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Biomedical subjects

M K Jasani

Publications and source records attributed to M K Jasani.

At least 19 recordsLinked to original sources
PubMed1995

Joint space width measures cartilage thickness in osteoarthritis of the knee: high resolution plain film and double contrast macroradiographic investigation.

OBJECTIVE: To test reliability of joint space width (JSW) measurements as a predictor of cartilage thickness in knees of patients with osteoarthritis (OA), using high definition microfocal radiography. METHOD: JSW was measured from weight bearing plain film macroradiographs taken in the tunnel view and compared with the sum of femoral and tibial cartilage thicknesses measured from double contrast macroarthrograms of the same regions of the same knees obtained in the non-weight bearing lateral position. RESULTS: All knees had medial compartment OA. Comparison of the JSW with the sum of the tibial and femoral cartilage thicknesses revealed a highly significant correlation (p < 0.0001) between the two measurements in the medial but not the lateral compartment. In the middle region of both compartments, JSW was smaller than the cartilage thickness, indicating that, on standing, the curvature of the femoral condyles compressed the cartilage in this region. CONCLUSIONS: JSW reliably measured cartilage thickness in the medial but not the lateral compartment of knees with medial compartment OA. Depending upon the stage of OA disease, JSW reliably reflects cartilage thinning and compression.

Adult↗
PubMed1995

Quantitative microfocal radiography detects changes in OA knee joint space width in patients in placebo controlled trial of NSAID therapy.

OBJECTIVE: To assess the usefulness of, and define the time course of changes in the features of osteoarthritic (OA) knees measurable using microfocal radiography, and to determine whether it differs in patients taking a nonsteroidal antiinflammatory drug (NSAID). METHODS: Forty-five patients with knee OA were randomly allocated to receive either diclofenac sodium or placebo for 18 months; 33 (17 NSAID, 16 placebo) completed the study. Clinical and 5 x high definition macroradiographic assessments of both knees in standing semiflexed views were carried out at 6-monthly intervals. Precise measurements were taken of the tibial and femoral subchondral thickness and osteophyte size, and of joint space width (JSW) across the narrowest part of the medial and lateral tibiofemoral compartments. RESULTS: In all knees as a group, there was no statistically significant difference in JSW between treatment groups. However, changes in JSW were significantly different (p < 0.04, multivariate analysis of variance) between treatments in 51 knees with early disease, i.e., those with initially > 50% JSW (22 active, 29 placebo), but not in 15 knees with severe disease, i.e., initially < 50% JSW (10 active, 5 placebo). During the study, osteophyte size in all knees and in those with > 50% JSW increased significantly (p < 0.016; p < 0.008) in the placebo group but remained unchanged in the treatment group. No significant changes were detected in subchondral cortical thickness. CONCLUSION: Using microfocal radiography the time course of changes in JSW and osteophyte size of knees with early, but not late OA, was found to differ in both pattern and magnitude in patients receiving NSAID: In knees with late stage OA the JSW progressively decreased irrespective of treatment. The observations may prove useful for the design of future therapeutic trials.

Adult↗
PubMed1994

Quantitative microfocal radiographic assessment of osteoarthritis of the knee from weight bearing tunnel and semiflexed standing views.

OBJECTIVE: Joint space width (JSW) in osteoarthritis (OA) knee radiography is reported to be optimally assessed from semiflexed standing and tunnel views although no detailed assessment of tunnel view radiography of OA knees has been done. The primary objective of our study was to determine the incidence of joint space narrowing (JSN) in semiflexed standing vs weight bearing tunnel views. The data were also analyzed to examined the degree and relationship of JSN and bony features of OA in the 2 views. METHODS: Ninety OA knees had macroradiographs at 5 times magnification taken in weight bearing standing semiflexed and weight bearing tunnel views. JSW and OA related bony features were measured and compared with reference values obtained from the knees of 14 healthy volunteers without arthritis. RESULTS: Comparison of JSW between the 2 radiographic views identified 3 locations of cartilage loss: JSN recorded in the tunnel only (22%), that in standing view only (8%), and that in both the views (30%). Subchondral sclerosis and osteophytes were significantly larger in 40% of OA knees despite a normal JSW. The tunnel view also enabled better visualization and measurement of osteophytes. CONCLUSION: Standing semiflexed view radiography alone failed to detect JSN in 22% of OA knees. Combined standing and tunnel radiographic views detected JSN more frequently than either view alone. Bony changes were radiographically evident without the presence of JSN indicative of cartilage thinning in as many as 40% of the patients with OA studied.

Aged↗
PubMed1993

Immunohistochemical localization of articular cartilage proteoglycan and link protein in situ using monoclonal antibodies and lectin-binding methods.

Lectins have specificity for certain carbohydrate structures in macromolecules. Lectins are, therefore, useful histochemical tools for demonstrating the composition and localization of components of connective tissue matrices, such as articular cartilage. In order to assess the significance of observed lectin-binding patterns, experiments were performed in which monoclonal antibodies against chondroitin sulphate- and keratan sulphate-containing proteoglycans and link proteins were applied to sections of bovine articular cartilage after enzymatic digestion with chondroitinase ABC and keratanase. The following conclusions were made: (1) Binding of peanut agglutinin (PNA) in the interterritorial matrix predominantly indicates the presence of keratan sulphate, but may also detect O-linked oligosaccharides of proteoglycans. (2) In normal cartilage wheat germ agglutinin (WGA) binds nearly exclusively to keratan sulphate. In cartilage degraded with chondroitinase ABC and keratanase this lectin may also detect carbohydrates in link protein due to enhanced accessibility. Binding of WGA to O-linked oligosaccharides may eventually occur. (3) In enzymatically digested cartilage matrix, staining with soybean agglutinin (SBA) may be due to link protein, but not to chondroitin sulphate, because specific breakdown of the glycosaminoglycan chain is required for binding of SBA. (4) Ulex europaeus agglutinin I (UEA I) binding sites are only detectable in digested cartilage matrix.

Animals↗
PubMed1993

A two-year, placebo-controlled trial of non-steroidal anti-inflammatory therapy in osteoarthritis of the knee joint.

Eighty-nine patients with established OA of the knee joint, already on regular NSAIDs for joint pain, were randomly allocated to receive 100 mg/day of slow release diclofenac (45 patients) or matching placebo (44), in place of their NSAID, for 2 years. Thirty-eight patients withdrew or dropped out of the study. The major causes for withdrawal were lack of efficacy (three active, 12 placebo, P < 0.01) or side effects (six active, five placebo), and most withdrawals occurred within the first 6 months. Long term follow up of these patients was not possible. Fifty-one patients completed the study (31 active, 20 placebo), 35 of whom reported that they were the same or better at the end of the 2-year period than at the beginning. Most of the recorded clinical parameters showed little or no change over 2 years in these 51 subjects, and in 70% there was no detectable change in the radiographs. We conclude that long term placebo-controlled trials are both feasible and ethical in knee OA, but that conventional clinical and radiographic techniques detect very little change in joint structure or function over a 2-year time period. This may reflect the insensitivity of the methods used to assess progression rather than absence of change. The fact that 20 of 44 patients changed from an NSAID to placebo completed the 2-year study without any symptomatic penalty indicates that not all patients entered needed or responded to NSAIDs.

Adult↗
PubMed1993

Chronic thromboxane synthase inhibition with CGS 12970 in human cyclosporine nephrotoxicity.

CsA nephrotoxicity in rats is associated with an increase in renal thromboxane production. Treatment with selective thromboxane synthase inhibitors or receptor antagonists improves renal function in these animal models. In humans, it is unclear whether intervention aimed at reducing the effects of thromboxane on the kidney will be clinically useful. However, we reported previously that thromboxane metabolite excretion is increased in CsA-treated renal allograft recipients with evidence of CsA toxicity and that 48-hr intravenous infusion of the selective thromboxane synthase inhibitor CGS 13080 improves renal function in such patients. We undertook the present study to determine the effect of more prolonged treatment with an oral thromboxane synthase inhibitor, CGS 12970, in renal transplant recipients taking CsA. We measured glomerular filtration rate and p-aminohippurate clearance before and after 4 weeks of treatment with CGS 12970 in 13 patients with renal allografts who had been treated with CsA for a mean 6.3 months and had mild renal insufficiency. Baseline serum creatinine was 1.8 +/- 0.3. Treatment with CGS 12970 resulted in 83% inhibition of urinary thromboxane B2 (TXB2), 93% inhibition of 2,3-dinor-TXB2, and 89% inhibition of 11-dehydro-TXB2, but no change in the urinary excretion of prostacyclin metabolites. However, suppression of urinary thromboxane metabolites to these levels did not significantly affect renal function. Glomerular filtration rate was 45 +/- 4 ml/min/1.73 m2 at baseline and 43 +/- 4 ml/min/1.73 m2 after 4 weeks of treatment with CGS 12970. Estimated renal plasma flow was 272 +/- 21 ml/min/1.73 m2 at baseline and 251 +/- 38 ml/min/1.73 m2 with thromboxane synthase inhibition. Thus, substantial suppression of thromboxane production with CGS 12970 did not improve renal function in CsA-treated renal allograft recipients.

Adult↗
PubMed1992

Chondrocytic monoamine oxidase activity in the development of natural murine osteoarthritis.

Most of the male STR/ORT mice develop osteoarthritis (OA) involving the medial tibial plateau. A peculiarity of two chondroprotective drugs is the presence of a nitrogen atom so that cleavage of the molecule could generate a molecule that might act as an inhibitor of monoamine oxidase (MAO). Direct examination showed abnormal localization of MAO in the potentially osteoarthritic cartilage indicating possible abnormal response to catecholamines. In normal cartilage, the direct effect of excessive concentration of adrenaline caused considerable oedema, as measured by microscopic interferometry. It is therefore suggested that the excess of water found in the matrix of osteoarthritic cartilage may be related to disturbance of the MAO activity.

Animals↗
PubMed1990

Changes in the orientation of proteoglycans during the early development of natural murine osteoarthritis.

At least 80% of male STR/ORT mice naturally develop osteoarthritis that predominantly affects the medial tibial cartilage. Overt osteoarthritic changes, as judged by radiological and histological abnormalities, become apparent after 30 weeks of age. Consequently, mice less than 30 weeks of age were used to investigate early changes in the cartilage matrix related to the natural development of osteoarthritis, without the need for experimental intervention to induce this condition. Quantitative Alcian blue staining showed little change in the total amount of proteoglycans in mice of this age. Polarized light microscopy of the birefringence induced by such staining demonstrated a progressive decline in the orientation of the proteoglycans in the medial cartilage of these mice. This decline was not found in CBA mice, which only very rarely develop osteoarthritis of this joint. Such progressive disorganization of the proteoglycans would be likely to permit the increase free water-content characteristic of osteoarthritic cartilage.

Aging↗
PubMed1989

Quantitative criteria for evaluating the early development of osteoarthritis and the effect of diclofenac sodium.

In assessing the possible efficacy of drugs for the treatment of osteoarthritis (OA), it may be helpful to have a model, in animals, of the early development of the disease prior to the expression of secondary phenomena. It is also necessary that such effects are quantifiable. To this end, the natural development of OA in the STR/ORT mouse has been investigated. It has been shown that very early events in the development of the disease are disturbances in the activity of chondrocytic glucose 6-phosphate dehydrogenase, the initial step in the pentose-phosphate pathway, and in the orientation of the proteoglycans of the matrix of the articular cartilage. The study has been done by reference to the effect of diclofenac sodium, which previously has been reported to retard the destruction of articular cartilage. The results appear to indicate that these markers may provide quantitative measures for assessing potential therapeutic agents.

Animals↗
PubMed1988

Dexamethasone modulated protein synthesis in polymorphonuclear leukocytes: response in rheumatoid arthritis.

Nine polypeptides whose rate of synthesis is modulated in polymorphonuclear leukocytes (PMNL) by dexamethasone were studied by 2-dimensional polyacrylamide gel electrophoresis. In each case, there was a time lag between addition of dexamethasone and the appearance of any change in rate of synthesis. In PMNL from a group of patients with rheumatoid arthritis, dexamethasone modulated the synthesis of the same polypeptides as in PMNL from a group of healthy volunteers, but the degree of response of their polypeptides to dexamethasone was significantly reduced as measured by assaying the level of synthesis of a polypeptide of molecular weight 16,000. Reduced responses of PMNL polypeptide synthesis to glucocorticoid may allow the development of rheumatoid inflammation despite apparently adequate levels of endogenous corticosteroids.

Arthritis, Rheumatoid↗
PubMed1988

Changes in oxidative activities of chondrocytes during the early development of natural murine osteoarthritis.

A high incidence of natural osteoarthritis of the knee joint is found in male mice of the STR/ORT strain. The condition affects mainly the medial tibial cartilage and by the age of 27 weeks most male mice of this strain show some osteoarthritic change. Analysis of the oxidative metabolism of the chondrocytes during the development of the lesion has been facilitated by the techniques of quantitative cytochemistry. The activity of glucose-6-phosphate dehydrogenase (G6PD) has been investigated as indicative of the NADPH-generating pentose-phosphate pathway; the activities of glyceraldehyde-3-phosphate (G3PD) and lactate dehydrogenase (LDH) have been studied as indicators of glycolytic activity. In young STR/ORT mice the G6PD activity of the lateral tibial cartilage was greater and more variable than in the control mice of the CBA/HT6 strain. The activity in the medial cartilage, relative to that in the lateral cartilage, decreased with age; this change was not reflected in the activities of the other enzymes. In the lateral cartilage, the expected relationship was found between the G6PD and the G3PD activities and between the LDH and the G3PD activities. In the medial cartilage, the G6PD activities were not related to the G3PD activities. The decreased proportionality of the G6PD activities in the medial cartilage as against that in the lateral cartilage was detected in mice as young as 9 weeks; by 27 weeks of age nine of the 13 mice showed marked depression of medial as against lateral G6PD activities. In contrast, only four of the 13 mice showed any overt histological charge until up to the age of 28 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The effects of immunosuppression and anticoagulation on fibrin deposition and swelling in rat cardiac allografts.

Rat cardiac allograft recipients were injected with radiolabeled human fibrinogen at intervals after transplantation. There was a progressive increase in tracer accumulation within graft ventricles, peaking at the time of rejection at about 30-fold that within syngeneic grafts. Protein extraction experiments indicated that ca. 90% of tracer was present as cross-linked fibrin at the time of rejection. Exudation within rejecting allografts was nearly threefold that in syngeneic grafts. The weight of allografts at different times after transplantation increased in close concordance with fibrin deposition. Pharmacologically immunosuppressed recipients showed negligible fibrin deposition and swelling whereas "B" rats and thoracic-duct-lymph-drained recipients showed moderate allograft swelling in the absence of significant fibrin deposition or rejection. The decreased fibrin deposition was not a result of depressed plasma clotting factor levels. B rats reconstituted with thoracic duct lymphocytes still had reduced allograft fibrin deposition in the presence of normal amounts of swelling and exudation. The anticoagulants warfarin and heparin greatly decreased allograft fibrin but were almost without effect on allograft swelling, exudation, and rejection. The possible participation of infiltrating macrophages in allograft fibrin deposition is discussed. Unlike cutaneous delayed hypersensitivity reactions, normal amounts of fibrin deposition appear not to be essential for full cardiac allograft rejection.

Animals↗
PubMed1987

The ex vivo measurement of malondialdehyde and chemiluminescence as possible indices for anti-inflammatory drug evaluation.

A well-established model of foot-pad oedema in the rat, an example of a cell-mediated hypersensitivity reaction, was used in this study. Male rats were immunized on day 0 with Freund's complete adjuvant (FCA) and then challenged 6 days later with FCA in one hind paw. Within 4 h of the initiation of this acute inflammatory reaction, the presence of free radicals was detected as luminol-amplified chemiluminescence (LAC) directly from the inflamed paws. In addition, an increase in malondialdehyde (MDA), an end product of lipid peroxidation, was measured in both inflamed tissue and plasma. Groups of animals were treated with either diclofenac sodium, indomethacin, piroxicam or prednisolone either 1 h before or 6 h after challenge, oedema, LAC and MDA being measured at various times after challenge. The three non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone, given 1 h before challenge, significantly inhibited LAC and plasma MDA levels at 4 h post challenge. When given 6 h after challenge all drugs significantly inhibited oedema at 24 h. Furthermore, all the drugs inhibited tissue MDA and LAC but only indomethacin and piroxicam reached significance. The data suggest a role for lipid peroxidation and free-radical generation in inflammation and provide possible indices for in vivo drug activity and evaluation.

Animals↗
PubMed1985

Quantification of lymphocyte activation by measurement of DNA polymerase alpha activity.

Measurement of the activity of the enzyme DNA polymerase alpha has been investigated with regard to its potential usefulness as a method for the detection and quantification of lymphocyte activation in vivo. A modified enzyme assay was developed in order to optimise measurement of activity in crude homogenates of cells or tissues, thus allowing the convenient handling of multiple samples. Specificity of the assay for polymerase alpha was ensured by the inclusion in the assay mixture of dideoxythymidine triphosphate, an inhibitor of the other eukaryotic DNA polymerases. The activity of DNA polymerase alpha was found to be closely correlated with [3H]thymidine incorporation in a mitogen-stimulated in vitro system. The usefulness of the polymerase alpha method for the quantification of lymphocyte activation was validated in 3 different in vivo systems of either immune-mediated or drug-induced lymphoid cell response.

Animals↗
PubMed1985

Effect of dexamethasone on polypeptides synthesised in polymorphonuclear leucocytes.

The effect of a glucocorticoid on protein synthesis in human polymorphonuclear leucocytes (PMNLs) was investigated by two-dimensional gel electrophoresis. In the peripheral blood PMNLs of healthy laboratory personnel, the rate of incorporation of L-[35S]methionine into a least nine polypeptides was consistently influenced by dexamethasone in a dose-dependent manner, being increased in the case of seven polypeptides and decreased in the remainder.

Blood Proteins↗
PubMed1985

An improved method for the demonstration of fibrin in biopsies of rabbit skin homografts.

Tissues embedded in resin are convenient for routine use when the presence or absence of fibrin in them is to be confirmed using the electron microscope. To visualize fibrin using the light microscope, sections (1.0-2.0 micron) from such specimens should be stained with Methylene Blue-Azure II-Basic Fuchsin (MBBF). Staining with MBBF is more controllable than with other methods and it requires only two short staining steps. Compared with Giemsa, MBBF provides a polychromatic, as opposed to a monochromatic end-result, sharply contrasting fibrin (blue) against collagen (pink-violet).

Animals↗
PubMed1984

Characteristics of spontaneously proliferating mononuclear cells in rheumatoid arthritis.

The phenomenon of increased spontaneous incorporation of 3H-thymidine (3H-TdR) into peripheral blood mononuclear cells in rheumatoid arthritis (RA) has been investigated. The activity was found to be short lived and affected less than 1% of cells. Using a Percoll density gradient we identified two populations of active cells. RA patients with active synovitis and increased 3H-TdR incorporation in the low density population of cells have higher overall 3H-TdR incorporation than normal controls and patients with inactive RA. The low density cell population is enriched for Ia+ cells. The data are consistent with raised spontaneous 3H-TdR incorporation being due to an in-vivo cell mediated immune response.

Arthritis, Rheumatoid↗