Search PubMed⌕ Search

Biomedical subjects

D Mosher

Publications and source records attributed to D Mosher.

At least 19 recordsLinked to original sources

Efficacy of sacroiliac corticosteroid injections in patients with inflammatory spondyloarthropathy: results of a 6 month controlled study.

OBJECTIVE: To evaluate changes in articular symptoms, spinal mobility, and global function over 6 months after intraarticular injections of long acting corticosteroid into the sacroiliac (SI) joints of patients with inflammatory low back pain (ILBP). METHODS: Nineteen patients with symptoms of ILBP were studied. Thirteen (68%) had radiographic evidence of sacroiliitis. The remaining 6 patients (32%) had normal imaging studies and thus were considered to have mechanical low back pain. All patients received bilateral SI joint injections of triamcinolone hexacetonide (40 mg/joint) under computer tomographic guidance. Outcome variables included the duration of low back morning stiffness, back pain (by visual analog scale, McGill Pain Questionnaire), spinal mobility (chest expansion, Schober test, 10 cm segments test, finger-fibula distance), and self-report health status (SF-36). RESULTS: Both groups of patients showed a transient improvement in stiffness and pain, spinal mobility, and general health status that was most pronounced at 1-3 months after intraarticular therapy. This did not reach statistical significance (p > 0.05) and by 6 months, followup all outcome variables had reverted to pretherapy levels in both groups. CONCLUSION: These preliminary observations suggest that SI corticosteroid injections are ineffective in the management of patients with inflammatory spondyloarthropathy.

Administration, Topical↗

Transient effusive-constrictive pericarditis due to chemotherapy.

Commonly used chemotherapeutic agents, specifically cytarabine and daunorubicin, can cause effusive-constrictive pericarditis. We describe a case of transient effusive-constrictive pericarditis in a patient with acute myelogenous leukemia. This is the first case report of a patient with transient effusive-constrictive pericarditis due to chemotherapy.

Antibiotics, Antineoplastic↗

Fibronectin fibrils and growth factors stimulate anchorage-independent growth of a murine mammary carcinoma.

Stromal cells are important regulators of mammary carcinoma growth and metastasis. We have previously shown that a 3T3-L1 adipocyte cell line secretes hepatocyte growth factor (HGF), which stimulates proliferation of a murine mammary carcinoma (SP1) in monolayer cultures (DNA Cell Biol. 13, 1189-1897, 1994). We now examine the role of growth factors and the extracellular matrix protein fibronectin in stimulation of anchorage-independent growth of SP1 cells. Purified transforming growth factor-beta (TGF-beta) stimulated significant colony growth in soft agar cultures, whereas HGF had a lesser effect. Analysis by confocal microscopy revealed that carcinoma cell colonies contained extracellular microfibrils composed of fibronectin. Partial depletion of fibronectin from 7% FBS/agar cultures reduced the number of colonies; colony growth could be recovered by adding back exogenous fibronectin. Addition of the 70-kDa N-terminal fragment of fibronectin, which inhibits fibronectin fibril formation, reduced growth of SP1 cell colonies, but an 85-kDa fragment containing the cell binding domain did not inhibit colony growth. These findings indicate that deposition of extracellular fibronectin fibrils is necessary, but not sufficient, for anchorage-independent growth of SP1 mammary carcinoma cells; growth factors are also required. SP1 cells had less fibronectin mRNA and secreted less fibronectin protein under anchorage-independent conditions than under anchorage-dependent conditions, as determined by Northern blotting and immunoprecipitation analysis. Thus, both growth factors (HGF and TGF-beta) and fibronectin may be important regulators of paracrine stimulation by stromal cells of anchorage-independent growth of mammary carcinoma cells.

3T3 Cells↗

Tissue transglutaminase and factor XIII in cartilage and bone remodeling.

While it is well established that factor XIII functions in crosslinking of the fibrin clot during blood coagulation and in wound healing, the physiological role of tissue transglutaminase is still unclear. Recent studies suggest that the expression of tissue transglutaminase correlates with (terminal) differentiation of cells and that the enzyme may play a role in extracellular matrix remodeling. In cartilage, tissue transglutaminase expression is restricted to hypertrophic chondrocytes and the enzyme is externalized at a distinct step in the chondrocyte maturation program. Upon activation by Ca2+, the transglutaminase modifies matrix constituents in a way that might predispose the matrix for the subsequent mineralization. Crosslinks of the structure gamma-glutamyl-epsilon-lysine are also abundant in bone matrix, but the transglutaminase expressed by osteoblasts and presumably involved in crosslinking of newly formed osteoid is likely to be distinct from both tissue transglutaminase and factor XIII. Matrix proteins thought to be crosslinked by transglutaminases in cartilage and bone matrix include glycoproteins such as osteonectin, osteopontin, fibronectin, fibrillin, and collagens II, III, V, and XI. Expression of the A subunit of factor XIII is restricted to megakaryocytes in the bone marrow cavity, and factor XIIIa is abundant in platelets that probably provide the major source for factor XIII in plasma.

Animals↗

Self-assessment of disease activity by patients with rheumatoid arthritis.

OBJECTIVE: To determine the reliability of self-assessment of disease by patients with rheumatoid arthritis (RA), with a particular emphasis on the assessment of articular swelling. METHODS: A questionnaire was developed using components from validated instruments. Information was obtained on global function, global joint tenderness/swelling, and joint pain (10 cm visual analog scales), duration of musculoskeletal morning stiffness (grade 1-6), ACR functional score (grade 1-4), tender joint count (0-20), tender joint score (0-60), swollen joint count (0-20), and swollen joint score (0-60). Data were collected prospectively on 61 patients with RA in a teaching clinic or office practice by 4 staff rheumatologists. Patient questionnaires were completed within 24 h before physician assessments. Followup assessments were carried out on 27 patients after a mean interval of 3 months (range 0.5-6). RESULTS: At the initial assessment there was a significant correlation between patient and physician assessments for global function (r = 0.83; p = 0.01) [intraclass correlation coefficient (ICC) = 0.83; p < 0.01], global joint tenderness/swelling (r = 0.83; p < 0.01) (ICC = 0.83; p < 0.01), global joint pain (r = 0.83; p < 0.01) (ICC = 0.81; p < 0.01), duration of morning stiffness (r = 0.83; p < 0.01) (ICC = 0.85; p < 0.01), ACR functional score (r = 0.61; p < 0.01) (ICC = 0.62; p < 0.01), tender joint count (r = 0.57; p < 0.01) (ICC = 0.31; p < 0.01), and tender joint score (r = 0.60; p < 0.01) (ICC = 0.35; p < 0.01). However, there was poor correlation between patient and physician assessments for both swollen joint count (r = 0.16; p > 0.05) (ICC = -0.02; p > 0.05) and swollen joint score (r = 0.24; p > 0.05) (ICC = 0.12; p > 0.05). Longitudinal analysis indicated significant correlation between changes in patient and physician assessments in all variables except swollen joint count and score. CONCLUSION: Although there was good correlation between most variables for patient and physician assessments of disease activity in RA, there were substantial differences in the assessment of joint swelling. This objective determinant of disease activity cannot be ascertained in self-report measures of health status.

Adult↗

Magnetic resonance imaging in the detection of sacroiliitis.

The value of magnetic resonance imaging (MRI) in establishing the diagnosis of sacroiliitis was studied in 20 patients with established or suspected disease on conventional radiographs and in 10 healthy subjects. Coronal T1 weighted, axial T2 weighted and proton density MRI images of the sacroiliac joints in addition to plain film radiographs were obtained. All films were graded from 0 to 4 according to the modified New York criteria and independently for changes in joint width, erosions, sclerosis and ankylosis. Using the modified New York criteria, more abnormalities were detected by MRI than by conventional radiography (p = 0.04). This was due to the detection of definite abnormalities (grades 2-4) by MRI in joints that were graded normal or suspicious (grades 0-1) on plain films (p = 0.01). MRI tended to be superior to plain films in visualizing erosions. Only MRI detected abnormalities of articular cartilage (19 patients) and in subchondral bone marrow (7 patients). The latter 2 types represented fatty infiltration and inflammatory change. Intraobserver and interobserver variation were similar for the interpretation of MRI scans and plain film radiographs. These results suggest that MRI detects changes of established sacroilitis. Due to its ability to directly image articular cartilage it may be particularly useful in patients with early disease.

Adult↗

Sequence location of a putative transglutaminase cross-linking site in human vitronectin.

We attempted to locate the glutamine residue in human vitronectin, susceptible to cross-linking by transglutaminases. Vitronectin was incubated with 14C-labelled putrescine and plasma factor XIIIa and, after reduction and alkylation, the vitronectin was digested with trypsin. HPLC of the digest followed by scintillation counting revealed one major and two minor radioactivity labelled peaks. Sub-digestion with Staphylococcus aureus protease, sequence analysis and mass-spectrometry of the resulting peptides demonstrated that Gln-93 of vitronectin had incorporated putrescine. Additionally, Gln-73, Gln-84 and Gln-86 were found to be minor sites for incorporation.

Amino Acid Sequence↗

Activation and complexation of protein C and cleavage and decrease of protein S in plasma of patients with intravascular coagulation.

Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C antigen in APC:inhibitor complexes, indicating that protein C activation and inhibition had occurred. In 24 normal plasmas, no detectable APC:PCI complexes were observed (less than 5%). Patients with higher levels of complexes had more abnormal coagulation test data for DIC. The major band of APC complexes detected by anti-protein C antibodies did not react with antibodies to the heparin-dependent protein C inhibitor (PCI-1) previously described. Rather, APC was complexed with another recently described plasma protein C inhibitor, PCI-2. Immunoblotting studies for protein S, the cofactor for APC, revealed that the majority of the DIC patient plasmas contained a higher than normal proportion of protein S in cleaved form, suggesting that protein S may have been proteolytically inactivated. Protein S total antigen levels were also found to be low in DIC patients, excluding those with malignancy. These studies support the hypothesis that the protein C pathway is activated during DIC.

Blood Coagulation Tests↗

Effects on mood of a life-styles program for the rehabilitation of injured workers.

This study reports an examination into the effects on daily mood of participation in a life-styles program by injured workers. In the current prospective study, 14 participants completed the Memorial University Mood Scale (MUMS) prior to starting the program, at 1 month, 2 months, and at 3 months. They also completed the Memorial University Scale of Happiness (MUNSH) prior to entry and after three months. There were significant improvements on the MUMS subscales of positive mood and vigor as well as overall mood. There were no changes in negative mood. Neither the positive nor the negative dispositional subscales of the MUNSH revealed any change. The results were interpreted as indicating strong psychologic benefits of the life-styles program for injured workers and are also consistent with a recently proposed two-factor state/trait model of well-being.

Adult↗

Plasma fibronectin concentration in animal models of sepsis and endotoxemia.

Plasma fibronectin is a nonspecific opsonin which mediates phagocytosis of particulate matter by macrophages. Fibronectin depletion results in depression of reticuloendothelial system phagocytic function. This may potentiate microvascular embolization and sludging in critical illness. It has been hypothesized that sepsis is a major cause of fibronectin depletion. To explore this hypothesis, plasma fibronectin concentrations were measured in rats with intraabdominal abscesses and in rabbits subjected to the generalized Shwartzman reaction (spaced doses of endotoxin). In both groups of animals there was a significant increase (P less than 0.05) rather than decrease in fibronectin concentrations at times when sepsis and disseminated intravascular coagulation were manifest. This study does not support the hypothesized relationship between sepsis and fibronectin depletion. Until the kinetics of fibronectin production and utilization are further delineated, caution must be exercised in the interpretation of immunoreactive plasma fibronectin levels.

Abdomen↗

Coagulation and complement studies in Rocky Mountain spotted fever.

A patient with laboratory-acquired Rocky Mountain spotted fever (RMSF) and concomitant influenza virus infection was studied from the third day of clinical illness. The course of his illness was marked by petechial rash, thrombocytopenia, and elevation of fibrin split products. No evidence of complement activation was observed. Plasma proteins were elevated in a pattern characteristic of the "acute phase reaction." The patient recovered completely, and vascular collapse or clinically important disseminated intravascular coagulation had developed. In febrile patients who had influenza or a clinically similar noninfluenzal respiratory syndrome, no changes in coagulation, complement, or plasma proteins developed. We conclude that aberrations in the patient's laboratory values reflected RMSF, and that complement played no critical role in his illness.

Blood Coagulation↗

Cultured human monocytes synthesize and secrete alpha2-macroglobulin.

alpha2-Macroglobulin levels in the supernates of cultures of different subpopulations of human peripheral blood mononuclear leukocytes were assayed by a radioimmunoassay. Unfractionated mononuclear leukocytes produced greater amounts of the macroglobulin (4.0 vs. 0.8 ng/10(6) cells) than did subpopulations enriched in T or B+T lymphocytes, by passage through nylon wool or cotton wool columns, respectively. Still higher concentrations of alpha2-macroglobulin (40 ng/10(6) cells) were measured in the supernates of glass-adherent mononuclear leukocyte cultures. These results suggest that cells of monocyte-macrophage lineage are mainly, if not exclusively, responsible for the appearance of alpha2- macroglobulin in the supernate of human peripheral blood leukocyte cultures. The de novo synthesis and release of alpha2-macroglobulin by cultured monocytes was demonstrated by immunoprecipitation of radioactivity from supernates of 32S-methionine-labeled glass-adherent cells. Antiserum against purified alpha2-macroglobulin was used in both Ouchterlony double diffusion and double antibody precipitation tests. SDS-polyacrylamide gel electrophoresis of immunoprecipitates showed that most of the radioactivity comigrated with authentic alpha2-macroglobulin subunit at about 160,000 daltons.

B-Lymphocytes↗