Hisako Yamamura

Bio: Hisako Yamamura is an academic researcher from Osaka University. The author has contributed to research in topics: Calponin & Gastric acid. The author has an hindex of 22, co-authored 62 publications receiving 1127 citations. Previous affiliations of Hisako Yamamura include Hirosaki University.

Values of carcinoembryonic antigen, elastase 1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas

Abstract: The levels of carcinoembryonic antigen (CEA), elastase 1, and carbohydrate antigen determinant (CA 19-9) in the pancreatic cystic fluid and the serum from five patients with cystadenocarcinoma of the pancreas, one patient with retention cyst due to pancreatic carcinoma, three patients with cystadenoma, and eight patients with benign pseudocyst accompanying or following pancreatitis, were determined by immunoassay technique. Fluid from pancreatic cysts was obtained by ultrasonically-guided percutaneous fine-needle aspiration biopsy. The specimens were centrifuged and the supernatant was used for the measurement of CEA, elastase 1, and CA 19-9, while the cell pellet was examined cytologically. The levels of CEA in the aspirated fluid were significantly higher in patients with malignant cysts of the pancreas than in those with benign cystadenomas and pseudocysts. In contrast, the levels of elastase 1 were significantly lower in patients with malignant cysts than in those with benign pancreatic cysts. Although the levels of CA 19-9 were significantly higher in patients with malignant cysts than in those with pseudocysts, the overlap between the values of patients with malignant and benign pancreatic cysts is too great. The serum CA 19-9 was most useful, however, to distinguish an individual patient with malignant cysts of the pancreas from those with benign pancreatic cyst, since there were no significant differences between the levels of serum CEA and elastase 1 in patients with malignant and benign pancreatic cysts. Correct diagnoses were made cytologically in 4 (66.7%) of 6 patients with malignant cysts. In two patients with malignant cyst, in whom no cancer cells were detectable in the aspirated materials, levels of CEA were abnormally high, but high levels of elastase 1 did not occur. Therefore, the combined measurement of CEA and elastase 1 in the aspirated cystic fluid of the pancreas could be used as an aid in diagnosis of malignant cysts of the pancreas.

Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses.

Abstract: Background Calponin is a calmodulin-and actin-binding protein expressed in smooth muscle. It promotes actin polymerization and inhibits actin-activated myosin ATPase activity. Despite the molecular and functional characterization of calponin in vitro, the physiological role of calponin in vivo has not been clarified. Results We investigated the in vivo function of smooth muscle calponin (also called basic calponin or calponin h1) by generating mice carrying a targeted mutation in both alleles of the calponin gene. Mice lacking basic calponin expression displayed enhanced ectopic bone formation in vivo, induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and an augmentation of the degree of osteoblastic differentiation of embryonic mesenchymal cells when they were stimulated by rhBMP-2. Basic calponin messenger RNA was shown to be expressed in developing and healing bone tissues, and in undifferentiated MC3T3-E1 osteoblasts. An examination of the skeletons of mutated mice showed an early onset of cartilage formation and ossification, and increased postnatal bone formation characterized by an increase in the number of activated periosteal osteoblasts. Bone fracture healing was accelerated in mutated mice. Conclusion This is the first demonstration of animals with enhanced BMP responsiveness in host cells, suggesting that endogenous basic calponin may play a negative role in an osteogenic programme.

Values of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic material in the diagnosis of malignant pancreatic tumor.

Abstract: The diagnostic accuracy of the measurement of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic fluid in the diagnosis of pancreatic tumors was assessed in 32 patients with malignant pancreatic tumors and 19 patients with pancreatitis. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation with a duodenofiberscope after intravenous administration of secretin. Pancreatic material was obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance. Abnormally high CA 19-9 levels in the serum were significantly more frequent in patients with malignant pancreatic tumors than in those with pancreatitis: they were elevated in 71.9% of the patients with pancreatic tumors. High CA 19-9 levels were found primarily in patients with a tumor of the head of the pancreas, in those with a tumor greater than 3 cm in its greatest diameter, and in those with an unresectable cancer. Only 57.1% of seven patients with a tumor of less than 3 cm in its greatest diameter showed an increase in CA 19-9 level. The CA 19-9 levels in pure pancreatic juice were significantly higher in patients with pancreatic tumors than in patients with pancreatitis without pancreatic stone. However, it was not useful for differentiating pancreatic tumors from pancreatitis with pancreatolithiasis. The CA 19-9 level in pancreatic materials obtained by aspiration biopsy was significantly higher in patients with malignant pancreatic tumors than in those with pancreatitis. Eight patients (80%) with pancreatic tumors had values above 1000 U/ml, whereas all five patients with pancreatitis had values of less than 30 U/ml. Although CA 19-9 levels in pancreatic materials was useful only when cytologic examination did not provide any evidence of malignancy, the combination of the CA 19-9 assay and the cytologic study of specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Identification of the Transcriptional Regulatory Sequences of Human Calponin Promoter and Their Use in Targeting a Conditionally Replicating Herpes Vector to Malignant Human Soft Tissue and Bone Tumors

Abstract: The calponin (basic or h1) gene, normally expressed in maturated smooth muscle cells, is aberrantly expressed in a variety of human soft tissue and bone tumors. In this study, we show that expression of the calponin gene in human soft tissue and bone tumor cells is regulated at the transcriptional level by the sequence between positions -260 and -219 upstream of the translation initiation site. A novel conditionally replicating herpes simplex virus-1 vector (d12.CALP) in which the calponin promoter drives expression of ICP4, a major trans-activating factor for viral genes was constructed and tested as an experimental treatment for malignant human soft tissue and bone tumors. In cell culture, d12.CALP at low multiplicity of infection (0.001 plaque-forming unit/cell) selectively killed calponin-positive human synovial sarcoma, leiomyosarcoma, and osteosarcoma cells. For in vivo studies, 10 animals harboring SK-LMS-1 human leiomyosarcoma cells were randomly divided and treated twice on days 0 and 9 intraneoplastically with either 1 x 10(7) plaque-forming units of d12.CALP/100 mm(3) of tumor volume or with medium alone. The viral treatment group showed stable and significant inhibition of tumorigenicity with apparent cure in four of five mice by day 35. Replication of viral DNA demonstrated by PCR amplification and expression of the inserted LacZ gene visualized by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry was associated with oncolysis of d12.CALP-treated tumors, while sparing normal vascular smooth muscle cells. In mice harboring two SK-LMS-1 tumors, replication of d12.CALP was detected in a nontreated tumor distant from the site of virus inoculation. These results indicate that replication-competent virus vectors controlled by the calponin transcriptional regulatory sequence may be a new therapeutic strategy for treatment of malignant human soft tissue and bone tumors.

Expression of the smooth muscle calponin gene in human osteosarcoma and its possible association with prognosis

Abstract: The basic calponin gene is a smooth muscle differentiation-specific gene that encodes an actin-binding protein involved in the regulation of smooth muscle contractility. We studied the expression of the calponin gene in 8 human osteosarcoma cell lines and 17 primary human osteosarcoma tissues by RT-PCR analysis. We also analyzed mRNA expression of smooth muscle-specific genes including SM22alpha, caldesmon and alpha-actin, and for neutral and acidic calponin isoforms. The genes were expressed at various levels by osteosarcoma cell lines and tissues of diverse histological subtypes. The basic calponin protein of an expected size was detected in osteosarcoma cell lines by immunoblot analysis and was localized by immunohistochemistry in the cytoplasm of the tumor cells in osteosarcoma tissues. Survival was found to be significantly increased in patients whose tumors exhibited basic calponin expression, compared with those with no expression. Alterations in the expression of other markers examined were not correlated with prognosis. Our results suggest that the basic calponin gene product may be a novel prognostic variable in patients with osteosarcoma.

Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7

Abstract: Chemotactic cytokines (chemokines) attract immune cells, although their original evolutionary role may relate more closely with embryonic development. We noted differential expression of the chemokine receptor CXCR7 (RDC-1) on marginal zone B cells, a cell type associated with autoimmune diseases. We generated Cxcr7−/− mice but found that CXCR7 deficiency had little effect on B cell composition. However, most Cxcr7−/− mice died at birth with ventricular septal defects and semilunar heart valve malformation. Conditional deletion of Cxcr7 in endothelium, using Tie2-Cre transgenic mice, recapitulated this phenotype. Gene profiling of Cxcr7−/− heart valve leaflets revealed a defect in the expression of factors essential for valve formation, vessel protection, or endothelial cell growth and survival. We confirmed that the principal chemokine ligand for CXCR7 was CXCL12/SDF-1, which also binds CXCR4. CXCL12 did not induce signaling through CXCR7; however, CXCR7 formed functional heterodimers with CXCR4 and enhanced CXCL12-induced signaling. Our results reveal a specialized role for CXCR7 in endothelial biology and valve development and highlight the distinct developmental role of evolutionary conserved chemokine receptors such as CXCR7 and CXCR4.

Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients

Abstract: Within a 12-year period we treated 67 patients (49 women, 18 men; mean age, 61 years) with cystic neoplasms of the pancreas, including 18 serous cystic adenomas, 15 benign mucinous cystic neoplasms, 27 mucinous cystadenocarcinomas, 3 papillary cystic tumors, 2 cystic islet cell tumors, and 2 cases of mucinous ductal ectasia. Mean tumor size was 6 cm (2 to 16 cm). In 39% the patients had no symptoms, and in 37% the lesions had been misdiagnosed as a pseudocyst. Computed tomography was useful for detection, for distinguishing the microcystic subgroup of serous cystadenoma, and for showing rim calcification (all 7 cases were malignant) but was not reliable for distinguishing neoplasm from pseudocyst, serous from mucinous tumors, or benign from malignant. Arteriography showed hypervascularity in 4 of 10 serous adenomas, 3 of 11 mucinous carcinomas, and 1 of 1 papillary cystic tumors. Endoscopic pancreatography showed no communication with the cyst cavity in 37 of 37 cases of cystic neoplasms but opacified the ectatic ducts in 2 of 2 cases of mucinous ductal ectasia. Stenosis or obstruction of the pancreatic duct indicated cancer. The tumor was resected by distal pancreatectomy in 25 patients, by proximal resection in 29, and by total pancreatectomy in one, with no operative deaths. Forty-four per cent of the tumors were malignant. In 10 cases the tumor was unresectable because of local extension or distant metastases, and those patients died at a mean of 4 months. Seventy-five per cent of those resected for cure are alive without evident recurrence. Because the epithelial lining of the tumor was partially (5% to 98%) absent in 40% to 72% of cases of the major tumor types, and the mucinous component comprised only about 65% of mucinous cystadenoma lining, misdiagnoses on frozen and even permanent sections were made. Mitoses and histologic solid growth correlated with malignancy. Neuroendocrine elements were seen in 87% of benign and 47% of malignant mucinous tumors. It is recommended that the terms macrocystic and microcystic be abandoned in favor of the histologic designations serous and mucinous. Incomplete examination of the cyst wall can be misleading, however. It is suggested that mucinous ductal ectasia be recognized separately from cystic tumors and that all of these lesions be resected, with the possible exception of asymptomatic confirmed serous cystadenomas.