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J Chayen

Publications and source records attributed to J Chayen.

At least 37 records · Page 2Linked to original sources
PubMed1990

T-cell mediated cytolysis: evidence for target-cell suicide.

The mechanism by which cytotoxic T-lymphocytes (Tc) induce the death of specific target cells is still controversial. We have used quantitative cytochemical methods to distinguish the metabolic activities of the target cells from those of the Tc, even when they are attached to each other. Early events following Tc-P8(15) target cell interaction were first, increased glucose 6-phosphate dehydrogenase activity and second, labilization of the lysosomes within the target cell: these changes could be mimicked, in part, by polyamines and could be inhibited by inhibiting ornithine decarboxylase (ODC) activity. The crucial role of ODC in the chain of events that led to cytolysis in this particular experimental system was shown first, by measuring ODC activity directly and secondly, by the inhibition of cytolysis by the presence of a selective inhibitor of ODC activity.

Animals↗
PubMed1989

Early strain-related changes in enzyme activity in osteocytes following bone loading in vivo.

The skeleton's architecture is matched to the changing loads to which it is subjected because mechanical loading directly or indirectly influences the activity of cell populations to deposit, maintain, or remove bone tissue as appropriate. This responsiveness to load bearing presupposes that certain cells are sensitive to load itself or to its consequences within the tissue. The nature of this effect and the cells concerned have not yet been determined. In this series of experiments, bones were exposed in vivo to a single short period of dynamic loading, which if repeated daily had been shown to result in increased new bone formation. There was an increase in the activity of glucose 6-phosphate dehydrogenase (G6PD) in the periosteal cells adjacent to the bone surface 6 min after this single period of loading. This increase was proportional to the strain magnitude in the bone tissue in the immediate vicinity of the cells. In osteocytes, although the G6PD activity in each individual cell was unchanged by loading, the number of cells displaying activity was increased. This increase was also directly proportional to the applied strain in that area of the cortex (52% compared with 26% active osteocytes at a strain of 0.002). Activation of G6PD was unaccompanied by any equivalent changes in the activities of either glyceraldehyde 3-phosphate dehydrogenase (GA3PD) or lactate dehydrogenase (LDH). This finding is consistent with loading increasing the activity of the oxidative part of the pentose monophosphate shunt pathway. It is also consistent with stimulation of a synthetic process, such as the production of RNA from ribose 5-phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
PubMed1989

Comparative metabolic enzymatic activity in trabecular as against cortical osteoblasts.

On the basis of studies with bone-seeking isotopes, it is generally believed that the metabolic activity of osteoblasts of the trabecular bone is greater than that of the osteoblasts of the cortex. This implies that the oxidative activity, which provides the energy for biosyntheses, will also be greater in the former than in the latter. In the present study, direct measurement of the activities of representative enzymes of the major oxidative pathways, as well as of alkaline phosphatase, showed that the reverse pertained. However, owing to the greater cellularity of trabecular bone, the activity per unit mass of bone may be higher in the trabecular bone.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1988

Rapid changes in target cell lysosomes induced by cytotoxic T cells: indication of target suicide?

Although many studies have attempted to elucidate how cytotoxic T (Tc) lymphocytes cause the death of target cells, the mechanism is still controversial. In the present study the effect on the integrity of the lysosomes of the target cell has been investigated. We show here that the specific recognition and attachment of cloned type A influenza-specific Tc cells to A/X31 influenza virus-infected target cells caused rapid change in the amount of lysosomal naphthylamidase activity that was bound within the lysosomes, indicating that the lysosomal membranes in the target cells had been totally labilized. Target cells infected with type B influenza virus served as controls. We therefore suggest that the viral specificity of Tc lymphocytes allows for recognition and intimate membrane contact with suitably infected targets. This intimate contact induces sufficient perturbation of the target cell plasma membrane so as to cause total labilization of the target cell lysosomes which could account for intracellular lysis.

Animals↗
PubMed1988

Loading-related reorientation of bone proteoglycan in vivo. Strain memory in bone tissue?

The load-carrying capacity of the skeleton is achieved and maintained as the result of a continued functional stimulus to the cell populations responsible for bone remodeling. Although some bone cells have been assumed to be influenced by the load-induced changes in strain throughout the matrix, no evidence is available to indicate which cells are susceptible to such strain change or how such transient events provide a sustained influence on cell behaviour. In the present study, we showed that a short period of dynamic loading in vivo affects the orientation of proteoglycan within bone tissue. This reorientation declines only slowly, thus providing a persistent record of the tissue's recent strain history. Such a record has the ability not only to "capture" strain transients but also to "update" and "average" them. In this way, the bone cells could be presented with a sustained and coherent stimulus directly related to dynamic strain transients. These transients are the tissue's principal function variable.

Adaptation, Physiological↗
PubMed1988

Circulating vitamin K levels in patients with fractures.

It is now clear that vitamin K1 is part of a biochemical cycle that is essential for the conversion of specific bone peptides into a form that can bind calcium. We have used a recently described procedure for assaying vitamin K1 in plasma to test the involvement of this vitamin in fracture healing. Markedly depressed circulating levels were found in patients with fractures and the time taken for this level to return to normal appeared to be influenced by the severity of the fracture.

Adolescent↗
PubMed1988

A reappraisal of the structure of normal canine articular cartilage.

It has been shown that some of the controversy over the structure of articular cartilage may be due to slight differences in the orientation of the sample that has been studied. As our decisive criterion we have used the simple physical fact that elongate proteins, such as collagen micelles, that can exhibit form-birefringence, had to show virtually straight extinction when viewed under crossed polars. The use of a variably adjustable microtome chuck facilitated small adjustments in the orientation of the cartilage to meet this criterion. Under these conditions, the collagen of the matrix has been shown to be aligned mainly perpendicularly to the surface which was bounded by a thin lamina in which the collagen showed birefringence at 90 degrees to that of the matrix. The conventionally described zonation of articular cartilage has been shown to be inadequate for that of the dog tibial plateau. The conventional Zone 2 has been shown to consist of two zones, Zones 2a and 2b, with different cell sizes, cell concentrations, and concentration of matrix components.

Animals↗
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

Altered organization of non-collagenous bone matrix in osteoporosis.

In osteoporosis it is postulated that while the amount of bone is diminished, the quality of the bone is unaltered. Recently relatively novel methods of analysis have shown that, at the fracture site of osteoporotic subcapital fractures, there is a marked change in the molecular orientation of components of the non-collagenous bone matrix. These procedures, now applied to iliac crest biopsies, confirm earlier findings of altered orientation of the proteoglycans at the subcapital fracture site but show that very similar changes occur even in the iliac crests from patients with both types of osteoporotic proximal femoral fracture. Thus, whereas the amount of these acidic moieties of the non-collagenous bone matrix was unchanged, the molecular orientation was markedly altered, albeit not to the same extent as that found at the fracture site. These results imply that the quality of the bone, as well as the quantity, may be generally affected in osteoporosis.

Adult↗
PubMed1987

Major components of bone in subcapital and trochanteric fractures. A comparative study.

Quantitative polarised light microscopy was applied to sections of unfixed, undecalcified bone taken at operation from patients with two types of proximal femoral fracture, subcapital and trochanteric. Specimens were also taken from the equivalent sites in otherwise normal subjects at autopsy, and from various other sites of traumatic fractures; these two latter groups acted as controls. Analysis of the 57 specimens disclosed changes in the nature of the bone at the site of subcapital fractures, namely the presence of relatively large crystals of hydroxyapatite and a change in the molecular orientation, but not total content, of the acidic proteoglycans of the bone matrix. Our results have confirmed and extended the findings of others on subcapital fractures, and have also shown very similar changes in the trochanteric fractures. It thus appears that the bony changes in the two types of proximal femoral fracture are not as different as has been suggested.

Adult↗
PubMed1987

The origin of the apparent synovial lining cell hyperplasia in rheumatoid arthritis: evidence for a deep stem cell.

The experimental model of inflammatory arthritis in the rabbit has been used to study the possible origin of the apparent synovial lining cell hyperplasia. A small amount of 3H-thymidine was injected into the joints and the fate of the labelled cells investigated by autoradiography. At times up to 24 h after the injection, most of the labelled cells occurred in the sub-lining region; this proportionality was reversed when the joints were sampled at later times. These results indicate that at least much of the increase of synovial lining cells may be derived from cells from deeper in the synovial tissue which move to the synovial surface.

Animals↗
PubMed1986

Putrescine may be a natural stimulator of glucose-6-phosphate dehydrogenase.

The possible relationship between pyridoxal phosphate-dependent ornithine decarboxylase (ODC) activity and glucose-6-phosphate dehydrogenase (G6PD) activity has been studied in the osteoblasts of the growth-plate of metatarsals of rats fed a pyridoxine-deficient diet, which caused depressed G6PD levels. The G6PD activity was fully restored when it was assayed in the presence of putrescine. It is suggested that this relationship may account for the correlation generally found between growth and ODC activity.

Animals↗
PubMed1986

Enzymic heterogeneity of normal canine articular cartilage.

Articular cartilage is generally considered to be an homogeneous tissue. It has now been shown that, although different regions of the medial tibial cartilage of the dog have very similar oxidative enzymic activities, each region is heterogeneous with respect to these activities. The conventional histological delineation of this cartilage has been modified, to take into account a narrow band (designated zone 2a), just below the most superficial spindle-shaped cells, that has higher oxidative enzymic activity than any other. Changes in the activity in this zone might be diluted by the lack of change in other zones if measured by conventional biochemical procedures which could not measure the activities of the different zones separately.

Alcohol Oxidoreductases↗
PubMed1986

Abnormalities in fracture healing induced by vitamin B6-deficiency in rats.

Vitamin K1 is the intermediate carrier of reducing equivalents in mineralization. In fracture-healing in the rat metatarsal the primary source of these reducing equivalents appears to be NADPH, generated from glucose 6-phosphate dehydrogenase (G6PD) activity. Because recent evidence indicated that stimulation of G6PD activity can be induced by putrescine, derived from pyridoxal phosphate-dependent ornithine decarboxylase activity, the effect of pyridoxine (vitamin B6) deficiency has been studied in this system. Vitamin B6-deficiency caused marked diminution in the G6PD activity in the periosteal region of bone-formation and in the developing callus, with significant delay in the maturation of the callus and union. It also caused changes in the bone suggestive of imbalance in the coupling between osteoblasts and osteoclasts. These results suggest that the vitamin B6-status may be important in fracture-healing.

Animals↗
PubMed1986

Decreased inhibition of proteolysis by osteoarthritic synovial fluids.

The hypothesis, that part of the pathogenesis of osteoarthritis may be due to the diminished ability of the osteoarthritic synovial fluid to restrict proteolysis, has been tested by a functional biochemical assay for such inhibitory activity. The results from six synovial fluids from normal or mildly osteoarthritic knees were compared with those from seven from joints showing moderately severe or severe osteoarthritis. Whether on the basis of 'per mg protein' or 'per millilitre' of the fluids, the latter showed a clearly diminished capacity for inhibiting proteolysis under the conditions of this assay.

Cartilage, Articular↗