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Biomedical subjects

M L Brown

Publications and source records attributed to M L Brown.

At least 19 recordsLinked to original sources
PubMed1992

Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation.

Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.

Acylation↗
PubMed1992

Human gastric and jejunal transit and motility after Roux gastrojejunostomy.

Upper gut transit and motility among 10 symptomatic and 9 asymptomatic patients with Roux gastrectomy were compared with those among 10 healthy, unoperated controls. Gastric emptying of solids and Roux limb and small intestinal transit of liquids were assessed scintigraphically. Motor patterns in the Roux limb or healthy jejunum were recorded manometrically. Whereas gastric emptying was sometimes faster and sometimes unchanged after Roux gastrectomy compared with controls, Roux limb transit in patients was consistently slower than jejunal transit in controls. Postprandially, the Roux limb showed decreased overall motility, fewer clustered waves, and less aboral migration of clustered waves than the healthy jejunum. Symptomatic Roux patients had jejunal transit and motor patterns similar to those of asymptomatic patients. Nonetheless, reflux from Roux limb to gastric remnant occurred in 4 of 10 symptomatic patients but in none of the asymptomatic patients. In conclusion, stasis and dysmotility are present in the Roux limb after Roux gastrectomy and Roux-gastric reflux can occur. Other factors, however, must have a role in determining whether symptoms appear.

Adult↗
PubMed1992

Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone.

Relaxation of penile corpus cavernosum smooth muscle is controlled by nerve and endothelium derived substances. In this study, endothelium-dependent relaxation of corporal smooth muscle was characterized and the role of arachidonic acid products of cyclooxygenase in endothelium-dependent relaxation was examined. Endothelium removal from rabbit corpora was performed by infusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate and was confirmed by transmission electron microscopy. Strips of human and rabbit corporal tissues were studied in the organ chambers for isometric tension measurement. The accumulation of cyclic guanosine monophosphate (cGMP) and the release of eicosanoids from corporal tissue was measured by radioimmunoassay and correlated to smooth muscle relaxation. Our study showed that relaxation of corpus cavernosum tissue to acetylcholine, bradykinin and substance P was endothelium-dependent; potentiated by indomethacin; and inhibited by NG-monomethyl-L-arginine, methylene blue or LY83583. Relaxation to papaverine and sodium nitroprusside was endothelium-independent, and unaffected by NG-monomethyl-L-arginine. Relaxation to vasoactive intestinal polypeptide was partially endothelium-dependent; potentiated by indomethacin; attenuated by NG-monomethyl-L-arginine or methylene blue. The tissue level of cGMP was enhanced by acetylcholine and nitric oxide. Methylene blue inhibited both basal and drug-stimulated levels of cGMP. The release of eicosanoids was enhanced by acetylcholine and blocked by indomethacin. In conclusion, nitric oxide or a closely related substance accounts for the activity of endothelium-derived relaxing factor in the corporal tissue. Inhibition of the release of eicosanoids potentiates the relaxing effect of nitric oxide. Nitric oxide increases tissue cGMP which appears to modulate corporal smooth muscle relaxation.

Acetylcholine↗
PubMed1992

Aldose reductase and myo-inositol in endothelial cell dysfunction caused by elevated glucose.

A possible relationship between aldose reductase activity and myo-inositol levels and endothelium-dependent relaxations was examined in isolated rabbit aorta incubated with elevated concentrations of glucose (44 mM) for 6 hr to mimic hyperglycemic conditions. Rings of aorta incubated in elevated glucose and contracted submaximally by phenylephrine showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with aorta incubated in control (5.5 or 11 mM) glucose. Acetylcholine-induced relaxations of aorta incubated in hyperosmotic mannitol (44 mM) were not different from those incubated in control glucose. Treatment with two structurally unrelated aldose reductase inhibitors, sorbinil or zopolrestat, or supplementation with myo-inositol, prevented the abnormal acetylcholine relaxations of aortic rings caused by elevated glucose. No effects of sorbinil, zopolrestat or myo-inositol were observed on the response to acetylcholine of aorta incubated in control glucose. Neither sorbinil nor myo-inositol affected the increase in release of vasoconstrictor prostanoids caused by elevated glucose. These findings suggest that sorbitol accumulation and myo-inositol depletion contribute to the abnormal endothelial cell function caused by exposure to elevated glucose. The increased release of vasoactive prostanoids is either independent of, or possibly contributes to, the abnormal aldose reductase activity and/or myo-inositol depletion in intact blood vessels exposed to elevated concentrations of glucose.

Acetylcholine↗
PubMed1992

Economic considerations in breast cancer screening of older women.

The incidence of breast cancer increases with age, tending to result in more favorable cost-effectiveness outcomes with more advanced age of the screened population. On the other hand, the decreased remaining life expectancy of older women can be expected to reduce the cost effectiveness of screening. To assess these competing factors, the cost effectiveness of a long-term breast cancer screening program was evaluated using a computerized simulation model. The cost per life year saved decreased when the 65-69 year age group was added to a program screening women aged 50-64. For older age groups, however, cost effectiveness became relatively less favorable. The cost per life year saved of screening the 80-84 year age group was 55% higher than for the 65-69 group.

Aged↗
PubMed1979

Interactions of cartilage proteoglycans with hyaluronate. The role of the hyaluronate acetamido groups.

Hyaluronate oligomers were treated with anhydrous hydrazine in the presence of hydrazine sulfate to remove the N-acetyl groups. Complete deacetylation could not be achieved without extensive degradation of the oligosaccharide chain. Partially deacetylated oligomers exhibited decreased inhibition of cartilage proteoglycan-hyaluronate interaction as compared to the unreacted starting material; re-N-acetylation by reaction with acetic anhydride restored the inhibitory activity to a great extent. When the hydrazine-treated oligosaccharides were reacted with other acyl anhydrides, the inhibitory potency was restored to an extent which was inversely related to the size of the acyl group. Thus, for maximal interaction between hyaluronate and proteoglycan, the glucosamine residue of hyaluronate must be N-acylated with a minimally sized acyl group.

Acetylglucosamine↗
PubMed1979

Interactions of cartilage proteoglycans with hyaluronate. Inhibition of the interaction by modified oligomers of hyaluronate.

Oligomers of hyaluronic acid were prepared by digestion of hyaluronic acid from rooster combs with testicular hyaluronidase (hyaluronate 4-glycanohydrolase, EC 3.2.1.35), leech head hyaluronidase (hyaluronate 3-glycanohydrolase, EC 3.2.1.36), and with fungal hyaluronidase (hyaluronate lyase from Streptomyces hyalurolyticus). The oligomers were fractionated by gel permeation, using Sephadex G-50. Oligomers isolated after incubation of the hyaluronic acid with the testicular hyaluronidase were further modified. To prepare oligomers with N-acetylglucosamine at both ends, terminal nonreducing glucuronic acid residues were removed with beta-glucuronidase. Reducing terminal N-acetylglucosamine residues were removed by reaction under mildly alkaline conditions. The reducing terminal N-acetylglucosamine residues were also reduced with sodium borohydride to form N-acetylglucosaminitol. The potentials of the various oligosaccharides to bind to the proteoglycan from bovine nasal septum cartilage were estimated by determining their effectiveness as inhibitors of the proteoglycan-hyaluronate interaction. The present study shows that, to bind maximally to the proteoglycan, the hyaluronate oligosaccharide must be at least 10 sugar residues in length and be terminated at the nonreducing and reducing ends with a glucuronate residue and an N-acetylglucosamine residue, respectively. Sugar residues extended beyond this basic decasaccharide, do not interact with the hyaluronate binding site on the proteoglycan.

Animals↗
PubMed1979

A simple model for anatomic bone scanning studies.

A simple anatomic model for studying the scintigraphic appearance of various skeletal structures is described. The technique makes use of the fact that technitium pyrophosphate uptake in bone occurs by chemisorption to the surface of crystals in the bone matrix. By soaking clean bones in solutions of technetium pyrophosphate they can be rendered radioactive and subsequently studied by various imaging techniques.

Bone and Bones↗
PubMed1979

Radiation absorbed dose to the lens in dacryoscintigraphy with 99mTcO4-.

Calculations of the radiation dose to the lens for 99mTcO4- in dacryoscintigraphy are developed in some detail. The results indicate that the absorbed dose to the germinal epithelium of the lens is 2.2 X 10(-5) to 1.4 X 10(-4) rad/microCi (5.9 x 10(-12) to 3.8 x 10(-11) Gy/Bq) 99mTcO4- under physiological conditions. With blockage of the lacrimal drainage apparatus, the dose to the lens could increase to 4 X 10(-3) rad/microCi (1 X 10(-9) Gy/Bq).

Cornea↗
PubMed1978

False negative bone scans in neuroblastoma metastatic to the ends of long bones.

Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup.

Bone Neoplasms↗
PubMed1978

Clinical comparison of cardiac blood pool visualization with technetium-99m red blood cells labeled in vivo and with technetium-99m human serum albumin.

Technetium-99m red blood cells (Tc-RBC) labeled by an in vivo technique were compared with two preparations of Tc-99m human serum albumin (HSA) for cardiac blood-pool imaging. Relative distribution of the tracers was analyzed on end-diastolic frames of gated blood-pool studies and on whole-body (head to mid-thigh) anterior pinhole images. The Tc-RBC demonstrated greater relative percentage localization in the cardiac blood pool, higher target-to-background ratios in the left ventricle, and less liver concentration. For cardiac blood-pool imaging, Tc-RBC labeled by the in vivo approach appears to be superior to the two Tc-HSA preparations studied.

Cardiac Volume↗
PubMed1978

Gallium-67 scintigraphy in untreated and treated non-hodgkin lymphomas.

One hundred and seventy-four gallium scans of patients with biopsy-proved non-Hodgkin lymphoma were reviewed. When the lymphomas were subdivided into histologic groups, there was a significant difference in detection rates, with 62% of the histiocytic lymphomas being identified, while only 39% of the poorly differentiated lymphocytic lymphomas were detected. There was a high detection rate for lesions in the mediastinum and in extranodal locations. When analyzed with regard to therapy, the detection rate was higher in all histologic subgroups after therapy than before.

Adult↗
PubMed1978

Multiple-gated acquisition cardiac blood-pool isotope imaging. Evaluation of left ventricular function correlated with contrast angiography.

Thirty-one patients were assessed by the multiple-gated acquisition cardiac blood-pool isotope-imaging technique using radiolabeled albumin within 24 hours of biplane contrast ventriculography. Data from the imaging method were analyzed by a semiautomatic technique with computer-generated edge detection and background subtraction. An excellent correlation was observed between ejection fractions determined with multiple-gated isotope imaging and those obtained by biplane contrast ventriculography (r = 0.93), and the same was true for average ejection rates (r = 0.80). For assessment of wall motion with this imaging technique, the anterior and the left anterior oblique left ventricular views were divided into nine segments, and a score was assigned to each segment based on the degree of wall motion. The cumulative anterior and left anterior oblique scores correlated well with the score from biplane contrast ventriculography (r = 0.90), and in 94% of segments in the left anterior oblique projection the assessment with multiple-gated isotope imaging was the same as or varied by only one class from the assessment by biplane contrast ventriculography. The multiple-gated acquisition cardiac blood-pool isotope-imaging technique is thus a valuable noninvasive method for assessing left ventricular function as measured by ejection fraction, ejection rates, and wall motion.

Adult↗