Biomedical subjects

E Mukai

Publications and source records attributed to E Mukai.

At least 37 records · Page 2Linked to original sources

PubMed1998

The novel insulinotropic mechanism of pimobendan: direct enhancement of the exocytotic process of insulin secretory granules by increased Ca2+ sensitivity in beta-cells.

Pimobendan is a new class of inotropic drug that augments Ca2+ sensitivity and inhibits phosphodiesterase (PDE) activity in cardiomyocytes. To examine the insulinotropic effect of pimobendan in pancreatic beta-cells, which have an intracellular signaling mechanism similar to that of cardiomyocytes, we measured insulin release from rat isolated islets of Langerhans. Pimobendan augmented glucose-induced insulin release in a dose-dependent manner, but did not increase cAMP content in pancreatic islets, indicating that the PDE inhibitory effects may not be important in beta-cells. This agent increased the intracellular Ca2+ concentration ([Ca2+]i) in the presence of 30 mM K+, 16.7 mM glucose, and 200 microM diazoxide, but failed to enhance the 30 mM K+-evoked [Ca2+]i rise in the presence of 3.3 mM glucose. Insulin release evoked by 30 mM K+ in 3.3 mM glucose was augmented. Then, the direct effects of pimobendan on the Ca2+-sensitive exocytotic apparatus were examined using electrically permeabilized islets in which [Ca2+]i can be manipulated. Pimobendan (50 microM) significantly augmented insulin release at 0.32 microM Ca2+, and a lower threshold for Ca2+-induced insulin release was apparent in pimobendan-treated islets. Moreover, 1 microM KN93 (Ca2+/calmodulin-dependent protein kinase II inhibitor) significantly suppressed this augmentation. Pimobendan, therefore, enhances insulin release by directly sensitizing the intracellular Ca2+-sensitive exocytotic mechanism distal to the [Ca2+]i rise. In addition, Ca2+/calmodulin-dependent protein kinase II activation may at least in part be involved in this Ca2+ sensitization for exocytosis of insulin secretory granules.

Androstadienes↗

PubMed1998

[A severe case of acute autonomic and sensory neuropathy].

Acute autonomic and sensory neuropathy (AASN) is a rare neuropathy characterized by acute autonomic dysfunction and objective sensory disturbances. A 26-year-old pregnant woman with severe autonomic and sensory dysfunction is reported. This patient suddenly developed marked nausea and vomitting in about 2 days after having a sore throat. She then developed signs of autonomic dysfunction including dilated non-reactive pupils, dryness of the eyes and oral mucous membranes, generalized anhidrosis, paralytic ileus, orthostatic hypotension, and continuous tachycardia. She also had severe generalized sensory impairments of all modalities, and all deep tendon reflexes were absent. Sensation was almost totally lost for all modalities below the neck. There was marked pseudoathetosis and sensory ataxia in all extremities. Motor examination was normal. She had inability to urinate. At this time she was 38 weeks pregnant, and when she showed signs of fetal distress, a Caesarean section was performed. Albumino-cytological dissociation was seen in the CSF. Serum noradrenaline was reduced, no sensory nerve action potentials could be elicited, and reduced coefficient of variation of the R-R interval on electrocardiography was observed. Plasma exchange was performed every other day for 3 days for about 3 weeks after the onset of the illness, but no favorable effects. Seven months after the onset, her autonomic dysfunction slightly improved, but there was no recovery from the sensory disturbances. Many symptoms and signs that characterize AASN occurred in this patient, and each was severe. The patient developed SIADH, sleep apnea, personality change, and amenorrhea in the course of the disease. We suggest that AASN patients might have both peripheral and central nervous system manifestations including seizures and personality changes.

Acute Disease↗

PubMed1995

Primary sensory neurons in X-linked recessive bulbospinal neuropathy: histopathology and androgen receptor gene expression.

Pathology of the primary sensory neurons was examined in 7 autopsied patients and 6 biopsied sural nerves from the patients with X-linked recessive bulbospinal neuronopathy (SBMA). Large myelinated fibers in the central rami (L-4 posterior root, L-4, T-7, and C-6 segment of the fasciculus gracilis), and in the peripheral rami (sural nerve) were diminished in a distally accentuated manner, while small myelinated and unmyelinate fibers were well preserved in number. Demylinating process and axonal atrophy was ubiquitous. The diameter frequency histograms of the dorsal root ganglion (DRG) neurons showed a decrease in the number of large diameter neurons and an increase in the number of small diameter neurons without substantial loss of whole number of neurons, which suggested that neuronal size was atrophied. These data suggested central and peripheral distal axonopathy with neuronal atrophy was the process of sensory neuron involvement. Expression of mutant androgen receptor mRNA with elongated CAG repeat in the DRG and sural nerve supported the view that sensory nerve involvement is the primary process in SBMA.

Aged↗

PubMed1995

X-linked recessive bulbospinal neuronopathy: clinical phenotypes and CAG repeat size in androgen receptor gene.

Clinical phenotypes and the CAG repeat size of the androgen receptor gene were assessed in 95 Japanese patients with X-linked recessive bulbospinal neuronopathy. There was an age- and duration-dependent deterioration of muscle strength, ADL scores, and plasma creatine kinase levels. However, there was no correlation between the presence of absence of gynecomastia or diabetes mellitus and the age at onset or duration of illness. Correlations were present between the CAG repeat size and the age at onset (P < 0.0001) as well as the presence or absence of gynecomastea (P < 0.05). Muscular weakness and ADL scores were also correlated with the CAG repeat size only when they were adjusted by the age at examination not by the duration of illness. These findings suggest that CAG repeat size is one of the determinant factors of disease progression. However, extensive variation in phenotypic severity in patients with the same size of CAG repeat was present even among the siblings, suggesting that other factors than CAG repeat size influence the phenotypic manifestation. The average gain of CAG repeat size expansion was a 1.4 repeat in paternal transmission which was more unstable than that in maternal transmission, but the magnitude of the expansion in paternal transmission was much smaller than is presently known for other diseases in which CAG repeat expansion is the responsible gene defect.

Adolescent↗

PubMed1995

CAG repeat expansion of Machado-Joseph disease in the Japanese: analysis of the repeat instability for parental transmission, and correlation with disease phenotype.

Machado-Joseph disease (MJD) is caused by abnormal expansion of an unstable CAG repeat in a novel gene locating on chromosome 14q32.1. We analysed this CAG repeat polymorphism with 66 Japanese MJD patients. All the patients were selectively associated with abnormal expansion of the CAG repeat. Repeat length of the mutant allele did not overlap that of normal allele and closely correlated with not only age at onset but also with clinical phenotypes. CAG repeat size is apparently related to a wide variety of phenotypic presentations in MJD.

Adult↗

PubMed1995

[Neurological manifestations of syringomyelia].

The subjects were among the patients registered at the Nagoya University Hospital, Aichi Medical University Hospital and Nagoya National Hospital between 1972 and 1995. There were 21 males and 21 females in this series. Symptoms began at 10 to 55 years of age. Cranial nerves were involved in 57% of the cases. The bulbar lesion was usually unilateral and on the same side as the cervical lesion. In regard to the cardinal signs of syringomyelia, segmental dissociated sensory loss was present in 95% of cases, segmental atrophy of upper limbs in 90%, and loss of sweating in 48%. Advanced cases became chair-bound because of spastic paralysis. However, they usually had no bulbar palsy nor sphincter disturbances, and the life expectancy was close to normal with adequate nursing. In twenty-one cases undergoing operation of posterior fossa decompression, the side of greater tonsilar herniation corresponded to the dominant side of cervical lesion.

Adolescent↗

PubMed1994

Aberrant androgen action and increased size of tandem CAG repeat in androgen receptor gene in X-linked recessive bulbospinal neuronopathy.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The testosterone, LH and FSH levels in the controls were markedly suppressed after administration, but in the patients with X-BSNP, they were suppressed significantly less. The level of suppression varied considerably with the patients, and those of plasma testosterone and FSH were significantly correlated with the number of CAG repeats in the androgen receptor gene. These findings suggest that the androgen action was aberrantly transduced in the target organs in the patients with X-BSNP and which is related to the elongated CAG repeat in the androgen receptor gene.

Adult↗

PubMed1993

Spinal fluid cells and protein in amyotrophic lateral sclerosis.

The cerebrospinal fluid total protein in 385 cases of sporadic amyotrophic lateral sclerosis showed no relationship to survival, but it was related to survival time in 34 cases of familial amyotrophic lateral sclerosis. Infrequent and mild pleocytosis, and oligoclonal bands seemed to have no clinical significance in well established cases of amyotrophic lateral sclerosis.

Aged↗

PubMed1993

Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy.

Four of 8 definite heterozygous female carriers determined by PCR amplification of tandem CAG repeat of the AR gene, from 4 families of X-linked recessive bulbospinal neuronopathy (X-BSNP) showed extensive high amplitude motor unit potentials in examined muscles although all subjects were neurologically normal. Plasma creatine kinase, myoglobin, myosin light chain, lactate and pyruvate were all normal even in the carriers who showed EMG abnormalities. Muscle biopsy showed a type 2 fiber preponderance and possible very mild type 2 fiber grouping in a carrier with an EMG abnormality. These results suggest that a mutant AR gene may express subclinical phenotypic manifestations in a subpopulation of the heterozygous females of X-BSNP.

Action Potentials↗

PubMed1993

Onset, natural history and outcome in idiopathic adult motor neuron disease.

Cases of adult-onset idiopathic motor neuron disease (MND) identified from January 1970 through December 1986 were studied in a defined area of California. The patients were followed prospectively throughout the illness in 99% of cases. Among 708 cases aged 25-74 years at onset, the most common type (86%) was typical, sporadic amyotrophic lateral sclerosis (SporALS). The risk of bulbar onset and shorter survival times increased with age in both men and women. About 4%, mainly younger men, experienced unusually long courses with milder paralysis, but could not be identified early in the illness. They probably represent one extreme of the ALS spectrum rather than a distinct subtype. Familial ALS (FamALS) was diagnosed in 7%. It developed earlier in life but ran a slightly longer course, which suggests a different disease process. Overall there was a statistically significant predominance of males, especially in 17 cases (2%) of progressive muscular atrophy (PMA). There were 26 cases (4%) classified as primary lateral sclerosis (PLS). Progressive bulbar palsy was not found; that diagnosis usually denotes merely the bulbar onset of ALS.

Adult↗

PubMed1993

Importance of the central region of 130-kDa insecticidal proteins of Bacillus thuringiensis var. israelensis for their activity in vivo and in vitro.

To delineate the mosquitocidal regions of the ISRH3 (CryIVB) and ISRH4 (CryIVA) proteins, which are two of the mosquitocidal 130-kDa proteins contained in the crystalline protein bodies (CPBs) of Bacillus thuringiensis var. israelensis (BTI), a deletion analysis of these protein genes has been done. Based on the evidence that each 130-kDa protein had two mosquitocidal regions, N-terminal and C-terminal ones, and these two regions shared a common part in the center of the 130-kDa proteins, deleted genes on this region were constructed. As the protein products which lacked the central region had reduced activities, the central region could be important for the mosquitocidal activity. The mosquitocidal and non-mosquitocidal truncated gene products of 130-kDa protein genes were also applied to a cultured lepidopteran cell line, TN-368. The mosquitocidal proteins caused the swelling and disruption of the cells in spite of the insecticidal specificity of CPBs of BTI, but the non-mosquitocidal proteins did not. Therefore, TN-368 cells were sensitive to the mosquitocidal fragments of 130-kDa proteins of BTI under the assay conditions used.

Animals↗

PubMed1992

Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene.

The genetic mutation of X-linked recessive bulbospinal neuronopathy is amplification of a polymorphic tandem CAG repeat in the androgen receptor gene. We studied this CAG repeat in 26 Japanese patients from 21 families with X-linked recessive bulbospinal neuronopathy. The number of CAG repeats was significantly correlated with the age at onset of limb muscular weakness (r = -0.596, p < 0.001) and age-adjusted scored disability (r = 0.446, p < 0.03). The length of the CAG repeat therefore seems to be a determinant factor of clinical severity.

Adult↗

PubMed1992

The association of hypopituitarism with small pituitary, invisible pituitary stalk, type 1 Arnold-Chiari malformation, and syringomyelia in seven patients born in breech position: a further proof of birth injury theory on the pathogenesis of "idiopathic hypopituitarism".

We report seven cases of hypopituitarism all having a history of breech delivery, asphyxia at birth, and syringomyelia. A small pituitary gland was found on MRI or CT in six cases, invisible pituitary stalk on MRI in five cases, and type 1 Arnold-Chiari malformation in six cases. A constellation of these abnormalities are best explained by traction of brain and spinal cord of the subjects exerted during breech delivery and further support the primary role of birth trauma in the genesis of "idiopathic hypopituitarism".

Adolescent↗

PubMed1992

[A case report of rheumatoid arthritis patient with thoracic myelopathy].

The authors report a 39-year-old woman with rheumatoid arthritis associated with myelopathy at the thoracic level. X-ray films of thoracic spine showed scoliosis which had its apex at T6. Myelography demonstrated incomplete block at the level of T6. Computerized tomogram revealed destruction of left pedicle of the sixth thoracic vertebra and dislocation of the sixth rib into the spinal canal which compressed cord at T6 level. Hemi-laminectomy at T5-T7 level and decompression were performed. Pathological investigations of soft tissue around the cord and dura mater showed infiltration of small round cells. We concluded that the synovitis of costo-transverse joint or costovertebral joint led to the destruction of the pedicle. As a result, dislocation of the rib, scoliotic deformity and thoracic myelopathy occurred.

Adult↗

PubMed1992

[DNA diagnosis of X-linked recessive bulbospinal muscular atrophy by androgen receptor gene mutations].

X-linked recessive bulbospinal muscular atrophy (BSMA) is an adult-onset form of motor neuron disease, of which androgen receptor (AR) gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region was found by Fischbeck et al (1991). We investigated this AR gene abnormality by polymerase chain reaction (PCR) in 16 unrelated Japanese BSMA pedigrees, including 21 patients, 11 male siblings without any neurological signs and 9 female siblings. PCR products for AR-CAG repeat obtained from 21 affected individuals were enlarged in fragment size (about 100 bp longer than normal control size), whereas those from clinically unaffected brothers of the patients and their offsprings were all normal in size. Moreover, PCR products from 8 obligate heterozygous females (carriers) consisted of two different fragments with enlarged and normal size. Our results confirmed the findings reported by Fischbeck et al, and indicated that the detection of this AR gene mutations with increased size of a polymorphic tandem CAG repeat is beneficial for pre-onset diagnosis or carrier detection of this disease.

Adolescent↗

PubMed1991

[A clinicopathological study of familial amyotrophic lateral sclerosis with special reference to the mode of motoneuron loss in the spinal ventral horn].

The authors analyzed clinicopathologically eight patients with familial amyotrophic lateral sclerosis (F-ALS). We performed the morphometric analysis on size and topographical distribution of the fourth lumbar spinal ventral horn cells, and correlated thus obtained results with the clinical, genetic and neuropathological features of these cases. The patients were consisted of six men and two women with age ranged between 40 and 58 years old. Six cases among them were involved predominantly in the lower-legs with generalized hyporeflexia and no Babinski's sign, which were compatible with the "pseudopolyneuritic" as a clinical form. Two other cases were involved in the upper limbs as the initial symptom and were considered to be "common form". Pathologically, five cases showed multiple system degenerations including the middle root zone of the posterior columns, Clarke's nuclei and posterior spinocerebellar tracts as well as the ventral horns and pyramidal tracts, which were designated as the form of "multiple system degeneration". In addition, three in these five cases were also associated with an extensive neuron loss and marked gliosis in the Onuf's nuclei, subthalamic, red and cerebellar dentate nuclei, suggesting that the involvement in certain F-ALS cases with a form of multiple system degeneration is more extensive in topography than ever believed. In other three cases, the neuronal degenerations were considerably restricted in the somatic motor efferent system, which were consistent with the classical pathology of the sporadic ALS, and were designated as "classical form". Five of seven cases showed a severe motoneuron loss in both the large and small neurons in the ventral horn. These five cases were heterogeneous in the pathological forms "multiple system degeneration" or "classical", but all were "pseudopolyneuritic" in clinical form. Moreover, these extensive motor neuron loss including small ones in the spinal ventral horn was similarly observed in the sporadic pseudopolyneuritic form of ALS cases. In two cases of F-ALS with "common" in clinical form, large motoneurons were fairly well preserved as are in the common form of sporadic ALS cases. Our tentative conclusion is that mode of motoneuron loss in the spinal ventral horn of F-ALS is more correlated to the clinical manifestations rather than the pathological or genetic background.

Adult↗

PubMed1991

[A clinicopathological study of the somatic motor efferents in the pseudopolyneuritic form of amyotrophic lateral sclerosis].

Histopathology of the somatic motor efferents of three cases with pseudopolyneuritic from of amyotrophic lateral sclerosis (ALS) was analyzed, and the results were correlated with the clinical symptoms. The population of myelinated fibers in the lateral corticospinal tract at the thoracic segment, and in the fourth ventral roots, and motor neurons in the fourth ventral horns were morphometrically quantified. The patients were two males and one female ranging in age from 43 to 67 years, and showed a clinical course of 1.8 to 9.5 years. All three cases did not show any pyramidal sign nor spasticity but showed an extensive leg involvement, particularly the distally accentuated muscular weakness with depressed deep tendon reflexes. The clinical manifestations were consistent with the pseudopolyneuritic form of ALS. Fiber size profile of the myelinated fibers in the lateral corticospinal tracts at T7 segments and L4 lumbar ventral roots were estimated on the epon-embedded transverse sections as previously described (Sobue et al, 1981). Number and size distribution of anterior horn cells in the L4 segments were measured on 300-500 consecutive 10 microns-thick paraffin sections stained with Klüver-Barrera technique, using a TGZ-3 particle size analyzer (Zeiss). The location of the remained anterior horn cells was also quantitatively estimated. Three cases with common form of ALS and three control cases were analyzed in the same manner. The large myelinated fibers in the lateral corticospinal tract were extensively and predominantly depleted in all three cases. The small myelinated fibers were also depopulated but in lesser degree. The mode of these myelinated fiber loss was almost compatible with those in common form of ALS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Phosphorylated high molecular weight neurofilament protein in lower motor neurons in amyotrophic lateral sclerosis and other neurodegenerative diseases involving ventral horn cells.

Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.

Adolescent↗