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Biomedical subjects

G C Smith

Publications and source records attributed to G C Smith.

At least 145 records · Page 8Linked to original sources
PubMed1997

Prolonged fetal pre-ejection period corrected for PR interval associated with cerebral palsy.

OBJECTIVE: To identify whether the correction of human fetal pre-ejection period (PEP) for the effect of catecholamines, as estimated by the PR interval (the interval of time measured between the P and R waves of the electrocardiogram (ECG)), might improve PEP as a measure of fetal cardiac contractility. METHODS: A retrospective analysis of PEP and PR intervals was carried out, using tape recordings of fetal ECG and Doppler ultrasound recordings of cardiac valve movements, from 43 human fetuses in the first stage of labour. RESULTS: There was a strong positive correlation between PEP and PR intervals in the population studied: r = 0.641, P < 0.0001, indicating that about 40% of the inter-patient variation in PEP could be corrected for by concomitant measurement of the PR interval. Only one fetus had markedly prolonged PEP when corrected for PR interval. This individual developed cerebral palsy over the first year of life. CONCLUSION: Correction of PEP for the effects of catecholamines may greatly improve its usefulness in detecting fetal compromise. Combined measurement of the PEP and PR interval needs to be evaluated as a technique of fetal monitoring.

Cerebral Palsy↗
PubMed1997

Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis.

Poly(ADP-ribose) polymerase (PARP) and DNA-dependent protein kinase (DNA-PK) are DNA break-activated molecules, Although mice that lack PARP display no gross phenotype and normal DNA excision repair, they exhibit high levels of sister chromatid exchange, indicative of elevated recombination rates. Mutation of the gene for DNA-PK catalytic subunit (Prkdc) cases defective antigen receptor V(D)J recombination and arrests B- and T-lymphocyte development in severe combined immune-deficiency (SCID) mice. SCID V(D)J recombination can be partly rescued in T-lymphocytes by either DNA-damaging agents (gamma-irradiation and bieomycin) or a null mutation of the p53 gene, possibly because of transiently elevated DNA repair activity in response to DNA damage or to delayed apoptosis in the absence of p53. To determine whether the increased chromosomal recombination observed in PARP-deficient cells affects SCID V(D)J recombination, we generated mice lacking both PARP and DNA-PK. Here, we show that thymocytes of SCID mice express both CD4 and CD8 co-receptors, bypassing the SCID block. Double-mutant T-cells in the periphery express TCR beta, which is attributable to productive TCR beta joints. Double-mutant mice develop a high frequency of T-cell lymphoma. These results demonstrate that increased recombination activity after the loss of PARP anti-recombinogenic function can rescue V(D)J recombination in SCID mice and indicate that PARP and DNA-PK cooperate to minimize genomic damage caused by DNA strand breaks.

Animals↗
PubMed1997

The effects of offspring gender on older mothers caring for their sons and daughters with mental retardation.

Most caregivers of adults with mental retardation are older women, yet information is sparse regarding the nature of this support. In this study we explore the relationship between offspring gender and caregiving by older mothers. Of the 235 caregivers interviewed, no demographic differences were found between mothers with daughters and sons. Despite these similarities, we found mothers less likely to use day services for their daughters. Mothers with daughters were more likely to feel burdened by caregiving and expressed a need to be constantly vigilant. However, mothers received the most help from daughters with household tasks. Gender differences have implications for outreach to, and services for, these families.

Activities of Daily Living↗
PubMed1997

Use of magnesium sulphate in Scottish obstetric units.

The greater efficacy of magnesium sulphate compared with diazepam or phenytoin in the treatment of eclampsia is now generally accepted. We used a postal questionnaire to establish the frequency and nature of use of magnesium sulphate in obstetric units in Scotland. Ninety percent of units responded and of these 90% were either using the drug or intended to do so. There was considerable heterogeneity in the indications for its use and some important omissions in the monitoring of patients receiving the drug. The introduction of magnesium sulphate for a rare indication to units with no previous experience of its use may be associated with significant risks to obstetric patients.

Clinical Protocols↗
PubMed1997

The relation between fetal abdominal circumference and birthweight: findings in 3512 pregnancies.

OBJECTIVES: To establish the relation between fetal abdominal circumference and birthweight in a large population of fetuses; to identify whether the error in estimating birthweight by abdominal circumference varied with the magnitude of abdominal circumference; and to establish whether adding femur length to abdominal circumference caused a clinically important reduction of error in predicting birthweight. DESIGN: A retrospective study. SETTING: The ultrasound department of a teaching maternity hospital offering a tertiary referral service. SAMPLE: From 3512 nondiabetic women with a normally formed singleton fetus, an abdominal circumference measurement of the infant was made within seven days of delivery; of these, 1213 had a femur length measurement performed at the same time. RESULTS: There was a linear relation between abdominal circumference and birthweight. There was a strong inverse correlation between the proportional error in predicting birthweight from the abdominal circumference and the magnitude of the abdominal circumference. Both the Campbell and Wilkin equation (abdominal circumference alone) and the Hadlock equation (abdominal circumference and femur length) were associated with systematic errors, especially with larger birthweight infants. The median absolute errors for the two equations were not significantly different overall (6.98% and 6.86% respectively), although the Hadlock equation was significantly more accurate in predicting birthweight in infants weighing greater than 4500 g. However, no threshold value of abdominal circumference or of estimated fetal weight using the Hadlock equation had a positive predictive value in estimating infants of > 4500 g of greater than 35%. CONCLUSIONS: Prediction of birthweight should be by abdominal circumference alone. Table 1 presents robust estimates of the error of predicting birthweight using fetal abdominal circumference.

Abdomen↗
PubMed1997

The effect of passive stretch on the response of the fetal rabbit ductus arteriosus to indomethacin, noradrenaline and prostaglandin E2.

The aim of this study was to determine the effect of varying stretch of the ductus arteriosus on its contractile response to indomethacin and noradrenaline, and its relaxant response to prostaglandin (PG) E2. Isolated rings of ductus arteriosus obtained from fetal New Zealand White rabbits at 28 days gestation were mounted in vitro for measurement of isometric tension by a transducer connected to a vernier control. The responses of the ductus to drugs at varying degrees of passive stretch were corrected to a standard contraction in response to 65 mM potassium at a standard level of stretch. Increasing stretch across the range 1.0-5.9 mN increased the contractile response to indomethacin and noradrenaline (the latter in the presence of 1 microM indomethacin and 1 or 10 nM PGE2) in a virtually identical manner. The sensitivity of the vessel to noradrenaline in the presence and absence of indomethacin and its sensitivity to the relaxant effect of PGE2 in the presence of indomethacin were unaffected by increasing stretch. The extent of contractile tone present which was not inhibited by endogenous PGE2 increased with increasing stretch. It was concluded that: (1) the contractile response to indomethacin can be profoundly altered by the degree of spontaneous tone in the vessel; (2) the magnitude of the contraction induced by indomethacin is not a good index of the degree of inhibition exerted by locally produced PGs in the vessel; and (3) locally produced PGs are likely to have a physiological role in maintaining patency of the ductus arteriosus in utero.

Animals↗
PubMed1997

Aging families of adults with mental retardation: patterns and correlates of service use, need, and knowledge.

Older mothers (N = 235, mean age = 70.3) of adult offspring were surveyed to identify patterns and correlates of the extent to which their families either used, knew about, needed, or had unmet needs for 17 family support services. Although variability was observed across these services, overall level of service use was low despite high knowledge. Also, the number of services needed exceeded number of services actually used. Greater service use occurred when offspring were younger, female, came from lower income households, and were receiving high levels of care from mothers who reported higher subjective burden and self-reported health. Families had larger unmet service needs when mothers were married, received less assistance from their children without mental retardation, and reported higher levels of subjective burden.

Adult↗
PubMed1997

Vitamin E supplementation of cattle and shelf-life of beef for the Japanese market.

Feeder steers (n = 84) were stratified into four weight groups to provide slaughter groups so that product that had been in vacuum packages at 0 to 2 degrees C for 40, 60, 80, or 100 d postmortem could be simultaneously evaluated. Each of the four groups was randomly divided into three subgroups so that vitamin E could be supplemented in the diet at rates of 0, 1,000, or 2,000 (E0, E1000, and E2000, respectively) IU.steer-1.d-1 for 100 d. After slaughtering, chilling, and fabricating, one ribeye-roll and one strip loin from each carcass was transported to the university laboratory for analyses, whereas the paired subprimals were transported to Japan. Based on metmyoglobin formation and lipid oxidation, strip loin steaks deteriorated at a faster rate during retail-display than did ribeye steaks. Steaks from subprimals that were stored for 100 d had inferior (P < .05) retail-display characteristics and a shorter (P < .05) caselife than steaks from the other storage periods. alpha-Tocopherol levels in longissimus muscle were lower (P < .05) for E0 than for E1000 and E2000 (3.51, 5.54, and 6.10 micrograms/g of tissue, respectively). Supplementing cattle with vitamin E resulted in steaks that exhibited superior lean color, less surface discoloration, more desirable overall appearance, and less lipid oxidation during retail display than control steaks; minimal differences were observed between E1000 and E2000 steaks. Steaks from cattle supplemented with vitamin E were preferred over control steaks by 91% of Japanese survey participants (n = 10,941), and 58% of all participants identified muscle color as the most important factor in selecting beef products.

Animals↗
PubMed1997

Using objective measures of muscle color to predict beef longissimus tenderness.

This research was conducted to determine whether objective measures of muscle color could be used to classify beef carcasses with respect to tenderness. Bos taurus (161 steers) and Bos indicus cross (101 steers, 55 heifers) cattle were fed a high-concentrate diet and slaughtered in seven groups when ultrasound scans indicated approximately 1.1 cm fat thickness. Following low-voltage electrical stimulation and a 24-h chill, all routine carcass data, USDA grade data, and colorimeter readings (luminance, L*; redness, a*; yellowness, b*) of the exposed longissimus muscle were obtained. The longissimus lumborum was sampled for ultimate pH (pHU) measurement, shear force at 1, 4, 7, 14, 21, and 35 d postmortem, and taste panel assessment at 14 d postmortem. The pHU was correlated (P < .05) with L*, a*, and b* values (r = -.48, -.52, and -.60, respectively). Correlations of color measurements with tenderness measurements were higher than correlations of marbling score with tenderness measurements. Of the three color measurements, b* value showed the highest correlation with shear force value (r = -.38) and taste panel tenderness rating (r = .37). A classification system (lowest 25%, middle 50%, highest 25%) based on marbling score resulted in classes of beef that were 9, 3, and 4% tough, respectively. A classification system (darkest/bluest 25%, middle 50%, lightest/yellowest 25%) based on colorimeter readings resulted in classes of beef that were 15, 3, and 0% tough, respectively. Bos taurus cattle had lower shear force values, higher panel tenderness ratings, higher L* values, and lower a* values (P < .05) than Bos indicus cross cattle.

Animals↗
PubMed1997

Performance, carcass, and palatability traits for cull cows fed high-energy concentrate diets for 0, 14, 28, 42, or 56 days.

Cull cows, thin to moderate in initial condition scores, were randomly assigned within breed to slaughter groups and fed a high-concentrate diet for 0, 14, 28, 42 or 56 d (n = 40). Carcass data were collected, and one side of each carcass was fabricated into boneless subprimals, lean trimmings, fat, and bone. Live and carcass weights, ADG, and dressing percentage increased through 28 d of feeding (P < .05), and lean firmness increased (P < .05) through 42 d of feeding. Adjusted preliminary yield grades and final yield grades increased (P < .05) with feeding, but not to levels requiring knife trimming of fat. Fat color became whiter (P < .05) but marbling was not affected (P > .05) by feeding. Weights of fat-free lean, fat, and bone and percentages of fat in soft tissues of cow carcasses increased (P < .05) by 28 d on feed. Overall steak tenderness was higher (P < .05) for cows fed 56 d than for cows fed 0 or 14 d. Warner-Bratzler shear force was not affected by feeding. Amounts of soluble collagen increased (P < .05) in the longissimus muscle between 0 and 28 d on feed, and total collagen decreased (P < .05) in the biceps femoris muscle between 0 and 42 d on feed. Continental European cow carcasses yielded more fat-free lean and less fat (P < .05) and dairy cows generally provided the most tender product across all slaughter periods. In general, sensory tenderness and yields of cow carcass components increased without requiring excessive trimming of fat by feeding cull beef and dairy cows for periods up to 56 d.

Animals↗
PubMed1997

Comparison of USDA quality grade with tendertec for the assessment of beef palatability.

Carcasses (n = 265) selected to differ in USDA yield grade were evaluated by expert graders and assessed for tenderness with the Tendertec Mark III Beef Grading Instrument. Tendertec measurements were collected on longissimus lumborum muscles in both sides of each carcass. During fabrication of each left carcass side, a rib section (later converted into three steaks) was removed for aging and subsequent sensory panel evaluation at 14 d and for Warner-Bratzler shear force measurements at 14 and 28 d. Correlation coefficients for repeatability of Tendertec output variables, between left and right carcass sides, were .57, .44, .70, and .65 for Area-2, Area-2B, Power-2, and Power-2B, respectively. Correlations between Tendertec output variables and Warner-Bratzler shear force evaluations performed on steaks aged 14 or 28 d were not different from zero. Sensory panel ratings for amount of connective tissue were correlated (P < .01) with Tendertec output variables Area-2 and Area-2B (r = -.168 and -.154, respectively), and ratings for overall tenderness were correlated (P < .05) with the Area-2 output variable (r = -.131) but the coefficients were very low. Segregation analysis, using Tendertec output variables Area-2 and Power-2, significantly (P < .05) stratified sensory panel ratings for connective tissue amount and overall tenderness. Even though the Tendertec probe detected some differences in connective tissue contributions to rib steak tenderness, it was not better than USDA quality grade at segmenting A-maturity carcasses into anticipated tenderness outcomes, and thus its applicability as a grading instrument may be limited to use on more mature beef carcasses.

Analysis of Variance↗
PubMed1997

Genetic effects on beef tenderness in Bos indicus composite and Bos taurus cattle.

Bos indicus composite and Bos taurus cattle, originating from diverse production environments, were used to quantify genetic variation in marbling, 24-h calpastatin activity, and beef tenderness and to identify strategies for prevention of beef tenderness problems in Bos indicus composite cattle. Comparisons among 3/8 Bos indicus breeds (Braford, Red Brangus, Simbrah) revealed significant differences in marbling and 24-h calpastatin activity, but not in tenderness. Compared with Bos taurus cattle, 3/ 8 Bos indicus cattle had similar marbling scores but higher 24-h calpastatin activities. Also, beef from 3/8 Bos indicus composites aged more slowly from 1 to 7 d and was less tender at 4, 7, 14, 21, and 35 d postmortem than beef from Bos taurus cattle. However, beef from 3/8 Bos indicus cattle was relatively tender if it was aged for a sufficient period of time (21 d). The delayed response to aging and greater toughness of beef from 3/8 Bos indicus cattle was associated with Brahman breed effects and was not related to the Bos taurus germplasm source. Marbling was moderately heritable (.52 +/- .21) but exhibited positive genetic correlations with shear force at d 1 through 14 of aging, suggesting that, in these cattle, selection for increased marbling would have an unfavorable effect on beef tenderness. A low heritability estimate for 24-h calpastatin activity (.15 +/- .15), coupled with low genetic correlations between calpastatin activity and shear force at 7, 14, and 35 d, suggested that selection for low calpastatin activity would have little effect on aged beef tenderness. Panel tenderness and shear force at 7, 14, and 21 d were moderately heritable (.27 to .47), indicating that aged beef tenderness could be improved by direct selection (via progeny testing). Comparisons among Simbrah, Senegus x Simbrah, and Red Angus x Simmental steers showed that inclusion of a tropically adapted Bos taurus breed (Senepol) could be an effective strategy for preventing beef tenderness problems in heat-tolerant cattle.

Animals↗
PubMed1996

Coexpression of a human P450 (CYP3A4) and P450 reductase generates a highly functional monooxygenase system in Escherichia coli.

The catalytic activities of recombinant cytochrome P450s expressed in E. coli have been impeded by the absence of endogenous P450 reductase. To solve this problem, we coexpressed P450 reductase with CYP3A4. Membranes from this strain contained 215 pmol P450/mg protein and a reductase activity of 1315 nmol cytochrome c reduced/min per mg. We detected 6beta-hydroxylation of testosterone and oxidation of nifedipine in vivo with turnover numbers of 15.2 and 17.3 min(-1), respectively. These values compare favourably with those obtained using an optimally reconstituted system. Our data demonstrate that a catalytically efficient human P450 system can be generated in E. coli.

Base Sequence↗
PubMed1996

Observation of structural variation and spin state conversion of cytochrome P450 CYP2B4 on binding of sterically different substrates.

Addition of sterically different substrates to CYP2B4 suggests perturbation of the environment of the haem ring and differing degrees of 6cls-5chs conversion. Strain on the ring, by implication induced by changes in the surrounding protein environment, is demonstrated by the emergence of the v29 band upon laurate binding. Furthermore, intensity differences and frequency shifts for non-Raman active (Eu) modes appear to be substrate dependent and are sensitive to haem/substrate interactions. The likelihood is that substrate induced distortion of the haem will have an effect on catalytic activities and attention needs to be directed towards substrate pocket interactions. SERRS (Surface enhanced resonance Raman scattering) provides a unique and sensitive spectroscopic probe of these interactions.

Animals↗
PubMed1996

DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis.

Radiosensitive cell lines derived from X-ray cross complementing group 5 (XRCC5), SCID mice and a human glioma cell line lack components of the DNA-dependent protein kinase, DNA-PK, suggesting that DNA-PK plays an important role in DNA double-strand break repair. Another enzyme implicated in DNA repair, poly(ADP-ribose) polymerase, is cleaved and inactivated during apoptosis, suggesting that some DNA repair proteins may be selectively targeted for destruction during apoptosis. Here we demonstrate that DNA-PKcs, the catalytic subunit of DNA-PK, is preferentially degraded after the exposure of different cell types to a variety of agents known to cause apoptosis. However, Ku, the DNA-binding component of the enzyme, remains intact. Degradation of DNA-PKcs was accompanied by loss of DNA-PK activity. One cell line resistant to etoposide-induced apoptosis failed to show degradation of DNA-PKcs. Protease inhibitor data implicated an ICE-like protease in the cleavage of DNA-PKcs, and it was subsequently shown that the cysteine protease CPP32, but not Mch2alpha, ICE or TX, cleaved purified DNA-PKcs into three fragments of comparable size with those observed in cells undergoing apoptosis. Cleavage sites in DNA-PKcs, determined by antibody mapping and microsequencing, were shown to be the same for CPP32 cleavage and for cleavage catalyzed by extracts from cells undergoing apoptosis. These observations suggest that DNA-PKcs is a critical target for proteolysis by an ICE-like protease during apoptosis.

Animals↗
PubMed1996

The neutrophil oxidative burst in diarrhoea-associated haemolytic uraemic syndrome.

Neutrophil-mediated tissue damage has been implicated in the pathogenesis of diarrhoea-associated haemolytic uraemic syndrome (D+ HUS). This study evaluates priming and activation of the neutrophil oxidative burst in D+ HUS using chemiluminescent techniques. Peripheral blood neutrophils from 11 children with acute D+ HUS were examined. No difference was found in the oxidative burst of neutrophils from patients and controls. Serum elastase levels were measured in 8 patients and found to be significantly elevated. Although elastase results suggest neutrophil activation, chemiluminescence studies do not confirm this in the peripheral blood neutrophil. This does not support a significant role for circulating agents in priming and activating the peripheral blood neutrophil.

Child↗
PubMed1996

Caregiving outcomes for older mothers of adults with mental retardation: a test of the two-factor model of psychological well-being.

A two-factor model of caregiving appraisal and psychological well-being, based on previous findings with caregiving spouses (M.P. Lawton, M. Moss, M.H. Kleban, A. Glicksman, & M. Rovine, 1991), was tested with 225 older mothers who provided care at home to an offspring with mental retardation. The effects of objective caregiving stressors, caregiver resources, and subjective appraisals (caregiving satisfaction and burden) on the positive and negative dimensions of psychological well-being were examined. LISREL 8 analyses revealed that the model differed in two key ways for caregiving mothers: (a) Positive psychological well-being appeared to diminish subjective burden, and (b) both objective stressors and resources were unrelated to subjective burden. These findings suggest the need for future research into how caregiving dynamics are influenced by the specific nature of the relationship between the caregiver and the recipient.

Adult↗