Correlation between portal vein anatomy and bile duct variation in 407 living liver donors.

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.

Apomictic parthenogenesis in a parasitoid wasp Meteorus pulchricornis, uncommon in the haplodiploid order Hymenoptera.

Although apomixis is the most common form of parthenogenesis in diplodiploid arthropods, it is uncommon in the haplodiploid insect order Hymenoptera. We found a new type of spontaneous apomixis in the Hymenoptera, completely lacking meiosis and the expulsion of polar bodies in egg maturation division, on the thelytokous strain of a parasitoid wasp Meteorus pulchricornis (Wesmael) (Braconidae, Euphorinae) on pest lepidopteran larvae Spodoptera litura (Fabricius) (Noctuidae). The absence of the meiotic process was consistent with a non-segregation pattern in the offspring of heterozygous females, and no positive evidence was obtained for the induction of thelytoky by any bacterial symbionts. We discuss the conditions that enable the occurrence of such rare cases of apomictic thelytoky in the Hymenoptera, suggesting the significance of fixed heterosis caused by hybridization or polyploidization, symbiosis with bacterial agents, and occasional sex. Our finding will encourage further genetic studies on parasitoid wasps to use asexual lines more wisely for biological control.

Excitability of small-diameter trigeminal ganglion neurons by 5-HT is mediated by enhancement of the tetrodotoxin-resistant sodium current due to the activation of 5-HT(4) receptors and/or by the inhibition of the transient potassium current.

The aims of the present study were to investigate whether the activation of the 5-HT receptor subtypes (5-HT(4) and 5-HT(3)) acted significantly on the modification of the tetrodotoxin-resistant sodium current (I(NaR)) in small-sized rat trigeminal ganglion (TG) neurons and whether the inhibition of the transient K(+) current (I(A)) contributed to the excitability in those neurons. 5-HT applications in at concentrations ranging from 0.01-10 microM significantly increased the peak I(NaR). One micromolar 5-HT application caused the greatest increase in the peak I(NaR) amplitude accompanied by a hyperpolarizing shift in the activation curve. A similar modification of I(NaR) properties was also obtained via the application of the 5-HT(4) receptor agonist, RS 67333, in concentrations ranging from 0.001-1 microM. The largest effects of 5-HT (1 microM) and RS 67333 (0.1 microM) on the modification of I(NaR) were abolished by pretreatment with ICS 205-930 (a 5-HT(3/4) receptor antagonist, 10 microM), which showed no significant effect on the baseline I(NaR). However, ICS 205-930 application at 30 microM caused a significant decrease in the baseline I(NaR). Phenylbiguanide (a 5-HT(3) receptor agonist) did not significantly alter I(NaR) properties when applied in concentrations ranging from 1 to 100 microM. The application of 0.1 microM RS 67333 decreased the transient K(+) current (I(A)) by approximately 31%. The threshold for action potential generation was significantly lower after the application of 0.1 microM RS 67333. Furthermore, 0.1 microM RS 67333 application increased the number of action potentials and the resting membrane potential got more positive, but it decreased the duration of depolarization phase of action potential. In addition, neither the additional application of 1 microM 5-HT in the presence of 10 microM forskolin, a stimulator of adenylyl cyclase, nor the opposite applications of 5-HT and forskolin caused the enhancement of increased I(NaR), which indicates the presence of an 'occluding effect.' These results suggest that the 5-HT-induced modification of I(NaR) is mediated by the activation of 5-HT(4) receptors, involving a cAMP-dependent signaling pathway, and that the inhibition of I(A) following the application of a 5-HT(4) receptor agonist also contributes to the increased number of action potentials.

Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus.

Murine cytomegalovirus (MCMV) immediate-early (IE) 2 protein has been reported to be dispensable for growth and latency in mice. Therefore, its role in viral pathogenesis and tissue tropism is not known. Here we prepared specific antibodies to the IE2 and IE3 proteins by using fusion proteins expressed in Escherichia coli as antigens. Immunostaining of MCMV-infected cultured fibroblasts revealed IE2 protein to be expressed diffusely in the nucleoplasm similar to the IE1 protein. In contrast, expression of the IE3 protein, 88 kDa, exhibited a punctate pattern in the nucleus in the early phase of infection then diminished. In the brain of neonatal mice infected with MCMV, both IE2 and IE3 proteins were detected immunohistochemically in the cells of the ventricular walls early in infection. When the infection was prolonged, the IE2 protein was expressed in neurons of the cortex and hippocampus, while the IE3 protein was preferentially expressed in glial cells in the early phase of infection, and its levels declined during the infection. These results suggest that the IE2 protein may play a role in persistent infection in neurons, whereas the IE3 protein, expressed preferentially in glial cells, may play the main role in acute infection.

A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle.

Pin2/TRF1 was independently identified as a telomeric DNA binding protein (TRF1) [1] and as a protein (Pin2) that can bind the mitotic kinase NIMA and suppress its ability to induce mitotic catastrophe [2, 3]. Pin2/TRF1 has been shown to bind telomeric DNA as a dimer [3-7] and to negatively regulate telomere length [8-11]. Interestingly, Pin2/TRF1 levels are regulated during the cell cycle, being increased in late G2 and mitosis and degraded as cells exit from mitosis [3]. Furthermore, overexpression of Pin2/TRF1 induces mitotic entry and then apoptosis [12]. This Pin2/TRF1 activity can be significantly potentiated by the microtubule-disrupting agent nocodazole [12] but is suppressed by phosphorylation of Pin2/TRF1 by ATM; this negative regulation is important for preventing apoptosis upon DNA damage [13]. These results suggest a role for Pin2/TRF1 in mitosis. However, nothing is known about how Pin2/TRF1 is involved in mitotic progression. Here, we describe a surprising physical interaction between Pin2/TRF1 and microtubules in a cell cycle-specific manner. Both expressed and endogenous Pin2/TRF1 proteins were localized to the mitotic spindle during mitosis. Furthermore, Pin2/TRF1 directly bound microtubules via its C-terminal domain. Moreover, Pin2/TRF1 also promoted microtubule polymerization in vitro. These results demonstrate for the first time a specific interaction between Pin2/TRF1 and microtubules in a mitosis-specific manner, and they suggest a new role for Pin2/TRF1 in modulating the function of microtubules during mitosis.

Items regarded as important for satisfaction in daily life by elderly residents in Kitakyushu, Japan.

The objective of this study was to determine what items were important for satisfaction in the daily life of elderly Japanese people living at home. The subjects consisted of 996 persons living in Yahatanishi Ward, Kitakyushu City, Japan, two percent of residents aged 60 years or over, who were randomly selected from the official register of voters. A questionnaire was sent to the subjects to determine their profiles and asking them to select the five items they considered most important for satisfaction in daily life from 35 predetermined items. The items with a significant difference using a chi 2 test between age groups, gender, place of residence, living conditions and level of disability were analyzed by logistic regression analysis. The top five items selected were "good health" (86%), "social security and pension" (47%), "self-care independence" (45%), "marital satisfaction" (34%), and a "good relationship with relatives" (33%). Logistic regression analysis showed gender, age group, living conditions, and level of disability significantly affected the preference for selection of 12 items. Men or younger persons regarded "health" and a "good relationship with a spouse" as very important, whereas women, older persons, or persons with a disability considered "self-care independence" and the "ability to walk" as important. The items selected for satisfaction in daily life and the order of preference yield important information about rehabilitative and social welfare services for elderly persons living at home.

Multiple interactions among the components of the recombinational DNA repair system in Schizosaccharomyces pombe.

Schizosaccharomyces pombe Rhp55 and Rhp57 are RecA-like proteins involved in double-strand break (DSB) repair. Here we demonstrate that Rhp55 and Rhp57 proteins strongly interact in vivo, similar to Saccharomyces cerevisiae Rad55p and Rad57p. Mutations in the conserved ATP-binding/hydrolysis folds of both the Rhp55 and Rhp57 proteins impaired their function in DNA repair but not in cell proliferation. However, when combined, ATPase fold mutations in Rhp55p and Rhp57p resulted in severe defects of both functions, characteristic of the deletion mutants. Yeast two-hybrid analysis also revealed other multiple in vivo interactions among S. pombe proteins involved in recombinational DNA repair. Similar to S. cerevisiae Rad51p-Rad54p, S. pombe Rhp51p and Rhp54p were found to interact. Both putative Rad52 homologs in S. pombe, Rad22p and Rti1p, were found to interact with the C-terminal region of Rhp51 protein. Moreover, Rad22p and Rti1p exhibited mutual, as well as self-, interactions. In contrast to the S. cerevisiae interacting pair Rad51p-Rad55p, S. pombe Rhp51 protein strongly interacted with Rhp57 but not with Rhp55 protein. In addition, the Rti1 and Rad22 proteins were found to form a complex with the large subunit of S. pombe RPA. Our data provide compelling evidence that most, but not all, of the protein-protein interactions found in S. cerevisiae DSB repair are evolutionarily conserved.

Water drinking causes a biphasic change in blood composition in humans.

To investigate precisely the fluid shifts associated with water drinking in humans, we measured continuously blood density and plasma electrolyte concentrations using the mechanical oscillator technique and ion-selective electrodes, respectively, in healthy young volunteers before (10 min) and after (48 min) water drinking for a period of 2 min. Beat-by-beat blood pressure was also monitored throughout the experiment. Drinking 1 l tap water caused a transient increase in blood density immediately after the drinking episode (from 1051.1+/-0.5 g/l before drinking to 1051.8+/-0.5 g/l 4 min after the start of drinking, P<0.05), followed by a gradual reduction (1050.1+/-0.5 g/l at 31 min). This drinking-induced change paralleled those of haematocrit, plasma density and plasma volume. Plasma [Na+] and [Cl-] and osmolality decreased after drinking without transient increases and reached minima at about 30 min. A transient increase in mean arterial blood pressure was observed prior to the increase in blood density. These findings suggest that water drinking causes a biphasic change in plasma volume: initial haemoconcentration, probably due to sympathetic acceleration, followed by haemodilution due to the post-absorptive effect, and further suggest that the fluid shift associated with the initial haemoconcentration is isosmotic.

Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice.

Cytomegalovirus (CMV) is the most common infectious cause of congenital anomalies of the CNS in humans. We recently reported that the murine cytomegalovirus (MCMV) immediate-early (IE) gene promoter directs astrocyte-specific expression in adult transgenic mice. In the present study, we analyzed the activation of the MCMV IE promoter in developing transgenic mouse brains and compared the activation with that of the Musashi 1 (Msi1) gene, which is expressed in neural progenitor cells, including neural stem cells. During the early phase of neurogenesis, the transgene was expressed predominantly in endothelial cells of the vessels, but not in neuroepithelial cells in which Msi1 was expressed. During later stages of gestation, expression of the transgene was largely restricted to the ventricular zone (VZ) in the CNS, similar to the expression of Msi1. In neurosphere cultures from transgenic embryos in the late phase of neurogenesis, the transgene was expressed in some cells of neurospheres expressing Msi1 and nestin. In neural precursor cells induced to differentiate from stem cells, expression of the transgene was detected in glial progenitor cells, expressing GFAP, nestin, and Msi1, but not in cells expressing MAP2 or MAG. In postnatal development, persistent expression of the transgene was observed in astrocyte lineage cells as was Msi1. These spatiotemporal changes of the MCMV IE promoter activity during development of transgenic mice correlated with susceptible sites in congenital HCMV infection. Moreover, this transgenic mouse model may provide useful model for analysis of the regulation of the switching of neuronal and astrocyte differentiation, and the maintenance of the astrocyte lineage.

A new endo aortic occlusion balloon for limited access cardiac surgery: development and clinical evaluation.

In recent years, minimally invasive cardiac surgery (MICS), or limited access cardiac surgery, has been presented as a promising operative procedure. We developed a new balloon device that is inserted directly into the ascending aorta to stop the heart during limited access cardiac surgery. The balloon has a three lumen structure: balloon lumen port, cardioplegia/vent lumen port, and aortic root lumen port. This direct EAC balloon catheter, designed to be inserted directly into the ascending aorta, is different from the Heartport system. The Heartport EAC balloon catheter is inserted into the aorta via an artery in the lower limb, making lower limb arterial disease a key concern. Our Direct Endo Aortic Clamp (EAC) balloon overcomes this problem. The device was clinically used in seven cardiac cases. All patients were discharged within 5 postoperative days, confirming the utility of the device.

An autopsy case of the schizophrenic 32 years after lobotomy.

An autopsy case is reported here of a 69-year-old patient with schizophrenia, who was known retrospectively to have had a prefrontal lobotomy 32 years previously. The patient was diagnosed as schizophrenic at the age of 24 and the lobotomy was undertaken 13 years later. The patient was recently found outside in a dehydrated condition and admitted to a general hospital, where he died of respiratory failure. Bilateral cystic lesions were found in the deep white matter of the frontal lobe. The cyst walls consisted of glial fibrous tissues, and severe demyelination with axonal destruction was diffusely observed in the white matter of the frontal lobe. In the thinner frontal cortex without arcuate fibers (U fibers) close to the cavities, cytoarchitectural abnormalities were observed. In the thalamic nuclei marked retrograde degeneration and astrocytic gliosis were observed. The detailed neuropathological findings of a lobotomized schizophrenic brain are reported here. It is proposed that one should be reminded of a lobotomized brain if bilateral cysts are found.

Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy.

We report a 56-year-old man in whom an olfactory neuroblastoma with epithelial and endocrine differentiation transformed into a mature ganglioneuroma after chemoradiotherapy. The tumor arising from the sphenoidal and maxillary sinuses showed rapid growth into the frontal lobe and metastasis to the cervical lymph nodes. The patient showed signs of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A radical craniofacial resection of the primary tumor was performed after 16 Gy of local irradiation and systemic chemotherapy. Three months after the operation, the patient died of mediastinal metastasis. The biopsy before chemoradiotherapy showed a neuroblastoma with Homer-Wright rosettes, fibrillary matrix, Flexner-Wintersteiner rosettes and antidiuretic hormone production. After chemoradiotherapy, the histology changed to that of a ganglioneuroma consisting of large ganglion cells and Schwann cells without immature neuroblastoma components. Although transformation to ganglioneuroma in an adrenal neuroblastoma is common, an olfactory neuroblastoma showing ganglioneuronal maturation after chemoradiotherapy has not been reported. The pluripotent progenitor cells of the olfactory neurons may be the origin and their existence explains why various neoplasms with neuronal and epithelial differentiation arise from the olfactory mucosa.

[A case of mesoblastic nephroma in an adult patient].

We treated a rare case of adult mesoblastic nephroma. The patient was a 52-year-old Japanese man with the chief complaint of intermittent gross hematuria and left lumbar pain. Abdominal ultrasonography, computed tomography, excretory urography, retrograde pyelography and angiography revealed a left renal tumor suspected to be a left pelvic tumor. A left nephroureterectomy was performed. The histologic examination showed a mesoblastic nephroma. A total of 38 adult mesoblastic nephroma cases were reviewed.

Phosphoglyceride crystal deposition disease.

An extremely rare phosphoglyceride deposition disease is reported. A healthy 62-year-old Japanese woman suffered from tumors that repeatedly appeared in injured soft tissues for more than 20 years. No immunologic disorders or abnormal laboratory data were found. Histology showed foreign body granulomas consisting of macrophages surrounding yellowish-white crystals. The crystals were weakly positive by von Kossa's method, were dissolved in 30% acetic acid with gas, and were easily dissolved in 0.1 N NaOH or potassium hydroxide, losing their crystal structure. Using a scanning electron microscopy X-ray microanalyzer, phosphorus and calcium peaks were detected. Phosphoglycerides were detected by microscopic infrared spectrophotometry and microsampling mass spectrometry. The gold hydroxamic acid method for detecting phosphoglyceride showed strong positive staining in the crystals. Based on the above analyses, the deposited crystals were regarded as phosphoglyceride, which bound calcium as a counter ion. The crystals tended to be deposited at sites of injury, where macrophages had accumulated. The patient had received many injections of a medicine made from alcohol extract from bovine liver. We suspect that this medicine was related to the cause of the deposition as the deposition repeatedly appeared at the site of the injections.

Participation of the conjugated diene part for potent cytotoxicity of callystatin A, a spongean polyketide.

5-epi, 10-epi, 8-Deethyl, and 10-demethyl analogues of callystatin A, a potent cytotoxic spongean polyketide, were synthesized to elucidate structure-requirement for cytotoxic potency. Inversion of the asymmetric center at C-10 in callystatin A minimally affected the activity, while lack of the 10-methyl group in callystatin A decreased cytotoxicity. In addition, the C-5 epimer and the 8-deethyl analogue of callystatin A showed weaker cytotoxicity.

Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus.

Cytomegalovirus (CMV) is the most frequent infectious cause of developmental disorders of the central nervous system (CNS) in humans. Infection of the CNS stem cells seems to be primarily responsible for the generation of the brain abnormalities. In this study, we evaluated the infectivity of murine CMV (MCMV) in epidermal growth factor (EGF)-responsive CNS stem cells prepared from fetal mouse brains, and studied the effect of infection on growth and differentiation of the stem cells. The CNS stem cells were permissive for MCMV infection, although MCMV replication was slower than in mouse embryonic fibroblasts. MCMV infection inhibited the growth and DNA replication of the stem cells. A clonogenic assay revealed that MCMV infection suppressed generation of colonies from single stem cells. When uninfected stem cells were induced to differentiate, a decrease in expression of the primitive neuroepidermal marker nestin was observed by immunocytochemistry and flow cytometry, whereas expression of neurofilament and glial fibrillary acidic protein (GFAP) were induced. In virus-infected CNS stem cells, nestin expression was retained, whereas the expression of neurofilament was more severely inhibited than that of GFAP in these cells. Two-color flow cytometry showed that differentiated glial precursor cells were preferentially susceptible to MCMV infection. MCMV-infected and uninfected CNS stem cells were transplanted into the neonatal rat brains. The reduced number of infected stem cells were engulfed into the subventricular zone and expressed GFAP, but did not migrate further, in contrast to the uninfected stem cells. These results suggest that suppression of the growth of the CNS stem cells and inhibition of the neuronal differentiation by CMV infection may be primary causes of disorders of brain development in congenital CMV infection.

Myoepithelial carcinoma of the lung arising from bronchial submucosa.

Myoepithelial neoplasm mainly occurs in the salivary glands and breasts and is extremely rare in the lung. To our knowledge, this report describes the first documented case of a myoepithelial carcinoma present in the lung. The tumor derived from the right main bronchial submucosa and exhibited a dual epithelial and smooth muscular phenotype by immunohistochemical and ultrastructural studies. It invaded the neighboring pulmonary tissue and the hilar lymph nodes. Despite a right pneumonectomy and chemotherapy, metastasis was found in the left lung 7 months later.

Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines.

Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.