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Biomedical subjects

H T Kim

Publications and source records attributed to H T Kim.

At least 91 records · Page 5Linked to original sources
PubMed1995

Pharmacokinetics and antitumor activity of a new platinum compound, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II), as determined by ex vivo pharmacodynamics.

The pharmacokinetics and ex vivo pharmacodynamics studies on cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP), and carboplatin (CBDCA) were performed in beagle dogs. Equitoxic doses of SKI 2053R, CDDP, and CBDCA (7.5, 2.5, and 15.0 mg/kg, respectively) were given by i.v. bolus to three beagle dogs in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the three drugs declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0-->infinity) determined for ultrafiltrable platinum derived from SKI 2053R, as an active component, was 7.72 +/- 2.74 micrograms h ml-1 (mean +/- SD), with an initial half-life of 0.37 +/- 0.20 h, a terminal half-life of 2.19 +/- 0.93 h, a total clearance of 16.83 +/- 4.76 ml min-1 kg-1, and a steady-state volume of distribution of 1.57 +/- 0.30 l/kg. The ex vivo antitumor activity of SKI 2053R was assessed using the ultrafiltrable plasma against two human lung-adenocarcinoma cell lines (PC-9 and PC-14) and five stomach-adenocarcinoma cell lines (MKN-45, KATO III, SNU-1, SNU-5, and SNU-16) by tetrazolium-dye (MTT) assay and was compared with that of CDDP and CBDCA using an antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value was shown to be ranked in the following order: SKI 2053R > CBDCA > CDDP. The mean ATI values recorded for SKI 2053R and CBDCA were significantly (P < 0.05) higher than that noted for CDDP; however, no statistically significant difference was observed between SKI 2053R and CBDCA, suggesting that the antitumor activity of SKI 2053R is superior to that of CDDP and is equivalent to that of CBDCA. These results suggest that SKI 2053R is a promising candidate for further development as a clinically useful anticancer drug.

Animals↗
PubMed1995

The "sagging rope sign" in avascular necrosis in children's hip diseases--confirmation by 3D CT studies.

Growth disturbance of the proximal femoral epiphysis and physis secondary to avascular necrosis (AVN) in a variety of children's hip disorders produces changes in the femoral head and neck that make radiographic interpretation difficult. The enlarged overhanging femoral head produces radiographic markings on the femoral neck which are sometimes confusing. These have sometimes been misinterpreted as growth arrest lines. Apley and Wientroub reintroduced Perkins' description of the "sagging rope" sign in AVN of the femoral head, and Clarke clarified that this puzzling radiographic transverse metaphyseal line overlying the femoral neck in fact represents the margin of the femoral head rather than a growth arrest line. Their report was made after studying plain and stereoscopic radiographs alone. Our review of 23 cases of femoral head AVN in children, documented by 3 dimensional computerized tomographic (3D CT) radiographs of the femoral head and pelvis, confirms Clarke's view of the nature of the "sagging rope" sign. These sophisticated radiographic studies provide new detail and understanding of head-neck relationship in AVN which allows better planning for surgical correction of hip disorders in children.

Adolescent↗
PubMed1994

Study of 5'-flanking region of human Cu/Zn superoxide dismutase.

The 5'-flanking region of human Cu/Zn superoxide dismutase (SOD1) was cloned from human genomic library for the study of regulation of human SOD1 gene. We determined 3678 nucleotide sequences of 5'-flanking region of human SOD1. The putative binding sites of transcriptional factors such as NF1, Sp1, AP1, AP2, GRE, HSE and NF kappa B were found. The upstream region of this gene was analyzed by deletion and measuring the linked chloramphenicol acetyltransferase (CAT) activities. Several deletion analyses of promoter activity indicated that there were positive and negative regulatory regions. The region from -1325 bp to -1040 bp was found to have a heat shock response element.

Base Sequence↗
PubMed1994

Synthesis and antitumor activity of a series of [2-substituted-4,5-bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes.

The synthesis, physical properties, antitumor activity, structure-activity relationships, and nephrotoxicity of a series of [2-substituted-4,5-bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes are described. The 42 platinum(II) complexes having a seven-membered ring structure in this series have been prepared and characterized by 1H NMR, 13C NMR, IR, FAB-MS, and elemental analysis. All members of the series were designed to have a 1,3-dioxolane ring moiety in their carrier ligands to increase water solubility. The solubility of platinum complexes was related to the nature of leaving ligands and 2-substituents in the 4,5-bis(aminomethyl)-1,3-dioxolane carrier ligands. In general, compounds having two different R1 and R2 substituents in the 4,5-bis(aminomethyl)-1,3-dioxolane moiety were more water-soluble than those having the same substituents. Most members of this series showed the excellent antitumor activity against murine L1210 leukemia cells transplanted in mice and were superior to cisplatin and carboplatin. The (4R,5R)-stereoisomer 1a-h exhibited the higher antitumor activity than the corresponding (4S,5S)-stereoisomer 2a-h in the (1,1-cyclobutanedicarboxylato)platinum(II) complexes. The (glycolato)-platinum(II) complexes were highly cytotoxic toward four human stomach cancer cell lines, SNU-1, SNU-5, SNU-16, and NCI-N87, and among them, complexes 3d-g were even more cytotoxic than cisplatin. The (malonato)platinum(II) complex 1m and the (glycolato)platinum(II) complexes 3d-g were selected for further studies based on the greater in vivo and in vitro antitumor activity and desirable physical properties. The complexes 3e-g were almost equally cytotoxic to cisplatin toward human stomach cancer cell lines, KATO-III and MKN-45, and a human non-small cell lung cancer cell line, PC14. In contrast with cisplatin and carboplatin, five complexes selected significantly increased in life span in mice transplanted with cisplatin-resistant L1210 cells. Nephrotoxicity studies in ICR mice indicated that serum BUN and creatinine levels were not elevated when five complexes were given at a dose equal to 1.5 times the optimal dose determined in the in vivo L1210 screening system.

Animals↗
PubMed1994

The effect of radiation therapy on immune function in patients with squamous cell lung carcinoma.

The immune response is impaired in patients with malignancy, and radiation therapy (RT) can exacerbate the cancer induced-attenuation of immune response. In order to search for the fine mechanisms behind the RT-induced attenuation of cell-mediated immune response, we measured the number of lymphocytes in peripheral blood, its subsets, and lymphoblast transformation induced by phytohemagglutinin (PHA), purified protein derivatives (PPD), mitogenic monoclonal antibody anti-CD3, and mitogenic combination of anti-CD2 antibodies 9-1 and 9.6 before and after RT in 19 patients with squamous cell lung cancer. Radiation therapy significantly decreased the total numbers of lymphocytes, CD-3, CD-4, and CD8-positive lymphocytes in peripheral blood. However, RT did not change the percentages of lymphocytes and its subsets. Radiation therapy increased the percentage of interleukin 2 (IL-2) receptor-positive lymphocytes, and RT significantly decreased in vitro lymphoblast transformation by PHA, PPD, or monoclonal antibodies to T-cell surface antigens (anti-CD2 or anti-CD3). In vitro incubation with IL-2 did not increase lymphoblast transformation by anti-CD3 before RT but significantly increased after RT. In conclusion, we suggest that one of the fine mechanisms behind the RT-induced suppression of immune responsiveness of patients with lung cancer is a defect in IL-2 synthesis by lymphocytes.

Adult↗
PubMed1994

The clearance rate of alveolar epithelium using 99mTc-DTPA in patients with diffuse infiltrative lung diseases.

The early diagnosis of diffuse infiltrative lung disease (DILD) is important in prognosis and it is necessary to develop a noninvasive, inexpensive, and rapid diagnostic tool for suspected cases of DILD. Thus, we measured the epithelial permeability via radioisotope (99mTc-DTPA) in 22 patients with DILD for clinical application of the clearance rate (T1/2LB) of radioisotope on the early diagnosis of DILD. We divided the patients with DILD into the early and late stages according to the derangements of the diffusion capacity for carbon monoxide. The T1/2LB in patients with DILD were significantly shorter when compared with those with normal control in all lobes. However, 40 to 58 percent of T1/2LB in patients with DILD overlapped normal values (2 SDs of mean of T1/2LB of normal control) dependent on specific lung regions. The T1/2LB of patients with early-stage DILD was longer than that of patients with late-stage DILD in right upper and middle lobes. Although T1/2LB of 99mTc-DTPA, the index of alveolar epithelial permeability, was shortened in patients with DILD with normal diffusing capacity, it was difficult to detect early-stage DILD by measuring alveolar epithelial permeability because of many overlaps of T1/2LB between early-stage DILD and normal control.

Adult↗
PubMed1994

Interleukin-2 and soluble interleukin-2 receptor in bronchoalveolar lavage fluid from patients with bronchial asthma.

To clarify the interrelation between interleukin-2 (IL-2) and soluble IL-2R receptor (sIL-2R), as products of T-cell activation in the bronchial tree of patients with bronchial asthma, we measured the concentration of IL-2, sIL-2R, and the cellular composition in bronchoalveolar lavage (BAL) fluid. We also measured physiologic parameters, including provocation concentration of histamine required to reduce the forced expiratory volume in 1 s by 20 percent of the prechallenge baseline (PC20). The concentrations of IL-2 and sIL-2R were higher in BAL fluid of symptomatic patients with bronchial asthma than those of normal subjects and asymptomatic patients. There was a significant correlation between IL-2 and sIL-2 concentrations in BAL fluid of the patients with bronchial asthma. Patients with other lung diseases had significantly higher concentration of IL-2 than normal control; however, sIL-2R was not detected in their BAL fluids. The concentration of IL-2 inversely correlated with FEV1 in symptomatic bronchial asthma. Among the inflammatory cells in BAL fluid, percentages of eosinophils showed significant correlation with the concentrations of IL-2 and sIL-2R in BAL fluid of the patients with bronchial asthma. In conclusion, IL-2 within the bronchial tree appears to be associated with eosinophil infiltration. This leads to physiologic changes in symptomatic patients with bronchial asthma, which may be influenced by the presence of sIL-2R in BAL fluid.

Adult↗
PubMed1994

A case of noncardiogenic pulmonary edema by ethanolamine oleate.

Endoscopic injection of sclerosing agents is a strategy for control of esophageal varix bleeding. Five percent solution of ethanolamine oleate(EO) has been used as sclerosing agent. It is well known that intravascular injection of oleic acid induces acute respiratory failure in animal models. However, EO-induced noncardiogenic pulmonary edema has not been reported in human. We report a case of noncardiogenic pulmonary edema developed after therapeutic trial of EO as sclerosing agent for esophageal varix.

Esophageal and Gastric Varices↗
PubMed1993

Genomic organization and transcriptional regulation of the RANTES chemokine gene.

RANTES is a member of a large supergene family of pro-inflammatory cytokines called CC chemokines that appear to play a fundamental role in inflammatory processes. The RANTES protein causes release of histamine from basophils and is a chemoattractant for CD45RO/CD4+ "memory" T lymphocytes, monocytes, and eosinophils. Although expression of RANTES was first thought to be limited to activated T cells, recent data have shown that it is produced by a variety of tissue types in response to specific stimuli. RANTES mRNA is expressed late (3 to 5 days) after activation of resting T cells whereas in fibroblasts, renal epithelial and mesangial cells, RANTES mRNA is quickly up-regulated by TNF-alpha stimulation. In order to gain a better understanding of the molecular mechanisms that regulate expression of the RANTES locus, we have characterized the RANTES gene and determined a putative promoter region. The RANTES gene spans approximately 7.1 kb and is composed of three exons of 133, 112 and 1075 bases and two introns of approximately 1.4 and 4.4 kb with the position of intron/exon boundaries conserved relative to the other CC chemokine family members. Approximately 1 kb of DNA from the immediate 5' upstream region of RANTES was sequenced and found to contain a large number of potential consensus elements for specific T cell/hemopoietic, myeloid, muscle, and ubiquitously expressed DNA-binding factors. RANTES-promoter-luciferase gene fusion assays demonstrate high levels of reporter gene activity in a "mature" T cell line Hut78, the erythroleukemic cell line HEL, and the rhabdomyosarcoma cell line RD, with little or no activity in the "early" T cell line Jurkat, the gamma delta T cell line PEER, the thymic tumor Molt4, or the pre-erythroid cell line K562. Deletion analysis of the promoter region indicates that different transcriptional mechanisms control expression of RANTES in the various tissues studied.

Base Sequence↗
PubMed1993

A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer.

BACKGROUND: With the introduction of cisplatin-containing regimens in the treatment of advanced gastric cancer, promising clinical results have been reported. A 61.5% response rate was observed with a combination of 5-fluorouracil (5-FU) infusion and bolus cisplatin; however, the superiority of cisplatin-containing regimens to other regimens has not been clearly verified in any randomized controlled studies. A prospective, randomized study of 5-FU and cisplatin (FP) versus 5-FU, doxorubicin, and mitomycin C (FAM) versus 5-FU alone (FU) in previously untreated patients with advanced gastric cancer is reported. METHODS: A total of 324 patients were entered into the trial and 295 patients (103 for FP, 98 for FAM, 94 for FU) were evaluable. The patients were randomized to receive FP, FAM, or FU after stratifying by the following factors: performance status, presence of measurable disease, and resection of the primary tumor. RESULTS: The overall response rate for patients with measurable disease in the FP arm was significantly higher than in the FAM and FU arms (51% for FP; 25% for FAM; 26% for FU). The durations of response for each arm, however, were not significantly different. Even though the median time to progression for the FP arm (21.8 weeks) was longer than that for the FAM arm (12 weeks; P < 0.05) and for the FU arm (9.1 weeks; P < 0.005), there was no statistical difference in overall survival among the three arms. Toxicity for all three regimens was moderate and consisted primarily of myelosuppression, nausea, vomiting, and alopecia. CONCLUSIONS: Although the FP regimen showed a significantly higher response rate and a longer time to progression than the FAM or FU regimens, a survival benefit was not observed.

Adenocarcinoma↗
PubMed1993

Soluble interleukin-2 receptor and cellular profiles in bronchoalveolar lavage fluid from patients with bronchial asthma.

BACKGROUND: To elucidate the role of T-cell activation in the physiologic changes and cellular infiltrations in the bronchial tree of patients with symptomatic bronchial asthma, we measured the concentration of soluble interleukin-2 receptor (sIL-2R), cellular compositions and IL-2R expression on cells in bronchoalveolar lavage (BAL) fluid. We also measured physiologic parameters, including a provocation concentration of histamine required to reduce the forced expiratory volume in 1 second by 20% of the prechallenge baseline (PC20). RESULTS: The concentration of sIL-2R and the ratio of IL-2R expression on CD3 positive lymphocytes were significantly higher in BAL fluid from 20 patients with symptomatic bronchial asthma than concentrations in fluid from nine healthy controls (p < 0.01) and six asymptomatic patients with bronchial asthma (p < 0.05). The concentration of sIL-2R correlated with the percentage of IL-2R expression on CD3 positive lymphocytes (rs = 0.709, p < 0.01). There was no difference in sIL-2R concentration of BAL fluid between the healthy control and the patient with asymptomatic bronchial asthma. Among the inflammatory cells recovered in BAL fluid, the percentages of eosinophils showed significant positive correlation with the concentration of sIL-2R in BAL fluid in the patients with bronchial asthma. The concentration of sIL-2R significantly correlated with forced expiratory volume one second, peak expiratory flow rate, and PC20 when observed in all study subjects, but not in the patients with bronchial asthma. CONCLUSION: We conclude that T-cell activation within the bronchial tree appears to have a role in the infiltration of eosinophils into the bronchial tree, which may lead to enhanced bronchial hyperreactivity in patients with bronchial asthma.

Adolescent↗
PubMed1993

Serial fiberoptic bronchoscopic observations of endobronchial tuberculosis before and early after antituberculosis chemotherapy.

STUDY OBJECTIVE: To evaluate the antituberculous treatment responsiveness of endobronchial tuberculosis in the different stages of evolution. DESIGN: A prospective study before and after trial with 9 months of antituberculosis chemotherapy without steroid. PATIENTS AND INTERVENTION: One hundred thirty-six endobronchial lesions in 62 patients were subdivided into four types according to initial fiberoptic bronchoscopic (FOB) findings. Follow-up FOB was performed in 29 patients with 56 endobronchial lesions to detect the changes in the initial endobronchial lesion and bronchostenosis within 3 months after completion of 9 months of chemotherapy. RESULTS: The endobronchial lesions could be classified into four types: exudative (59 lesions, 43.3 percent), ulcerative (13 lesions, 9.7 percent), cicatricial (36 lesions, 26.5 percent), and bronchoglandular (28 lesions, 20.5 percent). In the reassessment of 56 lesions, all 19 exudative and all 9 ulcerative lesions showed complete improvement. Of the cicatricial lesions, most (10 of 12 lesions) showed no change in bronchostenosis, whereas 2 lesions showed improvement. In the bronchoglandular lesions, 6 of 18 lesions showed progressed bronchostenosis. Overall, we observed improved responses in 53.6 percent, progressed bronchostenosis in 10.7 percent, and stationary responses in the remaining 35.7 percent. The progressed lesions were found only in the bronchoglandular lesions. CONCLUSION: In the exudative, ulcerative, and cicatricial lesions, the administration of antituberculous chemotherapy alone resulted in favorable responses in the early posttreatment period.

Adolescent↗
PubMed1993

Treatment of hemoptysis in patients with cavitary aspergilloma of the lung: value of percutaneous instillation of amphotericin B.

OBJECTIVE: Surgery has been the primary choice of treatment for cavitary aspergillomas of the lung, but it is associated with relatively high morbidity and mortality. The effectiveness of percutaneous intracavitary instillation of an antifungal agent in seven patients with hemoptysis caused by cavitary aspergilloma was evaluated. SUBJECTS AND METHODS: All patients had hemoptysis associated with a cavitary pulmonary aspergilloma. In four patients who had aspergillomas without lung interposed between the cavity and the chest wall, 50 mg of amphotericin B in 10 ml of 5% dextrose in water and then 8 mg of bromhexine (a mucolytic agent) mixed with 10 ml of normal saline were instilled into the cavity through an 8-French catheter daily for 15 days. In three patients who had lung interposed between the cavity and the chest wall, the treatment was administered twice at 3-day intervals through a 20-gauge needle. The presence or absence of hemoptysis was recorded after each instillation of amphotericin B, and the size of aspergilloma was assessed with follow-up radiographs. RESULTS: Hemoptysis ceased within 5 days after instillation of amphotericin B in all patients. In the four patients treated through a catheter, the aspergillomas resolved completely in three patients and resolved partially in one. In the three patients treated through a fine needle, the aspergillomas resolved partially. Mild hemoptysis during the procedure, a small pneumothorax, and subcutaneous emphysema occurred in one patient each. CONCLUSION: Our results suggest that percutaneous intracavitary instillation of amphotericin B is a safe and effective method of treating hemoptysis caused by aspergillomas.

Adult↗
PubMed1992

Internal capsular lesion associated with dizziness.

It has been known that the vestibular system is concerned with feelings of dizziness or vertigo. The vestibulo-thalamic pathway has also been described previously. However, there has been no confirmative report so far regarding the pathway through the internal capsule to the cortex. We have experienced 13 patients with symptoms of dizziness and/or vertigo whose lesions are located only around the internal capsule, mainly at the posterior limb and/or the genu. It is suggestive that fibers with dizziness may pass through a part of the internal capsule, probably through some part of the posterior limb and/or the genu.

Adult↗
PubMed1992

Avascular necrosis after fracture-separation of the distal end of the humerus in children.

Fracture-separation of the distal end of the humerus in children has been reported infrequently, and may be misdiagnosed as a fracture of the condyle or a traumatic dislocation of the elbow. We discuss eight cases of a seldom reported complication following fracture-separation of the distal end of the humerus. This complication consists of dissolution of the trochlea within three to six weeks postinjury and a defect of the medial or central part of the condyle that develops later. The fractures were severely displaced fracture-separation of the distal end of the humerus with large medial or lateral metaphyseal fragment, but initially misdiagnosed as a fracture of the medial, lateral condyle or a traumatic dislocation of the elbow in six of eight cases. We performed open reduction in six cases because of initial misdiagnosis or because of difficulty in satisfactory closed reduction. We speculated that this complication is due to avascular necrosis of the distal end of the humerus, and that fracture-separation of the distal end of the humerus is more common than reported.

Child↗
PubMed1990

Two cases of suspected arteriosclerotic optical chiasmal syndrome.

Optic chiasmal syndrome due to arteriosclerotic vascular changes is rate. To our knowledge, there has been no report of arteriosclerotic chiasmal syndrome in Korea. In our two cases, other causes of chiasmal syndrome were not detected by MRI, four-vessel cerebral angiography, CSF study, and special laboratory examinations including ANA test, RA factor, and LE cell. With conservative treatment, the visual fields of the two patients are showing progressive improvement. We report here two cases of suspected arteriosclerotic optic chiasmal syndrome.

Adult↗
PubMed1989

1,25-Dihydroxyvitamin D3 interaction with dexamethasone and retinoic acid: effects on procollagen messenger ribonucleic acid levels in rat osteoblast-like cells.

We previously have reported that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], dexamethasone, and retinoic acid inhibit collagen synthesis in rat osteoblast-like cell primary cultures. We also have found that dexamethasone increases 1,25-(OH)2D3 receptor levels in these cells. Furthermore, this increase in 1,25-(OH)2D3 receptor level is paralleled by an enhanced inhibition of collagen synthesis when dexamethasone and 1,25-(OH)2D3 are used in combination. In contrast, retinoic acid at high doses decreases 1,25-(OH)2D3 receptor level in rat osteoblast-like cells and attenuates 1,25-(OH)2D3 inhibition of collagen synthesis. In the present study, we have used a [32P]cDNA probe for rat pro alpha 1 (I) to determine if these osteotropic agents act by modulating steady state procollagen mRNA levels. Hybridization with a [32P]cDNA probe for human actin was used as a control. We find that the steady state levels of procollagen mRNA are decreased in all cases, while there are negligible changes in actin mRNA levels. Dexamethasone, at the low dose of 13 nM, acts synergistically with 1,25-(OH)2D3 in decreasing procollagen mRNA levels. The effects of retinoic acid and 1,25-(OH)2D3 are additive at low doses (13 and 130 nM); however, at a high dose of retinoic acid (1.3 microM), combined treatment with 1,25-(OH)2D3 does not reduce procollagen mRNA levels beyond the decrease due to retinoic acid alone. The reduction in procollagen mRNA level after each of these treatments falls in the same range as inhibition of collagen synthesis measured at the protein level. These data suggest that the synthesis of collagen under these treatments is controlled primarily through modulation of steady state procollagen mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗