratinocyte cell supernatants could be inhibited by anti-interleukin-8 (IL-8) serum. Using the same antibody, IL-8 was immunoprecipitated from the supernatants of TNF-stimulated 35S-labelled keratinocytes, and a single 7-kd band product detected by SDS-PAGE. In keeping with these biological activities and protein data, Northern blot analysis of total cellular RNA extracted from keratinocyte monolayers hybridized with a 32P-labelled 1-kb cDNA to IL-8 mRNA, revealed induction of the IL-8 gene in the presence of TNF-alpha and IL-1 beta, but not IFN-gamma. The protein kinase C agonist, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a known stimulator of psoriasiform cutaneous inflammation when applied directly to murine epidermis, strongly induced keratinocyte elaboration of IL-8 mRNA. These studies demonstrate that activated human keratinocytes are capable of producing biologically active IL-8, and provide evidence that keratinocytes can play a key role in mediating the influx of T cells and neutrophils into the epidermis.

Blotting, Northern↗

Laboratory evaluation of surgical ball hook crimping pliers.

Newly introduced crimping pliers for use with surgical ball hooks were laboratory tested against the previous design, because in the past hooks have been lost during the surgical procedure. The new pliers demonstrated an improved "friction lock" over the old design. However, it is still recommended that a continuous ligature be used with the final surgical arch wire to avoid the possibility of displacing hooks laterally off the arch wire during surgical and postsurgical procedures.

Dental Instruments↗

Contrasting roles for tumor necrosis factor in the pathogeneses of IgA and IgG immune complex lung injury.

Recent studies suggest that development of acute gamma G immunoglobulin (IgG) immune complex lung injury is partially dependent on a tumor necrosis factor (TNF)-dependent mechanisms of neutrophil (PMN) recruitment. The authors have sought to further define the role of intrapulmonary TNF in IgG alveolitis and to examine its role in IgA immune complex alveolitis, a neutrophil-independent model of acute lung injury. IgG immune complex lung injury resulted in a marked rise in intrapulmonary TNF activity accompanied by progressive pulmonary PMN accumulation. Intratracheal instillation of neutralizing concentrations of anti-TNF markedly reduced PMN influx measured at 4 hours but had no effect on PMN recruitment quantitated at 2 hours. IgA immune complex deposition resulted in acute lung injury accompanied by increased numbers of intrapulmonary mononuclear phagocytes but few neutrophils. Lung lavage fluids obtained from IgA immune complex-injured rats contained both neutrophil and monocyte chemotactic activities, albeit at twofold to fourfold lower concentrations than observed in IgG-mediated alveolitis. In contrast to IgG complex-mediated alveolitis, lung lavage fluids from IgA-injured rats contained no TNF activity. Intratracheal administration of anti-TNF antibodies had no effect on the development of IgA lung injury as assessed by morphology and measurements of vascular permeability. In vitro exposure of isolated alveolar macrophages to performed IgG immune complexes resulted in dose-dependent TNF secretion, while exposure to IgA complexes resulted in very low levels of TNF secretion. These data suggest that TNF-mediated pulmonary neutrophil recruitment (in IgG lung injury) is manifest chiefly in the late phase (approximately 4 hours) of developing alveolitis. The virtual absence of intrapulmonary TNF activity in evolving IgA immune complex alveolitis may in part account for the limited PMN recruitment observed in this model.

Animals↗

Three-dimensional analysis of orthodontic tooth movement.

A three-dimensional finite element model was used to investigate the biomechanical response of an upper canine tooth. The physical model was developed from ceramic replicas and X-rays, and consisted of cancellous and cortical bone, the periodontal ligament, dentine and pulp chamber. Horizontal forces were applied at the tip of the crown and at the cervical margin and a rotational force was applied at the cervical margin of the tooth crown. The resulting displacements and stress field for each load case are presented with particular emphasis being placed on the response of the periodontal ligament. The investigation shows that quantitative information on initial tooth movement can be accurately predicted and used to evaluate the response of orthodontic treatment.

Biomechanical Phenomena↗

The dimensional stability of self-disinfecting alginate impressions compared to various immersion regimes.

Alginate impressions of a master acrylic study model pair were made in order to assess the effect of various disinfection techniques on dimensional stability. Impressions were made using self-disinfecting alginate, traditional alginate which had been dipped or soaked in a disinfecting solution, and included was a control group which was not disinfected. Inter- and intra-arch linear measurements of the resultant study casts were made using a Reflex Metrograph. The small differences found for the variables measured were not statistically significant.

Alginates↗

The immune response to short-term nutritional intervention in advanced chronic obstructive pulmonary disease.

Nine patients with advanced chronic obstructive pulmonary disease (COPD) and recent weight loss resulting in a state of mild malnutrition were entered into a refeeding program at a clinical research center. They were divided into two groups, one using a hospital diet and the other a hospital diet with supplementation. Both groups of patients gained significant weight. Refeeding and weight gain were associated with a significant increase in absolute lymphocyte count and with an increase in reactivity to skin test antigens after 21 days of refeeding. Few changes occurred in large numbers of additional serum measurements during the study period. These preliminary observations suggest that dietary and supplementary refeeding may improve the immune responses in patients with COPD.

Aged↗

The Barry Project--a three-dimensional assessment of occlusal treatment change in a consecutively referred sample: the incisors.

The serial occlusal changes for a consecutively referred sample of malocclusion from a Welsh town are presented. The patients were assigned to one of four treatment regimes (meant to represent those commonly used in the U.K.) and treated to a rigid protocol. Twenty-five per cent of the cases were reviewed by an eight clinician panel. No bias in the original assignments was found although there was considerable interobserver variation. At defined pretreatment, post-treatment, and post-retention stages, records were collected and the study casts quantitatively measured using a reflex metrograph and an occlusal analysis programme. The results found for the overjet, overbite, crown inclination, and crown angulation are presented and discussed.

Analysis of Variance↗

Late management of cleft lip and palate problems: a joint orthodontic/surgical approach.

Three patients are presented from a larger case series of adolescent cleft lip and palate patients to illustrate a combined approach to the treatment of severe facial and dentoalveolar discrepancy. The following treatment regime was employed: orthopaedic expansion of the maxillary dentoalveolus; tertiary bone grafting of the alveolar cleft; upper and lower dental arch alignment and decompensation; and orthognathic surgery to correct the skeletal defect by means of a maxillary single unit advancement. The advantages of tertiary grafting (when secondary grafting has not been carried out) in the orthodontic and surgical management of these patients is discussed.

Adolescent↗