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Biomedical subjects

Y T Kim

Publications and source records attributed to Y T Kim.

At least 91 records · Page 5Linked to original sources
PubMed1997

Correlation between G1 cyclins and HPV in the uterine cervix.

G1 cyclin, as a candidate proto-oncogene, plays a key role as a cellular regulator through direct interaction with retinoblastoma gene product (pRB), p107, and cyclin-dependent kinase. Human papillomavirus (HPV) 16/18 E6/7 proteins may bind the unphosphorylated pRB and act as a down-regulator of cyclin D. However, this theory has not been proven and the relationship between cyclin E and HPV also remains unclear. Using formalin-fixed and paraffin-embedded cervical tissues, we examined for HPV types 16 and 18 by nested polymerase chain reaction (PCR), and for the accumulation of cyclin D1 and E by immunohistochemistry in 22 cases of normal cervix, 23 cases of cervical intraepithelial neoplasia (CIN), 39 cases of invasive squamous cell carcinoma (SCC), and 6 cases of adenocarcinoma. Cyclin index (CI) was defined as the percentage of positively labeled nuclei per 1000 cells. The accumulation of cyclin D1 was detected in the normal basal and parabasal epithelium and was markedly decreased in neoplastic epithelium (0.87% CI in CIN, 5.88% in SCC). However, cyclin E was absent in the normal cervix but increased in neoplastic epithelium (7.17% CI in CIN, 10.32% in SCC). Cyclin D1 expression was significantly low (p = 0.004), but cyclin E expression was significantly high (p = 0.026) in HPV-positive cases. Cyclin E plays a leading role in neoplastic transformation whereas cyclin D is down-regulated, especially when associated with HPV.

Adenocarcinoma↗
PubMed1997

Do sheep really have problems with cardiopulmonary bypass for total artificial heart implantation?

Although the use of sheep in total artificial heart (TAH) implantation has many advantages, they are known to show a significant morbidity rate on cardiopulmonary bypass (CPB); this has been considered to be a major limiting factor in using them for TAH experiments. We conducted a series of ovine CPB experiments to evaluate the sheep's pathophysiological response to CPB. CPB-related hemolysis, bleeding, and lung dysfunction were analyzed in 5 sheep, which had undergone CPB, used at our hospital for TAH implantation. Four of the 5 sheep survived the experimental procedures, and 3 of them survived on a long-term basis. Unacceptable degrees of hemolysis related to CPB were not observed. Postoperative bleeding was not remarkable, and coagulation test results did not show significant abnormal findings. Acute lung injuries of a mild to moderate degree were found mainly at the microscopic level, but rarely had clinical significance. In conclusion, this experiment suggests that sheep can be used for the animal model for TAH implantation with acceptable risk on CPB circuits and techniques are used.

3,4-Methylenedioxyamphetamine↗
PubMed1996

Reduced growth cone motility in cultured neurons from Drosophila memory mutants with a defective cAMP cascade.

Drosophila memory mutants dunce (dnc) and rutabaga (rut) are known to have altered intracellular cAMP levels, nerve terminal growth, and plasticity of synaptic transmission. Because the growth cone is responsible for neurite outgrowth and synaptogenesis, video microscopy was used to examine growth cone morphology and behavior of mutant neurons in larval CNS cultures. We found that growth cone exploratory movement was nearly arrested by both mutations, even though they change cAMP levels in opposite directions. The dnc phenotype could be mimicked by normal neurons when perfused with dibutyryl cAMP (db-cAMP) or forskolin. In contrast, rut growth cones became active when perfused with db-cAMP. Furthermore, motility was also restored by counterbalancing the effects of the two genes in double mutants, indicating that dynamic control of growth cone motility in developing Drosophila neurons requires optimal cAMP levels within an operational range. These findings represent the first demonstration of altered growth cone properties in learning and memory mutants and establish in a natural setting the role of cAMP in growth cone motility and neuronal plasticity.

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

p53 mutations and clonality in vulvar carcinomas and squamous hyperplasias: evidence suggesting that squamous hyperplasias do not serve as direct precursors of human papillomavirus-negative vulvar carcinomas.

Previous studies of vulvar carcinomas have shown two distinct subsets with respect to several clinicopathologic features. In younger women, the tumors are frequently human papillomavirus (HPV) positive, are usually of basaloid or warty histology, and are associated with vulvar intraepithelial neoplasia. In older women, the tumors are usually HPV negative, are typical keratinizing squamous carcinomas, and are associated with squamous hyperplasia--a lesion that has been purported to serve as a precursor to HPV-negative invasive carcinoma. In squamous carcinomas of the cervix, p53 inactivation (through gene mutation or interaction with the HPV E6 oncoprotein) occurs in most cases. Comparatively few studies have assessed p53 mutation and HPV status in vulvar carcinomas, and none has used molecular markers to evaluate squamous hyperplasias as direct precursors of HPV-negative invasive cancers. Of 18 invasive squamous carcinomas analyzed, seven (39%) were found to be HPV positive. Four p53 gene mutations were identified--all in HPV-negative tumors. DNA was subsequently prepared from microdissected archival tissues from all four specimens showing p53 gene mutations. DNA was separately isolated from normal squamous epithelium, invasive squamous carcinoma, and associated squamous hyperplasia. In each specimen, the p53 mutation was confirmed in the invasive tumor and absent in both normal and hyperplastic epithelium. To further investigate squamous hyperplasia as a potential precursor of HPV-negative invasive carcinoma, the authors determined the clonality of hyperplastic lesions adjacent to invasive carcinomas with p53 mutation. Clonality analyses were performed using a polymerase chain reaction (PCR)-based assay for X chromosome inactivation. Although all three informative carcinomas tested were monoclonal, corresponding normal epithelia and hyperplastic lesions were polyclonal. These findings underscore the heterogeneity of vulvar cancers with respect to loss of wild type p53 function either by interaction with the HPV E6 oncoprotein or somatic mutation of p53, and suggest that squamous hyperplasias do not serve as direct precursors of HPV-negative squamous carcinomas.

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

Q-switched ruby laser in the treatment of nevus of Ota.

The purpose of this study is to evaluate the efficacy of Q-switched ruby laser in the treatment of nevus of Ota, a pigmented lesion on the face. The Q-switched ruby laser has been shown to remove tattoos without scarring. With this in mind, the nevus of Ota with pigmented cells in the dermis could be effectively treated with Q-switched ruby laser. Eighty patients (19 men, and 61 women) with nevus of Ota on the face were enlisted to be tested in evaluating the efficiency of Q-switched ruby laser therapy. The age of patients ranged from 1 to 62 years. The energy fluence used varied from 6 to 8.5 J/cm2. Treatment intervals ranged from 4 to 16 weeks, and the number of treatment sessions varied between 1 to 9 visits. During a 2-year follow-up period, more than fifty percent removal of nevus-pigment was noted in 64 of the 80 patients. Transient hyperpigmentation was noted in 32 patients lasting for 2 to 6 months after treatment; transient hypopigmentation was seen in 3 cases which recovered within one year. No patients had permanent textural or pigmentary changes or scarring. Q-switched ruby laser therapy appears to be an effective and safe modality for the treatment of nevus of Ota.

Adolescent↗
PubMed1995

Association of activated phosphatidylinositol 3-kinase with p120cbl in antigen receptor-ligated B cells.

A 120-kDa protein that is tyrosine-phosphorylated upon antigen receptor ligation in B lymphocytes has been identified as the product of the c-cbl protooncogene. Tyrosine phosphorylation of Cbl depends on the efficient association of membrane immunoglobulin heavy chains with the Ig alpha/beta heterodimer but is unimpaired in splenic B cells from the Xid mouse. Cross-linking of membrane IgM and membrane IgG, but not of CD40, leads to the tyrosine phosphorylation of Cbl. In receptor-ligated B lymphocytes, p120cbl associates with an 85-kDa protein that has been identified as the 85-kDa subunit of phosphatidylinositol 3-kinase.

Animals↗
PubMed1995

Identification of Trp300 as an important residue for Escherichia coli leader peptidase activity.

We previously reported that leader peptidase from Escherichia coli was extensively inactivated by reaction with N-bromosuccinimide with concomitant and selective modification of the Trp300 and Trp310 residues [Kim, Y.-T., Muramatsu, T. & Takahashi, K. (1995) J. Biochem. (Tokyo) 117, 535-544]. This indicated that one or both of these tryptophan residues are important for the activity of the enzyme. In order to define further the role of individual tryptophan residues in the activity of leader peptidase, site-directed mutagenesis studies were performed to replace each tryptophan residue with phenylalanine and/or alanine. The replacements of Trp20, Trp59, Trp261, Trp284, and Trp310 with phenylalanine hardly affected the enzyme activity toward a synthetic peptide substrate and the ability to complement the temperature sensitivity of the mutant leader peptidase in E. coli IT41. In contrast, the activity toward the synthetic substrate was significantly decreased by replacement of Trp300 with phenylalanine or alanine. The kcat values of the W300F and W300A mutant enzymes were reduced to 42% and 22%, respectively, of that of the wild-type enzyme, whereas the Km values of these mutant enzymes were almost identical with that of the wild-type enzyme. Moreover, the complementing ability in E. coli IT41 was lost (almost) completely when Trp300 was replaced with phenylalanine or alanine. These results strongly indicate that Trp300 in leader peptidase is important for the catalytic mechanism and/or the construction of the active site structure of the enzyme.

Base Sequence↗
PubMed1995

The SH2 domains of Src family kinases associate with Syk.

Src family kinases (Lyn, Fyn, Lck, and Blk) and Syk, a tandem SH2 domain containing tyrosine kinase, have been demonstrated to be associated with the antigen receptor in B cells. Both of these categories of tyrosine kinases are presumed to be critical players in the process of antigen-mediated signal transduction. Cross-linking of membrane immunoglobulin on the surface of B cells leads to the activation of Lyn, Fyn, and Blk, which presumably associate with the cytoplasmic tails of the membrane immunoglobulin-associated Ig alpha/beta heterodimer. Receptor ligation also leads to the tyrosine phosphorylation and catalytic activation of Syk, but the mechanism of association of this kinase with the antigen receptor remains to be established. A number of phosphoproteins that can associate with the SH2 domains of Blk, Lyn, and Fyn have been described in activated B cells. We demonstrate here that Syk is one of the proteins in the lysates of activated B cells which bind to the SH2 domains of Src family kinases. Syk binds directly to the SH2 domain of Blk and complexes in vivo with Lyn and Blk in activated B cells.

Animals↗
PubMed1995

Leader peptidase from Escherichia coli: overexpression, characterization, and inactivation by modification of tryptophan residues 300 and 310 with N-bromosuccinimide.

We have overproduced the leader peptidase from Escherichia coli in a high yield by using a T7 RNA polymerase/promoter system and purified the enzyme. This leader peptidase showed an apparent pH optimum of about 10 toward a synthetic peptide substrate, and was stable at temperatures below 40 degrees C. Kinetic studies indicated that one of the active site residues in the enzyme has a pKa value of approximately 7.5. The enzyme was rapidly inactivated by reaction with N-bromosuccinimide (NBS). When approximately two tryptophan residues were oxidized with NBS, the activity was almost completely lost and this inactivation was markedly prevented by a substrate. These NBS-reactive tryptophan residues were identified as Trp300 and Trp310 by a peptide mapping analysis. This indicates that Trp300 and/or Trp310 are critically important for the activity of the leader peptidase. On the other hand, the enzyme was scarcely inhibited by treatment with N-acetylimidazole, iodoacetic acid, 5,5'-dithiobis(2-nitrobenzoic acid), succinic anhydride, or 2,4,6-trinitrobenzenesulfonate. Diethylpyrocarbonate inhibited the enzyme; however, this inhibition did not seem to result from the modification of histidine residues. Thus, there seem to be no functionally important tyrosine, cysteine, or histidine residues or amino groups among the residues which readily react with these reagents. However, the enzyme was inactivated significantly by treatment with phenylglyoxal or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Therefore, some of the arginine residues and the carboxyl groups appear to be important for the enzyme activity.

Amino Acid Sequence↗
PubMed1995

Bone SPECT imaging of vertebral hemangioma correlation with MR imaging and symptoms.

To evaluate the bone SPECT findings of vertebral hemangioma and their relationship to symptoms and MRI findings, the authors reviewed planar and SPECT bone scans and MR images of 15 vertebral hemangioma in 10 patients. All planar bone scan images demonstrated normal findings, except one, SPECT images demonstrated normal findings in 11 vertebral hemangioma less than 3 cm in diameter. Three of four vertebral hemangioma that were 3 cm or larger showed abnormally increased or decreased uptake on SPECT images. There was a disparity between SPECT imaging and MRI.

Adult↗
PubMed1995

Trauma-induced isomorphic lesions in morphea--a brief case report.

We describe a case of morphea which presented further typical lesions of the disease at the sites of mechanical trauma. It can be suggested that cutaneous lesions of morphea may be locally developed due to physical stimuli as an isomorphic response in patients or subclinical cases of the disease.

Female↗
PubMed1995

Loop diathermy and cold-knife conization in patients with cervical intraepithelial neoplasia: a comparative study.

One hundred and sixty-eight cases of cervical conization were performed for cervical intraepithelial neoplasia (CIN) in a 32-month study. The indications for conization were unsatisfactory colposcopic finding, abnormal epithelium that extended into the endocervical canal, a microinvasive cervical cancer, and significant discrepancy among cytology, colposcopy, and/or punch biopsy histology. In the early period of the study, conization was done by the cold-knife method (N = 107), whereas loop diathermy was used in the latter part of the study (N = 61). Both groups were similar in terms of age, indications for conization, and size of cervical cone specimens. Loop diathermy conization was done in a significantly shorter time (5.7 +/- 1.8 minute vs 15.2 +/- 6.1 minute)(P < 0.05) than cold-knife conization. However, the difference in the postoperative complications between loop diathermy(3.0%) and cold-knife conization(4.7%) was not significant. The incidence rate of residual CIN III lesions in the subsequent hysterectomy specimens, found by histological documentation on these specimens was 25.0 and 26.1 percent after loop diathermy and cold-knife conization respectively. These results suggest that loop diathermy is much easier to perform and a more time-conserving treatment modality than cold-knife conization in the management of patients with cervical intraepithelial neoplasia.

Adult↗
PubMed1995

The nerve endings of the acetabular labrum.

The nerve endings of the human acetabular labrum were investigated. Twenty-three acetabular labra were obtained from 24 fresh human cadavers, stained with Suzuki's silver impregnation and an immunohistochemical technique for neurogenic specific protein S-100, and examined by light and electron microscopy. Ramified free nerve endings were seen in all specimens by silver staining, and also were observed by the immunohistochemical technique for S-100 protein. Sensory nerve end organs, such as a Vater-Pacini corpuscle, Golgi-Mazzoni corpuscle, Ruffini corpuscle, and articular corpuscle (Krause corpuscle), were observed by silver staining. Collagen fibers were scattered sparsely in the superficial layer of the labrum, and nerve endings were observed mostly in this region. Collagen fibers were sparse, and nerve endings also were observed in some regions among the collagen fiber bundles in the inner layer. Innervation of the acetabular labrum was confirmed in this study, suggesting that nerve endings in the labrum may be involved in nociceptive and proprioceptive mechanisms.

Acetabulum↗
PubMed1994

Acidic carboxyl-terminal domain of gene 2.5 protein of bacteriophage T7 is essential for protein-protein interactions.

The product of gene 2.5 protein of bacteriophage T7, a single-stranded DNA-binding protein, physically interacts with phage encoded DNA polymerase and primase/helicase proteins. A truncated gene 2.5 protein (GP2.5-delta 21C) was constructed by in vitro mutagenesis and lacks the 21 carboxyl-terminal amino acids found in wild-type gene 2.5 protein, 15 of which are acidic. GP2.5-delta 21C cannot substitute for wild-type gene 2.5 protein in vivo; the phage are not viable and exhibit less than 1% of the DNA synthesis observed in wild-type phage-infected cells. GP2.5-delta 21C has been purified to apparent homogeneity from cells overexpressing its cloned gene and has a conformation that differs from that of the wild-type gene 2.5 protein as judged by its circular dichroism spectra. Purified GP2.5-delta 21C retains its ability to bind to single-stranded DNA; the association constant of the protein for single-stranded DNA, determined by nitrocellulose filter binding, is 3.2 x 10(6) M-1 and is identical to that determined for wild-type gene 2.5 protein. However, GP2.5-delta 21C is a monomer in solution, whereas the wild-type protein exists as a dimer. GP2.5-delta 21C does not physically interact with T7 DNA polymerase as measured by affinity chromatography and fluorescent emission anisotropy. The mutant protein cannot stimulate T7 DNA polymerase activity on primed single-stranded DNA templates.

Bacteriophage T7↗
PubMed1994

Endodermal sinus tumor arising from a dysgenetic gonad in a 46,XX female combined with müllerian agenesis.

The occurrence of neoplastic transformation in a dysgenetic gonad of a female with 46,XX karyotype is very rare. Moreover, to our knowledge, a case of endodermal sinus tumor arising from that setting combined with Müllerian agenesis has not been reported. This case suggests the possibility of development of cancer in a dysgenetic ovary of a female even with 46,XX or Müllerian agenesis.

Adult↗