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Biomedical subjects

I Matsuo

Publications and source records attributed to I Matsuo.

At least 37 records · Page 2Linked to original sources

A new murine zinc finger gene, Opr.

Here we report a novel murine zinc-finger gene, Opr, belonging to the opa/Zic family. Opr is expressed in the entire embryonic ectoderm before gastrulation, but gradually restricted to the anterior part from the mid to late streak stage. At the beginning of neural induction, Opr is expressed throughout the anterior neural plate, but is soon restricted to the neural ridge. After neural tube closure, its expression is maintained in the dorsal part of the neural tube, except for the roof of the telencephalon. Opr is also expressed in somites and limbs.

Amino Acid Sequence↗

Pyridoxine-induced photosensitivity and hypophosphatasia.

We describe a case of photosensitivity due to pyridoxine hydrochloride (vitamin B(6)) in a heterozygote of hypophosphatasia. Photopatch tests using pyridoxine hydrochloride and pyridoxal 5'-phosphate, compounds referred to as vitamin B(6), with ultraviolet light A irradiation were positive. Laboratory examination showed low serum alkaline phosphatase. Tissue-nonspecific alkaline phosphatase exon amplification from DNA of the patient's lymphocytes detected deletion 1154-1156 hypophosphatasia mutation, indicating that this patient was diagnosed to be a heterozygote of hypophosphatasia. The seric pyridoxal 5'-phosphate level of this patient with hypophosphatasia was higher than in normals. Furthermore, after oral administration of vitamin B(6) this level increased greatly and long-lastingly, and this might be related to the low level of alkaline phosphatase in this patient. Photosensitivity in this patient may have been caused by abnormal metabolism of vitamin B(6) under the hypophosphatic condition.

Adult↗

Angiotensin in the nucleus tractus solitarii contributes to neurogenic hypertension caused by chronic nitric oxide synthase inhibition.

Activation of the sympathetic nervous system and renin-angiotensin system has been suggested to contribute to the hypertension caused by chronic nitric oxide synthase inhibition. The aim of the present study was to determine whether angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation of the sympathetic nervous system in this model. Rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg. kg(-1). d(-1) in drinking water) for 2 weeks. Experiments were performed on anesthetized rats with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were measured. Microinjection of an angiotensin II type 1 (AT(1)) receptor antagonist (CV11974) or an angiotensin II type 2 (AT(2)) receptor antagonist (PD123319) into the depressor region within the NTS (identified by prior injection of L-glutamate) was performed. Microinjection of CV11974, but not of PD123319, produced greater decreases in arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control rats. The administration of hexamethonium resulted in a larger fall in arterial pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the brain stem was greater in L-NAME-treated rats than in control rats. These results suggest that increased sympathetic nerve activity plays a role in hypertension caused by chronic nitric oxide synthase inhibition and that activation of the renin-angiotensin system in the NTS is involved at least in part in this increased sympathetic nerve activity via AT(1) receptors.

Angiotensin Receptor Antagonists↗

Overexpression of eNOS in NTS causes hypotension and bradycardia in vivo.

The role of nitric oxide (NO) in the brain in the control of blood pressure and the sympathetic nervous system is debated. This study examined the effect of overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarii (NTS) on blood pressure in conscious rats. Adenovirus vectors encoding either eNOS (AdeNOS) or ss-galactosidase were transfected into the NTS in vivo. In the AdeNOS-treated rats, the local expression of eNOS in the NTS was confirmed by immunohistochemical staining and Western blot analysis for the eNOS protein and by increased production of nitrite/nitrate in the NTS measured by in vivo microdialysis. Blood pressure and heart rate, monitored by the use of a radiotelemetry system in a conscious state, were significantly decreased in the AdeNOS-treated group at day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion also was decreased at day 7 after the gene transfer in the AdeNOS-treated group. Our results indicate that overexpression of eNOS in the NTS decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats.

Animals↗

Oesophageal involvement in pemphigus vulgaris.

Oesophageal involvement of pemphigus vulgaris had been considered an exceptional event. However, our endoscopic study found oesophageal lesions in seven of eight (87.5%) patients with pemphigus vulgaris.

Adult↗

In vitro phototoxicity of new quinolones: production of active oxygen species and photosensitized lipid peroxidation.

To elucidate photosensitization potentials of new quinolone antibacterial agents, production of active oxygen species and peroxidation of squalene after ultraviolet A exposure were investigated. Production of singlet oxygen and/or hydrogen peroxide was estimated by bleaching of p-nitroso-N,N-dimethylaniline. Lomefloxacin showed the greatest ability to produce active oxygen species, and this ability was reduced by the addition of the singlet oxygen quencher sodium azide. Ciprofloxacin and fleroxacin also had strong activity. Photosensitized peroxidation of squalene was evaluated by measurement of thiobarbituric acid-reactive substances. Lomefloxacin was the strongest sensitizer, followed by fleroxacin and ciprofloxacin. These results suggest that certain new quinolones are involved in phototoxicity via the mechanism of active oxygen species.

Anti-Infective Agents↗

Functional equivalency between Otx2 and Otx1 in development of the rostral head.

Mice have two Otx genes, Otx1 and Otx2. Prior to gastrulation, Otx2 is expressed in the epiblast and visceral endoderm. As the primitive streak forms, Otx2 expression is restricted to the anterior parts of all three germ layers. Otx1 expression begins at the 1 to 3 somite stage in the anterior neuroectoderm. Otx2 is also expressed in cephalic mesenchyme. Otx2 homozygous mutants fail to develop structures anterior to rhombomere 3 (r3), and Otx2 heterozygotes exhibit craniofacial defects. Otx1 homozygous mutants do not show apparent defects in early brain development. In Otx1 and Otx2 double heterozygotes, rostral neuroectoderm is induced normally, but development of the mes/diencephalic domain is impaired starting at around the 3 to 6 somite stage, suggesting cooperative interactions between the two genes in brain regionalization. To determine whether Otx1 and Otx2 genes are functionally equivalent, we generated knock-in mice in which Otx2 was replaced by Otx1. In homozygous mutants, gastrulation occurred normally, and rostral neuroectoderm was induced at 7.5 days postcoitus (7.5 dpc), but the rostral brain failed to develop. Anterior structures such as eyes and the anterior neural ridge were lost by 8.5 dpc, but the isthmus and r1 and r2 were formed. In regionalization of the rostral neuroectoderm, the cooperative interaction of Otx2 with Otx1 revealed by the phenotype of Otx2 and Otx1 double heterozygotes was substitutable by Otx1. The otocephalic phenotype indicative of Otx2 haploinsufficiency was also largely restored by knocked-in Otx1. Thus most Otx2 functions were replaceable by Otx1, but the requirement for Otx2 in the anterior neuroectoderm prior to onset of Otx1 expression was not. These data indicate that Otx2 may have evolved new functions required for establishment of anterior neuroectoderm that Otx1 cannot perform.

Animals↗

HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303.

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.

Amino Acid Sequence↗

Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis.

Spontaneous regression of hepatocellular carcinoma is a rare phenomenon. Abscopal regression of tumours resulting from the effect of irradiation of a tissue on a remote non-irradiated tissue is also rare. The case of a 76 year old Japanese man with hepatocellular carcinoma that regressed after radiotherapy for thoracic vertebral bone metastasis is described. Serum levels of tumour necrosis factor-alpha increased after radiotherapy. The findings suggests that such abscopal related regression may be associated with host immune response, involving cytokines such as tumour necrosis factor-alpha.

Aged↗

Endothelin-1 increases the neuronal activity and augments the responses to glutamate in the NTS.

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to L-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

Animals↗

Role of endogenous nitric oxide in the brain stem on the rapid adaptation of baroreflex.

It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME, 8 micromol), N(omega)-nitro-D-arginine methyl ester (D-NAME, 8 micromol), L-arginine (40 micromol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. L-Arginine reversed the effects of L-NAME. However, D-NAME or L-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

Animals↗

alpha-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation.

Antibodies to an alpha-galactosyl saccharide structure are mainly responsible for hyperacute rejection after pig-to-primate xenotransplantation. The beneficial effect of alpha-galactosyl oligosaccharides has been shown on the inhibition of anti-pig natural antibodies. We synthesized polyethylene glycol (PEG)-conjugates of alpha-galactosyl disaccharide (Di) and trisaccharide (Tri) as potential inhibitors of the rejection reaction. The half lives of Di, Tri, PEG-conjugated Di (Di-PEG) and PEG-conjugated Tri (Tri-PEG) were 18.1 +/- 2.3 min, 20.2 +/- 0.9 min, 38.7 +/- 2.8 min and 35.8 +/- 1.6 min, respectively. Furthermore, Di-PEG and Tri-PEG showed biphasic clearance, and their half lives at the second phase were longer than 10 hours. PEG-conjugated oligosaccharides (Di-PEG, Tri-PEG) markedly inhibited cytotoxic action of human sera to pig kidney cell line (PK15) compared to unconjugated oligosaccharides (Di, Tri). The binding of IgM antibodies to PK15 cells, however, was more strongly blocked by unconjugated oligosaccharides than PEG-conjugated oligosaccharides. This phenomenon can be explained by the finding that PEG has anti-complement activity and masks antigenic sites of oligosaccharides. In conclusion, conjugation of PEG to oligosaccharides provided two beneficial effects; prolonged intravascular retention time and anti-complement activity, upon systemic application of the oligosaccharides. The present findings opened a new approach to treatment of hyperacute rejection after xenotransplantation.

Animals↗

Developmental patterning and evolution of the mammalian viscerocranium: genetic insights into comparative morphology.

The vertebrate cranium is generally classified into the neurocranium and the viscerocranium. The latter is derived from the neural crest and so is the prechordal portion of the neurocranium. A view we favor considers the prechordal neurocranium as the premandibular component of the viscerocranium, and the vertebrate skull to consist of the neural crest-derived viscerocranium and the mesodermal neurocranium. Of these developmental units, only the viscerocranium appears to have completely segmented metamerical organization. The Hox code which is known to function in specification of the viscerocranium does not extend rostrally into the mandibular and premandibular segments. By genetic manipulation of rostrally expressed non-Hox homeobox genes, the patterning mechanism of the head is now demonstrated to be more complicated than isomorphic registration of the Hox code to pharyngeal arches. The phenotype by haplo-insufficiency of Otx2 gene, in particular, implies the premandibular cranium shares a common specification mechanism with the mandibular arch. Our interpretation of the metamerical plan of the viscerocranium offers a new scheme of molecular codes associated with the vertebrate head evolution.

Animals↗

Malignant lymphoma of the stomach after chemotherapy for hepatocellular carcinoma.

A rare case of malignant lymphoma of the stomach after treatment for hepatocellular carcinoma (HCC) is reported. A 72-year old man presented with a large mass on the right hypochondrium, which was diagnosed as HCC associated with chronic hepatitis C with cirrhosis. The inoperable tumor was treated conservatively with cisplatin, etoposide, carboplatin, and Lipiodol infused into the hepatic artery, together with transcatheter arterial embolization. The patient presented 38 months later with features suggestive of gastric ulceration. Endoscopy and histological examination of biopsy material confirmed the presence of malignant lymphoma of the stomach. He ultimately died as a result of hepatic failure. The clinical presentation suggests that gastric lymphoma was possibly related to the lymphotropic effect of hepatitis C virus (HCV) and exacerbated by intraarterial injection of the cytotoxic drugs.

Aged↗