PubMed Health⌕ Search

Biomedical subjects

R W Moskowitz

Publications and source records attributed to R W Moskowitz.

At least 19 recordsLinked to original sources
PubMed1992

Physicochemical properties of the aging and diabetic sand rat intervertebral disc.

Hydration, fixed charge density, (FCD) and hydration under various osmotic pressures were compared in young, old, and young diabetic sand rats. This rat is a desert animal that may develop diabetes when fed a regular diet; it is also known to have radiographic and histologic evidence of intervertebral disc (IVD) disease. Forty-five rats and 180 IVD were used in this study; they were divided into three equal groups: young healthy, old healthy, and young diabetics. IVD, cancellous bone, and muscle were sampled from distal lumbar spines. The young diabetic rats (YD) were considerably heavier than the age-matched controls, had higher insulin and glucose levels, and all YD had cataracts. The discs of the young diabetic animals demonstrated decreased hydration, FCD and ability to resist compression under osmotic pressures as compared with the young and healthy discs and were more similar to the discs from old rats. The IVD is the most affected musculoskeletal connective tissue in sand rats with aging and diabetes. The aged and diabetic discs in the sand rat demonstrated changes similar to human changes with regard to lower hydration, FCD, and ability to resist osmotic pressure. Therefore, the sand rat may be a suitable animal model for studying the pathogenesis of disc degeneration.

Aging↗
PubMed1991

Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides.

The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's tau-test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5-D-4 and 2-D-3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS-bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high-density proteoglycans. Electrophoresis of pooled high-density KS fractions in polyacrylamide-agarose gels followed by Western blotting with MAb 5-D-4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement.

Arthritis, Rheumatoid↗
PubMed1991

Cartilage expression of a type II collagen mutation in an inherited form of osteoarthritis associated with a mild chondrodysplasia.

In a family who expressed severe dominantly inherited osteoarthritis, the underlying mutation was traced by genomic sequencing to a single base change which predicts an amino acid substitution of cysteine for arginine at residue 519 of the triple-helical domain of the type II collagen molecule (Ala-Kokko, L., C. T. Baldwin, R. W. Moskowitz, and D. J. Prockop. 1990. Proc. Natl. Acad. Sci. USA. 87:6565-6568). In the present study we examined whether this predicted protein phenotype was evident in articular cartilage obtained from an affected family member who underwent hip surgery. The cartilage collagen was solubilized by CNBr digestion. Cysteine residues were labeled by reduction and alkylation with 14C-iodoacetate. Collagen CNBr-peptides were fractionated by ion exchange and reverse phase column chromatography. One peptide from the alpha 1(II) chain, alpha 1(II) CB8, was found to be radiolabeled. Tryptic peptides were prepared from it and identified by microsequence analysis. The results show that approximately one-quarter of the alpha 1(II) chains present in the polymeric extracellular collagen of the patient's cartilage contained the Arg519-to-Cys substitution. The protein exhibited other abnormal properties including disulfide-bonded alpha 1(II)-dimers and signs of posttranslational overmodification. The premature cartilage failure and osteoarthritis are presumably a result of the abnormal type II collagen being expressed in the cartilage matrix.

Amino Acid Sequence↗
PubMed1991

The effects of Rumalon, a glycosaminoglycan peptide complex, in a partial meniscectomy model of osteoarthritis in rabbits.

The effects of Rumalon, a glycosaminoglycan peptide complex (GP-C), were evaluated in a partial meniscectomy model of osteoarthritis (OA). When rabbits were treated with Rumalon, 0.25 ml/kg 3 times/week for 12 weeks after partial meniscectomy, the proportion of animals that developed cartilage ulceration was lower than that in untreated meniscectomized rabbits (p less than 0.05). At 6 weeks sacrifice, the same dose of Rumalon was associated with a trend toward reduction in the number of animals with ulcerations. Rumalon administered at a dose of 0.5 ml/kg for 12 weeks reduced the number of animals with ulcers, although not at the p less than 0.05 level of significance. Semiquantitative histologic evaluations revealed no differences between control and treatment groups either in the thickness of articular cartilage, density of cells present, safranin-O stain or ratio of DNA/protein. Increased proteoglycan synthesis characteristic of OA was modulated toward normal in association with Rumalon therapy. Diminished OA changes in response to Rumalon are consistent with an ameliorative response to this agent in the partial meniscectomy model in the rabbit.

Animals↗
PubMed1991

The role of growth factors in degenerative joint disorders.

It is postulated that osteoarthritis (OA) is associated with an imbalance between cytokine related cartilage degradation, and maintenance of proliferative and synthetic cell responses related to growth factor activity. Insulin, insulin-like growth factor (IGF-1) and growth hormone (GH) were evaluated and compared in patients with OA, and nonosteoarthritic controls. Serum levels of IGF-1 were diminished, and levels of insulin and growth hormone elevated compared to controls. In patients with diffuse idiopathic skeletal hyperostosis (DISH), serum levels of insulin and GH were elevated, but IGF-1 levels were normal. Our results suggest an interplay of growth peptides in the pathophysiology of these common disorders. The profile of growth peptide findings further distinguishes DISH from OA.

Adult↗
PubMed1990

Early-onset primary osteoarthritis and mild chondrodysplasia. Radiographic and pathologic studies with an analysis of cartilage proteoglycans.

Three generations of a nonconsanguineous family with premature onset of primary (idiopathic) osteoarthritis (OA) were studied for clues to the etiopathogenesis of their disorder. Articular symptoms began in their second and third decades of life and involved multiple joints, both typical and atypical for primary OA. Radiographs of the majority of involved peripheral joints showed abnormalities typical of primary OA. Evidence of chondrodysplasia was found in the spines. Pathologic examination of femoral heads obtained at total hip arthroplasty from 3 affected family members showed moderate to severe OA. Articular cartilage proteoglycans from these specimens were evaluated for aggregatability with hyaluronic acid, levels of chondroitin sulfate and keratan sulfate, and core protein structure. The results from each patient's specimen differed from the results of the other specimens. We conclude that this family's disorder, primary OA associated with a mild chondrodysplasia, was a late-onset overlap form of an epiphyseal dysplasia, that a defect common to hyaline articular and physeal cartilage was primary, and that a single structural proteoglycan abnormality was not likely to be the underlying cause.

Cartilage↗
PubMed1990

Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis.

This study defines gross, histopathologic, and radiologic changes associated with intervertebral disc degeneration in a spontaneously occurring form of the disease in aging sand rats (Psammomys obesus). Sand rats (male/female) fed lab chow supplemented with desert salt bush were sacrificed at periods of 3-30 months. Lateral thoracolumbar spine films were obtained. At sacrifice, spines were surgically exposed and gross findings were recorded; after fixation/decalcification, histopathologic studies were carried out using hematoxylin and eosin, and Safranin-O with fast green counterstain. Metabolic studies included correlations of pathologic and radiologic findings with blood glucose and insulin levels. Disc-space narrowing and subchondral endplate sclerosis increased radiologically with age, with more severe lower lumbar disc lesions. Ligamentous calcifications ventral to involved discs and caudal vertebrae were common. Disc thinning and anterior vertebral bony/cartilaginous spurs were more marked with age. Microscopy revealed loss of nucleus pulposus physaliform cells, chondrocyte replication, disc necrosis, and ossification. Hyperglycemia with and without hyperinsulinemia was common. No statistically significant differences in pathologic findings were noted, neither in diabetic versus nondiabetic nor in hyperinsulinemic animals. The sand rat is a model of disc degeneration; similarities with possible overlap with diffuse idiopathic skeletal hyperostosis syndrome were noted.

Aging↗
PubMed1990

Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondrodysplasia.

A cosmid clone was isolated that contained an allele for the type II procollagen gene previously shown to be coinherited with primary generalized osteoarthritis in a large family. Affected members of the family had evidence of a mild chondrodysplasia, but they developed progressive osteoarthritic changes in many joints that had no epiphyseal deformities. The clone contained 52 of the 54 exons of the gene. Nucleotide sequencing of greater than 20,000 base pairs from the clone demonstrated that all the coding sequences and all the intron-exon boundaries were normal except for a single base mutation that converted the codon for arginine at position 519 of the alpha 1(II) chain to a codon for cysteine, an amino acid not found in type II collagen from humans or a variety of other species. The mutation was found in all affected members of the family but not in unaffected members or in 57 unrelated individuals.

Alleles↗
PubMed1990

The relevance of animal models in osteoarthritis.

Studies of osteoarthritis (OA) in humans are restricted by the slow rate at which the disease progresses, and the limited opportunity for study of the tissue changes over time. A range of animal models of OA have been developed which demonstrate histopathological and gross features typical of OA in humans. Animal models can be used to study OA, and to investigate the effects of a variety of agents, including so-called chondroprotective agents, on the progression of the disease.

Animals↗
PubMed1990

Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone.

Alterations of cartilage and bone, as seen radiographically, are fundamental features of osteoarthritis (OA). Endogenous compounds that regulate bone and cartilage metabolism were quantified by radioimmunoassay in patients with OA and in suitable normotensive controls matched for age, sex, race, height, and weight. Levels of 3 growth promoting compounds were abnormal in OA as demonstrated by low levels of insulin-like growth factor-1 (IGF-1) and elevated levels of insulin and growth hormone (GH) compared to controls. Our findings support a role for these peptides in the pathophysiology of OA.

Adult↗
PubMed1989

Serum keratan sulfate levels in rabbits with experimentally induced osteoarthritis.

Serum keratan sulfate (KS) levels were measured with an enzyme-linked immunosorbent assay using monoclonal antibody (MAb) 5-D-4 (anti-KS) in a rabbit model of osteoarthritis (OA) induced by partial meniscectomy. The partial medial meniscectomy produced pathologic changes of OA in the joints of the rabbits, which were seen when the animals were killed at 3, 6, 9, or 12 weeks postsurgery. Tibial or femoral osteophytes were seen in up to 90% of the operated joints; pitting and ulceration of medial femoral condyles were also frequently noted (77% of cases). Rabbits that underwent sham surgery, back-skin-operated rabbits, or nonoperated normal rabbits served as controls; the joints of these animals were normal at the time of killing. A rise in the level of serum KS was recorded in 50% of rabbits following partial meniscectomy, but this was matched by similar changes in the control groups. The mean serum KS level of the OA animals at serial intervals (3, 6, 9, or 12 weeks) following surgery was not significantly different from that in the control groups. When measured with a second MAb, 2-D-3, KS levels showed similar trends as with MAb 5-D-4, although lower assay values were obtained. These findings indicate that experimentally induced OA in rabbits is not associated with a significant rise in serum KS levels. KS levels did not differentiate OA from non-OA animals, nor did they parallel disease progression.

Animals↗
PubMed1989

Problems in access to benefits and services among persons with rheumatoid arthritis.

This exploratory survey of 100 patients with rheumatoid arthritis (RA) was conducted (1) to learn about the types and frequencies of disability law-related problems encountered as a result of having RA, and (2) to assess the respective relationships between the number of disability law-related problems reported and the patients' sociodemographic and RA disease characteristics. The underlying concern of health care and legal professionals was that the often protracted exclusionary RA diagnostic process and the episodic nature of RA could make it more difficult to establish a precise clinical diagnosis and level of disability. Therefore, patients with RA would encounter difficulties in accessing entitlements and benefits provided under disability laws. The findings from this survey were used to develop a legal manual to empower health care professionals and people with arthritis to take litigative, legislative, social action, and self-help measures to redress the disability-law related problems.

Adolescent↗
PubMed1987

Primary osteoarthritis: epidemiology, clinical aspects, and general management.

The etiology of osteoarthritis, the most common articular disorder, is still unknown. Epidemiologic studies demonstrate a relationship to aging and to certain occupations; relationships to obesity as an etiologic factor remain controversial. An inverse relationship of osteoarthritis and bony density has been observed. Medical management is primarily symptomatic; surgery, particularly of the hip or knee, restores function and relieves pain at late stages of the disease. Investigational trials of specific therapeutic agents suggest possible forthcoming interventions to prevent, retard, or reverse the disease process.

Adult↗
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↗