Search PubMed⌕ Search

Biomedical subjects

J Dunham

Publications and source records attributed to J Dunham.

32 records · Page 2Linked to original sources

Metabolic changes in the cells of the callus during fracture healing in the rat.

Unfixed, undecalcified sections from closed fractures of rat metatarsals have been studied by quantitative cytochemistry from the first week after fracture to late in the fracture-healing process. Alkaline phosphatase activity appeared to be related to calcification. Glucose 6-phosphate dehydrogenase activity was associated with proliferation and with calcification. Studies made with the critical electrolyte Alcian blue technique suggested that whether the ossification process is of the endochondral or membranous type might be predetermined in the relatively undifferentiated callus.

Alkaline Phosphatase↗

The effect of ionized calcium, pH, and temperature on bioactive parathyroid hormone during and after open-heart operations.

Normal myocardial function is dependent on the metabolic balance of a number of electrolytes and hormones. The calcium ion plays a major role in muscle contraction and is rigorously controlled within narrow limits. Open-heart surgery imposes metabolic disturbances on both electrolytes and hormones, especially ionized calcium. Normally, ionized calcium levels are controlled by parathyroid hormone with a negative feedback from the ionized calcium controlling the system, but the results from this study suggest that during open-heart procedures, ionized calcium does not impose its normal negative feedback on bioactive parathyroid hormone secretion. The low blood pH levels that occurred during the operative conditions of the patients studied and the level of hypothermia imposed on the circulating blood during cardiopulmonary bypass appeared to influence the control of parathyroid hormone secretion, causing high levels of hormone to be secreted during this period.

Adult↗

An effect of parathyroid hormone on the epiphyseal plate and osteoblasts: studies towards a cytochemical bioassay.

There are reports of an apparent dissociation between the responses of kidney and bone to parathyroid hormone (PTH): certain fragments or analogues have been shown to have differential activity in these two tissues. Consequently, cytochemical bioassay techniques have been applied to the development of an assay for PTH using the epiphyseal plate of the rat metatarsal as the target organ. Glucose 6-phosphate dehydrogenase activity in the zone of hypertrophic cartilage is stimulated in a log-linear fashion with increasing concentrations of parathyroid hormone over the range 0.001 - 1.0 pg/ml. A parallel response was found in the osteoblasts of the metaphysis. Measurements of a normal and a hyperparathyroid plasma sample showed good parallelism to the standard graph and good discrimination. Addition of a PTH - specific antibody inhibited both the effect of the standard preparation of the hormone, and the response induced by dilutions of a normal plasma.

Animals↗

Strategies for developing a cost-effective pulmonary rehabilitation program.

A cost-effective pulmonary rehabilitation program can be created by using strategic planning, a thorough budgetary process, and then promotion of the program. Strategic planning assesses the need for such a program, develops its overall direction, establishes priorities, assesses economic factors and the presence or absence of similar services already in existence, and identifies the proposed scope of the program. The budgetary process identifies the specific services to be offered and estimates the volume of services, their costs, and revenues. Promotion of the program serves to acquaint potential referring physicians and patients with the services to be offered. If preliminary investigation indicates that a pulmonary rehabilitation program is needed in the community, then strategic planning, careful budgeting, and creative promotion can help assure that the program is financially viable.

California↗

Circulating levels of biologically active parathyroid hormone in rheumatic diseases.

There has been doubt as to whether elevated levels of parathyroid hormone, reported previously by radioimmunoassay, reflect increased concentrations of the biologically active hormone. The application of a recently developed, highly sensitive bioassay has shown considerable disparity between bioactivity and immunoreactivity in 5 rheumatic conditions and in normal subjects. Six patients with chondrocalcinosis had elevated levels; 3 of these did not have hypercalcaemia or any obvious cause other than possible subclinical hyperparathyroidism. One patient, assayed during an acute episode, had an elevated concentration of the hormone which reverted to normal when she was asymptomatic. Most patients with osteoarthrosis (13 our of 15) had low normal levels; 2 showed unexplained slightly elevated concentrations. Of 6 patients with haemochromatosis 3 had elevated levels, though this may have been related to the associated presence of diabetes mellitus. A third of patients with ankylosing spondylitis (10 out of 30) showed elevated parathyroid hormone levels but without hypercalcaemia. A number of spondylitic patients also showed anomalous results in this assay, possibly due to the presence of an antagonist. This would be consistent with the absence of clinical or biochemical evidence of hyperparathyroidism.

Adult↗

Cleavage of peptide hormones by alpha 2-macroglobulin-trypsin complex and its relation to the pathogenesis and chemotherapy of acute pancreatitis.

Access to the active site of alpha 2-macroglobulin bound proteinases by macromolecular substrates and inhibitors is likely to be influenced by steric favourability and flexibility, as well as by molecular size. Hydrolysis of pure porcine cholecystokinin-pancreozymin 39, a flexible single chain peptide, by alpha 2-macroglobulin-trypsin complex resulted in a rapid up to 6-fold increase in cholecystokinin bioactivity; alpha 2-macroglobulin-trypsin rapidly abolished the bioactivity of endogenous parathormone in human plasma. Inhibition of both reactions was completed by low concentrations of antipain and leupeptin; Trasylol (aprotinin), a single chain peptide with three disulphide bonds, was an ineffective inhibitor even in massive molar excess. These findings may provide an explanation for the disordered calcium homeostasis in severe acute pancreatitis and for the failure of Trasylol to reduce mortality; they suggest that sterically favourable low molecular weight inhibitors may provide effective specific chemotherapy for the disease.

Acute Disease↗

A sensitive bioassay of parathyroid hormone in plasma.

Understanding of calcium metabolism in health and disease has been retarded by the lack of an adequately sensitive bioassay of parathyroid hormone. The problem of dissociation of bioactivity and immunoactivity, well recognized for other polypeptide hormones, is exaggerated in the case of parathyroid hormone by the disproportionately long half-time in the circulation of the immunoreactive fragments. A new method of assaying the biological activity of parathyroid hormone in plasma has been developed, based on the cytochemical methods which have yielded highly sensitive bioassays of other polypeptide hormones. It depends on the stimulation of glucose 6-phosphate dehydrogenase activity in the distal convoluted tubules of segments of guinea-pig kidney maintained in vitro, and measured by microdensitometry. The limit of sensitivity of the assay is 5 fh/ml (bPTH); the index of precision is 0.09 +/- 0.04 (mean +/- SEM; n = 11).

Animals↗

Pentose-shunt oxidation in the periosteal cells in healing fractures.

The activity of pentose-shunt dehydrogenases is very low in periosteal cells of normal rat metatarsals, but increases one day post-fracture and rises linearly over the next two days. By four days post-fracture, the distribution of this activity along the bone shows two centres of high activity: the first in the region of proliferation to form callus and the second at the site where new bone is first seen, one day later. The high rate of generation of NADPH would be expected to reduce glutathione; reduced glutathione has been shown to inhibit alkaline phosphatase activity in these cells.

Alkaline Phosphatase↗

Changes in alkaline phosphatase activity in periosteal cells in healing fractures.

The quantitative changes in alkaline phosphatase activity in the periosteal cells close to the fracture in rat metatarsal bones has been measured during the first 5 days postfracture. This study has been made possible by two technological advances, firstly the development of cryostat microtomy for cutting unfixed, undemineralised bone, and secondly the use of scanning and integrating microdensitometry for quantifying the activity in each periosteal cell. The results showed a loss of alkaline phosphatase activity close to the fracture site, with activity rising to normal values 0.8-1.0 mm from the site. No alkaline phosphatase activity was found in the cells which proliferated from the periosteum. It is suggested that reduced glutathione could cause such inhibition.

Alkaline Phosphatase↗