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Biomedical subjects

W J Johnson

Publications and source records attributed to W J Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1982

Differential effects of endocrine dysfunction on the axial and the appendicular skeleton.

In 100 patients with various types of endocrine dysfunction, we measured bone mineral density (BMD) at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry and at the lumbar spine (greater than 66% trabecular bone) using the new technique of dual photon absorptiometry. BMD in each endocrine disorder deviated in at least one site from the sex-specific age regression of 187 normal subjects. For patients with primary hyperparathyroidism, hypercortisolism, and hyperthyroidism this deviation was negative (suggesting bone loss), whereas for patients with secondary hyperparathyroidism due to chronic renal failure, acromegaly, and postsurgical hypoparathyroidism it was positive (suggesting bone gain). When all six states of endocrine dysfunction were compared concomitantly by multivariate analysis of variance, the profile of the changes in BMD differed significantly (P less than 0.001), indicating a nonuniform response of bone to the various hormonal alterations. When values for BMD at each of the three scanning sites were compared the midradius and distal radius did not differ significantly; either of the radius measurements, however, differed significantly (P less than 0.001) from the lumbar spine. Thus, the BMD of the axial skeleton cannot be reliably predicted from measurements made in the appendicular skeleton. We conclude that the effects of endocrine dysfunction on bone density are complex and are both disease and site specific.

Absorptiometry, Photon↗
PubMed1982

Cimetidine treatment of azotemic secondary hyperparathyroidism.

Cimetidine, an antagonist to histamine H2-receptors, reportedly lowers serum calcium and/or serum immunoreactive parathyroid hormone (iPTH) concentrations in some patients with primary and secondary (azotemic) hyperparathyroidism. We administered the drug orally (300 mg every 6 h) to five normal volunteers and four azotemic patients with secondary hyperparathyroidism who were not undergoing chronic hemodialysis. The normal persons and one azotemic patient took the drug for 5 weeks, and the remaining azotemic patients took it for 1 week. Before treatment, all patients had elevated levels of serum iPTH (two different assay systems), with or without elevated serum calcium concentrations, and increased urinary excretion of cAMP (per 100 ml glomerular filtrate). Cimetidine treatment caused no changes in serum calcium, phosphorus, or iPTH or in urinary cAMP (expressed as nanomoles per g creatinine). Serum creatinine, however, increased significantly in patients (P less than 0.02) and control subjects (P less than 0.025), which yielded statistically significant but spurious increases of urinary cAMP when expressed per 100 ml glomerular filtrate. We conclude that short term cimetidine administration has no effect on parathyroid function in normal persons or those with azotemic hyperparathyroidism. Because of its confusing effect on serum creatinine and a possible (albeit rare) adverse effect on renal function, the drug should be used with caution in azotemic patients not yet requiring chronic dialysis.

Adult↗
PubMed1982

Mechanisms of target recognition and destruction in macrophage-mediated tumor cytotoxicity.

Macrophages can be activated to kill neoplastic cells selectively and efficiently. Recent studies from his laboratory on mechanisms of target recognition and injury operative in such lysis have centered on the binding of tumor targets to the secretion of a cytolytic protease (cytolytic factor (CF]) by activated murine macrophages. Activated macrophages selectively and extensively bind neoplastic cells; nonselective binding of a low degree is seen between numerous cell pairs. The selective binding of three nonadherent tumors, which is much firmer than the nonselective binding, appears to depend on shared recognition structures contained within plasma membranes of the three tumors. Activated macrophages also secrete a potent, cytolytic, serine protease of molecular weight approximately 40,000. Secretion of CF is closely correlated with activation for cytolysis, and specific protease inhibitors of CF block macrophage-mediated cytotoxicity. Binding of tumor cells to activated macrophages triggers augmented secretion of CF. Several lines of evidence indicate that the capacity for selective binding and the capacity for secreting CF are separate and independently regulated functions of activated macrophages and that each is necessary but not sufficient for completion of macrophage-mediated tumor cytotoxicity. Analysis of the complete lytic interaction between activated macrophages and tumor cells suggests that binding and then secretion of CF are sequentially involved. These data have been integrated into a minimal hypothetical model, which suggests that macrophage-mediated tumor cytotoxicity is a multistep event encompassing 1) selective binding of tumor cells to the surface of activated macrophages and 2) secretion of multiple lytic effector substances, including CF, from the activated macrophages.

Animals↗
PubMed1981

The binding of BCG-activated macrophages to tumor targets stimulates secretion of cytolytic factor.

The binding of neoplastic targets and the secretion of a potent cytolytic protease (CF) by BCG-activated macrophages have previously been shown to be independent functions, both of which are necessary for completion of macrophage-mediated cytolysis. The present studies demonstrate that secretion of CF is triggered by the binding of neoplastic targets to BCG-activated macrophages. The binding of tumor targets, but not of normal lymphocytes, resulted in enhanced secretion of CF from BCG-activated macrophages, although not from macrophages elicited by thioglycolate broth. Dead or metabolically inactive tumor targets, as well as membrane preparations of tumor targets, induced secretion of CF from BCG-activated macrophages. The blocking of macrophage-target binding with a porous filter prevented augmented secretion of CF. Appreciable secretion of CF occurred in as little as 30 min after addition of tumor targets to BCG macrophages. Binding did not induce a generalized increase in secretion of neutral proteases by BCG macrophages, since secretion of plasminogen activator was actually decreased after the binding of P815 targets. The data suggest the selective binding of BCG-activated murine macrophages to neoplastic targets triggers the secretion of a potent CF.

Animals↗
PubMed1981

Metformin-induced lactic acidosis: potentiation by ethanol.

Although lactic acidosis has been recognized as a potential hazard in biguanide therapy, this complication has been claimed to be extremely rare with dimethylbiguanide (DMBG) (metformin). In the present studies, using the fasted guinea pig, DMBG (125-500 mg/kg i.p.) caused marked dose-related changes in both plasma glucose (43-88% reduction) and blood lactate (3.5-13 fold increase). Lactate/pyruvate ratios were substantially increased. While i.p. doses of 100 mg/kg of DMBG or of 1 g/kg of ethanol produced no changes in plasma glucose, lactate or pyruvate, the two drugs administered conjointly at the indicated doses produced a 53% decrease in plasma glucose and 2 and 10-fold increases in pyruvate and lactate levels respectively, and correspondingly, an increase in the lactate/pyruvate ratio. Ethanol decay curves indicated that DMBG did not significantly influence the disappearance of ethanol from the blood. These results indicate that: (1) doses of DMBG which produce hypoglycemia are associated with lactic acidosis, and (2) this effect of DMBG can be markedly potentiated by ethanol.

Acidosis↗
PubMed1981

Hydrogen peroxide and cytolytic factor can interact synergistically in effecting cytolysis of neoplastic targets.

Two secretory products from activated macrophages, which are thought to be involved in the lysis of tumor cells, are H2O2 and cytolytic factor (CF). To examine the potential of interaction between these 2 mediators of cytolysis, we first exposed MCA-I sarcoma targets to the 2 lytic agents. MCA-I targets, which have been previously shown to be lysed by CF, could also be lysed by H2O2 (the concentration of H2O2 causing 50% lysis of targets was approximately 1.4 x 10(-3) M). Exposure of the MCA-I targets to a nonlytic concentration of H2O2 for 1 hr potentiated the subsequent lytic effects of CF and did so synergistically. Exposure of targets to CF, however, did not potentiate the subsequent lytic effects of H2O2, even when the targets were treated with a lytic concentration of CF for 4 hr. Similar results were seen with P-388 lymphoma targets. The P388 cells were quite sensitive to the lytic effects of H2O2 (the concentration of H2O2 causing 50% lysis of these targets was approximately 2.0 x 10(-5) M) but proved relatively resistant to CF in comparison to the MCA-I targets. The data suggest that H2O2 and CF can interact synergistically to produce cytolysis of neoplastic targets if the targets are exposed to the 2 substances in a defined sequence.

Animals↗
PubMed1980

Persistent severe hypercalcemia during maintenance hemodialysis.

Hypercalcemia appeared shortly after induction of hemodialysis in three patients in whom serum parathyroid hormone concentrations were not markedly elevated, whose serum alkaline phosphatase values were normal, and in whom skeletal surveys did not show hyperparathyroid bone disease or metastatic calcification. Parathyroidectomy in two patients resulted in a decrease in parathyroid hormone concentration to normal, but hypercalcemia persisted. In a third patient, who was not subjected to parathyroidectomy, serum calcium values returned to normal after each of two renal transplantations but remained moderately elevated each time hemodialysis was resumed after allograft nephrectomy.

Adolescent↗
PubMed1980

Dialysis in the treatment of multiple myeloma.

Twenty patients with multiple myeloma and renal failure were treated by dialysis and chemotherapy consisting of prednisone and melphalan. Of nine patients treated by short-term dialysis, only two recovered renal function despite correction of fluid and electrolyte disorders, hypercalcemia, and hyperuricemia. The remaining seven patients died within 2 months in a uremic state, and one of the patients who recovered renal function died 14 months later of bronchopneumonia. In contrast, long-term hemodialysis and chemotherapy in 11 patients resulted in sufficient improvement in 8 patients to permit a degree of rehabilitation comparable to that achieved in patients with primary renal disease who have progression of the multiple myeloma. Of the 20 patients, 6 survive 7 to 48 months after beginning treatment.

Adult↗
PubMed1979

Renal transplantation in patients with diabetes mellitus--revisited.

Sixty-one patients with end-stage renal failure due to diabetic nephropathy received 68 renal allografts from June 1970 to February 1978. Patient and graft survival results equaled those for nondiabetic patients, as reported by the Human Renal Transplant Registry (HRTR). Renal allografts from siblings or pretreated cadaver donors had a significantly longer survival time than did allografts from nonpretreated cadaver donors. It is concluded that renal transplantation with living related and pretreated cadaver donor kidneys continues to be the treatment of choice and is superior to other forms of treatment in the insulin-dependent diabetic patient with end-stage renal disease.

Adult↗
PubMed1979

Chronic gouty nephropathy treated by long-term hemodialysis and allopurinol.

A patient with intractable tophaceous gout and advanced renal failure responded favorably to treatment by long-term hemodialysis and administration of allopurinol. Plasma uric acid levels returned to normal, tophi decreased in size, and the frequency of attacks of gout decreased markedly and permitted the patient to return to full-time employment.

Allopurinol↗