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Biomedical subjects

B Kim

Publications and source records attributed to B Kim.

At least 91 records · Page 5Linked to original sources

Medical ethics curriculum for surgical residents: results of a pilot project.

INTRODUCTION: This study sought to develop and evaluate a medical ethics curriculum designed specifically for surgical residents. METHODS: The learning needs of surgical residents relevant to ethics were determined by using a structured literature review and synthesis strategy. We identified 5 primary areas of importance for ethics education for surgical residents: withdrawing and withholding treatment, advance directives, do-not-resuscitate orders, informed consent, and communicating bad news. Learning objectives were developed, and teaching plans were designed for four 90-minute interactive teaching episodes on the basis of adult learning principles. We surveyed residents using a published survey instrument modified for surgery to identify residents' beliefs about the usefulness of ethics training, confidence in addressing ethical issues, and factual knowledge of ethics questions. RESULTS: Twenty surgical residents at a single institution completed the pretest and posttest close-ended surveys. Results showed that although 88% had formal ethics exposure in medical school, 93% considered ethics education at the resident level to be a "very important" or "important" topic. Residents' confidence in addressing ethical issues showed statistically significant improvement between pretest and posttest surveys for 13 of 23 items. There were no statistically significant linear relationships between postgraduate year of residency and the pretest confidence items or the number of correct responses on the pretest multiple-choice items. CONCLUSIONS: Despite the prevalence of ethics education during medical school, surgical residents welcome formal instruction on numerous ethical issues pertinent to surgical practice. A focused curriculum can be developed that has a measurable impact on residents' confidence in addressing ethical issues.

Adult↗

Molecular characterization of a novel Drosophila gene which is expressed in the central nervous system.

We have isolated and characterized a novel Drosophila melanogaster gene (noe) that is specifically and abundantly expressed in the central nervous system (CNS). The gene, which maps to 74B on the left arm of third chromosome, encodes a protein of 74 amino acids with no significant similarity to known protein sequences. The deduced amino acid sequence of the gene product is rich in basic amino acids, especially the lysine, and contains five potential phosphorylation sites. The noe gene lacks introns and seems to produce two transcripts by alternative polyadenylations. The promoter region deduced from 5'-RACE analysis contains a sequence similar to the TATA-box consensus sequence. RNA blot analysis detected 1.0 kb noe transcripts that are expressed from the third-instar larval stage to the adult stage and which are predominantly found in the adult heads. In situ hybridizations to tissue sections showed that the gene is abundantly expressed in neuronal cell bodies as well as in the neurophiles of adult and larval CNS (brain, optic lobe, and thoracic ganglia of adults and larval brain).

Amino Acid Sequence↗

Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling.

The major substrates for the type I insulin-like growth factor (IGF-I) receptor are Shc and insulin receptor substrate (IRS) proteins. In the current study, we report that IGF-I induces a sustained tyrosine phosphorylation of Shc and its association with Grb2 in SH-SY5Y human neuroblastoma cells. The time course of Shc tyrosine phosphorylation parallels the time course of IGF-I-stimulated activation of extracellular signal-regulated kinase (ERK). Transfection of SH-SY5Y cells with a p52 Shc mutant decreases Shc tyrosine phosphorylation and Shc-Grb2 association. This results in the inhibition of IGF-I-mediated ERK tyrosine phosphorylation and neurite outgrowth. In contrast, IGF-I induces a transient tyrosine phosphorylation of IRS-2 and an association of IRS-2 with Grb2. The time course of IRS-2 tyrosine phosphorylation and IRS-2-Grb2 and IRS-2-p85 association closely resembles the time course of IGF-I-mediated membrane ruffling. Treating cells with the phosphatidylinositol 3'-kinase inhibitors wortmannin and LY294002 blocks IGF-I-induced membrane ruffling. The ERK kinase inhibitor PD98059, as well as transfection with the p52 Shc mutant, has no effect on IGF-I-mediated membrane ruffling. Immunolocalization studies show IRS-2 and Grb2, but not Shc, concentrated at the tip of the extending growth cone where membrane ruffling is most active. Collectively, these results suggest that the association of Shc with Grb2 is essential for IGF-I-mediated neurite outgrowth, whereas the IRS-2-Grb2-phosphatidylinositol 3'-kinase complex may regulate growth cone extension and membrane ruffling.

Adaptor Proteins, Signal Transducing↗

Diarrhoea in nursing piglets associated with coccidiosis: prevalence, microscopic lesions and coexisting microorganisms.

A retrospective study was made of natural infections with Isospora suis in nursing piglets, recorded from April 1994 to May 1997, to determine the prevalence, microscopical lesions and other microorganisms associated with coccidiosis. One hundred and five (17.3 per cent) of the 605 nursing piglets submitted from 304 pig farms were diagnosed positive for coccidiosis. The affected piglets were from seven to 20 days old, with a mean age of 11.1 days. Coccidiosis occurred in each year but the incidence peaked in July (15 cases, 14.3 per cent), September (15 cases, 14.3 per cent), October (16 cases, 15.2 per cent) and November (18 cases, 17.1 per cent) and was lowest in May (no cases), August (two cases, 1.9 per cent) and June (four cases, 3.8 per cent). Histopathologically, villous atrophy resulting from the necrosis and sloughing of epithelial cells was a prominent feature of infection with I suis. In 49.5 per cent of the nursing piglets, other enteropathogens were identified, Escherichia coli (47.6 per cent) and transmissible gastroenteritis virus (3.8 per cent) being the most commonly diagnosed. Forty-five of 50 E coli isolates associated with coccidiosis tested negative by polymerase chain reaction for enterotoxigenic virulence factors, such as fimbriae and enterotoxins.

Animals↗

Characterization of bovine and human cDNAs encoding NAP-22 (22 kDa neuronal tissue-enriched acidic protein) homologs.

We have characterized the bovine and the human cDNAs encoding the NAP-22 (22 kDa neuronal tissue-enriched acidic protein) homologs. Both bovine and human cDNAs encode proteins of 227 amino acids. The deduced amino acid sequences of the bovine and the human proteins are 63% and 65% identical, respectively, to that of rat NAP-22 protein, strongly suggesting that both the cDNAs characterized encode NAP-22 proteins. They also share 45% and 41% amino acid sequence identities with chicken CAP-23 (23 kDa cytoskeleton associated protein). Several important protein motifs, including myristoylation and phosphorylation sites, are well conserved in sequences and positions in all three mammalian NAP-22 proteins and chicken CAP-23 proteins. The bovine cDNA was characterized further. Southern analysis of the bovine genomic DNA suggests that the bovine NAP-22 protein is encoded by a single-copy gene. RNA blot analysis revealed that the bovine gene for NAP-22 protein encodes a 1.7 kb transcript that is present only in the brain. Our data suggest that the four proteins, bovine and human NAP-22 homologs, rat NAP-22, and chicken CAP-23, have homologous functions in different organisms.

3' Untranslated Regions↗

Optical design of the U7 undulator beamline at the Pohang Light Source.

The first insertion-device beamline at the Pohang Light Source is designed for high-resolution spectroscopy and spectromicroscopy. The beamline will contain a variable-included-angle plane-grating monochromator (VIA-PGM) using a grating substrate which has seven different grooves with different depths. The advantages of this scheme will be the fixed exit-slit position and the mechanical stability of the grating scan mechanism while changing the photon energy range. The beamline is designed to cover the photon energy range 20-2000 eV. The estimated spectral resolution, E/DeltaE, is above 8000 in the photon energy range below 500 eV, and above 4000 for the remaining photon energy range. The estimated flux at the end-station is of the order of 10(12) photons s(-1) (0.1% bandwidth)(-1).

Journal Article↗

Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesis.

We have used random sequence mutagenesis and complementation in a bacterial selection system to establish a large library of immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutants with amino acid substitutions in the beta3-beta4 region of the fingers subdomain [Kim, B., Hathaway, T. R., and Loeb, L. A. (1996) J. Biol. Chem. 271, 4872-4878]. We show here that one of these mutants, D76V, exhibits increased accuracy of copying both DNA and RNA templates in a primer extension assay with biased dNTP pools. More detailed analysis of DNA-dependent polymerization showed that the D76V mutation conferred an up to 14-fold increase in fidelity of nucleotide insertion and a 9-fold reduced mutation rate in an M13mp2 lacZalpha forward mutation assay. Substitution at D76 with positively charged (D76R) and nonpolar (D76V and D76I) residues increased replicational accuracy, while substitutions with negatively charged (D76E) and polar residues (D76S and D76C) had little effect on fidelity. We propose that D76 affects replicational accuracy by mediating interaction between the fingers subdomain and the single-stranded template. Our work shows that the Escherichia coli complementation system can yield HIV RT mutants with increased fidelity that have not been isolated from the natural host and that are valuable in understanding the molecular bases of replicational accuracy.

Amino Acid Substitution↗

Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart.

Inhibitory G protein activity (Gi) and nitric oxide (NO) modulate muscarinic-cholinergic (MC) inhibition of cardiac beta-adrenergic inotropic responses. We hypothesized that Gi mediates MC-NO synthase (NOS) signal transduction. Isoproterenol (0.2-0.8 microg/min) and acetylcholine (1 microM) were administered to isolated perfused rat hearts pretreated with saline (controls; n = 8) or pertussis toxin (PT; 30 microg/kg intraperitoneally 3 d before study; n = 20). PT abrogated in vitro ADP-ribosylation of Gi protein alpha subunit(s) indicating near-total decrease in Gi protein function. Isoproterenol increased peak +dP/dt in both control (peak isoproterenol effect: +2, 589+/-293 mmHg/s, P < 0.0001) and PT hearts (+3,879+/-474 mmHg/s, P < 0.0001). Acetylcholine reversed isoproterenol inotropy in controls (108+/-21% reduction of +dP/dt response, P = 0.001), but had no effect in PT hearts. In controls, NG-monomethyl-L-arginine (100 microM) reduced basal +dP/dt, augmented isoproterenol +dP/dt (peak effect: +4,634+/-690 mmHg/s, P < 0.0001), and reduced the MC inhibitory effect to 69+/-8% (P < 0.03 vs. baseline). L-arginine (100 M) had no effect in controls but in PT hearts decreased basal +dP/dt by 1, 426+/-456 mmHg/s (P < 0.005), downward-shifted the isoproterenol concentration-effect curve, and produced a small MC inhibitory effect (27+/-4% reduction, P < 0.05). This enhanced response to NO substrate was associated with increased NOS III protein abundance, and a three- to fivefold increase in in vitro calcium-dependent NOS activity. Neomycin (1 microM) inhibition of phospholipase C did not reverse L-arginine enhancement of MC inhibitory effects. These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels.

Acetylcholine↗

Preparative gradient elution chromatography of chemotactic peptides.

Experimental and computational studies are carried out on the separation of a mixture of chemotactic peptides by reversed-phase gradient elution on commercial octadecyl silica supports with acetonitrile as the modulator. The solubility of this mixture is found to be a complex function not only of mobile phase composition, but also of the order in which the various constituents of the mobile phase are mixed together. In certain cases, the feeds seem to reach a metastable state in which they are fully soluble for several hours: this is exploited here for preparative separations. Separations are also carried out by stepwise and nonlinear isocratic elution, and the yields and productivities compared to those from gradient elution. Predictive simulations of all these separations are run using independently measured single component feed isotherms. Good agreement with experiment is found when multicomponent (nonlinear) feed interactions are accounted for, but not when the usual assumption of linear feed isotherms is made. Simultaneous concentration and separation of these feeds is easily achieved by gradient elution. Simulations indicate that the combination of the focusing power of the gradient with the multicomponent feed interactions is likely to give good separations even at high feed loadings.

Chemotactic Factors↗

Biliary cystadenoma of the liver.

Hepatobiliary cystadenoma is an uncommon lesion that is difficult to diagnose preoperatively. Here we report a 34-year-old woman who presented with enlargement of a cyst that had been observed for the previous 6 months. Diagnostic imaging revealed a 7-cm diameter cystic mass with irregular multiple septation in her liver. All laboratory test results were normal except for serum carbohydrate antigen (CA) 19-9 (62.5 U/ml). Because of the malignant potential and the history of enlargement, a complete surgical excision was performed. The patient was discharged after a good recovery; 2 months after surgery her serum CA19-9 level had returned to normal (32.9 U/ml). Regardless of the diagnostic modalities used, cystadenoma and cystadenocarcinoma cannot be differentiated with accuracy. Therefore complete surgical resection is the recommended therapy.

Adenoma, Bile Duct↗

Does volume of patients seen in an outpatient setting impact test scores?

BACKGROUND: Methods of teaching surgery in the outpatient setting and means to measure the effectiveness of these methods have not been defined. This study was designed to evaluate the impact of number of outpatient encounters on test scores for third-year medical students. METHODS: Students rotating on the required third-year surgery clerkship between July 1994 and June 1996 kept a log of their activities including number of patients seen in clinic, number of cases scrubbed, and pages read. At the end of the rotation the students were given an essay examination and a multiple-choice examination. The data were analyzed looking for correlation between examination scores and volume of patients seen. United States Medical Licensing Examination (USMLE) Step 1 scores were used as a baseline measure to compare the rotation groups. RESULTS: USMLE scores did not differ between groups. Mean essay examination scores varied significantly between some rotation groups, but did not follow a pattern. There was no correlation between the number of patients seen in clinic and essay examination scores. There was a significant correlation between essay score and USMLE Step 1 score (Pearson's r = 0.398) and between essay and multiple-choice examination scores (Pearson's r = 0.313). There was a significant negative correlation between number of patients seen in clinic and number of cases scrubbed (Pearson's r = -0.347). CONCLUSIONS: Participation in outpatient surgery clinics did not result in improved performance on written examinations in this surgery clerkship. To achieve the most benefit from the outpatient clinic, objectives of the experience need to be determined and appropriate tools used to measure their successful achievement.

Ambulatory Surgical Procedures↗

Inconclusive clinical and ultrasound evaluation of the scrotum: impact of magnetic resonance imaging on patient management and cost.

OBJECTIVES: To determine the diagnostic utility and net cost of magnetic resonance imaging (MRI) in the management of clinically and sonographically inconclusive scrotal lesions. METHODS: A multicenter retrospective review identified 34 patients diagnosed with scrotal MRI following inconclusive clinical and ultrasound (US) evaluation. Final diagnoses were based on surgery (n = 18) or clinical and US follow-up (n = 16). Final diagnoses of 29 testicular lesions were as follows: orchitis (n = 11), infarct (n = 6), neoplasm (n = 6), rupture (n = 3), torsion (n = 2), and radiation fibrosis (n = 1). Final diagnoses of five extratesticular lesions were as follows: epididymitis (n = 2), epididymal abscess (n = 2), and neoplasm (n = 1). Management plans prior to and following MRI findings were formulated by a general urologist and a urologic oncologist. The costs of the pre-MRI and post-MRI management plans were estimated using the Medicare reimbursement schedule. RESULTS: The leading US diagnosis was correct for 10 of 34 patients (29%) and the leading MRI diagnosis was correct for 31 of 34 patients (91%). MRI improved the management plan of the general urologist and urologic oncologist in 19 patients (56%) and 17 patients (50%), respectively. MRI worsened the management plan of both clinicians in 1 patient. Management was unchanged in all other patients. The overall net cost savings were $543 to $730 per patient for the urologic oncologist and the general urologist, respectively, and $3833 per patient originally scheduled for surgery. CONCLUSIONS: Use of MRI after inconclusive clinical and US evaluation of scrotal lesions may improve management, decrease the number of surgical procedures, and result in net cost savings.

Adolescent↗

Ovarian Brenner tumors: MR imaging characteristics.

This study describes the appearance of Brenner tumors on MR imaging and compares quantitative signal intensity measurements of Brenner tumors with that of other ovarian tumors. A search of pathologic and MR records disclosed patients who had MRIs showing Brenner tumors prior to surgical excision. Patients (21) with other surgically proven ovarian masses were randomly selected for comparison. MR imaging was performed at 1.5 T with phased array multicoils and fast spin echo T2-weighted images. Region-of-interest measurements of signal intensity (SI) were made to calculate signal intensity ratios (SIR = mass SI/muscle SI). Brenner tumors showed significantly lower SIR than other tumors on T2-weighted images (p = 0.004) and similar SIR on T1-weighted images. Brenner tumors show lower signal intensity on T2-weighted images than other non-fibrous ovarian tumors. This lower signal intensity may result from the extensive fibrous content of these tumors.

Adult↗

Differential regulation of focal adhesion kinase and mitogen-activated protein kinase tyrosine phosphorylation during insulin-like growth factor-I-mediated cytoskeletal reorganization.

In SH-SY5Y human neuroblastoma cells, insulin-like growth factor (IGF)-I mediates membrane ruffling and growth cone extension. We have previously shown that IGF-I activates the tyrosine phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated protein kinase (ERK) 2. In the current study, we examined which signaling pathway underlies IGF-I-mediated FAK phosphorylation and cytoskeletal changes and determined if an intact cytoskeleton was required for IGF-I signaling. Treatment of SH-SY5Y cells with cytochalasin D disrupted the actin cytoskeleton and prevented any morphological changes induced by IGF-I. Inhibitors of phosphatidylinositol 3-kinase (PI 3-K) blocked IGF-I-mediated changes in the actin cytoskeleton as measured by membrane ruffling. In contrast, PD98059, a selective inhibitor of ERK kinase, had no effect on IGF-I-induced membrane ruffling. In parallel with effects on the actin cytoskeleton, cytochalasin D and PI 3-K inhibitors blocked IGF-I-induced FAK tyrosine phosphorylation, whereas PD98059 had no effect. It is interesting that cytochalasin D did not block IGF-I-induced ERK2 tyrosine phosphorylation. Therefore, it is likely that FAK and ERK2 tyrosine phosphorylations are regulated by separate pathways during IGF-I signaling. Our study suggests that integrity as well as dynamic motility of the actin cytoskeleton mediated by PI 3-K is required for IGF-I-induced FAK tyrosine phosphorylation, but not for ERK2 activation.

Androstadienes↗

Cytotoxic T cells in basal cell carcinomas of skin.

Previous studies have suggested the importance of CD8+ cytotoxic T-cells of hosts against neoplasms. Earlier studies and our previous investigation showed that a majority of tumor infiltrating T-cells in human basal cell carcinomas (BCCs) belonged to CD4+ T-cells. CD8+ cells were also present in the peritumor areas of human BCCs, but in smaller numbers. Published evidence indicates the importance of cytotoxic T-cells in antitumor immunity. Cytotoxic T-cells have been identified by using monoclonal antibodies against various cytotoxic T-cell components. In this study, we used monoclonal antibodies to perforin to evaluate the role of cytotoxic T-cells in the host response against basal cell carcinomas. Perforin-expressing T-cells could be identified in the infiltrate of BCCs in frozen tissue sections, and also in antigen-retrieved paraffin-embedded sections of BCCs, and the presence of perforin-expressing T-cells correlated with the infiltration of CD8+ T-cells. These results suggest that cytotoxic T-cells play a role in host defense against human BCCs.

CD4-CD8 Ratio↗

Müllerian cysts of the mesentery and retroperitoneum: a case report and literature review.

Müllerian cyst of the mesentery and retroperitoneum is an extremely rare disease entity. Only two photomicrograph reports have been published. A 47-year-old Korean woman presented with abdominal distention. A mesenteric cystic mass, measuring 25 x 23 x 18 cm, was found between the liver and right adnexa without any connection with adjacent organs. The cyst was multilocular with gray-white, rubbery walls of relatively uniform 0.2 cm thickness. Microscopically, the lining cells were ciliated and cuboidal to low columnar with an incomplete lining of smooth muscle bundles, adipose tissues, lymphovascular spaces, and lymphocytic aggregates. Ultrastructurally, the lining cells had intercellular junctions, and cilia or microvilli on their luminal surface. The lining cells were immunoreactive for cytokeratin, epithelial membrane antigen and vimentin. To the best of our knowledge, this is the first demonstration of ultrastructural and immunohistochemical findings of Müllerian cyst of the mesentery and retroperitoneum in the English literature.

Cysts↗

Differential regulation of insulin receptor substrate-2 and mitogen-activated protein kinase tyrosine phosphorylation by phosphatidylinositol 3-kinase inhibitors in SH-SY5Y human neuroblastoma cells.

Insulin-like growth factor I (IGF-I) is a potent neurotropic factor promoting the differentiation and survival of neuronal cells. SH-SY5Y human neuroblastoma cells are a well characterized in vitro model of nervous system growth. We report here that IGF-I stimulated the tyrosine phosphorylation of the type I IGF receptor (IGF-IR) and insulin receptor substrate-2 (IRS-2) in a time- and concentration-dependent manner. These cells lacked IRS-1. After being tyrosine phosphorylated, IRS-2 associated transiently with downstream signaling molecules, including phosphatidylinositol 3-kinase (PI 3-K) and Grb2. Treatment of the cells with PI 3-K inhibitors (wortmannin and LY294002) increased IGF-I-induced tyrosine phosphorylation of IRS-2. We also observed a concomitant increase in the mobility of IRS-2, suggesting that PI 3-K mediates or is required for IRS-2 serine/threonine phosphorylation, and that this phosphorylation inhibits IRS-2 tyrosine phosphorylation. Treatment with PI 3-K inhibitors induced an increased association of IRS-2 with Grb2, probably as a result of the increased IRS-2 tyrosine phosphorylation. However, even though the PI 3-K inhibitors enhanced the association of Grb2 with IRS-2, these compounds suppressed IGF-I-induced mitogen-activated protein kinase activation and neurite outgrowth. Together, these results indicate that although PI 3-K participates in a negative regulation of IRS-2 tyrosine phosphorylation, its activity is required for IGF-IR-mediated mitogen-activated protein kinase activation and neurite outgrowth.

Adaptor Proteins, Signal Transducing↗