Hospital wins tax contest over pathology revenue: not unrelated business income.
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Biomedical subjects
Publications and source records attributed to R Schwartz.
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Several phorbol esters, the potent tumour-promoting agents isolated from croton oil, induce proliferation of human lymphocytes and enhance the mitogenic effect of lectins on bovine lymphocytes. While studying the mitogenic properties of one of these agents, phorbol myristate acetate (PMA), we found that dimethyl sulphoxide (DMSO), frequently used as a solvent for PMA, markedly inhibits PMA-induced mitogenesis at DMSO concentrations that have little effect on phytohaemagglutinin (PHA)-induced responses. DMSO, as well as a variety of other organic compounds, induce erythroid differentiation in Friend leukaemia (FL) cells. Phorbol esters, on the other hand, are potent inhibitors of both spontaneous and induced cellular differentiation. We therefore investigated the relationship between the potency of compounds to induce erythroid differentiation in FL cells and their potency to inhibit lymphocyte proliferation induced by PMA and other mitogens. We report here that many of the compounds that induce erythroid differentiation in FL cells are similar to DMSO in selectively suppressing PMA-induced lymphocyte mitogenesis.
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Glycohemoglobin (Hb Alc) was assayed sequentially during pregnancy and post partum in 53 women. In a group of nondiabetic women (N = 13) Hb Alc fell significantly (p less than 0.001) from the first to the third trimester and then rose to first-trimester levels by 12 weeks' post partum. Glycohemoglobin levels of insulin-dependent diabetic patients (N = 28) followed a similar pattern but at significantly elevated levels compared to nondiabetic patients (p less than 0.001). In contrast, patients with chemical diabetes (N = 12) did not manifest any change of Hb Alc with time, although they did have glycohemoglobin levels above those of the normal subjects during the third trimester (p less than 0.001) and before 12 weeks' post partum (p less than 0.02). It is speculated that these fluctuations in Hb Alc are most likely due to changes in long-term blood glucose control. Additionally, because Hb Alc increased in vitro oxygen affinity, some of these women were followed for parameters of oxygen transport as well. No significant changes of parameters of oxygen transport were found, with the exceptions of P50 in vivo and P50pH7.40 during the third trimester and of P50 in vivo before 12 weeks' post partum
Calcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2-21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed. Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.
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Organ-specific neoantigens (TA) shed from the tumours of patients with metastatic breast or colon cancer and which had filtered into the urine were partially purified by a combination of physicochemical methods and affinity chromatography. TA activity of the isolated materials was monitored by the blocking Tube LAI assay. Urinary protein was precipitated by 80% saturated ammonium sulphate. Albumin was removed by affinity chromatography with blue Sepharose CL-6B. Affinity columns of human IgG were prepared from sera of patients whose leucocytes were LAI+ to the breast- or colon-cancer extracts. The anti-breast-TA affinity column bound the TA in the urine of patients with metastatic breast cancer but not that of patients with metastatic colon cancer. The TA in urine of patients with metastatic colon cancer was bound by the anti-colon-TA affinity column. Analysis by SDS PAGE revealed that the isolates with and without TA activity were composed mostly of urinary protein which had bound nonspecifically to the human IgG affinity columns. With an affinity column of anti-NHS and Protein A, some of the contaminants were removed, to reveal SDD PAGE unique bands at about 38,000 and 12,000 mol. wt in the isolate with breast-TA activity. Rabbit antisera, raised to the material that had bound nonspecically to the anti-breast-TA affinity column, were used as an anti-nonspecific affinity column to remove the contaminants in the isolates from the affinity columns of anti-breast TA and anti-colon TA. After passage through the anti-nonspecific affinity column, the material that contained the putative breast or colon cancer TA revealed a unique band at about 38,000-40,000 mol. wt and residual fine bands at about 25,000-30,000 mol. wt. Both the control material and material with TA activity had similar bands at about 25,000 and 50,000 mol. wt. The specific activity of the putative colon or breast TAs, as measured by the blocking Tube LAI assay, was increased from about 30 to 5000-10,000 u/mg, a 125-400-fold enrichment.
The number and morphology of mast cells (MCs) in the duodenal submucosa and the histamine content of blood and isolated peritoneal mast cells were estimated sequentially in male weanling Sprague-Dawley rats magnesium (Mg)-depleted for up to 48 days. Blood histamine levels increased 4--5-fold by 14 days of Mg depletion and subsequently declined to levels similar to those in pair-fed Mg-adequate controls. In the same period, the submucosal MCs continuously increased in number, beginning to plateau at 6--7 times the control number between days 36--48 of Mg deficiency. Massive MC degranulation was seen in the early stages of Mg-depletion but subsided after 16--20 days. Subsequently, the submucosal MCs appeared small and rounded. They showed reduced staining with toluidine blue indicating a deficiency in the mucopolysaccharide component of the storage granules. Histamine content of purified peritoneal MCs from Mg-deficient rats was reduced by 10 days of Mg depletion and remained at or below one-third the control level throughout the depletion period. The data suggest that the MCs remaining or developed during chronic Mg depletion are deficient in their capacity to store and secrete histamine.
Five leafy vegetables were grown in nutrient solutions in which the natural magnesium was replaced by the stable isotope, 26Mg. They were fed to rats in a test meal together with the extrinsic tracer 28Mg: a) to determine to what extent the instrinsic tracer (26Mg) was exchangeable with extrinsic 28Mg during the digestion and absorption processes, and b) measure the relative Mg availability from the different vegetables. The two tracers, 26Mg and 28Mg, were close to 100% exchangeable, as judged by the ratio of 26Mg/28Mg in the livers. Mean relative Mg absorption from the various vegetables ranged from 108 to 118% of the Mg absorbed from a standard test meal containing MgSO4. There were no statistically significant differences between the rates of Mg absorption from the five vegetables although two of the vegetables tested contained oxalate. The usefulness of stable 26Mg as a tracer in Mg bioavailability tests is discussed.
The minor hemoglobins, which are formed post-translationally by acetylation or glycosylation, were studied in cord blood from 34 newborn infants. There were 9 normal infants, 8 infants of gestational (chemical) diabetics, and 17 infants of insulin-dependent diabetics. Among these groups, no significant differences in the acetylated fetal (FI) or other minor hemoglobin fractions were found by either isoelectric focusing in polyacrylamide gels or chromatography on DEAE-cellulose columns. These studies emphasize the technical limitations of detecting small amounts of glycosylated hemoglobin in newborns. The biological implications of the acetylated fetal hemoglobin fraction remain obscure.
Posthepatic insulin availability has been evaluated by steady-state insulin turnover studies with 131I-insulin. Spontaneously delivered term (age 3.3 +/- 0.8 days) (mean +/- S.E.) and prematurely delivered lambs (betamathasone treated at 132 days) (age, 1.1 +/- 0.2 days) were compared with 4- to 5-month-old sheep. After a 7-hr fast, animals received 0.45% saline or 5.7 mg/kg/min glucose (0.06 ml/kg/min) for 6-hr followed by the tracer insulin infusion for 110 min. Plasma glucose, insulin, and immunoprecipitable insulin were measured sequentially during the steady state. Endogenous posthepatic insulin secretion and metabolic clearance rates were derived. Neither endogenous posthepatic insulin secretion rates nor metabolic clearance rates were different among the three groups of animals when either 0.45% saline or 5.7 mg/kg/min exogenous glucose infusions were compared. Secretory response of the pancreatic beta cell to continuous glucose infusion seems similar for the term and preterm lamb when compared to adult sheep.