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Biomedical subjects

W S Kim

Publications and source records attributed to W S Kim.

At least 37 records · Page 2Linked to original sources

A phase III randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil and mitomycin C versus 5-fluorouracil alone in curatively resected gastric cancer.

BACKGROUND: A phase III single-center randomized trial was performed in order to determine whether the addition of mitomycin C (MMC) and/or doxorubicin to 5-fluorouracil (5-FU) as adjuvant chemotherapy could influence survival in patients with curatively resected gastric cancer. PATIENTS AND METHODS: A total of 416 patients who had undergone curative resection for stage IB-IIIB gastric adenocarcinoma were stratified according to the stage and type of surgery, and then randomized to receive one of the three chemotherapy regimens, 5-FU alone (F) or 5-FU and MMC (FM) or 5-FU, doxorubicin and MMC (FAM) within 5 weeks after surgery. RESULTS: Of 416 patients registered, 395 (133 in F, 131 in FM and 131 in FAM) were assessable. Median follow-up duration was 91 months. Five-year overall survival rates were 67.2% for F, 67.0% for FM and 66.7% for FAM (P = 0.97). Five-year disease-free survival rates were 62.1% for F, 63.3% for FM and 62.5% for FAM (P = 0.83). Hematological toxicities were more frequent in the FM and FAM groups, whereas stomatitis was more common in the F group. CONCLUSIONS: Compared with adjuvant 5-FU alone, the addition of MMC and/or doxorubicin to 5-FU did not influence survival in patients with resected gastric cancer.

Adenocarcinoma↗

Pathogenic role of endothelin 1 in hemodynamic dysfunction in experimental acute pulmonary thromboembolism.

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ET(A) receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ET(A) receptor antagonists might constitute a useful therapeutic tool for APE.

Acute Disease↗

Molecular cloning of kpcA gene encoding a Kex2p-like endoprotease from Aspergillus nidulans.

We cloned and sequenced a gene, kpcA (Kex2p-like proprotein convertase A), from a genomic library of Aspergillus nidulans. The kpcA gene encodes an 820-residue protein, named KpcA, which contains a putative subtilisin-like catalytic domain (residues 136-466) homologous to that of the subtilisin serine protease family. KpcA shows 56, 73, and 47% amino acid identities with Saccharomyces cerevisiae Kex2p, Aspergillus niger KexB, and mouse furin within the subtilisin-like catalytic domain, respectively. The sequences around the proposed active site Asp, His, and Ser residues of KpcA are similar to those of other Kex2p family members. The KpcA mRNA transcript with an expected size of approximately 2.8 kb was detected in A. nidulans. The substrate specificity of KpcA, expressed in CHO cells, is similar to that of A. niger KexB and yeast Kex2p. We conclude that KpcA is a resident Kex2p-like proprotein that processes endoprotease in A. nidulans.

Amino Acid Sequence↗

Lower respiratory tract infections due to adenovirus in hospitalized Korean children: epidemiology, clinical features, and prognosis.

On occasion, outbreaks of infection with adenovirus types 3, 7, and 21 cause severe lower respiratory tract infections (LRTIs) in children. From 1990 to 1998, all cases of LRTI due to adenovirus at the Seoul National University Children's Hospital, Seoul, Korea, were reviewed. Adenoviruses were recovered from nasal aspirate specimens of 87 (5.9%) of 1472 children with LRTI. The principal adenovirus serotypes were type 2 (13 [15%] of 87 strains), type 3 (13 [15%]), and type 7 (36 [41%]). Of the 87 infections, 62 (71%) occurred in children <2 years of age, and 81 (94%) occurred in children <5 years of age. Infections due to types 3 and 7 occurred during epidemics, whereas infections due to type 2 occurred sporadically. For patients who were infected with types 3 and 7, extrapulmonary abnormalities were more common and homogeneous consolidation and pleural effusion were frequently identified on radiographs. The mortality rate was 12% overall and 19% among patients who were infected with type 7. Residual sequelae were identified in 6 (50%) of 12 patients who were infected with type 3 and in 9 (25%) of 36 who were infected with type 7. The data confirm that adenovirus types 3 and 7 can cause epidemics of severe LRTI in young children. Epidemics of LRTIs caused by adenovirus types 3 and 7 in Korea have not been described in reports published elsewhere.

Adenovirus Infections, Human↗

Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study.

A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist. The goals of this study were to assess the safety and toxicities as well as the efficacy, and ancillarily the immunomodulatory effects, of peritumoral IL-12 gene transfer. Primary dermal fibroblasts cultured from the patients were transduced with retroviral vector carrying human IL-12 genes (p35 and p40) as well as the neomycin phosphotransferase gene (TFG-hIL-12-Neo). Patients received four injections at intervals of 7 days. Nine patients were enrolled in this dose-escalation study, with secreted IL-12 doses ranging from 300 ng/24 hr for the first three patients to 1000, 3000, and 5000 ng/24 hr for two patients in each subsequent dosage level. Although a definite statement cannot be made, there appears to be perturbation of systemic immunity. Also, the locoregional effects mediated by tumor necrosis factor alpha (TNF-alpha) and CD8+ T cells were observed with tumor regression. Treatment-related adverse events were limited to mild to moderate pain at the injection site; clinically significant toxicities were not encountered. Transient but clear reductions of tumor sizes were observed at the injected sites in four of nine cases, and at noninjected distant sites in one melanoma patient. Hemorrhagic necrosis of tumors was observed in two melanoma patients. These data indicate that gene therapy by peritumoral injection of IL-12-producing autologous fibroblasts is feasible, and promising in patients with advanced cancer.

Adult↗

Size analysis of automobile soot particles using field-flow fractionation.

Soot particles emitted from various automobile engines are analyzed for size distributions using field-flow fractionation (FFF). Soot samples are prepared for FFF analysis using a three-step procedure, where a layer of soot particles is focused between the layers of n-hexane and water, followed by dispersing of particles in water containing 0.05% Triton X-100. The mean diameters determined by FFF show similar trends with those obtained from dynamic light scattering (DLS) and scanning electron microscopy (SEM). Data from FFF are also compared with those from an on-line scanning mobility particle sizer (SMPS). SMPS size distributions extend further to larger size than those of FFF distributions, which indicates the three-step sample preparation procedure effectively disaggregates the agglomerated particles. Although the amount of particulate matter (PM) emitted from a heavy-duty diesel engine is much higher than that from a light-duty diesel engine, the size distributions of soot particles show no significant difference between heavy- and light-duty diesel engines. The engine-operating mode (engine speed and load rate) does not seem to affect significantly the size distribution of soot particles. It was found that the PM from a turbocharged diesel engine contains a higher percentage of particles smaller than 100 nm than an engine with a naturally aspirated (NA) air-inhalation system. As for gasoline engines, the PM collected after the catalytic converter has a narrower size distribution than those collected before and has a higher percentage of particles smaller than 100 nm.

Air Pollution↗

Expression patterns of Fgf-8 during development and limb regeneration of the axolotl.

Fgf-8 is one of the key signaling molecules implicated in the initiation, outgrowth, and patterning of vertebrate limbs. However, it is not clear whether FGF-8 plays similar role in development and regeneration of urodele limbs. We isolated a Fgf-8 cDNA from the Mexican axolotl (Ambystoma mexicanum) through the screening of an embryo cDNA library. The cloned 1.26-kb cDNA contained an open reading frame encoding 212 amino acid residues with 84%, 86%, and 80% amino acid identities to those of Xenopus, chick, and mouse, respectively. By using the above clone as a probe, we examined the temporal and spatial expression patterns of Fgf-8 in developing embryos and in regenerating larval limbs. In developing embryos, Fgf-8 was expressed in the neural fold, midbrain-hindbrain junction, tail and limb buds, pharyngeal clefts, and primordia of maxilla and mandible. In the developing axolotl limb, Fgf-8 began to be expressed in the prospective forelimb region at pre-limb-bud and limb bud stages. Interestingly, strong expression was detected in the mesenchymal tissue of the limb bud before digit forming stages. In the regenerating limb, Fgf-8 expression was noted in the basal layer of the apical epithelial cap (AEC) and the underlying thin layer of mesenchymal tissue during blastema formation stages. These data suggest that Fgf-8 is involved in the organogenesis of various craniofacial structures, the initiation and outgrowth of limb development, and the blastema formation and outgrowth of regenerating limbs. In the developing limb of axolotl, unlike in Xenopus or in amniotes such as chick and mouse, the Fgf-8 expression domain was localized mainly in the mesenchyme rather than epidermis. The unique expression pattern of Fgf-8 in axolotl suggests that the regulatory mechanism of Fgf-8 expression is different between urodeles and other higher species. The expression of Fgf-8 in the deep layer of the AEC and the thin layer of underlying mesenchymal tissue in the regenerating limbs support the previous notion that the amphibian AEC is a functional equivalent of the AER in amniotes.

Ambystoma↗

Virus-cell fusion inhibitory activity for the polysaccharides from various Korean edible clams.

In order to find potent virus-cell fusion inhibitory components from Korean edible clams, thirteen prepared polysaccharides were introduced to syncytia formation inhibition assay, which is based on the interaction between the HIV-1 envelope protein gp120/41 and the cellular membrane protein CD4 of T lymphocytes. Among them, Meretrix petechialis showed a potent virus-cell fusion inhibitory activity. Fusion index (FI) and percent (%) fusion inhibition of the polysaccharide of this clam were 0.21 +/- 0.02, and 67.52 +/- 4.09 at 100 microg/ml, respectively. It exhibited almost equivalent virus-cell fusion inhibitory activity to that of dextran sulfate which was used as a standard control.

Animals↗

Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome.

OBJECTIVES: To determine whether the response to the prone position differs between acute respiratory distress syndrome (ARDS) resulting from a pulmonary cause (ARDSp) and that from an extrapulmonary cause (ARD-Sexp). DESIGN AND SETTING: Prospective observational study in a medical ICU of a university-affiliated hospital. SUBJECTS: A consecutive series of 31 patients with ARDSp and 16 with ARDSexp within 3 days of onset of ARDS. INTERVENTION: Prone position for at least 2 h. MEASUREMENTS AND RESULTS: In ARDSp, compared with the supine position (121 +/- 49 mmHg), PaO2/FIO2 was not increased after 0.5 h but was increased after 2 h in the prone position (158 +/- 60 mmHg). In ARDSexp, compared with the supine position (106 +/- 53 mmHg), PaO2/FIO2 was increased after 0.5 h (155 +/- 91 mmHg), but was not further changed after 2 h. Marked oxygenation response (increase in PaO2/FIO2 > 40% from baseline) after 0.5 h was 23% in ARDSp and 63% in ARDSexp, and that after 2 h was 29% and 63%, respectively. Static respiratory compliance decreased in the prone position in ARDSexp (30 +/- 11 ml/cmH2O at baseline, 27 +/- 11 after 0.5 h and 25 +/- 9 after 2 h) but not in ARDSp. Consolidation score as determined on the first chest radiography taken in the prone position decreased to a greater degree in ARDSexp (-2.4 +/- 4.1) than in ARDSp (0.3 +/- 4.1). CONCLUSION: Pulmonary ARDS and extrapulmonary ARDS in their early stages respond differently to the prone position with regard to the time course of oxygenation, respiratory mechanical behaviour, and radiographic change. These findings suggest that the early pathophysiology of ARDS differs according to the type of primary insult to the lung.

Aged↗

MR diagnosis of cerebellar infarction due to vertebral artery dissection in children.

Posterior circulation infarction is uncommon in children. We describe the clinical presentation and radiological findings in two children with cerebellar infarction resulting from dissection of the vertebral artery. We emphasize that vertebral artery injury should be considered in a child with acute symptoms and signs of ischaemia in the posterior circulation. MRI and MRA may be helpful in the diagnosis of cerebellar infarction and vertebral artery abnormality.

Cerebellar Diseases↗

Complex bronchopulmonary foregut malformation: extralobar pulmonary sequestration associated with a duplication cyst of mixed bronchogenic and oesophageal type.

We report a 13-year-old girl with an unusual, complex bronchopulmonary foregut malformation. The malformation included extralobar pulmonary sequestration and a duplication cyst of mixed bronchogenic and oesophageal type. Preoperative CT and MRI demonstrated the cystic and solid portions of the mass and indicated an aberrant vascular supply, suggesting the possibility of bronchopulmonary foregut malformation and several other differential diagnoses. A direct communication between the cyst and the bronchus of the sequestrated lung was found on pathological examination. This unusual combination of an extralobar pulmonary sequestration and a foregut cyst points to a common embryological pathogenesis.

Adolescent↗

Gangliocytoma of the spinal cord: a case report.

We present a case of intramedullary spinal gangliocytoma in a 7-year-old girl who presented with scoliosis and progressive weakness of both legs. The tumour involved the whole spinal cord and medulla oblongata and was composed of inner cystic and outer solid components. On MRI, the solid portion of the lesion showed strong enhancement at the thoracolumbar level and mild enhancement at the cervical and medullary levels. Histological examination of the surgical specimen showed neoplastic ganglion cells arranged irregularly in benign normocellular glial background, which made a diagnosis of gangliocytoma.

Female↗

Herpes simplex encephalitis: MRI findings in two cases confirmed by polymerase chain reaction assay.

Herpes simplex virus (HSV) type I causes a fulminant necrotising meningoencephalitis distinguished from other encephalitides by its focal and often haemorrhagic nature. Specific antiviral therapy with acyclovir can significantly improve the prognosis. We present MRI findings of two cases of herpes simplex encephalitis (HSE) confirmed by PCR analysis, focusing on the serial changes after acyclovir therapy: gyral swelling, high signal intensity on T2-weighted images in the subfrontal region, temporal lobe and insula in the initial stage, then regional extension with enhancement and haemorrhage despite appropriate acyclovir therapy, and finally encephalomalacia and brain atrophy.

Acyclovir↗

Sequence and stress-response analyses of the DNA mismatch repair gene hexA in Lactococcus lactis.

The DNA mismatch repair gene hexA was identified in Lactococcus lactis by PCR amplification by using a pair of primers homologous to the DNA-binding Dps protein. The gene in its entirety, including the regulatory regions, was sequenced, by using a strategy of chromosomal walking based on two PCR protocols. The open reading frame of 2526 bp was preceded by a strong ribosome-binding site (AGGAAG) and was followed by a potential transcription terminator (hairpin loop structure). The 5' terminus of the hexA mRNA was located 135 bp upstream of the start codon, and putative -10 and -35 regions were identified. The deduced amino acid sequence revealed two motifs, the ATP/GTP-binding site (P-loop) and the "MutS family signature". The hexA promoter was cloned into pMU1327, which contained a promoter-less CAT reporter gene, and the promoter activity was examined under oxidative-stress conditions. It appears that the promoter activity is down-shifted by H2O2 at 4 mM.

Amino Acid Sequence↗

Assessment of stress response of the probiotic Lactobacillus acidophilus.

Different aspects of stress response of Lactobacillus acidophilus were investigated. First, the sublethal and lethal levels of bile, heat, and NaCl stresses were determined. They were 0.05% and 0.5% (bile), 53 degrees C and 60 degrees C (heat), and 2% and 18% (NaCl), respectively. To evaluate the effect of each stress at log phase, log-phase cultures were challenged directly with the lethal level of each stress (control) and were compared to log-phase cultures that were pre-exposed to the sublethal level prior to the exposure at the lethal level (test). Some, if not most, of the cells were killed in the control cultures against each of the three stresses. However, in the test cultures, the number of cells that had survived increased significantly. It appears that L. acidophilus is capable of displaying adaptive response to stress. The adaptive response to one stress was also shown to provide cross-protection against different stresses tested. The effect of each stress on stationary-phase cultures was also investigated. In contrast to log-phase culture, stationary-phase culture was inherently resistant to stress.

Bile↗

A novel pH-sensitive membrane from chitosan--TEOS IPN; preparation and its drug permeation characteristics.

A novel organic-inorganic composite membrane was prepared, using tetra ethyl ortho silicate (TEOS) as an inorganic material and chitosan as an organic compound. Equilibrium and oscillatory swelling studies were conducted to investigate swelling behaviors of the membrane according to the pH of the swelling medium. Drug permeation experiments were also performed in phosphate buffer solution of the pH of 2.5 and 7.5, respectively. Lidocaine HCl, sodium salicylate and 4-acetamidophenol were selected as model drugs to examine the effect of ionic property of drug on the permeation behavior. The effects of membrane composition and the external pH on the swelling and the drug permeation behavior of IPN membrane could be summarized as follows; chitosan incorporated into TEOS IPN swelled at pH 2.5 while shrunk at pH 7.5. This swelling behavior was completely reversible and the membrane responded rapidly to the change in environmental pH condition. According to swelling behavior, an increase in pH from 2.5 to 7.5 yielded an increase in the rate of drug permeation because of the shrinking of the incorporated chitosan in TEOS IPN, while decrease in pH resulted in low permeation rate. The optimal TEOS-chitosan ratio for maximum pH-sensitivity existed and drug permeation was influenced not only with the external pH but also with the ionic interactions between the drug and membrane.

Chitin↗

Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma.

Lovastatin, an inhibitor of mevalonate synthesis, demonstrated in vitro antitumor activity against a variety of human cancer cells, especially in gastric adenocarcinoma cells at pharmacologically achievable concentrations. To determine the antitumor activity of this drug in advanced measurable gastric adenocarcinoma as well as to assess the toxicities and the pharmacokinetic features, we carried out a phase II study of high-dose lovastatin. Patients received lovastatin 35 mg/kg/day for 7 consecutive days, with ubiquinone (60 mg qid p.o.) to prevent rhabdomyolysis. The treatment was repeated every 28 days. From March 1996 to January 1997, 16 patients (median age, 57 years; range, 34-68) were entered into the study, 14 of whom were evaluated for response and toxicity. No patient achieved a response. A total of 28 cycles were administered. The median number of cycles was 2 (range, 1 to 4). Anorexia was the most common toxicity (64%), but decreased oral intake was observed only in 3 cycles. Two patients developed myalgia with elevated muscle enzyme. When used in this dosage and schedule, lovastatin does not appear to be effective for patients with advanced gastric adenocarcinoma.

Adenocarcinoma↗

Effects of heat pretreatment on histopathology, cytokine production, and surfactant in endotoxin-induced acute lung injury.

To determine the effect of heat stress on histopathology of acute lung injury (ALI) caused by administration of lipopolysaccharide (LPS), and to determine the roles of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, interferon (IFN)-gamma, IL-10 and surfactants in heat-induced tolerance to ALI, we administered either saline or LPS (3 mg/kg of body weight) intravenously to male Sprague-Dawley rats without and with heat pretreatment. Five hours after LPS or saline treatment (23 h after heat-pretreatment), samples were obtained. We found that the histopathologic features of LPS-induced ALI were attenuated by heat-pretreatment. Heat-pretreatment did not decrease the elevated plasma or BAL fluid levels of TNF-alpha, IL-1beta, and IFN-gamma by LPS. The plasma level of IL-10 in LPS-treated rats with heat-pretreatment, however, was increased compared to that of LPS-treated rats without heat-pretreatment (P = 0.001). There were no differences in the BAL fluid concentrations of light or heavy density pulmonary surfactant phospholipids depending on heat-pretreatment in LPS-treated rats. These observations suggest that IL-10 might play a role in decreasing LPS-induced acute lung injury after heat-pretreatment.

Acute Disease↗