Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is caused by a mutation in the high-temperature requirement A serine peptidase 1 ( HTRA1 ) gene.1 Alopecia, spondylosis, and cognitive impairment are the clinical triad. Alopecia does not necessarily appear in all patients with CARASIL, but this feature contributes to an early diagnosis.1,2 We present the case of a patient with CARASIL who had a novel mutation in the HTRA1 gene and did not show alopecia even 10 years after onset. ### Case history. The patient was a 44-year-old woman. Her oldest brother had developed progressive dementia and motor dysfunctions from age 38. His imaging studies revealed spondylosis and extensive leukoencephalopathy. Although he did not lose hair even at 14 years after onset [figure, A(a)], he was clinically diagnosed with CARASIL at age 39. The patient's younger brother is healthy. Figure The novel high-temperature requirement A serine peptidase 1 (HTRA1) mutation detected in our patient with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) lacking alopecia (A) The pedigree of the family with CARASIL. Arrow, the patient; the number under each symbol, age; CI, cerebral infarction(s); squares, men; circles, women; rhombic symbols, patients of undefined sex; solid symbols, affected family members; asterisk, healthy sibling. Insets are pictures of the eldest brother (a) and the patient (b). (B) The novel mutation in the HTRA1 genomic DNA. Note that 2 patients with CARASIL have a novel homozygous mutation consisting of a substitution of guanine-to-adenine at codon 821. The healthy controls have G/G, and the younger sibling without any symptoms has the heterozygous mutation G/A at the corresponding codon. Arrows indicate codon 821. (C) Distribution of mutations inducing CARASIL and known functional …

Background: The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1) protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs) in the embryonic and post-natal central nervous system (CNS). Msi1 regulates the translation of its downstream targets, including m-Numb and p21 mRNAs. In vitro experiments using knockout mice have shown that Msi1 and its isoform Musashi2 (Msi2) keep NS/PCs in an undifferentiated and proliferative state. Msi1 is expressed not only in NS/PCs, but also in other somatic stem cells and in tumours. Based on previous findings, Msi1 is likely to be a key regulator for maintaining the characteristics of self-renewing stem cells. However, the mechanisms regulating Msi1 expression are not yet clear. Results: To identify the DNA region affecting Msi1 transcription, we inserted the fusion gene ffLuc, comprised of the fluorescent Venus protein and firefly Luciferase, at the translation initiation site of the mouse Msi1 gene locus contained in a 184-kb bacterial artificial chromosome (BAC). Fluorescence and Luciferase activity, reflecting the Msi1 transcriptional activity, were observed in a stable BAC-carrying embryonic stem cell line when it was induced toward neural lineage differentiation by retinoic acid treatment. When neuronal differentiation was induced in embryoid body (EB)-derived neurosphere cells, reporter signals were detected in Msi1-positive NSCs and GFAP-positive astrocytes, but not in MAP2-positive neurons. By introducing deletions into the BAC reporter gene and conducting further reporter experiments using a minimized enhancer region, we identified a region, "D5E2," that is responsible for Msi1 transcription in NS/PCs. Conclusions: A regulatory element for Msi1 transcription in NS/PCs is located in the sixth intron of the Msi1 gene. The 595-bp D5E2 intronic enhancer can transactivate Msi1 gene expression with cell-type specificity markedly similar to the endogenous Msi1 expression patterns.

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.

Myasthenia gravis (MG) patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG). We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6%) patients and 9 (4.9%) complained of migraine. Twenty-five (13.6%) complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients.