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C J Kim

Publications and source records attributed to C J Kim.

At least 109 records · Page 6Linked to original sources

Increased ciliary neurotrophic factor expression in reactive astrocytes following spinal cord injury in the rat.

Expression of ciliary neurotrophic factor (CNTF) was observed in reactive astrocytes in injured spinal cord of the adult rat. After unilateral incision of the dorsal funiculus at a midthoracic level, the rats were sacrificed on the day of postoperation (DPO) 3, 7, 14 or 28. Western blot analysis of spinal cord extracts showed that the intensity of the CNTF-immunoreactive band of 24 kDa was increased on DPO 3 and 7 and decreased on DPO 14. CNTF- or glial fibrillary acidic protein (GFAP)-like immunoreactivity was also increased progressively in the injured dorsal funiculus and adjacent gray matter. Double immunofluorescence histochemistry revealed that all CNTF-like immunoreactive cells showed GFAP-like immunoreactivity. The CNTF upregulation in the reactive astrocytes may play important roles in repair process after spinal cord injury.

Animals↗

Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination.

Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted. To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100(209-217). G209/g209-2M-reactive CTL were identified in post- but not prevaccination PBL. Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR Vbeta6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1-35. Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic lesion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone.

Amino Acid Sequence↗

Stringent allele/epitope requirements for MART-1/Melan A immunodominance: implications for peptide-based immunotherapy.

The exclusiveness of the relationship between peptide and HLA alleles, combined with their extensive polymorphism, emphasizes the need for immunization strategies based on endogenous processing of full length proteins (containing multiple epitopic determinants) for presentation to T cells. This could allow vaccination regardless of the patient's HLA phenotype, assuming that individual molecules can be efficient T cell Ags in association with various HLA alleles. An endogenous system of Ag presentation was developed using dendritic cells infected with recombinant viral vectors expressing the melanoma-associated Ag MART-1/Melan A. CD8+ T cells from melanoma patients were activated in vitro by coincubation with infected dendritic cells and tested for recognition of HLA-A-matched melanoma targets. This allowed the analysis of T cell induction in association with any HLA-A allele of a given patient's phenotype. In this system, MART-1/Melan A could not efficiently immunize in association with HLA-A alleles other than A*0201, including the one residue variant from A*0201: HLA-A*0226. Clonal analysis of MART-1/Melan A-specific CTL confirmed that MART-1/Melan A immunodominance is strongly restricted to the AAGIGILTV/HLA-A*0201 combination. The stringent epitope/allele requirements for MART-1/Melan A/TCR interactions were not associated with limitations in the TCR repertoire. In conclusion, autologous induction of MART-1/Melan A CTL by whole Ag processing and presentation is restricted to a unique allele/ligand combination and is excluded by minimal changes in HLA structure. Thus, whole protein vaccination for small m.w. Ags may provide no further advantage over a peptide-based approach.

Alleles↗

HPV-16-related proteins as the serologic markers in cervical neoplasia.

OBJECTIVE: Recently, a variety of HPV-related proteins have been synthesized and their utility as diagnostic and prognostic markers in cervical cancers needs to be assessed. The ability to generate preparative amounts of HPV-16 L1/L2 VLPs and E6, E7 proteins may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses. The purpose of the study is to improve the way of proper management of the cervical cancer by investigating the utility of the recently developed HPV-16 L1/L2 VLPs, HPV-16 E6, E7 proteins as the clinical serologic markers through antibody reactions by comparison with those of SCCA and CEA which have been used as tumor markers for cervical cancer. METHODS: The serologic responses in Korean women with cervical neoplasia by ELISA using HPV-16 L1/L2 VLPs and radioimmunoprecipitation assay (RIPA) using in vitro translated HPV-16 E6, E7 proteins were investigated. PCR using E6 type-specific primers for HPV-16/18 was used to determine the presence and type of HPV infection (normal controls, 15 cases; preinvasive lesions, 28 cases; invasive cervical cancers, 124 cases). RESULTS: The sera of 34% (42/124) of cervical cancers were positive for SCCA and the sera of 18% (22/124) of cervical cancers were positive for CEA. The positivity of SCCA was increased with advancing clinical stages, but the antibody levels were not correlated with clinical stage of disease. The sera of 7% (1/15) of normal controls, 39% (11/28) of preinvasive lesions, and 56% (70/124) of patients with cervical cancer were ELISA positive for HPV-16 L1/L2 VLPs (P < 0.05). The sera of 7% (2/28) of preinvasive lesions and 51% (63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 protein (P < 0.05) and the sera of 11% (3/28) of preinvasive lesions and 33% (41/124) of cervical cancers were positive for in vitro translated HPV-16 E7 protein (P < 0.05). The antibody levels to HPV-16 E7 protein were correlated to clinical stage and tumor burden in a significant number of cervical cancers. CONCLUSIONS: These data suggest that a considerable number of patients with cervical neoplasia generated positive antibody response to L1/L2 VLPs and in vitro translated E6, E7 proteins of HPV-16. These HPV-16-associated proteins might be disease-specific markers which could be useful in an adjunctive diagnostic assay and a seroepidemiologic study of HPV-related cervical neoplasia. In particular, the monitoring of antibody to HPV-16 E7 protein seems to be valuable in the proper management of cervical cancers for specific tumor markers.

Antibodies, Viral↗

Risk factors for the prediction of treatment failure in gestational trophoblastic tumors treated with EMA/CO regimen.

OBJECTIVE: The purpose of this study was to determine the independent risk factors for resistance to EMA/CO chemotherapy in gestational trophoblastic tumor (GTT), to develop a more accurate scoring system for the evaluation of high-risk GTT patients. METHODS: We performed a retrospective study and reviewed 165 GTT patients who received the EMA/CO regimen. Among these patients, 27 showed resistance to EMA/CO. RESULTS: According to the univariate analysis of risk factors, tumor age, initial human chorionic gonadotropin level, metastatic site, number of metastatic organs, unplanned operation, gravidity, and inadequate previous chemotherapy all showed statistical significance. However, the results of the stepwise-Cox proportional hazards regression of prognostic factors using multivariate analysis showed statistical significance for tumor age, number of metastatic organs, metastatic site, and previously inadequate chemotherapy. The results of the stepwise logistic regression of prognostic factors showed tumor age and number of metastatic organs as significant. According to the performance of the fitted logistic regression model, the accuracy of predicted death and survival was 80.5%. CONCLUSIONS: We determined that the following factors indicate a poor prognosis: (1) tumor age greater than 12 months, (2) number of metastatic organs greater 2, (3) incomplete previous treatment, including unplanned operation and inadequate chemotherapy. In patients with two and three of these factors, the death rates were 17.7 and 56.6%, respectively.

Adult↗

The involvement of protein kinase C and tyrosine kinase in vanadate-induced contraction.

Gastric smooth muscle of cats was used to investigate the involvement of protein kinase in vanadate-induced contraction. Vanadate caused a contraction of cat gastric smooth muscle in a dose-dependent manner. Vanadate-induced contraction was totally inhibited by 2 mM EGTA and 1.5 mM LaCl3 and significantly inhibited by 10 microM verapamil and 1 microM nifedipine, suggesting that vanadate-induced contraction is dependent on the extracellular Ca2+ concentration. and the influx of extracellular Ca2+ was mediated through voltage-dependent Ca2+ channel. Both protein kinase C inhibitor and tyrosine kinase inhibitor significantly inhibited the vanadate-induced contraction and the combined inhibitory effect of two protein kinase inhibitors was greater than that of each one. But calmodulin antagonists did not have any influence on the vanadate-induced contraction. On the other hand, both forskolin (1 microM) and sodium nitroprusside (1 microM) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinase C and tyrosine kinase are involved in the vanadate-induced contraction which required the influx of extracellular Ca2+ in cat gastric smooth muscle, and that the contractile mechanism of vanadate may be different from that of agonist binding to its specific receptor.

Animals↗

p53 mutation and overexpression in hepatocellular carcinoma and dysplastic nodules in the liver.

In hepatocarcinogenesis, both de novo and multistep pathways have been suggested and in the latter a dysplastic nodule is the proposed precancerous lesion. In this study, we tried to ascertain whether or not the p53 gene is altered in low-grade/high-grade dysplastic nodules (LDN/HDN) and to determine the role of p53 alteration in multistep hepatocarcinogenesis. Eight hepatocellular carcinomas (HCCs), 9 HDNs, 17 LDNs and 25 cirrhotic nodules (LCs) were examined by polymerase chain reaction-single strand conformation polymorphism/direct sequencing and immunohistochemical staining for p53. Four of the 8 HCCs (50%) revealed p53 overexpression and 2 (25%) had missense mutations. Four of the 9 HDNs (44%) showed weak and/or focal p53 overexpression but none had mutation in the exons examined. Neither p53 overexpression nor mutation was found in 17 LDNs and 25 LCs. These results suggest that p53 mutation might be an unusual event in precancerous lesions of multistep hepatocarcinogenesis (DN-HCC sequence) and may play a less crucial part than in colorectal carcinogenesis.

Aged↗

Erythrocyte lysate releases Ca2+ from IP3-sensitive stores and activates Ca(2+)-dependent K+ channels in rat basilar smooth muscle cells.

Erythrocyte lysate increases intracellular Ca2+ ([Ca2+]i), contracts cerebral arteries and has been suggested to be the causative agent for cerebral vasospasm. However, the mechanism of erythrocyte lysate-induced [Ca2+]i mobilization is not clear. This study was undertaken to investigate the action of erythrocyte lysate on [Ca2+]i mobilization by monitoring [Ca2+]i and the Ca(2+)-dependent K+ channels (KCa) in freshly isolated rat basilar artery smooth muscle cells. In a [Ca2+]i imaging study, erythrocyte lysate produced a biphasic response, a transient peak and a prolonged plateau [Ca2+]i elevation. In the absence of external Ca2+, erythrocyte lysate induced only a transient peak [Ca2+]i response without a marked plateau phase, indicating the [Ca2+]i was Ca2+ released from internal stores. Erythrocyte lysate-induced plateau [Ca2+]i response was resistant to nicardipine, a voltage-dependent Ca2+ channel blocker, but was abolished by EGTA. Elevation of [Ca2+]i induced by erythrocyte lysate contracted smooth muscle cells. In the electrophysiological study, elevation of [Ca2+]i by erythrocyte lysate increased KCa currents in whole-cell patch-clamp configuration. This effect of erythrocyte lysate on KCa was blocked by heparin, an antagonist of IP3 receptors. We conclude that erythrocyte lysate releases Ca2+ from IP3-sensitive intracellular stores and produces Ca2+ entry from voltage-independent Ca2+ pathways.

Animals↗

Expression of uroplakin Ib and uroplakin III genes in tissues and peripheral blood of patients with transitional cell carcinoma.

Uroplakins (UPs), urothelium-specific transmembrane proteins, are present only in urothelial cells. We have determined the nucleotide sequences of human UP-Ib and UP-III and synthesized specific primer pairs. The two UP genes were expressed in both cancerous and noncancerous urothelial taken from all patients examined by reverse transcription-polymerase chain reaction (RT-PCR). These genes were also detected in the peripheral blood of 3 patients with metastatic transitional cell carcinoma (TCC), but not in that from 9 patients with non-metastatic TCC or 3 healthy volunteers. The sensitivity of our assay was sufficient to detect one cancer cell in 5 ml of peripheral blood. Detection of UP gene-expression in blood by RT-PCR may provide helpful information for the diagnosis and management of TCC.

Adult↗

Azathioprine-induced megaloblastic anemia with pancytopenia 22 years after living-related renal transplantation.

Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in renal transplant recipients treated with azathioprine (Az). However, severe anemia is a rare side effect of Az. We recently observed a case of severe megaloblastic anemia with pancytopenia in a renal transplant recipient who had been receiving Az therapy for 22 years. The patient was a 46-year-old woman who had been administered Az and prednisolone at a dose of approximately 1.7 mg/kg and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She did not have vitamin B12 or folate deficiency. Therefore, FK506 (tacrolimus), a macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells and is known to have less myelosuppression than Az, was substituted for Az. Although the leukopenia improved, the anemia and thrombocytopenia did not improve in the short term. She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. Although it was impossible to evaluate the long-term effects of FK506 therapy for the pancytopenia in our case, the conversion from Az to a less myelosuppressive drug, such as FK506, should be considered in renal transplant recipients with severe myelosuppression caused by long-term Az treatment.

Anemia, Megaloblastic↗

Antitumor killer lymphocytes in the peripheral blood of a patient with transitional cell carcinoma of the bladder.

BACKGROUND: Peripheral blood lymphocytes (PBL) from patients with bladder cancer also contain cells possessing cytotoxic activity against autologous tumor cells. These cells are phenotypically heterogenous and include natural killer (NK) and cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes directed against autologous bladder cancer cells. METHODS: PBL were obtained at intervals before and after surgery and analyzed for cytotoxic activity against autologous bladder cancer cells in 4-hour 51Cr release assay. PBL stimulated with autologous tumor cells were also transformed with human T-lymphotropic virus type-1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic activity against the autologous tumor cells. RESULTS: PBL preoperative cytotoxic activity was low, but increased after surgery. Cytotoxic activity was found not only against autologous bladder cancer cells, but also against heterologous bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest activity against the heterologous cell lines. The cytotoxic activity of KB31 was 40% against autologous tumor cells 6 weeks after initiation of the cell line, but decreased to 5% by 6 months. This activity was lower than that against the other cell lines, and was similar to that of PBL in short-term culture. Fluorescence-activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks, CD8+ cells were dominant, but CD56+ cells predominated at 6 months. CONCLUSION: These results suggest that the presence of cytotoxic activity in the peripheral blood of the patient was due to both cytotoxic T cells and NK cells. The cytotoxic activity was lowest prior to surgery and increased postoperatively.

Aged↗

Choledochal cyst with or without biliary atresia in neonates and young infants: US differentiation.

PURPOSE: To differentiate at ultrasonography (US) between the choledochal cyst associated with biliary atresia (CCBA) and that in the absence of biliary atresia (CC) in neonates and young infants. MATERIALS AND METHODS: Preoperative US findings in 28 neonates and infants younger than 4 months in whom choledochal cyst was subsequently surgically confirmed were retrospectively analyzed. There was no statistically significant difference in age between the CCBA group (n = 19) and the CC group (n = 9). US findings in both groups were compared, with focus on the size of the cyst in the hepatic portal, dilatation of the intrahepatic bile ducts, and the size and morphology of the gallbladder. RESULTS: At US, the width and length of the cysts in the hepatic portal in the CC group were significantly larger than those in the CCBA group (P < .001). Dilatation of the intrahepatic bile ducts, seen in only one patient (5%) of the CCBA group, was observed in all patients (100%) of the CC group. The gallbladder was normal or distended in all patients of the CC group, while it was atretic or irregularly elongated in 17 patients (89%) of the CCBA group. CONCLUSION: US can be helpful in the preoperative differential diagnosis of choledochal cysts in neonates and infants. Cysts are larger, intrahepatic ducts are dilated, and gallbladders are not atretic in patients with CC as compared with those in patients with CCBA.

Bile Ducts, Intrahepatic↗

Gamma knife treatment of acoustic neurinoma.

The results of treatment of acoustic neurinomas using Gamma Knife radiosurgery (GKR) during a 6-year period in our center were reviewed. Since May 7, 1990, we treated 88 cases of acoustic neurinoma with GKR. During a 52-month mean follow-up period, MRI was obtained in 63 patients. Reduction in tumor size occurred in 34 (54%) cases, and another 27 (42.8%) tumors showed no change. The tumor control rate was thus 95%. Tumor size increased in 3 (4.8%) cases, but one case is still in early follow-up. Two cases were operated after GKR. Histological examination of the tumors removed at surgery 8 months after GKR were obtained. The examinations showed enlargement of nucleoli and cytoplasm and proliferation of endothelial cells due to delayed radiation changes. Post-GKR facial neuropathy was noted in 7 (8.8%) patients, of which 4 recovered during the follow-up period. The tumor volume, margin dose, number of isocenters and marginal isodose did not have any statistically significant relationship with the development of facial neuropathy. Transient trigeminal neuropathy were noted in 3 patients. Hearing was preserved in 2 of 3 hearing patients. In conclusion, our GKR results for acoustic neurinomas were very similar to the previously reported series, which makes GKR for acoustic tumors an excellent treatment modality for small- to medium-sized tumors with or without microsurgical tumor removal.

Adolescent↗

Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets.

This study investigated the effects of polymer molecular weight, drug solubility, addition of a water-soluble excipient, and drug loading on zero-order release kinetics and elucidated the release mechanism of a drug from directly compressed tablets. Directly compressed tablets consisting of polyethylene oxides (PEO) (MW = 0.9, 2.0 and 4.0 x 10(6)) and drugs (solubility ranging from 290 to 25,000 mg/l) were formulated with or without a water-soluble excipient (lactose). For PEO tablets (MW = 0.9 x 10(6)), drug release is primarily swelling/erosion controlled for drugs for which solubility is below 1%, resulting in zero-order release kinetics. For PEO tablets (MW = 4.0 x 10(6)), drug release is controlled at a zero-order rate by the dissolution rate of the drug at high loading (39%). At low loading (20%), drug diffusion through the swollen gel layer becomes the governing release mechanism. For a highly water-soluble drug (e.g., diclofenac Na), drug diffusion is the controlling mechanism regardless of the molecular weight of the PEOs. Zero-order release kinetics can be achieved with PEO tablets (MW = 0.9 x 10(6)) for drugs for which solubility is below 1%. PEO tablets (MW = 2.0 x 10(6)) provided zero-order release for poorly water-soluble drugs (below 0.2%) at 39% drug loading. It is possible to attain zero-order release kinetics with PEO tablets (MW = 4.0 x 10(6)) using a drug which has a solubility of less than 0.1%.

Diclofenac↗

Role of tyrosine kinase in erythrocyte lysate-induced contraction in rabbit cerebral arteries.

OBJECT: This study was undertaken to explore whether erythrocyte lysate, a proposed cause of vasospasm, produces vasoconstriction by activation of tyrosine kinase in rabbit cerebral arteries. METHODS: Isometric tension was used to monitor contractions in rabbit basilar arteries induced by erythrocyte lysate, 5-hydroxytryptamine (5-HT), or KCl in the absence or presence of tyrosine kinase inhibitors. Erythrocyte lysate, 5-HT, or KCl produced concentration-dependent contractions in rabbit basilar arteries. Preincubation with the tyrosine kinase inhibitors tyrphostin A23 and genistein (30 and 100 microM), but not diadzein, an inactive analog of genistein, attenuated significantly the contraction induced by erythrocyte lysate (p < 0.05). Tyrphostin A23, genistein, and diadzein (30 microM) failed to reduce the contraction caused by 5-HT. Genistein, but not tyrphostin A23 or diadzein (30 microM), attenuated significantly the contraction induced by KCl (p < 0.05). In another series, arterial rings were initially contracted with erythrocyte lysate, 5-HT, or KCl and the relaxant effect of genistein was then tested. Genistein relaxed rabbit basilar arteries that had been contracted by exposure to erythrocyte lysate, 5-HT, or KCl (30-100 microM; p < 0.05). CONCLUSIONS: These data indicate that tyrosine kinase may play a role in the regulation of cerebral arterial contraction and tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm.

Animals↗

Histotopographic distribution of placental inflammation: analysis of 22 cases.

Twenty-two placentas were investigated for the presence and patterns of inflammation by extensive examination, and divided into four groups: 1) term vaginal delivery [group I; n=6]; 2) term cesarean section delivery [group II; n=5]; 3) preterm vaginal delivery [group III; n=4], and 4) preterm cesarean section delivery [group IV; n=7]. In group I, all had deciduitis, and choriodeciduitis/ chorionitis was present in two cases (33.3%). In group II, four cases (80%) showed deciduitis and/or choriodeciduitis/chorionitis; three of these had intact membranes. In group III, three cases (75%) showed deciduitis, and two had chorionitis. In group IV, three cases (42.9%) showed no evidence of inflammation, three had deciduitis and one had deciduitis/chorioamnionitis. In all groups, membranitis was more severe, confined to the inner and mid segments in general, and deciduitis, choriodeciduitis/chorionitis and chorioamnionitis tended to overlap. The study newly demonstrates major characteristics of placental inflammation: higher prevalence and severity of inflammation in the inner segments of membrane and at the periphery of the placenta. Taking this histotopography into account, it is desirable to take sections from the placental margin, and the current concept of placental inflammation as a surrogate marker of intrauterine infection should be reevaluated.

Female↗

Fanconi anemia screening by diepoxybutane and mitomicin C tests in Korean children with bone marrow failure syndromes.

Fanconi anemia (FA) is an autosomal recessive disorder of progressive bone marrow failure in patients with congenital malformations. FA is different from acquired aplastic anemia (AA) in terms of the natural course and treatment options. As the frequency of FA is unknown in Korea, we conducted screening tests using DNA clastogenic agents, diepoxybutane (DEB) and mitomicin C (MMC) in southwestern Korea. Forty-three children with AA or other bone marrow failure syndromes and siblings of known FA were evaluated. Six patients with AA (6/24=25.0%) and a 2-month-old patient with myelodysplastic syndrome were found to have increased chromosomal breakage to both DEB and MMC, confirming the diagnosis of FA. No overlap in chromosomal breakage to both agents was found between the FA group and non-FA group. The frequency of FA in this study, much higher than those of previous studies in Korea which did not incorporate the above tests, was similar to that of other countries. DEB and MMC tests were readily feasible and useful in screening FA in patients with AA as well as other bone marrow failure syndromes. A nation-wide screening and registry for FA should be initiated since FA requires different therapeutic and management options from idiopathic AA.

Adolescent↗

[Adenocarcinoma of the bladder 19 years after the augmentation ileocystoplasty: report of a case].

We report a case of adenocarcinoma of the augmented bladder 19 years after ileocystolasty. The patient was a 53-year-old man who underwent right nephrectomy and ileocystoplasty (Pyrah's method) for contracted bladder due to tuberculosis in 1965. In another hospital, transurethral resection (TUR) was performed against a tumor in the anastomotic site between the bladder and the ileal segment in 1996. Histopathological examination of the specimen obtained by TUR revealed poorly-differentiated mucinous adenocarcinoma. In our hospital, partial cystectomy with total resection of ileal segment and ileocystoplasty were performed. The tumors located in the anastomotic site between the bladder and ileal segment as well as in the ileal segment. Histopathological examination revealed poorly-differentiated mucinous adenocarcinoma. The patient has survived 12 months without any evidence of tumor recurrence. To our knowledge, this is the eighth case report in Japan.

Adenocarcinoma, Mucinous↗