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Biomedical subjects

R E Larson

Publications and source records attributed to R E Larson.

At least 91 records · Page 5Linked to original sources
PubMed1980

Kinetic aspects of cycloheximide-induced reversal of adrenocorticotropin effects on steroidogenesis and adrenal phospholipids in vivo.

Intraperitoneal injection of maximally effective doses of corticotropin(1-24) [ACTH(1-24)] provoked maximal increases in rat adrenal phospholipids as follows: phosphatidic acid within 1.5-2 min, phosphatidylinositol and phosphatidylglycerol within 4-6 min, and polyphosphoinositides and corticosterone within 5-15 min. Continued maximal adrenal stimulation by ACTH(1-18) treatment caused sustained increases in adrenal phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, polyphosphoinositides, and corticosterone. Treatment with cycloheximide during this steady-state caused rapid decreases in all of these substances to basal levels. The observed half-lives of adrenal phosphatide acid, phosphatidylinositol, polyphosphoinositides, phosphatidylglycerol, and corticosterone during cycloheximide inhibition were 0.15, 1.0, 1.7, 3.3, and 3.5 min, respectively. Calculated production rates during maximal ACTH stimulation were 1060, 991, 90, 34, and 41 nmol/g of tissue per min, respectively. These findings suggest that (i) an initial effect of ACTH on de novo synthesis of phosphatidic acid can account for all subsequently observed increases in other phospholipid derivatives of CDP-diacylglycerol, (ii) a labile protein is required for the ACTH-induced increase in phosphatidic acid, (iii) the phosphatidate leads to polyphosphoinositide-polyglycerophospholipid pathway is rapidly and dramatically responsive to hormonal stimulation, (iv) changes in steroidogenesis correlate well with changes in this phospholipid pathway, and (v) stimulation of this pathway is rapidly reversible.

Adrenal Cortex↗
PubMed1980

Potassium and angiotensin II increase the concentrations of phosphatidic acid, phosphatidylinositol, and polyphosphoinositides in rat adrenal capsules in vitro.

We examined the effects of K+ and angiotensin II, the major regulators of aldosterone secretion, on phospholipid metabolism during incubation of glomerulosa-rich, adrenal capsules. Addition of increasing amounts of K+ and angiotensin II to the incubation media elicited progressive increases in corticosterone production and capsular concentrations of phosphatidic acid, phosphatidyl-inositol, and polyphosphoinositides. These effects are similar to those previously reported for ACTH in the whole adrenal cortex. A common mechanism, i.e., activation of the phosphatidate-polyphosphoinositide cycle, may be operative in the action of steroidogenic agents in their target tissues.

Adrenal Glands↗
PubMed1977

Thirteenth valuation of the railroad retirement system.

The most recent valuation of the financial condition of the railroad retirement system reveals that an existing actuarial deficiency will become more pronounced over time unless corrective action is taken. After projecting the progress of the fund under present law and certain assumptions about the future, the Railroad Retirement Board has concluded that the present value of benefits can be maintained only if the tax rate--already considerably higher for employers than under the social security program--is raised. An immediate increase of 4.1 percent of taxable payroll is required to effect an actuarial balance. Alternatively, a rise of 2.6 percent would be sufficient to prolong the fund until the year 2001. If the present tax rate is not changed, the fund is projected to run out in 1986.

Accounting↗
PubMed1976

Dissociation of 5-fluorouracil uptake from intracellular pH in Walker 256 carcinosarcoma.

The influence of intracellular pH (pHi) upon 5-fluorouracil (5-FU) uptake has been studied in slices of Walker 256 carcinosarcoma and rat liver. Alteration of pHi was achieved by the addition of either glucose alone or together with oxamic acid to the incubation medium. Results indicated that 5-FU uptake by the tumor slices was not dependent upon pHi, but was enhanced by the presence of glucose. Uptake of 5-FU by liver slices appeared to follow a pattern predictable from the pHi and the pK of the drug.

Animals↗
PubMed1975

Lipid peroxidation in isolated hepatocytes.

Intracellular lipid peroxidation was initiated by the addition of ADP-complexed ferric iron to isolated rat hepatocytes and the reaction monitored by the thiobarbituric acid method or by measurement of the formation of conjugated dienes. Both the production of malondialdehyde (thiobarbituric-acid-reacting substances) and of conjugated dienes was dependent, on the ADP-Fe-3+ concentration in a dose-related fashion. Malondialdehyde formation stopped spontaneously within 20 min after the initiation of the reaction and the plateau reached was also related to the ADP-Fe-3+ concentration. Control experiments revealed that more than 90% of the malondialdehyde accumulating during the incubation period could be ascribed to intracellular production. The cellular NADPH/NADP+ ratio was always high and only slightly decreased upon ADP-Fe-3+-induced lipid peroxidation which, however, was associated with a marked decrease in the cellular glutathione concentration. The rate of accumulation of malondialdehyde as well as the final level reached during ADP-Fe-3+-initiated lipid peroxidation was increased by the addition of chloral hydrate. This apparent stimulatory effect could, however, be ascribed to the inhibition of the mitochondrial oxidation of the malondialdehyde formed during cellular lipid peroxidation, thus allowing more malondialdehyde to accumulate during the process. ADP-Fe-3+-induced cellular lipid peroxidation was associated with a decrease in the concentration of glutathione. Also, lowering of the intracellular glutathione level by the addition of diethyl maleate or by simply preincubating the hepatocytes (up to 50 min) promoted the ADP-Fe-3+ malondialdehyde production and formation of conjugated dienes. Furthermore, when cellular glutathione concentration had been lowered by preincubation of the hepatocytes, significant malondialdehyde production could be observed even at ADP-Fe-3+ concentrations which were too low to induce measurable lipid peroxidation in fresh hepatocytes. It is thus concluded that glutathione has an important role in the cell defence against lipid peroxidation and suggested that the isolated hepatocytes provide a suitable experimental model system for the characterization of this and other possible cellular defence mechanisms and how they are affected by the nutritional status of the donor animal.

Adenosine Diphosphate↗