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Biomedical subjects

T Yamanaka

Publications and source records attributed to T Yamanaka.

At least 73 records · Page 4Linked to original sources

PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex.

BACKGROUND: PAR-6, aPKC and PAR-3 are polarity proteins that co-operate in the establishment of cell polarity in Caenorhabditis elegans and Drosophila embryos. We have recently shown that mammalian aPKC is required for the formation of the epithelia-specific cell-cell junctional structure. We have also revealed that a mammalian PAR-6 forms a ternary complex with aPKC and ASIP/PAR-3, and localizes at the most apical end of the junctional complex in epithelial cells. RESULTS: The ternary complex formation and junctional co-localization of PAR-6 with aPKC and ASIP/PAR-3 are observed during the early stage of epithelial cell polarization. In addition, over-expression of the PAR-6 mutant with CRIB/PDZ domain in MDCK cells disturbs the cell-cell contact-induced junctional localization of tight junction proteins, as well as inhibiting TER development. Furthermore, the binding of Cdc42:GTP to the CRIB/PDZ domain of PAR-6 enhances the kinase activity of PAR-6-bound aPKC. Detailed analyses suggest that the binding of PAR-6 to aPKC has the intrinsic potential to activate aPKC, which is only released when Cdc42:GTP binds to the CRIB/PDZ domain. CONCLUSION: The results indicate the involvement of PAR-6 in the aPKC function which is required for the cell-cell adhesion-induced formation of epithelial junctional structures, possibly through the cooperative regulation of aPKC activity with Cdc42.

Adaptor Proteins, Signal Transducing↗

Differential gene expression in the small intestines of wildtype and W/W(V) mice.

UNLABELLED: Much of the evidence demonstrating the role of interstitial cells of Cajal (ICC) in pacemaking and neurotransmission in the gastrointestinal tract comes from studies of W/W(V) mice. These animals have few pacemaker ICC in the small bowel due to reduced functional Kit protein. We examined gene expression in the small intestines of wildtype and W/W(V) mice. RNA expression in the jejunums of wildtype and W/W(V) mutants was studied using a differential gene expression METHOD: Seven known genes were differentially expressed in wildtype and W/W(V) mice. COX7B (cytochrome c oxidase, subunit VIIb) and SORCIN (encoding multidrug-resistance complex, class 4) were suppressed in both fed and fasted W/W(V) mice. Expression of another five genes was increased in W/W(V) mice: ADA (adenosine deaminase), MDH1 (malate dehydrogenase), RPL-8 (ribosomal protein L8), SPTB2 (spectrin, nonerythroid, beta subunit), and p6-5 (encoding phosphorylcholine [PC] T-cell suppressor factor [TsF]). Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state. We conclude that several genes are differentially expressed in the small intestines of W/W(V) mice where the major lesion is loss of pacemaker ICC. Differential gene display may help develop a molecular profile of motility disorders in which ICC are lost.

Adenosine Deaminase↗

A case of diastematomyelia associated with myeloschisis in a hemicord.

We report a case of myeloschisis on the right hemicord in a patient with diastematomyelia. The patient was a female neonate with myeloschisis visible at birth in the upper lumbar region. Radiological examination, including three-dimensional CT and MRI, clearly revealed a bony septum as well as the myeloschisis on the right hemicord, which enabled us to make a precise preoperative diagnosis of this complex anomaly. Closure of the myeloschisis and removal of the septum were successfully accomplished in one stage to prevent subsequent infection and neurological deterioration. The presence of combined diastematomyelia and myeloschisis is consistent with the hypothesis of an ontogenic basis of development and emphasizes the importance of early imaging for diagnosis in this complex anomaly.

Brown-Sequard Syndrome↗

Apoptotic response of eosinophils in chronic eosinophilic pneumonia.

To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The survival rate of eosinophils and the percentage of apoptotic cells of both types of eosinophils were examined, and the effects of interleukin 5 (IL-5) were evaluated. The role of Fas expression in apoptosis of these eosinophils was also studied. The survival rate of BAL-Eos on the third day of culture was significantly higher than that of PB-Eos (p < 0.01). This was associated with a lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4% and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic character of BAL-Eos differed from that of PB-Eos in at least three ways. Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h of incubation, whereas that on BAL-Eos did not change. Secondly, the expression of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05), whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/- 1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos, but not of BAL-Eos. These data suggested that Fas seemed to be involved in the apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by proinflammatory cytokines such as IL-5 leading to their accumulation in the lung. Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a crucial role chronic eosinophilic disorders.

Adult↗

Time-related changes of the cardiovascular system during maintenance anesthesia with sevoflurane and isoflurane in horses.

To clarify time-related changes in equine cardiovascular system during maintenance anesthesia (180 min, 1.2 minimum alveolar concentration) with sevoflurane (Sev-group) compared to isoflurane (Iso-group) as the basis for clinical use of Sev, horses were examined for the heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance (SVR) and pre-ejection period (PEP)/ejection time (ET) that is an index of the cardiac contractility. The HR was almost 30 beats/min in both groups without significant temporal change. MAP was significantly elevated with time but there was no significant difference between the groups. In the Sev-group, CI remained unchanged but the significant increase of CI with time was observed in the Iso-group. In the Sev-group SVR was significantly higher than that of the Iso-group and increased with time. No significant difference of PEP/ET was seen between the groups, but PEP/ET lowered with time in the Iso-group in association with prolonged ET. The results indicated that the time-dependent elevation of MAP in the Sev-group reflected increased SVR without increase of CI and that it reflected increased CI resulting from increased stroke volume in the Iso-group in association with lowered PEP/ET, that is, increased cardiac contractility.

Anesthesia, Inhalation↗

Cognitive behavioral therapy and fasting therapy for a patient with chronic fatigue syndrome.

Cognitive behavioral therapy temporarily alleviated symptoms of a chronic fatigue syndrome patient but the anxiety about rehabilitation into work became stronger and his symptoms worsened. This patient was successfully rehabilitated by fasting therapy. Natural killer cell activity and serum acylcarnitine levels recovered after fasting therapy. Though fasting therapy transiently increased physical and mental subjective symptoms, the patient gained self-confidence by overcoming difficulties after fasting therapy. A combination of cognitive behavioral therapy and fasting therapy is promising as a treatment for chronic fatigue syndrome.

Adult↗

Usefulness of the combination of pre- and intraoperative selective intraarterial calcium injection to detect residual insulinomas.

In a 35-year-old woman diagnosed with insulinoma selective intraarterial calcium injection was positive for proximal gastroduodenal artery and inferior pancreaticoduodenal artery involvement preoperatively. Although non-invasive imaging studies were negative, a mass was detected at the pancreatic uncus by intraoperative ultrasonography. Gastroduodenal artery calcium injection was performed after enucleation of the tumor. Following calcium injection, the insulin level was inappropriately increased and further pancreaticoduodenectomy was performed. After excision, another tumor was detected at the head of the pancreas by histopathological examination. As shown, selective intraarterial calcium injection is useful to localize tumors preoperatively and intraoperatively.

Adult↗

"Variable echo sign" (ultrasonographical alteration of echogenicity) in cavernous hepatic hemangioma.

There are few reports describing cavernous hepatic hemangiomas with alteration of ultrasonographical imaging during examinations. We performed ultrasonographic examination of 64 cavernous hepatic hemangiomas and recognized 26 cases (41%) with an alteration of echogenicity during the examinations. We refer to this alteration of echogenicity of cavernous hepatic hemangioma as a "variable echo sign". We performed angiography of the cavernous hepatic hemangiomas with variable echo sign. Most of these imaging patterns showed mild or moderate pooling, suggesting that the alteration of echogenicity might be based on a slow blood flow exchange. We suggest that a variable echo sign is specific to ultrasonographic imaging with cavernous hepatic hemangioma and may be useful to differentiate cavernous hepatic hemangioma from other tumors.

Adult↗

Combining transcatheter arterial chemoembolization with percutaneous ethanol injection therapy for small size hepatocellular carcinoma.

For patients with unresectable small size HCC, percutaneous ethanol injection therapy (PEIT) is used as a non-surgical treatment because it is difficult to achieve complete tumor necrosis by transcatheter arterial chemoembolization (TAE) alone. However, some small HCCs (<21 mm in diameter) are resistant to PEIT with incomplete tumor necrosis, which is associated with insufficient ethanol injection to the tumor. For more effective treatment for HCC, we performed a combination of TAE and PEIT on patients with small size HCC and evaluated the cumulative recurrence and survival rates. The recurrence rate in patients treated with the combination was less than that of TAE or PEIT alone. There were five patients without tumor recurrence during the follow-up period and three out of these underwent the combination treatment. The period of no recurrence was 33.4 months on average. In conclusion, we recommend combination therapy with TAE and PEIT for patients to accomplish more effective treatment of small size HCC.

Administration, Cutaneous↗

[A case of ovarian cancer with metastatic tumor in the liver with paclitaxel and carboplatin systemic chemotherapy was very effective].

An 82-year-old woman was admitted to the Dept. of Obstetrics and Gynecology, Yamanashi Medical University to try to identify the origin of a liver metastatic tumor. CT examination revealed a small tumor located adjacent to the uterine cervix in a cul-de-sac. With biopsy using MR, it was clearly shown histologically that the origin of the tumor was the ovary. Systemic chemotherapy with paclitaxel and carboplatin was selected as the most reasonable treatment for this case because of the patient's age. After 6 courses of this chemotherapy, the tumor in the cul-de-sac disappeared and the tumor in the liver decreased markedly. Furthermore, no severe side effects were seen during this treatment. This result indicated that systemic chemotherapy with paclitaxel and carboplatin is effective and safe in cases of advanced ovarian cancer.

Adenocarcinoma↗

Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue.

PURPOSE: Activation of transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappaB is constitutively activated in human gastric carcinoma tissues and, if so, to determine any correlation between NF-kappaB activity and clinicopathological features of gastric carcinoma. EXPERIMENTAL DESIGN: NF-kappaB activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 64 gastric carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-kappaB activation. RESULTS: Nuclear translocation of RelA was significantly high in tumor cells in comparison to that in adjacent normal epithelial cells (22.5 +/- 2.4% versus 8.6 +/- 1.5%, P < 0.0001). There was a significant correlation between NF-kappaB activation (nuclear translocation of RelA) and expression of urokinase-type plasminogen activator, an invasion-related factor and target of NF-kappaB in tumor cells (rho = 0.393; P = 0.0013). NF-kappaB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion of tumor cells (P = 0.0126), depth of invasion (P = 0.0539), peritoneal metastases (P = 0.0538), and tumor size (P = 0.0164). CONCLUSIONS: Collectively, the data show that NF-kappaB is constitutively activated in human gastric carcinoma tissues and suggest that NF-kappaB activity is related to tumor progression due to its transcriptional regulation of invasion-related factors such as urokinase-type plasminogen activator.

Active Transport, Cell Nucleus↗

Gamow-teller strengths of the inverse beta transition 176Yb-->176Lu for spectroscopy of proton-proton and other sub-MeV solar neutrinos

Discrete Gamow-Teller (GT) transitions 176Yb-->176Lu at low excitation energies have been measured via the ( 3He,t) reaction at 450 MeV and at 0 degrees. For 176Yb, two low-lying states are observed, setting low thresholds Q(nu) = 301 and 445 keV for neutrino ( nu) capture. Capture rates estimated from the measured GT strengths, the simple two-state excitation structure, and the low Q(nu) in Yb-Lu indicate that Yb-based nu detectors are well suited for a direct measurement of the sub-MeV solar electron-neutrino ( nu(e)) spectrum including pp neutrinos.

Journal Article↗

TOM1, an Arabidopsis gene required for efficient multiplication of a tobamovirus, encodes a putative transmembrane protein.

Host-encoded factors play an important role in virus multiplication, acting in concert with virus-encoded factors. However, information regarding the host factors involved in this process is limited. Here we report the map-based cloning of an Arabidopsis thaliana gene, TOM1, which is necessary for the efficient multiplication of tobamoviruses, positive-strand RNA viruses infecting a wide variety of plants. The TOM1 mRNA is suggested to encode a 291-aa polypeptide that is predicted to be a multipass transmembrane protein. The Sos recruitment assay supported the hypothesis that TOM1 is associated with membranes, and in addition, that TOM1 interacts with the helicase domain of tobamovirus-encoded replication proteins. Taken into account that the tobamovirus replication complex is associated with membranes, we propose that TOM1 participates in the in vivo formation of the replication complex by serving as a membrane anchor.

Amino Acid Sequence↗

Human galectin-3 is a novel chemoattractant for monocytes and macrophages.

Galectin-3 is a beta-galactoside-binding protein implicated in diverse biological processes. We found that galectin-3 induced human monocyte migration in vitro in a dose-dependent manner, and it was chemotactic at high concentrations (1.0 microM) but chemokinetic at low concentrations (10-100 nM). Galectin-3-induced monocyte migration was inhibited by its specific mAb and was blocked by lactose and a C-terminal domain fragment of the protein, indicating that both the N-terminal and C-terminal domains of galectin-3 are involved in this activity. Pertussis toxin (PTX) almost completely blocked monocyte migration induced by high concentrations of galectin-3. Galectin-3 caused a Ca2+ influx in monocytes at high, but not low, concentrations, and both lactose and PTX inhibited this response. There was no cross-desensitization between galectin-3 and any of the monocyte-reactive chemokines examined, including monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and stromal cell-derived factor-1alpha. Cultured human macrophages and alveolar macrophages also migrated toward galectin-3, but not monocyte chemotactic protein-1. Finally, galectin-3 was found to cause monocyte accumulation in vivo in mouse air pouches. These results indicate that galectin-3 is a novel chemoattractant for monocytes and macrophages and suggest that the effect is mediated at least in part through a PTX-sensitive (G protein-coupled) pathway.

Animals↗

Mediation by the protein-tyrosine kinase Tec of signaling between the B cell antigen receptor and Dok-1.

A variety of growth factor receptors induce the tyrosine phosphorylation of a nonreceptor protein-tyrosine kinase Tec as well as that of a Tec-binding protein of 62 kDa. Given the similarity in properties between this 62-kDa protein and p62(Dok-1), the possibility that these two proteins are identical was investigated. Overexpression of a constitutively active form of Tec in a pro-B cell line induced the hyperphosphorylation of endogenous Dok-1. Tec also associated with Dok-1 in a phosphorylation-dependent manner in 293 cells. Tec mediated marked phosphorylation of Dok-1 both in vivo and in vitro, and this effect required both the Tec homology and Src homology 2 domains of Tec in addition to its kinase activity. Expression of Dok-1 in 293 cells induced inhibition of Ras activity, suggesting that Dok-1 is a negative regulator of Ras. In the immature B cell line Ramos, cross-linking of the B cell antigen receptor (BCR) resulted in tyrosine phosphorylation of Dok-1, and this effect was markedly inhibited by expression of dominant negative mutants of Tec. Furthermore, overexpression of Dok-1 inhibited activation of the c-fos promoter induced by stimulation of the BCR. These results suggest that Tec is an important mediator of signaling from the BCR to Dok-1.

B-Lymphocytes↗

Anomalous X-Ray yields under surface wave resonance during reflection high energy electron diffraction and adatom site determination

In L x-ray emissions from a Si(111)-sqrt[3]xsqrt[3]-In surface induced by electron beam irradiation were measured as functions of the incident glancing angle. Under surface wave resonance conditions, anomalous x-ray intensities were clearly observed. Using dynamical calculations, these intensities are well explained as changes in density of the electron wave field at adatom positions. From these intensities, the adatom site was analyzed, and it was found that the T4 model is better than the H3 model.

Journal Article↗

Rapid compensatory changes in GABA receptor efficacy in rat vestibular neurones after unilateral labyrinthectomy.

1. The inhibitory effects of the GABAA agonist muscimol and the GABAB agonist baclofen on tonically active medial vestibular nucleus (MVN) neurones were recorded in slices of the rat dorsal brainstem in vitro, to determine whether any changes occurred in the functional efficacy of GABAergic inhibition in these cells during the initial rapid stage of 'vestibular compensation', the behavioural recovery that takes place after unilateral labyrinthectomy (UL). These experiments were carried out in preparations where the midline was cut, severing all commissural connections between the two vestibular nuclei. 2. Slices of the MVN were prepared from normal animals and animals that had been unilaterally labyrinthectomised 4 h earlier. The mean in vitro discharge rate of MVN neurones in the rostral region of the ipsi-lesional nucleus after UL was significantly higher than that in control slices, confirming our earlier reports of an increase in intrinsic excitability of these cells in the early stage of vestibular compensation. The in vitro discharge rates of caudal ipsi-lesional MVN cells, and rostral and caudal contra-lesional MVN cells, were not different from controls. 3. Muscimol and baclofen caused reversible, dose-related inhibition of the tonic discharge rate of MVN cells in control slices. In slices prepared from UL animals, MVN cells in the rostral region of the ipsi-lesional nucleus showed a marked downregulation of their response to both muscimol and baclofen, seen as a rightward shift and a decrease in slope of the dose-response relationships for the two agonists. In the contra-lesional nucleus, there was a small but significant upregulation of the responsiveness of both rostral and caudal MVN cells to baclofen, and a marked upregulation of the responsiveness of caudal MVN cells to muscimol. 4. In slices from animals that had undergone bilateral labyrinthectomy 4 h earlier, the downregulation of the functional efficacy of GABA receptors in the rostral MVN cells did not occur. The changes in GABA receptor efficacy after UL are therefore not due to the vestibular de-afferentation itself, but are instead due to the imbalance in excitability of the vestibular nuclei of the lesioned and intact sides, and the enhanced commissural inhibition of the ipsi-lesional MVN cells that follows UL. 5. The downregulation of GABA receptor efficacy in the ipsi-lesional MVN neurones is functionally compensatory, in that their response to commissural and cerebellar inhibitory drive will be significantly reduced after UL. Their intrinsic membrane conductances, and their remaining excitatory synaptic inputs, will consequently be more effective in causing depolarisation and the restoration of resting activity. Simultaneously the upregulation of GABAergic efficacy in the contra-lesional MVN will tend to reduce the hyperactivity on the contralateral side. These adaptive changes therefore represent a plausible cellular mechanism for the recovery of resting discharge in the ipsi-lesional MVN neurones, and the 're-balancing' of the excitability of the vestibular neurones of the lesioned and intact sides, as occurs after UL in vivo. 6. We propose that the adaptive regulation of the functional efficacy of GABA receptors in the MVN neurones may be an important cellular mechanism for the 'homeostasis of bilateral excitability' of the vestibular nuclei of the two sides.

Action Potentials↗