PubMed Health⌕ Search

Biomedical subjects

F R DeRubertis

Publications and source records attributed to F R DeRubertis.

119 records · Page 7Linked to original sources
PubMed1974

Release of prostaglandin by mitogen- and antigen-stimulated leukocytes in culture.

The prostaglandin (PG) content of mitogen- and antigen-stimulated leukocyte cultures was examined by a radioimmunoassay procedure empolying an antiserum reactive with PGB(1) and PGB(2), the alkaline dehydration products of PGE and PGA. At 48 h, mitogen-activated mouse spleen cell cultures showed 2-10-fold increases in the PGE, but not in the PGA, component of immunoreactive PG (iPG) fractionated by silicic acid column chromatography. Increases in iPG were detectable by h 16 in spleen cell cultures incubated with staphylococcal enterotoxin B. Since iPG levels rose only in the culture supernates and not in cells exposed to mitogens for 48 h, increases reflected extracellular release of PG. The validity of the radioimmunoassay determinations of PGE in spleen cell cultures was supported by the results of concomitant assessment of the PGE(2) content of basal and enterotoxin-stimulated cultures by gas chromatography/mass spectrometry. By the latter method, the PGE(2) content was three-fold higher in enterotoxin-activated, compared to basal, cultures at 48 h. Aspirin effectively suppressed increases in both iPG and PGE(2). In spleen cell cultures prepared from mice previously inoculated with an attenuated strain of yellow fever virus in vivo and then incubated with this virus in vitro, iPG levels increased twofold over basal at 48 h. By contrast, iPG content of spleen cell cultures prepared from saline-inoculated mice was not appreciably altered by exposure to the virus in vitro. The enhancement of iPG release from cultured spleen cells by mitogens did not correlate with an ability of these agents to increase cellular cyclic AMP (cAMP) levels. Moreover, epinephrine and cholera toxin markedly increased spleen cell cAMP content but had no demonstrable effect on basal iPG levels, suggesting iPG release from these cells was not mediated by cAMP. Incubation with mitogens also enhanced the iPG content of 72-cultures of human peripheral leukocytes and of human lymphocytes isolated by nylon chromatography. However, the iPG of cultures of human lymphocytes purified by glass bead chromatography and of mouse thymocytes was not appreciably altered when these cells were cultured with mitogens, even though DNA synthesis in both instances was markedly increased. Accordingly, iPG release was not an invariable concomitant of increased DNA synthesis in lymphoid cell cultures. In summary, the results demonstrate that mitogen and antigen stimulation of leukocytes in culture may be accompanied by enhanced release of PGE. The mechanisms mediating this phenomenon and its biologic significance remain to be delineated, but participation of PGE in immunologically induced inflammatory responses seems possible.

Animals↗
PubMed1973

Accelerated cellular uptake and metabolism of L-thyroxine during acute Salmonella typhimurium sepsis.

The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T(4)) distribution and metabolism and on serum total and free T(4) concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T(4) from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T(4) disposal. In the infected monkeys, serum total T(4) and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T(4) were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T(4) kinetics could neither be correlated with changes in the binding of T(4) in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T(4) disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T(4) during bacterial sepsis, possibly related to phagocytic cell function in the host.

Animals↗
PubMed1972

Evidence for enhanced cellular uptake and binding of thyroxine in vivo during acute infection with Diplococcus pneumoniae.

Previous work has demonstrated that acute pneumococcal infections in man and in the rhesus monkey are accompanied by accelerated metabolic disposal of L-thyroxine (T(4)). In order to study the influence of acute pneumococcal infection on the kinetics of hormone distribution, the early cellular uptake of T(4) (CT(4)), reflecting the net effect of plasma and cellular binding factors, was assessed in rhesus monkeys from the differences in instantaneous distribution volumes of T(4)-(131)I and albumin-(125)I during the first 60 min after their simultaneous injection. Hepatic and renal uptakes of (131)I were also determined. Plasma binding of T(4) was assessed by measuring the per cent of free T(4) (% FT(4)) in serum. Six monkeys were studied 12 hr (INF-12) and seven 24 hr (INF-24) after intravenous inoculation with Diplococcus pneumoniae; seven controls were inoculated with a heat-killed culture. CT(4) at 60 min as per cent administered dose was 31.5 +/-2.0 (mean +/-SE) in INF-12 and 33.0+/-0.8 in INF-24, values significantly greater than control (22.4+/-1.3). By contrast, mean% FT(4) was identical in control and INF-12 (0.028 +/-0.002 and 0.028 +/-0.001) and variably increased in INF-24 (0.034 +/-0.003). Thus, in the infected monkeys CT(4) and% FT(4) were not significantly correlated. The increased CT(4) in the infected monkeys could not be ascribed to an increase in vascular permeability and did not correlate with the magnitude of fever. Although the increased CT(4) could not be accounted for by increased hepatic or renal uptake of hormone, hepatic and renal T(4) spaces were increased, results consistent with increased binding by these tissues. Our data indicate that the cellular uptake of T(4) is increased early in acute pneumococcal infection and suggest that this results from a primary enhancement of cell-associated binding factors for T(4).

Animals↗
PubMed1972

Effect of prostaglandin E 1 on certain renal actions of parathyroid hormone.

Parathyroid hormone increased basal adenyl cyclase activity and that increase was inhibited by prostaglandin E(1) (PGE(1)). Tissue cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentrations were increased by parathyroid hormone and that increase was likewise inhibited by PGE(1). Both parathyroid hormone and dibutyryl cyclic AMP increased (32)P incorporation into renal cortical phospholipids. PGE(1) diminished the effect of parathyroid hormone but not dibutyryl cyclic AMP to influence that parameter. PGE(1) likewise modulated the effect of parathyroid hormone but not dibutyryl cyclic AMP to decrease fractional phosphate reabsorption by the renal tubule. It is suggested that PGE(1) inhibits the effect of parathyroid hormone by decreasing its effect on adenyl cyclase. Such interaction may be important in modulating the intracellular action of parathyroid hormone on kidney cortex.

Adenylyl Cyclases↗
PubMed1971

"Essential" hypernatremia due to ineffective osmotic and intact volume regulation of vasopressin secretion.

A physiological explanation for sustained hyperosmolality was sought in a patient with histiocytosis. During 23 days of observation with only sodium intake regulated at 100 mEq daily, elevation (mean 310 mOsm/kg of water) and fluctuation (range 298-323) of the fasting plasma osmolality were recorded. The presence of endogenous vasopressin was indicated by the patient's ability to concentrate the urine to as high as 710 mOsm/kg of water with a creatinine clearance of 84 cc/min, and by dilution of the urine in response to alcohol. The failure of increasing fluid intake to as high as 6.2 liters daily to lower the plasma osmolality indicated that deficient fluid intake was not solely responsible for the elevated plasma osmolality. Hypertonic saline infusion during water diuresis resulted in the excretion of an increased volume of dilute urine. The water diuresis continued despite a rise in plasma osmolality from 287 to 339. An isotonic saline infusion initiated during hydropenia resulted in a water diuresis which continued despite a rise in the plasma osmolality from 303 to 320. Stable water diuresis induced during recumbency by either oral ingestion of water or intravenous infusion of normal saline was terminated by orthostasis and resumed with the return to the recumbent position. Antecedent alcohol ingestion blocked the antidiuresis of orthostasis. The data are interpreted as indicating impairment of the osmoreceptor mechanism as the primary cause of the hyperosmolar syndrome. They also indicate that vasopressin secretion was regulated primarily by changes in effective blood volume. Chlorpropamide was found to be an effective treatment for the syndrome.

Adult↗
PubMedDate not supplied

Protein kinase C in diabetic nephropathy.

Protein kinase C is activated in numerous tissues obtained from diabetic animals and in several cultured cell systems exposed to high media glucose in vitro including glomerular mesangial cells. Several activators of protein kinase C, such as high media glucose, angiotensin II, phorbol ester, low density lipoprotein, and the thromboxane analogue U-46619, increase TGF beta bioactivity or mRNA expression and increase the synthesis of extracellular matrix proteins by mesangial cells in culture. The studies described in the present report support the hypothesis that activation of protein kinase C by thromboxane, an eicosanoid whose production is known to be elevated in diabetes, increases TGF beta production by mesangial cells in culture. TGF beta then acts to increase extracellular matrix protein synthesis through a mechanism that does not require active protein kinase C. Thus, activation of protein kinase C in the glomerulus in diabetes could contribute to mesangial expansion by stimulating active TGF beta production.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗