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Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 127 records · Page 7Linked to original sources

Cloning and expression of the axolotl proto-oncogene ski.

In vitro and in vivo overexpression studies have demonstrated that the c-ski proto-oncogene can influence proliferation, morphological transformation and myogenic differentiation. We report the isolation and expression of an axolotl (Ambystoma mexicanum) c-ski (aski) gene. Sequence analysis revealed a high degree of nucleotide and predicted amino acid (AA) homology with mammalian and anuran c-ski, showing the highest conservation to Xenopus laevis c-ski (74% nucleotide and 87% AA). Northern analysis showed that axolotl c-ski is expressed in unfertilized eggs and at increasing levels in embryos from blastula to tadpole stage. c-ski expression was also detected in larval limb muscle and in several stages of regenerating limb blastemas. These data indicate that axolotl c-ski is highly conserved among amphibians and mammals and suggests that it plays a role in urodele embryogenesis and limb regeneration.

Ambystoma↗

Effect of high-lipid high-nitrogen intravenous nutrition on total body nitrogen, visceral protein synthesis and nitrogen balance.

The impact of high-lipid intravenous nutrition (IVN) on selected indices of nitrogen retention following major surgical resection was studied. Twenty-two patients, randomly allocated to two equal well matched groups, received either high-lipid IVN (75 per cent non-protein calories supplied as lipid) or isocaloric isonitrogenous glucose IVN (100 per cent non-protein calories supplied as glucose). Total body nitrogen (assessed by in vivo neutron activation analysis), nitrogen balance and levels of circulating proteins were measured. Mean(s.d.) total body nitrogen and fat-free mass decreased (P = 0.04) in patients receiving high-lipid IVN, -109(36) gN and -1.7(0.4) kg respectively, but not in those given glucose-only IVN, 8(43) gN and 0.1(1.0) kg. This small loss of body protein does not appear to be clinically significant because postoperative hospital stay, complication rates and the acute-phase protein response (immunological and visceral) were similar in the two groups.

Body Composition↗

Shared T cell epitopes in epithelial tumors.

We have previously shown the importance of human leukocyte antigen (HLA)-A2 and the proto-oncogene HER2/neu in the T cell recognition of ovarian cancer. Since these proteins are ubiquitously expressed in epithelial-derived tumors, we have acid-eluted HLA-bound peptides from ovarian cancers, fractionated the peptides, and reconstituted T cell epitopes on the HLA-A2+ T2 cell line to determine if common tumor-associated antigens exist among HLA-A2+, HER2/neu+ epithelial cancers. We demonstrate that tumor-specific cytotoxic T lymphocytes (CTL) generated from tumor-infiltrating lymphocytes isolated from three ovarian, two breast, and two non-small-cell lung cancers recognize at least three of the same peptide fractions from multiple elutions. One of these peptide fractions coelutes with a HER2/neu-derived peptide which has been shown recently to be recognized by these same CTL. These findings demonstrate that a common peptide-based tumor vaccine is theoretically possible for many different epithelial-derived cancers.

Antigens, Neoplasm↗

The role of metabolites in strength training. I. A comparison of eccentric and concentric contractions.

This study examined the role of high forces versus metabolic cost in the adaptations following strength training. Ten young, healthy male and female subjects trained one leg using concentric (CL) and the other using eccentric (EL) contractions of the quadriceps muscle for 20 weeks. EL used weights which were 35% higher than those used for CL. Isometric strength, and the length:tension and force:velocity relationship of the muscle were measured before and after training. Muscle cross-sectional area (CSA) was measured near the knee and hip using computed tomography. Increases in isometric strength were greater for CL compared to EL, the difference being significant with the knee at 1.57 rad (90 degrees) [mean (SD), 43.7 (19.6)% vs 22.9 (9.8)%, respectively; P = 0.01]. Increases in isokinetic strength tended to be larger for EL, although the differences were not significant. Significant increases in CSA occurred near the hip for both EL and CL. These results suggest that metabolic cost, and not high forces alone, are involved in the stimuli for muscle hypertrophy and strength gains following high-resistance training.

Adult↗

Improving residents' confidence in using psychosocial skills.

OBJECTIVE: To evaluate an intensive training program's effects on residents' confidence in their ability in, anticipation of positive outcomes from, and personal commitment to psychosocial behaviors. DESIGN: Controlled randomized study. SETTING: A university- and community-based primary care residency training program. PARTICIPANTS: 26 first-year residents in internal medicine and family practice. INTERVENTION: The residents were randomly assigned to a control group or to one-month intensive training centered on psychosocial skills needed in primary care. MEASUREMENTS: Questionnaires measuring knowledge of psychosocial medicine, and self-confidence in, anticipation of positive outcomes from, and personal commitment to five skill areas: psychological sensitivity, emotional sensitivity, management of somatization, and directive and nondirective facilitation of patient communication. RESULTS: The trained residents expressed higher self-confidence in all five areas of psychosocial skill (p < 0.03 for all tests), anticipated more positive outcomes for emotional sensitivity (p = 0.05), managing somatization (p = 0.03), and nondirectively facilitating patient communication (p = 0.02), and were more strongly committed to being emotionally sensitive (p = 0.055) and managing somatization (p = 0.056), compared with the untrained residents. The trained residents also evidenced more knowledge of psychosocial medicine than did the untrained residents (p < 0.001). CONCLUSIONS: Intensive psychosocial training improves residents' self-confidence in their ability regarding key psychosocial behaviors and increases their knowledge of psychosocial medicine. Training also increases anticipation of positive outcomes from and personal commitment to some, but not all, psychosocial skills.

Clinical Competence↗

Identification of an endogenous inhibitor of prostatic carcinoma cell growth.

The rate of expansion of primary prostatic carcinoma is comparatively slow, with tumours frequently taking years or decades to reach clinically relevant size. We now report the presence of an endogenous inhibitor, derived from aqueous extracts of human prostate tissue, which blocks prostatic carcinoma cell proliferation in vitro and prevents subcutaneous tumour expansion in vivo. Purification and characterization revealed the inhibitor to be spermine, a polyamine known to be locally abundant in the prostate. These results suggest that endogenous polyamine can negatively regulate the growth of prostatic carcinoma cells at their primary site in vivo and may explain the slow rate of primary tumour expansion in the prostate.

Adenocarcinoma↗

A strategy for improving patient satisfaction by the intensive training of residents in psychosocial medicine: a controlled, randomized study.

PURPOSE: To use a controlled, randomized design to assess the effect on patient satisfaction of an intensive psychosocial training program for residents. METHOD: Twenty-six first-year residents, in two internal medicine and family practice community-based programs affiliated with the Michigan State University College of Human Medicine, were randomly assigned during 1991 and 1992 to a control group or a one-month intensive training program. Experiential teaching focused on many psychosocial skills required in primary care. A 29-item questionnaire administered before and after the residents' training evaluated their patients' satisfaction regarding patient disclosure, physician empathy, confidence in physician, general satisfaction, and comparison of the physician with other physicians. Analyses of covariance with groups and gender as factors and pre-training patient satisfaction scores as the covariate evaluated the effect of the training. RESULTS: The patients of the trained residents expressed more confidence in their physicians (p = .01) and more general satisfaction (p = .02) than did the patients of controls. The effect of training on patient satisfaction with patient disclosure (p < .01) and physician empathy (p < .05) was greater for female than for male residents. CONCLUSION: The intensive psychosocial training program for residents improved their patients' satisfaction.

Clinical Competence↗

Soft lens movement: effects of humidity and hypertonic saline on lens settling.

Hydrogel contact lenses require a settling period before lens fit stabilizes, but the process underlying the initial reduction in lens mobility is poorly understood. Explanations for this phenomenon include base curve steeping with dehydration, expulsion of postlens tear fluid, and osmotic flow of hypotonic tears into the cornea. We conducted two randomized, single-masked interocular comparisons for ten subjects wearing HEMA lenses for 1 h. We investigated potential mechanisms of dehydration-dependent lens tightening, by limiting dehydration in one eye using a high humidity environment (experiment 1), and of a hypotonic lacrimation-dependent decrease in lens movement, by presoaking lenses in isotonic (0.9%) or hypertonic (1.5%) saline (experiment 2). Lens mobility profiles were not significantly affected by modification of environment; lenses in both normal and high humidity environments displayed a significant reduction in lens movement during the first 15 min of wear (ANOVA, p = 0.0001), and no change in lens mobility thereafter. Lens mobility profiles were identical for lenses presoaked in isotonic and hypertonic saline, with initial lens movement being significantly greater than for subsequent measurements (ANOVA, p < 0.05). These studies find no evidence to support dehydration-dependent steepening of base curve, or osmotic-dependent binding from hypotonic lacrimation as mechanisms for the initial postinsertion decrease in lens movement.

Adult↗

MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation.

The terminal differentiation of C2C12 skeletal muscle cells involves the activation of unique sets of genes and an irreversible withdrawal from the cell cycle. This process is associated with a decrease in cdk2 activity in cell extracts. The decrease in cdk2 activity correlates with diminished levels of cdk2 and cyclin A and with a marked induction of the p21 cyclin-dependent kinase (cdk) inhibitor. The upregulation of p21 occurred at the levels of mRNA and protein, and p21 formed a complex with the cyclin kinases in myotubes. Further, the immunodepletion of p21 from myotube extracts neutralized the heat-stable cdk2 inhibitory activity that was induced upon myogenic differentiation. The levels of p21 mRNA, protein, and activity remained constant in myotubes when they were reexposed to mitogen-rich growth medium, indicating that permanent changes in the cell's genetic program contribute to its sustained expression following terminal differentiation. Indeed, 10T1/2 fibroblasts transformed with the myogenic factor MyoD, but not the parental multipotent cells, upregulated p21 transcript levels when induced to differentiate by serum withdrawal, demonstrating that the upregulation is an integral feature of myogenic commitment and differentiation. The functional consequences of this upregulation were indicated by ectopically expressing p21 in myoblasts; this was sufficient for cell cycle arrest in mitogen-rich growth medium. The induction and sustained expression of p21 appears to be a contributory mechanism by which myocytes irreversibly exit the cell cycle upon terminal differentiation.

Base Sequence↗

Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with MR imaging. Work in progress.

PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging to determine the depth of myometrial invasion in patients with clinical stage I endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length, tumor signal intensity, appearance of the junctional zone, presence of large polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB, and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep myometrial invasion (stage IC) from superficial disease (stages IA and IB) was 78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors (P = .025), and difficulty in pathologic staging (P < .005) were significantly associated with incorrect MR assessment. CONCLUSION: When present, large polypoid tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal anatomy may make it difficult to assess myometrial invasion at MR imaging.

Aged↗

Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography.

PURPOSE: To compare non-contrast-enhanced computed tomography (CT) and intravenous urography (IVU) in the evaluation of patients who present with acute flank pain and in whom ureteric obstruction is suspected. MATERIALS AND METHODS: The findings at non-contrast-enhanced CT and IVU in 20 patients with acute flank pain were compared for the presence or absence of ureteric obstruction and delineation of ureteric stones. RESULTS: Twelve of the 20 patients had non-contrast-enhanced CT and IVU findings consistent with ureteric obstruction. Of these 12 patients, five had a ureteric stone that was demonstrated on both non-contrast-enhanced CT scans and IVU radiographs, six had a stone that was depicted on non-contrast-enhanced CT scans only, and in one patient a stone could not be delineated definitively on either non-contrast-enhanced CT scans or IVU radiographs. Eight patients had findings at non-contrast-enhanced CT and IVU consistent with the absence of obstruction. CONCLUSION: Non-contrast-enhanced CT is more effective than IVU in precisely identifying ureteric stones and is equally effective as IVU in the determination of the presence or absence of ureteric obstruction.

Acute Disease↗

Absorption of silicon and aluminum by hens fed sodium zeolite A with various levels of dietary cholecalciferol.

Two experiments were conducted to determine whether 1) serum Si and Al is increased in hens intubated with sodium zeolite A (SZA); and 2) dietary cholecalciferol (vitamin D3) influences the absorption of Si or Al by hens fed SZA. In Experiment 1, hens were intubated at oviposition with 0, 1, or 2 g of SZA. Blood samples were collected from the brachial vein at oviposition, and 4, 8, 12, 16, and 20 h postoviposition. Serum samples were analyzed for Si and Al. Peak serum Si and Al were observed at 4 and 8 h postoviposition, respectively. In Experiment 2, hens consumed commercial layer diets ad libitum containing five levels of dietary cholecalciferol (100 to 500 IU/kg) with or without .75% SZA for 6 wk. Blood samples were collected at the end of the 6-wk period by cardiac puncture at oviposition. When dietary cholecalciferol was increased from 100 to 200 IU/kg of diet there was an increase (P < .05) in serum Si but not Al. Levels of cholecalciferol above 200 IU/kg did not produce an additional increase in serum Si. The results showed increased (P < .01) serum concentrations of Si and Al for hens intubated with or fed SZA. It was concluded that Si and Al from SZA are absorbed by commercial Leghorn hens, and a possible involvement of Si or Al should be considered in the mechanism of action of SZA associated with improved eggshell quality and bone development.

Absorption↗

Frequent loss of heterozygosity at 11p loci in testicular cancer.

Deletions of segments of chromosome 11 have been found to be involved in several human tumors. Specific deletion of chromosomal band 11p13 has been associated with Wilms' tumors and gonadoblastomas. We performed a deletion analysis of 11p using 6 polymorphic probes and DNA from 30 testicular malignancies with corresponding normal DNA in 19 patients. A cDNA probe (WT 33) was used to evaluate the Wilms' tumor suppressor gene (WT1) for loss by gene dosage analysis. Results using the polymorphic probes revealed loss of heterozygosity on 11p in 59% of informative samples, while use of the WT1 probe revealed loss of hemizygosity in 27% of the samples. Northern blot analysis of WT1 was performed on mRNA from 3 normal and 1 malignant testis, as well as from 4 testicular cancer cell lines (TERA 1, TERA 2, HTE and HTH). Northern blot analysis of the normal testes revealed the presence of the expected 3.2 and 2.7 kb transcripts. The TERA 1, TERA 2 and HTH cell lines were found to express only the 3.2 kb transcript and at levels only 3.3%, 29% and 2.8% of normal testes. The HTE cell line did not express either of the normal transcripts. Our results reveal considerable allelic loss at 11p13 and 11p15, suggesting that these loci may harbor one or more tumor suppressor genes important in the development of testicular cancer.

Adult↗

Physicians' emotional reactions to patients: recognizing and managing countertransference.

Traditionally, physicians have been socialized to repress emotional responses to patients in an effort to maintain clinical objectivity. In this article we call into question that assumption, maintaining that rather than being hindrances such natural responses can be facilitators to the development of stronger physician-patient relationships. We focus on the concept of countertransference, defined here broadly as incompletely recognized emotional reactions a physician has toward a patient or his/her circumstances. In this article we differentiate between internally-focused and externally-focused countertransference. Internally-focused countertransference refers to unrecognized reactions that reflect the unique psychological state of the physician, whereas externally-focused countertransference focuses on the reactions that primarily derive from the behaviors or other characteristics of the specific patient or circumstances. We conclude by presenting a 3-step strategy for recognizing and managing countertransference responses to patients.

Countertransference↗

Magnetic resonance imaging of the female pelvis: technical considerations.

To perform magnetic resonance imaging of the female pelvis, one must be familiar with the imaging appearance of normal structures as well as the disease entities that may be encountered. However, it is also important to be familiar with and understand the basic physical principles of the available imaging techniques to be able to optimize image quality and the detection of abnormalities. This discussion is intended to describe the available imaging techniques used in evaluation of the female pelvis. Following a discussion of conventional spin echo (CSE) techniques, the fast spin echo (FSE) technique will be described in detail. This will include how the FSE sequence generates images, the choice of imaging parameters, and the unique contrast characteristics and artifacts associated with the FSE technique. Pelvic multicoils will also be described in detail, including the choice of imaging parameters when using these coils and the unique artifacts that can be encountered. Chemical-selective imaging and motion artifact reduction techniques will additionally be described. At the end of the discussion, suggested imaging parameters are given for CSE and FSE sequences and for body coil and multicoil imaging.

Artifacts↗

Peripheral versus central intravenous nutrition: comparison of two delivery systems.

Forty-six surgical patients who required intravenous nutrition (IVN) were randomly allocated to receive complete IVN by a peripheral (n = 23) or central (n = 23) venous delivery system. The peripheral IVN system combined a fine-bore silicone catheter with lipid-based nutrient solutions whereas the central system used a conventional glucose-based nutrient regimen and a single-lumen central venous catheter. The incidence of catheter complications and the complication-free system function over time were compared. Problems of venous access were not observed with peripheral IVN but occurred with one central catheterization. Three patients with central venous catheters developed bacteraemia but only one incident was thought to be catheter related (bacterial translocation). There were no such episodes with peripheral IVN. Peripheral catheterization was not associated with infective phlebitis, although late-onset chemical phlebitis occurred on four occasions after a mean(s.e.m.) time of 22.8(6.1) days, representing a daily risk of phlebitis of 0.009. There was no significant difference in the probability of complication-free system function with time between peripheral and central IVN (P = 0.14). The fine-bore silicone catheter peripheral IVN delivery system resulted in long-term phlebitis-free infusion for periods that were similar to those of single-lumen central catheterization by life-table analysis.

Bacterial Infections↗