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M Segawa

Publications and source records attributed to M Segawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan (incidence is 0.7-1.2 per 10,000 births), is characterized by congenital muscular dystrophy associated with brain malformation (micropolygria) due to a defect in the migration of neurons. We previously mapped the FCMD gene to a region of less than 100 kilobases which included the marker locus D9S2107 on chromosome 9q31. We have also described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. Here we report that there is a retrotransposal insertion of tandemly repeated sequences within this candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence is about 3 kilobases long and is located in the 3' untranslated region of a gene encoding a new 461-amino-acid protein. This gene is expressed in various tissues in normal individuals, but not in FCMD patients who carry the insertion. Two independent point mutations confirm that mutation of this gene is responsible for FCMD. The predicted protein, which we term fukutin, contains an amino-terminal signal sequence, which together with results from transfection experiments suggests that fukutin is a secreted protein. To our knowledge, FCMD is the first human disease to be caused by an ancient retrotransposal integration.

Amino Acid Sequence↗
PubMed1998

Novel imidazole derivatives with subtype-selective antimuscarinic activity (1).

A series of N-substituted 4-amino-2,2-diphenylbutyramide derivatives was prepared as part of a search for subtype-selective antimuscarinic agents. The representative compound KRP-197, bearing a 2-methylimidazole ring as a surrogate of aliphatic amine, was found to be a highly potent and both M1- and M3-selective antimuscarinic agent.

Animals↗
PubMed1998

Effect of age on brown adipose tissue activity in the obese (ob/ob) mouse.

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity.

Adipose Tissue, Brown↗
PubMed1998

A case of myasthenia gravis in childhood associated with chronic inflammatory demyelinating polyradiculoneuropathy.

We report a 14-year-old girl who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia gravis, which was clinically of ocular type, but with waning phenomenon of the extremities, occurred at 2 years and 4 months of age. Muscle weakness of the lower extremities gradually developed over the next 6 years. The electrophysiological and pathological findings fulfilled the criteria of "possible CIDP" with severe axonal involvement. The signs of myasthenia gravis and CIDP fluctuated synchronously. A common immunological abnormality was suggested to underlie this rare association of myasthenia gravis and CIDP in childhood.

Adolescent↗
PubMed1998

Video analysis of gross body movements during sleep.

Gross body movements (GM) during sleep, classified into four GM types by the involved parts of body, were evaluated using two-dimensional video analysis in five normal children aged 4-12 years. The rate of occurrence of all GM types showed apparent sleep stage dependency. Among four GM types, GM-1 (GM with axial rotation) was the most frequent. Averaged duration of GM-1 was the longest. A total of 77.2% of GM-1 started with the contraction of chin muscle and 35% of total sleep changes (tSC) were related to GM. A total of 5.6% of tSC following GM shifted to the deeper stage. Further evaluation is necessary in order to understand the physiological mechanism of GM.

Child↗
PubMed1998

Effect of running training on brown adipose tissue activity in rats: a reevaluation.

The effect was investigated of running training on the thermogenic activity of brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training, a significantly lower rate of increase in body weight was found, suggesting some training effect, whereas the training failed to induce a decrease in BAT mass. As previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats; nevertheless, no definite effect of the running training was noted on either UCP content or guanosine 5'-diphosphate binding in the mitochondria recovered from BAT. The results obtained suggest that running training has no overt effect on the thermogenic activity of BAT in rats.

Adipose Tissue, Brown↗
PubMed1997

[Causative factors resulting in intractability of congenital hydrocephalus--analysis of psychomotor development and MRI findings of the brain in sixteen congenitally hydrocephalic patients].

Sixteen patients out of 58 children with congenital hydrocephalus were retrospectively investigated in terms of their psychomotor development and morphological findings of the brain by magnetic resonance imaging (MRI), and morphological backgrounds of the brain in patients affected by "intractable hydrocephalus" were intended to be clarified. The 16 patients were primarily diagnosed as having aqueductal stenosis or communicating hydrocephalus during the era before introduction of MRI. On the basis of the rate of head growth, sixteen patients were divided into three groups; group-1: overt neonatal hydrocephalus (5 cases) ; group-2: rapidly progressive hydrocephalus with normal head circumference at birth (5 cases); and group-3: slowly progressive hydrocephalus with its onset after the neonatal period (6 cases). Psychomotor development of the 16 cases was analyzed by using various methods including the Tanaka-Binet intelligence test and WISC-R. Four cases in group-1 and all cases in group-2 were found to have IQ or DQ below 50, while the other remaining cases were found to have IQ of 82 in group-1 (one case) and IQ ranging from 67 to 113 in group-3. MRI performed in those 9 cases with IQ below 50 revealed various morphological abnormalities of the brain. Those abnormalities were characterized by disturbance of organogenesis and/or histogenesis of the brain dating from the first 20 weeks of fetal life. It is strongly suggested that in the pathogenesis of intractable hydrocephalus developmental malformation of the brain occurring during the first 20 weeks of gestation are involved. Functional and morphological impairments of the brain possibly caused by progression of fetal hydrocephalus and delay of CSF diversion before and after birth seem important in the pathogenesis of intractable hydrocephalus.

Adolescent↗
PubMed1997

[Involuntary movements caused by basal ganglia-disorders and their age dependency: introductory remarks].

The basal ganglia modulate voluntary movements involving the neural circuit of the cortex-basal ganglia-thalamus-cortex. The basal ganglia receive all of the afferents at the striatum and project the efferents from two output structures, the medial segment of the globus pallidus and pars reticulata of the substantia nigra. Besides the cortex, the basal ganglia receive inputs from pars compacta of the substantia nigra (SNc) and centromedian nuclei of the thalamus. The afferent from the SNc is the nigrostriatal (NS) dopamine (DA) neuron and has important roles in functional modulation of the basal ganglia. As for efferents, the basal ganglia also have output projections to the superior colliculus and pedunculo-pontine nuclei. In the basal ganglia, the striatum has two efferent pathways; one is the direct projection which projects directly to the output structure and the other is the indirect pathway which projects to the output structures via the lateral segment of the globus pallidus and the subthalamic nuclei, changing synapses at these nuclei. The lesions in the basal ganglia show various movement disorders or involuntary movements depending on their foci. Basal ganglia lesions also develop symptoms age dependently; a certain lesion develops dystonia in younger brains, while revealing parkinsonism in adult or older brains. This age dependency depends on the difference in the course of the functional maturation of each component and pathway of the basal ganglia. At this symposium we tried to show the basic pathophysiologies of age dependency by discussing basal ganglia disorders in children compared to those in adults and referring to the basic science of the basal ganglia.

Adult↗
PubMed1997

[Jejunal pouch interposition and distal gastrectomy].

We developed a new technique of reconstruction in Billroth 1 gastrectomy, jejunal pouch interposition (JPI). The interposed jejunal segment consists of a proximally double-plicated pouch and a distally isoperistaltic conduit. From 1987 to 1994, the JPI was performed on 102 patients with gastric carcinoma. The postoperative functional assay was carried out at least one year later after surgery. Sixty-five patients with the conventional Billroth 1 reconstruction (B-1) during the same period were employed as the control. Gastric emptying time estimated with scinti-scanning was significantly delayed in the JPI group compared with the B-1 group (p < 0.05). All individuals with JPI had meals three times a day whereas 13% of those with B-1 required those more than three times (p < 0.05). The incidence of dumping syndrome was significantly lower in the JPI group (6%) than the B-1 group (20%) (p < 0.05). The reflux of bile into the residual stomach was observed in the scintiscanning at 78% of patients with B-1 whereas 10% of those with JPI (p < 0.01). Endoscopy revealed that regurgitation gastritis was significantly decreased in the JPI group compared with that in the B-1 group (p < 0.01). These results suggest that the JPI prevents small stomach syndrome, dumping syndrome and alkaline reflux gastritis after the B-1 reconstruction.

Dumping Syndrome↗
PubMed1997

Involvement of the autonomic nervous system in the pathophysiology of Rett syndrome.

Clinical observations and physiological evidence suggest involvement of the autonomic nervous system (ANS) in Rett syndrome (RS). We studied sympathetic skin response (SSR) and sleep-wakefulness-rhythm (SWR) in patients with RS and discussed involvement of the ANS in reference to the pathophysiology. The age dependent alteration in the parameters in SSR was suggested. Some patients showed absence of SSR and some showed asymmetric involvement of the parameters of the SSR, which suggested involvement of the ANS at a peripheral level and possible influences from higher centers. The asymmetry correlated with side of the scoliosis, but not with handedness or position of the hand on stereotypy. In reference to the scoliosis of RS, asymmetrical involvement of dopamine neurons is suggested, but reduced secretion of melatonin was proposed and possible influence of the sympathetic nervous system for it was discussed. Long lasting abnormalities of SWR as well as leakage of axial atonia into NREM stage are due to an early involvement of noradrenergic neurons. The latter implied the loss of integration of the central ANS. Based on these observations and references, it was speculated that the ANS is involved in RS at various levels from the central to peripheral nervous system.

Adolescent↗
PubMed1997

Pathophysiology of Rett syndrome from the standpoint of early catecholamine disturbance.

The polysomnography of Rett syndrome (RS) revealed early disturbance, hypofunctioning, of the noradrenaline, serotonin, and dopamine neurons. Neuropathologically, early lesions of the dopamine neurons in the pars compacta of the substantia nigra and the ventrotegmental areas were observed. These aminergic neurons have roles in the functional maturation of their targets in the brain and for synaptogenesis of the cortex at critical ages. Early hypofunctioning of the dopamine neurons results in receptor supersensitivity of the receptors, which could cause the characteristic clinical features of RS in which particular signs and symptoms appear age dependently. The correlating lesions of the cholinergic neurons in the Meynert basal nucleus might relate to the deterioration of higher cortical function which becomes apparent from early childhood.

Age Factors↗
PubMed1996

Strong linkage disequilibrium and haplotype analysis in Japanese pedigrees with Machado-Joseph disease.

To identify the markers tightly linked to Machado-Joseph disease (MJD) and to investigate whether a limited number of ancestral chromosomes are shared by Japanese MJD pedigrees, a detailed linkage analysis employing D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1, D14S81, D14S265, D14S62, and D14S65 was performed. The results of multipoint linkage analysis as well as detection of critical recombination events indicate that the gene for MJD is localized in a 4-cM region between D14S280-D14S81. We found strong linkage disequilibria at AFM343vf1 and D14S81, and association of a few common haplotypes with MJD. These results indicate that there is an obvious founder effect in Japanese MJD and suggest the possibility of the existence of predisposing haplotypes which are prone to expansions of CAG repeats.

Ataxin-3↗
PubMed1996

Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats.

Esophageal adenocarcinoma arises from Barrett's esophagus, which is induced by gastro-esophageal reflux. This refluxate often contains duodenal contents, whose backflow triggers gastric carcinoma, suggesting the hypothesis that refluxed duodenal contents cause esophageal carcinoma. This study examines the role of duodenal and gastric reflux in the absence of exogenous carcinogens in esophageal carcinogenesis. Wistar male rats, 120 in all, each weighing approximately 250 g, were used. Three experimental procedures were performed to produce gastro-duodeno-esophageal reflux, duodeno-esophageal reflux and gastro-esophageal reflux, for comparison with 2 control procedures, Roux-en-Y reconstruction and a sham operation. The animals were fed a standard diet and were examined 50 weeks after surgery. While no carcinoma was found among the 16 gastro-esophageal-reflux, 11 Roux-en-Y and 12 sham-operation animals, 10 of the 12 animals with gastro-duodeno-esophageal reflux (83%) and 10 of the 13 with duodeno-esophageal reflux (77%) developed esophageal carcinoma. The difference between groups was significant (p < 0.001). Two animals with gastro-duodeno-esophageal reflux had esophageal double and triple carcinomas respectively. Of the 23 carcinomas, 16 were adenocarcinoma, 4 adenosquamous carcinoma, and 3 squamous-cell carcinoma. Adenocarcinoma developed from the columnar-lined epithelium near the esophago-jejunostoma, while adenosquamous and squamous-cell carcinoma arose from the squamous esophagitis. These observations demonstrate that refluxed duodenal contents per so are responsible for esophageal carcinogenesis.

Adenocarcinoma↗
PubMed1996

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

Amino Acid Sequence↗
PubMed1996

Serum androsterone levels in children.

Serum androsterone was measured by radioimmunoassay in 79 girls and 80 boys aged between six months to sixteen years. In boys, androsterone levels were found to be low until the age of 12 years and then rapidly increased between the ages of 12-13 years. This increase of serum androsterone in boys seems to be related to the rapid increase of testosterone. On the other hand, in girls the androsterone levels were found to be low until the age of 10 years. However, from this age onwards, although individual values were variable, androsterone levels did not increase as rapidly as in boys but rather gradually with age which appeared to be influenced by the progressive increase of dehydroepiandrosterone (DHEA) in girls.

Adolescent↗
PubMed1996

[A 63-year-old woman with muscle weakness, myotonia, and parkinsonism].

We report a 63-year-old woman who presented myotonia and parkinsonism. The patient was well until 15 years of the age when she noted that the ring finger of her left hand at times flexed when she did not intend to do so. She noted weakness in her left upper extremity at the age of 40, and difficulty in relaxing her hand grip at 45. She had an onset of tremor in her right foot at age 50, which was followed by difficulty in gait and hand writing. She was admitted to Juntendo University Urayasu Hospital when she was 63-year-old. Her mother, two sisters, and a son were affected with similar muscle weakness and myotonia. Although some of them developed stooped posture in the late stage of the disease, none of them had overt parkinsonism. General physical examination was unremarkable. Neurologic examination revealed an alert and oriented woman with some recent memory loss. She had bilateral ptosis, facial weakness, and a masked face. Myerson's sign was present. Her speech was small and monotonous. The sternocleidomastoid muscles were markedly atrophic and weak. The remaining of the cranial nerves were intact. She walked in small steps with freezing with support. She showed bradykinesia, retropulsion, and resting tremor in her right leg. Slight distal dominant weakness was noted in both upper and lower extremities more on the left. No cerebellar signs were noted. Muscle stretch reflexes were within normal limits in the upper extremities and diminished in the lower limbs. Sensation was intact. Routine laboratory findings were unremarkable. Cranial CT scan and MRI revealed slight cortical atrophy and leukoaraiosis. She responded to levodopa and she became able to walk by herself. She was transferred to another hospital one month after her admission. She had several bouts of airway obstruction with one episode of respiratory arrest. She expired six month after the transfer. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that this patient suffered from myotonic dystrophy and Parkinson's disease which set in later years. Postmortem examination on the iliopsoas muscle revealed uneven muscle fiber diameters, central nuclei, and type 1 fiber predominance; the pathologic finding was consistent with myotonic dystrophy. The substantia nigra showed marked cell loss and Lewy bodies in the remaining neurons. The finding was consistent with Parkinson's disease. In myelin stain, diffuse myelin pallor was noted in the cerebral white matter which was the pathologic substrate of leukoaraiosis in this patient. Combination of these two disorders have never been reported in the literature to our knowledge. It appears to be that the coincidence is just a by-chance phenomenon, but it seems interesting to note that accelerated aging process appears to be present in both myotonic dystrophy and Parkinson's disease.

Diagnosis, Differential↗
PubMed1996

[Segawa disease (hereditary progressive dystonia with marked diurnal fluctuation-HPD) and abnormalities in pteridin metabolism].

From its characteristic clinical features, decrease of tyrosine hydroxylase (TH) in the terminal of the nigrostriatal (NS) dopamine (DA) neuron is considered the main lesion of HPD and the decrease of neopterin as well as biopterin in the cerebrospinal fluid suggested GTP cyclohydrolase I (GCH-I) as the responsible enzyme. By detecting the gene locus of GCH-I, Ichinose and his colleagues showed the abnormalities of GCH-I gene located on 14q 22.1 q22.2 as the cause of HPD. Since the first report of Ichinose et al, 11 mutations and frame shifts of the gene have been detected, in which the locus of abnormality differed among families but is identical in a family, but more than several families have been left with undetected abnormalities including those having linkage to 14q. However, the DNA of these families as well as those with detected gene abnormalities failed to synthesize GCH-I if inoculated with E. coli and the levels of GCH-I in mononuclear blood cells were below 20% of normal values in HPD patients while they were 37 and 38% in two asymptomatic carriers. Ratio of mutant mRNA of GCH-I gene was 28% in a patient and 8.3% in an asymptomatic case. These lines of evidence on GCH-I show HPD is a dominant inherited disorder with abnormalities of GCH-I gene. GCH-I is the limiting enzyme for synthesizing tetrahydrobiopterin (BH4), coenzyme transmitters for the synthesizing hydroxylases of aminergic neurotransmitters, but the affinity is the least for TH. This might cause a rather selective involvement of TH preserving serotonin synthesis un- or less affected. Fluoro-DOPA and [11C] racropride PET studies were normal in HPD. Studies of an autopsied case with dopa responsive dystonia, which was confirmed to have GCH-I gene abnormalities, neuropathologically revealed no abnormalities except for a decrease in melanin pigmentation in the substantia nigra and histochemically a decrease in TH enzyme activities and its protein only in the striatum. There was mild decrease of DA content, the interregional caudate/putamen and subregional rostrocaudal patterns which were similar to Parkinson disease, but subdivisionally different with predominant reduction in the ventral subdivision of the caudate nucleus. In the ventral part of the basal ganglia the striatal direct projection exists predominantly. Cases with recessive abnormalities of pteridin metabolism other than HPD, 6-pyruvoyl-tetra-hydropterin synthase (PSPS) deficiency and dihydropteridine reductase deficiency also show dystonia with diurnal fluctuation responding to levodopa, though not as marked as HPD. MPTP monkey studies revealed no involvement of striatal indirect pathway for peak dose dystonia. So it is suggested that in HPD, decrease of TH at the terminal of the NS-DA neuron due to partial reduction of GCH-I develops postural dystonia through the striatal direct projection in childhood with diurnal fluctuation depending on age and circadian variation of TH activities at the terminals.

Adult↗