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Biomedical subjects

T Kim

Publications and source records attributed to T Kim.

At least 163 records · Page 9Linked to original sources

Effects of endoscopic variceal sclerotherapy on azygos vein blood flow and systemic haemodynamics.

The present study was designed to determine the systemic haemodynamic effects of obliterating oesophageal varices by endoscopic sclerotherapy. We evaluated systemic and splanchnic haemodynamics before and after the first course of sclerotherapy in cirrhotic patients. The baseline cardiac index was significantly correlated with baseline azygos vein blood flow (r = 0.64; P < 0.01) and the azygos vein blood flow and cardiac index significantly decreased (-33% and -16%, respectively; P < 0.01) following sclerotherapy. The systemic vascular resistance index was also increased significantly (+ 20%; P < 0.01) in these patients. Moreover, the per cent change in azygos vein blood flow was directly correlated with that of the cardiac index (r = 0.51; P < 0.03). We conclude from these findings that the obliteration of portosystemic collaterals by sclerotherapy significantly reverses hyperdynamic circulation in such patients via a decrease in cardiac preload. The blood flow of the portosystemic shunt per se is a leading contributor to the hyperdynamic circulation observed in patients with well-developed portal systemic collateral vessels.

Adult↗

Retroviral mutation rates and A-to-G hypermutations during different stages of retroviral replication.

Retroviruses mutate at a high rate in vivo during viral replication. Mutations may occur during proviral transcription by RNA polymerase II, during minus-strand DNA synthesis (RNA template) by viral reverse transcriptase, or during plus-strand DNA synthesis (DNA template) by reverse transcriptase. To determine the contributions of different stages of replication to the retroviral mutation rates, we developed a spleen necrosis virus-based in vivo system to selectively identify mutations occurring during the early stage (RNA transcription plus minus-strand synthesis) and the late stage (plus-strand synthesis plus DNA repair). A lacZalpha reporter gene was inserted into the long terminal repeat (LTR) of a spleen necrosis virus shuttle vector, and proviruses were recovered from infected cells as plasmids containing either one or both LTRs. Plasmids containing both LTRs generated a mutant phenotype only if the lacZalpha genes in both LTRs were mutated, which is most likely to occur during the early stage. Mutant phenotypes were identified from plasmids containing one LTR regardless of the stage at which the mutations occurred. Thus, mutant frequencies obtained after recovery of plasmids containing both LTRs or one LTR provided early-stage and total mutation rates, respectively. Analysis of 56,409 proviruses suggested that the retroviral mutation rates during the early and late stages of replication were equal or within twofold of each other. In addition, two mutants with A-to-G hypermutations were discovered, suggesting a role for mammalian double-stranded RNA adenosine deaminase enzyme in retroviral mutations. These experiments provide a system to selectively identify mutations in the early stage of retroviral replication and to provide upper and lower limits to the in vivo mutation rates during minus-strand and plus-strand synthesis, respectively.

Animals↗

Dynamic MR imaging and early-phase helical CT for detecting small intrahepatic metastases of hepatocellular carcinoma.

OBJECTIVE: We performed a study to evaluate the sensitivities of multislice dynamic MR imaging and early-phase helical CT as noninvasive methods for detecting small intrahepatic metastases of hepatocellular carcinomas. MATERIALS AND METHODS: Dynamic and spin-echo MR imaging and early- and delayed-phase helical CT of the liver were performed for patients with multiple hepatocellular carcinomas before transcatheter arterial chemoembolization. Forty-nine patients had 242 intrahepatic metastases less than 3 cm in diameter. Using iodized-oil CT after transcatheter arterial chemoembolization as a gold standard, the sensitivity of MR imaging for detecting intrahepatic metastases was compared with that of CT. RESULTS: Of the 242 nodules, 225 were diagnosed as hepatocellular carcinomas by iodized-oil CT. Of these, dynamic MR imaging and early-phase CT were significantly superior to those of spin-echo MR imaging (p < .0001) and delayed phase CT (p < .0001) for tumors less than 1 cm in diameter. CONCLUSION: Dynamic MR imaging and early-phase CT of the liver are the most sensitive noninvasive means of detecting small intrahepatic metastases of hepatocellular carcinoma before and after treatment.

Carcinoma, Hepatocellular↗

CT and MR imaging of abdominal liposarcoma.

OBJECTIVE: CT and MR images were reviewed to correlate the histologic subtypes of abdominal liposarcoma with the radiologic findings. SUBJECTS AND METHODS: Ten patients with liposarcoma who underwent CT or MR imaging before surgery were included in this study. CT and MR imaging findings for these patients were compared retrospectively with histologic findings. RESULTS: Major histologic subtypes found in our group of patients were five well-differentiated, three myxoid, one pleomorphic, and one round-cell liposarcomas. The well-differentiated subtype consisted of lipoma-like and/or sclerosing components. The predominant attenuation and signal intensity characteristics of the lipoma-like components on CT and MR images resembled those of fat, whereas the predominant attenuation and signal intensity characteristics of the sclerosing components resembled those of muscle. The myxoid subtype showed, on unenhanced images, predominant attenuation and signal intensity characteristics that resembled those of water; on contrast-enhanced images, this subtype showed gradual reticular enhancement. The appearance of the round-cell and pleomorphic subtypes was that of heterogeneous, nonfatty tumors. Their characteristics were indistinguishable from those of other malignant soft-tissue masses. CONCLUSION: Each histologic subtype of abdominal liposarcoma showed different CT attenuation or MR imaging signal intensity characteristics. A clear understanding of these findings should prove helpful in the diagnosis of liposarcoma.

Abdominal Neoplasms↗

Transport of aminothiol radioprotectors into mammalian cells: passive diffusion versus mediated uptake.

Water:n-octanol partition coefficients (KD) were determined for a series of radioprotective thiols to ascertain whether these could be used to estimate reliably their rates of uptake into mammalian cells by passive diffusion. Values of KD determined for thiols in 0.1 M potassium phosphate, pH 7.4, at 22 degrees C were: N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065, WRSH), 2.0 x 10(3); dithiothreitol, 1.4; 2-mercaptoethanol, 1.7; cysteamine, 180; 3-mercaptopropanoic acid, 450; mercaptosuccinic acid, 5 x 10(6) (extrapolated value). Predictions of uptake rates by passive diffusion into mammalian cells using these values and values for the membrane diffusion rate derived from empirical evaluation of appropriate values from the literature for erythrocyte permeability paralleled the experimental rates for WR-1065 and dithiothreitol but were about threefold lower. Although the utility of KD values for quantitative prediction of uptake rates is limited, the analysis clearly indicated that uptake of aminothiols having three or more ionized amino groups will not occur at useful rates by passive diffusion. Studies of WR-1065 import by Chinese hamster V79-171 cells at micromolar levels of WR-1065 revealed an uptake that could not be explained by passive diffusion. This uptake was not inhibited by substrates for common amino acid transport systems but was inhibited by polyamines and by 1 mM DTT, which suggested that WR-33278 (WRSSWR) formed by oxidation of WRSH was being transported by a polyamine transport system. This was confirmed by showing that WRSSWR is imported efficiently by V79-171 cells treated with D,L-2-difluoromethylornithine to deplete intracellular polyamines and hence enhance their transport. Spermine inhibited uptake of WRSSWR and WRSSWR inhibited uptake of [14C]spermine, confirming that a common system is involved in the uptake of these similar molecules, both having +4 charge. It was shown that after import WRSSWR is reduced to WRSH and that uptake at low micro-molar concentrations of WRSSWR results in marked cellular concentration of the drug. These results indicate that the spermidine/spermine transport system may also provide a feasible route for import of radioprotective aminothiols bearing net charges of +3 or +4 into mammalian cells.

Animals↗

Related donor marrow transplant for chronic myeloid leukemia: patient characteristics predictive of outcome.

Pre-transplant characteristics of 137 consecutive patients (including 103 patients with one or more features suggesting advanced disease) undergoing related donor marrow transplant for chronic myeloid leukemia (CML) were analyzed to determine their association with outcome. Multivariate analysis identified increased recipient age (relative risk (RR) for patients over 30 years of relapse or death 2.37; P = 0.004), and longer interval between diagnosis and transplant (RR 1.20; P = 0.0001) as significant adverse influences on disease-free survival (DFS). The 5-year DFS for patients transplanted within 1 year of diagnosis (¿early transplant', n = 71) was significantly higher (51%) than that for patients transplanted beyond 1 year from diagnosis ('delayed transplant', n = 55) (34%; log rank P = 0.02). For early transplant patients, poor prognostic features included myelofibrosis (RR 3.53; P = 0.018), splenomegaly (RR 2.22; P = 0.029) and the use of a female donor (RR 3.16; P = 0.002). The 5-year DFS for patients transplanted within 1 year of diagnosis and without signs of advanced disease was 67%. The presence of increasing numbers of features suggesting acceleration prior to transplant had a cumulative adverse influence of DFS. The risk of relapse (5 year estimate 20%) was also independently and significantly increased in association with a longer interval from diagnosis to transplant (P = 0.012). Early transplant is an important influence on DFS and relapse after related donor transplant therapy for CML, although additional patient characteristics influencing outcome can be identified and may have cumulative adverse effects.

Adolescent↗

Nitrate kinetics in patients with compensated cirrhosis: correlation with hemodynamics.

OBJECTIVES: The serum nitrate concentration is known to be increased in patients with cirrhosis. This study was designed to determine the kinetics of nitrate in the splanchnic vascular areas and its relationship with hepatic hemodynamics in patients with compensated cirrhosis. METHODS: We measured the serum nitrate concentration of various sites, including the femoral artery, hepatic vein, azygos vein, and pulmonary artery, and compared these values with hepatic hemodynamics. RESULTS: The nitrate concentrations of hepatic vein and azygos vein were significantly greater in cirrhotic patients compared with those of control subjects. The values were particularly elevated in patients with Child-Pugh's class B. In control subjects, hepatic vein and azygos vein nitrate concentrations were significantly lower than arterial nitrate concentrations whereas nitrate concentrations were significantly greater in the hepatic and azygos veins than femoral artery in cirrhotic patients, and nitrate kinetics was that of the net release of nitrate from the hepatic and azygos veins. The portal vein blood flow positively correlated with the nitrate concentration of azygos vein, pulmonary artery, and femoral artery. CONCLUSIONS: The present results implicate the enhanced production of nitric oxide in the mesenteric vascular beds in patients with cirrhosis. The positive correlation between portal vein blood flow and serum nitrate concentrations suggests that endogenous nitric oxide may have an important role in the regulation of portal hemodynamics in these patients.

Blood Flow Velocity↗

Donor factors associated with epithelial defects after penetrating keratoplasty.

The records of 39 patients undergoing 40 consecutive penetrating keratoplasties were reviewed to identify donor factors that might correlate with the presence of an epithelial defect on the first postoperative day. Of the 40 transplanted corneas, 13 (32.5%) had no epithelial defect, 18 (45%) had some epithelial defect, and nine (22.5%) had a total epithelial defect 1 day postoperatively. The status of the epithelium was correlated with several donor factors. The only factor that had a statistically significant association with the degree of epithelial defect was the time interval from preservation to surgery (p = .001). Based on a logistic regression model, the probability of having an epithelial defect 1 day after penetrating keratoplasty increased with respect to longer storage times. These results may aid the surgeon in the selection of donor tissue, particularly when performing penetrating keratoplasty on patients with ocular surface disorders.

Adolescent↗

The corneal epithelium after optisol-GS storage.

The objective of this study was to evaluate the epithelium of human corneas stored in Optisol-GS (Chiron Intraoptics, Irvine, CA) for extended periods (2-34 days). Human corneas stored in Optisol-GS (n = 64) were obtained from the Georgia Eye Bank. Corneal epithelial viability was assessed by using the Calcein-AM (Molecular Probes, Inc., Eugene, OR) ethidium homodimer stain, a fluorescent assay used to distinguish live from dead cells. Scanning and transmission electron microscopy was used to evaluate epithelial ultrastructure. The results showed that corneas stored up to 6 days in Optisol-GS had minimal damage of the epithelium. Calcein-AM ethidium homodimer staining showed 20-25% epithelial damage. Corneas stored 7-10 days had a further increase in epithelial damage (30-35%). Corneas stored for 11-15 days had marked increases in epithelial damage (40-50%), and corneas stored 16-34 days showed significant epithelial damage (60-70%). The data show that corneas stored in Optisol-GS are able to maintain the epithelium up to 6 days. A gradual decrease in epithelial viability and loss of epithelial cells occurs in corneas stored 6-10 days. Corneas stored for > 10 days have a marked loss of epithelial cells with extensive epithelial damage.

Cell Survival↗

[Cardiac injury successfully treated by emergency cardiorrhaphy--a report of 5 cases].

Five cases who were successfully treated for cardiac injuries by emergency cardiorrhaphy were reported. The range of the ages of the patients was 14 to 71 years. Four of the 5 were males with stab wounds and one was a 71-year-old female with a blunt injury by motor vehicle accident. As to the site of cardiac wounds, all of the cases suffered single chamber injury. In the cases of stab wounds, the right atrium was involved in one case and the right ventricle was involved in the three others. The site of the blunt injury was the left auricle. However there was only one case with the pre-operative diagnosis of cardiac injury. The emergency room thoracotomy was done in 2 cases. One was stab injury and the other was blunt trauma. Both of them had an uneventfull post-operative course without any infection. In conclusion, ERT is most helpful when used in the cases with PI* < or = 15. *: physiologic index (Ivatury).

Adult↗

[Blood flow measurement of portal vein with fast cine phase contrast MR imaging under breath-holding].

Flow measurements of the right portal vein were performed in seven healthy volunteers with the segmented k-space fast gradient-echo phase-contrast (fcard-PC) sequence under breath-holding. The mean velocity and the flow rate of the right portal vein at maximal expiration, 14.3 +/- 4.4cm/sec and 457 +/- 218 ml/min, were significantly greater (p < 0.01) than those at maximal inspiration: 11.8 +/- 3.8cm/sec (mean +/- SD) and 364 +/- 191ml/min, respectively. Fcard-PC enabled flow measurements to be obtained under breath-holding. Using this technique, we demonstrated portal venous flow changes according to respiratory phase.

Adult↗

Cloning and characterization of MVP17: a developmentally regulated myelin protein in oligodendrocytes.

The remarkable quantities of myelin membrane produced by oligodendrocytes has led us to examine the mechanisms involved in the sorting and transport of proteins and lipids during myelinogenesis. Noting that it has been proposed that proteins destined for the apical surface of polarized epithelial cells co-cluster with glycolipid-rich microdomains during sorting and transport from the trans-Golgi network (Simons and van Meer: Biochemistry 27:6197-6202, 1988; Simons and Wandinger-Ness: Cell 62:207-210, 1990), we hypothesized that the glycolipid-rich oligodendrocytes may adopt this mechanism for myelinogenesis. Protein-lipid complexes from oligodendrocytes and myelin were isolated utilizing detergent insolubility and two-dimensional gel electrophoresis. A developmentally regulated protein, MVP17 (myelin vesicular protein of 17 kDa), was identified. Microsequencing of the N-terminal peptide revealed a high homology to human T-cell MAL protein (Alonso and Weissman: Proc Natl Acad Sci USA 84:1997-2001, 1987). The corresponding MVP17 cDNA was isolated from an oligodendrocyte cDNA library. The predicted protein sequence showed 88.9% identity with MAL, and the hydrophobicity profile suggested four transmembrane domains. In vitro translation demonstrated a signal at the deduced Mr of approximately 17 kDa. Northern analyses indicated that MVP17 mRNA expression is restricted to brain and kidney and that this expression is up-regulated in oligodendrocytes and brain during the period of active myelination. These data suggest that MVP17 is involved in myelin biogenesis and/or myelin function.

Amino Acid Sequence↗

Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain.

During T-cell activation, Ser59 in the unique N-terminal region of p56lck is phosphorylated. Mutation of Ser59 to Glu59 mimics Ser59 phosphorylation, and upon CD4 crosslinking, this mutant p56lck induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56lck. Mutant and wild-type p56lck have similar affinities for CD4 and similar kinase activities. In glutathione S-transferase fusion proteins, the p56lck Src homology 2 (SH2) domain with the SH3 domain and the unique N-terminal region (including Ser59) has a different binding specificity for phosphotyrosyl proteins than the SH2 domain alone. Either deletion of the unique N-terminal region or mutation of Ser59 to Glu59 in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser59 regulates the function of p56lck by controlling binding specificity of its SH2 domain.

Amino Acid Sequence↗

Computational simulation of worker exposure using a particle trajectory method.

The velocity field downstream of a worker is approximated with a discrete vortex algorithm. This information is used to calculate trajectories of massless tracer 'particles' released from a point-source of contaminant. Concentrations in the plane of this source are estimated by averaging over a number of such trajectories. Approximations include: (1) representing the worker by a two-dimensional elliptical cylinder; and (2) representing tracer gas contaminant by massless particles generated without momentum. These particles are transported by both vortex shedding and turbulent diffusion. Computer-predicted mean concentrations in the near-wake region downstream of the worker compare well with results from wind-tunnel tracer gas experiments employing a mannequin. Subsequently, the concept of a computational breathing zone is introduced, and predictions of worker exposure are made. These simulations of time-integrated breathing zone concentration also compare well with measured values.

Air Movements↗

Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial.

OBJECTIVES: Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic regional drug concentrations, particularly in areas of poor vascularization, including wound sites. We have developed a lipid-based drug delivery system to provide prolonged levels of gentamicin in local tissues after local administration. Multivesicular liposomes are microspheres composed of lipid bilayer membranes surrounding multiple aqueous compartments that can contain drug. The preparation may be effective for the prevention and treatment of a variety of infections, including infections associated with indwelling vascular catheters. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Mice, 6 to 12 wks of age, weighing 20 to 30 g. INTERVENTIONS: We administered 0.5 mg of gentamicin encapsulated in multivesicular liposomes to dorsal subcutaneous tissue in mice. Animals were inoculated with 10(5) to 10(7) colony-forming units (cfu) of Staphylococcus aureus 2, 4, 6, and 8 days later. The cfu/g of tissue values were determined 2 days after inoculation. MEASUREMENTS AND MAIN RESULTS: With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular liposome/gentamicin had a 4 log10 reduction in cfu/g of tissue compared with controls. When 10(5) cfu of Staphylococcus aureus were inoculated after 2- and 4-day pretreatment with multivesicular liposome/gentamicin, a 6 log10 reduction in bacteria colony-forming units was observed. CONCLUSION: Local injection of multivesicular liposome/gentamicin provides sustained drug concentrations in regional tissues that protect against a massive bacterial challenge for at least four subsequent days.

Animals↗

Serum hepatocyte growth factor levels in patients with chronic renal failure.

The serum levels of hepatocyte growth factor (HGF) were determined in chronic renal failure (CRF) patients. Nondialysis patients with renal insufficiency had significantly higher serum HGF than normal subjects (0.34 +/- 0.10 ng/ml, n = 21 vs. 0.19 +/- 0.05 ng/ml, n = 15; p < 0.001), and the elevated serum HGF correlated with their serum creatinine levels. Hemodialysis (HD) patients treated for 5-10 years showed higher serum HGF than those receiving HD for 1 year or less (0.45 +/- 0.14 ng/ml, n = 8 vs. 0.33 +/- 0.11 ng/ml, n = 9; p < 0.05). Continuous ambulatory peritoneal dialysis patients also showed elevated serum HGF levels comparable to those of HD patients. There was no difference in serum HGF levels in HD patients with or without acquired cystic disease of kidney. Consequently, serum HGF is elevated in CRF, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients.

Adult↗