Maternal immunoglobulin G affects brain development of mouse offspring.

Maternal immunoglobulin (Ig)G is present in breast milk and has been shown to contribute to the development of the immune system in infants. In contrast, maternal IgG has no known effect on early childhood brain development. We found maternal IgG immunoreactivity in microglia, which are resident macrophages of the central nervous system of the pup brain, peaking at postnatal one week. Strong IgG immunoreactivity was observed in microglia in the corpus callosum and cerebellar white matter. IgG stimulation of primary cultured microglia activated the type I interferon feedback loop by Syk. Analysis of neonatal Fc receptor knockout (FcRn KO) mice that could not take up IgG from their mothers revealed abnormalities in the proliferation and/or survival of microglia, oligodendrocytes, and some types of interneurons. Moreover, FcRn KO mice also exhibited abnormalities in social behavior and lower locomotor activity in their home cages. Thus, changes in the mother-derived IgG levels affect brain development in offsprings.

Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder.

An 84-year-old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high-intensity signal lesions on fluid-attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well-defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8-positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti-AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing-remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS.

[A case of intravascular large B-cell lymphoma manifested as lacunar infarction].

A 79-year-old man was admitted to our hospital because of sudden onset of left ataxic hemiparesis. Brain MRI diffusion weighted images showed typical lacunar infarction on the right internal capsule. He had no risk factors of cerebrovascular disorder such as hypertension, diabetes mellitus, hyperlipidemia and arrhythmia. On admission, he had a slight fever and his laboratory data showed anemia, thrombocytopenia and elevation of CRP and LDH. Intravascular large B-cell lymphoma (IVLBCL) was suspected because the serum level of soluble IL-2 receptor was also elevated. Pathological diagnosis of IVLBCL was underwent by the skin biopsy from his senile hemangiomas. Although IVLBCL was known to demonstrate various CNS lesions, it is extremely rare to be manifested as a single lacunar infarction, and this case must be important for the differential diagnosis.

[A case of neuromyelitis optica associated with pulmonary Mycobacterium avium complex disease].

A 62-year-old woman suffering from pulmonary Mycobacterium avium complex (MAC) disease was admitted to our hospital with fever, visual impairment, and lower limb weakness. MRI detected lesions in the optic chiasm and spinal cord extending the length of 6 vertebrae. The anti-aquaporin 4 (AQP4) antibody titer determined by ELISA was elevated to 8.3 IU/l. On the basis of these findings, the patient was diagnosed as having neuromyelitis optica (NMO), when chest CT also demonstrated exacerbation of pulmonary lesions. Methylprednisolone pulse therapy and double-filtered plasma exchange ameliorated the symptoms, and the EDSS score improved from 8.5 to 6.5. Six months later, visual impairment recurred, although ELISA showed that the anti-AQP4 antibody titer had become undetectable. Also, the CSF interleukin-6 (IL-6) level was elevated to 34.8 pg/ml. There have been few reports of NMO associated with pulmonary MAC disease. An increase of IL-6 is considered to exacerbate the clinical picture of NMO, whereas it may suppress progression of the pulmonary MAC disease. Exacerbation of the pulmonary MAC disease and the following internal counteraction with IL-6 may have resulted in a NMO relapse. The present patient was therefore administered eculizumab but not satralizumab, a humanized anti-IL-6 receptor antibody, for prevention of NMO recurrence.

Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030.

1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (2) was isolated from Curcuma domestica as a curcumin (1)-related compound, which we named C5-curcumin. Intrigued by the potent antitumor activity of C5-curcumin (2)-related 1,5-bisaryl-1,4-pentadiene-3-ones [bis(arylmethylidene)acetones, termed C5-curcuminoids], we previously conducted a structure-activity relationship study of C5-curcuminoids and showed that highly active GO-Y030 [1,5-bis(3,5-bis(methoxymethoxy)phenyl)-1,4-pentadiene-3-one (4)] is the most promising antitumor compound. In this study, a panel of C5-curcuminoids based on GO-Y030, consisting of 30 new and 10 known compounds, was synthesized to elucidate in detail which moiety of GO-Y030 is significant for antitumor activity. The results confirmed that both the cross-conjugated dienone moiety and the 3,5-bis(methoxymethoxy) substituent are important for the antitumor activity.

Demethylesterification of the primary wall by PECTIN METHYLESTERASE35 provides mechanical support to the Arabidopsis stem.

Secondary cell walls, which contain lignin, have traditionally been considered essential for the mechanical strength of the shoot of land plants, whereas pectin, which is a characteristic component of the primary wall, is not considered to be involved in the mechanical support of the plant. Contradicting this conventional knowledge, loss-of-function mutant alleles of Arabidopsis thaliana PECTIN METHYLESTERASE35 (PME35), which encodes a pectin methylesterase, showed a pendant stem phenotype and an increased deformation rate of the stem, indicating that the mechanical strength of the stem was impaired by the mutation. PME35 was expressed specifically in the basal part of the inflorescence stem. Biochemical characterization showed that the activity of pectin methylesterase was significantly reduced in the basal part of the mutant stem. Immunofluorescence microscopy and immunogold electron microscopy analyses using JIM5, JIM7, and LM20 monoclonal antibodies revealed that demethylesterification of methylesterified homogalacturonans in the primary cell wall of the cortex and interfascicular fibers was suppressed in the mutant, but lignified cell walls in the interfascicular and xylary fibers were not affected. These phenotypic analyses indicate that PME35-mediated demethylesterification of the primary cell wall directly regulates the mechanical strength of the supporting tissue.