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Biomedical subjects

R A Kandel

Publications and source records attributed to R A Kandel.

49 records · Page 3Linked to original sources
PubMed1991

Interleukin 1 induces the expression of a heat-shock gene in chondrocytes.

The presence of T cells and antibodies reactive with heat-shock proteins (hsps) in the joints of patients with rheumatoid arthritis may indicate a role of hsps in this disease. In the present study we examined whether increased temperature and interleukin 1 (IL 1), both of which are elevated in arthritic joints, induced the expression of two hsp70 genes in bovine chondrocyte cultures. We found that heat shock resulted in increased expression of constitutive and inducible hsp70 mRNA species. IL 1 and phorbol 12-myristate 13-acetate (PMA) also induced an increase in the constitutive hsp70 mRNA species, but without affecting the expression of the inducible hsp70 gene. The increase induced by IL 1 was observed only after 3 h, whereas increases induced by PMA were observed within 1 h. For all treatments, the hsp70 mRNA decreased by 24 h. Heat treatment of chondrocytes did not affect levels of collagenase and caseinase activity in the medium, nor did it alter proteoglycan synthesis by these cells.

Animals↗
PubMed1990

Inverse correlation between tyrosine phosphorylation and collagenase production in chondrocytes.

Collagenase production by chondrocytes appears to play a major role in the development of osteoarthritis. Although the mechanisms regulating collagenase production by chondrocytes are not known, incubation of bovine chondrocytes in serum markedly decreases collagenase production. Since serum has been demonstrated to increase levels of phosphotyrosine (P-Tyr) in several cell types, we determined the effect of altering intracellular levels of P-Tyr on collagenase production. Both orthovanadate, a potent inhibitor of tyrosine phosphatases, and serum caused a marked increase in tyrosine phosphorylation. The increase in P-Tyr was associated with a decrease in the production of collagenase, suggesting that two processes may be linked. Orthovanadate caused an increase in P-Tyr in the absence of serum, suggesting that P-Tyr levels in resting chondrocytes are regulated through activity of both tyrosine kinases and phosphatases. Orthovanadate and serum induced a synergistic increase in P-Tyr levels, suggesting that serum functions through increasing kinase activity rather than decreasing phosphatase activity. In the absence of serum, concentrations of orthovanadate which maximally inhibited collagenase production primarily increased phosphorylation of a 36 kDa protein, suggesting that the phosphorylation of this protein may play a major role in regulating collagenase production. Orthovanadate had limited effects on chondrocyte proteoglycan synthesis, morphology or viability in the presence or absence of serum, suggesting that the decrease in collagenase production was not due to non-specific inhibition of protein synthesis or cellular toxicity. Inhibition of tyrosine phosphatases by orthovanadate or activation of tyrosine kinases by addition of serum correlated with the inhibition of collagenase production.

Animals↗
PubMed1990

Fetal bovine serum inhibits chondrocyte collagenase production: interleukin 1 reverses this effect.

Bovine articular chondrocytes incubated in medium which was serum free or contained low levels of fetal bovine serum (less than 5%) constitutively produced collagenase. Increasing the concentration of serum in the culture medium inhibited the production of collagenase. Addition of interleukin 1 and lipopolysaccharide reversed the inhibitory effect of serum. Phorbol esters only stimulated collagenase production when the serum concentration was at least 10%. These data suggest that there is a factor(s) in fetal bovine serum that inhibits collagenase production by chondrocytes and this can be reversed by agents such as interleukin 1.

Animals↗
PubMed1990

Comparison of the effect of interleukin 6 and interleukin 1 on collagenase and proteoglycan production by chondrocytes.

In order to determine whether interleukin 6 (IL-6) is involved in the pathogenesis of the cartilage destruction observed in arthritis, the effect of human recombinant IL-6 on collagenase production and proteoglycan synthesis by bovine articular chondrocytes was examined. Addition of IL-6 (1.0 to 1000 U/ml) to the culture medium did not stimulate collagenase production or alter proteoglycan secretion. Whereas human purified interleukin 1 (IL-1) (20 U/ml) stimulated collagenase production and inhibited proteoglycan synthesis. Furthermore addition of IL-1 (20 U/ml) to chondrocyte cultures did not stimulate the chondrocytes to produce IL-6. Under our experimental conditions, IL-6 did not stimulate chondrocytes to proliferate as measured by [3H] thymidine incorporation. This would suggest that IL-6 is not involved in mediating cartilage loss.

Animals↗
PubMed1987

The stimulation of collagenase production in rabbit articular chondrocytes by interleukin-1 is increased by collagens.

Osteoarthritis is characterized by a loss of articular cartilage due at least in part to the action of degradative enzymes secreted by chondrocytes. We have investigated the effect of type II collagen from cartilage and interleukin 1 on collagenase production in cultures of rabbit articular chondrocytes. Interleukin 1 alone stimulated the chondrocytes to secrete collagenase but this response was increased as much as fivefold by the addition of rabbit type II collagen. Bovine type II and chick type I collagens were also stimulatory. The native form of the collagens was not required since denatured collagens and purified chick type II alpha chains were effective. The observed effects of collagens and interleukin 1 may contribute to the progressive nature of osteoarthritis.

Animals↗
PubMed1984

Lymphoma. Presenting as an intramuscular small cell malignant tumor.

The authors report two patients who presented with a mass in their thigh muscles. On the basis of the histologic appearance, a diagnosis of small cell malignancy was made. Further investigations including electron microscopy and immunoperoxidase techniques were necessary to accurately identify these tumors as lymphoma. Intramuscular lymphoma is rare, but it should be considered in the differential diagnosis, when the tumor consists of small cells. Special techniques are mandatory for a definitive diagnosis.

Aged↗
PubMed1984

The pathologic features of massive osseous grafts.

The authors studied histologically six of 35 massive osseous or osteochondral transplants that had been inserted following radical resection of musculoskeletal malignancies. The six transplants consisted of three allografts removed because of infection within 12 weeks following insertion and two allografts and one vascularized autograft resected between 52 and 72 weeks because of recurrent tumor. The infected allografts were necrotic and showed extensive osteomyelitis and septic arthritis. Focal areas of cartilage still had chondrocytes. The two non-infected allografts were also necrotic, and host bone had grown into donor bone at the graft--host interface. The vascularized autograft was viable. Articular cartilage was present in only one of the non-infected allografts and was necrotic. Ultrastructurally, allograft cartilage, although necrotic, showed marked destruction of the matrix only when infected. Allograft bone seems to act purely as a strut, inciting little immune response. It is unable to respond to infection and has little osteoinductive ability. Vascularized autograft, in contrast, appeared to contribute to graft union. Articular cartilage can survive transplantation but may become necrotic and undergo marked degeneration when infected. The histologic findings and clinical courses support the conclusion that graft failure within 72 weeks after transplantation is not due to immunologic rejection.

Adult↗
PubMed1983

Analytical scanning and transmission electron microscopy and x-ray microdiffractometry of calcium pyrophosphate dihydrate crystal deposits in tissues.

This paper reviews current methods and applications for the detection and identification of calcium pyrophosphate dihydrate (CPPD) crystals. Methods reviewed include compensated polarized light microscopy, scanning electron microscopy, transmission electron microscopy, x-ray energy-dispersive elemental analysis, x-ray powder microdiffractometry, and selected area electron diffractometry. Although compensated polarized light microscopy is the best technique for crystal detection in pathologic fluids and tissues, because of crystal size this technique cannot discriminate easily between CPPD(M) and CPPD(T) polymorphs. To determine the presence and relative concentration of CPPD(M) and CPPD(T), x-ray or electron microdiffractometry is required. Analytical scanning and transmission electron microscopy are needed to localize crystals ultrastructurally and to determine the relationship of the crystal deposits to tissue components. The correlative application of multiple techniques on the same sample or adjacent samples provides more precise localization and identification than any single technique.

Calcium Pyrophosphate↗
PubMed1982

Extramedullary hematopoiesis simulating parasagittal meningioma.

We report a patient with polycythemia vera and myeloid metaplasia of nine years duration who developed raised intracranial pressure related to a mass obliterating the sagittal fissure. Although clinically and radiologically simulating a meningioma, biopsy revealed extramedullary hematopoiesis involving the falx cerebri. Although uncommon, this case illustrates that myeloproliferative disease can present with symptomatology and radiologic features similar to primary intracranial tumours.

Adult↗
PubMed1981

Symmetrical fibro-osseous dysplasia of rib--post-traumatic dysplasia?

We describe two patients with a distinctive histological condition which clinically and radiologically mimics fibrous dysplasia of the rib. Both patients presented with chronic pain confined to one rib. In each case their radiographs showed a solitary, fusiform expansion of a rib with variable calcification. Histologically the lesions were characterized by a central core of xanthomatous macrophages surrounded by cancellous bone that showed symmetrical and progressive maturation centrifugally towards the cortex, a pattern which distinguishes these lesions from the irregular pattern of fibrous dysplasia.

Aged↗
PubMedDate not supplied

Histopathology of failed osteoarticular shell allografts.

Fresh cadaveric osteochondral fragment allografts were used to replace damaged articular surfaces of knee joints. Of the original 100 patients, 22 experienced graft failure necessitating graft removal. From these patients, a total of 44 osteochondral allografts were extirpated between 12 and 84 months after insertion. These were examined radiologically, histologically, and ultrastructurally. The bone and bone marrow were necrotic and had undergone variable replacement by host bone, which appeared to be independent of the duration of the graft. The articular cartilage showed degenerative changes ranging from fibrillation to erosion. Viable donor cartilage was present as late as seven years, proving that fresh graft cartilage can survive transplantation. Host bone interfaced with the cartilage, but in 14 grafts there was focal invasion of the cartilage. In some grafts, pannus formation with resorption of cartilage was evident. There was no histologic evidence of transplant rejection. This study is encouraging because hyaline cartilage has been shown to survive for as long as seven years and because bone can be replaced in a homogeneous fashion if the correct biomechanical conditions are met.

Adolescent↗