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Biomedical subjects

S Miyagawa

Publications and source records attributed to S Miyagawa.

At least 19 recordsLinked to original sources

Molecular genetic cascades for external genitalia formation: an emerging organogenesis program.

External genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud-shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages. The transient embryonic epithelia located in the distal GT are called the distal urethral epithelium (DUE) regulating, at least in part, the (distal) GT development. This review covers the available data about early patterning of GT and discusses the molecular developmental similarities and points of divergence between the different appendages. Development of the male and female external genitalia is also reviewed.

Animals↗

Cross-species function of the pig C1 esterase inhibitor.

BACKGROUND: The use of a bioartificial liver with pig cells for the treatment of fulminant hepatic failure will require research on the plasma complement regulatory proteins of the pig, because the liver produces most of the complement components and plasma complement regulatory proteins. In our previous study, the pig C1 esterase inhibitor (C1-INH), which functions as an inhibitor of the complement reaction in the first step of the classical pathway in the fluid phase, was cloned and some relevant features of the molecule were characterized, especially its cross-species regulation, in comparison with human C1-INH. In a further analysis, the species specificity of C1-INH was examined, using pig endothelial cells (PEC) and several types of sera. MATERIALS AND METHODS: The cDNA of pig C1-INH was used to produce the membrane type pC1-INH, pC1-INH-PI, and inserted into the cloning site of pCXN2 (chicken beta actin promoter). The pCX/pCl-INH-PI plasmid was then transfected into PEC to establish stable PEC with pCl-INH-PI. The expression of the pCl-INH-PI was evaluated by a FACS analysis, and complement-dependent cell lysis with human, dog, rabbit, and mouse sera was then assessed. RESULTS: The transfectant with pig Cl-INH-PI showed a high level of expression on PEC. The PEC transfectants showed an inhibitory effect on complement-dependent PEC lysis. Pig Cl-INH did not show the same suppressive effect for each serum. However, considering the alternative pathway activation of each serum on the pig cell membrane, it can be concluded that pCl-INH has a relatively small species restriction. CONCLUSION: Pig Cl-INH, having a similar structure to human Cl-INH, shows a strong complement regulatory function on other species sera.

Actins↗

Domino liver transplantation in living donors.

Domino liver transplantation (DLT) has been developed as a method to expand the donor pool. In living donors DLT, the prime concern is to avoid any disadvantage to the donor and the first recipient. Seven DLTs were performed among 211 patients who underwent living donor liver transplantation. The domino recipients included six with hepatocellular carcinoma and one with citrullinemia. The domino grafts were obtained from patients with familial amyloid polyneuropathy (FAP) including the left liver in three cases and the right liver in four. Among the seven domino recipients, a 64-year-old woman with advanced hepatocellular carcinoma died of lung metastasis. The other six domino recipients are alive without FAP symptoms. In living donor liver transplantation, because the vessels of the graft from the first donor are not long enough for anastomosis, the hepatic vessels must be left as long as possible when removing the liver from the FAP patients in order to ensure sufficient safety for vascular reconstruction. With careful decision making during the procedure, such as where to divide the vessels in the FAP patients, DLT may help address the shortage of liver grafts.

Amyloid Neuropathies, Familial↗

Roles of virD4 and cagG genes in the cag pathogenicity island of Helicobacter pylori using a Mongolian gerbil model.

BACKGROUND AND AIMS: The roles of the virD4 and the cagG genes in the cag pathogenicity island of Helicobacter pylori for gastroduodenal pathogenesis are unclear and their roles in vivo have not been examined. METHODS: Seven week old male Mongolian gerbils were inoculated with the wild type H pylori TN2GF4, its isogenic virD4, or cagG mutants. Animals were sacrificed at 4, 12, and 24 weeks after inoculation. Gastric inflammation and H pylori density were evaluated by histology, inflammatory response (as measured by interleukin (IL)-1beta mRNA levels), proliferative activity (as assessed by 5'-bromo-2'deoxyuridine labelling indices), and host systemic reaction (as measured by anti-H pylori IgG antibody). RESULTS: Degree of gastric inflammation, proliferative activity, and mucosal IL-1beta mRNA levels remained low throughout the first 12 weeks in gerbils infected with the virD4 mutants. Degree of gastric inflammation and proliferative activity increased at 24 weeks with the virD4 mutants reaching levels comparative with those seen at four weeks with the wild-type strains. Mucosal IL-1beta mRNA levels were also increased at 24 weeks with the virD4 mutants and levels at 24 weeks were similar between the wild-type and virD4 mutants. In contrast, gerbils infected with the cagG mutants had reduced ability to colonise gerbils, and no or little gastric inflammation or proliferative activity was observed. CONCLUSIONS: Loss of the virD4 gene temporally retarded but did not abrogate gastric inflammation. Loss of the cagG gene abolished gastric inflammation partially via reduced ability to colonise gerbils. Unknown factors related to the type IV secretion system other than CagA may influence gastric inflammation.

Animals↗

Conversion from tacrolimus to cyclosporine microemulsion therapy in liver transplant recipients.

The calcineurin inhibitors cyclosporine and tacrolimus have distinct advantages and drawbacks. Therefore it is important to tailor their use to the patient's tolerance. In some patients, the need to ameliorate the adverse effects of tacrolimus may necessitate a switch to cyclosporine-based therapy. Rescue therapy with a cyclosporine microemulsion (Neoral)-based regimen for transplant patients intolerant of tacrolimus has been evaluated to assess the best method of switching and determine the initial and maintenance doses of Neoral in children and adults. Our aims were to evaluate not only these facets, but also the pharmacokinetics of Neoral in stable patients, including target 2-hour postdose blood concentrations (C2) of cyclosporine in liver transplant recipients. Eighteen liver transplant patients switched from tacrolimus to Neoral underwent a program of cyclosporine blood level monitoring. The conversions were conducted safely; the incidence of acute rejection episodes was low (11.1%). Statistical analysis showed that the C2 correlated with the area under the time-blood concentration curve of cyclosporine for 0 to 4 hours after dosing (R=0.970). We determined the maintenance doses of Neoral for pediatric and adult patients as well as the feasibility of C2 quantitated monitoring in liver transplantation.

Administration, Oral↗

Autoimmune thyroid disease in anti-Ro/SS-A-positive children with annular erythema: report of two cases.

Anti-Ro/SS-A-associated recurrent annular erythema is a rare disorder, and represents a cutaneous manifestation of primary Sjögren's syndrome (SS). We report two childhood cases complicated with autoimmune thyroid disease, one with Graves' disease and the other with autoimmune thyroiditis. Both children were positive for anti-Ro/SS-A and anti-La/SS-B antibodies. One patient was lacking clinical SS with objective evidence of salivary gland involvement, while the other was diagnosed with primary SS. Our observation suggests that autoimmune thyroid disease in the subset of anti-Ro/SS-A-positive children with annular erythema might occur with similar frequency to that in adult primary SS.

Adolescent↗

Thoracoscopic enucleation of esophageal stromal tumor.

Gastrointestinal stromal tumor is a rare entity, especially in the esophagus. We report a patient with a stromal tumor of the esophagus who underwent a thoracoscopic enucleation of the tumor. The patient was a 61-year-old man complaining of slight dysphagia. A submucosal tumor of the middle thoracic esophagus was found endoscopically. The tumor was approximately 4.0 cm in diameter measured by endoscopic ultrasonography. On 17 May 2001, thoracoscopic enucleation of the esophageal tumor was performed using a Kodama Di-suction. The Kodama Di-suction was useful for the thoracoscopic enucleation of the submucosal tumor of the esophagus, acting as both a dissector and a sucker. The patient's course was uneventful after surgery. Histopathologically the esophageal tumor revealed a high cellularity, consisting of spindle cells, and the tumor cells were immunohistochemically positive for CD34 and c-kit protein, but not for a-smooth muscle actin or S-100 protein. From these findings, the esophageal submucosal tumor was diagnosed as gastrointestinal stromal tumor, distinguished from leiomyoma.

Biopsy, Needle↗

Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol.

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life. To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR. We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling. This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

Animals↗

Overexpression of transforming growth factor beta1 in smooth muscle cells of human abdominal aortic aneurysm.

OBJECTIVE: to examine the expression of transforming growth factor beta1 (TGF-beta1) and the cell kinetics of smooth muscle cells (SMCs) at the neck of abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: expression of alpha-smooth muscle actin and TGF-beta1 was evaluated by immunostaining, and cell kinetics were estimated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay and Ki-67 immunostaining in 11 AAAs (at both the dilated region and the neck) and eight occlusive aortas. RESULTS: the TUNEL-positive SMC ratio in the neck and dilated region was significantly higher than in the occlusive aorta (p<0.01). The percentage of Ki-67-positive SMCs in the neck was significantly higher than in the dilated region (p<0.01) and the occlusive aorta (p=0.032). When compared with the occlusive aorta, the aneurysmal neck had increased TGF-beta1 expression (p=0.01) and reduced SMC density, and the aneurysmal dilated aorta had much more increased TGF-beta1 expression (p<0.01) and much more reduced SMC density (p<0.01). CONCLUSIONS: these results suggest that overexpression of TGF-beta1 might be associated with the reduction of SMC density through SMC apoptosis and reduced proliferative ability of SMCs, leading to dilatation in AAAs.

Aged↗