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Objective: To clarify the genetic, clinicopathologic, and neuroimaging characteristics of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) with the colony stimulating factor 1 receptor ( CSF-1R ) mutation. Methods: We performed molecular genetic analysis of CSF-1R in patients with HDLS. Detailed clinical and neuroimaging findings were retrospectively investigated. Five patients were examined neuropathologically. Results: We found 6 different CSF-1R mutations in 7 index patients from unrelated Japanese families. The CSF-1R mutations included 3 novel mutations and 1 known missense mutation at evolutionarily conserved amino acids, and 1 novel splice-site mutation. We identified a novel frameshift mutation. Reverse transcription PCR analysis revealed that the frameshift mutation causes nonsense-mediated mRNA decay by generating a premature stop codon, suggesting that haploinsufficiency of CSF-1R is sufficient to cause HDLS. Western blot analysis revealed that the expression level of CSF-1R in the brain from the patients was lower than from control subjects. The characteristic MRI findings were the involvement of the white matter and thinning of the corpus callosum with signal alteration, and sequential analysis revealed that the white matter lesions and cerebral atrophy relentlessly progressed with disease duration. Spotty calcifications in the white matter were frequently observed by CT. Neuropathologic analysis revealed that microglia in the brains of the patients demonstrated distinct morphology and distribution. Conclusions: These findings suggest that patients with HDLS, irrespective of mutation type in CSF-1R , show characteristic clinical and neuroimaging features, and that perturbation of CSF-1R signaling by haploinsufficiency may play a role in microglial dysfunction leading to the pathogenesis of HDLS.

This paper explores the interplay of (inter)subjectivity and social norm. (Inter)subjectification is a diachronic process, strengthening the speaker’s (inter)subjective meanings. However, when language change, including (inter)subjectification, occurs, what roles do society or any other social factor play in such change? To address this question, I suggest a specific mechanism behind the speaker’s choice of linguistic forms. As episodes exemplifying intersubjectification, the meaning shifts of Japanese “involvement markers”, na elements, are examined. Their meaning shifts include: (1) from “self-addressed” (subjective) to “other-addressed” (intersubjective) meanings; and (2) from intersubjective to more intersubjective meanings. The (inter)subjective conversational strategies with the use of na elements contribute to fulfill one Japanese social norm, “harmony (wa)” (Ide and Kataoka 2002: v; Nakane 1970: 49). In this paper, the close connection between intersubjectivity and social norm is also shown, being supported by a classic cross-linguistic study of European T-V languages (Brown and Gilman 1960) and a cross-linguistic analysis of Korean and Japanese intersubjectification.

As periphery research is still in its infancy as a field of study, there is some merit, in the first instance, in focusing on empirical data with a view to discerning which elements appear at the LP and RP in different languages and what such elements do on their respective peripheries. This chapter reviews and synthesizes existing literature on elements which appear at the LP and RP in Japanese and examples are provided to illustrate the functions of LP and RP elements in conversational Japanese and to throw light on their historical evolution. On the basis of such studies across different languages, it may be possible to arrive at some cross-linguistic generalizations and a contribution may be made to theory in this area. It is important to remember that in Japanese discourse, both subjective and intersubjective meanings are expressed at both the LP and RP. Keywords: cross-linguistic generalizations; historical evolution; Japanese; Left Periphery (LP)

This paper suggests the independence of grammaticalization and pragmaticalization processes. These two processes are originally and self-evidently autonomous evolutionary paths that occur independently of each other. However, grammaticalization is often discussed, indeed in the majority of the recent studies, in correlation to some unidirectional features that co-occur with grammaticalization. Such features include, structurally, for example, “bondedness” and “structural scope” (Lehmann 1995), and functionally, for example, “increase in abstraction” and “pragmaticalization”. These unidirectional features are at times even considered too authoritatively criterial to judge a given language change as an instance of grammaticalization. This study illustrates a piece of evidence for the asymmetric relationship of grammaticalization and pragmaticalization. That is, the two groups of Japanese discourse markers — (1) demo type connectives and (2) na elements — experience quite different historical changes. The group (1) undergoes both grammaticalization and pragmaticalization, but the group (2) undergoes pragmaticalization without involving grammaticalization.

This book reminds us that code-switching is not only a classic topic, but also an important and highly challenging one. In distinction from previous studies, this work reveals that a bilingual community of second-generation Japanese Canadians (Niseis), in Toronto, has three distinct types of bilingual speech: a basically Japanese variety, a basically English variety, and a mixed variety. Nishimura analyzes these three bilingual speech varieties and provides an answer to the fundamental question in code-switching: “Who speaks what language to whom, and on what occasions?” That is, this research ascribes the motivation of this variability to the “intended audience.” These Niseis choose the basically Japanese variety when they speak to native Japanese people; when they speak to fellow Niseis who have always lived in Canada, they choose the basically English variety; and when they speak to a group comprising both native Japanese and Niseis, they use the mixed variety, oscillating between Japanese and English. They switch among these codes even in the middle of storytelling. What is important here, for the bilingual speakers, is to address two questions: “Who is present in the audience of the ongoing conversational situation?”; and more specifically, “To whom is the current production of this utterance directed?”

This article deals with the processes associated with the grammaticalisation of discourse markers. It provides a theoretical outline of discourse markers and an overview of how the development of discourse markers has recently been treated in the study of language change. It describes a new reformulated model of grammaticalisation and compares it with its traditional counterpart. It also discusses the kind of expressions in terms of structure and meaning which occur in initial and final positions in the grammaticalisation of discourse markers.

Hypersonic liquid jets were generated using a single-stage powder gun. The jets and shock waves were visualized using a double exposure holographic interferometry. In the injection of diesel fuel, self-ignition and combustion were found.

Phosphorylated TDP-43 (pTDP-43) is the pathological protein responsible for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Recently, it has been reported that accumulation of pTDP-43 can occur in the brains of patients with argyrophilic grain disease (AGD), in which phosphorylated 4-repeat tau is the pathological protein. To elucidate the association of ALS with AGD, we examined the brains from 37 consecutively autopsied patients with sporadic ALS (age range 45-84 years, mean 71.5 ± 9.0 years).Sections from the frontotemporal lobe were stained with the Gallyas-Braak method and also immunostained with antibodies against phosphorylated tau, 4-repeat tau and pTDP-43.Fourteen (38%) of the 37 ALS patients were found to have AGD. With regard to staging, 5 of these 14 cases were rated as I, 4 as II and 5 as III. pTDP-43 immunohistochemistry revealed the presence of positive neuronal and glial cytoplasmic inclusions in the affected medial temporal lobe in many cases (93% and 64%, respectively). On the other hand, pTDP-43-positive small structures corresponding to argyrophilic grains were observed only in one case. A significant correlation was found between AGD and the Braak stage for neurofibrillary pathology (stage range 0-V, mean 2.1). However, there were no significant correlations between AGD and any other clinicopathological features, including dementia.The present findings suggest that co-occurrence of AGD in ALS is not uncommon, and in fact comparable with that in a number of diseases belonging to the tauopathies or α-synucleinopathies.

Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Zmax = 9.719).

Objective This study aimed to determine the spectrum of pathological involvement of the striatonigral (StrN) and olivopontocerebellar (OPC) systems in Japanese patients with multiple system atrophy (MSA). This study also aimed to compare the pathological spectrum of Japanese MSA patients with the previously reported results in British MSA patients. Methods A semiquantitative pathological analysis of 50 MSA patients9 brains that were referred to the Brain Research Institute, Niigata University, Japan, was performed. The severity of neuronal cell loss was determined as previously described by the study from the Queen Square Brain Bank (QSBB), UK. Results The mean neuronal cell loss score was significantly higher in the OPC area than in the basal ganglia sites examined, except the dorsolateral putamen. The relative prevalence of pathological phenotypes showed that 40% of cases had OPC-predominant pathology, 18% had StrN-predominant pathology and the remaining (42%) had equivalent StrN and OPC pathology. None of the MSA cases had coexistent Lewy bodies in the dorsal motor nucleus of the vagus and the substantia nigra. Conclusions In contrast to the previously reported results involving British patients9 brains from the QSBB (OPC-predominant pathology 17%, StrN-predominant pathology 34%, equivalent StrN and OPC pathology 49%), the results of the present study showed more pathological involvement of the OPC system than of the StrN system. The rarity of Lewy bodies may underlie the phenotypic expression of Japanese MSA. The present observations reflect the disequilibrium in the phenotype distribution between the two populations.

The reflection and diffraction of a planar shock wave around a circular cylinder are a typical problem of the complex nonlinear shock wave phenomena in literature. It has long been studied experimentally, analytically as well as numerically. Takayama in 1987 obtained clear experimental pictures of isopycnics in shock tube under the condition that the impinging shock wave propagates as far as 3 diameters away from the cylinder. To know more completely the whole unsteady process, it is desirable to get experimental results in a region which is more than 10 diameters away from the cylinder. This is what has been done in this paper by using the pulsed laser holographic interferometry for several shock Mach numbers of the impinging shock. Results for several moments are shown, giving more knowledge about the whole unsteady flow field. This is useful for a reliable and complete understanding of the changing force acting on the cylinder, and provides interesting data to check the performance of many recently developed high resolution numerical methods for unsteady shock wave calculation.

The clinical-genealogic and molecular-genetic investigation of oculopharyngeal muscular dystrophy (OPMD) in the Republic of Sakha (Yakutia) was performed. It was investigated 33 unrelated Yakut families with 38 patients and 2 russian families with 2 patients and 59 their healthy relatives as well. The high clinical polymorphism of disease was found in patients with OPMD. The mutation in exon 1 of the PABPN1 gene resulting in the expansion of GCG-repeats up to 10 is revealed. Using direct sequencing of the PABPN1 gene in 17 families (16 Yakut, 1 Russian), we identified a type of this mutation as an insertion of 4 GCG-repeats. Frequency of OPMD in the Yakut population is 1:11 680 that is 10-20 times higher comparing to european populations. This is a first report on the patients with OPMD from the Republic of Sakha with diagnosis confirmed by molecular-genetic analysis.

This book is one of the pioneering historical pragmatic studies of Japanese. It closely illustrates the usage and contributions of some Japanese discourse markers, and reveals their developmental history. The section on Synchronic Analysis explores the previously uninvestigated functions of some discourse markers used in Present Day Japanese. Moment by moment in on-going conversations, where culturally rigidly-defined interactional norms are highly valued, a specific marker is chosen and used by the speakers as their strategy, based on their quite subjective judgment. The section on Diachronic Analysis then demonstrates chronologically how the meanings and forms of the same markers have come into being. Results include some noticeable changes related to the strengthened intersubjectivity. This multi-dimensional study also discusses the relevance of findings to typological characteristics and productivity. Consideration is further given to why certain expressions (rather than others) become discourse markers and independent forms in Japanese.

Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

We report a 10-year-old boy with chronic enteroviral meningitis associated with agammaglobulinemia (CEMA) and hydrocephalus. He was treated with a low-dose intravenous administration (100 mg/kg/4 weeks) of gammaglobulin (gamma-gl) since he was diagnosed as having Bruton type agammaglobulinemia at 1 year of age. At this admission, neurological examination revealed meningeal signs, Babinski sign, frontal signs, urinary incontinence, and mental retardation (IQ = 48) which was considered to be a sequela of the enteroviral encephalitis which had occurred in his first year of life. T 1-weighted MR imaging of the brain following gadolinium administration revealed a marked dilatation of the lateral ventricles and dense enhancement of the meninges. Enterovirus was detected in the cerebrospinal fluid (CSF) using tissue culture. Histological examination of a biopsied leptomeningeal specimen revealed inflammatory thickening, which was a likely cause of the obstruction to the flow of CSF. The hydrocephalus in this patient was treated with external drainage of CSF from the lateral ventricle. The CEMA was brought into remission by means of the intraventricular administration of gamma-gl, at a dose of 125-250 mg/week (total dose: 1.5 g/8 weeks), in addition to the high dose intravenous administration (400 mg/kg/4 weeks) of gamma-gl. Because of the poor prognosis of patients with CEMA, the intraventricular administration of gamma-gl should be initiated immediately following a diagnosis of enteroviral meningitis.

This report concerns a 66-year-old man suffering from prevertebral abscesses with a protracted insidious clinical course and subsequent lethal and acute pyogenic meningitis. The patient had a three-month history of mild neck pain, and died as a result of septic shock due to staphylococcus aureus (methicillin susceptible) infection two days after admission to the hospital. At autopsy, abscesses encapsulated by fibrous connective tissue were found on the ventral surfaces of the cervical and thoracic regions of the spine. The prevertebral abscess on the upper cervical region was organized with dense fibrous tissue and contained a small number of inflammatory cells. On the other hand, the prevertebral abscess on the thoracic region was purulent and contained numerous inflammatory cells, macrophages and gram-positive cocci. Pyogenic spondylitis and discitis accompanying the prevertebral abscesses were multiple and widespread. These features suggested that the abscesses developed initially on the cervical region, extended caudally through the prevertebral space, directly involving the corpus vertebrae and discs, and ultimately caused sepsis. It is important to note that prevertebral abscesses can exhibit a protracted clinical course with only mild symptom such as minor neck pain and then manifest abruptly as acute meningitis and sepsis.

Autosomal dominant dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) are neurodegenerative disorders caused by CAG trinucleotide repeat expansions. An inverse correlation of age at onset with the length of the expanded CAG trinucleotide repeats has been demonstrated, and the intergenerational instability of the length of the CAG trinucleotide repeats, which is more prominent in paternal than in maternal transmissions, has been shown to underlie the basic mechanisms of anticipation in DRPLA and MJD. Our previous observations on DRPLA and MJD pedigrees, as well as a review of the literature, have suggested that the numbers of affected offspring exceed those of unaffected offspring, which is difficult to explain by the Mendelian principle of random segregation of alleles. In the present study, we analyzed the segregation patterns in 211 transmissions in 24 DRPLA pedigrees and 80 transmissions in 7 MJD pedigrees, with the diagnoses confirmed by molecular testing. Significant distortions in favor of transmission of the mutant alleles were found in male meiosis, where the mutant alleles were transmitted to 62% of all offspring in DRPLA (chi2 = 7.69; P

We assessed the anatomical findings and auditory comprehension of six patients with transcortical motor aphasia due to medical lesions of the left frontal lobe. All patients were right-handed and were initially mute for several hours after the onset, and they exhibited mild paresis of the right lower extremity. Their spontaneous speech was sparse and not fluent, and sometimes accompanied by echolalia, but their articulation was normal and repetition was excellent. They had difficulty in recalling words. A diagnosis of transcortical motor aphasia was made on the basis of their clinical symptoms. All patients were found to have an infarct in the left medial frontal region by MRI and/or CT. We administered the Western Aphasia Battery and 50 line drawing pointing task in order to evaluate auditory comprehension. Based on the results we concluded that there is no impairment of auditory comprehension of single words when lesions are limited to the superior frontal gyrus, but that lesions extending to the middle frontal gyrus interfere with auditory comprehension of single words. Our observations indicate that the middle frontal gyrus plays an important role in auditory comprehension of single words. All of the patients displayed impaired auditory comprehension of sentences even when their lesions were strictly limited to the medial frontal lobe. This suggests that the medial frontal lobe plays some role in the auditory comprehension of sentences.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by genetic anticipation and variable combinations of symptoms including myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Recently, we discovered that DRPLA is caused by unstable expansion of a CAG repeat of a gene on the short arm of chromosome 12. We determined the consensus DRPLA cDNA sequence containing the complete coding region for 1,185 amino acids. The CAG repeat, which is expanded in DRPLA, is located 1,462 bp downstream from the putative methionine initiation codon and encodes a poly-glutamine tract. Although poly-serine and proline tracts exist near the CAG repeats, these polyserine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat. Northern blot analysis revealed a 4.7-kb transcript that is widely expressed in various tissues including heart, lung, kidney, placenta, skeletal muscle, and brain. Reverse transcription-PCR analysis revealed that the expanded alleles are transcribed to levels comparable to those of normal alleles. These results indicate that there is no difference in transcriptional efficiency between expanded and normal alleles. Furthermore, mRNA from cerebellar hemispheres of DRPLA patients showed smaller sizes of CAG repeats compared with other regions of the brain, which reflects somatic mosaicism of the expanded alleles of the DRPLA gene.

A group of patients with paraneoplastic cerebellar degeneration (PCD) have shown to produce autoantibody to both neurons and tumor cells (anti-Yo antibody). More than 60% of these patients have shown neurological symptoms and anti-Yo antibody production before the underlying cancers were found, which suggests that the test for anti-Yo antibody is important for the early detection and treatment of cancer. Originally, anti-Yo antibody has been characterized as 1) labelling the cytoplasm of cerebellar Purkinje cells immunohistochemically, 2) binding to the 62 and 34kDa bands on immunoblots of Purkinje cell extracts, 3) being present in female patients with gynecological or breast cancers. Recently, the common binding-epitope of anti-Yo antibody has been reported as leucine-zipper protein. In order to detect the anti-Yo antibody precisely, we examined the immunohistochemical and western blot characters of the recombinant leucine-zipper protein-reactive (anti-Yo) antibody. The results were, 1) sera containing leucine-zipper protein-reactive antibody labels both cerebellar Purkinje cells but some sera might contain other antibodies together with anti-Yo that confuse the immunostaining character of anti-Yo antibody, 2) the antibody binds to 58 kDa band and sometimes co-binds to 34kDa on immunoblots of cerebellar tissue extracts. The underlying cancers are mainly adenocarcinoma in the ovary, fallopian tube, uterus, or breast but occasionally large cel lung and bile duct cancers have been found. Interestingly, a male patient had an antibody similar in character to be anti-Yo antibody immunohistochemically and on immunoblots, that did not recognize leucine-zipper protein and the underlying carcinoma was small cell lung cancer. These results suggest that 1) the diagnosis of anti-Yo antibody should be based on the antibody's reactivity with leucine-zipper protein, 2) some sera with the anti-Yo antibody label other tissues besides the Purkinje cell cytoplasm because of the co-existence of other antibodies seen immunohistochemically and on immunoblots, 3) the search for underlying cancers should not be limited to gynecological or breast carcinomas.

Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat effects the clinical manifestations of dentatorubral-pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = -0.696, p0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62-79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non-progressive myoclonus epilepsy phenotype showed smaller expansions (54-67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral-pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral-pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

Passive transfer of anti-Yo antibody from patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecological or breast carcinoma has not been successful in inducing an animal model. We used active immunization with recombinant Yo protein of four strains of mice bearing different MHC molecules: BALB/c (H-2d), C3H (H-2k), C57BL/6 (H-2b), SJL/J (H-2s). All the strains produced high anti-Yo antibody titer but none developed cerebellar ataxia or showed Purkinje cell loss. Spleen cells from the immunized mice also reacted with recombinant protein. Because C57BL/6(nu/nu) mice produce no anti-Yo antibody, mature helper T cells are required for its production. Results suggest that antibody production in peripheral blood alone is not sufficient for the development of PCD and that MHC class II molecules function in the activation of T cells to help B cells to help B cells produce antibodies.

Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss.

Paper reports on the effects of viscosity and back pressure on shock wave formation in an automobile exhaust pipe. In the present experiment, a periodic wave generator was designed and built for investigating the transition of compression waves into shock waves. Pipes with various diameters were tested to observe compression waves developing into shock waves under the influence of viscosity. A numerical simulation was also conducted using the TVD (Total Variation Diminishing) finite difference scheme applied to the Navier-Stokes equations. It was found that the viscosity hardly affects the transition of compression waves into shock waves as long as the pipe has a practical size suitable to automobile exhaust systems. The back pressure in the exhaust pipe is more important than the viscosity for the transition of compression waves into shock waves.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA.

Converging cylindrical and spherical shock waves are particularly useful for producing high temperatures and pressures at the center of convergence. The efficiency of this method of generation of high temperatures and pressures depends on the stability of the converging shock wave. However, the stability of the converging shock wave is a difficult problem to analyse since the behaviour of the converging shock wave is primarily dependent on nonlinear characteristics. When the stability of converging shock waves is discussed from the viewpoint of the effects of growth of initial disturbances on final shock wave convergence, it is first necessary to generate converging shock waves free of initial disturbances.

A 58-year-old woman presented with sudden onset of numbness and weakness of the lower limbs. She showed paraparesis associated with hyperreflexia and pathological reflexes in lower limbs. She showed decreased sensation of vibration and proprioception in lower limbs, as well as tingling sensation below Th11 level. Pinprick and thermal sensations were spared. Magnetic resonance imaging (MRI) of the spinal cord revealed a symmetric high signal intensity area at the posterior medial part of the spinal cord spanning Th9 to Th11 on T2-weighted and proton density images. On the basis of clinical findings as well as MRI findings, we made a diagnosis of posterior spinal artery syndrome. The MRI findings are considered to be highly useful for the diagnosis of PSAS.

The mutation in myotonic dystrophy gene has recently been identified as an unstable expansion of trinucleotide CTG repeat located at the 3'-untranslated region of myotonin protein kinase gene. In this paper we report the correlation between the degree of CTG amplification and clinical features in 35 individuals with myotonic dystrophy. The analysis of CTG repeat expansion was performed with Southern blot hybridization. Genomic DNA from peripheral blood leukocytes was digested with a restriction endonuclease, Pst I, instead of commonly used EcoRI. Since small expansion (about 100 bp) could be detected with PstI digestion and furthermore, the DNA fragment did not contain insertion/deletion polymorphism, we were able to accurately determine the exact sizes of CTG repeat expansion. We have observed a tendency of earlier ages of onset with larger allele sizes. The good correlation between the size of the expansion and the severity in muscle weakness was clearly demonstrated especially if the analysis was focused on the patients at same age group at 40-45 years. The severity of motor disability was classified into three stages. The mean size of expansion was 0.33 +/- 0.17 (M +/- SD) kbp in stage I, 2.58 +/- 1.42 kbp in stage II, and 4.75 +/- 0.93 kbp in stage III. The tendency was also observed when patients were categorized according to the intellectual grade. The anticipation was observed in all the parent-child pairs. When the increases of the repeat expansions were compared between father-child and mother-child transmissions, broader variation of the increases was observed in father-child transmissions.(ABSTRACT TRUNCATED AT 250 WORDS)

Paraneoplastic cerebellar degeneration (PCD) is a remote effect of cancer mediated by possibly immunological mechanisms. The sera and cerebrospinal fluid of PCD patients containing high titer autoantibody against cerebellar Purkinje cells had been reported. This antibody binds to 62-kD and 34-kD bands of cerebellar Purkinje cell homogenates (anti-Yo antibody). However, it is not always true that the autoantibody of this character on immunoblot and immunohistochemistry recognizes the same molecule. Recently, the DNA sequence encoding the Yo antigen, whose common epitope is a sequence containing leucine-zipper motif, was reported. We made the recombinant protein deduced from the cDNA clone encoding the leucine-zipper motif of the Yo antigen. Using this recombinant protein as the antigen for ELISA, the anti Yo antibodies in the sera and CSF were examined and 3 new patients with PCD possessing anti-Yo antibody were found. The sera of one patient, serially taken during several kinds of treatment were examined with this ELISA system, which revealed that the anti-Yo antibody titer was increased after plasmapheresis and reduced after tumor resection and anti-cancer chemotherapy. The early resection of malignant tumors may prevent the continuous production of high titer anti-Yo antibody and stop the progression of cerebellar tissue damage.

Partial complementary DNAs for the epsilon 1, epsilon 3 and zeta 1 subunits of the human N-methyl-D-aspartate (NMDA) receptor channel were cloned using the corresponding mouse subunit cDNA clones as probes. Genomic DNA clones for the human epsilon 1, epsilon 3 and zeta 1 subunit genes were isolated using the corresponding partial cDNA clones as probes. By the fluorescence in situ hybridization, we mapped the genes for the epsilon 1, epsilon 3 and zeta 1 subunits of the human NMDA receptor channel to chromosomes 16p13, 17q25 and 9q34, respectively.

Several strategies for isolating disease genes have been developed. In functional cloning, the gene is isolated based on information on the function of gene products (proteins). In contrast, positional cloning is based on the isolation of the disease gene, starting from the knowledge of its location on the genome. The flow chart of positional cloning was described as follows; 1) identification of the location of the disease gene by linkage analysis. 2) construction of the physical map spanning the region. 3) isolation of the candidate genes from the region. 4) identification of mutations in the candidate genes, which is specific to the disease. The current concept and strategies on the positional cloning is discussed.

Olivopontocerebellar atrophy (OPCA) and Machado-Hoseph disease (MJD) occasionally show similar clinical signs and symptoms, which makes differential diagnosis of OPCA and MJD difficult. In 1990, Savoiardo et al. reported that the transverse pontine fibers of OPCA patients had high signal intensity on T2 weighted MR images. To determine if the high signal intensity of the transverse pontine fibers is useful for the differential diagnosis of OPCA and MJD, we examined this abnormal intensity in patients diagnosed as OPCA or MJD. We observed the high intensity of transverse pontine fibers in all of the 18 OPCA patients. This finding, however, was not observed in any of the patients with the MJD. The high signal intensity of the transverse pontine fibers in T2 weighted images is characteristic of OPCA patients. Furthermore the atrophy of pontine tegmentum is characteristic of patients with MJD. These findings correlate well with pathological findings of OPCA and MJD, indicating the usefulness of these MRI findings for the differential diagnosis of OPCA and MJD.

The interaction between a shock wave and an air bubble‐adjacent to a gelatine surface is investigated in order to simulate human tissue damage resulting from extracorporeal shock wave lithotripsy. Using high speed cine photography it is found that a shock wave of strength 11 MPa causes 1–3 mm diameter bubbles to produce high velocity microjets with penetration rates of approximately 110 m/s and penetration depths approximately equal to twice the initial bubble diameter. Theoretical considerations for liquid impact on soft solid of similar density indicate that microjet velocities will be twice the penetration rate, i.e. 220 m/s in the present case. Such events are the probable cause of observed renal tissue damage.

This paper is concerned with the internal structure of pseudo‐shock waves in a straight square duct. The experiments were carried out for M1=1.77 using a dual‐beam Laser Doppler Velocimeter (LDV) and Double Exposure Laser Holographic Interferograms, where M1 was the flow Mach number just ahead of pseudo‐shock wave were measured in detail, and the variations of velocity and the boundary layer displacement thickness were clarified. The displacement thickness increased at the shock wave locations and decreased in the regions between the shock waves. The velocity distributions calculated from the density distributions, which were measured by holographic technique, were compared with the results obtained by LDV. As each shock wave in the pseudo‐shock wave was very weak, the flow in the central part of the duct seemed to be an isentropic flow, while the flow near the wall seemed to be an irreversible adiabatic flow.

Paper reports a successful application of a holographic interferometry to a flow visualization study of a shock transition over wedges in a shock tube. Experiments were conducted on a 60 mm x 150 mm shock tube of the Institute of High Speed Mechanics, Tohoku University for Mach numbers from 1.1 to 3.0 in air. Using a pulsed laser double exposure holographic interferometry the shock transition over concave or convex walls and multiple straight wedges was quantitatively observed. Consequently the critical transition angles over these wedges were determined and in addition to this a hysterisis effect in the truly non-stationary transition phenomena was clarified. Advantages of applying the holographic interferometry to the high speed gasdynamics were demonstrated.

An experimental investigation using a pulsed laser holographic interferometry, was made of propaqation and focusing of underwater spherical shock waves produced by micro-explosions. A technique was developed to obtain underwater spherical shock waves. To obtain spherical shock waves in good reproducibility, a lead azide pellet of 4.0 mg which was stuck on a thin cotton thread and suspended in distilled water was ignited by radiating it with a Q-switched ruby laser beam. The movement of underwater spherical shock waves and their isopycnics were quantitatively determined with the double exposure holographic interferometry. As an application, the underwater shock wave focusing from aopropriate reflectors was observed by means of a diffuse or a non-diffuse hologrpahic interferometry. Advantages of the holographic interferometry to the underwater shock wave research were demonstrated.

Attelocollagen obtained by pepsin treatment from calf skin is very poor antigen. Attelocollagen is the most promising implantable biomaterial because of its lower antigenic property and excellent tissue compatibility. The purpose of this study is to examine that attelocollagen suppress an out-flow of hydroxyapatite. The subject were 16 patients with moderate to advanced periodontal disease who visited Meika university hospital. The clinical examination were performed immediately after the surgery, 1, 2, and 4 weeks after postsurgery. The remains of hydroxyapatite were measured by the roentgenograph and an image analyzer system. As a result, the hydroxyapatite in attelocollagen treated group was remained much more than of control group in 4 weeks (p less than 0.01). In clinical finding, wound healing of attelocollagen treated group was accomplished in 4 weeks and it did not prevent the wound healing of periodontal tissue.