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Biomedical subjects

J S Kim

Publications and source records attributed to J S Kim.

At least 19 recordsLinked to original sources

Cyclic AMP induces inhibition of cyclin A expression and growth arrest in human hepatoma cells.

Classical cytotoxic therapy has been minimally useful in the treatment of hepatocellular carcinoma. In an effort to develop a new approach to the treatment of this neoplasm, we have investigated the signal transduction pathways regulating the growth of human hepatoma cells. In the data reported here, cyclic AMP (cAMP), a negative growth regulator for many cells of epithelial origin, induced G1 synchronization and apoptosis in the HepG2 human hepatoma cell line. The effects of cAMP on the components of the G1/S transition were analyzed. There was no detectable effect of two different cAMP analogs, 8-bromo cAMP or dibutyryl cAMP on the level of the D-type cyclins, cyclin E, cyclin-dependent kinase 2, cyclin-dependent kinase 4, p53, or the cyclin-dependent kinase inhibitors p21 or p27. In contrast, the cAMP analogs induced a dramatic downregulation of cyclin A protein, cyclin A messenger RNA, and cyclin A-dependent kinase activity. Cyclin A-dependent kinase has been shown to be required for the G1-S transition. Furthermore, cyclin A deregulation has been implicated in the pathogenesis of hepatocellular carcinoma. The data reported here suggest a novel signal transduction-based approach to hepatoma therapy.

Apoptosis

Improved cycle sequencing of GC-rich DNA template.

Even when DNA sequencing of purified DNA template failed under the optimal condition, it can be generally contributed to high GC content. GC-rich region of template causes a secondary structure to produce shorter readable sequence. To solve this problem, the sequencing reaction was modified by using dimethyl sulfoxide (DMSO). It was found that 5% (v/v) of DMSO in the reaction mixture recovers sequencing signal intensity with reduced frequency of ambiguous bases. When DMSO was added to sequencing reaction of DNA template with normal GC content, it did not show any adverse effect. Sequencing accuracy and unambiguous base frequency were significantly improved at concentration of 2% to 5% (v/v) DMSO in GC-rich DNA template. DMSO has been empirically introduced to enhance the efficiency of PCR in GC-rich templates. However, the underlying mechanism of improved cycle sequencing by DMSO is unknown. Thus, cycle sequencing reaction was remodified with other additives such as N-methyl imidazole, N-methyl2-pyrrolidone, N-methyl-2-pyridone and glycerol, possessing the similar chemical properties as DMSO. Most of methyl nitrogen ring-containing chemicals did not improve sequencing accuracy, whereas only glycerol mimicked the positive effect of DMSO by the same extent. In the present study, we suggest that the treatment of DMSO improve cycle sequencing by the alteration of structural conformation of GC-rich DNA template.

Base Composition

Determination of the limited trypsinolysis pathways of tumor necrosis factor-alpha and its mutant by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) is employed to directly analyze the limited trypsinolysis products of wild-type tumor necrosis factor-alpha (wtTNF-alpha) and its mutant, M3S. To determine the charge numbers of peaks of relatively small peptides in the ESI mass spectrum of a digest, a series of sodium-adduct ion peaks of each peptide are generated by adding a small quantity of NaCl to the digest before taking the spectrum. From the monitoring of the composition of proteolytic mixture as the incubation time is lengthened, it has been learned that the proteolysis of wtTNF-alpha by trypsin occurs sequentially: Arg2, Arg6, Arg32, Arg31, and Arg44, and that M3S is strongly resistant to the proteolysis. Since the cleavage sequence of wtTNF-alpha and the mutation-induced resistance of M3S are consistent with the structural features of the proteins, we can suggest a mutant more resistant to proteolysis than M3S, which has an additional point mutation, Ala35Leu or Ala35Ile.

Amino Acid Sequence

Antiangiogenesis treatment for gliomas: transfer of antisense-vascular endothelial growth factor inhibits tumor growth in vivo.

Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Angiogenic factors are potentially optimal targets for therapeutic strategies because they are essential for tumor growth and progression. In this study, we sought a strategy for efficiently delivering an antisense cDNA molecule of the vascular endothelial growth factor (VEGF) to glioma cells. The recombinant adenoviral vector Ad5CMV-alphaVEGF carried the coding sequence of wild-type VEGF165 cDNA in an antisense orientation. Infection of U-87 MG malignant glioma cells with the Ad5CMV-alphaVEGF resulted in reduction of the level of the endogenous VEGF mRNA and drastically decreased the production of the targeted secretory form of the VEGF protein. Treatment of s.c. human glioma tumors established in nude mice with intralesional injection of Ad5CMV-alphaVEGF inhibited tumor growth. Taken together, these findings indicate that the efficient down-regulation of the VEGF produced by tumoral cells using antisense strategies has an antitumor effect in vivo. This is the first time that an adenoviral vector is used to transfer antisense VEGF sequence into glioma cells in an animal model, and our results suggest that this system may have clinical and therapeutic utility.

Adenoviridae

Thrombotic thrombocytopenic purpura associated with ticlopidine use: a report of 3 cases and review of the literature.

Ticlopidine hydrochloride is an antiplatelet agent used for an increasing number of indications, including cerebrovascular disease, unstable angina, coronary artery stenting, and peripheral vascular bypass grafting. It has uncommon but severe hematologic effects, including thrombotic thrombocytopenic purpura. We report 3 new cases of ticlopidine-associated thrombotic thrombocytopenic purpura and review the English-language literature. Of the 13 patients described (10 from published articles), an equal number were women and men. The median age of the women was 50 years, and that of the men was 72 years. Thrombotic thrombocytopenic purpura occurred within 2 to 8 weeks of starting ticlopidine therapy. Survivors received plasma therapy, but of the 4 who died, 3 had received platelet transfusions. With discontinuation of the drug and prompt plasma exchange therapy, mortality was comparable to that seen with idiopathic thrombotic thrombocytopenic purpura, and relapse was uncommon. Physicians and patients should be aware of this potentially fatal but treatable complication of ticlopidine therapy.

Aged

Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma.

BACKGROUND: Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5-fluorouracil (5-FU), and cisplatin in the treatment of patients with advanced gastric carcinoma. METHODS: Forty-one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3-hour intravenous (i.v.) infusion on Day 1, 5-FU 750 mg/m2 by 24-hour continuous i.v. infusion on Days 1-5, and cisplatin 20 mg/m2 by 2-hour i.v. infusion on Days 1-5. Twenty-six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity. RESULTS: Twenty-one of the 41 patients (51%; 95% confidence interval [CI], 36.5-65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9-22.5%). Sixty-five percent of the patients with measurable disease (17 of 26; 95% CI, 58-92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1-52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4-90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred. CONCLUSIONS: Paclitaxel, 5-FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting.

Adult

Internal auditory artery infarction: clinicopathologic correlation.

OBJECTIVE: To study the pathophysiology of labyrinthine infarction. BACKGROUND: The syndrome of sudden onset vertigo or hearing loss is commonly attributed to inner ear vascular disease, yet histologic studies of isolated labyrinthine infarction in humans have been rare and have not included a complete examination of the vertebrobasilar vascular system. METHODS: Temporal bones, brainstem, cerebellum, and the supplying blood vessels were subjected to gross and microscopic postmortem examinations in a 92-year-old woman who had a sudden onset of vertigo and hearing loss in the right ear 7 years before death. RESULTS: There were prominent atherosclerotic changes at the vertebrobasilar junction, but the internal auditory artery and its branches were patent on both sides. Histologic studies showed degenerative changes in the cochlea and vestibular labyrinth on the right. The posterior canal ampulla and saccular macule were relatively preserved showing partial areas of intact sensory epithelium with underlying nerve fibers. The right vestibulocochlear nerve showed a fibrotic scar and multiple patchy areas of degeneration. These findings are most consistent with a transient period of reduced perfusion of the internal auditory artery. CONCLUSION: The partial sparing of the inferior vestibular labyrinth may indicate a decreased vulnerability to ischemia because of its better collateral blood supply.

Aged

Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist.

LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.

8-Hydroxy-2-(di-n-propylamino)tetralin

Change in corneal sensitivity following laser in situ keratomileusis.

PURPOSE: To evaluate the change in corneal sensitivity following laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, Maryknoll Hospital, Pusan, Korea. METHODS: The corneal sensitivity in 40 eyes (32 patients) was measured before and 1 and 2 weeks and 1, 3, and 6 months after LASIK. Sensitivity measurements were made with an esthesiometer at central, temporal, inferior, nasal, and superior points on the corneal flap. The eyes were grouped by ablation depth: Group 1, corneal ablation depth less than 100 microns; Group 2, corneal ablation depth more than 100 microns. RESULTS: Corneal sensitivity did not recover to the preoperative level by 6 months after LASIK. Except at the hinge of the corneal flap, the pattern of sensitivity recovery was similar among the various points. Recovery was more rapid at the hinge than at other areas (P < .05). There was a trend toward a greater reduction in corneal sensitivity in Group 2, the group with deeper ablations, than in Group 1. CONCLUSION: The results suggest that lamellar cutting of the cornea during LASIK impairs corneal sensitivity and that the depth of the corneal ablation affects the extent of corneal sensitivity loss and recovery.

Adult

Cytotoxic polyacetylenes from the marine sponge Petrosia sp.

Three C46 (1-3) and three C30 (4-6) polyacetylenic alcohols with cytotoxic activity against a small panel of human solid-tumor cell lines have been isolated from the marine sponge Petrosia sp. Although compound 1 was identified as the stereoisomer of petrocortyne A, the structures of compounds 2-5 have not been previously reported and were established by spectral methods. Compound 6 was identified as the known compound petrosiacetylene D. The stereochemistry of compounds 1-5 was determined by the modified Mosher's method.

Acetylene

The nuclei innervating digastric muscle do not project to the hypoglossal nucleus in the rat.

We employed the retrograde neural tracing method using the pseudorabies virus bartha strain (PRV-Ba) to investigate the projection from accessory trigeminal nucleus (Acc5) or accessary facial nucleus (Acc7) to hypoglossal nucleus (HP). After injection of PRV-Ba into the bellies of the digastric muscle, the PRV-Ba containing neurones were observed in Acc5 of the cranial belly injected rats and Acc7 of caudal belly injected rats ipsilaterally, but not in HP. These results suggest that Acc5 and Acc7 may not project to HP and that movements of the digastric muscle are not related to cooperation with tongue movements during mastication.

Animals

The coexistence of calcitonin gene-related peptide and substance P in pericellular arborization and satellite cell of goat trigeminal and nodose ganglia.

Pericellular arborization is reported to be the self-regulating structure in sensory ganglia. Although the calcitonin gene-related peptide (CGRP) or substance P (SP) immunoreactive pericellular arborization appeared in the sensory ganglia, there was no available information that CGRP and SP colocalize in this structure. As the attempts to resolve the question described above, the present study was undertaken to identify the coexistence of CGRP and SP in pericellular arborizations of the goat nodose and trigeminal ganglia by double immunohistochemistry. As the results show, CGRP immunoreactivity was present in every pericellular arborization containing SP immunoreactivity in trigeminal ganglia, however, pericellular network containing CGRP or SP immunoreactivity was not present in nodose ganglia. Unexpectedly, a few small satellite elements were observed to contain intense CGRP and SP immunoreactivity at the periphery of CGRP and SP immunoreactive neurones in nodose ganglia. Therefore, these results suggest that CGRP and SP coexist in pericellular arborizations, and that satellite cell as well as pericellular arborization may be involved in intraganglionic regulation of goat sensory ganglia.

Animals

Eradication of Helicobacter pylori infection did not lead to cure of duodenal mucosa-associated lymphoid tissue lymphoma.

Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or association with Helicobacter pylori infection. This report describes the case of a 76-year-old man with a polypoid mass in the duodenal bulb, diagnosed as low-grade MALT lymphoma. H. pylori infection in the duodenal mucosa was confirmed by histology with silver stain. Endoscopic examination showed that the gross lesion regressed after the eradication of H. pylori despite its histopathologic persistence. Ten months later, however, cervical and intraperitoneal lymphadenopathy and bone marrow involvement was observed, and the pathologic diagnosis of the cervical lymph node was identical with that of the duodenal lesion.

Aged

Primary total hip arthroplasty with the AML total hip prosthesis.

Primary total hip arthroplasty using an uncemented AML total hip prosthesis (trispiked cup and a 4/5 porous coated stem) was performed in 50 patients (52 hips). The average age of the patients at the time of surgery was 47.6 years (range, 19-68 years), and the diagnosis was osteonecrosis of the femoral head in 18 hips, osteoarthritis in 16, fracture of the femoral neck in 14, osteoarthrosis secondary to childhood pyogenic arthritis in two, childhood tuberculous arthritis in one, and traumatic arthritis in one. The average followup was 11.3 years (range, 11-12 years). The average preoperative Harris Hip Score was 59 points, which improved to 90 points. Twenty-five (48%) hips had excellent results, 14 (27%) had good results, three (6%) had fair results, and 10 (19%) had poor results. The overall rate of revision was 15% (eight hips). The rate of revision of the femoral component was 2% (one hip), and the rate of revision of the acetabular component was 15% (eight hips). Twenty (38%) hips had acetabular and femoral osteolysis. Nine (17%) hips had femoral osteolysis only. Thirty-four (65%) hips had an average of 3.3 mm (range, 2-12 mm) of wear in the polyethylene liner. The average wear rate was 0.29 mm (range, 0.17 to 1.04 mm) per year.

Adult

Two cases of Chromobacterium violaceum infection after injury in a subtropical region.

Chromobacterium violaceum is a gram-negative rod and is isolated from soil and water in tropical and subtropical regions. The species have pigmented and nonpigmented colony types. Infections caused by nonpigmented strains are rare. We report on two cases of infection caused by both pigmented and nonpigmented strains of C. violaceum. Two 24-year-old Korea Airline stewardesses were admitted to Inha University Hospital, Inchon, South Korea, on 9 August 1997, 3 days after an airplane accident in Guam. Both had multiple lacerations on exposed parts of their bodies. There was swelling, tenderness, and pus discharge. The wounds contained many small fragments of stones and weeds. A pigmented strain was isolated from the left hand and a nonpigmented strain was isolated from the left knee of one patient. For the other patient only a nonpigmented strain was isolated from a foot wound. The nonpigmented colonies from the left-knee and the left-foot wounds did not produce any pigment even after an extended period of incubation. The biochemical characteristics were the same for each strain except for oxidase and indole reactions. The pigmented strain was oxidase negative and indole positive, whereas the nonpigmented strains were oxidase positive and indole negative. The patients were successfully treated by debridement and with appropriate antibiotics.

Accidents, Occupational

Total knee arthroplasty in bony ankylosis in gross flexion.

Between June 1993 and December 1994, we performed total knee arthroplasty (TKA) on 27 knees in 24 patients with spontaneous bony ankylosis in severe flexion. The mean age at operation was 43.5 years (30 to 60). No patient had preoperative pain. Three were unable to walk and 21 could manage less than five blocks. The mean duration of the ankylosis was 18.7 years (13 to 25) and its mean position was 105 degree flexion (75 to 135). The preoperative Hospital for Special Surgery Knee Score of 60 points was improved to 87 at the final follow-up three to five years later. All knees were free from pain. The mean range of active flexion in 24 knees was 97 degrees (78 to 115) and the mean arc of movement 91 degrees (78 to 98). The mean fixed flexion deformity was 6 degrees (0 to 25) and the extension lag 8 degrees (0 to 25). Angular deformity was corrected to between 0 degrees and 10 degrees of valgus. Four patients were able to walk one block and 20 five to seven blocks. Thirteen knees (48%) showed some necrosis at the skin edge; one knee required arthrodesis and another resection arthroplasty. One had a recurrence of tuberculous infection requiring arthrodesis. One patient had a rupture of the quadriceps tendon. To date no prosthesis has required revision for loosening. Radiolucency of 1 mm or less about the tibial prosthesis was observed at follow-up in four of the 24 knees. Our results have shown that one-stage TKA and skeletal traction after operation can achieve correction of severe flexion deformity of the knee with marked improvement in the function and quality of life.

Adult

High-resolution CT findings of varicella-zoster pneumonia.

OBJECTIVE: The purpose of this study is to describe the high-resolution CT findings of varicella-zoster pneumonia in three immunocompetent patients. CONCLUSION: High-resolution CT findings of varicella-zoster pneumonia include nodules, nodules with surrounding ground-glass attenuation, patchy ground-glass attenuation, and coalescence of nodules; the disappearance of these features on imaging studies corresponded to healing of skin lesions in patients after antiviral chemotherapy.

Adult