Recurrent attacks of optic neuritis and myelitis are the hallmarks of both neuromyelitis optica (NMO) and multiple sclerosis (MS). NMO immunoglobulin G (NMO-IgG), which recognizes astrocytic ...aquaporin-4 (AQP4) water channels, is a specific serum autoantibody that distinguishes NMO from MS. The pathogenic role of the anti-AQP4 antibody (AQP4-Ab, NMO-IgG) in NMO has been speculated based on several studies in vitro. The aim of this study was to demonstrate the pathogenicity of AQP4-Ab in vivo. We obtained IgG from patients who underwent therapeutic plasmapheresis, and developed an animal model by passive transfer of IgG to rats. The active lesions of the rats exhibited pathological characteristics strikingly similar to those of NMO, marked by astrocytic loss and perivascular deposition of immunoglobulin and complements. These findings provide the first evidence of the pathogenicity of AQP4-Ab in vivo and support the therapeutic efficacy of eliminating the antibodies by plasmapheresis.
Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and ...autoimmune diseases; one of which is Multiple sclerosis (MS) which affects the central nervous system. We investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
P. acidilactici R037 was orally administered to EAE mice to investigate the effects of R037. R037 treatment suppressed clinical EAE severity as prophylaxis and therapy. The antigen-specific production of inflammatory cytokines was inhibited in R037-treated mice. A significant increase in the number of CD4(+) Interleukin (IL)-10-producing cells was observed in the mesenteric lymph nodes (MLNs) and spleens isolated from R037-treated naive mice, while no increase was observed in the number of these cells in the lamina propria. Because only a slight increase in the CD4(+)Foxp3(+) cells was observed in MLNs, R037 may primarily induce Foxp3(-) IL10-producing T regulatory type 1 (Tr1) cells in MLNs, which contribute to the beneficial effect of R037 on EAE.
An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing IL10-producing Tr1 cells. Our findings indicate the therapeutic potential of the oral administration of R037 for treating multiple sclerosis.
Although semaphorins were originally identified as axonal guidance molecules during neuronal development, it is emerging that several semaphorins play crucial roles in various phases of immune ...responses. Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors plexin-B1 and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We found that Sema4D promoted inducible NO synthase expression by primary mouse microglia, the effects of which were abolished in plexin-B1-deficient but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein-derived peptides, we observed that the expression of Sema4D and plexin-B1 was induced in infiltrating mononuclear cells and microglia, respectively. Consistent with these expression profiles, when myelin oligodendrocyte glycoprotein-specific T cells derived from wild-type mice were adoptively transferred into plexin-B1-deficient mice or bone marrow chimera mice with plexin-B1-deficient CNS resident cells, the development of EAE was considerably attenuated. Furthermore, blocking Abs against Sema4D significantly inhibited neuroinflammation during EAE development. Collectively, our findings demonstrate the role of Sema4D-plexin-B1 interactions in the activation of microglia and provide their pathologic significance in neuroinflammation.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system, and humoral immunity is suggested to play an important role in the pathogenesis. The identification ...of an anti-aquaporin-4 antibody (AQP4-Ab, neuromyelitis optica immunoglobulin G) in the sera of patients with NMO has led to the investigation on the pathogenicity of the autoantibody. Recent immunohistological analyses revealed the primary loss of AQP4 on astrocytes and complement deposition in active lesions of NMO. In this report, we show that astrocytes are susceptible to sera from AQP4-Ab-positive patients and undergo necrosis in a complement-dependent manner. Our results suggest the primary pathogenic role of AQP4-Ab in NMO.
Objective: We report a case of acute middle cerebral artery (MCA) occlusion caused by tumor embolism.Case Presentation: A 64-year-old man with lung cancer presented with sudden onset left-sided ...hemiparesis and sensory disturbance. Diffusion-weighted imaging (DWI) revealed hyper-intense foci in the right MCA territory and magnetic resonance angiography (MRA) demonstrated right MCA M2 segment occlusion. Mechanical thrombectomy (MT) was performed with Thrombolysis in Cerebral Infarction 2B recanalization. On histopathology, thrombus composed of fibrin and squamous cell carcinoma was observed. We diagnosed him with tumor embolism from lung cancer that invaded the pulmonary vein and the left atrium.Conclusion: Tumor cells may be confirmed by pathological examination regardless of the morphology of the embolus. Pathological examination of the cerebral embolus is useful for the accurate diagnosis of ischemic stroke subtypes.
Objective: Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy (MT) are effective treatments for acute ischemic stroke (AIS). However, the treatment for AIS ...in pregnancy is not established because no clinical trials have included pregnant patients. We present a case of middle cerebral artery (MCA) M2 segment occlusion in pregnancy treated with IV thrombolysis and endovascular therapy.Case Presentation: A 36-year-old woman being 6 weeks pregnant presented with right-sided hemiparesis and aphasia. MRI showed a high-intensity area on diffusion-weighted imaging of the left parietal lobe, and MRA showed left MCA M2 segment occlusion. She underwent IV rt-PA and MT and achieved thrombolysis in cerebral infarction 2b revascularization without complications. The protein S concentration was lower than that in the physiological changes during pregnancy. She was diagnosed with embolic stroke related to coagulopathy in pregnancy, and she underwent anticoagulation. At the 3-month follow-up, the modified Rankin Scale was 0. She miscarried at 4 months, and the fetal death was presumed to be obstetric cause.Conclusion: IV rt-PA and MT may be effective and safe treatments for pregnant patients. Estimated fetal radiation exposure during MT is low and is presumed not to affect fetal development. We should mitigate the radiation dose and reduce the dose of iodinated contrast agents, particularly in pregnant patients.
Mouse G258 mutant stopped both cell growth and the synthesis of lipid-linked oligosaccharide at the Man
3
GlcNAc
2
-P-P-Dolichol at a restricted temperature with a single gene mutation. To clarify ...the lesion in the G258 mutant, we isolated human genomic DNA transformants of the G258 mutant, which recovered from both defects by way of cell hybridization with X-ray irradiated HeLa cells. We detected a common 1.3-kb product by inter-human specific sequence in the L1 (L1Hs) PCR in the transformants (Kataoka et al., Somat. Cell Mol. Genet., 24, 235-243 (1998)). In the present study, we screened a human mega yeast artificial chromosome (YAC) library by PCR with primers designed according to the 1.3-kb DNA, and selected YAC clone 923f5. Moreover, we found by spheroplast fusion that YAC clone 923f5 complemented both defects of the G258 mutant. Since the human counterpart of the yeast ALG11 gene is localized in the region, the G258 mutant might have a defect in the mouse ALG11 gene.
PDF
