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T Martin

Publications and source records attributed to T Martin.

At least 109 records · Page 6Linked to original sources
PubMed1998

Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor.

IL-18 inhibits osteoclast (OCL) formation in vitro independent of IFN-gamma production, and this was abolished by the addition of neutralizing antibodies to GM-CSF. We now establish that IL-18 was unable to inhibit OCL formation in cocultures using GM-CSF-deficient mice (GM-CSF -/-). Reciprocal cocultures using either wild-type osteoblasts with GM-CSF -/- spleen cells or GM-CSF -/- osteoblasts with wild-type spleen cells were examined. Wild-type spleen cells were required to elicit a response to IL-18 indicating that cells of splenic origin were the IL-18 target. As T cells comprise a large proportion of the spleen cell population, the role of T cells in osteoclastogenesis was examined. Total T cells were removed and repleted in various combinations. Addition of wild-type T cells to a GM-CSF -/- coculture restored IL-18 inhibition of osteoclastogenesis. Major subsets of T cells, CD4+ and CD8+, were also individually depleted. Addition of either CD4+ or CD8+ wild-type T cells restored IL-18 action in a GM-CSF -/- background, while IL-18 was ineffective when either CD4+ or CD8+ GM-CSF -/- T cells were added to a wild-type coculture. These results highlight the involvement of T cells in IL-18-induced OCL inhibition and provide evidence for a new OCL inhibitory pathway whereby IL-18 inhibits OCL formation due to action upon T cells promoting the release of GM-CSF, which in turn acts upon OCL precursors.

Animals↗
PubMed1998

Mobilization of peripheral blood progenitor cells by Betafectin PGG-Glucan alone and in combination with granulocyte colony-stimulating factor.

Betafectin PGG-Glucan, a novel beta-(1,6) branched beta-(1,3) glucan purified from the cell walls of Saccharomyces cerevisiae, has been shown to synergize with myeloid growth factors in vitro and to enhance hematopoietic recovery in myelosuppressed mice and primates. Here we report that PGG-Glucan is also capable of mobilizing peripheral blood progenitor cells (PBPC). PGG-Glucan (0.5 mg/kg to 16 mg/kg) was administered intravenously to C3H/HeN male mice and blood collected at times ranging from 30 min to seven days after injection. Based on granulocyte-macrophage colony-forming cell (GM-CFC) levels, peak mobilization occurred 30 min after a 2 mg/kg PGG-Glucan dose. At this time GM-CFC numbers in PGG-Glucan-treated mice were approximately fourfold greater than in saline-treated control mice. A second, smaller wave of GM-CFC mobilization (approximately twofold increase) also occurred on days 4 and 5 after PGG-Glucan treatment. Mobilization was not associated with the induction of alpha-chemokines, which have recently been reported to induce rapid progenitor cell mobilization. Competitive repopulation experiments performed in irradiated female C3H/HeN mice revealed that, at three months after transplantation, more male DNA was present in bone marrow, splenic, and thymic tissues from animals transplanted with cells obtained from mice 30 min after a 2 mg/kg PGG-Glucan dose than in tissues from animals transplanted with cells obtained from saline-treated mice. Additional experiments evaluated the mobilization effects of PGG-Glucan (2 mg/kg) administered to mice which had been pretreated for three consecutive days with G-CSF (125 microg/kg/day). When blood was collected 30 min after PGG-Glucan treatment, the number of GM-CFC mobilized in combination-treated mice was additive between the number mobilized in mice treated with G-CSF alone and the number mobilized in mice treated with PGG-Glucan alone. These studies demonstrate that: A) PGG-Glucan can rapidly mobilize PBPC; B) the kinetic pattern of PGG-Glucan-induced mobilization is different from that of the CSFs; C) the reconstitutional potential of PGG-Glucan mobilized cells is greater than that of steady-state PBPC, and D) PGG-Glucan can enhance G-CSF-mediated PBPC mobilization.

Adjuvants, Immunologic↗
PubMed1998

Magnetic sensor data acquisition for three-dimensional ultrasound of the orbit.

PURPOSE: Three-dimensional (3D) B-mode ultrasound imaging is now possible using a magnetic sensor data acquisition system to localise data points, allowing free-hand scanning. We report the first use of this freehand scanning system for insonation of the orbit. METHODS: We insonated 10 orbits in 5 volunteers (all men; mean age 37 years) with an Acuson 128XP ultrasound system and a 7.5 MHz transducer. Power-Doppler was used to image vascular structures. Data were acquired using a new magnetic sensor system with detectors mounted on the transducer. Free-hand scanning was done using sweeping or fan-like and linear movements over 20-30 s to cover the orbit, with retrospective measurements of orbital structures. A 3D reconstruction was performed via an external workstation. RESULTS: All orbits were adequately imaged by one data acquisition. Selected intraorbital structures were identified and their course followed, including optic nerve and central vessels, as well as short and long ciliary vessels. The mean transverse area of the optic nerve was 5.6 +/- 1.1 mm2; the diameter of the optic nerve was 3.0 +/- 0.3 mm. The lateral rectus muscle was clearly seen, with a mean diameter of 4.9 +/- 0.3 mm, at the level of optic nerve head. CONCLUSION: Three-dimensional ultrasound of the orbit allows imaging of the location, course and relationships of intraorbital vessels, the optic nerve and the lateral rectus muscles with one data acquisition, as well as quantitative measurements not possible with 2D images alone. This method allows rapid, free-hand data acquisition, with a multitude of potential clinical applications.

Adult↗
PubMed1998

Clinical validation of ineffective breathing pattern, ineffective airway clearance, and impaired gas exchange.

PURPOSE: To describe the clinical validation of symptoms or defining characteristics of three respiratory diagnoses. The contributing factors or etiologies of the diagnoses were identified and the degree of importance of 30 nursing interventions, 15 direct care and 15 teaching, was rated for each diagnosis and each patient. Three nursing diagnoses--ineffective breathing pattern (IBP), ineffective airway clearance (IAC), and impaired gas exchange (IGE)--were among the most frequently used, yet no reported clinical studies validated the defining characteristics of these diagnoses. This study answers the research questions: What are the defining characteristics of IBP, IAC, and IGE? What are the etiologies of IBP, IAC, AND IGE? What are the most important interventions for IBP, IAC, and IGE? DESIGN: Standardized clinical validation using a convenience sample of 76 people hospitalized with medical and surgical diagnoses, in one U.S. city, and identified as having one of the three diagnoses. Data were collected in 1992-1993. METHODS: A literature-based concept analysis generated 37 possible defining characteristics for the three diagnoses which were included in the instrument. The nurse experts conducted a health history and physical examination of each patients and decided (a) whether the 37 defining characteristics were present or absent, (b) the degree of importance of each possible defining characteristic for making one or more of the diagnoses, (c) the etiologies, and (d) which of the 30 nursing interventions were important for each diagnosis and patient. FINDINGS: For each diagnosis, many of the 37 possible defining characteristics were judged as present but few reached the criterion of .50 as important for making one of the diagnoses. Two of the possible defining characteristics reached this criterion for IBP, seven for IAC, and two for IGE. In contrast to the defining characteristics approved by NANDA, the subjective cues of "expresses fatigue" and "expresses anxiety" were judged as important for making one or more of the diagnoses. CONCLUSIONS: Clinical validation methods allow discriminating among defining characteristics. Data that are present are not necessarily characteristic of a diagnosis, and the subjective cues of expresses fatigue or anxiety may be important for making these diagnoses.

Adult↗
PubMed1998

The effect of aerobic exercise training on the distribution of succinate dehydrogenase activity throughout muscle fibres.

We evaluated the effect of endurance training (cycling 3 times per week for 12 weeks) on succinate dehydrogenase (SDH) activity in the subsarcolemmal (SS) and intermyofibrillar (IMF) regions of vastus lateralis muscle fibres in 7 individuals (4 females and 3 males). SDH activity of the SS region increased 9.4% and 12.8% in type I and II fibres, respectively (p < .05). SDH activity of the IMF region increased 4.7% and 6.7% in type I and II fibres, respectively (p < .05). This was less than the increase in the SS region (p < .05). No significant changes were observed in a control group (4 females and 3 males). These data suggest that mitochondria in the SS and IMF regions of human vastus lateralis muscle fibres are sensitive to endurance training. The greater response in the SS region suggests that the metabolic requirements of SS mitochondria were stressed to a greater extent than IMF mitochondria with endurance training.

Adult↗
PubMed1998

IL-1beta-induced monocyte chemoattractant protein-1 gene expression in endothelial cells is blocked by proteasome inhibitors.

Human monocyte chemoattractant protein-1 (MCP-1) is expressed by a variety of cell types in response to various stimuli. MCP-1 expressed by the endothelium plays an important role in cell migration and activation. MCP-1 is a major chemoattractant for monocytes, T lymphocytes, and basophils. In the present study, we present evidence that the proteasome complex is involved in mediating the interleukin (IL)-1beta induction of MCP-1 in endothelial cells. We present evidence that a proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal (norLeu), and the protease inhibitor tosyl-Phe-chloromethylketone (TPCK) block IL-1beta induction of MCP-1 protein expression. norLeu and TPCK also blocked IL-1beta-induced MCP-1 promoter-driven reporter gene expression as well as nuclear factor (NF)-kappaB-mediated reporter gene expression. The effects of norLeu were due to its inhibition of the proteasome rather than calpain, because other calpain inhibitors had no effect on MCP-1 expression. In contrast to TPCK, which blocked NF-kappaB translocation to the nucleus, norLeu had no effect on NF-kappaB nuclear translocation or IL-1beta-induced phosphorylation of p65. This study demonstrates that the proteasome pathway is involved in IL-1beta-induced MCP-1 gene expression in human endothelial cells.

Cells, Cultured↗
PubMed1998

Splenic macrophages from the NOD mouse are defective in the ability to present antigen.

IDDM results from the destruction of pancreatic beta-cells by autoreactive T-cells that appear to avoid deletion early in development, possibly due to improper interaction with antigen-presenting cells (APCs) resident in the thymus or periphery. In the nonobese diabetic (NOD) mouse, there exists a defect in APC function characterized by its failure to fully mature upon stimulation. The NOD mouse thus provides an excellent model for the investigation of APC dysfunction and development and how these relate to the incidence of autoimmune diabetes. We initiated studies of APC function in the NOD mouse with respect to antigen processing and presentation, using a well-characterized antigen hen egg lysozyme (HEL) and comparing it with the closely related, major histocompatibility complex (MHC) (I-Ag7) identical, diabetes-resistant mouse strain NOR. Proliferation assays comparing NOD and NOR HEL-specific T-cells demonstrated that the T-cell proliferation response of the NOD mouse to both native and denatured forms of the antigen is lower than that of NOR. When crisscross proliferation experiments were conducted using purified T-cells and irradiated spleen cells as APCs from both strains, the results demonstrated that the defect in proliferation resided in the APC compartment of activation. The levels of intracellular glutathione (GSH) were compared in splenic macrophages from NOD and NOR mice; it was found that on antigenic stimulation, NOR macrophages produced significantly more intracellular GSH than did NOD macrophages, even under hyperglycemic (50 mmol/l glucose) conditions. The lower amount of GSH seen in the NOD may result in less efficient processing of antigen, and subsequently, lower levels of T-cell activation.

Animals↗
PubMed1998

In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan.

Betafectin PGG-glucan is a novel beta-(1,3)glucan that has broad-spectrum anti-infective activities without cytokine induction. Here we report that PGG-glucan also has both in vitro and in vivo hematopoietic activities. In vitro studies with bone marrow target cells from the C3H/HeN mouse revealed that although PGG-glucan alone had no direct effect on hematopoietic colony-forming cell (CFC) growth, when combined with granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF, it increased CFC numbers 1.5- to 2.0-fold over those obtained with CSFs alone. Bone marrow cells cultured for high-proliferative-potential CFCs in the presence of interleukin (IL)-1, IL-3, macrophage CSF, and stem cell factor (SCF), or cultured for erythroid burst-forming units in the presence of IL-3, SCF, and erythropoietin, also exhibited enhanced growth in the presence of PGG-glucan. The synergistic effect of PGG-glucan was specific and could be abrogated by anti-PGG-glucan antibody. The ability of PGG-glucan to modulate hematopoiesis in vivo was evaluated in myelosuppressed rodents and primates. C3H/HeN female mice were intravenously administered saline solution or PGG-glucan (0.5 mg/kg) 24 hours before the intraperitoneal administration of cyclophosphamide (200 mg/kg), and the recovery of bone marrow cellularity and granulocyte-macrophage progenitor cells was evaluated on days 4 and 8 after cyclophosphamide treatment. At both time points, enhanced hematopoietic recovery was observed in PGG-glucan-treated mice compared with saline-treated control mice. In a final series of in vivo experiments, we evaluated the ability of therapeutically administered PGG-glucan to enhance hematopoietic recovery in cyclophosphamide-treated cynomolgus monkeys. Monkeys received intravenous infusions of cyclophosphamide (55 mg/kg) on days 1 and 2, followed on days 3 and 10 by intravenous infusion of PGG-glucan (0.5, 1.0, or 2.0 mg/kg). Compared with those in saline-treated monkeys, accelerated white blood cell recovery and a reduction in the median duration of neutropenia were observed in PGG-glucan-treated monkeys. These studies illustrate that PGG-glucan has both in vitro and in vivo hematopoietic activities and that this agent may be useful in the prevention and/or treatment of chemotherapy-associated myelosuppression.

Animals↗
PubMed1998

Physical and occupational therapy in the treatment of patients with multiple sclerosis.

The interdisciplinary approach to the management of MS patients includes the services of both physical and occupational therapy. These professions complement one another in their concerted effort to mobilize the patient, thereby minimizing the symptoms of progressive weakness, fatigue, and spasticity. The ambulant patient is far less likely to develop complications of inactivity such as contractures, decubitus ulcers, venous thrombosis, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.

Contracture↗
PubMed1997

Autoantibodies in mice lacking terminal deoxynucleotidyl transferase: evidence for a role of N region addition in the polyreactivity and in the affinities of anti-DNA antibodies.

The generation of terminal deoxynucleotidyl transferase knockout mice (TdT0) has demonstrated that TdT is the only major activity involved in N region addition. This enzyme generates diversity by adding random nucleotides at the V-D-J junctions and by disrupting the formation of repetitive "homology-directed" junctions. Several studies have demonstrated that the Ig heavy chain third complementarity-determining region (H-CDR3) and the N region play a critical role: 1) in distinguishing between polyreactive and monospecific combining sites in natural and Ag-induced Abs; and 2) in the specificity and polyreactivity of natural autoantibodies (autoAbs) and in particular of anti-DNA Abs. To examine the impact of the lack of TdT on the natural autoAb repertoire in adult mice, we have stimulated TdT0 and TdT+ littermates with LPS. Serum studies demonstrate that TdT is not critical for the generation of B cells expressing autoAbs including anti-DNA Abs and rheumatoid factors. However, the generation of a large collection of hybridomas indicates that the frequencies of these cells are reduced in TdT0 mice mainly due to a lower incidence of polyreactivity; also, the lack of N region diversity seems to negatively affect the affinity of anti-DNA Abs. The physiologic relevance of these data is discussed.

Amino Acid Sequence↗
PubMed1997

The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection.

The plasma membrane remodeling, including the early transverse redistribution of phosphatidylserine, is a general feature occurring in cells in which a death program has been induced. In most cases, studies of this kind have focused mainly on cells. In this study, we report a clear correlation between the degree of apoptosis induced by a variety of agents in several types of cultured cells and the amount of shed membrane microparticles captured in the corresponding supernatants by insolubilized annexin V, a protein showing a strong affinity for phosphatidylserine. Such particles carry membrane antigens specific of the cells they stem from, and through which capture is also feasible. Homologous circulating microparticles were captured in peripheral blood from individuals with HIV-1 infection. A substantial proportion bore CD4 antigen. In some cases, CD4+ particles could be detected even in the absence of circulating CD4+ T cells, testifying to the presence of such resident cells in lymphoid tissues. These results suggest that shed membrane particles are one of the hallmarks of programmed cell death, of particular interest when the corresponding cells are hardly accessible.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1.

Chemokines are potent mediators of cell migration and activation and therefore play an essential role in early events of inflammation. In conjunction with cell adhesion molecules, chemokines help to localize cells to a specific site and enhance the inflammatory reaction at the site. Clinically, elevated levels of chemokines have been found in a variety of inflammatory diseases. The prototype C-C chemokine is monocyte chemoattractant protein-1 (MCP-1) which is synthesized by variety of cell types including endothelial cells in response to a variety of stimuli. MCP-1 is a major chemoattractant for monocytes, T lymphocytes, and basophils. In the present study, we investigated the factors involved in cytokine-induced MCP-1 gene expression in human endothelial cells. We present evidence that the nuclear factor (NF)-kappa B-like binding site and the AP-1 binding site located 90 and 68 base pairs upstream of the transcriptional start site, respectively, are required for maximal induction of the human MCP-1 promoter by interleukin-(IL)-1 beta. Site-directed mutagenesis or deletion of the NF-kappa B-like site decreased the cytokine-induced activity of the promoter. Site-directed mutagenesis of the AP-1 binding site also decreased the cytokine-induced activity of the promoter. We show that the NF-kappa B-like site located at-90 in the MCP-1 promoter binds to the p50/p65 heterodimer of the NF-kappa B/Rel family in IL-1 beta-stimulated human endothelial cells. Overexpression of p65 results in the transactivation of the MCP-1 promoter as well. The data presented in this study suggest that cytokine-induced MCP-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1.

Base Sequence↗
PubMed1997

[Lipomatosis induced by corticosteroid therapy].

Steroid-induced lipomatosis usually presents as a localized hypertrophy of the adipose tissue and seems more common than previously thought. Most patients develop this phenomenon after prolonged administration of moderate to high doses of oral corticosteroids. The localizations are numerous and determine the clinical presentation. Often asymptomatic, they can also be revealed by worrying symptoms usually due to a compressive syndrome. The most frequently reported localizations (spinal epidural, retro-orbital, mediastinal) are also the most clinically apparent. The cessation or reduction of steroid therapy, when medically possible, inconsistently results in the decrease or disappearance of the lipomatosis deposits. Computerized tomography or magnetic resonance imaging are the most helpful diagnostic means. Interestingly, these lipomatoses have rarely been reported in patients with Cushing disease. Their pathophysiology remains poorly elucidated and may imply an inhibition of the brown adipose tissue lipolysis.

Adult↗