Claudins in occluding junctions of humans and flies.

The epithelial barrier is fundamental to the physiology of most metazoan organ systems. Occluding junctions, including vertebrate tight junctions and invertebrate septate junctions, contribute to the epithelial barrier function by restricting free diffusion of solutes through the paracellular route. The recent identification and characterization of claudins, which are tight junction-associated adhesion molecules, gives insight into the molecular architecture of tight junctions and their barrier-forming mechanism in vertebrates.

Rho GTPases in animal cell mitosis.

The Rho GTPases have been thought to influence cell morphogenesis through remodeling of the actin cytoskeleton. Consistently, downstream targets such as the mDia family of formins and the WASP family proteins induce actin nucleation and polymerization, and another set of downstream effectors, the ROCK family protein kinases, are involved in regulation of actomyosin contractility. However, evidence has now accumulated that Rho GTPases also regulate local dynamics of microtubules.

Prostaglandin E receptor EP1 controls impulsive behavior under stress.

Animals under stress take adaptive actions that may lead to various types of behavioral disinhibition. Such behavioral disinhibition, when expressed excessively and impulsively, can result in harm in individuals and cause a problem in our society. We now show that, under social or environmental stress, mice deficient in prostaglandin E receptor subtype EP1 (Ptger1(-/-)) manifest behavioral disinhibition, including impulsive aggression with defective social interaction, impaired cliff avoidance, and an exaggerated acoustic startle response.

Living donor liver transplantation for biliary atresia complicated by situs inversus: technical highlights.

Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties.

ROCK-I and ROCK-II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo.

Rho-associated kinase (ROCK) is a serine/threonine kinase working in the Rho signaling to actin cytoskeleton. We previously reported that loss of ROCK-I results in the eyelid open at birth (EOB) and omphalocele phenotype in mice, while loss of ROCK-II results in placental dysfunction leading to intrauterine growth retardation and fetal death. Here, we report that after backcross to the C57BL/6 N genetic background, ROCK-II knockout (KO) neonates are born also with open eyelid and umbilical hernia, a phenotype similar to that of ROCK-I KO mice.

Successful liver transplantation for congenital absence of the portal vein complicated by intrapulmonary shunt and brain abscess.

A 27-day-old boy had convulsion associated with brain abscesses and severe hypoxemia at the age of 3 months. Congenital absence of the portal vein (CAPV) and some associated anomalies were detected by radiological examinations. Brain abscess and hypoxemia were thought to be serious complications resulting from CAPV and were successfully corrected by living donor liver transplantation at the age of 4 months.

Portal vein complications in the long-term course after pediatric living donor liver transplantation.

The frequency and the outcome of patients with portal vein (PV) complications in the long-term course after pediatric living donor liver transplantation (LDLT) have rarely been reported. Between June 1990 and September 2003, 527 pediatric patients underwent primary LDLT with left lobe grafts, among which 479 patients with functioning grafts at 3 months after LDLT were included in this analysis. The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and body weight from 3.

Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice.

Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2-/- knockout (KO) mice to explore the physiological role of mGluR2 in brain function.

ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.

Rho-associated kinase (ROCK) I mediates signaling from Rho to the actin cytoskeleton. To investigate the in vivo functions of ROCK-I, we generated ROCK-I-deficient mice. Loss of ROCK-I resulted in failure of eyelid closure and closure of the ventral body wall, which gave rise to the eyes open at birth and omphalocele phenotypes in neonates.

Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.

Although Rho regulates cytokinesis, little was known about the functions in mitosis of Cdc42 and Rac. We recently suggested that Cdc42 works in metaphase by regulating bi-orient attachment of spindle microtubules to kinetochores. We now confirm the role of Cdc42 by RNA interference and identify the mechanisms for activation and down-regulation of Cdc42.

Zebrafish GADD45beta genes are involved in somite segmentation.

Somites in vertebrates are periodic segmented structures that give rise to the vertebrae and muscles of body. Somites are generated from presomitic mesoderm (PSM), but it is not fully understood how cellular differentiation and segment formation are achieved in the anterior PSM. We report here that zebrafish gadd45beta1 and gadd45beta2 genes are periodically expressed as paired stripes adjacent to the neural tube in the anterior PSM region where presomitic cells mature.

Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoE-deficient mice.

Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP).

Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia.

Ezrin/radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that radixin-deficient (Rdx(-)(/)(-)) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset ( approximately 2 wk), in the cochlea and vestibule of Rdx(-)(/)(-) mice, stereocilia developed normally in which ezrin was concentrated.

JACOP, a novel plaque protein localizing at the apical junctional complex with sequence similarity to cingulin.

The apical junctional complex is composed of various cell adhesion molecules and cytoplasmic plaque proteins. Using a monoclonal antibody that recognizes a chicken 155-kDa cytoplasmic antigen (p155) localizing at the apical junctional complex, we have cloned a cDNA of its mouse homologue. The full-length cDNA of mouse p155 encoded a 148-kDa polypeptide containing a coiled-coil domain with sequence similarity to cingulin, a tight junction (TJ)-associated plaque protein.

Establishment and characterization of cultured epithelial cells lacking expression of ZO-1.

In well polarized epithelial cells, closely related ZO-1 and ZO-2 are thought to function as scaffold proteins at tight junctions (TJs). In epithelial cells at the initial phase of polarization, these proteins are recruited to cadherin-based spotlike adherens junctions (AJs). As a first step to clarify the function of ZO-1, we successfully generated mouse epithelial cell clones lacking ZO-1 expression (ZO-1-/- cells) by homologous recombination.

A new look at Rho GTPases in cell cycle: role in kinetochore-microtubule attachment.

Rho GTPases including Rho, Rac and Cdc42 are involved in cell morphogenesis by inducing specific types of actin cytoskeleton and alignment and stabilization of microtubules. Previous studies suggest that they also regulate cell cycle progression; Rho, Rac and Cdc42 regulate the G(1)-S progression and Rho controls cytokinesis. However, a role of Rho GTPases in nuclear division has not been definitely shown.

Cdc42 and mDia3 regulate microtubule attachment to kinetochores.

During mitosis, the mitotic spindle, a bipolar structure composed of microtubules (MTs) and associated motor proteins, segregates sister chromatids to daughter cells. Initially some MTs emanating from one centrosome attach to the kinetochore at the centromere of one of the duplicated chromosomes. This attachment allows rapid poleward movement of the bound chromosome.

Actin polymerization-driven molecular movement of mDia1 in living cells.

mDia1, a Rho effector, belongs to the Formin family of proteins, which shares the conserved tandem FH1-FH2 unit structure. Formins including mDia1 accelerate actin nucleation while interacting with actin filament fast-growing ends. Here our single-molecule imaging revealed fast directional movement of mDia1 FH1-FH2 for tens of microns in living cells.

Regeneration of the vocal fold using autologous mesenchymal stem cells.

The aim of this study was to regenerate the injured vocal fold by means of selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle dogs were used for this experiment. Selective incubation of MSCs from bone marrow was done.

Prostanoids in immunity: roles revealed by mice deficient in their receptors.

Prostanoids including prostaglandins (PGs) and thromboxanes (TX) are a group of lipid mediators formed and released in response to various, often noxious, stimuli. While the roles of prostanoids in acute inflammatory responses are well known and have been extensively studied, it is generally believed that they play very little in immunity. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis have little effects on immune processes in vivo.

Advanced cholangiocarcinoma in a patient with stage I primary sclerosing cholangitis.

A 29-year-old woman presented with jaundice and fever in May 2001. Cholangiography showed multiple strictures and beading of the biliary tree, with a large stricture in the common bile duct and marked dilatation of the hilar bile ducts. Typical cholangiography findings and elevated hepatobiliary enzymes suggested primary sclerosing cholangitis (PSC).

mGluR2 postsynaptically senses granule cell inputs at Golgi cell synapses.

In the cerebellar circuit, Golgi cells are thought to contribute to information processing and integration via feedback mechanisms. In these mechanisms, dynamic modulation of Golgi cell excitability is necessary because GABA from Golgi cells causes tonic inhibition on granule cells. We studied the role and synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) at granule cell-Golgi cell synapses, using whole-cell recording of green fluorescent protein-positive Golgi cells of wild-type and mGluR2-deficient mice.