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Biomedical subjects

H Toriyama

Publications and source records attributed to H Toriyama.

15 recordsLinked to original sources
PubMed2001

Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel.

The importance of voltage-dependent Ca2+ channels (VDCCs) in pain transmission has been noticed gradually, as several VDCC blockers have been shown to be effective in inhibiting this process. In particular, the N-type VDCC has attracted attention, because inhibitors of this channel are effective in various aspects of pain-related phenomena. To understand the genuine contribution of the N-type VDCC to the pain transmission system, we generated mice deficient in this channel by gene targeting. We report here that mice lacking N-type VDCCs show suppressed responses to a painful stimulus that induces inflammation and show markedly reduced symptoms of neuropathic pain, which is caused by nerve injury and is known to be difficult to treat by currently available therapeutic methods. This finding clearly demonstrates that the N-type VDCC is essential for development of neuropathic pain and, therefore, controlling the activity of this channel can be of great importance for the management of neuropathic pain.

Acetic Acid↗
PubMed1999

Abundant expression and cytoplasmic aggregations of [alpha]1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6.

Spinocerebellar ataxia type 6 (SCA6) is one of the eight neurodegenerative diseases caused by a tri-nucleotide (CAG) repeat expansion coding polyglutamine (CAG repeat/polyglutamine diseases) and is characterized by late onset autosomal dominant cerebellar ataxia and predominant loss of cerebellar Purkinje cells. Although the causative, small and stable CAG repeat expansion for this disease has been identified in the [alpha]1A voltage-dependent calcium channel gene (CACNA1A), the mechanism which leads to predominant Purkinje cell degeneration is totally unknown. In this study, we show that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intra-nuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The present study indicates that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the [alpha]1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A.

Animals↗
PubMed1996

Surgical approaches for treatment of ischaemic cerebral stroke other than moyamoya disease in children.

Ischaemic cerebral strokes in children are relatively uncommon. With the exception of patients with moyamoya disease, there is no effective treatment for these lesions. One potential approach is encephalo-duro-arterio-synangiosis (EDAS). This is a safe neurosurgical procedure that promotes spontaneous transdural anastomosis that may provide additional blood flow to ischaemic regions. We present eight children with ischaemic strokes other than moyamoya disease, and discuss surgical attempts to treat this entity. The mean age of the eight children was 3.6 years (range: 13 months to 9 years). All children presented with acute childhood hemiplegia. Ischaemic stroke had occurred in association with a head injury in three children, but without an apparent cause in five. Five children underwent stable xenon-enhanced computed tomography to evaluate cerebral blood flow and all but one patient underwent EDAS. One child with no angiographic abnormalities recovered to a normal neurological state without surgery. Following surgery, another child also fully recovered, and the remaining six children recovered with only a slight hemiparesis. Revascularization was observed on a follow-up angiogram in three children. Our surgical experiences suggest that revascularization is influenced by haemodynamic demand and recanalization of the occluded artery. We favour the use of indirect anastomosis (EDAS) for selected patients and suggest that chronic ischaemia probably contributes to surgical success.

Anastomosis, Surgical↗
PubMed1991

The formation of gastric ulcers with a tendency to hemorrhage in association with aortic aneurysms.

It is widely accepted that patients with aortic aneurysm (AA) show a higher incidence of peptic ulcers than those without. However, the pathogenesis of peptic ulcers associated with AA remains obscure. We measured the gastric mucosal blood flow (GMBF) endoscopically and also determined the gastric mucosal prostaglandin (PG) levels of these AA patients to investigated the mechanism behind gastric ulcer formation. Moreover, we investigated the consumption coagulopathy (CC) of AA responsible for inducing the hemorrhage from ulcers. The GMBF values of 7 AA cases, taken at the antrum, angle and corpus, were significantly decreased compared with those of control cases, while the PGE2 levels of the gastric mucosa were also significantly reduced. With regard to CC, the serum levels of fibrinogen or platelets were significantly lower than those of the control group. These results indicate that the decrease in GMBF, followed by the reduction in endogenous PG, might contribute to the gastric ulcer formation in AA patients, and that CC associated with AA could be an important factor causing the hemorrhage from these ulcers. AA patients should therefore be treated with focusing attention on the possibility of an associated ulcer and ulcer bleeding.

Aged↗
PubMed1989

[Antitumor effect of IL-2 entrapped in liposomes on rat hepatoma, AH-66].

The human recombinant interleukin 2 (IL-2) was entrapped in liposomes, and the therapeutic effects of the liposomes containing IL-2 (Lip-IL-2) were experimentally studied using the rat hepatoma strain, AH-66, maintained in donryu rats and challenged subcutaneously in the inguinal region. The peri-tumor injections of Lip-IL-2 (15 X 10(4)/kg units for the IL-2 dose) significantly inhibited the tumor growth as determined from the relative mean tumor weight, although no therapeutic effects were observed when the unentrapped IL-2 or liposomes containing saline was administered rats in the same way as the injections of Lip-IL-2. They also prolonged the survival time of rats. The studies of serum IL-2 values after i.v. or s.c. injections of Lip-IL-2 revealed that IL-2 was released gradually from the liposomes containing IL-2 into the circulation. As the result of the tumor tissue staining of the immunoperoxidase 18 hrs after the peri-tumor injection of IL-2, it was shown that a number of macrophages infiltrated into the tumor tissue and degenerated tumor cells were observed adjacent to those macrophages. It is suggested that Lip-IL-2 is useful as an antineoplastic agent in the immunotherapy and that the therapeutic effects of Lip-IL-2 would be related to both the slow release of IL-2 and the cytotoxicity on the tumor cells mediated by the macrophages.

Animals↗
PubMed1988

[Repeated intra-abdominal administration of CDDP in carcinomatous peritonitis due to gastric cancer--a case report].

Two years and 10 months after gastrectomy, a 38-year-old man was diagnosed as having carcinomatous peritonitis due to gastric cancer. He was treated by intra-abdominal administration of 100 mg CDDP three times in addition to UFT. After each administration of CDDP, the amount of ascites and the serum value of CEA were decreased. Subjective symptoms, such as epigastric pain or sensation of fullness, were also improved. Although one year and 8 months has passed since the first administration of CDDP, the performance status of the patient remains 0. Nausea or vomiting was noted within 2 days after each administration. However, severe complications, like renal failure or intra-abdominal hemorrhage, were not observed. These findings suggest that repeated intra-abdominal administration of CDDP may be a useful therapy for carcinomatous peritonitis due to gastric cancer.

Adenocarcinoma↗
PubMed1972

Migration of Calcium and Its Role in the Regulation of Seismonasty in the Motor Cell of Mimosa pudica L.

Volume and conformational changes of the contractile tannin vacuoles of the abaxial motor cells of the primary pulvinus of Mimosa pudica L. parallel the seismonastic leaf movement. Since such changes in cells and organelles of animal systems are often regulated by calcium, we studied Ca(2+) movement in the motor cells and tissue. By fixation with Lillie's neutral buffered formalin, followed by staining with alizarin red sulfate (ARS), calcium was localized in the tannin vacuoles of the motor cells of the primary pulvinus. After treatment with ethylenediaminetetraacetate, 8-hydroxyquinoline, and several other calcium-complexing or extracting agents, the color reaction due to alizarin red sulfonate was no longer present. By using an analytical method, it was shown that the effluent from stimulated pulvini has significantly more Ca(2+) than that from unstimulated controls. Ten millimolar LaCl(3) inhibits recovery of the tannin vacuole in vivo in 10 mm CaCl(2) or in distilled water. Quantitative data obtained by microspectrophotometry demonstrated calcium migration during the bending movement of the primary pulvinus. In the adaxial motor cells a small amount of calcium migrates from the tannin vacuole, and calcium on the cell wall moves to the central vacuole. In the abaxial half, a large amount of calcium from the tannin vacuole moves to the central vacuole of the motor cell. It is probable that the calcium binds to the microfibrillar contents of the central vacuole. These observations support the contention that Ca(2+) migrates between the surface of the tannin vacuole and the inside of the central vacuole. The recovery and maintenance of the tannin vacuole in the spherical form may play a role in maintaining turgor in the motor cells of the abaxial half of the primary pulvinus of Mimosa.

Journal Article↗