Biomedical subjects

T Shimokawa

Publications and source records attributed to T Shimokawa.

At least 19 recordsLinked to original sources

PubMed2006

Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor.

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.

Cell Division↗

PubMed2006

Coincidence of a right retroaortic circumflex coronary artery and a right-sided aortic arch with a retroesophageal course of the left subclavian artery (arteria lusoria).

An anomalous branch of the right coronary artery was found in a 71-year-old male cadaver with a right-sided aortic arch. The anomalous artery arose from the proximal portion of the right coronary artery and ran in a retroaortic course, before reaching the posterior wall of the heart. It was recognized as the right-sided variation of the circumflex coronary artery. The aortic arch had as branches the left common carotid, right common carotid, right subclavian, and left subclavian arteries, in that order, and the descending aorta was located in the right thorax. The left subclavian artery arose from a Kommerell's diverticulum and ran behind the esophagus, and the left-sided ligamentum arteriosum was also connected at the diverticulum. Therefore, the right aortic arch was classified as type N according to Adachi-Williams-Nakagawa and type III-B1 in accordance with Stewart-Edwards. The Kommerell's diverticulum in this case seemed to press on the posterior wall of the esophagus.

Aged↗

PubMed2006

[Mitral valve plasty for acute infective endocarditis; report of a case].

A 68-year-old woman was admitted with congestive heart failure and septic shock associated with suspected mitral valve acute infective endocarditis. Echocardiography revealed vegetations attached to both mitral leaflets, prolapse of the posterior mitral leaflet and severe mitral regurgitation. Emergent surgery was performed. The anterior mitral leaflet displayed multiple vegetations. The entire anterior leaflet of mitral valve was replaced with pericardium. The posterior mitral leaflet of the middle scallop was prolapsed with an attached vegetation. Quadrangular resection was performed. A commissural reconstruction by sliding commissuroplasty for a prolapse of both anterior and posterior leaflets in the paracommissural area and autologous pericardial mitral annuloplasty was performed. Mitral regurgitation disappeared postoperatively, and the patient is now doing well as of 5 years postoperatively.

Acute Disease↗

PubMed2005

Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle.

AIM: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) protein in rat skeletal muscle. METHODS: We measured PGC-1alpha content in the skeletal muscles of male Sprague-Dawley rats (age: 5-6 weeks old; body weight: 150-170 g) after a single session of high-intensity intermittent exercise (HIE) or low-intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20-s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10-s pause. LIE rats swam with no load for 6 h in two 3-h sessions, separated by 45 min of rest. RESULTS: After HIE, the PGC-1alpha protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age-matched sedentary control rats' muscle. Immediately, 6 and 18-h after LIE, the PGC-1alpha protein content in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC-1alpha protein content observed 6 h after HIE tended to be higher than that observed after LIE. However, there was no statistically significant difference between the two values (P = 0.12). CONCLUSION: The present investigation suggests that irrespective of the intensity of the exercise, PGC-1alpha protein content in rat skeletal muscle increases to a comparable level when stimuli induced by different protocols are saturated. Further, HIE is a potent stimulus for enhancing the expression of PGC-1alpha protein, which may induce mitochondrial biogenesis in exercise-activated skeletal muscle.

Adenylate Kinase↗

PubMed2005

[Therapeutic strategies for postinfarction left ventricular free wall rupture].

We treated 93 patients who developed left ventricular free wall rupture after acute myocardial infarction. Medical management including pericardial drainage was performed in 78 patients (84%), but 67 of them died. All 11 surviving patients showed an oozing type rupture. Surgical repair was performed in 15 patients (16%). As a result, 9 patients died and 6 survived. All but 1 of the patients who died presented with a blow-out rupture. Blow-out type rupture occurred in 3 and oozing type rupture in 3 of the surviving patients. One patient with blow-out type rupture underwent implantation of a left ventricular assist device following percutaneous cardiopulmonary support (PCPS), because of low output syndrome after the operation. The device was successfully removed 7 days after implantation. In all of the 3 patients with oozing type rupture, sutureless technique was successfully performed using fibrin-glue or fibrin-glue sheet fixation. After a mean follow-up period of 7 years after operation, 5 of 6 are still alive. To improve the clinical outcome of left ventricular free wall rupture, it is important for surgeons to closely liaise with physicians, to perform surgical repair as soon as possible, and to utilize a circulatory support system after operation. Therefore, we developed a new PCPS system compatible with emergency cardiac surgery and a new left ventricular assist system draining via the left ventricle.

Aged↗

PubMed2004

An extremely rare inversion of the preduodenal portal vein and common bile duct associated with multiple malformations. Report of an adult cadaver case with a brief review of the literature.

A preduodenal position of the portal vein (PDPV) is a very rare congenital anomaly; even rarer is its association with a preduodenal position of the common bile duct (PDCBD). To the seven cases of PDCBD mentioned in the literature, we add this particularly rare case which is associated with multiple abnormalities such as situs inversus totalis, intestinal malrotation, short pancreas, bilobed spleen, accessory spleen, and abnormal ramification of the celiac axis, superior mesenteric artery and renal arteries. Besides describing and illustrating this case, we also discuss the anatomy and embryology of these structures and briefly review the patterns of previously reported cases that we found. We performed an immunohistochemical examination of the pancreas to demonstrate the ventro-dorsal pancreas in our case. For the explanation of the embryology of the PDCBD, the ventro-dorsal pancreas and PDPV malformation, we emphasized the reverse rotation of the ventral pancreas and duodenum.

Abnormalities, Multiple↗

PubMed2004

Glucose catabolic gene mRNA levels in skeletal muscle exhibit non-coordinate expression in hyperglycemic mice.

To assess the correlation between hyperglycemia and glucose catabolic gene levels in diabetic and healthy mice, we determined mRNA levels of pivotal proteins such as glucose transporters, hexokinase II, glycogen synthase, glutamine:fructose-6-phosphate amidotransferase and uncoupling proteins. Both KK and KKAy mice showed marked decreases of Glut1 and Glut4 mRNA levels in soleus compared to C57BL; db/db and ob/ob mice exhibited significantly decreased Glut4 mRNA levels, but not Glut1, in soleus. KK and KKAy mice showed a decrease of soleus HKII gene level, which may indicate decreased intracellular catabolism of glucose. Likewise, GS mRNA level was decreased in soleus muscle tissue in KK and KKAy mice. GFAT mRNA levels was no different between hyperglycemic and normoglycemic mice. In contrast, UCP2 and UCP3 mRNA levels were higher in KK and KKAy mice. Conversely, db/db and ob/ob mice showed a significant decrease in UCP3 mRNA. Individual correlation analysis indicated that the decrease in Glut4 gene levels was only observed in hyperglycemic mice. The more important observation is that the glucose catabolic genes do not exhibit any clear coordinate expression. Abnormal expression of glucose catabolic genes may contribute to hyperglycemia and muscle insulin resistance in these four strains.

Animals↗

PubMed2003

An anatomical study of the levator veli palatini and superior constrictor with special reference to their nerve supply.

We dissected 50 head halves of 25 Japanese cadavers (10 males, 15 females) to investigate the innervations of the levator veli palatini (LVP) and superior constrictor pharyngis. The branches supplying the LVP were classified into the following three types according to their origins: supplying branches that originated from the pharyngeal branch of the glossopharyngeal nerve (type I, four sides, 8%), branches that originated from a communicating branch between the pharyngeal branches of the glossopharyngeal and vagus nerves (type II, 36 sides, 72%), and those that originated from the pharyngeal branch of the vagus nerve (type III, 10 sides, 20%). In previous studies, supplying branches of type I were seldom described. Regarding the innervation of the superior constrictor, some variations were observed, and we consider it likely that there is a close relationship between these variations and the type of innervation of the LVP.

Female↗

PubMed2003

Monocyte chemoattractant protein (MCP)-1 production via functionally reconstituted Fcalpha receptor (CD89) on glomerular mesangial cells.

BACKGROUND: Fc alpha receptor (FcalphaR; CD89) is the receptor for Fc portion of IgA in various cells, and displays various immunological responses on binding. It is important to analyze the mesangial functions via FcalphaR in the pathogenesis of IgA nephropathy. However, it is still controversial whether FcalphaR is expressed on mesangial cells. To assess biological functions of FcalphaR on the mesangial cells, we established mesangial transfectants that expressed FcalphaR with or without FcRgamma chain that is a common signaling molecule of FcRs. The production of monocyte chemoattractant protein-1 (MCP-1) by mesangial cells is known to contribute to cellular infiltration into glomeruli and subsequent glomerular injuries. METHODS: Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of the human FcalphaR. Furthermore, we co-transfected some of the FcalphaR transfectants with cDNA of human FcRgamma chain. The tyrosine phosphorylation of the intra-mesangial proteins after FcalphaR cross-linking was examined by immunoprecipitation. MCP-1 production from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA. RESULTS: Two kinds of mesangial transfectants stably expressed human FcalphaR with or without FcRgamma chain (FcalphaR(+), FcalphaR(+)/gamma(+)). Phosphorylation of FcRgamma chain and syk kinase was detected in FcalphaR(+) and FcalphaR(+)/gamma(+) cells, but not in untransfected cells. Aggregated IgA induced significantly higher MCP-1 production in FcalphaR(+)/gamma(+) than those in FcalphaR(+) or untransfected control. CONCLUSIONS: Present study demonstrated that FcalphaR and FcRgamma chain could be reconstituted in mesangial cells and mediated MCP-1 production by aggregated IgA in a dose-dependent manner. Current data would argue that FcalphaR can be activated in mesangial cells through their own machinery, although underlying mechanisms for FcalphaR induction in mesangial cells remain unclear.

Animals↗

PubMed2003

A chemically driven fluctuating ratchet model for actomyosin interaction.

With reference to the experimental observations by Yanagida and his co-workers on actomyosin interaction, a Brownian motor of fluctuating ratchet kind is designed with the aim to describe the interaction between a Myosin II head and a neighboring actin filament. Our motor combines the dynamics of the myosin head with a chemical external system related to the ATP cycle, whose role is to provide the energy supply necessary to bias the motion. Analytical expressions for the duration of the ATP cycle, for the Gibbs free energy and for the net displacement of the myosin head are obtained. Finally, by exploiting a method due to Sekimoto [J. Phys. Soc. Jpn. 66 (1997) 1234], a formula is worked out for the amount of energy consumed during the ATP cycle.

Actins↗

PubMed2003

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation.

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.

Adolescent↗

PubMed2002

Nervous branch passing through an accessory canal in the sphenozygomatic suture: the temporal branch of the zygomatic nerve.

A nervous branch which passes through a small canal in the sphenozygomatic suture is sometimes observed during dissection. To examine the origin, course and distribution of this nervous branch, 42 head halves of 21 Japanese cadavers (11 males, 10 females) and 142 head halves of 71 human dry skulls were used. The branch was observed in seven sides (16.7%); it originated from the communication between the lacrimal nerve and the zygomaticotemporal branch of the zygomatic nerve or from the trunk of the zygomatic nerve. In two head halves (4.8%), the branch pierced the anterior part of the temporalis muscle during its course to the skin of the anterior part of the temple. The small canal in the suture was observed in 31 head halves (21.8%) of the dry skulls. Although this nervous branch is inconstantly observed, it should be called the temporal branch of the zygomatic nerve according to the constant positional relationship to the sphenoid and zygomatic bones. According to its origin, course and distribution, this nervous branch may be considered to be influential in zygomatic and retro-orbital pain due to entrapment and tension from the temporalis muscle and/or the narrow bony canal. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0027-4.

Cadaver↗

PubMed2001

Aberrant muscle between the temporalis and the lateral pterygoid muscles: M. pterygoideus proprius (Henle).

During examination of the positional relationships between the lateral pterygoid and the temporalis muscles and the innervating nerves, an aberrant muscle was observed in three of 66 head halves. The aberrant muscle originated from the medial surface of the anteromedial muscle bundle of the temporalis (Shimokawa et al. 1998, Surg. Radiol. Anat. 20:329-334) and inserted into the inferolateral surface of the lower head of the lateral pterygoid. Due to its location, origin and insertion this aberrant muscle slip is considered to correspond to the pterygoideus proprius described by Henle (1858, Handbuch der Anatomie des Menschen). Based on the innervation findings, the present aberrant muscle might be considered as a remnant muscle bundle between the anteromedial muscle bundle of the temporalis and the lateral pterygoid during differentiation of the lateral masticatory muscle anlage.

Adult↗

PubMed2001

Polymorphism in promoter region of Fcalpha receptor gene in patients with IgA nephropathy.

We have recently identified two novel polymorphisms (-114T/C and +56T/C relative to the major transcription start site) in the functional promoter region of the Fcalpha receptor (FcalphaR) gene. Since altered FcalphaR expression may be associated with IgA nephropathy, we examined these promoter polymorphisms in this disease. Patients with IgA nephropathy (n = 90), patients with other primary glomerulonephritis (n = 50), and healthy adults (n = 83) were studied. Genotyping was performed by the polymerase chain reaction (PCR) followed by direct sequence analysis and was subsequently confirmed by PCR with mismatched primers followed by restriction fragment length polymorphism analysis. The study demonstrated that the frequency of the +56C allele in patients with IgA nephropathy (0.511) was significantly (P < 0.01) higher than that in patients with other primary glomerulonephritis (0.350) and healthy adults (0.337). In addition, a significant increase in the frequency of the +56CC genotype was observed in patients with IgA nephropathy (27.8% vs 10.0% in other GN and vs 9.6% in healthy adults). In contrast, no significant difference in the frequencies of the +56CC genotype and +56C allele was observed between other primary glomerulonephritis patients and healthy adults. The frequency of the -114CC genotype in patients with IgA nephropathy was significantly increased compared with those in both control groups (15.6% vs 4.0% in other GN and vs 2.4% in healthy adults). Polymorphisms of the FcalphaR promoter region therefore appear to be associated with susceptibility to IgA nephropathy, suggesting the importance of the FcalphaR gene and its expression in this disease.

Adolescent↗

PubMed2001

Application of pressure-controlled colon delivery capsule to oral administration of glycyrrhizin in dogs.

A colon delivery system has been used to improve the bioavailability of glycyrrhizin, a glycoside of glycyrrhetic acid. The bioavailability of glycyrrhizin is low when administered in conventional oral galenic dosage forms because glycyrrhizin is enzymatically hydrolysed both in the stomach and in the intestine. It was reasoned that if large amounts of glycyrrhizin were directly delivered to the colon, enzymatic activity should be reduced due to saturation so that intact glycyrrhizin could be absorbed into the systemic circulation. Based on this assumption, pressure-controlled colon delivery capsules (PCDCs) were used as a colon delivery system. Eight types of glycyrrhizin solution were prepared and were introduced into PCDCs. After oral administration of the test PCDCs to beagle dogs, blood samples were obtained over 24 h and plasma glycyrrhizin concentrations were measured by an HPLC method. With PCDCs containing aqueous glycyrrhizin and propylene glycol solutions, plasma glycyrrhizin levels were extremely low and the bioavailabilities of glycyrrhizin were 0.6% and 0.4%, respectively. When Labrasol was added to both types of glycyrrhizin solution, the bioavailability was improved to 4.6% for aqueous solution and 3.8% for propylene glycol solution. When a surfactant, Polysorbate 80, was added in combination with Labrasol, synergistic effects were not obtained. Furthermore, dose-dependent effects of Polysorbate 80 were not obtained. Labrasol, which is a component of self-emulsifying drug delivery systems (SEDDS), has been shown to strongly improve the bioavailability of glycyrrhizin from the colon.

Administration, Oral↗

PubMed2001

Expression of protein S in the murine heart and cultured mouse cardiomyocytes is down-regulated by cytokines.

Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependent anticoagulant protein and is known to be produced extrahepatically. In the present study, the concentration of PS mRNA was determined tissue by tissue in the mouse, and it was high in lung, adrenal and heart as well as in liver. We further investigated the effects of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1) on the PS mRNA expression in murine tissues in vivo. Although LPS and TNF-alpha significantly decreased the expression level of PS mRNA in all tissues examined (e. g., lung, liver, heart, and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell line, and again, treatment with IL-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regional anticoagulant potential in heart, and suggest that the decreased PS expression by cytokines may result in an increase in the systemic and/or regional prothrombotic potential under inflammatory conditions.

Adrenal Glands↗

PubMed2000

Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.

We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.

Animals↗

PubMed2000

Down-regulation of murine tissue factor pathway inhibitor mRNA by endotoxin and tumor necrosis factor-alpha in vitro and in vivo.

Tissue factor pathway inhibitor (TFPI) is the protease inhibitor that regulates the extrinsic coagulation pathway initiated by the factor VIIa/TF complex. In this study, we first investigated tissue distribution of TFPI mRNA in the mouse and found that TFPI mRNA expression level was by far the highest in the lung, followed by the heart, adrenal, and adipose tissue. Since little has been known concerning the regulation of TFPI gene expression in vivo, we further analyzed the changes in the TFPI mRNA level in murine tissues after intraperitoneal injection of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1). LPS and TNF-alpha dramatically decreased TFPI mRNA expression in four tissues examined (e.g., lung, heart, kidney, and adipose tissue), whereas the suppressive effect of IL-1 on TFPI mRNA was limited. The down-regulation of TFPI mRNA expression by LPS and TNF-alpha was also observed in cultured mouse endothelial cells and in cardiomyocyte cell lines. The decreased TFPI mRNA expression by LPS and TNF-alpha in tissues and in the specific cell types may contribute to an increase in the local procoagulant potential, resulting in the thrombotic tendency under septic and/or inflammatory conditions.

Animals↗