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Biomedical subjects

U Kim

Publications and source records attributed to U Kim.

At least 19 recordsLinked to original sources

The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India.

AIM: To determine if antioxidant supplements (beta carotene and vitamins C and E) can decrease the progression of cataract in rural South India. METHODS: The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time. RESULTS: Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables. CONCLUSION: Antioxidant supplementation with beta carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants.

Adult↗

Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery.

BACKGROUND: Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown. METHODS AND RESULTS: Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and alpha-granule secretion were effectively inhibited by 30 or 100 micromol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG. CONCLUSIONS: Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.

Arachidonic Acid↗

A novel fibroblast growth factor receptor-5 preferentially expressed in the pancreas(1).

Using the polymerase chain reaction on human embryonic cDNAs, we isolated a cDNA encoding a novel 504 amino acid protein, termed fibroblast growth factor receptor (FGFR)-5, which is highly homologous to known FGFRs. The NH(2)-terminal portion of FGFR5 contains a putative secretory signal sequence, three typical immunoglobulin-like domains, six cysteines, and an acidic box, but no HAV motif. The COOH-terminal portion of FGFR5 contains one transmembrane domain but no intracellular kinase domain. Recombinant FGFR5 expressed in COS-7 cells is not secreted, but recombinant truncated FGFR5 lacking the predicted transmembrane domain is secreted. Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) do not bind to FGFR5. Among 23 adult human tissues, FGFR5 mRNA is preferentially expressed in the pancreas. These results suggest that FGFR5 may provide a binding site for some other fibroblast growth factors and may regulate some pancreatic function.

Amino Acid Sequence↗

A retrospective study of diagnosis and management of mesenteric vein thrombosis.

BACKGROUND: Mesenteric vein thrombosis (MVT) is an uncommon type of intestinal ischemia associated with significant mortality and morbidity because of its delay in diagnosis. METHODS: A retrospective analysis of 9 patients treated surgically for MVT during 1982 to 1997 was performed. RESULTS: Nine patients underwent surgical therapy for intestinal ischemia due to MVT. The most common presenting symptom was abdominal pain with bloody diarrhea in 3 patients; preoperative diagnosis of MVT was suspected in 2. Radiologic tests included plain roentgenograms, computed axial tomography, and ultrasound. Time to surgery ranged from 3 hours to 7 days after admission. All patients underwent resection of infarcted bowel with primary anastomosis and immediate postoperative anticoagulation. No patient underwent a second-look operation. The postoperative morbidity and mortality rates were 55% and 11%, respectively. CONCLUSION: Diagnosis of intestinal ischemia from MVT is often delayed, and strong clinical suspicion and aggressive treatment are necessary in its management.

Adult↗

Outcomes-based trial of an inpatient nurse practitioner service for general medical patients.

Although teaching hospitals are increasingly using nurse practitioners (NPs) to provide inpatient care, few studies have compared care delivered by NPs and housestaff or the ability of NPs to admit and manage unselected general medical patients. In a Midwest academic teaching hospital 381 patients were randomized to general medical wards staffed either by NPs and a medical director or medical housestaff. Data were obtained from medical records, interviews and hospital databases. Outcomes were compared on both an intention to treat (i.e. wards to which patients were randomized) and actual treatment (i.e. wards to which patients were admitted) basis. At admission, patients assigned randomly to NP-based care (n = 193) and housestaff care (n= 188) were similar with respect to demographics, comorbidity, severity of illness and functional parameters. Outcomes at discharge and at 6 weeks after discharge were similar (P>0.10) in the two groups, including: length of stay; charges; costs; consultations; complications; transfers to intensive care; 30-day mortality; patient assessments of care; and changes in activities of daily living, SF-36 scores and symptom severity. However, after randomization, 90 of 193 patients (47%) assigned to the NP ward were actually admitted to housestaff wards, largely because of attending physicians and NP requests. None the less, outcomes of patients admitted to NP and housestaff wards were similar (P>0.1). NP-based care can be implemented successfully in teaching hospitals and, compared to housestaff care, may be associated with similar costs and clinical and functional outcomes. However, there may be important obstacles to increasing the number of patients cared for by NPs, including physician concerns about NPs' capabilities and NPs' limited flexibility in managing varying numbers of patients and accepting off-hours admissions.

Activities of Daily Living↗

In vitro and in vivo (SCID mice) effects of phytosterols on the growth and dissemination of human prostate cancer PC-3 cells.

The dietary effect of phytosterols (PS) versus cholesterol on the growth and metastasis of the PC-3 human prostate cancer cells in SCID mice was studied. Also, their direct effect on the growth and migration of these cells in vitro was analysed. In the in vivo experiment, SCID mice were fed a diet containing 2% of either PS mixture or cholesterol plus 0.2% cholic acid and implanted with 2 x 10(6) tumour cells per mouse. Tumour growth was monitored for 8 weeks post inoculation. Animals fed the PS diet had tumours 40-43% smaller than those fed the cholesterol diet. Furthermore, the number of mice with lymph node and lung metastasis was almost one-half that of the cholesterol-fed group. In the in vitro studies, both beta-sitosterol and campesterol inhibited the growth of PC-3 cells by 70% and 14%, respectively, while cholesterol supplementation increased the growth by 18% when compared with controls. PS inhibited the invasion of PC-3 cells into Matrigel-coated membranes by 78% while cholesterol increased it by 43% as compared with the cells in the control media. Migration of tumour cells through 8 microm pore membranes was reduced by 60-93% when the PC-3 cells were in PS media, as compared with a 67% increase after cholesterol supplementation. PS supplementation reduced the binding of PC-3 cells to laminin by 15-38% and fibronectin by 23% while cholesterol increased binding to type IV collagen by 36%. It was concluded that PS indirectly (in vivo as a dietary supplement) and directly (in tissue culture media) inhibited the growth and metastasis of PC-3 cells. beta-Sitosterol was more effective than campesterol in offering this protection in most of the parameters studied.

Animals↗

Clinical features of vivax malaria.

Plasmodium vivax malaria reemerged in the Republic of Korea in 1993 near the Demilitarized Zone (DMZ). We reviewed clinical features of 101 symptomatic patients with vivax malaria. Of the patients, 77 patients (76.3%) were veterans who had served near the DMZ; their median age was 23 years. The duration of the minimum latent period was > 6 months in 66.2% (51 of 77) of the patients (median, 278 days). Tertian fever developed in 69 patients (68.3%). Severe thrombocytopenia with platelet counts < 60,000/microL was common (29.6% of patients). The parasite densities ranged 32-52,127 parasites per microliter of blood (geometric mean, 1,287). The only complication was a splenic rupture in one patient. All patients responded promptly to chloroquine therapy. Our data suggest that the clinical features of reemerging vivax malaria may be similar to those of Korean vivax malaria reported in the past.

Adolescent↗

Genetic analyses of NFKB1 and OCA-B function: defects in B cells, serum IgM level, and antibody responses in Nfkb1-/-Oca-b-/- mice.

Defined patterns of gene expression during cell differentiation are likely to be ensured by multiple factors playing redundant roles. By generating mice deficient in both NFKB1 and OCA-B, we show here that the two transcription factors are required for B-1 cell differentiation and serum IgM production. In addition, relative to Nfkb1(-/-) or Oca-b(-/-) mice, the Nfkb1(-/-)Oca-b(-/-) mice show a decrease in conventional B cell frequencies in the spleen and augmented reductions in T-independent and T-dependent Ab responses. These results suggest that NFKB1 and OCA-B play compensatory roles in multiple aspects of B cell differentiation.

Animals↗

The Giardia genome project database.

The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.

Animals↗

Role of OCA-B in 3'-IgH enhancer function.

OCA-B (alternately called Bob1 and OBF-1) is a B cell-specific coactivator that interacts with the ubiquitously expressed Oct-1 and the B cell-restricted Oct-2 to activate transcription via the octamer site (5'-ATGCAAAT-3'). OCA-B-/- mice appear to undergo normal Ag-independent B cell maturation. However, Ag-dependent B cell differentiation, including germinal center formation, production of secondary Ig isotypes, and proliferation in response to surface Ig cross-linking, is greatly affected. We demonstrate that the observed reductions in expression of class-switched isotypes in OCA-B-/- mice may be due in part to deficiencies in the function of the 3'-IgH enhancer elements. Furthermore, we find that surface Ig cross-linking represses all the Ig enhancers and that this repression is absent in OCA-B-/- B cells. These results suggest an important role for OCA-B in Ig enhancer function in vivo.

3' Untranslated Regions↗

Respiratory syncytial virus infection induces expression of the anti-apoptosis gene IEX-1L in human respiratory epithelial cells.

By means of differential display reverse-transcriptase polymerase chain reaction, increased expression of the mRNA encoding the anti-apoptosis gene IEX-1L was found in respiratory epithelial cells infected with respiratory syncytial virus (RSV). IEX-1L mRNA expression increased 5-7-fold in RSV-infected cells at 72 h after infection but remained unchanged in cells exposed to irradiated, replication-incompetent RSV. Because IEX-1L is reported to protect cells from apoptosis induced by tumor necrosis factor (TNF)-alpha, the effect of TNF-alpha on epithelial cell apoptosis in the context of RSV infection was determined. Epithelial cells were exposed to vehicle, RSV, or irradiated RSV for 72 h, and then TNF-alpha was added to appropriate cultures. Cytochemical staining of cellular DNA with 4,6-diamidino-2-phenylindole demonstrated TNF-alpha-induced apoptosis in 23.4% of control cells but only 5% of RSV-infected cells. These data show that RSV infection protects epithelial cells from TNF-alpha-induced apoptosis and that this effect is temporally associated with IEX-1L gene expression.

Adenoviridae↗

The frequency of mutation in CCR5 gene among Koreans.

To better understand a role of the delta32 allele of the CCR5 gene in HIV-1 transmission and disease progression, we determined the CCR5 genotypes within several groups of Koreans. Amplification of DNA from each subject was achieved with polymerase chain reaction, using the CCR5 specific primer pair, which flanks the 32 bp deletion. The 1.2 kb coding sequences of CCR5 were examined to see the possible effects of CCR5 polymorphism. All of the 339 healthy, HIV-uninfected individuals had no mutation in the CCR5 gene. All of the 115 HIV-1-infected patients including 11 long-term non-progressors (LTNPs) and 18 discordant spouses were also wild homozygotes. No variation in the 1.2kb CCR5 coding sequence was found in 5 LTNPs and 5 discordant spouses. In conclusion, the 32 bp deletion mutant is rarely present in Koreans. Our data suggest that factors other than the CCR5 coding sequences may also play a role in the resistance to HIV infection.

Alleles↗

Inhibition of MT-450 rat mammary tumour growth by antibodies recognising subtypes of blood group antigen B.

Using subtractive immunization to identify cell surface epitopes expressed in a metastasis-specific fashion on cells of the rat MT-W9 mammary carcinoma model, we generated a monoclonal antibody called M-N#1. This antibody binds specifically to metastasizing cells of the MT-W9 series and also to certain other metastasizing rat mammary carcinoma cell lines. We demonstrate that the M-N#1 antibody recognizes a fucosylated N-glycosyl sugar modification, and furthermore show that the epitope specificity of the M-N#1 antibody is for blood group antigen B subtypes 2, 3 and 4 with slight cross-reactivity with blood group antigen A subtype 2. The expression of these carbohydrate epitopes on MT-450 cells is functionally important, because the M-N#1 antibody efficiently inhibits MT-450 tumour growth in spontaneous metastasis assays. These results suggest that expression of the subtypes of blood group antigen B recognized by the M-N#1 antibody does not directly participate in the metastatic cascade but rather confers a growth or survival advantage on the tumour cells.

ABO Blood-Group System↗

AsGM1+ NK cells prevent metastasis of invading LD-MCA-38 tumor cells in the nude mouse.

BACKGROUND: Although the liver is a potent tumor cell killing organ it is frequently the site of lethal metastases often signifying the endstage for patients with colorectal cancers. Enhancing hepatic-associated immunity remains elusive until the interactions among hepatic nonparenchymal cells (NPC) are deciphered. We sought to modulate the cellular components of the hepatic immune system of mice with anti-NK and anti-T-cell-neutralizing antibodies in order to determine the cell type most efficacious in preventing liver metastasis. MATERIALS AND METHODS: Liver-derived murine colon adenocarcinoma (LD-MCA-38) cells were injected into the ileocolic vein (ICV) of immunocompetent and immunodeficient C57BL/6 mice. Mice were pretreated 1 day prior to tumor cell injection with one of three antibodies: anti-AsGM1, Anti-NK1.1, or Anti-Thy1.2. On Day 21 laparotomy was performed to determine the extent of hepatic tumor foci. The number of hepatic tumor foci was recorded and compared by the Wilcoxon rank sum test. RESULTS: Mice pretreated with anti-AsGM1 or Anti-NK1.1 developed a massive increase in the number of hepatic tumor foci and decreased survival compared to the control treated mice. Pretreatment with anti-Thy1.2 antibody resulted in a significant decrease in the number of hepatic tumor foci. LD-MCA-38 tumor cells were unable to colonize the liver of C57BL/6 athymic nude mice; however, anti-AsGM1 antibody abolished this antimetastatic effect. There was no difference in the extent of hepatic metastasis and survival between immunodeficient C57BL/6 bg/bg and their conventional littermates bg/+. CONCLUSION: AsGM1+ NK cells exhibit a significant antitumor response in the absence of T-cells. The concept of stimulating NK cell activity and suppressing T-cell function may enhance liver-associated immunity and serve as a deterrent for blood-borne tumor cells metastasizing to the liver.

Adenocarcinoma↗

Barrels and septa: separate circuits in rat barrels field cortex.

The neural circuitry within sensory cortex determines its functional properties, and different solutions have evolved for integrating the activity that arises from an array of sensory inputs to cortex. In rodent, circumscribed receptors, such as whiskers, are represented in somatic sensory (S-I) cortex in islands of cells in layer IV called "barrels" surrounded by narrow channels that separate barrels called "septa." These two cortical domains were previously shown to receive sensory inputs through parallel subcortical pathways. Here, by using small biocytin injections, we demonstrate that distinct intrinsic and corticocortical circuitries arise from barrel and septal columns. The intracortical S-I projections originating from barrel columns are rather short-ranged, terminating for the most part within the far boundaries of the most immediate neighboring barrel columns, whereas corticocortical projections reach the second somatosensory (S-II) cortex. In contrast, the intrinsic projections arising from septal columns extend two to three barrels' distance along the row of whisker representation, producing terminals preferentially in other septal columns. Septal corticocortical projections terminate in the dysgranular cortex anterior to E-row barrels and in the posteromedial parietal cortex in addition to S-II. Whereas layer IV barrels are largely isolated from lateral connections, septa are the main conduits of intracortical projections arising from neighboring barrel and septal columns. These results indicate that the two subcortical pathways from whiskers to cortex continue as two distinct partially segregated pathways in cortex.

Animals↗