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W M Moore

Publications and source records attributed to W M Moore.

At least 37 records · Page 2Linked to original sources
PubMed1994

L-N6-(1-iminoethyl)lysine: a selective inhibitor of inducible nitric oxide synthase.

L-N6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS). L-NIL has an IC50 of 3.3 microM for miNOS compared to an IC50 of 92 microM for rat brain constitutive NOS indicating that L-NIL is 28-fold more selective for inducible NOS. L-N5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by having one less methylene group, has very similar potency for inducible NOS, but lacks selectivity. DL-N7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediate selectivity for inducible NOS. These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the role of this enzyme in disease models.

Amino Acid Oxidoreductases↗
PubMed1994

Characterization of human uroguanylin: a member of the guanylin peptide family.

Guanylin, a peptide homologue of the bacterial heat-stable enterotoxins (ST), is an endogenous activator of guanylate cyclase C (GC-C). We have initiated a search for other members of the guanylin peptide family and in the current study describe a "guanylin-like peptide" from human urine. Bioactivity was monitored by determining the effect of urine extracts on T84 cell guanosine 3',5'-cyclic monophosphate (cGMP) levels. Purification yielded two bioactive peaks of peptides that, when sequenced by NH2-terminal analysis, possessed 15 and 16 amino acids. The sequence of the smaller peptide represented an NH2-terminal truncation of the larger peptide. We have termed the larger peptide human uroguanylin; it has the following amino acid sequence: NDDCELCVNVACTGCL. Human uroguanylin shares amino acid sequence homology with guanylin and ST. Synthetic uroguanylin increased cGMP levels in T84 cells, competed with 125I-labeled ST for receptors, and stimulated Cl- secretion as reflected by an increased short-circuit current. Thus we report the isolation from human urine of a unique peptide, uroguanylin, that behaves in a manner similar to guanylin and appears to be a new member of this peptide family.

Adult↗
PubMed1993

Selective inhibition of the inducible nitric oxide synthase by aminoguanidine.

Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell, and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

Amino Acid Oxidoreductases↗
PubMed1993

A fluorometric assay for the measurement of nitrite in biological samples.

The increasing importance of nitric oxide synthase has been underscored by the elucidation of its role in a growing number of normal and pathophysiological processes. Therefore, techniques for detection of nitrite/nitrate, oxidation products of the enzymatic conversion of arginine to citrulline and nitric oxide, should serve as useful tools in defining the contribution of NO synthase to these processes. We have developed a rapid and sensitive fluorometric assay for quantification of nitrite/nitrate based upon the reaction of nitrite with 2,3-diaminonaphthalene to form the fluorescent product, 1-(H)-naphthotriazole. The assay can be used to detect 10 nM nitrite, making it 50-100 times more sensitive than the well-known Griess assay. Moreover, the assay is adaptable to a 96-well plate format, facilitating the handling of a large number of samples including conditioned media from cell culture or the nitrite generated by the purified enzyme. Nitrite/nitrate levels in blood can also be monitored using this assay when it is combined with a filtration step (to remove hemoglobin) followed by conversion of the nitrate to nitrite by nitrate reductase. Thus, this fluorometric method combines speed and sensitivity with the handling of a large number of samples for the quantification of nitrite generated from in vivo and in vitro sources.

2-Naphthylamine↗
PubMed1993

Influence of audit and feedback on use of caesarean section in a geographically-defined population.

The influence of audit and feedback on use of caesarean section was investigated in a geographically defined population. At the beginning of 1986 and throughout that year the three principal reasons for the increased use of caesarean section were drawn to the attention of the resident obstetricians in the hospital where 85% of the women resident in the health district gave birth. A repeat survey of the indications for caesarean section was conducted for 1986 births. Despite an increase in the number of women delivered in 1986 who had previously had two or more sections, the caesarean section rate fell from 15.9% in 1982 to 12.7% in 1986 (P < 0.005). Most of this decrease was due to a reduction in caesarean section for the three indications that were the main contributors to the increased rate between 1974 and 1982. The rate for the women who gave birth in the hospital whose resident obstetricians had been informed about the preceding audit was 12.2%, compared with 15.6%, for the women who gave birth in other hospitals. Audit and feedback of specific information, imparted in a non-directive way to resident obstetricians responsible for performing caesarean section, probably accounted for a more rational use of caesarean section.

Cesarean Section↗
PubMed1993

Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation.

This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity and AGE formation, to inhibit diabetic vascular dysfunction developing early after the onset of diabetes. In rats with STZ-induced diabetes of 5-wk duration, regional vascular [125I]albumin permeation was increased about two- to threefold in ocular tissues, sciatic nerve, and aorta; in general, both guanidine compounds normalized albumin permeation in diabetic rats without affecting it in controls. Methylguanidine was only approximately 7% as effective as aminoguanidine as an inhibitor of AGE formation from L-lysine and G6P; both compounds were poor inhibitors of AR. Methylguanidine was approximately 1-5% as potent as aminoguanidine and L-NMMA as an inhibitor of the cytokine- and endotoxin-inducible isoform of NO synthase. In contrast, the potency of methylguanidine as an inhibitor of the constitutive isoform of NO synthase was comparable to that of aminoguanidine, and both guanidine compounds were much less effective than L-NMMA. These observations suggest a role for a relative or absolute increase in NO production in the pathogenesis of early diabetic vascular dysfunction and raise the possibility that inhibition of diabetic vascular functional changes by aminoguanidine may reflect inhibition of NO synthase activity rather than, or in addition to, prevention of AGE formation.

Aldehyde Reductase↗
PubMed1993

Evaluation of the strength of vascular anastomotic techniques.

The strength of various anastomotic techniques was examined in a canine model utilizing a strain gauge to determine the force required to disrupt single/double/multiple sutures placed at 1,2, and 3 mm depth of bite. Pull-out strength was found to be primarily a factor of the plane of preliminary arterial dissection, reflected as the amount of adventitia included in each bite; the depth of the suture was a lesser contributory factor. Pull-out strengths of complete vascular anastomoses were no stronger than their constituent single stitches. An optimal vascular anastomotic technique is therefore advocated.

Anastomosis, Surgical↗
PubMed1992

Prediction of birthweight by fetal ultrasound biometry.

A total of 104 women with singleton pregnancies who were delivered between 37 and 42 weeks gestation had ultrasound scans during the fortnight before delivery. The biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were measured in all cases. Estimation of fetal weight (EFW) was done by four different methods: using AC alone, AC/BPD, AC/FL and AC/BPD/FL. Results were compared with values of actual birthweights at delivery. There was no significant difference between the mean birthweights of the 47 boy and 57 girl fetuses studied. The EFW(Shepard) method showed the least bias overall: mean percentage error 1.7%, standard deviation (SD) 10.6%. The other three methods significantly underestimated birthweights on average: EFW(Deter), mean error 2.2%, SD 9.3%, p < 0.02; EFW(Campbell), mean error 5.4%, SD 9.5%, p < 0.001; EFW(Hadlock), mean error 5.6%, SD 9.3%, p < 0.001. The percentage error in each group was significantly negatively correlated (p < 0.001) with the scan-delivery interval. Two new equations were generated which gave more accurate predictions for the cases under study using AC, BPD and FL as a combination and also in addition to scan-delivery interval (SDI) in days.

Abdomen↗
PubMed1991

Phosphoramidon blocks the pressor activity of porcine big endothelin-1-(1-39) in vivo and conversion of big endothelin-1-(1-39) to endothelin-1-(1-21) in vitro.

In porcine aortic endothelial cells, the 21-amino acid peptide endothelin-1 (ET-1) is formed from a 39-amino acid intermediate called "big endothelin-1" (big ET-1) by a putative ET-converting enzyme (ECE) that cleaves the 39-mer at the bond between Trp-21 and Val-22. Since big ET-1 has only 1/100-1/150th the contractile activity of ET-1, inhibition of ECE should effectively block the biological effects of ET-1. Big ET-1 injected intravenously into anesthetized rats produces a sustained pressor response that presumably is due to conversion of big ET-1 into ET-1 by ECE. We determined the type of protease activity responsible for this conversion by evaluating the effectiveness of protease inhibitors in blocking the pressor response to big ET-1 in ganglion-blocked anesthetized rats. The serine protease inhibitor leupeptin, the cysteinyl protease inhibitor E-64, and the metalloprotease inhibitors captopril and kelatorphan were all ineffective at blocking the pressor response to big ET-1. However, the metalloprotease inhibitors phosphoramidon and thiorphan dose-dependently inhibited the pressor response to big ET-1, although phosphoramidon was substantially more potent than thiorphan. None of the inhibitors blocked the pressor response to ET-1 and none had any effect on mean arterial pressure when administered alone. In a rabbit lung membrane preparation, ECE activity was identified that was blocked by the metalloprotease inhibitors phosphoramidon and 1,10-phenanthroline in a concentration-dependent manner. This enzyme converted big ET-1 to a species of ET that comigrated on HPLC with ET-1 and produced an ET-like contraction in isolated rat aortic rings. Our results suggest that the physiologically relevant ECE is a metalloprotease.

Animals↗
PubMed1991

The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia.

To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia.

Animals↗
PubMed1991

Phosphoramidon blocks the pressor activity of big endothelin[1-39] and lowers blood pressure in spontaneously hypertensive rats.

In porcine aortic endothelial cells, the 21-amino acid peptide endothelin-1 (ET-1) is formed from a 39-amino acid intermediate big endothelin (big ET) by a putative endothelin-converting enzyme (ECE) that cleaves the 39-mer at the Trp21-Val22 bond. Because big ET has less than 1% of the contractile activity of ET-1, inhibition of ECE should effectively block the biological effects of big ET. Big ET injected intravenously into anesthetized rats produces a sustained pressor response that presumably is due to conversion of big ET to ET-1 by ECE. We determined the type of protease activity responsible for this conversion by evaluating the effectiveness of protease inhibitors in blocking the pressor response to big ET in ganglion-blocked anesthetized rats. The serine protease inhibitor leupeptin, the cysteinyl protease inhibitor E-64, and the metalloprotease inhibitors captopril and kelatorphan were ineffective at blocking the pressor response to big ET. However, the metalloprotease inhibitors phosphoramidon and thiorphan both dose-dependently inhibited the pressor response to big ET, although phosphoramidon was substantially more potent than thiorphan. None of the inhibitors blocked the pressor response to ET-1 and none had any effect on blood pressure when administered alone as an i.v. bolus to the ganglion-blocked anesthetized rat. However, phosphoramidon infused intravenously at 20 mg/kg/h for 4 h lowered the mean arterial pressure (MAP) in conscious spontaneously hypertensive rats (SHRs) whereas kelatorphan at the same dose did not. Our results suggest that ECE is a novel metalloprotease and that ECE inhibitors could have therapeutic potential for the treatment of hypertension.

Animals↗
PubMed1991

Superior vena cava and central venous reconstruction.

Partial or complete obstruction of the superior vena cava and its major tributaries occassionally results in incapacitating venous hypertension of the upper extremities and/or head and neck. Factors intrinsic and extrinsic to the central veins play a role in the pathogenesis. The more common causes include mechanically and chemically induced intimal injury with resultant fibrosis, sclerosis, or thrombosis and neoplastic masses with external compression or direct extension in the central venous structures. Medical therapy is indicated in the acute situation and generally allows the time necessary for development of collateral drainage routes. Persistent or progressive symptomatic venous hypertension develops in 5% to 40% of these patients, and approximately 10% of the patients will remain incapacitated. Presented here is a series of 10 patients who underwent reconstruction of the superior vena cava or central veins for incapacitating venous hypertension of the upper extremities and/or head and neck. Reconstruction was accomplished by venous transposition (three patients), externally reinforced ePTFE (six patients), and reversed saphenous vein graft (one patient). No perioperative deaths occurred; however, two late deaths occurred at 3 and 9 months after reconstruction from causes unrelated to the operative procedure. One patient experienced early postoperative graft thrombosis requiring thrombectomy, after which the graft remained patent. All patients had patent grafts and were asymptomatic with respect to their venous disease at the time of preparation of this manuscript, with a mean follow-up period of 30 months. Specific details concerning these 10 cases are discussed and integrated with a focused review of the literature and the historic development of the intraoperative techniques and postoperative care that facilitate the successful management of patients with symptomatic central venous occlusion.

Blood Vessel Prosthesis↗
PubMed1991

Mesenteric artery occlusive disease.

The age and advanced stage of atherosclerosis in this patient population require careful preoperative evaluation and attention to detail in the perioperative period in an effort to avoid complications in other organ systems resulting from diffuse occlusive disease. The keys to accurate diagnosis and successful management of patients with acute or chronic mesenteric ischemia include a detailed history, focusing on the quality and temporal relation of the symptoms; an accurate vascular assessment on physical examination, with attention directed to ruling out nonvascular causes of the symptoms; a high index of suspicion of vascular origin for otherwise unexplainable abdominal pain in the patient population at risk; an aggressive diagnostic approach with a low threshold for obtaining mesenteric angiography; CT of the abdomen to rule out occult pancreatic carcinoma; expeditious correction of metabolic and electrolyte abnormalities and optimization of cardiac function; and early surgical intervention, with directed revascularization in an effort to minimize loss of bowel from infarction.

Acute Disease↗
PubMed1990

Sleep in the first year of life.

The sleep patterns of 174 infants were recorded on one typical day at six, 13, 26 and 52 weeks of age, using a 24-hour log. During the first year of life the number of episodes of sleep was reduced by about 50 per cent, but total sleep time was reduced by only two hours. A circadian rhythm was established by six weeks of age. Smaller infants slept more than larger ones in the first months of life. Sex or birth-order of the child did not affect the duration or number of sleep episodes, but sleep pattern related significantly to whether or not mothers found their infants difficult to feed. Introduction of weaning food at an early stage reduced the number of sleep episodes, but increased the average length of each episode. Socio-economic status showed no significant relationship with number of episodes or total length of sleep.

Circadian Rhythm↗