TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway.

TAK1 mitogen-activated protein kinase kinase kinase participates in the Interleukin-1 (IL-1) signaling pathway by mediating activation of JNK, p38, and NF-kappaB. TAK1-binding protein 2 (TAB2) was previously identified as an adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1.

Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis.

Epsin is a key molecule in receptor-mediated endocytosis. Epsin is phosphorylated and ubiquitinated, and these post-translational modifications are necessary for the regulation of endocytosis. Since human Epsin (hEpsin) has two ubiquitin-interacting motifs (UIMs), we investigated the roles of these UIMs in endocytosis.

[Clinical investigation of the 8 cases with AIDS (acquired immunodeficiency syndrome)-associated progressive multifocal leukoencephalopathy (PML)].

We experienced 8 cases of progressive multifocal leukoencephalopathy (PML) complicated by human immunodeficiency virus (HIV) type-1 infection from 1985 to 1999. These cases showed dementia, bradykinesia, dysarthria, hemiparesis, and so on. All of the cases were severely immunocompromised hosts, because none had more than 150/mm3 CD4 + lymphocytes; indeed, 5 of the cases were below 20/mm3.

Delayed ischemic stroke associated with methamphetamine use.

A 19-year-old woman had right occipital infarction 3 months after she had injected methamphetamine. No other possible causes of stroke could be found in this case. Magnetic resonance angiography revealed beading of the right posterior cerebral artery, which suggested vasculitis.

[The neurology of HIV infection: clinical features of HIV encephalopathy and future problems in the HAART era].

Since the introduction of highly active antiretroviral therapy (HAART), which has been available for most patients in developed world, HIV/AIDS has become a chronic disorder with dramatic reduction in mortality and morbidity due to HIV/AIDS and related diseases. However, from the nationwide survey of HIV-related neurological complications and analysis of our series of total 290 AIDS patients before and after HAART introduction, main neurological complications and opportunistic infections of AIDS patients remain unchanged after the introduction of HAART in Japan. It is crucial that we let a people know that the prevention and treatment of HIV infection is impotant.

Incapacitating lower limb pain syndrome in cord blood stem cell transplant recipients with calcineurin inhibitor.

Calcineurin-inhibitor induced pain syndrome (CIPS) is a newly described entity with a characteristic feature of sudden onset of severe lower limb pain, and high levels of cyclosporine or tacrolimus may be involved in the pathogenesis. This syndrome is rarely seen in recipients of hematopoietic stem cell transplantation (HSCT) compared with other organ transplant recipients, however, heightened awareness of this complication after HSCT may be needed for hematologists, as misdiagnosis can result in catastrophic consequences. We report herein two cases of lower limb pain syndrome, with some clinical features resembling CIPS, occurring during the early phase of cord blood stem cell transplantation for hematological malignancy.

[A case of Crow-Fukase syndrome showing improvement following excision and irradiation of bone lesions].

A 57-year-old woman suffering from pleural and pericardial effusion, pulmonary hypertention, lymphadenopathy, hepatosplenomegaly, edema, hypertrichosis, small hemangioma and polyneuropathy was diagnosed as Crow-Fukase syndrome. Osteoctomy of the left second rib and irradiation of this rib and the left iliac bone were performed. Serum vascular endothelial growth factor (VEGF) level decreased to less than one-half the level before the operation (from 5,180 to 2,150 pg/ml).

[Immunosuppressive-associated encephalopathy in bone marrow transplant recipients].

We studied clinical features of immunosuppressive (cyclosporine, tacrolimus) associated encephalopathy in bone marrow transplant patients. 378 cases of allogeneic bone marrow transplant recipients over fifteen years old of chronic and acute leukemia (CML, ANLL, ALL) (n = 311), myelodysplastic syndrome (MDS) (n = 42) and severe aplastic anemia (SAA) (n = 25) were investigated. Immunosuppressive associated encephalopathy occurred in 12 cases.

Synaptic scaffolding molecule interacts with axin.

Synaptic scaffolding molecule (S-SCAM) is a synaptic protein that consists of PDZ domains, a guanylate kinase domain, and WW domains. It interacts with N-methyl-d-aspartate receptor subunits, neuroligin, and beta-catenin. Here, we identified Axin as a novel binding partner of S-SCAM.

Sall1, a causative gene for Townes-Brocks syndrome, enhances the canonical Wnt signaling by localizing to heterochromatin.

The Spalt (sal) gene family plays an important role in regulating developmental processes of many organisms. Mutations of human SALL1 cause the autosomal dominant disorder, Townes-Brocks syndrome (TBS), and result in ear, limb, anal, renal, and heart anomalies. Targeted deletion of mouse Sall1 results in kidney agenesis or severe dysgenesis.

Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase.

Dvl is a key protein that transmits the Wnt signal to the canonical beta-catenin pathway and the noncanonical planar cell polarity (PCP) pathway. We studied the roles of Rho-associated kinase (Rho-kinase), which is activated by Dvl in the PCP pathway of mammalian cells. The expression of Dvl-1, Wnt-1, or Wnt-3a activated Rho-kinase in COS cells, and this activation was inhibited by the Rho-binding domain of Rho-kinase.

Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.

The c-myb proto-oncogene product (c-Myb) regulates both the proliferation and apoptosis of hematopoietic cells by inducing the transcription of a group of target genes. However, the biologically relevant molecular mechanisms that regulate c-Myb activity remain unclear. Here we report that c-Myb protein is phosphorylated and degraded by Wnt-1 signal via the pathway involving TAK1 (TGF-beta-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase).

Identification and characterization of a novel Dvl-binding protein that suppresses Wnt signalling pathway.

Background: Dvl is a cytoplasmic protein to regulate the stability of beta-catenin in the Wnt signalling pathway. However, the molecular mechanism by which Dvl regulates the Wnt signalling pathway is not fully understood.

Results: We identified a novel protein that binds to Dvl and named it Daple.

Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation.

The mammalian mitogen-activated protein (MAP) kinase kinase kinase apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component in cytokine- and stress-induced apoptosis. It also regulates cell differentiation and survival through p38 MAP kinase activation. Here we show that Ca2+ signalling regulates the ASK1-p38 MAP kinase cascade.

Effects of information and reward on stimulus-preceding negativity prior to feedback stimuli.

The purpose of the present study was to investigate the effects of informational and motivational level of feedback stimuli on the stimulus-preceding negativity (SPN). In the time estimation task, in which a visual stimulus was presented 3 s after a voluntary movement, (a) the information level (high information and low information) and (b) the motivation level (reward and no-reward) for feedback stimuli were manipulated. Under the high-information condition, subjects received feedback information about (1) correctness (correct or incorrect), (2) direction of error (under- or overestimate), and (3) degree of accuracy (accurate or less accurate) of their time estimation.

A novel laparoscopic technique for stapled colon and rectal anastomosis.

Background: We present new techniques of stapling anastomosis at laparoscopic colorectal surgery with retrospective review of data.

Methods: A triangulating stapling technique (T method) was performed in 101 laparoscopic colectomies. Adouble stapling technique (DST) with rectal division by a conventional linear stapler (Abd method) was used in 5 cases of upper/middle rectal cancers and subsequent eversion of the distal rectum from the anus (Ev method) was used for 4 low rectal cancers.

Novel non-peptide inhibitors targeting death receptor-mediated apoptosis.

We have previously reported that ECH, (2R, 3R, 4S)-2,3-epoxy-4-hydroxy-5-hydroxymethyl-6-(1E)-propenyl-cyclohex-5-en-1-one inhibits Fas-mediated apoptosis by blocking self-activation of pro-caspase-8 in the death-inducing signaling complex (DISC). A series of ECH derivatives were asymmetrically synthesized via key synthetic intermediates obtained from lipase-catalyzed kinetic resolution. Inhibitory activities of the derivatives towards death receptor-mediated apoptosis both in type I and type II cells were investigated, revealing that novel non-peptide inhibitors, RKTS-33 and RKTS-34, are effective as ECH.

Siah-1 facilitates ubiquitination and degradation of synphilin-1.

Parkinson's disease is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and appearance of Lewy bodies, cytoplasmic inclusions that are highly enriched with ubiquitin. Synphilin-1, alpha-synuclein, and Parkin represent the major components of Lewy bodies and are involved in the pathogenesis of Parkinson's disease. Synphilin-1 is an alpha-synuclein-binding protein that is ubiquitinated by Parkin.

The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.

Wnt signaling controls a variety of developmental processes. The canonical Wnt/beta-catenin pathway functions to stabilize beta-catenin, and the noncanonical Wnt/Ca(2+) pathway activates Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In addition, the Wnt/Ca(2+) pathway activated by Wnt-5a antagonizes the Wnt/beta-catenin pathway via an unknown mechanism.

[A clinical study of pachymeningitis].

We report five patients with cranial and spinal pachymeningitis not associated infections or tumors. The underlying causes of pachymeningitis in four patients were Sjögren syndrome, Wegener's granulomatosis, microscopic polyangitis, and dermatomyositis, respectively. In one patient, the cause was unknown.

Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway.

Duplin binds to beta-catenin and inhibits the Wnt signaling pathway, thereby leading to repression of the beta-catenin-mediated transactivation and Xenopus axis formation. To find an additional function of Duplin, yeast two-hybrid screening was carried out. Importin alpha was isolated as a binding protein of Duplin.

Facial myokymia associated with an isolated lesion of the facial nucleus.

We report on a patient with transient facial myokymia. He had an isolated lesion of the right facial nucleus in the pontine tegmentum. Facial myokymia is a rare symptom and its pathogenesis is not known.