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Biomedical subjects

R W Moskowitz

Publications and source records attributed to R W Moskowitz.

At least 73 records · Page 4Linked to original sources
PubMed1987

Correlates of community resource information needs of arthritis patients.

One hundred eighty-nine ambulatory arthritis patients were interviewed to assess needs for information about community resource services. Participants were asked how frequently they needed 66 specific information items. Three categories of resource needs in arthritis care were identified: general information, personal care and medical services, and assistive devices and equipment. In the first category, results indicated that the greater the impairment in functional ability, the greater the need for general information about arthritis. When functional ability was held constant, younger patients with lower family income displayed a greater need for arthritis resource information. Lower functional ability and family income were associated with a greater need for personal care and medical service information. Lower functional ability contributed the most to the need for information about assistive devices and equipment. We suggest that, as an essential component of the long-term care of patients with rheumatic diseases, individuals who provide educational counseling should clearly understand the community resource needs of patients, and should be able to match articulated needs with the existing services. Health professionals should be aware that certain patient characteristics (specifically, family income, functional ability, and age) are related to a need for this type of information. The large percentage of patients who could not name their rheumatic disease diagnosis (65%) presents a major concern and challenge to patient educators.

Activities of Daily Living↗
PubMed1987

Osteophyte evolution: studies in an experimental partial meniscectomy model.

Osteophytes are considered characteristic manifestations of osteoarthritis (OA) but may be seen independent of structural cartilage erosive lesions. Etiopathogenic mechanisms for osteophyte formation may involve responses to synovial inflammation, stretching of the synovial membrane, general mechanical instability, and vascular metaplasia. Experimentally induced OA following partial menisectomy in rabbits demonstrates active cellular replication at the normal joint periphery. Vascular responses are seen late in parallel with osteophyte formation rather than preceding it. Osteophyte ossification is primarily endochondral. The parallel stimulatory response to perichondrium, cartilage, and bone allows speculation on the interplay of mechanical/electrical forces and chemical/hormonal transducers in the development of osteophytes.

Adrenal Cortex Hormones↗
PubMed1987

Studies of osteophyte pathogenesis in experimentally induced osteoarthritis.

Osteophyte formation in a partial meniscectomy model of osteoarthritis (OA) in rabbits was studied. Serial sacrifices were performed at 1 day, 3 days, and 1, 4, 6, 8, 12 weeks in partial meniscectomy (15), nonoperated (14) and sham-operated (7) animals. H and E, safranin-O/fast green and toluidine blue stains were performed on coronal sections and pathologic findings correlated with 3H-thymidine autoradiography. Sham-operated and nonoperated control animals (similar findings) revealed grade 1 synovial/periosteal proliferation. Sixty percent of control animals exhibited small nubbin-like spurs at the medial tibial plateau. In partial meniscectomy animals, osteophytes occurred as early as 1 week, and in 7/9 (78%) animals after 4 weeks. Grade 2-4 synovial, perichondrial/periosteal thickening, cell proliferation and vascularity were seen. Soft tissue and bone responded in parallel. Results demonstrated normally high cellular activity at the joint periphery; vascular responses did not precede osteophyte formation.

Animals↗
PubMed1986

Analysis of osteoarthritic cartilage using monoclonal antibodies reactive with rabbit proteoglycan.

Femoral and tibial cartilage specimens from nonoperated, sham operated, and partially meniscectomized knees of New Zealand white rabbits were studied, using fluorescein-conjugated mouse IgG or 3 monoclonal antibodies (2G2, 2E9, and 6C9) that portrayed differing fine antigenic specificity for rabbit cartilage proteoglycan monomer. In nonoperated and sham operated animals, monoclonal antibodies 2G2 and 2E9 stained cellular/pericellular (C/PC) and matrix areas; antibody 6C9 stained only C/PC areas. Augmented C/PC and matrix staining of osteoarthritic femoral cartilage occurred with 2G2 and 6C9; tibial cartilage staining was reduced. Increased 2E9 staining of C/PC regions was seen in tibial cartilage. The differential staining patterns indicate that proteoglycan macromolecular changes occur in experimental osteoarthritis and that these monoclonal antibodies can be utilized as probes for the connective tissue changes observed.

Animals↗
PubMed1986

Estrogens and osteoarthritis.

Clinical and laboratory observations suggest that a relationship exists between sex hormones and the development of osteoarthritis. The mechanisms whereby these hormones influence the pathophysiology of osteoarthritis have been explored. Tamoxifen, an estrogen antagonist, reduced erosive changes in meniscectomy-induced osteoarthritis in rabbits. By contrast, estradiol worsened it. There was no effect of either agent on the incidence of osteophytes in this model. Both estradiol and tamoxifen affected proteoglycan, prostaglandin, and proteoglycanase production by cartilage components. These observations suggest that cartilage is a sex hormone-sensitive tissue. This may have therapeutic implications in the future.

Animals↗
PubMed1986

Immunofluorescent analysis of experimental osteoarthritic cartilage and synovium: evidence for selective deposition of immunoglobulin and complement in cartilaginous tissues.

Femoral and tibial cartilage as well as synovium derived from knees of nonoperated, sham-operated and partially meniscectomized NZW rabbits were studied using fluorescein conjugated goat IgG, goat antirabbit IgM, IgG and C3. Nonoperated and sham-operated animals revealed negative or minimal staining. Cartilaginous tissues from animals after partial meniscectomy showed uniform deposition of rabbit IgG and C3 in parallel at the surface; contralateral knees from these animals were negative for similar staining patterns. The data indicate that IgG and C3 deposition occurs in experimental secondary osteoarthritis and that immune complex deposition may contribute to the pathology of osteoarthritis.

Animals↗
PubMed1986

Efficacy of diflunisal versus naproxen in osteoarthritis of the knee: an open study.

Thirty-one patients with osteoarthritis of the knee were treated with either diflunisal (n = 17) or naproxen (n = 14) in a 12-week open-label study. Treatment was begun with 500 mg BID of diflunisal or 375 mg BID of naproxen. Patients not showing an adequate response to these dosages were given increases to 750 mg BID of diflunisal (n = 7) or 500 mg BID of naproxen (n = 8). Both drugs achieved statistically significant improvements in pain indices, tenderness, swelling, morning stiffness, functional capacity, knee flexion, and 50-foot walking time, and no significant difference was found between the two drugs. At the end of the study, all patients taking diflunisal and 11/14 patients taking naproxen felt that they had improved with treatment. Drug safety and tolerability were assessed in 21 patients given diflunisal and 16 given naproxen (including patients not part of the efficacy evaluation). Six (29%) patients in the diflunisal group and four (25%) in the naproxen group experienced side effects; three were withdrawn from the diflunisal group and one from the naproxen group because of adverse effects. In general, both drugs were well tolerated.

Adult↗
PubMed1985

Sustained-release indomethacin in the comprehensive management of osteoarthritis.

Osteoarthritis, although primarily a degenerative joint disease, may be associated with significant secondary inflammation. Hydrolytic enzymes result in primary cartilage degradation; secondary inflammation occurs in response to degenerative cartilage breakdown products and crystal deposition. Humoral and cell-mediated immune responses have been described. Analgesic and anti-inflammatory agents play a major role in symptomatic relief. Anti-inflammatory activity of the nonsteroidal anti-inflammatory drugs has been ascribed to prostaglandin synthesis inhibition; recent studies suggest additional effects based on inhibition of neutrophil aggregation, superoxide radical generation, and lysosomal enzyme release. Indomethacin, the first of the newer nonsteroidal anti-inflammatory drugs, has a long history of use and patient acceptance. Sustained-release indomethacin (Indocin SR), a 75 mg formulation equivalent to three consecutive doses of conventional indomethacin, adds ease of administration and potential for improved compliance. Nonsteroidal anti-inflammatory drugs, used in conjunction with other therapeutic approaches, provide the opportunity for response that can be gratifying for both patients and physicians.

Adrenal Cortex Hormones↗
PubMed1985

Fine specificity of serum anticollagen molecules in experimental immune synovitis.

Serum anticollagen antibodies to the native and denatured interstitial collagens were measured by solid phase radioimmunoassay (RIA) in a rabbit model of IgG-induced immune synovitis. Serum antibodies binding the native interstitial collagens and denatured type II collagen were observed in 100% of the animals tested (n = 6). Titerable antibodies to the alpha 1 (III) collagen polypeptide chain were observed in 83% of the animals, whereas serum antibodies to denatured type I collagen were observed in 33%. Inhibition studies showed that the observed serum anticollagen antibodies were conformationally dependent and collagen type specific. In addition these antibody populations varied in their affinities by as much as a factor of 2.81 for the specific substrates. Mean value of the average binding constants (Ka) for synovitis anticollagen antibodies binding native type II collagen was 5.47 X 10(6)mol; while the Ka determined for synovitis antibodies binding denatured type III collagen was 1.94 X 10(6)/mol. The data indicate that unique anticollagen antibody populations are expressed in the serum of animals with experimental IgG-induced chronic immune synovitis.

Animals↗
PubMed1985

Adoptive transfer of suppression of arthritis in the mouse model of collagen-induced arthritis. Evidence for a type II collagen-specific suppressor T cell.

This study details the suppressive mechanism involved in the antigen-specific suppression of collagen-induced arthritis. Intravenous injection of 500 micrograms of soluble native type II collagen 3 d before immunization with native type II collagen emulsified in complete Freund's adjuvant resulted in animals with decreased in vitro cellular and humoral immune response to native and denatured type II collagen compared with control groups. Control groups were composed of animals preinoculated with saline and type I collagen and established the antigen-specific nature of the observed suppression. Mice with reduced immune responses to type II collagen also were observed to portray little or no erythema and edema associated with collagen-induced arthritis. Adoptive transfer experiments established the requirement of T cells for the suppression of collagen-induced arthritis. Analysis of the phenotype of responding splenic cells in chronic immunotherapeutically suppressed mice in vitro revealed that responding cells were Ly1-2+ (suppressor/cytotoxic) T cells. On the other hand, the cellular phenotype of T cells responding to type II collagen in nonsuppressed collagen-induced arthritic mice was Ly1+2- (helper/inducer T cells). The data indicate that type II collagen-specific T cells are generated on intravenous inoculation of soluble native type II collagen. These cells are observed in type II collagen-immune animals, which are nonarthritic and portray reduced humoral and in vitro cellular immune response to type II collagen. This study suggests that specific suppression of immune responses to type II collagen by T-suppressor cells can be immunotherapeutic in certain forms of arthritis.

Animals↗
PubMed1985

Idiopathic adolescent scoliosis--a prototype of degenerative joint disease. The relation of biomechanic factors to osteophyte formation.

A study was performed to evaluate the presence of degenerative joint disease (DJD) in idiopathic adolescent scoliosis (IAS) and correlate DJD with biomechanic factors. The average age of the subjects was 19 years (range, 12-30). Osteophytes reflecting the presence of degenerative joint disease occurred in apophyseal and/or intervertebral joints of 74% of 100 subjects. Osteophytes were correlated with curve angle and apical rotation. Compression forces are of pathogenic significance in the localization of osteophytes in IAS. IAS can serve as a naturally occurring prototype for the study of the influence of biomechanic factors on the pathogenesis of DJD.

Adolescent↗
PubMed1984

Characterization of newly synthesized proteoglycans from rabbit menisci in organ culture.

Rabbit menisci were incubated with Na2 35SO4 in short-term organ culture to label newly synthesized proteoglycans. The radioactive products present in both tissue and culture medium were characterized separately with respect to distribution after ultracentrifugation in CsCl isopycnic density gradients, hydrodynamic size, interaction with hyaluronic acid, and glycosaminoglycan composition (types, size and content). Analysis of proteoglycan size by gel-filtration chromatography of the most-dense CsCl fractions (A1) on Sephacryl S-500 (associative conditions) resolved three species. A peak with Kav. approx. 0.7 was present in each chromatogram, and constituted the principal component in tissue extracts. Two other peaks with Kav. values of approx. 0.2 and 0.45 were also found. When the A1 fraction from tissue was subjected to CsCl-density-gradient ultracentrifugation under dissociative conditions, 71% of the recovered radioactivity was present in the most dense (A1D1) fraction. Incubation with hyaluronic acid of either A1 or A1D1 fraction from associative extract did not alter the apparent size of the labelled product, indicating a lack of aggregate formation. Meniscal proteoglycans showed an unusual and marked tendency to adsorb irreversibly to agarose and agarose-containing gel-filtration-chromatography media. High-pressure liquid-chromatographic analyses indicated that the sulphated glycosaminoglycans consisted of chondroitin 6-sulphate (72%), chondroitin 4-sulphate (19%) and dermatan sulphate (5%). Endo-beta-galactosidase (keratanase) digestion of the material failed to detect the presence of keratan sulphate. Of the labelled glycosaminoglycans, 95% was eluted from Sephacryl S-400 as a single symmetrical peak with a Kav. of 0.5. The results of studies with tissue extracts and culture medium were similar.

Animals↗
PubMed1984

Correlation of histopathology and sulfated proteoglycans in human osteoarthritic hip cartilage.

The histopathologic characteristics, in vitro proteoglycan and glycosaminoglycan biosynthesis, and proteoglycan content of osteoarthritic (OA) cartilage tissue types from human femoral heads obtained at the time of total joint replacement were compared. Articular cartilage from fibrillated or discolored cartilage surfaces demonstrated overlapping histopathologic patterns, while cartilage from osteophytic areas was distinct. 35SO4 from each of these three tissue types was found in two peaks of radioactivity on a Sepharose CL-2B column. The average partition coefficient (Kav) of the first peak (peak I) was 0.07, while that of the second (peak II) was 0.63. Proteoglycan monomer predominated in discolored, fibrillated, and osteophytic OA cartilage in peak I. The hydrodynamic size on Sepharose CL-2B of the synthetic proteoglycan monomer was the same for discolored, fibrillated, and osteophytic samples (Kav, 0.25-0.28). Discolored and fibrillated tissues showed a similar percentage of proteoglycan monomer in peak II, whereas osteophyte was reduced in proteoglycan monomer content in peak II. In addition, the endogenous proteoglycans extracted from each cartilage area were generally of a smaller hydrodynamic size than the newly synthesized peak I or proteoglycan monomer. Glycosaminoglycans were predominantly chondroitin 6-sulfate. These results indicated that OA discolored and fibrillated cartilage tissue types from defined topographical areas of human femoral heads possessed neither unique histopathologic nor synthetic or endogenous proteoglycan characteristics. Osteophytic cartilage appeared more histopathologically distinct than either discolored or fibrillated OA cartilage, but synthesized proteoglycan monomer with similar hydrodynamic size to the other cartilage tissue types.

Aged↗
PubMed1984

Immunoglobulin G-induced experimental chronic immune synovitis: cell-mediated immunity to native interstitial collagen molecules and their constituent polypeptide chains.

In vitro cell-mediated immune responses to homologous rabbit immunoglobulin G (IgG), purified protein derivative (PPD), native Type I, II, and III collagen, and denatured Type I, II, and III collagen were studied in an IgG-induced animal model of immune synovitis. Immune response was measured as augmented [3H]thymidine incorporation by spleen cells on exposure to antigen. Immune responses were observed in vitro after 72 hr of culture with antigen, while a majority of responses to antigens occurred after 96 hr of incubation. Separation of spleen cell subpopulations showed that measured immune responses were of T-cell origin. In vitro cell-mediated immune responses were observed for native and denatured collagen in splenic cell cultures from six of seven synovitic rabbits (P less than 0.01) but not in control spleen cell cultures derived from normal, adjuvant-primed or IgG-immune nonsynovitic rabbits. The incidence of cellular reactivity to incubation with native interstitial collagens was as follows: Type I, 43%; Type II, 43%; Type III, 57%. The incidence of in vitro immune responses to denatured collagens in cultures derived from rabbits with synovitis was: Type I, 50%; Type II, 50%; Type III, 67%. The relatively high incidence of immune response to both native and denatured collagens suggests that immunity to structural components of the synovial membrane and the adjacent surface of articular cartilage may play a role in the inflammation observed in immune synovitis.

Animals↗