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Biomedical subjects

G C Smith

Publications and source records attributed to G C Smith.

At least 127 records · Page 7Linked to original sources
PubMed1998

DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D.

DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-strand break repair and V(D)J recombination, is comprised of a DNA-targeting component termed Ku and an approximately 465-kD catalytic subunit, DNA-PKcs. Although DNA-PK phosphorylates proteins in the presence of DSBs or other discontinuities in the DNA double helix in vitro, the possibility exists that it is also activated in other circumstances via its association with additional proteins. Here, through use of the yeast two-hybrid screen, we discover that the recently identified high affinity DNA binding protein C1D interacts with the putative leucine zipper region of DNA-PKcs. Furthermore, we show that C1D can interact with DNA-PK in mammalian cells and that C1D is a very effective DNA-PK substrate in vitro. Finally, we establish that C1D directs the activation of DNA-PK in a manner that does not require DNA termini. Therefore, these studies provide a function for C1D and suggest novel mechanisms for DNA-PK activation in vivo.

3T3 Cells↗
PubMed1998

Sticky egyptians: a technique for assembling genes encoding constrained peptides of variable length.

Naturally occurring peptides, such as those produced by the poisonous marine snails of the genus Conus , have the ability to form tight, highly specific molecular interactions. The rigidity of the peptide framework which promotes these interactions is usually maintained by disulphide bonds, and it seems that the overall main chain conformation (or fold) of the peptide is determined by its length and the sequence distribution of the pairs of cysteine residues participating in these bonds. The fold of the peptide in turn is largely responsible for its shape. Since highly effective molecular interactions occur between species complementary in shape, we reasoned that peptides with the greatest potential in therapy or diagnosis would be found in a library of shapes, those peptides with a shape complementary to a given target being identified, for example, by selection. As a first step towards constructing such a peptide shape library, we have developed a method for assembling DNA fragments which encode an even number of cysteine residues and which are of variable length. We describe this method here.

Cysteine↗
PubMed1998

Molecular and biochemical characterisation of DNA-dependent protein kinase-defective rodent mutant irs-20.

The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) is a member of a sub-family of phosphatidylinositol (PI) 3-kinases termed PIK-related kinases. A distinguishing feature of this sub-family is the presence of a conserved C-terminal region downstream of a PI 3-kinase domain. Mutants defective in DNA-PKcs are sensitive to ionising radiation and are unable to carry out V(D)J recombination. Irs-20 is a DNA-PKcs-defective cell line with milder gamma-ray sensitivity than two previously characterised mutants, V-3 and mouse scid cells. Here we show that the DNA-PKcs protein from irs-20 cells can bind to DNA but is unable to function as a protein kinase. To verify the defect in irs-20 cells and provide insight into the function and expression of DNA-PKcs in double-strand break repair and V(D)J recombination we introduced YACs encoding human and mouse DNA-PKcs into defective mutants and achieved complementation of the defective phenotypes. Furthermore, in irs-20 we identified a mutation in DNA-PKcs that causes substitution of a lysine for a glutamic acid in the fourth residue from the C-terminus. This represents a strong candidate for the inactivating mutation and provides supportive evidence that the extreme C-terminal motif is important for protein kinase activity.

Animals↗
PubMed1998

Regional variations in contractile responses to prostaglandins and prostanoid receptor messenger ribonucleic acid in pregnant baboon uterus.

OBJECTIVES: The aims of this study were to compare (1) the contractile responses of the lower uterine segment and fundus to prostaglandins, (2) expression of genes encoding prostanoid receptors in myo-metrium from different regions of the uterus, and (3) the distribution of expression of genes encoding prostanoid receptors (P receptors) in key intrauterine tissues. STUDY DESIGN: Cesarean hysterectomy was performed in 8 pregnant baboons, not in labor, in the last third of pregnancy. Contractile responses of fresh tissue were quantified in a superfusion system. Polyadenylated ribonucleic acid was extracted from frozen tissue and gene expression was quantified by Northern blot analysis with complementary deoxyribonucleic acid probes. RESULTS: Prostaglandin E2 contracted strips of myometrium from the fundus but had no significant effect on strips from lower uterine segment. Prostaglandin F2 alpha contracted myometrium from both regions equally. Compared with fundus tissue, lower uterine segment tissue had greater expression of EP2 receptor messenger ribonucleic acid, less expression of EP3 receptor messenger ribonucleic acid, but similar levels of EP4 receptor and FP receptor messenger ribonucleic acid. EP2 receptor, EP3 receptor, and EP4 receptor messenger ribonucleic acids were also detected in cervix, decidua, and chorion. EP2 receptor messenger ribonucleic acid was most abundant in the cervix, EP3 receptor messenger ribonucleic acid was most abundant in the myometrium, and EP4 receptor messenger ribonucleic acid was most abundant in the decidua. CONCLUSIONS: The reduced contractile response of lower uterine segment tissue to prostaglandin E2 is paralleled by greater inhibitory EP2 receptor expression and less contractile EP3 receptor expression, a pattern similar to that seen in the cervix. Drugs with selective activity at prostanoid receptor types and subtypes are likely to allow safer and more effective control of the uterus and cervix than native prostaglandins.

Animals↗
PubMed1998

Parathyroid hormone-related peptide (1 to 34) inhibits in vitro oxytocin-stimulated activity of pregnant baboon myometrium.

OBJECTIVES: We sought to determine the in vitro effect of parathyroid hormone-related protein fragment 1 to 34 on oxytocin precontracted myometrium from baboons in late gestation and to explore possible regional uterine differences in responsiveness comparing muscle strips from the lower uterine segment, posterior and anterior corpus, and fundus. STUDY DESIGN: We used cumulative concentration response (1 to 100 nmol/L) curves to parathyroid hormone-related protein (1 to 34) in isolated strips of baboon myometrium obtained at cesarean hysterectomy of 6 pregnant baboons in the last third of pregnancy. RESULTS: Parathyroid hormone-related protein (100 nmol/L) decreased both amplitude and frequency of contraction. The maximum effect of parathyroid hormone-related protein on the amplitude of contractions was greater than saline solution (2-way analysis of variance, F ratio 424.0, P < .001), but there was no difference comparing the four regions of the uterus (F ratio 1.342, P = .286). The maximum effect of parathyroid hormone-related protein on the frequency of contractions was greater than saline solution (2-way analysis of variance, F ratio 162.5, P < .0001), but no difference in response was noted in the 4 regions of the uterus (F ratio = 0.682, P = .572). CONCLUSION: Parathyroid hormone-related protein completely inhibited the contractile effect of high doses of oxytocin in the lower segment, corpus, and fundus of the baboon uterus. No difference in response of myometrium was obtained from different regions of the uterus.

Animals↗
PubMed1998

Adjustment disorder: a multisite study of its utilization and interventions in the consultation-liaison psychiatry setting.

The consultation-liaison (C-L) psychiatry services of seven university teaching hospitals in the United States, Canada, and Australia (the MICRO-CARES Consortium) used a common clinical database to examine 1039 consecutive referrals. A diagnosis of adjustment disorder (AD) was made in 125 patients (12.0%); as the sole diagnosis, in 81 (7.8%); and comorbidly with other Axis I and II diagnoses in 44 (4.2%). It had been considered as a rule-out diagnosis in a further 110 (10.6%). AD with depressed mood, anxious mood, or mixed emotions were the commonest subcategories used. AD was diagnosed comorbidly most frequently with personality disorder and organic mental disorder. Sixty-seven patients (6.4%) were assigned a V code diagnosis only. Patients with AD were referred significantly more often for problems of anxiety, coping, and depression; had less past psychiatric illness; and were rated as functioning better--all consistent with the construct of AD as a maladaptation to a psychosocial stressor. Interventions were similar to those for other Axis I and II diagnoses, in particular, the prescription of antidepressants. Patients with AD required a similar amount of clinical time and resident supervision. It is concluded that AD is an important and time-consuming diagnostic category in C-L psychiatry practice.

Adjustment Disorders↗
PubMed1998

Geographical change in residential care provision for the elderly in England, 1988-93.

This paper offers an investigation of the spatial consequences of changes in the structural organization of residential care in England between 1988 and 1993. Data from various government publications were analysed using descriptive and spatial statistical methods. While the study period witnessed an overall levelling of residential care growth, the independent (i.e. private and voluntary) sector's share of all elderly residents in England increased from 56% to 73%. At both national and intra-regional scales, the structural changes resulted in an increasing geographical concentration of public sector residents and a moderate trend towards a more uniform spatial distribution of private residents.

Aged↗
PubMed1998

Isolation of La Crosse, Cache Valley, and Potosi viruses from Aedes mosquitoes (Diptera: Culicidae) collected at used-tire sites in Illinois during 1994-1995.

Prospective studies were conducted at used-tire sites in Illinois during 1994-1995 in an effort to isolate arboviruses from mosquitoes, particularly Aedes albopictus (Skuse) and Aedes triseriatus (Say). Three isolates of Potosi virus were obtained from Ae. albopictus collected at a waste tire site in Jasper County during 1994 and 1995. Also, a single isolate of Cache Valley virus was obtained from Ae. albopictus collected at the Jasper County site during 1995. These are the first records of arbovirus isolations from Ae. albopictus in Illinois and the first isolate of Cache Valley virus from this mosquito species. During 1994, two isolates of La Crosse virus were made from Ae. triseriatus collected at a used-tire site in Peoria County in proximity to the residence of a human La Crosse encephalitis case. This is the first evidence in Illinois that indicates increased risk to humans living near used-tire sites, which may serve as foci for production of Ae. triseriatus, the vector of La Crosse virus. Tire removal and improved environmental sanitation at such sites may greatly reduce the abundance of vector mosquitoes, and, therefore, the risk of arbovirus transmission.

Aedes↗
PubMed1998

National Beef Quality Audit-1995: survey of producer-related defects and carcass quality and quantity attributes.

The National Beef Quality Audit-1995 was conducted to evaluate the progress of the beef industry since the time of the National Beef Quality Audit-1991 in improving quality and consistency of beef. Nine plants were assigned for auditing to Colorado State University, Oklahoma State University, and Texas A&M University. Personnel from each institution visited three of their nine plants twice, once in the spring/summer and once in the fall/winter. Data were collected on 50% of each lot on the slaughter floor and 10% in the cooler during a single day's production (one or two shifts, as appropriate). Of the cattle audited on the slaughter floor, 47.7% had no brands, 3.0% had a shoulder brand, 16.8% had a side brand, 38.7% had a butt brand, and 6.2% had brands in multiple locations. Data revealed that 51.6% of the carcasses had no bruises, 30.9% had one bruise, 12.8% had two bruises, 3.7% had three bruises, .9% had four bruises, and .1% had more than four bruises. In addition, 7.2% of the bruises evaluated were located on the round, 41.1% were on the loin, 20.8% on the rib, and 30.8% on the chuck. Livers, lungs, tripe, heads, tongues, and whole carcasses were condemned at rates of 22.2, 5.0, 11.0, .9, 3.8, and .1%, respectively. Mean USDA yield grade and quality grade traits were as follows: USDA yield grade, 2.8; carcass weight, 338.4 kg; adjusted fat thickness, 1.2 cm; longissimus muscle area, 81.9 cm2; kidney, pelvic, and heart fat, 2.1%; USDA quality grade, High Select; overall maturity, A60; and marbling score, Small-minus.

Animal Identification Systems↗
PubMed1998

Simulated instrument augmentation of USDA yield grade application to beef carcasses.

Because no instrument technology has been shown to predict beef carcass composition better than USDA yield grades, this study was conducted to determine whether an instrument could be used to augment and improve the accuracy of USDA yield grade placement. Adjusted preliminary yield grade (PYG), ribeye area (REA), estimated percentage of kidney, pelvic, and heart fat (KPH), hot carcass weight (HCW), and USDA yield grade (called and computed) were determined by five on-line USDA graders and two USDA grading supervisors for beef carcasses (n = 550) selected randomly in a commercial beef packing plant. Data were compared (2,737 comparisons) to Gold Standard yield grades and yield grade factors determined by an expert panel of carcass evaluators (unrestrained in access or time to evaluate carcasses). On-line USDA grader PYG were closely related (mean absolute error of .15 +/- .14 yield grade units; r = .91), and on-line REA and KPH were nominally related (mean absolute error of .51 +/- .35, .06 +/- .07 yield grade units and r = .48 and .66, respectively), to Gold Standard yield grade factors. On-line USDA graders determined adjusted PYG effectively, but they may require instrument assistance to evaluate carcass muscling traits and perform time-sensitive computations. To explain why instrument technology may not estimate beef carcass fatness as accurately as USDA yield grades, the absolute mean difference between Gold Standard measured PYG and adjusted PYG were compared. Only 5.6% of the sample population required no PYG adjustment, 94.4% required some adjustment, and 11.0% required over a .5 yield grade unit adjustment. Yield grades for beef carcasses, called by the USDA graders and supervisors at chain speeds, resulted in greater accuracy (absolute mean error of .24 +/- .43 yield grade units; r = .82) than when yield grades were computed for carcasses using the yield grade factors determined by on-line USDA graders and supervisors at chain speeds (absolute mean error of .52 +/- .41 yield grade units; r = .75). Gold Standard yield grade factors were sequentially substituted into the short-cut USDA yield grade equation for the yield grade factors determined at chain speeds by the USDA graders and supervisors. Results suggested that instrument augmentation would improve accuracy and precision of yield grade placement if on-line USDA graders determined PYG and an instrument determined REA and performed the necessary computations, incorporating KPH and actual HCW (P < .05).

Adipose Tissue↗
PubMed1998

Factors contributing to the incidence of dark cutting beef.

The 1995 National Beef Quality Audit reported that dark cutting beef (dark cutters) cost $6.08 per animal harvested in the United States. Feedlot data were obtained over a 3-yr period from nine commercial feedyards (15,439 pens of cattle; 2,672,223 total cattle). Feedyard, sex, implant treatment, days from final implant to harvest, maximum and minimum daily temperatures, and temperature fluctuations from 2 d before harvest to the day of harvest all contributed (P < .05) to the incidence of dark cutters. Heifers yielded a higher (P < .05) percentage of dark cutters per pen and, when reimplanted a second time with an estrogenic implant, produced greater (P < .05) mean percentages of dark cutters per pen than heifers reimplanted with either androgens or combination (androgen and estrogen) growth promotants. Furthermore, heifers produced higher (P < .05) mean percentages of dark cutters per pen than steers during periods of hot (> 35 degrees C) weather 2 to 1 d before harvest. Steers, when treated with a combination (androgen and estrogen) implant when entering the feedyard and as a reimplant, produced higher (P < .05) mean percentages of dark cutters per pen when compared to other moderate growth-promoting implant strategies. When producers opted to implant steers with estrogenic growth promotants, either as the cattle entered the feedlot or as a final reimplant before harvest, the occurrence of dark cutters was reduced from 9.2 per thousand cattle shipped to 2.0 and .5 per thousand cattle shipped, respectively. Producers that reimplanted heifers before harvest with products that were not primarily estrogenic reduced the occurrence of dark cutters from 10.4/1,000 cattle shipped to 5.2/1,000 cattle shipped when androgen-based growth promotants were used and to 3.5/1,000 cattle shipped when combination (androgen and estrogen) implants were administered. In addition to implant selection, those producers that held cattle on-feed over 100 d past reimplantation reduced the incidence of dark cutters per pen by an average of 38% among heifers and 69% among steers. By reducing the occurrence of dark cutters, there is an opportunity for beef producers to realize large economic savings.

Androgens↗
PubMed1998

An evaluation of current and alternative systems for quality grading carcasses of mature slaughter cows.

Strip loins from 354 female bovine carcasses, selected to represent 30 skeletal maturity (A, B, C, D, and E) x marbling score (SA/MA/AB, MD, MT, SM, SL, and TR/PD) subclasses, were used to evaluate current and alternative systems for classifying cow carcasses into expected-palatability groups. Strip loins were vacuum-packaged, stored for 14 d postmortem at 2 degrees C, and frozen (-27 degrees C). Five steaks from each strip loin, each cooked to a different internal temperature (60, 66, 71, 77, or 82 degrees C), were used for shear force determinations. Two steaks from each strip loin, one cooked to 66 degrees C and the other to 77 degrees C, were used for sensory evaluation. Increased carcass maturity was associated with decreased tenderness and juiciness, increased flavor intensity, and a higher incidence of flavors described as "painty," "fishy," and "grassy." Position of a carcass within a maturity group had a negligible effect on palatability. Increased marbling was associated with greater tenderness and juiciness, a lower incidence of steaks with a "grassy" flavor, and a higher incidence of steaks with a flavor described as "fatty." Relationships between marbling and beef palatability traits were consistent across all maturity groups. Carcasses of maturities A through E were most effectively stratified according to differences in palatability when marbling scores were grouped as follows: 1) MD and higher; 2) SL, SM, MT; and 3) TR/PD. Among mature (C, D, and E maturity) carcasses, yellow-colored fat was associated with greater beef toughness and higher detection rates for "grassy" and "fishy" flavors. Higher end-point temperatures were associated with higher shear force values and lower ratings for muscle fiber tenderness, connective tissue amount, overall tenderness, and juiciness. Two alternative grading approaches (one involving current quality grading factors and the other involving the use of fat color as an additional grade factor) were developed for possible use in classification of cow carcasses into expected-palatability groups. Both alternative systems provided a more effective stratification of cow carcasses according to palatability differences than did the current USDA quality grading system.

Age Factors↗
PubMed1998

From consultation-liaison psychiatry to psychosocial advocacy: maintaining psychiatry's scope.

OBJECTIVE: To review the status of consultation-liaison (C-L) psychiatry and the forces shaping it, and to propose strategies for dealing with the crisis in which it finds itself. METHOD: A Medline search of C-L psychiatry and related terms, together with hand-searching of C-L psychiatry and psychosomatic journals and bibliographies of found articles, was used for the literature base. The experience of membership of the committees of national and international C-L psychiatry organisations and their interaction with health care administrators was used as the basis for the discussion of strategies. RESULTS: It is argued that patients with physical/psychiatric comorbidity and somatisation have been marginalised by application of narrow definitions of what constitutes 'serious mental disorder' in the public sector. Evidence is presented to support the argument that physical/psychiatric comorbidity is the most common form of psychiatric presentation in the community, that such comorbidity has serious consequences in terms of morbidity, mortality and health-care costs, and that even subthreshold psychiatric symptoms have serious implications when physical comorbidity exists. CONCLUSION: It is concluded that a number of strategies, including pre-admission screening, integrated discharge planning, liaison, as well as shared care with general practitioners, advanced training in C-L psychiatry and more research to establish practice guidelines, are required if psychiatry is to remain a broad-based discipline rather than retreat to being a specialty for psychosis. Consultation-liaison psychiatrists must become the advocates for the psychosocial system.

Australia↗
PubMed1998

Bacterial growth in ground beef patties made with meat from animals fed diets without or with supplemental vitamin E.

A study was designed to determine populations of aerobic bacteria, coliforms, sorbitol-negative bacteria, and Listeria monocytogenes during display at 4 and 12 degrees C of ground beef patties made with meat from animals fed diets supplemented daily (for 100 days) with 0, 1,000, or 2,000 IU of vitamin E. The patties (113.5 g) were either left uninoculated or were inoculated with Escherichia coli O157:H7 or L. monocytogenes and were tray-overwrapped and stored (at 4 or 12 degrees C for 8 to 10 or 4 to 6 days, respectively) while being continuously exposed to fluorescent light in a display setting. Patties were visually evaluated for overall appearance (based on color and/or discoloration) twice a day and analyzed for microbiological counts at 2-day intervals during display at 4 degrees C and at 0, 1, 2, 3, 4, and 6 days during display at 12 degrees C. Use of beef from animals fed supplemental vitamin E ("high-vitamin E beef") resulted in ground beef patties which, when stored at 4 degrees C, maintained visually acceptable color longer than did patties made from control beef (from animals not fed supplemental vitamin E), but effects on microbial growth were less pronounced. In general, use of high-vitamin E beef versus control beef in patty manufacture had no major effect on populations of aerobic bacteria, coliforms, sorbitol-negative bacteria, or L. monocytogenes in ground beef patties displayed at 4 or 12 degrees C. Listeria monocytogenes multiplied at 12 degrees C, but growth was similar among ground beef patties made from high-vitamin E beef versus control beef. Overall, changes in bacterial populations were similar in ground beef patties derived from meat from animals with or without added vitamin E in their diets, but control ground beef became visually unacceptable sooner.

Animal Feed↗
PubMed1997

Cognitive-existential group therapy for patients with primary breast cancer--techniques and themes.

We describe a model of cognitive-existential group therapy designed to be integrated over 6 months with regimens of adjuvant chemotherapy given as conventional medical treatment to breast cancer patients with stage 1 and 2 disease. Our broad therapy goals are for members to develop a supportive network, work through grief over losses, improve problem solving and develop cognitive strategies to maximise coping, enhance a sense of mastery over life and re-evaluate priorities for the future. Specific group themes include death anxiety, fear of recurrence, living with uncertainty, understanding treatment with chemotherapy, radiotherapy and hormone regimens, the collaborative doctor-patient relationship, body and self image, sexuality, relationships with partner, friends and family, surgical reconstruction, life style effects and future goals. Active coping skills are developed through teaching formal problem solving and cognitive restructuring of automatic negative thoughts. Technical aspects of the therapy are discussed.

Adaptation, Psychological↗
PubMed1997

Complement activation in Henoch-Schönlein purpura.

The pathogenetic mechanism underlying Henoch-Schönlein purpura (HSP) is poorly understood. Complement activation has been thought to have a role, but despite the demonstration of complement components in skin and renal biopsy material, serological evidence of complement activation is not convincing. We have assessed complement activation in 64 children with acute HSP. We used an enzyme-linked immunosorbent assay to measure plasma levels of three multimolecular complement activation protein (CAP) complexes: C1r:C1s:C1-inhibitor, C3bP and C5b-9. We found no significant difference between the levels of CAPs in children with acute HSP and a control group of children. This study does not support a role for complement activation in the pathogenesis of HSP.

Adolescent↗
PubMed1997

alpha-Toxin-permeabilised rabbit fetal ductus arteriosus is more sensitive to Ca2+ than aorta or main pulmonary artery.

OBJECTIVES: The Ca2+ sensitivity of contractile protein-generated tension production was measured in the smooth muscle of the rabbit ductus arteriosus and compared with two neighbouring fetal blood vessels (main pulmonary artery and aorta). The effect of prostaglandin E2 (PGE2), 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor), cyclic adenosine 3'5'-monophosphate (CAMP) and forskolin (an activator of adenylate cyclase) on Ca(2+)-activated force generated by preparations from ductus arteriosus was also examined. METHODS: Strips of smooth muscle from the three vessels were permeabilised using crude alpha-toxin from Staphylococcus aureus. The relationship between [Ca2+] and force production was then measured in the three tissues and the effect of PGE2, cAMP, IBMX and forskolin was examined on submaximal Ca(2+)-activated force (0.3 microM Ca2+) in preparations from rabbit ductus arteriosus. RESULTS: Permeabilised smooth muscle from fetal rabbit ductus arteriosus was significantly more sensitive to Ca2+ (EC50, 0.20 microM) than its two neighbouring blood vessels aorta (EC50, 0.52 microM) and main pulmonary artery (EC50, 0.72 microM). Submaximal Ca(2+)-activated force (0.3 microM Ca2+) was depressed by PGE2 (1 nM) in the presence of IBMX (10 microM), by cAMP (10 and 100 microM) and by forskolin alone (0.1 microM and 1 microM). CONCLUSION: PGE2-mediated depression of Ca(2+)-activated force in the smooth muscle of the ductus arteriosus may play a role in the maintenance of a patent ductus arteriosus in the fetus. The intrinsically high Ca2+ sensitivity of smooth muscle contractile proteins may aid the sustained vasoconstriction of the ductus when the PGE2 levels fall after birth.

1-Methyl-3-isobutylxanthine↗