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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 55 records · Page 3Linked to original sources
PubMed2001

The Arabidopsis sensor His-kinase, AHk4, can respond to cytokinins.

His-to-Asp (His-->Asp) phosphorelay mechanisms are presumably involved in propagation of certain environmental stimuli, including phytohormones, in Arabidopsis thaliana. In addition to the previously characterized His-kinases, namely, the ETR1 family of ethylene receptors, CKI1 cytokinin-sensor, and ATHK1 osomo-sensor, this higher plant has three more His-kinases (named AHK2, AHK3, and AHK4). By employing the well-known His-->Asp phosphorelay systems in both the fission yeast and Escherichia coli, evidence is presented showing that the AHK4 His-kinase has an ability to serve as a cytokinin-responsive environmental sensor. Taking advantage of this AHK4-dependent His-->Asp phosphorelay system in E. coli, a phosphorelay interaction between the Arabidopsis His-kinase and histidine-containing phosphotransmitters (AHPs) was also demonstrated for the first time.

Arabidopsis↗
PubMed2001

The Arabidopsis AHK4 histidine kinase is a cytokinin-binding receptor that transduces cytokinin signals across the membrane.

Common histidine-to-aspartate (His-->Asp) phosphorelay is a paradigm of signal transduction in both prokaryotes and eukaryotes for the propagation of certain environmental stimuli, in which histidine (His)-kinases play central roles as sensors for environmental signals. For the higher plant, Arabidopsis thaliana, it was recently suggested that the His-kinase (AHK4 / CRE1 / WOL) is a sensor for cytokinins, which are a class of plant hormones important for the regulation of cell division and differentiation. Interestingly, AHK4 is capable of functioning as a cytokinin sensor in the eubacterium, Escherichia coli (Suzuki et al. 2001, Plant Cell Physiol. 42: 107). Here we further show that AHK4 is a primary receptor that directly binds a variety of natural and synthetic cytokinins (e.g. not only N(6)-substituted aminopurines such as isopentenyl-adenine, trans-zeatin, benzyl-adenine, but also diphenylurea derivatives such as thidiazuron), in a highly specific manner (K(d) = 4.55+/-0.48x10(-9) M). AHK4 has a presumed extracellular domain, within which a single amino acid substitution (Thr-301 to Ile) was shown to result in loss of its ability to bind cytokinins. This particular mutation corresponds to the previously reported wol allele (wooden leg) that causes a striking phenotype defective in vascular morphogenesis. Collectively, evidence is presented that AHK4 and its homologues (AHK3 and possibly AHK2) are receptor kinases that can transduce cytokinin signals across the plasma membrane of A. thaliana.

Adenine↗
PubMed2001

Adenomyomatosis of the papilla of Vater: a case illustrating diagnostic difficulties.

AIMS: To describe the extremely rare case of an adenomyoma of the papilla of Vater. CASE REPORT: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. CONCLUSION: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.

Abdominal Pain↗
PubMed2001

Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway.

The aims of this study were to evaluate the functional expression of Fas receptors (Fas) in human pancreatic cancer cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2 and to search for the mechanisms of receptor-mediated inhibition of Fas signaling in these cells. Despite the expression of Fas receptors at considerable levels, exposure of these cells to agonistic Fas antibodies (500 ng/ml) induced only minimal apoptosis in 4 cell lines. The mechanisms allowing resistance to Fas-mediated apoptosis are complex. Using RT-PCR, we identified molecules which might counteract the apoptogenic signal at several levels of Fas signal transduction pathway. The most striking findings were the overexpression of Fas decoy receptors (DcR3), Fas associated phosphatase-1 (FAP-1), and FLICE-inhibitory protein (c-FLIP) in the resistant cell lines as well as in pancreatic cancer surgical specimens. In conclusion, pancreatic cancer cells express three molecules that can abrogate Fas function at different levels of Fas signaling cascade, resulting in resistance to Fas-mediated apoptosis, and this may promote the progression of this malignancy.

Adenocarcinoma↗
PubMed2001

Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma.

S100A4 has been implicated in invasion and metastasis of cancer, but prognostic significance of its expression in esophageal squamous cell carcinoma remains unclear. In this study, we examined the expression of S100A4 by Western blot analysis and immunohistochemistry in surgically resected esophageal squamous cell carcinoma. The relationship between S100A4 tissue status and clinicopathological findings was analyzed to assess the prognostic significance of S100A4 in esophageal squamous cell carcinoma. The S100A4 protein level was significantly higher in tumor tissue than in corresponding normal esophageal mucosa (p<0.05) in 22 cases of esophageal carcinoma by Western blot analysis. S100A4 expression was detected in 25% of 52 cases of esophageal squamous cell carcinoma by immunohistochemistry and correlated with the depth of invasion (p<0.05). Patients with S100A4-positive carcinoma had significantly poorer prognosis than those with S100A4-negative carcinoma, which was also true in the cases with deep invasion of the primary cancer (T3, T4) (p<0.01 and p<0.05, respectively). Moreover, S100A4 tissue status remained the only independent prognostic parameter in the multivariate analysis. Our results suggest that S100A4 may play a key role in the progression of esophageal carcinoma and that immunohistochemical detection of S100A4 in the primary tumor may be useful for the prediction of a poor prognosis.

Adult↗
PubMed2001

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

Apoptosis↗
PubMed2001

[Optimal nodal dissection for early gastric cancer].

Extensive lymphadenectomy (D2) in 295 patients with early gastric cancer (EGC) resulted in a significantly lower 10-year recurrence rate than limited lymph node dissection (D1) in 97 patients (2.1% vs. 11.9%, p < 0.005). Among node-positive patients, the recurrence rate following D2 was significantly lower than that after D1 (12.5% vs. 44.4%, p < 0.02). Among node-negative patients, there was no difference in recurrence rate between two groups (0.6% vs 3.3%, p < 0.2). These observations suggest that there are two optimal methods of node dissections in EGC surgery based on nodal status. The sentinel node concept is important to understand nodal status. In 1993, we developed intraoperative endoscopic lymphatic mapping with 2% patent blue to demonstrate the lymphatic basins in EGC. Frozen sections of the blue nodes in 203 patients had a high predictive value for nodal metastasis, with a sensitivity of 89%, specificity of 100%, and accuracy of 98%. Four false-negative cases had clinical metastasis, which was diagnosed at surgery. In 34 of 35 patients, metastatic nodes were located along the lymphatic basins. Among them, 15 patients had metastasis only in the sentinel lymph nodes. Of 5 gastric lymphatic basins, 42% of the patients had involvement of one, 47% 2, and 12% 3. These results show that each EGC has its own lymphatic basins in which metastasis can develop. The more numbers of the sections there are, the higher the likelihood of nodal metastasis. This means that each frozen section slice carries the risk of being false negative. Therefore we should always dissect the lymphatic basins even in cases with no sentinel node metastasis. In addition, patients with sentinel nodes containing metastasis should be treated with the D2 procedure.

Humans↗
PubMed2001

[A case of retroperitoneal ancient schwannoma in the pelvis].

We treated a case of retroperitoneal ancient schwannoma in the pelvis detected incidentally at a health examination without clinical manifestation in a 59-year-old Japanese man found to have hypertension. Computed tomography showed a heterogeneously enhanced 8 x 7 cm solid mass in the pelvic retroperitoneal space. Magnetic resonance imaging revealed an encapsulated tumor, showing a low intensity on the T1-weighted image, heterogeneously high intensity on the T2-weighted image and the tumor homogeneously enhanced with Gd-DTPA. It was suspected to be a mesenchymal tumor. The tumor was resected en bloc. The histologic examination of the extirpated tumor was an ancient schwannoma. A total of 11 retroperitoneal ancient schwannoma cases were reviewed.

Humans↗
PubMed2001

[A case report of rectal cancer with liver and pulmonary metastases responding to TS-1].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Adenocarcinoma↗
PubMed2001

[Chemotherapy (low-dose CDDP + UFT) to advanced pancreatic cancer in an ambulatory setting improved survival and quality of life].

The prognosis of pancreatic cancer is very poor. Past attempts to treat advanced pancreatic cancer with single agent or combination chemotherapy have yielded low response rates and little reproducible impact on patient survival or quality of life. We performed systemic chemotherapy in case of unresectable or recurrent pancreatic cancer with CDDP 25 mg/body intravenous weekly or biweekly and oral administration of UFT (300-400 mg/day) as an outpatient treatment. Tumor markers were well controlled for about over one year or more. This ambulatory combination is a well-tolerated regimen that results in improved survival and quality of life.

Ambulatory Care↗
PubMed2001

[Four cases of multiple liver metastasis of colorectal cancer treated with hepatic resection after chemotherapy].

Four cases of multiple liver metastasis of colorectal cancer treated with hepatic resection after chemotherapy were investigated. The 4 patients consisted of 3 males and 1 female with a mean age of 67.8 years. Two patients underwent systemic chemotherapy, and the other 2 received hepatic arterial infusion chemotherapy. The effect was PR in all patients, and mean duration until resection was 8.5 months. One patient had lung metastasis and one had recurrence in a local lesion and residual liver after hepatic resection, but all patients remain alive. The longest survival periods in 4 patients who underwent hepatic resection and 13 who did not were 32 and 24 months, respectively. It is suggested that hepatic resection after chemotherapy for multiple liver metastasis of colorectal cancer may be useful for improvement of outcome.

Aged↗
PubMed2000

Exercise-induced negative U waves in precordial leads as a marker of viable myocardium in patients with recent anterior myocardial infarction.

Patients with recent anterior myocardial infarction and a significant stenosis in the left anterior descending coronary artery were divided into two groups according to the presence (Group A, n=24) or absence (Group B, n=77) of negative U waves in the precordial leads during exercise stress test to compare the coronary arteriographic findings. Both total occlusion of the left anterior descending coronary artery (79% vs. 31%, P<0.01)) and good (index=2, 3) collateral circulation to the territory of this artery (92% vs. 36%, P<0.01) were observed more often in group A than in group B. In order to determine whether detection of exercise-induced negative U waves in precordial leads can predict the presence of viable myocardium, the 56 patients (20 of group A and 36 of group B) with total or subtotal occlusion of the left anterior descending coronary artery were studied further. The coronary arteriographic and exercise 201Tl scintigraphic findings were compared between the groups. Good collateral circulation to the territory of this artery was observed significantly (P<0.05) more often in group A (100%) than in group B (61%). Patients with multivessel disease were significantly (P<0.05) more prevalent in group A (70%) than in group B (33%). The incidence of a significant partial redistribution in the anteroseptal area in the 20Tl images 4 h after exercise was significantly (P<0.01) higher in group A (85%) than in group B (39%). In 29 patients with anterior Q-wave myocardial infarction and exercise-induced ST elevation in precordial leads, a significant 201Tl redistribution in the anteroseptal area was observed in 8 (80%) of 10 patients of group A in contrast to only 4 (21%, P<0.05) of 19 in group B. In the diagnosis of the viability associated with 201Tl redistribution in the anteroseptal area by the finding of exercise-induced negative U waves, the sensitivity was 67% and the specificity was 88% in these patients. We conclude that exercise-induced negative U waves in precordial leads are a convenient and specific marker for the presence of viable myocardium in patients with recent anterior myocardial infarction.

Collateral Circulation↗
PubMed2000

Alteration of beta-catenin expression in esophageal squamous-cell carcinoma.

beta-catenin regulates cadherin-mediated cell-cell adhesion and also functions as a signaling molecule. In this study, we examined the expression pattern of E-cadherin, alpha-catenin and beta-catenin in 22 cases of esophageal squamous-cell carcinoma by Western-blot analysis. Expression of E-cadherin, alpha-catenin and beta-catenin was lower in carcinomas than in normal esophageal mucosa in 4 cases (18.2%) for E-cadherin, 6 cases (27.3%) for alpha-catenin and 9 cases (40.9%) for beta-catenin. Expression of beta-catenin was not always correlated with that of E-cadherin. Over-expression of beta-catenin was observed in 3 cases (13.6%). Of 3 cases that presented with over-expression of beta-catenin, 2 showed cytoplasmic staining by immunohistochemistry. Nuclear localization of beta-catenin was observed in one case that had higher beta-catenin level in tumor tissue (1.4-fold higher than normal mucosa). The genomic DNA sequences of the beta-catenin and the APC gene were analyzed. No mutation of the beta-catenin gene was observed in any cases. Silent mutation of the APC gene was found in all the cases that showed over-expression or nuclear localization of the beta-catenin protein. These results indicate that alterations of the cadherin-catenin complex may play an important role in a sub-set of esophageal carcinogenesis. Furthermore, it is suggested that beta-catenin over-expression is not caused by genetic alteration of either the beta-catenin or the APC gene.

Blotting, Western↗
PubMed2000

Exercise-induced U-wave alterations as a marker of well-developed and well-functioning collateral vessels in patients with effort angina.

OBJECTIVES: We sought to determine whether exercise-induced U-wave alterations are observed in association with well-developed and well-functioning collateral vessels. BACKGROUND: Although exercise-induced electrocardiographic (ECG) U-wave alterations including negative and prominent U waves have been established as a marker of significant or critical narrowing of a major coronary artery, the relation between this finding and the degree of collateral development has not yet been determined. METHODS: Patients with stable effort angina were divided into two groups according to the presence (group A, n = 46) or absence (group B, n = 79) of exercise-induced either negative or prominent U waves in the precordial leads; the clinical profiles, coronary angiographic findings and also ischemic status during 60 s of coronary balloon occlusion were compared between the two groups. RESULTS: The incidence of severe angina (CCS [Canadian Cardiovascular Society] class III or IV) was higher (p < 0.05) in group A (52%) than in group B (32%) patients. Good collateral vessels (Rentrop grade 2 or 3) into the perfusion territory of the culprit vessel were observed more frequently (p < 0.05) in group A (70%) than in group B (43%) patients. Coronary balloon angioplasty was carried out in 23 patients of group A and 40 patients of group B. Both ischemic ST changes (52% vs. 85%) and angina (57% vs. 80%) during balloon inflation were less (p < 0.05) frequently observed in group A than in group B. The incidence of no apparent myocardial ischemia with ST deviation or angina during the balloon inflation was higher (p < 0.05) in group A (39%) than in group B (10%) patients. In the prediction of the absence of myocardial ischemia during balloon inflation by the presence of exercise-induced U-wave alterations, the sensitivity was 69% (9/13) and the specificity was 72% (36/50) in the study patients. CONCLUSIONS: Exercise-induced U-wave alterations are a marker for well-developed collateral circulation in patients with stable but severe effort angina. This finding is also highly predictive of the absence of myocardial ischemia during transient coronary balloon occlusion and possibly of low-risk for development of acute myocardial infarction or hemodynamic instability upon abrupt closure of the culprit coronary artery.

Angina Pectoris↗