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Biomedical subjects

J A Moore

Publications and source records attributed to J A Moore.

At least 109 records · Page 6Linked to original sources

Pachyonychia congenita tarda. A late-onset form of pachyonychia congenita.

Pachyonychia congenita is an autosomal dominant disorder that usually develops in early infancy. We have observed five patients with the onset of the typical subungual hyperkeratoses of pachyonychia during the teenage years. Leukokeratosis and keratoderma of the palms and soles were associated. The family history of three of the patients suggests that pachyonychia congenita tarda is also inherited in an autosomal dominant manner.

Adult↗

Contrasting effects of urethane and pentobarbitone anaesthesia on the electrical properties of rat jaw-elevator motoneurones.

Our main finding is that elevator motoneurones do not show sustained firing to intracellular injections of depolarising current pulses in rats anaesthetised with urethane. In contrast, virtually all elevator motoneurones show sustained firing in pentobarbitone-anaesthetised rats. The differences in firing are not associated with significant differences in membrane potential, spike amplitudes, AHP amplitude or duration, input resistance, time constant or rheobase (P greater than 0.06 in all cases). However, there are clear differences in the extent of sag seen under the two anaesthetics and so we tentatively suggest that the anaesthetics may differ in their effects on the inward rectifier.

Anesthesia↗

Influence of age, growth, and sex on cardiac myocyte size and number in rats.

The effects of altered neonatal nutrition on cardiac myocyte size and number was examined in 21-day-old and 3-month-old rats. Nutritional differences in growth rate were produced in newborns by adjusting litter size to four (fast-growing), eight (normally growing), or 16 (slow-growing) pups per litter. Isolated myocytes were prepared from animals in each group to evaluate changes in cell size and number. Heart weight (mg +/- S.D.), at 21 days of age, was 398 +/- 51 for "fast-growing" rats, 329 +/- 43 for "normally growing" rats, and 228 +/- 24 for "slow-growing" rats. Body weights showed a comparable decline with reduced nutrition. In adults, treatment-related differences in body and heart weight were present in males but not females. "Slow-growing" rats had 21% fewer myocytes than "fast-growing" rats at 21 days of age, a change that persisted in adults. Values for myocyte number from "normally growing" rats were intermediate between those of "fast and slow-growing" rats at both 21 days and 3 months of age. In each heart region of weanling rats, myocyte length and volume were smallest in 16 per litter rats. Cellular dimensions increased progressively with better nutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Properties of a cleaved two-chain form of recombinant human growth hormone.

Escherichia coli cells transformed with plasmids engineered for the expression of recombinant human growth hormone as a secreted product also produced a proteolytically cleaved form of rhGH. This variant is isolated at a high resolution anion exchange chromatography stage during the manufacturing process. The higher isoelectric point of this form is demonstrated by isoelectric focusing and chromatofocusing and the two-chain nature by tryptic mapping, N- and C-terminal sequence analyses, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. These data indicate that the single site of cleavage is between Thr-142 and Tyr-143, in contrast to the two-chain variant isolated from human pituitary glands, which has a clip after residue Phe-139. The recombinant two-chain form was further characterized by reversed-phase high performance liquid chromatography at both acidic and basic pHs. The assay utilizing bicarbonate-containing mobile phases was determined to be the most efficient and sensitive method. The bioactivity of this two-chain form was measured by the in vivo rat weight gain assay and by the in vitro Nb2 cell bioassay. Its immunological similarity to intact one-chain rhGH was demonstrated with an enzyme-linked immunosorbent assay.

Amino Acid Sequence↗

Frame junction vibration transmission with a modified frame deformation model.

A previous paper dealt with vibration transmission through junctions of connected frame members where the allowed frame deformations included bending, torsion, and longitudinal motions [J.A. Moore, J. Acoust. Soc. Am. 88, 2766-2776 (1990)]. In helicopter and aircraft structures the skin panels can constitute a high impedance connection along the length of the frames that effectively prohibits in-plane motion at the elevation of the skin panels. This has the effect of coupling in-plane bending and torsional motions within the frame. This paper discusses the transmission behavior through frame junctions that accounts for the in-plane constraint in idealized form by assuming that the attached skin panels completely prohibit inplane motion in the frames. Also, transverse shear deformation is accounted for in describing the relatively deep web frame constructions common in aircraft structures. Longitudinal motion in the frames is not included in the model. Transmission coefficient predictions again show the importance of out-of-plane bending deformation to the transmission of vibratory energy in an aircraft structure. Comparisons are shown with measured vibration transmission data along the framing in the overhead of a helicopter airframe, with good agreement. The frame junction description has been implemented within a general purpose statistical energy analysis (SEA) computer code in modeling the entire airframe structure including skin panels.

Acoustics↗

Influence of roughage source on kinetics of digestion and passage, and on calculated extents of ruminal digestion in beef steers fed 65% concentrate diets.

Roughage sources were compared in flaked milo-based diets that contained 35% chopped alfalfa hay (AH, control diet) or with cottonseed hulls (CSH) or chopped wheat straw (WS) replacing half the AH. Latin square experiments were used to measure total tract digestion coefficients, particulate passage rates (rare earths), liquid turnover rates (Co-EDTA), and rumination time in six growing steers (Exp. 1) and in situ digestion of DM and NDF, ruminal pH and ruminal DM distribution in three mature, ruminally cannulated steers (Exp. 2). Rates of passage from Exp. 1 and rates and extents of digestion from Exp. 2 were used to calculate apparent extent of ruminal digestion (AED). In Exp. 1, total tract digestibilities of DM and NDF were lower (P less than .05) by 7 and 22%, respectively, when CSH, but not WS, were included in the diet. Digestibility of cell solubles was not different (P greater than .10) among diets. Inclusion of WS increased (P less than .10) rumination time by 36%, and CSH increased intake (P less than .10) by 17% over the control diet. In Exp. 2, there tended to be (P less than .20) increased in situ digestion of milo and AH in the WS diet. Measures of ruminal pH were similar for all diets. The AED for AH and milo DM and NDF, and the proportion of total tract NDF digestion occurring in the rumen (50, 47 and 62% for control, CSH and WS diets, respectively), were highest (P less than .05) for the WS diet. This resulted in similar total tract digestibilities for the WS and AH diets. The two low-digestibility roughages had different effects at this concentrate level; wheat straw enhanced apparent extent of ruminal digestion for NDF of other ingredients in the mixed diets, but cottonseed hulls did not.

Animal Feed↗

Differential passage rates and digestion of neutral detergent fiber from grain and forages in 30, 60 and 90% concentrate diets fed to steers.

Six ruminally cannulated steers were used to determine the effects of altering dietary concentrates on fiber digestion. Diets contained 30, 60 or 90% of a concentrate based on flaked sorghum grain plus a 50:50 mixture of wheat straw and alfalfa hay. Total tract digestibility of NDF was not altered, but digestibility of potentially digested NDF (PDF) decreased (P less than .05) from 92 to 48% as concentrates increased from 30 to 90% of diet DM. Ruminal passage rate for straw (3.4 and 3.0%/h) and for hay (4.6 and 4.7%/h) was unchanged when concentrate was increased from 30 to 60%, but it decreased by 28 (2.2%/h) and 13% (4.1%/h), respectively (P less than .05), when concentrates were increased to 90%. Passage rate for grain (5.3, 5.1 and 4.4%/h) and fluid (9.3, 10.0 and 8.2%/h) was not influenced by concentrate percentage. Calculated ruminal digestibilities of NDF in individual ingredients did not differ between 30 and 60% concentrates, but they decreased (P less than .05) by 72, 57 and 34% for straw, hay and grain when concentrate was increased to 90%. Because of their relative contribution to total diet NDF, straw, hay and grain accounted for 28, 18 and 54% of the total decrease in estimated fiber digestion. It is concluded that PDF as well as NDF should be evaluated in studies of concentrate effects on fiber digestion, and that dietary concentrate level has more influence on passage rate of low-quality forage than on passage rate of grain or high-quality forage. In 90% concentrate diets, although fiber digestibility was depressed more for forage than for grain, grain accounted for most of the depression in fiber digestion because grain was the primary source of dietary fiber.

Animal Feed↗

The morphology of the axons and axon collaterals of rat jaw-elevator motoneurones.

We have made intracellular injections of horseradish peroxidase into the somata of jaw-elevator motoneurones and subsequently reconstructed the axonal morphology of 4 cells. In each case the axons gave off collaterals which were essentially restricted to the ventral portion of the V motor nucleus. This observation provides the first evidence that these motoneurones may exert recurrent synaptic effects.

Action Potentials↗

The monosynaptic excitatory connections of single trigeminal interneurones to the V motor nucleus of the rat.

1. We have used the extracellular spike-triggered averaging method to identify a population of trigeminal interneurones that make monosynaptic connections within the V motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone (60 mg/kg I.V.; supplementary doses given as necessary to maintain a deep level of anaesthesia). 2. A tungsten microelectrode (tip exposure of some 200 microns) was inserted into the masseter motoneurone pool to allow recording of extracellular activity. A glass electrode filled with DL-homocysteic acid was used to make simultaneous extracellular recordings of the firing of single neurones in the region immediately caudal to the motor nucleus. 3. Fifty-eight out of 166 interneurones tested gave unitary extracellular fields in the motor nucleus. The responses consisted of a terminal spike (presynaptic spike) followed by a negative field of duration approximately 3 ms and amplitude 0.4-10.8 microV. The mean latency between the positive peak of the terminal spike and the onset of the field (synaptic delay) was 0.43 ms (S.D. = 0.10 ms), and the mean latency from the onset of the interneurone spike to the positive peak of the presynaptic spike was 0.35 ms (S.D. = 0.22 ms). Thus the interneurones project directly to the motor nucleus where they then make monosynaptic connections. 4. The negative extracellular fields were taken to reflect an excitatory synaptic input onto neurones within the motor nucleus. The fields were of maximum amplitude at the point of maximum masseter motoneurone antidromic field, suggesting that the connection may be onto elevator motoneurones. 5. The location of the interneurone appeared to the main factor governing the likelihood of obtaining a field. Interneurones located more than 400 microns from the caudal border of the motor nucleus rarely produced fields whereas most of those located within this distance gave fields. This pattern of distribution is strikingly similar to that of trigeminal interneurones labelled by the transneuronal transport of wheatgerm agglutinin-horseradish peroxidase after an intramuscular injection of the tracer into the masseter muscle. We suggest that this provides electrophysiological support for the suggestion that the tracer does indeed label interneurones by means of retrograde transsynaptic transport.

Animals↗

Repair of full-thickness defects in the femoral trochlea of dogs after trochlear arthroplasty.

Trochlear arthroplasty was performed on one stifle in each of 18 Greyhounds; their contralateral pelvic limbs and the pelvic limbs of 2 dogs treated with sham surgery were controls. At 2, 4, 8, and 16 weeks, radiography, glycosaminoglycan histochemical analysis, histologic examination, and scanning electron microscopy of the trochlear surface were done. All dogs used the limb and walked without an observable limp within 2 weeks after surgery. Radiography at euthanasia did not reveal degenerative changes. Well-vascularized, highly cellular, loose fibrous connective tissue was reorganized with time into a dense fibrous connective tissue covering the entire wound. Scanning electron microscopy revealed that the replacement tissue surface was rough, torn, and debris-covered. Differential histologic staining established that change to fibrocartilage had begun deep within the replacement tissue. Histochemical analyses corroborated those observations.

Animals↗

1-Ethynyl-4-hydroperoxy-1,2,3,4-tetrahydro-1-naphthol.

C12H12O3, Mr = 204.2, monoclinic, P2(1)/c, a = 11.815 (2), b = 7.673 (2), c = 12.580 (3) A, beta = 115.06 (2) degree, V = 1033.1 (9) A3, Z = 4, Dx = 1.313 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 7.34 cm-1, F(000) = 432, T = 299 K, R = 0.065 for 1420 observations (of 2131 unique data). The stereochemistry of the hydroxyl and hydroperoxyl groups is cis. The hydroperoxyl O-O bond distance is 1.476 (2) A. The hydrogen-bonding pattern consists of two intermolecular interactions: a hydroperoxyl donor to the hydroxyl group, with an O...O distance of 2.818 (2) A and an O-H...O angle of 168 (2) degree, and a hydroxyl donor to O(3) of the hydroperoxyl group, with a distance and angle of 2.670 (2) A and 170 (2) degree, respectively.

Molecular Conformation↗

Carcinogen testing. Fact and fallacy.

In the absence of human information on the carcinogenicity of chemical substances, one must rely primarily on information from long-term animal testing. Although far from perfect, animal studies seem to be reasonable predictors of the human experience, both qualitatively and quantitatively. Short-term tests for genotoxicity may be helpful for establishing priorities for chemical testing, but they are not as strong indicators of potential carcinogenicity as had been previously thought. New directions in toxicologic research hold the promise for scientists being able to perform more reasoned assessments of carcinogenic risk.

Animals↗

Primary pulmonary adenocarcinoma with brain stem metastasis in a dog.

Primary pulmonary adenocarcinoma with metastatic spread to the brain stem was diagnosed at necropsy in an aged Bulldog. Initial clinical signs included coughing, decreased exercise tolerance, and personality changes. Primary differential diagnoses after thoracic radiography were multicentric metastatic neoplasia or fungal disease. Later clinical signs (inappetence, unilateral facial paralysis and decreased sensation, and hemiparesis) were referable to the effect of the tumor on cranial nerves V and VII and other brain stem structures. Primary lung tumors are uncommon, as are metastatic tumors within the CNS. Radiographic appearance alone of lung lesions is insufficient for accurate diagnosis.

Adenocarcinoma↗

Pathology of Schistosoma haematobium infection in the capuchin monkey (Cebus apella).

Capuchin monkeys exposed to 500-2000 Schistosoma haematobium cercariae were followed for up to 6 1/2 years after infection. Worm burdens decreased as infections became more chronic and decreasing numbers of eggs and active circumoval lesions were found in the bladder and elsewhere. Nodular and hyperplastic epithelial lesions of the urinary bladder were not seen during the first year of infection but occurred in 30% of monkeys examined 1-2 years after infection and in 23% of those examined between the second and third years; they were present in only 3% of monkeys studied 3-6 1/2 years after infection. These epithelial proliferative lesions were located near foci of egg deposition and occurred in the monkeys with the most intense active lesions in the bladder. The lesions regressed in animals followed sequentially. The lesions thus appear not to be neoplastic. Obstructive lesions of the ureter accompanied by hydronephrosis were present in a few animals. The obstructive uropathy did not appear to cause significant morbidity. Mortality was substantial among infected monkeys at most intervals after infection but was rare among uninfected controls.

Animals↗

Resistance of capuchin monkeys to reinfection with Schistosoma haematobium.

Capuchin monkeys were resistant to reinfection with Schistosoma haematobium one year after exposure to 500 cercariae, but worms in these monkeys continued to produce normal numbers of eggs. Monkeys were apparently completely refractory to reinfection when challenged 2-5 years after an initial exposure of 1000 to 2000 cercariae.

Animals↗

Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine.

Two forms of human GH (hGH) have been produced by recombinant DNA technology. One form has an amino acid sequence identical to that of the natural pituitary hormone (rhGH) and the other form has an additional N-terminal methionine (Met-hGH). The biological potencies of these 2 polypeptides have been compared in hypophysectomized rats in a multidose study measuring body weights and several long bone growth parameters. The pharmacokinetic profiles after iv and sc injection were determined in cynomolgus monkeys in a 4-period cross-over study. All of the measured parameters in all the studies indicated that there was no difference in the two forms of hGH. Measurements taken after 27 daily injections of rhGH or Met-hGH (30-500 micrograms/kg.day) indicated that femur length and width of the proliferative zone in the tibial epiphysis showed dose-related effects for both forms of hGH but no difference between them. The relative potency, based on body weight gain, was calculated using a parallel line bioassay. Weight gain after 8 daily injections in the 5-dose long bone growth study indicated a rhGH potency of 0.80 (95% confidence interval, 0.5-1.23) relative to Met-hGH. It was concluded that the presence of an N-terminal methionine on hGH has no effect on potency in this model. The pharmacokinetic parameters after iv administration were estimated by fitting serum concentration-time data to a 2-compartment model. Parameters after sc injection were computed by compartment-independent methods. Met-hGH and rhGH had very similar pharmacokinetic profiles after both routes of administration. Comparison of the pharmacokinetic parameters indicated that the clearance after iv administration (rhGH, 15 ml/min; Met-hGH, 13 ml/min) and the sc bioavailability (rhGH, 0.72 +/- 0.21; Met-hGH, 0.59 +/- 0.21) were not significantly different for the 2 forms of hGH. It was concluded that rhGH and Met-hGH have equivalent bioavailability and pharmacokinetics in cynomolgus monkeys.

Amino Acid Sequence↗

Equations for the prediction of resting energy expenditure in chronic obstructive lung disease.

Resting energy expenditure can be obtained either by indirect calorimetry or from prediction equations. Several prediction equations were compared to the measured value of REE in a group of COPD patients with moderate to severe disease. Then, using the same group of patients, a new equation was derived by regression analysis and was prospectively tested on patients with similar characteristics. Equations derived from normal populations (Harris-Benedict, Wilmore nomogram) were shown to underestimate REE by 300-400 Kcal. Equations that use body weight as the only variable were found to be easier to use and did not appear to sacrifice accuracy. Quebbeman Ausman body weight, Quebbeman Ausman body surface area and a regression equation derived from COPD patients (males, REE = 11.5 x wt [kg] + 952; females, REE = 14.1 x wt [kg] + 515) performed better than other currently used equations. In both stable COPD and COPD with exacerbation, the mean predicted values fell within a standard deviation (+/- 167 Kcal) of measured values.

Body Surface Area↗