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R M Edwards

Publications and source records attributed to R M Edwards.

139 records · Page 8Linked to original sources

Vasopressin-prostaglandin interactions in isolated tubules from rat outer medulla.

Interactions between AVP and prostaglandins were investigated in MAL and MCT microdissected from the rat outer medulla. Incubation of MCT with 14C-arachidonic acid resulted in the formation of 14C-PGE2 and 14C-PGF2 alpha; however, when MAL was incubated under the same conditions, only traces of prostaglandins were formed. Prostaglandin synthesis in MCT was inhibited (-50%) by the prostaglandin cyclo-oxygenase inhibitor ibuprofen (10(-6)M). Preincubation with ibuprofen enhanced the stimulation of adenylate cyclase by 5 x 10(-9)M AVP in MCT but, in contrast, decreased the stimulation of adenylate cyclase by AVP in MAL. The effects of a second PG cyclo-oxygenase inhibitor naproxen (10(-5)M) were similar to those of ibuprofen. Ibuprofen did not influence cAMP phosphodiesterase activity in MCT or in MAL. Exogenous PGE2 or PGF2 alpha (10(-6)M) had no effect on either basal or AVP-stimulated adenylate cyclase activity in MCT. The present results demonstrated that MCT but not MAL is a site of active synthesis and accumulation of prostaglandin. Although both MAL and MCT have AVP-sensitive adenylate cyclase, incubation with prostaglandin cyclo-oxygenase inhibitors have, in the presence of arachidonic acid, an opposite effect on this enzyme in these two segments, resulting in increased AVP stimulation in MCT and decreased stimulation in MAL. Results also suggest that products of prostaglandin synthesis from arachidonic acid inhibit AVP-sensitive adenylate cyclase activity in MCT but not that located in MAL. Although not totally excluding the primary prostaglandins (PGE2, PGF2 alpha), these observations suggest that they are not responsible for AVP modulation in MCT.

Animals↗

Diazontized (125I) diiodosulafanilic acid as a label for cell surface membranes. Studies on erythrocytes.

1. Diazotized 2,6-diiodosulfanilic acid (DDISA) appears to have properties suitable to serve as an artificial, non-penetrating label of cell surface membranes. Therefore, the conditions for selective labeling of cell surface membranes as compared to intracellular proteins as well as a method for its chemical determination were explored in the present study. 2. DDISA reacts with alpha-naphthol at neutral pH to produce a compound (1-hydroxy-4-(2,6-diiodo-4-sulfo-1-phenylazo-(naphthylene)), DSPN) with a characteristic spectrum in the visible range (Amax 430 nm). The absorbance of the reaction product, DSPN, is linearly proportional to the concentration of DDISA and can be used as a method for the colorimetric determination of DDISA. Reaction of DDISA with a molar excess of alpha-naphthol was also used as a method for inactivating unreacted DDISA to terminate labeling prior to cell fractionation. 3. [125I]DDISA reacts avidly with a variety of basic, neutral and acidic proteins as well as with cell membranes to form an acid-stable covalent azo linkage. 4. Effectiveness of labeling of the surface membrane of intact erythrocytes after incubation with [125I]DDISA was assessed by th ratio of 125I incorporated into membrane proteins compared to intracellular proteins. When intact erythrocytes were exposed to [125I]DDISA, the optimal labeling of membranes occurred at 37 degrees C after 20 min of incubation time and at a concentration of 10(-4) M [125I]DDISA in the incubation media. Under these conditions the ratio of the specific activity (cpm 125I/mg protein) of the membrane fraction to the specific activity of the soluble protein fraction (membrane/supernatant ratio) was greater than 500. When incubations were conducted at 4 degrees C this ratio was less than 50. However, when osmotically lysed erythrocytes were incubated with [125I]DDISA the majority of the label reacted with the soluble protein fraction resulting in a membrane/supernatant ratio of 0.14. 5. The results thus suggest that [125I]DDISA used under the appropriate incubation conditions, including the inactivation and removal of [125I]DDISA by washing with alpha-naphthol, can serve as a highly selective membrane label with minimal incorporation into intracellular soluble proteins. The general applicability of this method for other cell types remains to be explored.

Diazonium Compounds↗

Modulation of cyclic nucleotides in islated rat glomeruli: role of histamine, carbamylcholine, parathyroid hormone, and angiotensin-II.

Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+Delta% 675+/-87) and, to a lesser degree, increased cAMP in tubules (+Delta% 103+/-25) or in tissue slices. This stimulation was dose-dependent in the range of 1 muM-1 mM histamine. Metiamide (an H(2)-antagonist), but not pyrilamine (an H(1)-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H(2) receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+Delta 295+/-7) and a much lower increase in tubules (+Delta% 70+/-20); these effects were blocked by atropine. Parathyroid hormone (1 mug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused much more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-II (2 muM) markedly lowered cAMP in glomeruli (-Delta% -45+/-8) and in tubules (-Delta% 33+/-7) but had no effect on cGMP. Bradykinin (20 muM) did not consistently influence either cAMP or cGMP in glomeruli or tubules. Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediated by cAMP and (or) cGMP through interaction with H(2) receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both.

Angiotensin II↗

Inexpensive device for the aerobic and anaerobic sampling of microorganisms in lake and shallow ocean waters.

An inexpensive device suitable for sampling microorganisms in water and easily constructed from readily available laboratory equipment is described. The need to transfer subsamples to culturing flasks after collection is eliminated by partly filling the sampling vessels with growth medium prior to sampling. The device is readily adapted for sampling different volumes, is simple and quick to operate, and is suitable for use with prereduced media. Contamination from layers others than that being sampled is insignificant.

Aerobiosis↗

Interactions of radiofrequency radiation on 2-methoxyethanol teratogenicity in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with microelectronics industry, plastic sealers and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats. A subsequent study replicated and extended that research by investigating the interactive dose-related teratogenicity of r.f. radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20 or 30 min by r.f. radiation absorption) and 2ME (0, 75, 100, 125 or 150 mg/kg) on gestation days 9 or 13 of rats. The purpose of the present research is to determine the effects of r.f. radiation (sufficient to maintain colonic temperatures at 42.0 degrees C for 10 min) on a range of doses of 2ME (0, 20, 40, 60, 80, 100, 120 and 140 mg kg-1) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Dose-related developmental toxicity was observed for 2ME both in the presence and absence of r.f. radiation. However, concurrent RF radiation exposure changed the shape of the dose-effect curve of 2ME. These data indicate that combined exposure effects should be considered when developing exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗

Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in anuran (frog) skins.

The distribution of cyclo (His-Pro)-like immunoreactivity in frog skins from seven frog species was examined. The chromatographic elution profile of cyclo (His-Pro)-like immunoreactivity in amphibian skins measured by radioimmunoassay corresponded precisely to that of [3H-Pro]-cyclo (His-Pro) after DEAE-Cellulose, Sephadex G-25 and high-pressure liquid chromatography. The concentrations of cyclo (His-Pro) in frog skins were much higher than the concentrations of TRH previously observed in skin and the concentrations of cyclo (His-Pro) in both brain and gastrointestinal tract.

Animals↗

Freshmen baccalaureate nursing students' perceptions of their academic and nonacademic experiences: implications for retention.

As a component of the evaluation for a program designed to enhance recruitment and retention of disadvantaged nursing students, qualitative interviews were conducted, with a sample of 20 baccalaureate nursing students at the end of their freshman year. Students were asked to describe positive aspects of their academic and nonacademic experiences as well as problems that were experienced, with recommendations for resolving these problems. Positive aspects of the freshman experience that were identified included academic, social, familial, and financial support. Problems cited were related to two categories of factors, external and internal. Problems related to external factors included excessive academic loads, course-specific problems such as with the sciences, large class size, faculty inattentiveness, racial tensions, dorm/roommate problems, and parking or commuting time. Problems related to internal factors included poor study habits, loneliness, homesickness, family conflicts, and difficulties with peer relationships. The findings can be used by nursing faculty to determine the extent to which programs address students' perceived needs and to identify innovative retention strategies that would enhance students' perceptions of their college experience.

Alabama↗

Platelet-activating factor (PAF) has no direct effect on rat intracerebral arterioles in vitro.

We examined the effect of platelet activating-factor (PAF) on lumen diameter of penetrating intracerebral arterioles (diameter less than 50 microns) dissected from rat brains. PAF over a concentration range of 10(-12)-10(-6) M had no effect on lumen diameter. However, the arterioles were capable of both vasodilation in response to calcitonin gene-related peptide (EC50 = 4.4 nM) and vasoconstriction in response to the thromboxane mimetic, U44619 (EC50 = 5.8 nM). We conclude that the effects of PAF on the cortical circulation observed in vivo are indirect and may be due to PAF-induced changes in other humoral or cellular mediators.

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

Adrenomedullin: a new peptide involved in cardiorenal homeostasis?

Adrenomedullin (ADM) was originally discovered in human pheochromocytoma but is now known to be widely distributed in various organs including the kidney. ADM is a potent hypotensive peptide that increases renal blood flow and causes natriuresis and diuresis. While ADM may act in a paracrine manner, circulating levels are increased in hypertension, chronic renal failure and congestive heart failure. Current evidence suggests that ADM may play an important role in cardiorenal homeostasis.

Adrenomedullin↗