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Biomedical subjects

G C Smith

Publications and source records attributed to G C Smith.

At least 181 records · Page 10Linked to original sources

Fos induced in brain of spontaneously hypertensive rats by angiotensin II and co-localization with AT-1 receptors.

The induction of Fos-like immunoreactivity (FLI) by peripheral administration of angiotensin II (Ang II) was used to determine whether central activation was greater in spontaneously hypertensive rats (SHR) than in normotensive WKY and outbred Wistar controls. FLI was induced in the same brain regions (circumventricular organs and neurosecretory hypothalamic cell groups) in all three groups of rats, but the FLI in several of these regions was markedly less in WKY than in either SHR or Wistar. This reduced responsiveness in supraoptic and paraventricular nuclei was selective to Ang II, because the FLI induced in these nuclei by hypertonic NaCl did not differ between groups. We also report that a considerable number of cells in the SON and PVH expressing FLI to these stimuli show immunostaining with an antibody to the AT-1 Ang II receptor. These data indicate that central angiotensinergic pathways may be more sensitive in SHR than WKY, and that WKY are less sensitive than outbred Wistars.

Angiotensin I↗

Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation.

Murine cells homozygous for the severe combined immune deficiency mutation (scid) and V3 mutant hamster cells fall into the same complementation group and show similar defects in V(D)J recombination and DNA double-stranded break repair. Here we show that both cell types lack DNA-dependent protein kinase (DNA-PK) activity owing to defects in DNA-PKcs, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial chromosomes containing the DNA-PKcs gene complement both the DNA repair and recombination deficiencies of V3 cells, and we conclude that DNA-PKcs is encoded by the XRCC7 gene. As DNA-PK binds to DNA ends and is activated by these structures, our findings provide novel insights into V(D)J recombination and DNA repair processes.

Amino Acid Sequence↗

The recognition of depression in patients referred to a consultation-liaison service.

The recognition of depression was examined in 987 medical and surgical patients referred to a consultation-liaison psychiatry service. Overall concordance of recognition of depression by the referring doctor and diagnosis of depression by the consultant psychiatrist was 74%; 41% false-positive rate, 15% false-negative rate. Concordance was higher in the Renal Unit and lower in the General Medical Unit. Patients for whom there was discordance were significantly older than those for whom there was concordance. Patients referred for depression but not diagnosed as such by psychiatrists received DSM-III-R diagnoses of Organic Mental Disorder, Somatoform and Related Disorders, Psychoactive Substance Use Disorders and Personality Disorders. On the other hand, patients diagnosed as having depression but not referred as such were referred instead for ill-defined reasons (suspected psychological component to illness, coping problems), suicide risk evaluation and routine pre-operative or pre-dialysis assessment. The results highlight the continuing misdiagnosis of psychiatric disorders, especially Organic Mental Disorders, as well as the mislabelling of the syndrome described by psychiatrists as depression. This is part of the wider problem of defining the boundaries of a clinical depressive syndrome in the physically ill.

Adolescent↗

Contractile effects of prostanoids on fetal rabbit ductus arteriosus.

We wished to determine whether any evidence indicates that the ductus arteriosus has prostanoid receptors coupled to contractile pathways and whether the sensitivity of the ductus to the dilator effect of prostaglandin E2 (PGE2) was inhibited by other prostanoids. Rings of ductus arteriosus were isolated from fetal New Zealand White rabbits (28 days of gestation) and mounted in vitro. In the presence of 1 microM indomethacin, the vessel was relaxed with either 300 nM forskolin or 10 nM PGE2, and cumulative concentration-contraction response curves to several synthetic prostanoids were obtained with or without a receptor antagonist when available. The vessel was also precontracted with 1 microM indomethacin and 25 mM K+ in 13-14.5 kPa O2, and cumulative concentration-relaxation response curves to PGE2 were obtained with and without addition of prostanoids. In 300 nM forskolin, both U46619 and sulprostone caused concentration-dependent contractions of the ductus in the nanomolar range (EC50 values, i.e., the interpolated molar concentration of the drug causing 50% of its own eventual maximum response of 33 and 42 nM, respectively). Responses to GR63799X and PGF2 alpha were complicated by the fact that these agonists caused relaxation at high concentrations (> or = 30 nM). The response to U46619 was shifted to the right by the thromboxane receptor antagonist EP 092. In 10 nM PGE2, U46619, sulprostone, and GR63799X elicited similar contractile responses, whereas PGF2 alpha had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Injection-site lesions in carcasses of cattle receiving injections at branding and at weaning.

Crossbred steer and heifer calves (n = 84) were given injections at branding and at weaning (using a completely randomized block design); 225 to 376 d later, pairs of two subprimal cuts from each animal were evaluated for incidence and severity of injection-site lesions. The four products compared were 1) a 2-mL clostridial, 2) a 5-mL clostridial, 3) vitamin AD3, and 4) a long-acting oxytetracycline antibiotic (OTC). Branding-age calves (mean 48.3 d of age) received intramuscular injections of two of the four products, in the semimembranosus (inside round) muscles (one in the left muscle and one in the right); at weaning age (mean 199.3 d of age), calves received injections of the remaining two products in the gluteus medius (top sirloin butt) muscles (one in the left and the other in the right). Injections at branding of 2 mL of clostridial, 5 mL of clostridial, vitamin AD3, and OTC caused injection-site lesions in 72.5, 92.7, 5.3, and 51.2%, respectively, of inside rounds from slaughter cattle. Incidence of injection-site lesions was lowest (P < .05) among inside rounds and top sirloin butts from animals given vitamin AD3 (as calves, and at both branding and weaning times) and was highest (P < .05) in inside rounds from cattle given, as calves, injections of 5 mL of clostridial at branding or of OTC at weaning. Less trimming was required to remove the lesions resulting from injections of all four products when they were given at weaning time. Before completion of the present study, it was thought that injection-site lesions were from damage that subsisted only briefly following an inoculation; these results make it abundantly clear that intramuscular administration of clostridials and certain antibiotics will cause damage so severe that it will be evident in beef muscle 7.5 to 12 mo later.

Aging↗

Effects of a dexamethasone implant on deposition of intramuscular fat in genetically identical cattle.

Administration of exogenous glucocorticoids has been shown to enhance deposition of intramuscular fat in cattle. In this study, six pairs of genetically identical (cloned) steers were used to determine the effects of an implant containing 100 mg of dexamethasone on intramuscular fat deposition and on other carcass and meat quality traits. One steer in each pair served as a negative control (CON), whereas the other steer received a dexamethasone implant 30 to 60 d from slaughter (DEX). Treatment with dexamethasone did not (P > .05) enhance intramuscular fat deposition. However, DEX steers had greater (.33 cm; P < .05) thickness of external fat, larger (5.94 cm2; P < .05) longissimus muscle areas, and higher (1.9 percentage points; P < .05) dressing percentages than did CON steers. In addition, treatment with dexamethasone increased (P < .01) serum insulin concentrations. Dexamethasone had no effect (P > .05) on cooked beef palatability traits or on 24-h calpastatin activity. Although the DEX implant tested in this study was not effective for improving carcass quality grade, use of the implant increased external fat thickness and was effective for increasing carcass muscularity and dressing percentage.

Adipose Tissue↗

Use of genetically identical (clone) steers to determine the effects of estrogenic and androgenic implants on beef quality and palatability characteristics.

Six sets of four genetically identical Brangus steers (n = 24; mean weight = 413 kg, SD = 19.8) were used to study the effects of estradiol and trenbolone acetate on beef quality and palatability characteristics. Steers in each clone set were randomly assigned to the following treatment groups: 1) a nonimplanted control; 2) a single estrogenic implant, containing 20 mg of estradiol benzoate and 200 mg of progesterone; 3) a single androgenic implant, containing 140 mg of trenbolone acetate; or 4) a single combination implant, containing 24 mg of 17-beta estradiol and 120 mg of trenbolone acetate. Following implantation, the steers were fed a high-concentrate finishing diet for a period of 112 d. Compared with control steers, implanted steers had higher (P < .05) average daily gains and heavier (P < .05) finished live weights and carcass weights. However, there were no differences (P > .05) among treatment groups with respect to their effects on growth rate, live weight, carcass weight, dressing percentage, fat thickness, longissimus muscle area, percentage of kidney, pelvic, and heart fat, or USDA yield grade. Moreover, marbling scores for implanted steers were not statistically different from marbling scores for control steers. However, a comparison among implant types showed that steers implanted with the estrogenic implant had significantly lower marbling scores than did steers implanted with the androgenic or combination implants. Use of androgenic and combination implants had no effect (P > .05) on beef tenderness of strip loin, top sirloin, or top round steaks; however, use of estrogenic implants decreased (P < .05) tenderness of top sirloin steaks.

Anabolic Agents↗

Injection-site lesions: incidence, tissue histology, collagen concentration, and muscle tenderness in beef rounds.

The national incidence and extent of injection-site lesions in the muscles of the round were determined via audits conducted at retail stores and in purveying establishments. Two additional experiments were conducted to examine the subsequent effects of pharmaceutical administration on tissue histology, soluble and insoluble collagen concentration, and muscle tenderness in beef bottom-rounds. Injection-site lesion incidence in beef round cuts audited at retail (n = 3,538) and in steak-cutting facilities (n = 15,464) was 8.45 and 10.04%, respectively, with an average lesion-trim of 314.7 and 191.59 g, respectively, in these two studies. Lesion classification revealed that 93.20 and 99.91% of lesions reported for the retail and purveyor audits, respectively, were chronologically aged lesions. Overall, 19,002 round cuts were examined, and injection-site lesion incidence (nationally) was 9.74%, whereas lesion-trim averaged 211.8 g. Warner-Bratzler shear measurements taken near lesions and in areas 7.62 cm from the lesions were higher (P < .001) for lesioned, than for control bottom-round steaks. Warner-Bratzler shear values for lesion cores were 3.5 times greater than those in paired control (non-affected) steaks. Concentrations of insoluble and soluble collagen were much higher (P < .001) at the site of the lesion center in lesion-afflicted vs control steaks. Histological determinations of the relative proportions of muscle, connective tissue and fat to a distance of 5.08 cm from the site of the lesion center confirmed that severe disruption of muscle tissue constituents and architecture had occurred. Injection-site lesions occur at an unacceptable frequency in the muscles of the round, and severe tissue changes accompany these lesions that can dramatically affect tenderness of those cuts.

Animals↗

Feedlot performance, carcass traits, and palatability traits of Hereford and Hereford x Brahman steers.

Short-yearling steer of known genotypes-straightbred Hereford (100H, n = 80) 75% Hereford x 25% Brahman (75H:25B, n = 80), and 50% Hereford x 50% Brahman (50H:50B, n = 80) were sampled serially at four time-on-feed endpoints (84, 98, 112, 126 d) to compare feedlot performance and carcass and palatability traits of Hereford and Hereford x Brahman steers. After slaughter, USDA yield grade and quality grade factors were recorded, and a portion of the longissimus muscle was removed from the left side of each carcass and fabricated into four 2.54-cm steaks for palatability analyses. Paired steaks from each carcass were aged (6 and 18 d after death), and sensory panel and shear force evaluations were performed. At a constant live weight, 100H steers had higher ADG and produced less mature carcasses with smaller longissimus muscle areas and higher marbling scores than did 75H:25B and 50H:50B steers. The 50H:50B steers had the highest (P < .05) values for dressing percentage. Loin steak tenderness and juiciness decreased (P < .05) and shear force values increased (P < .05) as the percentage of Brahman breeding increased. EXtending the postmortem aging period from 6 to 18 d improved shear force values by 20% and panel tenderness ratings by approximately 14%. Beef from steers of the three breeds responded similarly to aging. When Certified Hereford Beef (CHB) specifications were applied, steaks from 100H steers and 75H:25B steers had similar shear force values, suggesting that beef from quarter-blood Brahman crossbred steers could be included in the CHB Program without detrimental effects on product tenderness.

Aging↗

Effects of dietary supplementation of vitamin E on storage and caselife properties of lamb retail cuts.

Thirty wether lambs were randomly assigned to three treatments consisting of a control (C) and two vitamin E-supplemented treatments (VE), one fed 500 IU of vitamin E.lamb-1.d-1 (E500) and the other fed 1,000 IU of vitamin E.lamb-1.d-1 (E1000). After a 56-d feeding period, lambs were slaughtered and carcass traits were evaluated. Wholesale legs and loins were vacuum-packaged, stored at 4 degrees C for 7, 14, 21, or 28 d, fabricated into retail cuts, and packaged and displayed to simulate retail industry conditions. The E1000 lambs gained less (P < .05) (kg/d; total gain) and had lower (P < .05) carcass weights than the E500 lambs. Alpha-tocopherol levels in the longissimus lumborum were higher (P < .05) (5.79 vs 3.50 micrograms/g of tissue) for VE than for C; however, there was no difference in alpha-tocopherol level in longissimus lumborum between E500 and E1000. Leg retail cuts experienced greater (P < .05) lipid oxidation and received lower (P < .05) lean color scores than did loin retail cuts. Less (P < .05) lipid oxidation occurred from 1 to 7 d of display in VE retail cuts than in C retail cuts. Longer storage periods before retail display resulted in greater (P < .05) lipid oxidation at both 1 and 7 d of display and a higher (P < .05) rate of lipid oxidation during the display period. Supplementing vitamin E had the greatest effect in reducing lipid oxidation when cuts were stored for longer periods before retail display.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Consultation-liaison psychiatry in general medical units.

The activities of a consultation-liaison psychiatry service to general medical units in a university affiliated suburban teaching hospital are described, with a report from the MICRO-CARES clinical database on 165 consecutive referrals over a 12 month period. The referral rate was 4.2% of admissions. The data confirm the association of psychiatric referral and prolonged length of hospital stay (mean of 18 days for referred patients, 9 days for non-referred patients). The most common reasons for referral were depression, suicide risk evaluation, organic brain syndrome and suspected psychological component to illness. The most common psychiatric diagnoses were Mood Disorders (55%), Organic Mental Disorders (35%), Adjustment Disorders (19%), Somatoform and other Somatic Disorders (16%) and Personality Disorders (15%). Although 67% of patients received at least one confirmed diagnosis, 39% of all diagnoses remained "differential", or unconfirmed, at discharge. Concordance with drug recommendations was 97% and with non-drug recommendations 95%. Two groups of patients were prominent among the referrals: the young self-poisoning patient, and the older patient living alone. The issues involved in providing a liaison psychiatry service to general medical units with these characteristics are described.

Adaptation, Psychological↗

Isolation of potosi virus from Aedes albopictus in North Carolina.

A total of 4,169 adult mosquitoes were aspirated from 3 tire disposal sites in North Carolina for virus assays. Aedes albopictus was the dominant species, with a relative abundance of approximately 99%. Potosi virus was isolated from one pool of 68 female Ae. albopictus. Priorities for future Potosi virus research and the implications of the North Carolina isolate are discussed.

Aedes↗

Elderly mothers caring at home for offspring with mental retardation: a model of permanency planning.

A theoretical model of permanency planning based on the double ABCX model of family stress and adaptation (McCubbin & Patterson, 1982) was tested using structural equation modeling. We interviewed 235 mothers, ages 58 to 96, who cared for adult offspring with mental retardation at home. Four variables were confirmed to directly influence their stage of planning: use of services for offspring, non-use of avoidance coping, the self-perception of being adversely affected by age-related changes, and help from offspring without mental retardation. Variables found to affect planning indirectly were perceived need for services, mothers' subjective burden, extent of caregiving tasks, offsprings' disability, and mothers' disability.

Adaptation, Psychological↗

Involvement of angiotensin in water intake induced by peripheral administration of a serotonin agonist, 5-carboxyamidotryptamine.

Rats were given peripheral injections of a 5HT1 agonist, 5-carboxy-amidotryptamine (5-CT), and various behavioral, physiological, and neuronal outcomes were documented. 5-CT caused short latency water intake. In rats with a choice between water and hypertonic NaCl, about half of the rats drank only water while the other half showed an initial robust intake of NaCl. Blood pressure was reduced and plasma renin activity increased following 5-CT. The effective half life was 1-3 h, with water intake inhibiting further consumption. Fos-like immunoreactivity (FLI) was induced by 5-CT in regions of the brain identical to those previously shown to be activated by peripheral administration of angiotensin (Ang) II. The role of endogenously-generated Ang II in the dipsogenic action of 5-CT was suggested because captopril inhibited the water intake. Possible mechanisms of 5-CT and Ang II-induced thirst are reviewed, including roles of hypotension and the vagus nerve.

Analysis of Variance↗

Dissection of NADPH-cytochrome P450 oxidoreductase into distinct functional domains.

NADPH-cytochrome P450 oxidoreductase transfers electrons from NADPH to cytochrome P450 and catalyzes the one-electron reduction of many drugs and foreign compounds. This enzyme is a flavoprotein containing the cofactors FMN and FAD, which are essential for its function. We have expressed the putative FMN and FAD/NADPH binding domains of P450 reductase and show that these distinct peptides fold correctly to bind their respective cofactors. The FAD/NADPH domain catalyzed the one-electron reduction of a variety of substrates but did not efficiently reduce cytochrome c or cytochrome P450 (as judged by the oxidation of the CYP1A1 substrate 7-ethoxyresorufin). However, the domains could be combined to provide a functional enzyme active in the reduction of cytochrome c and in transferring electrons to cytochrome P450. Both the reconstitution of the domains and the direct binding of cytochrome c to the FMN domain were ionic-strength dependent. The FMN domain containing the hydrophobic membrane anchor sequence was a potent inhibitor of reconstituted monooxygenase activity. These data strongly support the hypothesis that FMN/FAD-containing proteins have evolved as a fusion of two ancestral genes and provide fundamental insights into how this and structurally related proteins, such as nitric oxide synthase and sulfite reductase, have evolved and function.

Cloning, Molecular↗