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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 1,171 records · Page 65Linked to original sources
PubMed1988

Effects of sodium deoxycholate on the mechanical and electrical activities and ultrastructure of guinea pig atria.

The mechanism of cardio-inhibitory effects of sodium deoxycholate (DOC) was investigated by studying its effects on the contractility, action potentials (APs) and ultrastructure of guinea pig atrial preparations. DOC (10(-7)-10(-4) M) caused reversible negative ino- (NIE) and chrono-tropy in spontaneously beating (SBA) and NIE in electrically driven left (EDA) atria. At higher doses (greater than or equal to 1.10(-3) M) DOC caused irreversible inhibition of contractions. Atropine (10(-7)-10(-4) M) failed to inhibit both the reversible and irreversible effects of DOC. The NIE due to lower doses of DOC (less than or equal to 1.10(-4) M) was inhibited by higher [Ca2+]0, isoprenaline (10(-6)-10(-4) M), and noradrenaline (10(-6)-10(-5) M), which did not alter the dose of DOC required for the irreversible and complete NIE. In lower doses (10(-7)-10(-4) M) DOC caused a reversible inhibition of the AP durations at -20 and -40 mV (APD20 and APD40, respectively), but increased the AP duration at 90% repolarisation (APD90). At higher doses (greater than 5.10(-4) M) it caused an irreversible membrane depolarization, reduction in APD20 and APD40, and complete cessation of electrical activity. The ultrastructural changes in atria treated with 1.10(-4) M DOC were characterized by poorly delineated glycocalyx and at greater than 1.10(-3) M by disruption of sarcolemma and sarcoplasmic reticulum and swelling disruption of mitochondria. Taken together these observations show that DOC caused reversible and irreversible inhibition of atrial contractions at low (10(-7)-10(-4) M) and high (greater than 5.10(-4) M) concentrations, respectively, by different mechanisms. The former effect is due to inhibition of Ca2+ channel activity and the latter due to its detergent property causing removal of subcellular components.

Action Potentials↗
PubMed1988

Lumbar vertebral pedicles: radiologic anatomy and pathology.

With the advancement of high-resolution computed tomography (CT) scanning the spine has added new knowledge to the various conditions affecting the pedicles. We wish to review the entire spectrum of pedicular lesions: the embryology, normal anatomy, normal variants, pitfalls, congenital anomalies, and pathological conditions are discussed. Different imaging modalities involving CT, isotope bone scanning, and Magnetic Resonance Imaging (MRI) are used to complement plain films of the lumbar spine. This subject review is an excellent source for future reference to lumbar pedicular lesions.

Fractures, Bone↗
PubMed1987

Observations on the binding of lanthanides and calcium to vitamin D-dependent chick intestinal calcium-binding protein. Implications regarding calcium-binding protein function.

The binding of calcium and terbium to purified chick vitamin D-dependent intestinal calcium-binding protein was studied by terbium fluorescence, circular dichroism, and intrinsic protein fluorescence techniques. Calcium-binding protein bound, with high affinity, at least 3 mol of terbium/mol of protein; numerous low affinity terbium-binding sites were also noted. The three highest affinity sites were resolved into one very high affinity site (site A) and two other sites (sites B and C) with slightly lower affinity. Resonance energy transfer from tryptophan residues to terbium occurred only with site A. This site was filled before sites B and C. Competition experiments in which calcium was used to displace terbium bound to the protein showed that larger amounts of calcium were needed to displace terbium from site A than from sites B and C. Energy transfer from terbium to holmium indicated that the terbium-binding sites (B and C) were located close to each other (about 7-12 A) but were distant (greater than 12 A) from site A. The addition of EDTA to calcium-binding protein resulted in a 25% decrease in intrinsic protein fluorescence, suggesting a conformational change in the protein. The titration of EDTA-treated calcium-binding protein with calcium resulted in recovery of intrinsic protein fluorescence. A reversible calcium-dependent change in the ellipticity of calcium-binding protein in circular dichroism experiments was also seen. These observed properties suggest that vitamin D-dependent chick intestinal calcium-binding protein behaves in a manner similar to other well-known calcium-binding regulatory proteins.

Animals↗
PubMed1987

Occurrence of an endogenous inhibitor of platelet-activating factor in rat liver.

Hepatocytes obtained from livers derived from fed rats perfused with a collagenase-containing mixture were found to contain significant levels of platelet-activating factor activity as isolated by Silica Gel G thin layer chromatography. However, when soybean trypsin inhibitor was included in the collagenase-containing perfusion medium for hepatocyte preparation, platelet-activating factor activity could not be detected on Silica Gel G chromatograms. Examination of the lipids extracted from freeze clamped perfused rat livers revealed low, but detectable, levels of platelet-activating factor. Further investigation of these observations indicated that a lipid-like inhibitor was present in freeze-clamped perfused livers as well as in hepatocytes isolated in the presence of soybean trypsin inhibitor. In each instance platelet-activating factor and this newly discovered inhibitor, which comigrated at the same RF value on Silica Gel G thin layer chromatography plates, could be separated by further chromatography on high performance thin layer plates. The present study shows that platelet-activating factor is present in unstimulated liver and that its detection is masked by an endogenous lipid-like inhibitor.

Animals↗
PubMed1987

Metabolism of platelet-activating factor (alkylacetylphosphocholine) by type-II epithelial cells and fibroblasts from rat lungs.

The uptake and metabolism of 3H-labeled platelet-activating factor by interstitial and epithelial cells from rat lungs was investigated. The uptake of 1-O-[3H]octadecyl-2-acetyl-sn-glycero-3-phosphocholine (3H-AGEPC) by alveolar type-II cells was linear with time from 5 to 60 min, with an average rate of 660 and 450 fmol/10(6) cells for cells in primary culture for 48 to 72 h, respectively. AGEPC was rapidly metabolized and by 10 min 60% of AGEPC was converted into long-chain acylphosphatidylcholine (PC) (50%) and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-GEPC) (10%). By 60 min radioactivity in AGEPC was less than 10% of the total intracellular activity. Lyso-GEPC remained at about 10% throughout the incubation period. The uptake of 3H-AGEPC by fibroblasts was very similar to type II cells, but the rate of metabolism was slower. AGEPC in fibroblasts constituted 85% of the cellular counts after 10 min of incubation, and 50% by 60 min. After 60 min only 30% of the AGEPC was converted to alkylacyl-PC. Characterization of the fatty acids in the alkylacyl-PC of both the type-II cells and lung fibroblasts indicated that arachidonic acid was preferentially (more than 90%) inserted at the 2-position.

Animals↗
PubMed1987

Effect of aging on vitamin D stores and bone density in women.

It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33-94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage form of vitamin D, as well as 25OHD3 (representing both endogenous and exogenous sources of vitamin D), and 25OHD2 (representing only exogenous sources). Both baseline serum total 25OHD (r = -0.29, P less than 0.001) and the metabolite 25OHD3 (r = -0.41, P less than 0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD2, 25OHD3, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.

25-Hydroxyvitamin D 2↗
PubMed1987

Effect of cortisol on [3H] 1,25-dihydroxyvitamin D3 uptake and 1,25-dihydroxyvitamin D3-induced DNA-dependent RNA polymerase activity in chick intestinal cells.

The influence of cortisol on intestinal DNA-dependent RNA polymerase activity was studied in purified nuclei of vitamin D-deficient or 1,25-dihydroxyvitamin D3-treated chicks. Six- to 7-week-old vitamin D-deficient cockerels were given 5 mg of cortisol or vehicle intraperitoneally 24 and 48 hours before sacrifice. Three hours before sacrifice, 200 ng of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was administered intracardially. Cortisol did not alter the uptake or metabolism of 1,25(OH)2D3 in the intestinal mucosa. After a 200 ng dose of 1,25(OH)2D3 the in situ intestinal ligated loop technique revealed a 39% increase in calcium absorption compared to control birds (P less than 0.001). The administration of cortisol (5 mg) to chickens given 1,25(OH)2D3, however, resulted in a significant decrease in intestinal calcium transport in vivo (P less than 0.0025). When intestinal nuclei were prepared from birds treated in a manner identical with that described above, 1,25(OH)2D3-treated and 1,25(OH)2D3 plus cortisol-treated chicks had intestinal RNA polymerase II transcriptional activities that were significantly greater than those of vitamin D-deficient controls (P less than or equal to 0.02, P less than or equal to 0.005). There was no difference between RNA polymerase II and I + III activities of the 1,25(OH)2D3-treated birds and that of the cortisol plus 1,25(OH)2D3-treated birds. Vitamin D-deficient chicks treated with cortisol alone showed RNA polymerase I + III activity that was significantly higher (P less than or equal to 0.01) than that of birds treated with vehicle alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Some unique features of the metabolic conversion of platelet-activating factor (AGEPC) to alkyl acyl PC by washed rabbit platelets.

Recently several synthetic analogs of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC; platelet-activating factor) were characterized as selective inhibitors of this agonist's effects on rabbit platelets (Tokumura, A., Homma, H., and Hanahan, D. J. (1985) J. Biol. Chem. 260, 12710-12714). In this current investigation, these studies have been extended to include a further inquiry into the biochemical nature of the metabolic inactivation of AGEPC in rabbit platelets, and the effect of these analogs on this process. Two of the latter components (U66985 and CV3988), which blocked AGEPC biological activity on rabbit platelets, also blocked the metabolism of this agonist. The metabolic conversion of AGEPC to alkyl acyl PC was inhibited nearly sevenfold by the most potent analog, U66985. Those analogs with low (U68043) or no biological inhibitory activity (lysoGEPC) had marginal effects on the metabolism of AGEPC. The effects of these compounds on the metabolism of AGEPC was not simply due to competitive inhibition. In platelets which had been pretreated with AGEPC in absence of extracellular Ca2+ (desensitized) and washed, the metabolic conversion of AGEPC to alkyl acyl PC was actually enhanced. This enhanced metabolic inactivation of AGEPC was also observed upon the treatment of the cells with thrombin, collagen, or ionophore A23187, indicating that the metabolism of AGEPC in platelets was enhanced not only by AGEPC itself but by other agonists as well. Nearly 85% of the fatty acyl residues was arachidonate in the alkyl acyl PC derived from AGEPC. This specific acylation with arachidonate was observed in the presence and absence of the inhibitor and in desensitized cells, indicating that selectivity for arachidonate is not dependent on the enhancement of the metabolism of AGEPC. The alkyl acyl PC found in the cells treated with thrombin, collagen, or A23187 was also predominantly alkyl arachidonoyl PC. Thus it has been shown that the inactivation of AGEPC by its conversion to alkyl acyl PC by rabbit platelets is enhanced by this agonist itself and that excess amounts of AGEPC could be further inactivated by the enhanced capacity of the metabolism process.

Animals↗
PubMed1987

Synthesis, biologic activity, and protein binding characteristics of a new vitamin D analog, 22-hydroxyvitamin D3.

We synthesized a novel vitamin D analog, 22-hydroxyvitamin D3 9 and tested its biologic activity (and antivitamin properties) in vivo in vitamin D-deficient rats, and in vitro in the chick embryonic duodenum. We examined its ability to bind to the sterol carrier protein, vitamin D binding protein and the chick intestinal cytosol receptor for 1,25-dihydroxyvitamin D3. The new vitamin 9 was synthesized from 3 beta-hydroxy-22,23-dinorcholenic acid 1 in 12 steps. The vitamin 9 displayed no vitamin D agonist activity in the intestine or in bone in vivo and did not block the activity of vitamin D3 or 25-hydroxyvitamin D3. It was a weak vitamin D3 agonist in the chick embryonal duodenum in vitro. It did not antagonize the activity of 1,25-dihydroxyvitamin D3. Vitamin 9 bound to the chick intestinal cytosol receptor with low affinity. 22-Hydroxyvitamin D3 and various vitamin D sterols were bound to vitamin D binding protein in the following order: 25-hydroxyvitamin D3. (24R)-24,25-dihydroxyvitamin D3, and (25S)-25,26-dihydroxyvitamin D3 greater than 22-hydroxyvitamin D3 greater than 11 alpha-hydroxyvitamin D3 greater than 1,25-dihydroxyvitamin D3 greater than vitamin D3. We conclude that the introduction of a hydroxyl group at C-22 in the side chain of the vitamin D3 molecule decreases its biological activity.

Animals↗
PubMed1987

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension.

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.

Adult↗
PubMed1987

Nicotine cue in rats: effects of central administration of ganglion-blocking drugs.

In rats trained to discriminate nicotine from saline, a single intraventricular injection of a small dose of the quaternary ganglion-blocking drug chlorisondamine blocked the response to nicotine for four weeks. pentolinium was only weakly active and hexamethonium was inactive as a nicotine antagonist under the conditions used, even in doses that were just below those producing myoclonic jerks. Chlorisondamine had no blocking effect in rats trained to discriminate the non-nicotinic drugs midazolam or morphine from saline. Intraventricular injections of chlorisondamine have a specific and unusually persistent nicotine-blocking action, the mechanism of which requires further investigation.

Animals↗