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K Phadke

Publications and source records attributed to K Phadke.

At least 37 records · Page 2Linked to original sources
PubMed1986

Role of interleukin 1 and interleukin 2 in rat and mouse arthritis models.

The production of interleukin 1 (IL 1) and interleukin 2 (IL 2) by macrophages and lymphocytes from three animal models commonly used for rheumatoid arthritis, viz. adjuvant-induced and type II collagen-induced rat arthritis, and MRL/1 murine arthritis was studied. Although the peritoneal macrophages from adjuvant-arthritic rats in culture produced increased amounts of prostaglandin E2 (PGE2) and lower levels of IL 1 than the control group, cells from collagen-arthritic rats released normal levels of PGE2, but increased amounts of IL 1. After activation with lipopolysaccharides, the IL 1 production by macrophages from all groups was comparable. Addition of indomethacin did not significantly change the IL 1 production in any of these groups. In the absence of any exogenous mitogen, IL 2 production by the lymphocytes of adjuvant-arthritic rats was low, but could be restored to the normal levels when phytohemagglutinin A (PHA) or concanavalin A (Con A) was added. The lymphocytes from collagen-arthritic rats were capable of producing IL 2 without the need of any T cell mitogen. The lymphocytes from MRL/1 mice seemed to lack the functionality in terms of IL 2 production. The macrophagic IL 1 production in these animals was normal. Our data suggest that the type II collagen arthritis model may closely resemble human rheumatoid arthritis in which IL 1 and IL 2 production by the mononuclear cells is significantly enhanced.

Animals↗
PubMed1986

Characteristics of cellular immune responses to collagen type I or collagen type II.

We have examined the murine cell-mediated immune (CMI) response to collagens type I (CI) and type II (CII) as measured by in vivo delayed-type hypersensitivity responses. We have verified the histopathology and kinetics of the cell-mediated immune responses. Predominant cell-mediated responses were obtained 7, 10, or 14 days following immunization. A presumed antibody-mediated reaction was observed at later times (e.g., greater than 21 days following immunization). The CMI responses to the collagens show a strain-dependent relationship. For CI, the CMI response profile shows H-2b greater than or equal to H-2k = H-2q much greater than H-2d. For bovine CII, the response profile is H-2d greater than H-2b = H-2k = H-2q; the chick CII response profile is H-2q = H-2k greater than H-2b = H-2d, and in limited testing, only the H-2q strain could generate murine CII-specific cell-mediated immune responses. The CII-specific CMI response is cross-reactive with CII from several species of animals, but not with CI. Further, the collagen-specific CMI response can be elicited with certain cyanogen-bromide fragments of bovine CII. Finally, our study also demonstrates that there is a non-H-2-linked locus(i) involved in the development of CII-induced arthritis.

Animals↗
PubMed1985

Evaluation of the effects of various anti-arthritic drugs on type II collagen-induced mouse arthritis model.

A battery of drugs which are commonly used as therapeutic agents for arthritis was tested for effects on the inflammatory and immunological responses of DBA/1J mice, after immunization with type II collagen. All the drugs were tested at more than one dosage. The mice were protected from the development of arthritis by treatment with paramethasone (0.25 mg/kg/day) or cyclophosphamide (5 mg/kg/day). The nonsteroidal anti-inflammatory drugs used in these studies, viz. aspirin (200 mg/kg/day), benoxaprofen (100 mg/kg/day) and naproxen (200 mg/kg/day), had no significant effect on the joint involvement, although naproxen and benoxaprofen at these high doses caused some reduction of immune responses of mice to collagen. Chloroquine (100 mg/kg/day), levamisol (50 mg/kg/day) and gold chlorophosphene (5 mg/kg/day) had no effect on the inflammatory or humoral response, while treatment with D-penicillamine (100 mg/kg/day) led to an early onset of arthritis in mice. These data suggest that the type II collagen-induced mouse arthritis model may not be highly suitable for detection of the traditional nonsteroidal anti-inflammatory class of drugs or the anti-rheumatic drugs, although the possibility remains that some new and novel immunosuppressive agents may be detected with this model.

Adjuvants, Immunologic↗
PubMed1985

Renal lesions in sickle cell nephropathy in children.

Sickle cell nephropathy characterized by proteinuria and predominantly glomerular lesions has not been studied as extensively as renal tubular alterations in sickle cell disease. We reviewed our experience with this entity over a 14-year period. Of 13 children with either proteinuria or the nephrotic syndrome, 8 showed focal and segmental glomerulosclerosis, and 5 had mesangial proliferation. Children with focal and segmental glomerulosclerosis were older at onset of nephropathy and presented with the nephrotic syndrome more frequently than those with mesangial proliferation (p less than 0.05). All patients with mesangial proliferation and half of the focal and segmental glomerulosclerosis patients had supranormal renal clearances at onset of nephropathy suggesting hyperfiltration. Hyperfiltration seen in animals with reduced renal mass, and in human diabetic nephropathy before reduction in nephron units leads to mesangial proliferation and sclerosis. Our study suggests that sickle cell disease produces similar lesions in patients with sickle cell nephropathy.

Adolescent↗
PubMed1985

Efficacy of cyclophosphamide in steroid-sensitive childhood nephrotic syndrome with different morphological lesions.

We have reviewed the efficacy of cyclophosphamide in 39 steroid-sensitive frequently relapsing nephrotic children. Cyclophosphamide was used because of heavy steroid dependence and steroid toxicity. A percutaneous renal biopsy done prior to administration of cyclophosphamide showed the lesion to be minimal change in 7 children, IgM nephropathy in 17 children, and evolving from minimal change nephrotic syndrome to focal segmental sclerosis (FSGS) in 15 children. 100% of patients with minimal change nephrotic syndrome responded to cyclophosphamide, but only 58% of IgM patients responded (p less than 0.05). Only 1 of 15 FSGS patients responded (p less than 0.001 vs. minimal change nephrotic syndrome and p less than 0.01 vs. IgM). In view of the failure of cyclophosphamide to produce a remission in FSGS and its potential for long-term impairment of suppressor T cell function, we suggest that it should not be used in patients whose disease has evolved from minimal change to FSGS.

Child, Preschool↗
PubMed1984

Autoreactivity to collagen in a murine lupus model.

MRL/l mice exhibit many characteristics of human systemic lupus erythematosus including antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and II collagen. The levels of antibodies against native or denatured types I and II collagen in the sera of 4-5-month-old MRL/l mice are significantly higher than those in the sera of age-matched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1- or 2-month-old MRL/l mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type II collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/l mice.

Animals↗
PubMed1984

Collagen-induced and adjuvant-induced arthritis in rats. Post-immunization treatment with collagen to suppress or abrogate the arthritic response.

Immunization of Lewis rats with native type II collagen results in an inflammatory arthritis and increased humoral and cellular immune responses to type II collagen. The exposure of rats to native type II collagen at day 7 or 10 after immunization suppressed the incidence of arthritis and anticollagen antibody levels, although the cellular response was not affected. The exposure to denatured type II collagen offered partial protection, while type I collagen had no significant effect. Rats immunized with Mycobacterium tuberculosis also showed reduced arthritic response when subsequently treated with type II collagen. The common modalities between the 2 models and the possible role of type II collagen in the interference with the inflammatory arthritic events are discussed.

Animals↗
PubMed1984

Acute renal failure as the initial manifestation of systemic lupus erythematosus in children.

In two patients with systemic lupus erythematosus, acute renal failure was the initial manifestation. The diagnosis was eventually established on the basis of serologic tests and characteristic renal histopathologic findings. We emphasize the need to consider systemic lupus erythematosus as a cause of acute renal failure of glomerular origin, because appropriate therapy may alter the outcome of the disease.

Acute Kidney Injury↗
PubMed1983

Long-term evaluation of children with nephrotic syndrome and focal segmental glomerular sclerosis.

We studied the long-term outcome of a group of children with the nephrotic syndrome who showed the histological lesion of focal segmental glomerular sclerosis (FSGS) during the course of their illness. Of 25 such children studied, a complete follow-up ranging from 3 to 19 years was available in 24. Two distinct groups could be identified. Patients in the first group were characterized by steroid resistance (SR) from the onset, whereas those in the second group were initially steroid sensitive (SS), and had the histological lesion of minimal change which, over time, evolved into FSGS. SR patients had a mean age of 7.7 +/- 3.7 years compared to SS patients who were 3.5 +/- 2.5 years old (p less than 0.01). There were more females (11 of 14) in the SR group than in the SS group (3 of 10; p less than 0.02). The incidence of hematuria was higher in the SR patients (9 of 14) than SS patients (2 of 10; p less than 0.05). SR patients also exhibited a greater degree of growth retardation at the end of the follow-up period (9 of 13 compared to 1 of 8 SS patients; p less than 0.02). SR patients reached end-stage renal failure earlier (2.3 +/- 1.3 years) than SS patients (10 +/- 5.8 years; p less than 0.01) after the initial biopsy. Of the 13 kidney transplanted into 9 SR patients, recurrence of FSGS was noted in two allografts. Of the 4 kidneys transplanted into 2 SS patients, recurrence was seen in 1. The overall recurrence rate of FSGS in allografts was 17.6%. Our study suggests that the two varieties of FSGS occurring in nephrotic patients may be distinct nosologic entities rather than a single disease with varied manifestations.

Adolescent↗
PubMed1983

Familial focal segmental glomerulosclerosis.

We have observed the nephrotic syndrome in more than one sibling in three unrelated hispanic families. The histological lesion in the involved children was either focal segmental glomerulosclerosis or IgM nephropathy evolving into focal sclerosis. Tissue typing revealed the presence of HLA DRw8 in six out of eight patients. The frequency of this antigen in our patients, when compared with its frequency in a group of unrelated normal hispanic children was highly significant (p less than 0.0001). Our study suggests that there may be a genetic predilection towards developing focal segmental glomerulosclerosis.

Adolescent↗
PubMed1983

Secretion of chondrocyte stimulating factor by macrophages as a result of activation with collagen and proteoglycans.

In this study, we have investigated the role of extracellular matrix components of connective tissue, collagen and proteoglycans, in the activation of rabbit macrophages and articular chondrocytes. Addition of type II collagen, in native or denatured form, or proteoglycan subunits, led to the activation of macrophages and release of chondrocyte stimulating factor. Type I collagen, when used at higher concentrations, was also capable of macrophage activation. The conditioned media of activated macrophages induced an increased protease synthesis by chondrocytes. Collagen or proteoglycan subunits did not have any direct stimulatory effect on chondrocytes. Intraperitoneal injections of collagen induced infiltration of macrophages into the peritoneal cavity. Although these macrophages failed to produce significant levels of chondrocyte stimulating factor by themselves, they could be activated in culture with lipopolysaccharides or collagen to produce chondrocyte stimulating factor. The chondrocytes, treated with the conditioned medium of activated macrophages (with lipopolysaccharides or cartilage matrix components), failed to survive in suspension cultures.

Animals↗
PubMed1983

Regulation of metabolism of the chondrocytes in articular cartilage--an hypothesis.

Over a number of years, researchers in many laboratories have studied the changes occurring in an osteoarthritic joint. Most of these studies involved the biomechanical properties of the joint, biochemistry and physiology of cartilage as a whole tissue or at the cellular level. As the involvement of cartilage in the early stages of osteoarthritis is of focal nature, the results of these various studies have been conflicting. Until recently, the chondrocytes were not assigned a major role in the degradation of cartilage matrix. Instead, the matrix-destruction was believed to occur by mechanical attrition. In this paper we discuss the changes occurring in the osteoarthritic joint and provide an hypothesis for understanding the interactions between inflammatory cells and the chondrocytes, leading to an altered metabolism of chondrocytes and loss of cartilage structure.

Animals↗
PubMed1982

The "hot spleen" phenomenon in metastatic malignant melanoma: its incidence and relationship with the immune system.

Of patients with Stage II and III malignant melanoma, 34.7% display reversal of the liver-spleen ratio on technetium-99m-sulphur colloid isotope scans. Such an occurrence does not suggest a greater likelihood of relapse or a worse survival. The phenomenom is more common in female patients and there is a significant relationship between the presence of a "hot spleen" and a high IgM level. Patients with Stage II disease and high IgM levels have relapses more quickly than do those with normal IgM levels. Lymphopenia is common in patients with Stage II and III disease and the survival of these patients is worse than that of those with normal lymphocyte counts. In this report, the data are discussed together with results from other investigations, and a unifying hypothesis is presented which explains the phenomenon and relates it to increased activity of macrophages as a result of the presence of the tumor. The usefulness of isotope liver scanning in stage III malignant melanoma is also discussed.

Bacterial Vaccines↗
PubMed1982

Effects of various anti-inflammatory drugs on type II collagen-induced arthritis in rats.

The effects of some commonly used anti-inflammatory and anti-arthritic drugs on the inflammatory and immunological manifestations of type II collagen-induced arthritis in rats were studied. Among the anti-inflammatory drugs tested at a given dosage (mg/kg/day), benoxaprofen (10), aspirin (25) and indomethacin (3) inhibited the hind paw swelling and anti-type II collagen antibody formation in type II collagen-treated rats. Benoxaprofen also inhibited the delayed type hypersensitivity (DTH) response to type II collagen. Phenylbutazone (30) and fenoprofen (40) partially suppressed the paw swelling, but had no significant effect on humoral and cellular responses. Among the other anti-arthritic drugs, levamisol (25), chloroquine (25) and D-penicillamine significantly suppressed the paw swelling, anti-type II collagen antibody titres and DTH response. Gold chlorophosphene (10) and colchicine (3) had no effect on any of these three parameters. Paramethasone (0.1), cyclophosphamide (1) and azathioprine (10) were very effective when dosed daily, or once (at a different dose) 72 hr prior to immunization with type II collagen.

Animals↗
PubMed1982

Effects of benoxaprofen on the inflammatory, humoral and cellular components of type II collagen-induced arthritis in rats.

The effects of benoxaprofen and some other anti-inflammatory drugs on the inflammatory, cellular, and humoral components of type II collagen-induced arthritis in rats were studied. At the given dosage (mg/kg/day), benoxaprofen (10), aspirin (25), and indomethacin (3) inhibited the hindpaw swelling and development of anti-type II collagen antibodies in collagen-treated rats. Benoxaprofen also inhibited the delayed-type hypersensitivity response to collagen. Phenylbutazone (30) failed to show significant effect on these parameters. The treatment of rats with benoxaprofen throughout the test period or during days 14 to 28 was more effective than the treatment in the initial phases only.

Animals↗
PubMed1981

Platelet dysfunction in myeloproliferative syndromes.

The most common abnormality of the platelets in 43 patients with a variety of myeloproliferative syndromes was impaired or absent aggregation when stimulated with collagen and adrenaline. Eight unselected cases studied in more detail showed a normal prostaglandin synthesis pathway as evidenced by normal aggregation with arachidonic acid and the production of normal amounts of malonyldialdehyde. Mixing experiments with aspirin-tested platelets showed correction of the abnormal adrenaline and collagen responses and confirmed that the nature of the defect was different from that induced by aspirin. Stimulation of "myeloproliferative" platelets with thrombin after blocking the prostaglandin pathway with aspirin resulted in reduced aggregation, indicating either a deficiency of the storage pool of adenine nucleotides in the platelets or an abnormality of a membrane receptor for thrombin.

Aspirin↗
PubMed1981

Release of chondrocyte-stimulating factor by rabbit peritoneal macrophages.

Cultured rabbit peritoneal macrophages, after stimulation with lipopolysaccharides (LPS), produce a factor that induces normal rabbit articular cartilage cells (chondrocytes) to release collagenase and other neutral proteases in their culture medium. The release of the factor as well as the activation of chondrocytes can be significantly inhibited by paramethasone (10(-6) M). Rabbit peripheral blood monocytes produce this factor in smaller quantities. Activation with LPS does not enhance the release of factor any further by these cells. Lymphocytes have no direct effect on the chondrocytic protease synthesis. Furthermore, conditioned medium of activated lymphocytes failed to stimulate monocytes or macrophages in the absence of LPS. The macrophage medium exhibits mitogenic and phytohaemagglutinin-enhancing activity towards thymocytes of C3H/HeJ mice, but not against species-specific rabbit lymphocytes. The lymphocyte-activating factor, derived from a mouse macrophage cell line, P388D1 cells, or from other sources, was unable to stimulate chondrocytic protease secretion. Such specific induction of chondrocytic proteases by a macrophage-derived factor may have an important role in cartilage destruction in arthritic conditions, where synovium is only marginally involved.

Animals↗