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Biomedical subjects

T Kim

Publications and source records attributed to T Kim.

At least 37 records · Page 2Linked to original sources

Fulminant leptospirosis in a patient with human immunodeficiency virus infection: case report and review of the literature.

We report a case of fulminant leptospirosis that was acquired in New York City by a patient with underlying infection with human immunodeficiency virus (HIV). Review of the literature on leptospirosis in HIV-infected persons showed that all patients were severely ill but responded well to treatment, which highlights the importance of recognizing this potentially life-threatening illness, especially in unusual settings.

AIDS-Related Opportunistic Infections↗

Generation of multiple electrosprays using microfabricated emitter arrays for improved mass spectrometric sensitivity.

Arrays of microelectrospray emitters were fabricated on polycarbonate substrates using a laser etching technique. Stable multielectrosprays were successfully generated in the liquid flow rate range relevant to mass spectrometric applications. Comparison of electrosprays generated from the microfabricated emitter array and conventional fused-silica capillaries showed similar spray characteristics and reliability. Higher total electrospray ion currents were observed as the number of electrosprays increased at a given total liquid flow rate. Consistent with the theoretical prediction, the total spray current at a constant total liquid flow rate was shown experimentally to be approximately proportional to the square root of the number of electrosprays. It is further projected that when total flow rate is optimized the maximum achievable total current will be proportional to the number of emitters. Evaluation of the multielectrospray device using a triple quadrupole mass spectrometer showed a factor of 2-3 sensitivity enhancement for the spray numbers ranging from two to nine compared to a conventional single electrospray ionization source under the same operating conditions.

Algorithms↗

A cofactor of tRNA synthetase, p43, is secreted to up-regulate proinflammatory genes.

An auxiliary factor of mammalian multi-aminoacyl-tRNA synthetases, p43, is thought to be a precursor of endothelial monocyte-activating polypeptide II (EMAP II) that triggers proinflammation in leukocytes and macrophages. In the present work, however, we have shown that p43 itself is specifically secreted from intact mammalian cells, while EMAP II is released only when the cells are disrupted. Secretion of p43 was also observed when its expression was increased. These results suggest that p43 itself should be a real cytokine secreted by an active mechanism. To determine the cytokine activity and active domain of p43, we investigated tumor necrosis factor (TNF) and interleukin-8 (IL-8) production from human monocytic THP-1 cells treated with various p43 deletion mutants. The full length of p43 showed higher cytokine activity than EMAP II, further supporting p43 as the active cytokine. p43 was also shown to activate MAPKs and NFkappaB, and to induce cytokines and chemokines such as TNF, IL-8, MCP-1, MIP-1alpha, MIP-1beta, MIP-2alpha, IL-1beta, and RANTES. Interestingly, the high level of p43 was observed in the foam cells of atherosclerotic lesions. Therefore, p43 could be a novel mediator of atherosclerosis development as well as other inflammation-related diseases.

Amino Acyl-tRNA Synthetases↗

Molecular cloning and characterization of a novel mouse betaPix isoform.

BetaPix, a Pak-interacting guanine nucleotide exchange factor is known to be involved in the regulation of Cdc42/Rac GTPases and Pak kinase activity. Currently, three 1Pix isoforms, betaPix-a, -b, and -c have been reported. In this study, the cDNA of a novel Pix splice variant was isolated from a mouse brain cDNA library. The cloned betaPix isoform, named betaPix-d, lacks leucine zipper domain that is present in other Pix isoforms, and has a 11 amino acid addition at carboxyl terminus and distinct 3'-UTR Analysis of the tissue distribution of betaPix-d using RT-PCR revealed that its message was present mainly in brain and testis but in lower levels in heart, spleen, lung, liver, skeletal muscle and kidney. In situ hybridization studies with the 13Pix-d specific probes in the rat embryo show that betaPix-d isoform is expressed mainly in the central nervous system. Moreover, temporal expression pattern of the isoform is correlated with the active neurogenesis period in the cerebral cortex and cerebellum during rat brain development. These findings suggest that betaPix-d isoform may be developmentally regulated.

Alternative Splicing↗

Regulation of macrophage migration inhibitory factor and thiol-specific antioxidant protein PAG by direct interaction.

Macrophage migration inhibitory factor (MIF) is an important mediator that plays a central role in the control of the host immune and inflammatory response. To investigate the molecular mechanism of MIF action, we have used the yeast two-hybrid system and identified PAG, a thiol-specific antioxidant protein, as an interacting partner of MIF. Association of MIF with PAG was found in 293T cells transiently expressing MIF and PAG. The use of PAG mutants (C52S, C71S, and C173S) revealed that this association was significantly affected by C173S, but not C52S and C71S, indicating that a disulfide involving Cys(173) of PAG is responsible for the formation of MIF-PAG complex. In addition, the interaction was highly dependent on the reducing conditions such as dithiothreitol or beta-mercaptoethanol but not in the presence of H2O2. Analysis of the activities of the interacting proteins showed that the D-dopachrome tautomerase activity of MIF was decreased in a dose-dependent manner by coexpression of wild-type PAG, C52S, and C71S, whereas C173S was almost ineffective, suggesting that the direct interaction may be involved in the control of D-dopachrome tautomerase activity of MIF. Moreover, MIF has been shown to bind to PAG and it also inhibits the antioxidant activity of PAG.

Cell Line↗

Developmental potential and transgene expression of porcine nuclear transfer embryos using somatic cells.

We examined whether porcine nuclear transfer (NT) embryos carrying somatic cells have a developmental potential and NT embryos carrying transformed fibroblasts express transgenes in the preimplantation stages. In Experiment 1, different activation methods were applied to NT embryos and the development rates were examined. Relative to A23187 only or A23187/6-DMAP, electrical pulse made a significant increase in both cleavage rate (58.1+/-13.9 or 60.7+/-6.3 vs. 74.9+/-7.5%) and development rate of NT embryos to the blastocyst stage (2.2+/-2.8 or 2.2+/-1.5 vs. 11.0+/-4.1%). In Experiment 2, in vitro developmental competence of NT embryos was investigated. The developmental rate to the blastocyst stage of NT embryos (9.9+/- 2.4% for cumulus cells and 9.8+/-1.6% for fibroblast cells) was significantly lower than that (22.9+/-3.5%) of IVF-derived embryos (P<0.01). NT blastocysts derived from either cumulus (28.9+/-11.4, n = 26) or fibroblast cells (30.2+/-9.9, n = 27) showed smaller mean nuclei numbers than IVF-derived blastocysts (38.6+/-10.4, n = 62) (P<0.05). In Experiment 3, nuclear transfer of porcine fibroblasts expressing the GFP (green fluorescent protein) gene resulted in green blastocysts without losing developmental potential. These results suggest that porcine embryos reconstructed by somatic cell nuclear transfer are capable of developing to preimplantation stage. We conclude that somatic cells expressing exogenous genes can be used as nuclei donors in the production of NT-mediated transgenic pig.

Adenine↗

Correlation of hematopoietic progenitor cell count determined by the SE-automated hematology analyzer with CD34(+) cell count by flow cytometry in leukapheresis products.

The yield of stem cell collection after mobilization is crucial for autologous peripheral blood stem cell (PBSC) transplantation. Quantitative determinations of CD34(+) cells using flow cytometry or stem cell culture have been used, but these methods require much time, technical experience, and expensive reagents. The automated hematology analyzer (Sysmex SE-9000trade mark, TOA, Japan) equipped with the Immature Information (IMI) channel for immature myeloid cells can detect IMI(+) cells within 90 sec. Detection is made possible by the combination of a special reagent system and direct current/radiofrequency biosensors. We studied the relation of IMI(+) cells and variable cell counts with CD34(+) cell yield in autologous stem cell harvest. In a series of 32 patients (median age, 44 years; M:F = 11:21), 184 leukaphereses were performed after mobilization regimens with chemotherapy and G-CSF or G-CSF alone. Full blood cell counts were enumerated on peripheral blood (PB) samples taken prior to each leukapheresis. Mononuclear cell (MNC) and IMI(+) cell counts by automated hematology analyzer and flow cytometry based CD34(+) cell yield were measured on the harvested product. The relationship among PB white blood cells (WBC), PB monocytes, IMI(+) cells, MNC, and CD34(+) cell yield in a single leukapheresis was estimated by Pearson correlation analysis. PB WBC count showed no correlation with CD34(+) cell yield in a single leukapheresis (r = 0.02, P = 0.81). PB monocyte count showed a weak correlation (r = 0.21, P = 0.01) and MNC in harvest also showed a weak correlation (r = 0.36, P = 0.0001) with CD34(+) cell yield. In contrast, CD34(+) cell yield correlated well with IMI(+) cell count (r = 0.68, P = 0.0001), and data could be fitted by a linear regression equation, y = 0.330 + 0.974x. IMI(+) cell assay by the automated hematology analyzer correlated well with the CD34(+) cell yield in a mobilized autologous stem cell harvest. The IMI(+) cell count might be used as a simple and efficient indicator of blood stem cell mobilization and collection.

Adolescent↗

Combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin for metastatic urothelial cancer.

PURPOSE: To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS: A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four drugs were given intravenously on days 1 through 3 and the treatment was repeated every 3 weeks. Of the 29 patients, 14 had lymph node metastasis alone, and 15 had visceral lesions. RESULTS: An objective response was achieved in 17 patients (59%). There was no difference in response rates according to metastatic site including osseous lesions, which responded well in four of six patients. The 3-year survival rate for all patients was 16% with four patients who had undergone salvage surgery being alive with no evidence of disease 15 to 61 months after initiation of the treatment. A good performance status, lymph node metastasis alone and administration of chemotherapy at the full dosage had a significantly favorable impact on patient survival. Bone marrow toxicity was significant and one patient died of treatment-related sepsis. CONCLUSIONS: Ifosfamide, 5-fluorouracil, etoposide and cisplatin combination chemotherapy appeared to be active in the treatment of metastatic urothelial cancer. Although bone marrow toxicity was significant, the treatment was well tolerated by the majority of the patients. Further study may be warranted.

Adult↗

Induced corneal astigmatism after macular translocation surgery with scleral infolding.

OBJECTIVE: To document the corneal astigmatism that occurs with macular translocation after scleral infolding surgery. DESIGN: Retrospective case series of a nonrandomized clinical trial. PARTICIPANTS: Eight consecutive age-related macular degeneration patients (eight eyes) with choroidal neovascularization who underwent macular translocation with scleral infolding at the Duke University Eye Center from December 1998 through October 1999. METHODS: We retrospectively reviewed the charts of eight consecutive patients who underwent macular translocation surgery involving scleral infolding in the superotemporal quadrant. Two patients subsequently underwent release of scleral infolding. MAIN OUTCOME MEASURES: After surgery, these eyes were evaluated for corneal astigmatism with manifest refraction, keratometry, and computerized corneal topography. RESULTS: All eight eyes of eight patients revealed marked degrees of corneal astigmatism. Measurement of astigmatism via manifest refraction, keratometry, and corneal topography confirmed postoperative astigmatism corresponding to the axis of the scleral infolding. The amount of corneal astigmatism ranged from 1.75 to 7.37 diopters (D; mean, 4.60 D), with steepening along the axis of scleral infolding in the superotemporal quadrant of each eye (mean, 42.50 degrees from vertical; range, 24 degrees -66 degrees from vertical). Release of scleral infolding in two patients resulted in significant reduction of corneal astigmatism. CONCLUSIONS: Scleral shortening procedures used in macular translocation surgery may induce large amounts of corneal astigmatism. These patients should be assessed with keratometry and corneal topography to determine the accurate amount and axis. Thereafter, contact lens fitting or scleral infolding release may be considered as therapeutic options for large amounts of astigmatism persisting after surgery.

Astigmatism↗

Implantation metastasis of head and neck cancer after fine needle aspiration biopsy.

One possible complication of the aspiration biopsy of malignant tumors is dissemination of tumor cells along the needle track. However, a search of the literature revealed few definite reports of implantation metastases of head and neck tumors after fine needle aspiration biopsy (FNAB). Here we report two cases of skin metastasis of head and neck cancer after FNAB, including a patient with papillary adenocarcinoma of the thyroid and one with adenoid cystic carcinoma of the submandibular gland. Surgical treatment prevented the spread of the tumor in both cases and there have been no evidence of recurrence to date. This report should alert head and neck surgeons to the possibility of implantation metastasis after FNAB.

Adenocarcinoma, Papillary↗

Microwave coagulation therapy with interruption of hepatic blood in- or outflow: an experimental study.

PURPOSE: To determine how interruption of hepatic blood in- or outflow affects the coagulation diameter of microwave coagulation therapy (MCT) in the liver. MATERIALS AND METHODS: Laparotomic MCT at 60 W for 1 minute was performed in 11 Landrace pigs. MCT was performed under six different conditions: without occlusion (Group N; in seven lobes of seven pigs); with occlusion of the hepatic artery (Group A; in five lobes of five pigs); with occlusion of the portal vein (Group P; in five lobes of five pigs); with occlusion of the hepatic artery and portal vein (Group AP; in six lobes of six pigs); with occlusion of the hepatic vein (Group V; in five lobes of four pigs); and with occlusion of the hepatic artery and vein (Group AV; in seven lobes of seven pigs). The maximum diameters for each group were compared. RESULTS: The coagulation diameters (mean +/- SD) were 8.5 mm +/- 2.0, 10.0 mm +/- 1.6, 14.3 mm +/- 2.5, 14.4 mm +/- 2.4, 13.0 mm +/- 0.8, and 14.4 mm +/- 1.5 for Groups N, A, P, AP, V, and AV, respectively. The coagulation diameters for groups P, AP, V, and AV were statistically larger than those for groups N and A (P < .05). There was no significant difference between the coagulation diameters of Groups P, AP, V, and AV. CONCLUSION: The coagulation diameter depends mainly on the portal venous flow. In addition of direct interruption of the portal vein, interruption of the hepatic vein can also result in a substantial increase in the coagulation diameter.

Animals↗

PCI complexes: pretty complex interactions in diverse signaling pathways.

Three protein complexes (the proteasome regulatory lid, the COP9 signalosome and eukaryotic translation initiation factor 3) contain protein subunits with a well defined protein domain, the PCI domain. At least two (the COP9 signalosome and the lid) appear to share a common evolutionary origin. Recent advances in our understanding of the structure and function of the three complexes point to intriguing and unanticipated connections between the cellular functions performed by these three protein assemblies, especially between translation initiation and proteolytic protein degradation.

Animals↗

Evaluation of regional liver damage by magnetic resonance imaging with superparamagnetic iron oxide in rat liver.

The purpose of this study was to investigate whether regional liver damage could be detected by means of enhanced MR imaging with a superparamagnetic iron oxide (SH U 555A) in an ischemia-reperfusion model of rat liver. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 minutes (I-90). There was no significant difference in relative enhancement (RE) between the ischemic and nonischemic lobes in the sham, I-30 and I-60 groups, while RE of the ischemic lobe was significantly lower than that of its nonischemic counterpart in the I-90 group as seen on SH U 555A enhanced proton density spin echo images (P < 0.05). Histological examination revealed that iron deposits were significantly smaller in the ischemic than the nonischemic lobe in the I-90 group (P < 0.05), although there was no significant difference in the number of Kupffer cells. Our results indicate that severe regional liver damage can be evaluated by MR imaging with SH U 555A.

Animals↗

Renal transplantation with aged donors.

Research indicates that aged heart-beating cadaveric donors cause greater risk factors in kidney transplantation. The influence of age on the outcome of non-heart-beating (NHB) cadaveric renal transplantations has not yet been clarified. From July 1986 to May 1999, 63 patients who received cadaveric renal transplantation at Osaka City University Hospital and Osaka City General Hospital were divided into two groups according to their age. Renal function and graft-survival rates of the two groups were compared. The mean values of nadir donor serum creatinine were significantly worse (P < 0.05) in the aged donor group. In the aged donor group the percentage of immediately functioning grafts was lower and the percentage of non-functioning grafts was higher. During the first 10 years post-transplant, graft survival in the aged donor group was significantly lower than that in the younger donor group. We conclude that cadaveric renal transplantation from NHB aged donors can be to the detriment of renal function and graft survival rates compared to transplantation from younger donors.

Age Factors↗

The economic impact of methicillin-resistant Staphylococcus aureus in Canadian hospitals.

OBJECTIVES: To determine the costs associated with the management of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA), and to estimate the economic burden associated with MRSA in Canadian hospitals. DESIGN: Patient-specific costs were used to determine the attributable cost of MRSA associated with excess hospitalization and concurrent treatment. Excess hospitalization for infected patients was identified using the Appropriateness Evaluation Protocol, a criterion-based chart review process to determine the need for each day of hospitalization. Concurrent treatment costs were identified through chart review for days in isolation, antimicrobial therapy, and MRSA screening tests. The economic burden to Canadian hospitals was estimated based on 3,167,521 hospital discharges for 1996 and 1997 and an incidence of 4.12 MRSA cases per 1,000 admissions. SETTING: A tertiary-care, university-affiliated teaching hospital in Toronto, Ontario, Canada. PATIENTS: Inpatients with at least one culture yielding MRSA between April 1996 and March 1998. RESULTS: A total of 20 patients with MRSA infections and 79 colonized patients (with 94 admissions) were identified. This represented a rate of 2.9 MRSA cases per 1,000 admissions. The mean number of additional hospital days attributable to MRSA infection was 14, with 11 admissions having at least 1 attributable day. The total attributable cost to treat MRSA infections was $287,200, or $14,360 per patient The cost for isolation and management of colonized patients was $128,095, or $1,363 per admission. Costs for MRSA screening in the hospital were $109,813. Assuming an infection rate of 10% to 20%, we determined the costs associated with MRSA in Canadian hospitals to be $42 million to $59 million annually. CONCLUSIONS: These results indicate that there is a substantial economic burden associated with MRSA in Canadian hospitals. These costs will continue to rise if the incidence of MRSA increases further.

Cost of Illness↗

Se-methylselenocysteine induces apoptosis through caspase activation in HL-60 cells.

Apoptosis, a programmed process of cell suicide, has been proposed as the most plausible mechanism for the chemopreventive activities of selenocompounds. In our study, we found that Se-methylselenocysteine (MSC) induced apoptosis through caspase activation in human promyelocytic leukemia (HL-60) cells. Measurements of cytotoxicity, DNA fragmentation and apoptotic morphology revealed that MSC was more efficient at inducing apoptosis than selenite, but was less toxic. Moreover, MSC increased both the apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activity, whereas selenite did not. We next examined whether caspases and serine proteases are required for the apoptotic induction by MSC. A general caspase inhibitor, z-VAD-fmk, dramatically decreased cytotoxicity in MSC-treated HL-60 cells and several other apoptotic features, such as, caspase-3 activation, the apoptotic DNA ladder, TUNEL-positive staining and the DNA double-strand break. Interestingly, a general serine protease inhibitor, AAPV-cmk, also effectively inhibited MSC-mediated cytotoxicity and apoptosis. These results demonstrate that MSC is a selenocompound that efficiently induces apoptosis in leukemia cells and that proteolytic machinery, in particular caspase-3, is necessary for MSC-induced apoptosis. On the other hand, selenite-induced cell death could be derived from necrosis rather than apoptosis, since selenite did not significantly induce several apoptotic phenomena, including the activation of caspase-3.

Amino Acid Chloromethyl Ketones↗

Acute corneal endothelial changes after laser in situ keratomileusis.

PURPOSE: To report the acute effects of laser in situ keratomileusis (LASIK) on the corneal endothelium. METHODS: Twenty eyes of 10 consecutive patients (mean age, 38.1 +/- 10.84 years) underwent bilateral simultaneous LASIK for myopic astigmatism (spherical equivalent ranging from -1.75 to -7.13 diopters) without any complications. Each eye was evaluated by slit-lamp biomicroscopy and noncontact specular microscopy preoperatively, within 15 minutes after LASIK and 1 day after surgery. Specular microscopy images were then analyzed to calculate endothelial cell density (ECD), coefficient of variation (CV) of cell size, and percentage of hexagonal cells. RESULTS: All corneas demonstrated marked alterations in endothelial cell morphology by slit-lamp biomicroscopy within 15 minutes after surgery that resolved by the first postoperative day. Central corneal endothelial analysis by noncontact specular microscopy confirmed pleomorphism with definite loss of hexagonality. Mean ECD was calculated to be 2,816.3 +/- 286.02 cells/mm(2) preoperatively, 2,750.85 +/- 327.95 cells/mm(2) on day 0 (p = 0.395), and 2,810.55 +/- 218.48 cells/mm(2) on day 1 (p = 0.461). Mean CV was 32.65 +/- 7.29 preoperatively, 34.4 +/- 6.19 on day 0 (p = 0.412), and 30.9 +/- 5.54 on day 1 (p = 0.067). Mean percentage of hexagonal cells was 63.35 +/- 10.76 preoperatively, 47.55 +/- 9.69 on day 0 (p = 0.000009), and 60 +/- 9.3 on day 1 (p = 0.00003). CONCLUSION: Qualitative and quantitative changes in endothelial cell morphology (i.e., decreased endothelial cell hexagonality) demonstrate that LASIK does induce an acute effect on the corneal endothelium that may represent transient endothelial cell edema.

Acute Disease↗