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Biomedical subjects

G Sobue

Publications and source records attributed to G Sobue.

At least 253 records · Page 14Linked to original sources

Nerve growth factor prevents neurotoxic effects of cisplatin, vincristine and taxol, on adult rat sympathetic ganglion explants in vitro.

Anti-cancer drugs, cisplatin, vincristine and taxol clinically induce toxic sensory as well as autonomic neuropathy. Administration of nerve growth factor (NGF) has been found to prevent experimental sensory neuropathies induced by these anti-cancer drugs, but the information about autonomic neuropathy is lacking. We developed an adult rat superior cervical ganglion (SCG) explant culture, which we treated with cisplatin, vincristine and taxol either in the presence or absence of NGF. The maximum length of regenerated neurites was shortened by cisplatin, vincristine and taxol in a dose-dependent manner. However cotreatment with NGF significantly promoted the regeneration of neurites in all drug-treated explants. The effect of NGF was clearly blocked by the anti-NGF antibody. These findings suggest that cotreatment of NGF prevents and reverses the toxic effects of the anti-cancer drugs on the sympathetic neurons.

Animals↗

Sensory conduction study in chronic sensory ataxic neuropathy.

Sensory conduction was studied in six patients with chronic sensory ataxic neuropathy of an idiopathic type and associated with Sjögren's syndrome. Motor nerve conduction velocities were normal in most cases, but sensory nerve potentials could not be evoked in a routine peripheral nerve conduction study. Cortical and cervical somatosensory evoked potentials (SEPs) and evoked potentials from Erb's point were barely recorded by median nerve stimulation at the wrist. When the median nerve was stimulated at more proximal points, clear potentials were recorded from Erb's point, but cortical SEPs were still hardly elicited. Thus the sensory nerves are centrally and peripherally involved in this condition, and the involvement is more prominent in the distal portion in the peripheral nerve. These findings suggest that central-peripheral distal axonopathy is a process involved in this illness and that the dorsal root ganglia may be primarily involved, in accord with previous pathological studies.

Aged↗

Gm haplotypes in chronic inflammatory demyelinating polyradiculoneuropathy in Japanese patients.

We studied the serum Gm allotype of 58 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 236 nonrelated normal controls in Japan. The incidences of the Gm phenotype and haplotype in the patients were not significantly different from those in the normal controls. When CIDP was classified into two subgroups in terms of clinical course, the chronic relapsing (CR) and chronic nonrelapsing type (CNR), the distribution of all Gm haplotypes was significantly different between CR and CNR (total chi 2 = 8.319; corrected p < 0.05). Our findings suggest that the clinical course of CIDP may be associated with the Gm haplotype.

Chronic Disease↗

[The corticospinal tract lesion of amyotrophic lateral sclerosis--magnetic resonance imaging of the spinal cord].

Magnetic resonance imaging by gradient echo method demonstrated lesions of the lateral corticospinal tract at cervical cord levels in three ALS patients. Patient 1 was a 43-year-old woman with common form of ALS. She developed right-side predominant pyramidal signs, and right-side predominant prolongation of central motor conduction time. MRI showed hypersignal intensity areas in the dorsal region of the lateral column at the 4th and 5th cervical segments with right-side predominancy. Patient 2 was a 65-year-old man with pseudopolyneurtic form of ALS, who showed lower motor neuron signs without a pyramidal sign. MRI of the 3rd and 4th cervical cord segments demonstrated bilateral hypersignal intensity areas in the dorsal part of the lateral column. Patient 3 was a 62-year-old man with common form of ALS, who showed marked bilateral pyramidal signs with Babinski's sign. MRI of the 5th cervical spinal cord segment demonstrated bilateral hypersignal intensity areas in the dorsolateral column. Thus obtained MR images of the spinal cord corresponded well to the postmortem-confirmed degeneration of the spinal corticospinal tract. MRI of the spinal cord performed by gradient echo method would provide additional information on the upper motor neuron involvement in ALS.

Adult↗

[Chronological changes in MR imaging of inferior olivary pseudohypertrophy--report of two cases].

Olivary pseudohypertrophy (OH) and its chronological change was examined by MR images in two patients with brainstem vascular disease. Patient 1 was a 63-year-old woman who developed an infarction in the red nuclei associated with "top of the basilar" syndrome. Two months later, she showed 2-4 c/s rhythmic myoclonus (rubral tremor) involving four extremities. Palatal myoclonus was absent. MR images of the inferior olives did not demonstrate a significant lesion in 10 days after the onset, but showed OH in 6 months, and then their size attained a maximum in 10 months after. On T2-weighted (T2) images and proton-density-weighted (PD) images obtained at 20 and 24 months, OH gradually became irregular but discrete in their intensity, and the intensity had also decreased to some extent. Rhythmic myoclonus had subsided to some extent after 20 to 24 months. Patient 2 was a 62-year-old woman who had a small hemorrhage in the pontine tegmentum. She developed 2.5 c/s vertical ocular myoclonus without palatal myoclonus two months after the onset. MR images showed OH in 6 and 8 months after the onset. On T2 and PD images obtained at 20 months, the image of OH gradually developed to become irregular in intensity and slightly atrophic in size. The ocular myoclonus somewhat reduced in their intensity 12 months after the onset. These serial changes in MR images were considered to correspond to the chronological changes of the pathology of OH. Appearance and subsidence of the myoclonic movement was also considered to correlate to the sequential changes of MR images of OH.

Cerebrovascular Disorders↗

[Hemodynamic TIA associated with severe anemia--a case report].

A 62-year-old man developed recurrent TIAs presenting as mild unconsciousness, dysarthria and weakness of the right upper extremity lasting for 15 to 20 minutes. He was found to have severe iron deficiency anemia (hemoglobin: 5.5-5.9g/dl; hematocrit: 18.4-19.5%) which insidiously developed through the chronic bleeding from the gastric ulcer. He had slight hypertension (184/86mmHg), but no orthostatic hypotension. DSA and MR angiography showed severe stenosis at the origin of the bilateral internal carotid arteries and of the left vertebral artery. There was also hypoplasia of the right vertebral artery. Blood circulation detected by 123I-IMP-SPECT was markedly decreased in the whole brain and in the right hemisphere of the cerebellum. TIA was, however, completely disappeared following to the recovery of anemia. The present case suggested that the presence of severe anemia accelerated the occurrence of hemodynamic TIA (regional cerebral anemic hypoxia), which is probably the consequence of the reduced oxygen-transporting capacity of the blood.

Aged↗

[Skin sympathetic nerve activity in amyotrophic lateral sclerosis].

Skin sympathetic nerve activity (SSNA) was microneurographically analyzed in five patients with amyotrophic lateral sclerosis (ALS) (four men, one woman; age ranges between 36 and 68 years) and 16 age- and sex-matched controls. The duration of illness after the onset was ranged between 1 and 3 years. Three cases were the common form of ALS showing a moderate to severe involvement of the upper extremities and mild degree of bulbar signs. Two were the pseudopolyneuritic form with lower motor neuron sign predominant in the legs. All these patients could walk by alone and did not show any respiratory distress. SSNA was recorded directly by inserting a tungsten microelectrode into the tibial nerve at the popliteal fossa as described before. The sweat rate and skin blood flow on the area innervated by the tibial nerve were also monitored. Resting activity of the SSNA (bursts/minute) was significantly higher (p < 0.05) in patients with ALS as compared with the controls. The rate of increase in SSNA under the load of mental arithmetic, tone, electric stimulation of the median nerve and immersion of the hand into cold water were only slightly higher in ALS. The rate of increase in SSNA response by these stimuli against the basal SSNA, however, was not significant. These results indicate that skin sympathetic nerve functions are hyperactive in ALS particularly in the basal resting level, though the underlying mechanism is unclear.

Adult↗

Gene expression of high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system.

Steady-state mRNA levels and immunoreactive proteins for high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system (PNS) were examined in autopsied material. trk mRNA expression was observed only in the sympathetic and dorsal root ganglia, while LNGFR mRNA was expressed widely through the PNS as well as non-neural tissues. Immunoreactive trk proto-oncogene product (p140trk) and LNGFR occurred in the perikarya of the subset of the sympathetic and dorsal root ganglion neurons, but only LNGFR immunoreactivity also occurred in the perineurium and the outer layer of the vessels. The spatial patterns of the trk and LNGFR gene expression in the adult human PNS were similar to those observed in the rat, mouse and chick, and their expression was well preserved in the aged.

Aged↗

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and low-affinity nerve growth factor receptor (LNGFR) mRNA levels in cultured rat Schwann cells; differential time- and dose-dependent regulation by cAMP.

Steady-state mRNA levels for NGF, BDNF, and NT-3, and their receptors, LNGFR, trk, trkB, and trkC, were examined in cultured rat Schwann cells. NGF, BDNF, and LNGFR mRNAs were expressed in control Schwann cells, but NT-3, trk, trkB and trkC mRNAs were not. As previously reported, when Schwann cells were treated with forskolin or 8-bromo-cAMP, NGF mRNA expression was enhanced, while BDNF and LNGFR mRNA levels were suppressed. The optimal concentration of forskolin for NGF mRNA enhancement and BDNF mRNA suppression was similar to that for LNGFR mRNA suppression, which coincided with the optimal concentration for Schwann cells to differentiate. However, the lag-time for forskolin-induces down-regulation of LNGFR mRNA was far greater than that for NGF mRNA increase and BDNF mRNA suppression.

8-Bromo Cyclic Adenosine Monophosphate↗

Chronic progressive sensory ataxic neuropathy: clinicopathological features of idiopathic and Sjögren's syndrome-associated cases.

Eleven patients with chronic progressive sensory ataxic neuropathy were examined clinicopathologically. Three cases were associated with primary Sjögren's syndrome (SS-SAN) and the others were considered to be idiopathic (ISAN). The major clinical symptom in both was loss of proprioceptive and kinesthetic sensation with some impairment of superficial sensation, with multifocal and asymmetrical distribution and progression. The truncal and trigeminal nerves were frequently involved. The motor system was substantially preserved. These somatic sensory and motor symptoms did not differ between ISAN and SS-SAN, but autonomic nervous system signs were more frequent in SS-SAN. Polyclonal elevations of serum IgG and/or IgA were seen in 8 patients. One autopsied case with ISAN combined with previous reports suggested that systemic T- and B-cell infiltration into the nervous tissues, as well as a wide variety of the visceral organs, may be a common finding in ISAN and SS-SAN, and could participate in the cause of this neuropathy and polyclonal hypergammaglobulinaemia.

Aged↗

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↗

Laminin A, B1, and B2 chain gene expression in transected and regenerating nerves: regulation by axonal signals.

Laminin A, B1, and B2 chain mRNA levels in degenerating and regenerating mouse sciatic nerves were examined using northern blot analysis. In normal intact nerves, B1 and B2 mRNA steady-state levels were high, but when the nerves were crushed, the steady-state levels of B1 and B2 mRNA per milligram wet tissue weight of the distal segments of the nerves increased five- to eightfold over that of control levels as the total RNA and beta-actin mRNA levels increased, suggesting that these increases were the consequence of Schwann cell proliferation after axotomy. When the steady-state levels of B1 and B2 mRNA were normalized as the ratio to total RNA or beta-actin mRNA levels, however, they drastically decreased to about 20% of the normal nerve levels in the nerve segments distal to both the crush and transection sites 1 day after injury. In the crushed nerves, B1 and B2 mRNA levels gradually increased as the regenerating nerves arrived at the distal segments and reestablished normal axon-Schwann cell contact, and then returned to normal levels on the 21st day. In the transected nerves, where Schwann cells continued to be disconnected from axons, both B1 and B2 mRNA levels remained low. Cultured Schwann cells expressed detectable levels of B1 and B2 chain mRNA which significantly increased when the cells were cocultured with sensory neurons. However, mRNA for A chain was not detectable in the normal, axotomized nerves or in cultured Schwann cells. These data indicate that Schwann cells express laminin B1 and B2 chain mRNA that are up-regulated by axonal or neuronal contact, but they do not express A chain mRNA.

Actins↗

Skin sympathetic nerve activity in acquired idiopathic generalized anhidrosis.

We recorded skin sympathetic nerve activity (SSNA) microneurographically from the right tibial nerve of a patient with acquired idiopathic generalized anhidrosis (AIGA). The patient did not show any spontaneous sweating or pilocarpine- and nicotine-induced sweat response. Histopathologic examination showed degenerated eccrine glands associated with surrounding inflammatory cellular infiltration. Electrical nerve stimulation produced a two-peak pattern of SSNA reflex discharge representing sudomotor and vasoconstrictor components. The frequency of spontaneous SSNA bursts (burst rate), presumably of a sudomotor nature, at the ambient temperature of 25 degrees C was significantly higher than in a healthy control subject and was further increased at a temperature of over 38 degrees C. Thus, sudomotor sympathetic nerve activity is well preserved or even increased in AIGA. We conclude that anhidrosis of AIGA results from the generalized sweat gland dysfunction rather than decreased sympathetic outflow to the skin.

Adult↗

Segmental anhidrosis in the spinal dermatomes in Sjögren's syndrome-associated neuropathy.

We describe two women with primary Sjögren's syndrome and sensory neuropathy who had anhidrosis segmentally along the dermatomes of the spinal segment, along with sensory loss. Intradermal administration of cholinergic agents elicited no sweat response in the spinal segments with anhidrosis, whereas a normal response was present in the segments with obvious sweating. These features suggest segmental involvement of the postganglionic sympathetic ganglion cells.

Aged↗

[A case of asymptomatic common carotid artery occlusion with the persistent proatlantal intersegmental artery].

A case of asymptomatic common carotid artery occlusion with direct vertebrocarotid anastomosis (proatlantal intersegmental artery) in a 70-year-old male is reported. Despite the acquired left common carotid artery occlusion, there was no demonstrable neurologic deficits that would occur by the involvement of the area supplied by the occluded carotid system. Cerebral angiography revealed, in addition to efficient collateral circulation from the contralateral carotid system through the anterior communicating artery, a collateral channel from the left vertebral artery to the ipsilateral external carotid artery via the proatlantal intersegmental artery. These collateral circulations were indicated to be important in prevention of possible grave neurologic consequences. The proatlantal intersegmental artery, though rarely visualized by ordinary cerebral angiographic procedures, was thus demonstrated to be capable of serving as a collateral channel of potential usefulness in the event of severe intracranial hemodynamic alterations, including acquired common carotid artery occlusion.

Aged↗

[Autonomic dysfunction in sensory ataxic neuropathy with Sjögren's syndrome].

Sjögren's syndrome (SjS) is occasionally associated with chronic progressive sensory neuropathy, and its major pathology is suggested to be dorsal root ganglionitis with the T-lymphocyte invasion. Autonomic dysfunction is frequently accompanied by SjS-associated sensory neuropathy but its underlying pathology is uncertain. We reported four patients with SjS-associated sensory ataxic neuropathy who satisfied the diagnostic criteria of Sjögren's syndrome and also showed a wide variety of autonomic disturbances. The sensory involvement was initially those of multiple mononeuritis in the distal extremities, but in the advanced stage it involved the area distributed along the spinal segmental dermatomes particularly in the trunk. Complete anhidrosis with discrete segmental distribution, as well as absence of response to cholinergic agents, was observed in three cases. Surface skin temperature recorded by a thermoviewer also showed a segmental involvement along the spinal dermatomes in two cases. Adie's pupils were present in two cases. These features suggested that the segmental involvement of the postganglionic sympathetic ganglion cells could be present in the underlying pathological condition. As for the other autonomic dysfunction, two cases showed severe postural hypotension and three cases had an abnormal heart rate variation (R-R interval). Our cases indicated that SjS-associated sensory ataxic neuropathy also manifest variable autonomic disturbances and suggested that similar pathological process to that involving the dorsal root ganglia would be present in the pathology of sympathetic and ciliary ganglion cells.

Aged↗