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K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 181 records · Page 10Linked to original sources
PubMed1999

New therapeutic strategy for gastric carcinoma: a two-step evaluation of malignant potential from its molecular biologic and pathologic characteristics.

BACKGROUND AND OBJECTIVES: A previous study of ours indicated that platelet-derived growth factor-A (PDGF-A) mRNA expression in biopsy specimens can identify a subgroup of high-risk gastric carcinoma patients, while clinicopathologic studies have shown that lymph node involvement is an important risk factor for predicting overall survival. To identify gastric carcinoma patients at high risk for recurrence, we assessed a two-step evaluation consisting of mRNA expression of tumor growth-related factors and the histopathologic findings. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay the gene expression of PDGF-A and transforming growth factor-beta1 (TGF-beta1) in 69 gastric carcinoma endoscopic biopsy specimens (prospective cohort). The corresponding gastric carcinoma surgical specimens were classified histologically. Finally, the patients' survival curves were calculated. The relationships among the mRNA expression, histopathologic findings, and survival period were analyzed statistically. RESULTS: Nodal involvement correlated with PDGF-A and TGF-beta1 mRNA expression in early and advanced carcinomas, respectively. Both PDGF-A mRNA and TGF-beta1 mRNA expression were independent preoperative prognostic indicators in advanced cases. The ratio of involved nodes (n1) to total perigastric lymph nodes dissected (percentage of involved nodes) was the most independent postoperative prognostic indicator in advanced cases. Early carcinomas were divided preoperatively into two types. Advanced carcinomas were divided preoperatively into three. These were divided again postoperatively according to the percentage of involved nodes into high- and low-malignacy groups. CONCLUSIONS: A two-step evaluation of the malignant potential of gastric carcinoma by a combination of preoperative evaluation for PDGF-A and TGF-beta1 expression and postoperative pathologic examination would yield a more accurate prognosis for patients with gastric carcinoma.

Humans↗
PubMed1999

Bilateral granulosa cell tumor in a patient with blepharophimosis syndrome.

Blepharophimosis syndrome is a rare, autosominal, dominant ocular disorder and has been reported to be associated with ovarian dysfunction and premature menopause. We report a case of bilateral granulosa cell tumor associated with blepharophimosis syndrome. The combination of the long-term hypergonadotrophism and oocyte depletion associated with blepharophimosis syndrome may have contributed to the pathogenesis of the granulosa cell tumors. In female patients with blepharophimosis syndrome, close gynecologic surveillance should be instituted.

Aged↗
PubMed1999

Laparoscopic splenectomy for a giant splenic epidermoid cyst: report of a case.

The use of laparoscopic splenectomy has increased in recent years, primarily for patients with idiopathic thrombocytopenic purpura (ITP). We describe herein the first known case of a laparoscopic splenectomy to be performed in Japan for a patient with a giant splenic epidermoid cyst. A 26-year-old woman presented to our hospital with the major complaint of a feeling of abdominal fullness. Prior to surgery, an ultrasound-guided splenic cyst puncture was conducted for diagnostic purposes as well as to reduce the size of the cyst. The carbohydrate antigen 19-9 (CA 19-9) level was found to be elevated in the cystic contents and in the serum. Under laparoscopic guidance, the splenic vessels were ligated using a device for extracorporeal ligation, then divided. After the resected spleen had been placed in a retrieval bag, it was delivered out of the abdominal cavity without fragmentation. Following surgery, the patient's serum CA 19-9 level returned to normal. Splenic epidermoid cysts are most often encountered in young women, and laparoscopic surgery to remove cysts of this type is both minimally invasive and excellent from a cosmetic standpoint. Thus, laparoscopic surgery should be considered as the method of choice for the majority of patients diagnosed with a splenic epidermoid cyst.

Adult↗
PubMed1999

Exploring nonnatural evolutionary pathways by saturation mutagenesis: rapid improvement of protein function.

Random point mutagenesis does not access a large fraction of protein sequence space corresponding to primarily nonconservative amino acid substitutions. The cost of this limitation during directed evolution is unknown. Random point mutagenesis over the entire gene encoding the psychrophilic protease subtilisin S41 identified a pair of residues (Lys211 and Arg212) where mutations provided significant increases in thermostability. These were subjected to saturation mutagenesis to test whether the amino acids not easily accessible by point mutagenesis provide even better "solutions" to the thermostabilization challenge. A significant fraction of these variants surpassed the stability of the variants with point mutations. DNA sequencing revealed highly hydrophobic residues in the four most stable variants (Pro/Ala, Pro/Val, Leu/Val, and Trp/Ser). These nonconservative replacements, accessible only by multiple (two to three) base substitutions in a single codon, would be extremely rare in a point mutation library. Such replacements are also extremely rare in natural evolution. Saturation mutagenesis may be used advantageously during directed evolution to explore nonnatural evolution pathways and enable rapid improvement in protein traits.

Amino Acid Substitution↗
PubMed1999

Matrilysin as a target for chemotherapy for colon cancer: use of antisense oligonucleotides as antimetastatic agents.

Matrilysin (MMP-7) is the smallest member of the matrix metalloproteinase (MMP) family. It is frequently expressed in various types of cancer including colon, stomach, prostate, and brain cancers. Previous studies have suggested that matrilysin plays important roles in the progression and metastasis of colon cancer. Recently, we have examined the effects of a matrilysin-specific antisense phosphorothioate oligodeoxyribonucleotide on in vitro invasion and liver metastasis in nude mice of two human colon carcinoma cell lines (CaR-1 and WiDr). In culture, the antisense oligonucleotide effectively inhibited both the secretion of matrilysin by CaR-1 cells and their in vitro invasion through a reconstituted basement membrane. In a nude mouse model, the antisense oligonucleotide potently suppressed the experimental liver metastasis of WiDr cells from the spleen. These results suggest that matrilysin has an important role in the liver metastasis of human colon cancer and that matrilysin antisense oligonucleotides have therapeutic potential for the prevention of metastasis.

Animals↗
PubMed1999

Increased prevalence of luteinizing hormone beta-subunit variant in patients with premature ovarian failure.

OBJECTIVE: To evaluate the significance of an LH variant with a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15) in gynecologic disease, including infertility. DESIGN: Clinical study. SETTING: Department of Obstetrics and Gynecology, Shimane Medical University Hospital, Izumo, Japan. PATIENT(S): Two hundred forty-five Japanese women with endocrine disorders and/or gynecologic disease and 153 healthy, nonpregnant, fertile Japanese women. INTERVENTION(S): A blood sample was collected. MAIN OUTCOME MEASURE(S): The ratio of LH values from the SPAC-S and Immulyze assays (LH ratio: SPAC-S LH/Immulyze LH) was used to determine variant (< or =0.5) or wild-type (>0.5) LH status according to a demonstrated relation between the ratio and the sequence of the LH beta-subunit gene. RESULT(S): The LH ratio was lower (0.80+/-0.31) in the 245 patients than in the controls (1.00+/-0.38), and the variant was more frequent in the patients (18.4%) than in the controls (8.5%). We found no difference in the frequency of the variant between infertile and fertile patients. The prevalence of infertility did not differ between patients with variant LH and patients with normal LH. Ovulatory disorders, hyperprolactinemia, premature ovarian failure, menstrual disorders, and luteal insufficiency were significantly more frequent in patients with the variant. CONCLUSION(S): Variant LH may contribute to female reproductive disorders, including infertility and premature ovarian failure.

Adolescent↗
PubMed1999

Color Doppler energy and related quantitative analysis of gestational trophoblastic tumors.

OBJECTIVE: To assess the reliability of color Doppler energy (CDE) and a related quantitative analysis for detection and follow-up of uterine involvement in gestational trophoblastic tumor. METHOD: CDE was performed in 19 patients with trophoblastic tumor, in 25 women in early pregnancy and 25 non-pregnant women. The blood flow area ratio (BFAR) in CDE was used as an index representing uterine involvement. In nine of the 19 patients, BFAR was measured before, during and at termination of chemotherapy. RESULT: The BFAR (mean +/- S.D.) of uterine profiles in 19 patients (39.9 +/- 1.3%) was significantly higher than that in 25 pregnant women (24.6 +/- 10.1%, P = 0.002) and in 25 non-pregnant women (14.8 +/- 5.7%, P = 0.001). In the follow-up of nine patients, when beta-hCG was less than 3.1 ng/ml during the treatment, the BFAR (38.7 +/- 11.9%) decreased below that (44.2 +/- 14.6%) seen prior to treatment (P = 0.009) and was much lower at termination of treatment (27.5 +/- 12.3%, P = 0.048). CONCLUSION: These data support the use of CDE and the related quantitative analysis as a new method for detecting and follow-up of uterine involvement in patients with trophoblastic tumors.

Adult↗
PubMed1999

Basement membrane patterns, gelatinase A and tissue inhibitor of metalloproteinase-2 expressions, and stromal fibrosis during the development of peripheral lung adenocarcinoma.

To clarify the process and mechanisms of the development and progression of peripheral lung adenocarcinoma, we investigated the relationships among the patterns of basement membrane (BM), stromal fibrosis, and the expressions of gelatinase A and tissue inhibitor of metalloproteinases-2 (TIMP-2) in 33 lesions of atypical alveolar cell hyperplasia (AAH) and 48 lesions of lung adenocarcinoma, including 24 lesions of bronchioloalveolar carcinoma (BAC). We found that the architecture of alveolar BM was intact in all 33 AAH lesions and 11 nonsclerosing BAC lesions that formed no central scar, suggesting that these lesions are early-stage intraepithelial neoplasia. The preexistent BM of the lung was disrupted, and the BM components around the neoplastic glands were disrupted or absent in the area of the central scar of some sclerosing BAC lesions with collapse fibrosis alone (2 of 4) and in those of all of the adenocarcinoma lesions associated with desmoplastic stromal fibrosis (nine sclerosing BAC and 24 non-BAC tumors). These results suggested that, in lung adenocarcinomas, destruction of the BM was correlated with the formation of a central scar, particularly with desmoplasia. It is likely that adenocarcinomas with a central scar are advanced and invasive cancers potentially having metastatic activity. The expression of gelatinase A and TIMP-2 was associated with central scar formation as well as with destruction of the BM components. Both the neoplastic and stromal cells expressed gelatinase A and TIMP-2 and probably play a role in tumor cell invasion.

Adenocarcinoma↗
PubMed1999

Effect of dentin primers containing N-methylolacrylamide or N-methylolmethacrylamide on dentin pretreatment.

The effect of experimental dentin primers containing N-methylolacrylamide (MEAA) or N-methylolmethacrylamide (MEMA) on the bonding of three commercial light-cured resin composite systems [Restorative Z 100 (Scotchbond), Palfique Estelite (Macbond) and Photo Clearfil A (Clearfil Photobond)] to etched dentin was investigated. Water solutions of 35% hydroxyethyl methacrylate (HEMA). 50% MEAA or 30% MEMA were used as dentin primers. The dentin etched with 10% phosphoric acid solution was pretreated with dentin primers for 30 s. The resin composite systems were applied in a Teflon tube positioned onto pretreated dentin surfaces. After water immersion for 1 day, the shear bond strengths were measured. The thicknesses of hybrid layers at dentin-resin interfaces treated with 6 mol/l HCl and 1% NaOCl were measured by scanning electron microscopy. The dentin primer pretreatment increased the bond strengths of all resin composite systems. For Macbond and Clearfil Photobond, the bond strengths (14.2-26.5 MPa) with MEAA and MEMA were higher than those (10.5 and 17.8 MPa) with HEMA. All hybrid layer thicknesses were 1-1.5 microns after HCl immersion. The hybrid layers after NaOCl immersion become narrower. The main fracture pattern of specimens exhibiting high bond strengths (more than 14.2 MPa) was dentin cohesive fracture after bond test. For Macbond and Clearfil Photobond, the layers of specimens pretreated with MEAA and MEMA were clearly thicker than those pretreated with HEMA after NaOCl immersion. MEAA and MEMA solutions were more effective in improving the bond strength of Macbond and Clearfil Photobond to etched dentin than was HEMA. Macbond and Clearfil Photobond created good hybrid dentin layers which could resist NaOCl-attack when MEAA and MEMA solutions were used as dentin primers.

Acrylamides↗
PubMed1999

Utility of early second-look laparoscopy after infertility surgery.

STUDY OBJECTIVE: To evaluate the efficacy of early second-look laparoscopy (ESLL) and the usefulness of the American Fertility Society (AFS) adhesion score at ESLL in terms of reproductive prognosis. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Ninety-two consecutive women undergoing infertility surgery between January 1983 and December 1996. INTERVENTION: We performed ESLL in all but 32 patients, 27 of whom underwent surgery before institution of the protocol. MEASUREMENTS AND MAIN RESULTS: The pregnancy rate in 1 year was significantly higher in women having ESLL than in those not having the surgery. The AFS score was not significantly different in pregnant and nonpregnant patients. CONCLUSION: Early second-look laparoscopy may improve fecundity in women requiring fertility surgery. (J Am Assoc Gynecol Laparosc 6(2):165-168, 1999)

Adult↗
PubMed1999

Effects of interactions between drugs on the renal excretion of trientine in rats--acetazolamide and furosemide increase trientine excretion.

PURPOSE: To elucidate the effects of drug interactions on the urinary excretion of trientine in rats. METHOD: Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles. RESULTS: Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles. CONCLUSIONS: There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.

Acetazolamide↗
PubMed1999

Expression of the thymidine phosphorylase gene in epithelial ovarian cancer.

Thymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumours. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear cell and two undifferentiated) were analysed by polymerase chain reaction of RNA after reverse transcription. These included eight of low malignant potential. Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the beta2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III-IV was significantly higher than that of TP gene expression in stage I-II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases after complete resection of the primary tumours by surgical operation was performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to, or greater than, median) was to be significantly worse than patients with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumour phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated.

Adult↗
PubMed1999

Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury.

BACKGROUND: A number of studies have demonstrated an important role for macrophages (M phi) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate M phi infiltration in this disease. This study examined the expression of M phi chemotactic molecules M phi migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular M phi infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. METHODS: Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. RESULTS: ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ M phi at week 1, which was further increased at week 6, when M phi-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular M phi expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant M phi infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. CONCLUSION: These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described M phi chemotactic and adhesion molecules, which results in M phi recruitment and the development of glomerular injury.

Animals↗
PubMed1999

Three-dimensional ultrasonographic evaluation of ovarian tumours: a preliminary study.

Our objective was to determine the accuracy of three dimensional (3D) ultrasonography in the differentiation of ovarian tumours. Women (n = 20) with ovarian tumours (13 benign and seven malignant) were first examined using two-dimensional (2D) ultrasonography and were then evaluated with three-dimensional (3D) ultrasonography. All patients underwent surgery within 7 days of 2D and 3D ultrasonographic evaluations, and a histopathological diagnosis was made. A 2D ultrasonographic diagnosis of malignancy was done using an established scoring system. Diagnostic criteria for ovarian malignancy by 3D ultrasonography were: irregular thick septa, irregular papillary projection, mostly solid tumour, high echogenicity, and irregular inner wall. Compared with 2D ultrasound, 3D ultrasound had a significantly higher specificity (P < 0.005) and accuracy (P < 0.01), and a significantly lower false positive rate (P < 0.005). Our results suggest that 3D ultrasonography might be a better means of differentiating between malignant and benign ovarian tumours. However, in view of the small number of ovarian tumours, these observations must be considered preliminary.

Adult↗
PubMed1999

Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy.

The purpose of this study was to evaluate the role of nitric oxide in the vasodilative effect of dehydroepiandrosterone sulphate (DHEA-S) in term pregnant women. Circulating nitrite, nitrate and oestradiol concentrations were measured on 10 normal full-term pregnant women before (-30 min) and after (10, 30, 60, 90 and 120 min) administration of a 200 mg i.v. dose of DHEA-S dissolved in 20 ml of 5% dextrose (DHEA-S group). Ten normal full-term pregnant women received 20 ml of 5% dextrose as controls (control group). Maternal blood pressure and heart rate were also recorded. The median oestradiol concentration increased significantly after the infusion in DHEA-S group (P < 0.001), whereas there was no significant change in plasma oestradiol in the control group. In the DHEA-S group, plasma circulating nitrate and nitrite increased significantly at 10 and 30 min after DHEA-S administration respectively (P < 0.05). In the control group, there was no change in plasma nitric oxide (NO) metabolites. No change was found in heart rate or mean arterial blood pressure in the control or DHEA-S groups. These results suggest there may be a link between increased NO and increased oestrogen after DHEA-S injection but their peak values did not coincide. Both may be associated with vasodilation in term pregnant women.

Blood Pressure↗
PubMed1999

Expression of trypsin in human cancer cell lines and cancer tissues and its tight binding to soluble form of Alzheimer amyloid precursor protein in culture.

It was recently found that overexpression of the trypsin gene in tumor cells stimulates their growth in culture and in nude mice. In the present study, expression of trypsin in various human cancer cell lines and tissues was studied by gelatin zymography and immunoblotting before and after enterokinase treatment and by immunohistochemistry. The analyses showed that many stomach, colon, and breast cancer cell lines secreted trypsinogens-1 and/or -2, as well as an unidentified serine proteinase of about 70 kDa, into culture medium. Lung cancer cell lines secreted 18- and 19-kDa unidentified trypsin-like proteins. Stomach cancer cell lines frequently secreted active trypsin, suggesting that they produced an endogenous activator of trypsinogen, most likely enterokinase. Active trypsin formed a complex with a soluble form of Alzheimer amyloid precursor protein (sAPP), a Kunitz-type trypsin inhibitor, which was secreted by all cell lines tested. This indicated that sAPP is a primary inhibitor of secreted trypsin. Immunohistochemical analysis showed that trypsin(ogen) was frequently expressed at high levels in stomach and colon cancers, but scarcely in breast cancers. In the stomach cancers, the trypsin immunoreactivity was higher in the malignant, non-cohesive type than in the cohesive type. These results support the hypothesis that tumor-derived trypsin is involved in the malignant growth of tumor cells, especially stomach cancer cells.

Amyloid beta-Protein Precursor↗
PubMed1999

Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells.

We examined whether mitogen-activated protein (MAP) kinase is activated by thyrotropin-releasing hormone (TRH) in GH3 cells, and whether MAP kinase activation is involved in secretion of prolactin from these cells. Protein kinase inhibitors--such as PD098059, calphostin C, and genistein--and removal of extracellular Ca2+ inhibited MAP kinase activation by TRH. A cAMP analogue activated MAP kinase in these cells. Effects of cAMP on MAP kinase activation were inhibited by PD098059. TRH-induced prolactin secretion was not inhibited by levels of PD098059 sufficient to i activation but was inhibited by wortmannin (1 microM) and KN93. Treatment of GH3 cells with either TRH or cAMP significantly inhibited DNA synthesis and induced morphological changes. The effects stimulated by TRH were reversed by PD098059 treatment, but the same effects stimulated by cAMP were not. Treatment of GH3 cells with TRH for 48 h significantly increased the prolactin content in GH3 cells and decreased growth hormone content. The increase in prolactin was completely abolished by PD098059, but the decrease in growth hormone was not. These results suggest that TRH-induced MAP kinase activation is involved in prolactin synthesis and differentiation of GH3 cells, but not in prolactin secretion.

Androstadienes↗