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Biomedical subjects

J Dunham

Publications and source records attributed to J Dunham.

At least 19 recordsLinked to original sources
PubMed1994

Testing drugs on human osteoarthritic articular cartilage.

New drugs are generally developed against animal models of the human disease. Before they are subjected to clinical trials it might be helpful to be able to test whether they are as effective against the disease in human tissue as they were in animals. It is proposed that this can be achieved by the use of organ maintenance culture of the human diseased tissue, the relevant biochemical parameters being measured by quantitative cytochemistry. In the present studies differences between the effect of indomethacin and of the 'chondroprotective' drug diclofenac sodium, on human osteoarthritic cartilage, have been measured.

Aged↗
PubMed1993

Prolonged effect of iodoacetate on articular cartilage and its modification by an anti-rheumatic drug.

The intra-articular injection of iodoacetate into the knee joint of rats produced changes in the articular cartilage which resembled those of osteoarthritis. It caused virtually total loss of many of the oxidative enzymes, indicating inhibition of the main oxidative pathways. Treatment with an anti-rheumatic drug had little early effect but ultimately led to partial restoration of these pathways. The reduced progression of cartilage degradation induced by this drug was accompanied by some unusual histological features.

Animals↗
PubMed1992

Structural and metabolic changes in articular cartilage induced by iodoacetate.

The chemically induced injury to articular cartilage, caused by two successive intra-articular injections of sodium iodoacetate, has been used in studies on the effects of anti-inflammatory and of potentially chondroprotective agents. It has been assumed that the injurious effects are caused by inhibition of the glycolytic pathway. In the present study this inhibition has been shown to be greater than expected from in vitro studies, and to influence equally other oxidative pathways. However, the response is clearly not a simple one in that some of the surface chondrocytes, and synovial lining cells in close proximity to the cartilage, show virtually no inhibition.

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↗
PubMed1990

Transformational leadership and the nurse executive.

Effective nurse executive leadership is paramount in today's health care environment. Such leadership includes the qualities of a transformational leader and, to a lesser extent, a transactional leader. A study conducted among excellent nurse executives and members of their immediate staff showed that all executives were predominantly transformational leaders but also possessed transactional leadership skills.

Administrative Personnel↗
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

The metatarsal cytochemical bioassay of parathyroid hormone: validation, specificity, and application to the study of pseudohypoparathyroidism type I.

The most sensitive method for assaying the bioactivity of PTH in unextracted plasma is the renal cytochemical bioassay. However, PTH acts on bone as well as kidney and clinical studies have suggested that the actions of circulating PTH level may be different at the two sites. We developed cytochemical bioassay for PTH based on the stimulation of glucose 6-phosphate dehydrogenase activity in the hypertrophic chondrocytes of the growth plate and the osteoblasts lining the metaphyseal trabeculae of rat metatarsal bones. The index of precision was 0.14 +/- 0.02 (SE) and the interassay variation was 31%. With this assay, plasma bioactive PTH levels in normal subjects and patients with primary hyperparathyroidism ranged from 0.5-18 ng/L and from 27-850 ng/L, respectively. Studies of patients with pseudohypoparathyroidism type I indicated that plasma PTH bioactivity in such patients is greater in the metatarsal bioassay than in the renal bioassay; no such differences were found in normal subjects or patients with primary hyperparathyroidism.

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↗
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↗
PubMed1985

Altered orientation of glycosaminoglycans and cellular changes in the tibial cartilage in the first two weeks of experimental canine osteoarthritis.

Changes in the cellularity and in the nature of the matrix were studied in the cartilages of the tibial plateau in experimentally induced arthritis in the dog, 7 and 14 days after section of the anterior cruciate ligament. Samples from the different regions of these cartilages were chilled and sectioned in a cryostat, with a variable microtome chuck to allow precise orientation of the specimens. The samples were examined by normal light microscopy, by microscopic interferometry, and by quantitative polarized light microscopy. The orientation of the glycosaminoglycans was assessed by the new "induced birefringence" method. The results indicated that only the region of the medial tibial cartilage that was unprotected by the meniscus was affected, showing increased water content, loss of superficial cells, and a decrease in orientation of the glycosaminoglycans. Whereas the birefringence of the collagen was unaffected, the superficial area that lacked oriented glycosaminoglycans was markedly increased; this may be a useful indicator of early osteoarthritic changes.

Alcian Blue↗
PubMed1984

Hormonal and electrolyte responses during and after open heart surgery.

Maintenance of the balance of electrolytes and hormones within their normal range is necessary for normal myocardial metabolism. Open heart surgery involving cardiopulmonary bypass produces metabolic disturbances which affect normal metabolic homeostasis. Several studies have suggested that pulsatile cardiopulmonary bypass causes less severe metabolic disturbance than non-pulsatile bypass and that non-pulsatile bypass causes hypofunction of the anterior pituitary and adrenal glands. The present study, however, with non-pulsatile flow showed that there was no evidence of hypothalamo-pituitary-adrenal axis hypofunction when the hormonal values of corticotrophin (ACTH), cortisol and cortisone were corrected for the hemodilution involved in cardiac surgery. Electrolytes, particularly calcium, play an important role in myocardial contractility. The levels of ionized calcium are normally controlled by parathyroid hormone (PTH) with a negative feedback of calcium controlling the system. However, this study showed that significant increases in bioactive PTH during cardiopulmonary bypass were not related to the calcium concentration, but appeared to be influenced by low blood pH values and by the degree of hypothermia.

Adrenocorticotropic Hormone↗
PubMed1983

Aerobic glycolysis of bone and cartilage: the possible involvement of fatty acid oxidation.

The apparent paradox of aerobic glycolysis has been investigated in bone and in cartilage. A new cytochemical procedure for hydroxyacyl dehydrogenase (HOAD) activity showed that the maximal activity of this enzyme in both tissues was equivalent to the maximal activity of glyceraldehyde 3-phosphate dehydrogenase (GAPD). The sum of these activities gave a measure of the maximum amount of acetyl-coenzyme A that could be produced. In these tissues, but not in liver which does not exhibit aerobic glycolysis, this summed value exceeded the maximal activity of succinate dehydrogenase (SDH). Consequently, it suggested that where fatty acid oxidation is sufficient to supply all the acetyl-coenzyme A required for the Krebs' cycle, that derived from fatty acid oxidation may inhibit pyruvate dehydrogenase causing accumulation of pyruvate which must be converted to lactate if pentose-shunt activity is to be maintained.

3-Hydroxyacyl CoA Dehydrogenases↗