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Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 37 records · Page 2Linked to original sources

Combined evaluation of mucin antigen and E-cadherin expression may help select patients with gastric cancer suitable for minimally invasive therapy.

BACKGROUND: MUC1 mucin is known to be highly expressed in carcinomas that show invasive growth and poor prognosis. Impairment of adhesion molecule E-cadherin expression has been widely accepted as a critical event for cancer invasion and metastasis. The present study evaluated the combination of mucin and E-cadherin status as a possible predictor of patients suitable for minimally invasive therapy for gastric cancer. METHODS: Two hundred and nine paraffin-embedded specimens of gastric carcinoma (141 early, 68 advanced) were examined by immunohistochemical staining using monoclonal antibodies against MUC1 mucin (MUC-1-CORE, DF3), MUC2 mucin (Ccp58) and E-cadherin (anti-E-cad). RESULTS: Gastric carcinoma with MUC1-positive expression demonstrated malignant characteristics. Normal E-cadherin expression showed an inverse correlation with MUC1 expression. Patients with early gastric carcinoma who had a combination of normal E-cadherin and MUC1-negative expression had no recurrence and a favourable prognosis. Moreover, cancers with normal E-cadherin/MUC1-negative expression were not found at an advanced stage in differentiated-type carcinoma. CONCLUSION: A normal E-cadherin/MUC1-negative expression pattern in gastric cancer is a favourable marker. Preoperative estimation of the E-cadherin and MUC1 status of an endoscopic biopsy specimen may help select appropriate patients for minimally invasive treatment of gastric cancer.

Antibodies, Monoclonal↗

Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts.

In adult-to-adult living donor liver transplantation (LDLT), the graft volume is inevitably much smaller than the ideal liver mass (standard liver volume) for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver support. However, little is known about the influence of CVVHD on the elimination of tacrolimus. The objective of this study was to elucidate the effect of CVVHD on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size grafts. Three liver transplant recipients (one male and two females) and donors (two males and one female) were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD. Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no significant difference between concentrations of tacrolimus in blood sampled at inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD.

Adult↗

Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants.

AIMS: The F1S and A genetic variants of alpha1-acid glycoprotein (AAG) change under various physiological and pathological conditions. They also vary in their drug binding abilities. We have studied the stereoselective binding ability of each of the AAG variants using enantiomers of disopyramide (DP) and warfarin (WR). METHODS: The AAG variants were separated by hydroxyapatite chromatography. Binding of drug enantiomers to the AAG variants was studied by the Hummel-Dreyer method. The characteristics of the binding activities were examined by Scatchard plot analysis. The first five amino-terminal amino acids (residues 112-116) of the cyanogen bromide (CNBr) fragment (residues 112-181) of each of the separated AAG fractions were elucidated by Edman degradation. RESULTS: Commercial AAG was separated into two main fractions. Residues 112-116 of fraction 2 were identical to the amino acid sequences predicted from the AAG A gene, LAFDV, and encode the F1S variant. In fraction 3, the deduced amino acid sequence of the AAG B gene, FGSYL, was established, and encodes the A variant. The binding affinities of both DP enantiomers in fraction 3 were significantly higher than those in fraction 2. The differences between dissociation constants (Kd) in fractions 2 and 3 were 5.2-fold for (S)-DP (P < 0.05) and 3.7-fold for (R)-DP (P < 0.001). The dissociation constant of (S)-DP (0.39 +/- 0.08 micro m) was lower than that of (R)-DP (0.53 +/- 0.10 micro m) in fraction 3 [95% confidence interval (CI) - 0.282, - 0.010; P < 0.05], although the binding activities of the DP enantiomers were almost the same in fraction 2. By contrast WR enantiomers had a higher binding affinity in fraction 2 than in fraction 3, the differences in dissociation constants between fractions 2 and 3 being 12.6-fold for (S)-WR (P < 0.001) and 8.3-fold for (R)-WR (P < 0.001). The dissociation constant of (S)-WR (0.28 +/- 0.10 microm) was significantly lower than that of (R)-WR (0.48 +/- 0.08 microm) in fraction 2 (95% CI - 0.369, - 0.028; P < 0.05), but there were no significant differences between the binding activities of WR enantiomers in fraction 3. CONCLUSIONS: DP and WR enantiomers bind preferentially to fraction 3 and fraction 2, respectively. Fractions 2 and 3 are encoded by the AAG A and the AAG B genes, respectively.

Amino Acid Sequence↗

Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo.

Hepatocellular carcinoma is a well-known malignancy in the world. However, the molecular mechanism of carcinogenesis and tumour progression remains unclear. Recently, reduced E-cadherin expression due to transcriptional suppressor Snail was proven in a panel of epithelial and dedifferentiated cells derived from carcinomas of various etiologies. In the present study, we examined Snail and E-cadherin mRNA/protein expression in five hepatocellular carcinoma cell lines with variable phenotypes (HuL-1, Hep-G(2), Changliver, HLE, and HLF). The results demonstrated that the presence of Snail mRNA in HuL-1, Changliver, HLE and HLF cells detected by RT-PCR, which was further proven by in situ hybridization in tumours induced by HuL-1, Changliver, and HLF cells where Snail mRNA signals expressed in each of the sections. By contrast, E-cadherin mRNA and protein expression were only detected in Hep-G(2) cells by RT-PCR and Western blot, respectively. These results were also consistent with the data obtained from in vivo immunohistochemical staining where membranous expression of endogenous E-cadherin protein was revealed only in tumour sections induced by Hep-G(2) cells. Here we are the first to report that there is an inverse correlation between Snail and E-cadherin expression in HCC cells as well.

Animals↗

Evaluation of acrosome reaction and viability of human sperm with two fluorescent dyes.

OBJECTIVE: To evaluate the usefulness of the Hoechst 33258/FITC-Pisum sativum agglutinin (FITC-PSA) staining for simultaneous assessment of viability and acrosome reaction rate (%AR) of human sperm. MATERIAL AND METHODS: Fresh sperm was collected 13 fertile donors provided fresh semen. We used motile sperm selected by the "swim-up" procedure using modified HTF. Hoechst 33258 was added and co-incubated with sperm for 10 min. Samples were washed free of unbound stain and the sperm were mounted as smears on glass slides. After drying, sperms were incubated with FITC-PSA for 30 min. Sperm were examined by fluorescence microscopy. Also, FITC-Concanavalin A (FITC-ConA) staining and vital staining with yellowish eosin were performed simultaneously. The correlation of viability and %AR were analyzed. RESULTS: Four different staining patterns were observed and clearly distinguished as follows: a) Viable acrosome-reacted sperm, b) Viable acrosome-intact sperm, c) dead acrosome-reacted sperm, d) dead acrosome-intact sperm. There was significant correlation between the results obtained by Hoechst 33258 and vital staining methods in viability of human sperm (r = 0.927, P < 0.001). There was significant correlation between the two methods (FITC-PSA and FITC-ConA) in %AR of human sperm (r = 0.92, P < 0.001). CONCLUSION: Viability and acrosome status of a human sperm can be easily assessed simultaneously by Hoechst 33258/FITC-PSA staining method. This combination method is considered useful to evaluate sperm function.

Acrosome Reaction↗

Abnormal expression of E-cadherin and beta-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer.

BACKGROUND: Impaired expression of E-cadherin and alpha- and beta-catenin is frequently observed in several human cancers. The aim of this study was to examine immunohistochemical expression of these adhesion molecules, focusing on early gastric carcinomas, and to investigate differences between differentiated and undifferentiated gastric cancer at the early phase of carcinogenesis. METHODS: Immunohistochemical staining of E-cadherin and alpha- and beta-catenin was performed using specimens from 143 patients with early gastric cancer. RESULTS: Abnormal E-cadherin and beta-catenin staining correlated with depth of tumour invasion in differentiated-type tumours. In contrast, abnormal staining was frequently found even in intramucosal carcinoma of undifferentiated-type tumours, suggesting an apparent difference in the onset of E-cadherin-catenin complex abnormality between the two cancer types. Absent staining of beta-catenin was associated with lymph node metastasis. Multivariate analysis revealed abnormal E-cadherin expression as an independent factor that correlated with submucosal invasion in early gastric cancer. CONCLUSION: Abnormal E-cadherin expression is a possible marker of submucosal invasion in differentiated-type early gastric cancer and absent beta-catenin staining could be used as a predictor of lymph node metastasis in both types.

Biomarkers, Tumor↗

Increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and lymphocyte recruitment in murine gastritis induced by Helicobacter pylori.

Although T cell involvement in Helicobactor pylori-induced gastritis is known, mechanism about T cell recruitment is not understood. In this study we examined how mucosal addressin cell adhesion -molecule-1 (MAdCAM-1) is involved in lymphocyte recruitment in murine chronic gastritis induced by H. pylori. C57 BL/6 mice were infected with Sydney strain (SS1). Six months after infection, the stomach was removed. The expression of adhesion molecules, MAdCAM-1, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the cell surface antigens CD4, CD8, CD45R/B220 or beta7-integrin were determined by immunohistochemistry. A significant increase in CD4 lymphocytes was observed in the body portion of stomach in SS1-infected mice and most of these CD4 cells express beta7-integrin, a known counter ligand for MAdCAM-1 molecule. Strong MAdCAM-1 expression was observed adjacent to these cells in the lamina propria as well as in the submucosa of SS1-infected stomach. Quantitative analysis showed that the area of MAdCAM-1 expression well correlated with the infiltration of beta7-integrin positive lymphocytes. On the other hand, expression of ICAM-1 or VCAM-1 in the lamina propria was few even in the SS1-infected stomach. Increased expression of MAdCAM-1 was well correlated to the location of lymphocytes, which express CD4 and beta7-integrin. These results suggest the possibility that MAdCAM-1 may be largely involved in the lymphocyte recruitment in the gastritis mucosa with H. pylori.

Animals↗

Prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer.

OBJECTIVE: To evaluate the prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer. DESIGN: Color Doppler imaging and pulsed Doppler spectral analysis were used in the investigation of 49 patients with epithelial ovarian cancer (19 serous, 15 mucinous, eight endometrioid, four clear cell and three Brenner cell) immediately before laparotomy. Twenty-two were stage I, six were stage II, 17 were stage III and four were stage IV. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. Moreover, the apoptotic index was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method. Intratumoral peak systolic velocity was tested for correlation with patients' age at diagnosis, stage of disease, presence of a residual tumor, histological subtype and grade, thymidine phosphorylase expression, apoptotic index, microvessel count and patient survival. RESULTS: Histological grade (P = 0.025), thymidine phosphorylase expression (P = 0.044), apoptotic index (P = 0.039) and microvessel count (P = 0.014) were all significantly associated with peak systolic velocity. Stage of disease (P = 0.002), presence of residual disease (P = 0.0002) and peak systolic velocity (P = 0.041) were found by univariate Cox regression analysis to be significantly associated with a poor prognosis. Multivariate Cox regression analysis revealed that stage of disease (P = 0.006) and peak systolic velocity (P = 0.008) are independent prognostic factors. CONCLUSIONS: Intratumoral peak systolic velocity could be a preoperatively pertinent prognostic predictor of survival in patients with epithelial ovarian cancer.

Adult↗

Utility of color Doppler indices of dominant follicular blood flow for prediction of clinical factors in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To investigate the relationship between color Doppler indices of dominant follicular blood flow and clinical factors in in vitro fertilization-embryo transfer cycles. SUBJECTS AND METHODS: This was a prospective study involving 26 patients completing a total of 33 in vitro fertilization cycles. Dominant follicular blood flow indices, peak systolic velocities, the resistance index and the pulsatility index were evaluated using transvaginal color Doppler. The indices were compared to the clinical outcomes of in vitro fertilization-embryo transfer. RESULTS: There was a significant correlation between dominant follicular peak systolic velocities and the number of oocytes retrieved, as well as the number of mature oocytes obtained. There was no significant correlation between dominant follicular resistance index or pulsatility index and the number of follicles > 10 mm in diameter, the number of oocytes retrieved or the number of mature oocytes. There were no significant differences between dominant follicular peak systolic velocities, resistance index or pulsatility index, and fertilization rate or the ratio of good quality embryos. However, significant differences were found between the number of oocytes retrieved, as well as the number of mature oocytes for those patients in which the peak systolic velocity was below 25 cm/s. CONCLUSIONS: Doppler assessment of dominant follicle blood flow alone is useful for predicting the number of retrievable oocytes. However, morphological quality of the embryo produced or the pregnancy rate cannot be predicted by this method.

Adult↗

Popliteal venous aneurysms: involvement of tibial nerve in aneurysmal wall.

Primary popliteal venous aneurysms are very rare vascular abnormalities, with 50 cases reported in the English literature. Thromboembolic complications are common in popliteal venous aneurysms. Since medical treatment has been proved inadequate, surgical repair is recommended with a minimum time delay. However, it involves some risk because of the complex anatomy of the popliteal space. We report on a case of popliteal venous aneurysm, in which the tibial nerve was involved in the aneurysmal wall and was injured by surgical repair.

Adult↗

Glomerulocystic kidney disease (GCKD) associated with Henoch-Schoenlein purpura: a case report and a review of adult cases of GCKD.

We report on a 71-year-old male with Henoch-Schoenlein purpura (HSP) who developed glomerulocystic kidney disease (GCKD) without congenital abnormality. He had mild renal dysfunction. Renal biopsy findings showed mild proliferation of mesangial cells and matrixes, and tubular atrophy, interstitial fibrosis, cystic dilation of Bowman's capsule and atrophy of the glomerular tuft. The deposition of IgA and C3 in the mesangial area was observed with the fluorescent antibody technique. Therefore he was diagnosed with GCKD-associated HSP. This was the oldest patient among the previous case reports and the patient was the first case to be reported for concurrent GCKD and HSP. In this study, we also reviewed the patient to previously reported adult patients with GCKD.

Aged↗

Prosthetic grafts for above-knee femoropopliteal bypass. A multicenter retrospective study of 564 grafts.

BACKGROUND: Many prosthetic grafts including expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron) have recently been used for above-knee femoropopliteal bypass. The purpose of this study was to identify the factors affecting patency performance and patient survival. METHODS: A multicenter retrospective analysis of 496 patients who received 564 grafts between 1990 and 1999 (325 ePTFE and 239 Dacron). Follow-up extended to 114.5 months, with a mean of 30.8 months (+/-25.9 months). RESULTS: The overall primary patency rate for all grafts was 71.4% at 5 years, 73.7% for ePTFE, and 68.9% for Dacron grafts. The secondary patency rates at 5 years were 84.1% for ePTFE, and 83.8% for Dacron. No significant differences were found. The logistic regression analysis revealed that younger age at operation and smoking history were correlated with decreased primary patency rate. The patency rates were unaffected by postoperative administration of oral anticoagulants or antiplatelet agents, although pharmacotherapy contributed to the improvement of survival rates. Renal failure, cerebral infarction and Dacron decreased survival rate. CONCLUSIONS: We conclude that the patency performances of prosthetic grafts are satisfying. However, the choice of prosthetic grafts for younger patients or patients with a smoking history need to be carefully considered. Cerebral infarction, chronic renal failure and Dacron grafts may decrease the survival rate. The operative indications should be determined carefully in these cases. The administration of beraprost sodium is recommended for postoperative pharmacotherapy.

Aged↗

A rare case of atherosclerotic popliteal artery aneurysm in a young adult.

Popliteal artery aneurysms are not so clinically frequent but are the most common peripheral aneurysms. They usually affect older men aged over 60 and are caused by atherosclerosis. Whenever they occur in younger men, other more unusual etiologies such as trauma, infection, inflammatory arteritis or popliteal entrapment are responsible. In this paper we present the case of a young male with an atherosclerotic popliteal artery aneurysm without a history of penetrating trauma or other possible etiologies.

Adult↗

Albumin-coated knitted Dacron aortic prosthses. Study of postoperative inflammatory reactions.

BACKGROUND: The purpose of this study was to investigate the postoperative inflammatory reactions to albumin-coated Dacron grafts (ACGs), which are used in the repair of abdominal aortic aneurysm (AAA). METHODS EXPERIMENTAL DESIGN: a retrospective study with a follow-up period of 14 days. SETTING: University hospital. PATIENTS: 50 patients admitted for elective AAA repair from January 1997 to January 2000. INTERVENTIONS: each patient underwent AAA repair with an ACG (Bard, albumin-coated Dacron graft). MEASURES: the white blood cell (WBC) count, plasma C-reactive protein (CRP) concentration, and body temperature (BT) were determined. The preoperative data, the highest values of the postoperative data, and the values 2 weeks postsurgery were analyzed. RESULTS: The BT, CRP, and WBC increased and peaked at the 1st week postsurgery and then decreased gradually. The BT and WBC levels returned to normal within 2 weeks. The CRP level continued to show slightly elevated values in the 2nd week, but it was not significantly different compared to the preoperative data. CONCLUSIONS: The use of an albumin-impregnated prosthesis for the reconstruction of AAA is biocompatible, since no significant increases in inflammatory reactions are observed in the 2nd week postsurgery.

Aged↗

Combined spinal and epidural anesthesia for abdominal aortic aneurysm surgery in patients with severe chronic pulmonary obstructive disease.

BACKGROUND: The presence of chronic obstructive pulmonary disease (COPD) should not be considered a contraindication to operation but should rather identify those patients that require special preoperative and postoperative pulmonary care. The purpose of this paper is to report our experience in the use of combined spinal and epidural anesthesia (CSEA) for open AAA repair in such patients. METHODS: From April 1997 to November 1998, three patients with severe COPD underwent elective open infrarenal AAA repair under CSEA. All the patients satisfied one or more of the following criteria: a room air PaO2 =or<60 mmHg, PaCO2 =or>45 mmHg, FEV1 =or<50% of predicted, and/or FVC =or<75% of predicted, and one of them was on home oxygen preoperatively. Preoperative preparation of the patients consisted of breathing exercises with incentive espirometry, elimination of underlaying pulmonary infections and usage of bronchodilator therapy. RESULTS: All the patients tolerated surgery safely. None of them developed postoperative complications, including pneumonia and other respiratory conditions. No significant changes in room air arterial blood gas or pulmonary function was recognized before and after surgery. CONCLUSIONS: CSE anesthesia is a viable anesthetic option for conventional AAA surgery in patients with severe COPD since it can preserve spontaneous breathing and provide additional respiratory benefits over general anesthesia.

Aged↗

Induction of angiotensin converting enzyme in neointima after intravascular stent placement.

BACKGROUND: To investigate the morphological changes of the arterial wall and the expression of angiotensin converting enzyme (ACE) in the arterial wall after stent placement in a canine model. METHODS: Seventeen mongrel dogs underwent stent placement (Gianturco's Z stent) in the aorta. Six animals were sacrificed at 4 weeks after stent implantation, and the other 5 animals at 12 weeks. The normal aorta was harvested from 6 dogs. The specimens were stained with hematoxylin-eosin (H&E) as well as by immunohistochemistry (smooth muscle specific a-actin, and ACE). Histomorphometric analysis was performed using the sections stained with H&E and smooth muscle specific a-actin. RESULTS: The total intimal area was significantly increased at all time points as compared with the control aorta. The a-actin positive intimal area was also significantly increased at all time points as compared with the control aorta. In the control aorta, luminal endothelial cells as well as a-actin positive medial cells occasionally exhibited faint cytoplasmic staining for ACE. In the 4- and 12-week stented aorta, a-actin positive cells in the neointima and media as well as macrophages in the adventitia stained strongly positive for ACE. CONCLUSIONS: ACE was induced in the neointima after stent placement of the canine aorta. Considering its multiple biological actions, ACE may be associated with the pathogenesis of neointimal hyperplasia after stent placement.

Actins↗

Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors.

The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1 % of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCAI, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues.

Chromosome Aberrations↗

Low M(r) protein tyrosine phosphatase inhibits growth and migration of vascular smooth muscle cells induced by platelet-derived growth factor.

Vascular smooth muscle cell (VSMC) migration and growth are positively regulated by protein tyrosine phosphorylation. Therefore, a dephosphorylation process controlled by protein tyrosine phosphatases (PTPs) must also be critical. The present study identified six cytoplasmic PTPs expressed in VSMCs: low M(r) protein tyrosine phosphatase (LMW-PTP), SHP-2, PTP36, PTP2, PTP1B, and FAP1. We further examined the functions of LMW-PTP in VSMCs using the adenovirus-mediated gene transfer of recombinant LMW-PTP. PDGF-induced activation of p38, but not of ERK MAP kinase, was blocked by LMW-PTP. LMW-PTP as well as the p38 inhibitor SB203580 inhibited DNA synthesis and cell migration upon PDGF stimulation. LMW-PTP dephosphorylated activated PDGF receptors in NIH3T3 cells, but not in VSMCs. Thus, LMW-PTP negatively regulates PDGF functions by inhibiting the p38 pathway in VSMCs although its substrate is unclear. These findings strongly demonstrate that PTPs are important as negative regulators for VSMC growth and migration, processes that are closely related to the progression of atherosclerosis.

3T3 Cells↗