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Biomedical subjects

W M Moore

Publications and source records attributed to W M Moore.

At least 55 records · Page 3Linked to original sources

In vitro and in vivo activity of chymotrypsin-activated big endothelin (porcine 1-40).

We investigated whether big endothelin (porcine 1-40) had contractile activity in isolated rat aorta or pressor activity when injected intravenously into the anesthetized rat. When isolated rat aorta was exposed to a 100 nM concentration of big endothelin, 4.8% of a maximal KCl contraction was observed, compared to 131% of KClmax when paired aortic rings were exposed to an equivalent concentration of synthetic endothelin. Likewise, big endothelin had very weak pressor activity when injected intravenously into anesthetized, ganglion-blocked rats at 10 nmol/kg. When big endothelin was incubated with chymotrypsin, native endothelin and other peptide fragments were formed. Chymotrypsin-treated big endothelin produced an endothelin-like contraction when applied to isolated rat aortic rings, and a characteristic endothelin-like effect on blood pressure in vivo. Our results indicate that the biological activity of endothelin could be effectively blocked by inhibiting the enzyme which converts big endothelin to endothelin.

Amino Acid Sequence↗

Weight and recumbent length from 1 to 12 mo of age: reference data for 1-mo increments.

Serial data from 504 infants were used to develop reference data for 1-mo increments in weight and recumbent length by fitting a family of three-parameter mathematical functions to the serial data for each individual. The percentiles for status and for increments tended to be larger for the boys than for the girls except for the lower percentiles of increments for weight after 9-10 mo and for recumbent length after 8-9 mo. These data can be used to assess growth in white or black infants whether they are breast-fed or formula-fed. These new data will allow earlier evaluation of growth velocity than the reference data for 3- and 6-mo increments that were available previously. This can lead to the earlier initiation of diagnostic procedures and treatment. The present data should be useful also in research studies.

Body Height↗

Reference data for head circumference and 1-month increments from 1 to 12 months of age.

Serial head circumference measurements in 462 participants in the Fels Longitudinal Study were used to develop reference data for ages 1 to 12 months. We used a three-parameter mathematical function to model the serial head circumference data for each individual and estimated head circumference at 1-month intervals. Reference data for selected percentiles of head circumference status and 1-month increments were calculated from the estimated head circumferences. These reference data are presented in tables and charts for use in testing hypotheses about group differences or to monitor changes within individuals.

Cephalometry↗

Sex difference in fetal head growth.

Growth of the fetal biparietal diameter (BPD) throughout the second and third trimesters was measured in a prospective longitudinal study. Linear-cubic equations were fitted to the data of individual fetuses and from these equations mean growth curves were produced for males and females. The head growth trajectories of males and females were significantly different. The study illustrates why the practice of dating pregnancies by ultrasonic fetal BPD measurement at about 16 weeks gestation can lead to error.

Cephalometry↗

Assessment of transmural force during application of vascular occlusive devices.

An in vivo system was established whereby the transmural forces exerted across the arterial wall during vascular occlusion were directly measured. Evaluation of various currently available vascular occlusive devices was conducted and transmural force transmission data were recorded. The clamps were classified according to their mechanical design characteristics. The magnitude of force required to obtain cessation of distal flow varied significantly among devices of differing mechanical design but correlated well when compared with clamps of similar design. This information was then compared with graded analysis of the degree of intimal injury created by these specific devices as assessed with scanning electron microscopy. The amount of transmural force exerted by each individual device correlated with the grade of intimal injury created by that device. We conclude that fundamental clamp design dictates the magnitude of applied transmural force, that force and the vectors of the application of that force are directly responsible for the degree of resultant intimal injury, and that the intima appears to possess an injury threshold of approximately 5 x 10(4) dynes/cm2. Intimal injury may determine success or failure of vascular surgical procedures; therefore it is prudent to seek the least traumatic means of vascular occlusion.

Animals↗

Traumatic hemipelvectomy.

Management of patients who have suffered traumatic hemipelvectomy is one of the most difficult challenges to confront a trauma surgeon. We present a case of a female survivor of traumatic hemipelvectomy and factors in the care of these patients that can lead to a successful outcome.

Accidents, Traffic↗

The changing incidence of caesarean section in the health district of Central Manchester.

The caesarean section rate in England and Wales has practically doubled from 5.6% in 1974 to 10.6% in 1982. Because most statistical reports are based on the practice of individual hospitals and do not reflect what is occurring in a particular community, a retrospective study of the incidence of, and reasons for, caesarean section performed in residents of the geographically defined Health District of Central Manchester was carried out for 1974 and 1982. The caesarean section rate in this community increased from 7% in 1974 to 16% in 1982. Caesarean sections performed for failure to progress in labour, previous caesarean section and preterm fetal compromise before labour accounted for three quarters of the increase. Breech presentation was not a significant contributor to the increase. The reasons for the increase in caesarean sections performed for failure to progress in the first stage of labour were not clarified in the records, and is the subject of prospective investigation.

Adolescent↗

Head circumference reference data: birth to 18 years.

Highly reliable data from a sample of 888 white US children, measured serially in a single study, have been used to provide reference data for head circumference from birth to 18 years of age. The present data differ little from those already available for the age range from birth to 36 months of age, but they are considerably higher (about 0.5 cm) at older ages for boys and tend to be slightly higher for girls. These new reference data are smoother across age than those used currently for screening and evaluation. Percentiles for 6-month increments from birth to 6 years have been provided.

Cephalometry↗

Production of interleukin 1 by SK hepatoma tumor cells.

SK hepatoma cells and SK hepatoma conditioned media contain an 18,000-dalton factor which is pyrogenic, stimulates collagenase and prostaglandin production in skin and synovial fibroblasts, induces bone resorption, and stimulates the proliferation of murine thymocytes. These results are consistent with the finding that this tumor cell line produces interleukin 1 [Doyle, M. V., Brindley, L., Kawasaki, E., & Larrick, J. (1985) Biochem. Biophys. Res. Commun. 130, 768-773] since all these activities have been associated with this cytokine. Greater than 80% of the cellular activity has a molecular weight of 30,000, while in contrast, greater than 80% of the activity in the tumor-conditioned media has a molecular weight of 18,000. When active material from the cells is incubated with trypsin, this high molecular weight material is completely converted into an active 18,000 molecular weight species. The isoelectric point of all active material is always between pI 4.0 and 5.1, regardless of molecular weight. All of these results are consistent with the hypothesis that active, high molecular weight interleukin 1 alpha is first synthesized and stored by the tumor cell. This cytokine is then cleaved by a trypsin-like protease to an active, lower molecular weight species which can be secreted into the media.

Animals↗

Purification of human collagenases with a hydroxamic acid affinity column.

Human collagenase has been isolated from skin fibroblasts and rheumatoid synovium by using an affinity matrix, prepared by coupling Pro-Leu-Gly-NHOH to agarose. Following the methodology described herein, the skin enzyme was isolated in two steps in 76% yield and the synovial enzyme was purified in three steps in 71% yield. Importantly, each enzyme hydrolyzed collagen into 3/4-1/4 cleavage fragments, indicating that a true collagenase had been isolated. The column was specific for the human enzyme since the collagenase from Clostridium histolyticum did not bind. The affinity ligand was designed according to the formalism proposed by Holmquist and Vallee [Holmquist, B., & Vallee, B. L. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6216] that effective metalloenzyme inhibitors can be synthesized by coupling a suitable metal-coordinating group to a substrate analogue. In this case, the hydroxamic acid probably coordinates to the active-site metal and the Pro-Leu-Gly moiety is similar to the carboxyl side of the cleavage site of collagen, the enzyme's substrate. The IC50 for N-(benzyloxycarbonyl)-Pro-Leu-Gly-NHOH is 4 X 10(-5) M for both enzymes. The affinity chromatographic procedures described here should aid in future studies on vertebrate collagenases.

Amino Acid Sequence↗

Peptide hydroxamic acids inhibit skin collagenase.

A number of peptide hydroxamic acids have been synthesized and have been shown to be inhibitors of human skin collagenase. One of these, Z-Pro-Leu-Gly-NHOH, has an IC50 value of 4 X 10(-5)M. Corresponding peptides with different C-terminal functional groups, such as amide, carboxylate and aldehyde, showed little or no inhibition, indicating the importance of the hydroxamate functional group. In addition, the peptide sequence of this effective inhibitor corresponds closely to that of the cleavage site of native collagen, the substrate for the enzyme. Thus, substrate analogs incorporating a suitable metal coordinating group serve as potential inhibitors of human collagenase.

Anti-Bacterial Agents↗

Electrical activity and sodium transfer across in vitro pig placenta.

Electrical activity generated by pieces of pig placenta, taken from anesthetized animals and mounted in Ussing chambers, has been investigated. Ten minutes after the start of voltage clamping, potential difference (PD; fetal side positive, open circuit), short circuit current (SCC), and resistance were 5.9 +/- 0.4 (SE) mV, 8.6 +/- 0.5 microA X cm-2, and 720 +/- 45 omega X cm2, respectively (n = 50). Ouabain (10(-4) M) added to the fetal side caused a maximum decline in PD and SCC from the time of addition of -3.7 +/- 0.98 mV and -3.9 +/- 1.4 microA X cm-2 (n = 6); epinephrine (10(-5) M) added to the fetal side caused increases of +1.0 +/- 0.2 mV and +4.0 +/- 1.4 microA X cm-2, respectively (n = 14). Drug concentrations for 50% maximum response for the effect of a series of adrenergic agonists on SCC were (in M) isoproterenol 1.2 +/- 0.05 X 10(-8), norepinephrine 6.1 +/- 0.3 X 10(-8), epinephrine 2.4 +/- 0.1 X 10(-7), and phenylephrine 4.7 +/- 0.2 X 10(-5), suggesting the involvement of fetally oriented beta-adrenergic receptors. Fetal epinephrine (10(-5) M) also stimulated net Na+ flux (Jnet) toward the fetal side to an extent equal to its effect on SCC. In control experiments Jnet was small but was inhibited by fetal side ouabain (10(-4) M) to produce a maternally directed Jnet, significantly different to the SCC. Replacement of Na+ by choline reduced SCC markedly but did not abolish it. In the absence of Na+, epinephrine had no effect on SCC. These results suggest that active Na+ transfer is not completely responsible for the control electrical activity of pig placenta. Epinephrine, however, modulates SCC entirely by stimulating net Na+ transfer toward the fetal side.

Adrenergic Agonists↗

In vitro permeability of the pig placenta in the last third of gestation.

The pig placenta is membranous throughout gestation and is suitable for investigation as a membrane system. The site of maternal-fetal exchange in vivo is used for permeability measurements in vitro and its surface area can be measured morphometrically. Fetal weight, placental weight, placental DNA content, placental macroscopic surface area, epithelio-chorial membrane area and thickness, and permeability in vitro to urea, tritiated water and sodium were measured in eight conceptuses aged between 79 and 111 days. These solutes were selected in order to facilitate comparison with data for sheep. Urea permeability per unit DNA increased throughout the last third of gestation although placental weight and DNA content ceased to increase before term.

Animals↗

Parent-specific adjustments for evaluation of recumbent length and stature of children.

A clinical "parent-specific" method for evaluating recumbent length and stature of children, allowing for the stature of parents, is presented. This method uses midparent stature and allows adjustment of recumbent length (birth to 3 years) and stature (3 to 18 years) of US children relative to National Center for Health Statistics growth charts. The method is based on parent-child relationships for 586 midparent-child pairs participating in the Fels Longitudinal Study, and on more than 16,000 serial measurements of recumbent length and stature. The method provides a clinical tool to separate the normal genetic contribution of parental stature to stature of children from other factors that affect stature such as malnutrition or disease.

Adolescent↗

Differential endothelial injury caused by vascular clamps and vessel loops. I. Normal vessels.

Silicone rubber looped tourniquets were compared with standard crossmembered metallic peripheral vascular occlusive clamps in a canine aorto-iliac vessel model to compare the degree and severity of endothelial injury as demonstrated by scanning electron microscopy. The moderate-to-severe injury incurred by the standard clamps was not seen whatsoever with the looped tourniquets. Selective and preferential use of silastic rubber vessel tourniquet loops for vascular occlusion and control is thus advocated.

Animals↗

Differential endothelial injury caused by vascular clamps and vessel loops. II. Atherosclerotic vessels.

Performance of a vascular anastomosis or repair requires meticulous, gentle technique and a bloodless operative field. Many vascular surgeons rely on commercial "atraumatic" vascular clamps for the latter; however, most experimental evidence incriminates clamps as agents of moderate to severe endothelial and medial injury. Our previous studies in normal canine aortoiliac vessels have demonstrated that silastic rubber vessel loops did not cause injury in that setting; this study examines in vivo atherosclerotic human femoropopliteal artery segments. Ten centimeter segments of perfused femoropopliteal arteries were exposed during performance of above-knee lower extremity amputation for endstage vascular insufficiency. DeBakey, Cooley, Fogarty, and bulldog vascular clamps, and double-looped silastic rubber vessel loops were applied at 3-centimeter intervals for 15 minutes. Each segment was then examined under scanning electron microscopy. All vascular clamps caused endothelial and presumed medial injury; no injury was seen with the vessel loops. Selective and preferential use of silastic rubber vessel loops is thus advocated to minimize iatrogenic complications.

Adult↗

Pyruvoyl-dependent histidine decarboxylases from Clostridium perfringens and Lactobacillus buchneri. Comparative structures and properties.

Histidine decarboxylase (EC 4.1.1.22) was purified to homogeneity from Clostridium perfringens and also from Lactobacillus buchneri. Both enzymes are composed of alpha and beta subunits, with an essential pyruvoyl group bound to the alpha subunit. In this respect and also in molecular weight of both the alpha and beta subunits and the native enzyme, they closely resemble the previously described (Riley, W.D., and Snell, E. E. (1970) Biochemistry 9, 1485-1491) histidine decarboxylase from Lactobacillus 30a. Rabbit antibodies to the latter enzyme cross-react incompletely with the decarboxylase from L. buchneri but not with that from C. perfringens in double diffusion tests. The clostridial decarboxylase differs substantially from the Lactobacillus 30a enzyme in amino acid composition and, unlike the latter enzyme, requires high ionic strength (I approximately 1.4 M) for maximum activity. The enzymes also differ in rates of electrophoretic migration. A proenzyme for the decarboxylase similar to that previously found in Lactobacillus 30a was detected in immunoprecipitates of extracts of L. buchneri. We conclude that these proteins arise from pyruvate-free precursor proteins by similar mechanisms and probably have diverged from a common ancestral protein.

Amino Acids↗