Search PubMed⌕ Search

Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 217 records · Page 12Linked to original sources
PubMed1997

Regression analysis of interval-censored survival data with covariates using log-linear models.

We considered the regression analysis of the event time data with left-, right-, or interval-censored observations. We extended life-table techniques for censored survival data using log-linear models to incorporate interval-censored failures. The EM algorithm was used to calculate maximum likelihood estimates for the parameters. We assumed that the hazard function was a stepwise function over disjoint intervals of time; thus, the nonparametric model, the parametric exponential model, and the semiparametric Cox proportional hazard model were easily implemented as special cases. We adapted the restricted EM algorithm to test hypotheses and to construct confidence intervals for the parameters. These methods were applied in an analysis of the recurrence time for treated melanoma patients.

Adult↗
PubMed1996

Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25.

Presynaptic Ca2+ channels are crucial elements in neuronal excitation-secretion coupling. In addition to mediating Ca2+ entry to initiate transmitter release, they are thought to interact directly with proteins of the synaptic vesicle docking/fusion machinery. Here we report isoform-specific, stoichiometric interaction of the BI and rbA isoforms of the alpha1A subunit of P/Q-type Ca2+ channels with the presynaptic membrane proteins syntaxin and SNAP-25 in vitro and in rat brain membranes. The BI isoform binds to both proteins, while only interaction with SNAP-25 can be detected in vitro for the rbA isoform. The synaptic protein interaction ("synprint") site involves two adjacent segments of the intracellular loop connecting domains II and III between amino acid residues 722 and 1036 of the BI sequence. This interaction is competitively blocked by the corresponding region of the N-type Ca2+ channel, indicating that these two channels bind to overlapping regions of syntaxin and SNAP-25. Our results provide a molecular basis for a physical link between Ca2+ influx into nerve terminals and subsequent exocytosis of neurotransmitters at synapses that have presynaptic Ca2+ channels containing alpha1A subunits.

Amino Acid Sequence↗
PubMed1996

Role of the 70-kDa subunit of human replication protein A (I). Single-stranded dna binding activity, but not polymerase stimulatory activity, is required for DNA replication.

Replication protein A (RPA), also known as human single-stranded DNA-binding protein, is a three-subunit protein complex with multiple functions. Here, we investigated the role of the 70-kDa RPA subunit (p70) in DNA replication, by generating a series of deletion mutants. Mutant p70, which lacked 50 amino acids at the C-terminus, failed to interact with the 11-kDa RPA subunit (p11) and, when deleted further at the C terminus, was unable to interact with either the 34-kDa subunit (p34) or with p11, suggesting that p70 directly interacts with both p34 and p11. Studies with purified RPA mutants indicated that deletions at the N-terminal domain of p70 had very little effect on RPA's single-stranded DNA (ssDNA) binding activity, whereas deletion of amino acids 169-246 significantly weakened the DNA binding ability of RPA. By deleting amino acids 296-373 or 374-458, we totally abolished p70's ssDNA binding activity, suggesting that multiple p70 domains are involved in DNA binding. Two p70 domains, the N-terminal domain and the DNA binding domain, were required to stimulate DNA polymerase (pol) alpha, yet the DNA binding domain alone supported pol delta activity. Interestingly, RPA containing p70 with a zinc-finger domain deletion retained its DNA binding activity, but inhibited pol alpha and delta activity. RPA that lacked ssDNA binding activity failed to support simian virus 40 (SV40) DNA replication in vitro, whereas mutant RPA that lacked pol alpha stimulatory activity (including the zinc-finger p70 mutant) functioned normally. We conclude that RPA's DNA binding activity, but not its pol alpha stimulatory activity, is required for DNA replication.

Animals↗
PubMed1996

Expression of epidermal growth factor receptor in carcinoma of the cervix.

Increased expression of the epidermal growth factor receptor (EGFR) gene has been shown in a large number of tumors, generally indicating a more aggressive biological behavior of cancers than those with low or normal expression. The role of EGFR in the tumorigenesis of the uterine cervix has been poorly understood and controversial. In order to explore the relationship between EGFR status and cervical carcinoma, tissues were analyzed from 40 patients, each of whom had invasive cervical carcinoma prior to treatment, 20 patients with cervical intraepithelial neoplasia (CIN) and 10 control cases who underwent hysterectomy due to benign gynecological disease at Yonsei University College of Medicine. We measured EGFR with an enzyme-linked immunosorbent assay which was a sandwich type using a mouse monoclonal capture antibody and a rabbit antiserum as detector. Patients with invasive cervical cancer were found to have significantly higher median EGFR expression than either the patients with CIN (P = 0.002) or the control (P = 0.001), respectively. However, there was no significant difference in EGFR status between CIN and the control groups. Overexpression of EGFR was found in 29 of 40 (72.5%) invasive cervical cancers and in 5 of 20 (25%) CIN patients. In invasive cervical cancer, no significant difference in EGFR levels was noted when stratified according to age, menopausal status, histological cell type, or clinical stage. With regard to tumor size, lesions of 4 cm and larger had significantly higher receptor levels than those lesions under 4 cm (P = 0.003). Even though quantitative EGFR status did not correlate with other prognostic parameters except tumor size, our results were consistent with the concept that EGFR may play an important role in malignant transformation and tumorigenesis in cervical cancer.

Adult↗
PubMed1996

Antianaphylactic activity of Poncirus trifoliata fruit extract.

The effect of an aqueous extract of Poncirus trifoliata (L.) Raf. (Rutaceae) fruits (PTFE) on compound 48/80-induced mortality associated with anaphylaxis was studied in rats. PTFE inhibited compound 48/80-induced anaphylaxis 100% with a dose of 1.6 mg/g body weight (BW) 1 h before or 5 min after injection of compound 48/80. PTFE inhibited compound 48/80-induced anaphylaxis almost 100% with doses above 0.4 mg/g BW intraperitoneally administered. PTFE (1-1000 micrograms/ml) also dose-dependently inhibited the histamine release induced by compound 48/80 (5 micrograms/ml) in rat peritoneal mast cells. The level of cAMP in peritoneal mast cells, when PTFE was added, increased transiently, and significantly increased 53-fold at 10 s compared with that of basal cells. Moreover, PTFE inhibited intracellular calcium release induced by compound 48/80. These results suggest that PTFE has antianaphylactic activity by stabilizing the peritoneal mast cell membrane.

Anaphylaxis↗
PubMed1996

Meningiomas in the region of the cavernous sinus: a review of 21 patients.

This is a review of 21 patients with meningiomas involving the region of the cavernous sinus. All underwent surgery, and the fronto-zygomatic (F-Z) approach, first described by Fujitsu and Kubawara, was employed in every case. The mean age at presentation was 47 years; seven patients were male and 14 female. The mean duration of symptoms before surgery was 4 years. In 10 patients, resection was considered to be complete. Peri-operatively there were two deaths, but the majority of deficits in the survivors were temporary and quickly resolved. The mean follow-up period was 48 months. In that time, five patients experienced recurrence or progression of tumour, of whom three required repeat operation (followed by radiotherapy); and two patients were referred for radiotherapy alone. These five patients appear to be disease-free 2-5 years after their additional treatment. Of the 19 patients who left hospital, 17 were able to live independent lives. It would appear from this review that: (1) F-Z craniotomy usually gives excellent exposure to the region of the cavernous sinus; (2) selected patients should undergo angiography with balloon occlusion to evaluate the collateral vascular supply; (3) regular review should include annual MRI. Evaluation over a much longer time of both surgery and radiotherapy, individually and in combination, is needed before it will be possible to furnish a treatment protocol for individual cases at initial presentation or recurrence.

Adult↗
PubMed1996

Effect of 13-cis-retinoic acid with neoadjuvant chemotherapy in patients with squamous cervical carcinoma.

Retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. Recently, therapeutic trials of retinoids have demonstrated activities in cervical cancer and precancerous lesion of cervix. Our purpose was to determine whether additional administration of 13-cis-retinoic acid would improve the treatment effect of neoadjuvant chemotherapy in patients with squamous cell carcinoma of the cervix. From January 1994 through January 1995, 40 patients with invasive cervical cancer were enrolled in this prospective study and randomized into the two groups. Group 1 had neoadjuvant chemotherapy alone and group 2 had neoadjuvant chemotherapy plus 13-cis-retinoic acid (RA) at a dosage of 1 mg/kg/day for 1 month. Patients in group 1 and group 2 were similar with respect to age, parity, clinical stage, and histological subtype. Therapeutic responses were compared using Fisher's exact test, Mann-Whitney test, and Wilcoxon signed-rank test. RA increased the complete response rate of neoadjuvant chemotherapy from 0% in group 1 to 5% in group 2. However, a difference of overall clinical response rate between the two groups was not evident. The drug toxicities in group 1 and group 2 included anemia in 30.0% and 23.7%, leukopenia in 6.7% and 15.2%, and hepatotoxicity in 6.7% and 6.8%, respectively. More frequent incidence of mucocutaneous side effects was seen in group 2 than group 1, but these side effects were mild and reversible. The clinical response rate achieved in this trial indicates that the combination of 13-cis-retinoic acid and neoadjuvant chemotherapy, at least when used on the schedule reported herein, is not superior to treatment of neoadjuvant chemotherapy alone for patients with squamous cell carcinoma of the cervix. However, a single patient achieved a complete response on this therapy, and the impact of such a treatment on survival needs to be explored.

Adult↗
PubMed1996

Hydrocephalus secondary to diffuse villous hyperplasia of the choroid plexus. Case report and review of the literature.

Diffuse villous hyperplasia of the choroid plexus, which is distinct from bilateral choroid plexus papillomas, is extremely rare and is often associated with hydrocephalus due to the overproduction of cerebrospinal fluid (CSF). The authors describe an infant with hydrocephalus, diagnosed by computerized tomography scanning, who developed ascites following placement of a ventriculoperitoneal shunt and, subsequently, demonstrated excessive CSF production when the shunt was externalized. The patient was later successfully treated by placement of a ventriculoatrial shunt. Magnetic resonance imaging demonstrated diffuse villous hyperplasia of the choroid plexus as the cause of the patient's hydrocephalus. The literature on diffuse villous hyperplasia of the choroid plexus is reviewed.

Choroid Plexus↗
PubMed1996

Fibroepithelial ureteral polyp--a case report; endoscopic removal of large ureteral polyp.

We report a case of primary fibroepithelial polyp of the right midureter. The patient was a 41-year-old-woman, complaining of right flank pain. An excretory urogram revealed right hydronephrosis and a filling defect of the the right midureter. The filling defect was produced by a large fibroepithelial polyp that was diagnosed and removed by ureteroscopy without open surgery. Large fibroepithelial ureteral polyps are relatively rare and ureteroscopy is the gold standard of diagnosis for ureteral filling defect.

Adult↗
PubMed1996

Pharmacokinetics of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane]platinum(II) in rats.

The blood concentration-time profile, distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane]platinum(II) (CAS 146665-77-2, SKI 2053R), a new potential anticancer agent, were investigated in rats after intravenous administration of 14C-SKI 2053R. After a single intravenous administration, the radioactivity of blood declined in a biexponential fashion with the initial half-lives of 0.42 h and 0.37 h and with the terminal half-lives of 68.67 h and 64.67 h in male and female rats, respectively. Radioactivity was distributed very rapidly and extensively into all tissues except the central nervous system. The major amount of the radioactivity was found in the gastrointestinal contents, urine, and organs of elimination at all time points. The distribution pattern of 14C-SKI 2053R observed by the measurement of tissue concentrations was in accordance with that observed by whole-body autoradiography. The 0-7 days cumulative urinary and fecal recoveries of total radioactivity after a single dose were 83.0 +/- 4.5 (mean +/- S.D.) and 11.3 +/- 1.0% in male rats and 85.1 +/- 2.6 and 11.3 +/- 2.3% in female rats, respectively, resulting in total recoveries of 94.3 +/- 3.6% in male rats and 96.3 +/- 1.1% in female rats. The 0-24 h cumulative excretions of total radioactivity in the bile after a single dose were 8.7 +/- 0.4 and 15.8 +/- 3.5% in male and female rats, respectively, showing a significant sex difference.

Animals↗
PubMed1996

Mammary excretion and placental transfer of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) in rats.

The mammary excretion and placental transfer of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (CAS 146665-77-2, SKI 2053R), a new potential anticancer agent, were investigated in the lactating or pregnant rats after a single intravenous administration of 14C-SKI 2053R (20 mg/kg, 100 microCi/kg). The radioactivity of the milk declined in a biexponential fashion with an initial half-life of 0.39 h and with a terminal half-life of 14.05 h in the lactating rats. The radioactivity of the milk was lower than that of plasma until 1 h after dosing, but was higher than that of plasma from 4 h after dosing. 14C-SKI 2053R was well distributed to most tissues including uterus and placenta in the pregnant rats, but the levels of radioactivity in the amniotic fluid and fetuses were markedly lower than that in the maternal plasma. Therefore, it is concluded that SKI 2053R scarcely passes the blood-placenta barrier, which was confirmed by the whole-body autoradiography study.

Animals↗
PubMed1996

Preoperative endovascular embolization of craniospinal hemangioblastomas.

PURPOSE: To determine whether hemangioblastomas, highly vascular tumors requiring surgery that is potentially complicated by excessive bleeding, can be embolized safely by using interventional techniques that furnish a more avascular surgical field. METHODS: Nine hemangioblastomas involving either the cerebellum or the spinal cord were embolized preoperatively. In each case the feeding artery was selectively catheterized with a microcatheter and the hypervascular tumor nidus was devascularized with polyvinyl alcohol particles. RESULTS: Two patients who had undergone recent attempts as surgical resection at another institution had repeat surgery after endovascular embolization rendered the tumor nidus avascular. At surgery, the tumor was completely removed in one case and markedly debulked in the other. In all nine cases, blood loss after embolization was reported to be less than expected by experienced surgeons. In addition, manipulation and removal of the tumor was reported to be subjectively easier in these embolized tumors. The embolization procedure caused no permanent complications; however, one patient with a posterior fossa hemangioblastoma and hydrocephalus worsened clinically within 12 hours of embolization. This event was thought to be caused by obstructive hydrocephalus resulting from tumor swelling. Emergency craniotomy, ventricular decompression, and surgical resection of the tumor produced complete resolution of the signs and symptoms. CONCLUSIONS: Our results indicate that preoperative embolization of hemangioblastomas is a safe procedure that is useful in aiding surgical resection of these highly vascular tumors.

Adolescent↗
PubMed1995

Human xeroderma pigmentosum group A protein interacts with human replication protein A and inhibits DNA replication.

Human replication protein A (RPA; also known as human single-stranded DNA binding protein, or HSSB) is a multisubunit complex involved in both DNA replication and repair. While the role of RPA in replication has been well studied, its function in repair is less clear, although it is known to be involved in the early stages of the repair process. We found that RPA interacts with xeroderma pigmentosum group A complementing protein (XPAC), a protein that specifically recognizes UV-damaged DNA. We examined the effect of this XPAC-RPA interaction on in vitro simian virus 40 (SV40) DNA replication catalyzed by the monopolymerase system. XPAC inhibited SV40 DNA replication in vitro, and this inhibition was reversed by the addition of RPA but not by the addition of DNA polymerase alpha-primase complex, SV40 large tumor antigen, or topoisomerase I. This inhibition did not result from an interaction between XPAC and single-stranded DNA (ssDNA), or from competition between RPA and XPAC for DNA binding, because XPAC does not show any ssDNA binding activity and, in fact, stimulates RPA's ssDNA binding activity. Furthermore, XPAC inhibited DNA polymerase alpha activity in the presence of RPA but not in RPA's absence. These results suggest that the inhibitory effect of XPAC on DNA replication probably occurs through its interaction with RPA.

DNA Helicases↗
PubMed1995

Glutamate stably enhances the activity of two cytosolic forms of phospholipase A2 in brain cortical cultures.

The mechanisms by which glutamatergic neurotransmitters modulate neuronal lipid metabolism are not well established. We have directly measured phospholipase A2 (PLA2) enzymic activity in cell-free extracts from cortical neuronal cultures from rat brain and have found that the PLA2 activity is up-regulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA2 activity. Down-regulation of protein kinase C activity partially blocked glutamate's effects. Two Ca(2+)-and pH-dependent forms of PLA2 were identified in cytosolic extracts. Activation of both forms of PLA2 was enhanced by prior exposure of the cultures to glutamate. One of the two forms had chromatographic characteristics on heparin-Sepharose, Mono Q and Superose 12 columns similar to the 100 kDa cytosolic PLA2 (cPLA2), and was recognized by an antibody raised to pig spleen cPLA2. The second form was similar in size to Group-I and -II PLA2s but differed in chromatographic characteristics. It was not inhibited by dithiothreitol, and did not react with antibodies to pancreatic Group-I PLA2, features that distinguish it from Group-I and -II PLA2. In extracts from cells pretreated with glutamate, the activity-Ca2+ concentration dose-response relationship of the 13.5 kDa form of PLA2 was shifted to the left with activation at lower Ca2+ concentration as the result of stable modification of the enzyme induced by glutamate. Thus glutamate-induced stable enhancement of PLA2 activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch probably mediating changes in synaptic function and contributing to excitotoxicity.

Animals↗
PubMed1995

The role of the 34-kDa subunit of human replication protein A in simian virus 40 DNA replication in vitro.

Human replication protein A (RPA) is a three subunit protein complex involved in DNA replication, repair, and recombination. We investigated the role of the 34-kDa subunit (p34) of RPA in DNA replication by generating a series of p34 mutants. While deletion of the N-terminal domain of p34 prevented its phosphorylation by both cyclin-dependent kinase (Cdk) and DNA-dependent kinase, a double point mutant that lacks the major phosphorylation sites for Cdk could be phosphorylated by DNA-dependent kinase. In simian virus 40 (SV40) DNA replication, RPA containing either of these mutants functioned as efficiently as wild-type RPA. However, mutant RPA containing C-terminally deleted p34 was only marginally active. This indicates that the C-terminal region, but not the phosphorylation domain of p34, is necessary for RPA function in DNA replication. Furthermore, RPA containing the C-terminally deleted p34 mutant could stimulate DNA polymerase alpha, and bind to single-stranded DNAs but was limited in its ability to unwind DNA or interact with SV40 large T antigen (T Ag). These results suggest that RPA p34 interacts with SV40 T Ag during the initiation of SV40 DNA replication and may be necessary for DNA unwinding.

Base Sequence↗