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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 505 records · Page 28Linked to original sources

A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. In order to investigate the effects of ET-1 on retinal vessels, ET-1 (1-1000 pmol) was injected into the posterior vitreous body in rabbits. A high dose of ET-1 induced transient complete obstruction of the retinal vessels. In this experimental model of transient complete obstruction of the retinal vessels, the effects of ET-1 on retinal function were further analyzed by means of electroretinograms. The scotopic a-wave was not affected, but the amplitude of the scotopic b-wave was significantly elevated. The amplitude of oscillatory potentials was significantly reduced. These phenomena suggested that retinal ischemia without choroidal ischemia was brought about due to severe vasoconstriction of the retinal arteries. These findings indicate that intravitreal injection of ET-1 causes a transient cessation of blood supply from retinal vessels and that oscillatory potentials in electroretinograms appear to be sensitive for detecting changes of retinal circulation. This new model of transient complete obstruction of retinal vessels might be useful for studying the pathophysiology of severe retinal ischemia.

Animals↗

Abnormal localization of laminin subunits in muscular dystrophies.

To address potential involvement of muscle basal lamina and membrane cytoskeleton proteins in the etiology of non-dystrophinopathy muscular dystrophies, we examined the immunostaining intensity and distribution of laminin subunits (A, B1, B2 and M), type IV collagen, dystrophin and spectrin in skeletal muscle biopsies from 64 myopathic patients (17 Fukuyama congenital muscular dystrophy: FCMD, 13 congenital muscular dystrophy unrelated to FCMD: other CMD, 16 Duchenne muscular dystrophy: DMD, and 18 other neuromuscular diseases. In FCMD muscle, we found a significant reduction of laminin M (merosin; a striated muscle specific basal lamina-associated protein) with approximately 26% of levels seen in controls by quantitative immunofluorescence. Other CMD and DMD muscles showed less dramatic reductions (78%, 80%, respectively). The localization of laminin M was also abnormal in FCMD muscle. Laminin B1 and B2 showed abnormalities similar to those observed with laminin M, but were less marked. Laminin A was only detected in rare regenerating fibers in control biopsies, whereas it was seen around most muscle fibers in FCMD patients, and in dystrophin deficient muscle fibers from DMD patients and its carrier. Staining intensity of type IV collagen in FCMD muscle was not significantly different from the other diseases. These findings may implicate a primary or central role for the basal lamina in FCMD muscle.

Adolescent↗

Analysis of vasocontractile responses to endothelin-1 in rabbit retinal vessels using an ETA receptor antagonist and an ETB receptor agonist.

To study the role of endothelin receptor subtypes in rabbit retinal arteries, endothelin-1 (ET-1)-induced vasoconstriction was analyzed using the ETA receptor antagonist BQ-123 and the ETB receptor agonist BQ-3020. A cumulative injection of ET-1 (1 approximately 100 pmole) into the posterior vitreous body in anesthetized rabbits caused dose-dependent vasoconstriction in the retinal arteries, and ultimately caused complete obstruction. Fifteen minutes after BQ-123 (1 mumole) was injected into the posterior vitreous body, the dose-response curve of ET-1 was significantly shifted to the right. Intravitreal injection of BQ-3020 caused a significant retinal vasoconstriction only at the highest dose (1000 pmole). Therefore, in rabbit retinal arteries, ET-1-induced vasoconstriction appears to be mediated mainly through ETA receptors.

Animals↗

Endothelin-1-induced gastric ulcer is attenuated by cetraxate.

We investigated the effect of the anti-ulcer drug cetraxate on the development of the gastric ulcer induced by the submucosal injection of endothelin-1 in the rat gastric body, and its effects on gastric mucosal hemodynamics and tissue oxygenation by Laser doppler flowmetry and tissue spectrophotometry. Endothelin-1 induced gastric ulcer (ulcer length: 11.85 +/- 0.89 mm, mean +/- SEM, n = 4) which was strongly attenuated by cetraxate (ulcer length: 3.27 +/- 0.3 mm, mean +/- SEM, n = 8, p < 0.0001). Cetraxate maintained also tissue oxygenation without causing any significant effect on the endothelin-1-induced changes in gastric mucosal blood flow and volume. These results show that cetraxate exerts its cytoprotective action partly by maintaining mucosal oxygenation.

Animals↗

Balloon occlusion of a spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome type IV.

A case of spontaneous carotid-cavernous fistula associated with Ehlers-Danlos syndrome Type IV was treated successfully by transarterial balloon embolization. To minimize the stress to the arterial wall, we detached three silastic balloons with low-attachment force in the cavernous sinus with the aid of a proximal balloon to control the high flow of the fistula. To achieve complete obliteration, we had to inflate the third balloon to dimensions that occluded the cavernous portion of the internal carotid artery. Patients with Ehlers-Danlos syndrome Type IV carry a high risk when undergoing any diagnostic or therapeutic endovascular procedure due to the fragility of their blood vessels. Recognition of this entity is important and special attention should be paid to its pathophysiology for a successful treatment.

Adult↗

A Globosus amorphus from an in vitro fertilized embryo transferred to a Japanese black cow.

A Globosus amorphus along with a living calf was encountered following the transfer of blastocysts obtained by in vitro fertilization of in vitro-matured follicular oocytes in Japanese black cattle. Two embryos obtained 9 days after in vitro fertilization developed into either a hatched blastocyst with distinct inner cell mass or an expanded blastocyst with indistinct inner cell mass. The embryos were loaded into a 0.25-ml plastic straw and were nonsurgically transferred to the uterus of a heifer on Day 8 (Day 0 = estrus). On Day 75, a twin pregnancy was ultrasonically diagnosed in the right uterine horn, in which a live fetus with distinct limbs and a concomitant ovoid mass were detected. On Day 287, the dam developed parturient paralysis with dropsy of the fetal membranes. By palpation per rectum an ovoid mass was detected in the body of the uterus [corpus uteri] and a larger live fetus was in the uterine horn. A cesarean section was performed to extract a live fetus and a Globosus amorphus. The live fetus was female with the 60, XX female complements.

Journal Article↗

Cardio-respiratory control in an infant with Ondine's curse: a multivariate autoregressive modelling approach.

We applied spectral analysis through multivariant autoregressive model fitting [1] to RR interval (RRI) and respiratory (RES) oscillation obtained during quiet sleep in an infant with congenital central hypoventilation syndrome (Ondine's curse), a child with obstructive sleep apnea, and two healthy children. Power spectra, impulse response and noise contribution ratio between RRI and RES oscillation were calculated by using a minicomputer PFU-1200 (FACOM) to determine the structure of the feedback system between RRI and RES within the central nervous system. We found that the respiratory noise contribution ratio to RRI was significantly smaller in Ondine's curse (37 +/- 7.7%, at 0.23 Hz) than in obstructive sleep apnea (90 +/- 6.7%, at 0.39 Hz) and healthy subjects. We postulate that the result shows disturbance of the central autonomic control of breathing and heart rate in Ondine's curse.

Autonomic Nervous System↗

Development of ultradian rhythm of EEG activities in premature babies.

Ultradian rhythms in electroencephalogram (EEG) activity in premature neonates were studied. The values of square roots of total power (SQP) of EEG showed a normal Gaussian distribution. We analyzed the smoothed time series of SQP by autoregressive analysis and component analysis. Ultradian rhythm was divided into four groups by period length (group I: 5-30 min, group II: 30-60 min, group III: 60-100 min, group IV: longer than 100 min). Group IV rhythms were not detected before 32 weeks of gestation. Changes in the characteristic values of ultradian components in group II showed that there were critical periods in the development of central nervous activity at 29 and 33 weeks of gestation. This method allowed detection of ultradian rhythms, even at very early gestation, directly from the neonatal central nervous system. This method may be applicable to ill infants.

Activity Cycles↗

Traditional medicine in Turkey. IV. Folk medicine in the Mediterranean subdivision.

The traditional utilization of plants as medicine in the Mediterranean region has been investigated. Field surveys were carried out among the people who live in the Taurus Mountains. Sixty-nine medicinal plants have been identified, which are listed with the vernacular names, the parts used, the methods of preparing the drugs and their traditional usages.

Humans↗

The ETA antagonist BQ-123 inhibits anoxic contractions of canine coronary arteries without endothelium.

Experiments were designed to determine whether or not endogenous endothelin (ET) contributes to endothelium-independent anoxic contractions of canine coronary arteries. Rings without endothelium were suspended for isometric tension recording in conventional organ chambers filled with modified Krebs-Ringer bicarbonate solution. Anoxia (PO2 < or = 1 mm Hg) caused reproducible contractions. The anoxic contractions were augmented by exogenous endothelin-1 (ET-1). At 10(-6) M and 10(-5) M, BQ-123 (a specific endothelin antagonist) inhibited both the facilitatory effect of ET-1 and the anoxic contractions. At these concentrations BQ-123 caused a parallel shift to the right of the concentration-response curve to ET-1 and a small but significant depression of the response to norepinephrine, without affecting the maximal response to the catecholamine. BQ-123 did not significantly affect the concentration-response curve to Ca2+ in depolarizing solution (60 mM KCl). Monoclonal antibodies against ET-1 (70 micrograms/ml) inhibited the response to exogenous ET-1 and abolished the facilitating effect of the peptide, but did not affect the anoxic contractions. These results suggest that ET-1 contributes to anoxic contractions in canine coronary arteries without endothelium. The receptor involved belongs to the ETA-subtype and is not accessible to monoclonal antibodies.

Animals↗

Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary hypertension.

To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg), rats (PH rats, n = 6) were sacrificed. Vehicle-injected rats (n = 6) served as controls. The right ventricular systolic pressure of PH rats [58.0 +/- 4.7 mm Hg (mean +/- SEM)] was significantly higher than that in the vehicle-treated control rats (29.2 +/- 2.1; p < 0.01). Northern blot analysis showed that the expression of ETB-receptor mRNA decreased in the lung of PH rats. The venous plasma concentration of ET-1 measured by a sandwich-enzyme immunoassay was significantly higher in PH rats than in control rats (5.1 +/- 0.7 versus 1.3 +/- 0.2 pg/ml; p < 0.01). The present findings suggest that the expression of ETB-receptor mRNA decreases in the lung of PH rats, which might be closely related to the increase in plasma ET-1 concentration in these rats.

Animals↗

A case of malignant haemangioendothelioma treated with recombinant interleukin-2.

A case of malignant haemangioendothelioma of the scalp in an 82-year-old female treated with intralesional, intra-arterial and intravenous recombinant interleukin-2 (rIL-2) is reported. The scalp lesions disappeared after injection of 35,350,000 Japan reference units of rIL-2 and excision of the residual tumour. Immunohistochemical characterization of the cells infiltrating the lesion after rIL-2 administration revealed 30-40% CD4+ and CD8+ T lymphocytes, 20-30% macrophages and 5-10% natural killer cells. These findings are similar to those in other human cancers. Almost all of the cells in the intersticies of the lesion after rIL-2 injection expressed leucocyte function-associated antigen-1, and some of the tumour cells and the infiltrating cells around them expressed intercellular adhesion molecule-1. HLA-DR-positive cells markedly increased in number after rIL-2 administration. This report suggests that rIL-2 administration is the most effective therapy for malignant haemangioendothelioma.

Aged↗

Accidental poisoning of children in Japan: a report from the Japan Poison Information Center.

The Japan Poison Information Center (JPIC) was founded only 6 years ago as a result of co-operation between the Ministry of Health and Welfare, the Japanese Association for Acute Medicine, the Japan Pediatric Society and other related medical organizations. The JPIC is the only poison information center admitted by the Ministry of Health and Welfare to provide toxicological information to medical personnel and the general public, and has two offices on duty in alternating 24 h shifts. Every year, JPIC receives about 30,000 inquiries. About 82% of these inquiries are from the general public and 84% of the patients are children 5 years and younger. We contrasted the data in the fiscal year 1991 with the data of the American Association of Poison Control Centers (AAPCC). Child poison exposure in Japan is characterized by a high exposure rate of children under 1 year of age to (mostly) household products. The JPIC also analyzed the cause of tobacco ingestion. It is considered that the Japanese lifestyle causes differences from those reported by AAPCC. We report the accidental poisoning of children in Japan.

Accidents↗

Mechanism of rat uterine smooth muscle contraction induced by endothelin-1.

1. Endothelin (ET)-1 has been demonstrated to cause contraction of uterine smooth muscle. We investigated the role of ET receptor subtypes (ETA and ETB receptors) in ET-1-induced contraction of rat uterine smooth muscle by using the ETA receptor antagonist BQ-123 and the ETB receptor agonist BQ-3020. 2. ET-1 caused a contraction with superimposed oscillations of the rat isolated uterus suspended in Krebs-Ringer solution; both the amplitude of contraction as well as the oscillation frequency increased in a dose-dependent manner (10(-11)-10(-7)M). 3. BQ-123 (10(-6)M) markedly shifted the dose-response curve of ET-1 for both contractile effects and oscillation frequency to the right. 4. BQ-3020 (10(-11)-3 x 10(-7) M) did not cause uterine contraction; neither did it affect the dose-response curve of ET-1 for either the contractile effect or the increase in oscillation frequency. Thus, stimulation of ETB receptors is not involved in these responses. 5. The present findings suggest that ET-1-induced contractile responses and the increase in oscillation frequency in rat uterine smooth muscle is mediated through ETA receptors, and that ETB receptors play no role in these responses.

Amino Acid Sequence↗

Gastric ulcer induced by submucosal injection of ET-1: role of potent vasoconstriction and intraluminal acid.

To investigate whether submucosally applied endothelin-1 (ET-1) can induce gastric ulcer, ET-1 (62.5, 125, 250, and 500 pmol/kg) was injected in the submucosal layer of the rat gastric body. Twenty-four hours later, gastric ulcer (ulcer area: 10.31 +/- 5.13 mm2, mean +/- SE, at 500 pmol/kg, n = 8) was induced. The mucosal damage induced by the two highest doses was present even at 2 wk after their injection. Measurement of the mucosal blood flow at the injected area with three different methods (laser-Doppler flowmetry, hydrogen gas clearance, and reflectance spectrophotometry) revealed that injected ET-1 produced an extremely long-lasting vasoconstriction. Pretreatment with nicardipine, a Ca(2+)-channel blocker (1 mg/kg iv), significantly attenuated the ET-1-induced mucosal damage as well as the decrease in mucosal blood flow. Pretreatment with omeprazole (5-40 mumol/kg) also, significantly attenuated the ET-1-induced mucosal damage. Combined pretreatment with omeprazole (40 mumol/kg) and nicardipine almost abolished the ET-1-induced damage. The present study shows that a novel model for experimental ulcers can be induced by submucosal injection of ET-1.

Acids↗

An adult case of Fanconi syndrome due to a mixture of Chinese crude drugs.

We examined a 35-year-old male case of acquired Fanconi syndrome induced by a mixture of Chinese crude drugs. Renal glycosuria, hypokalemia, hypophosphatemia, metabolic acidosis, a low threshold of tubular bicarbonate excretion, and generalized aminoaciduria were observed after the patient had taken the drugs for 6 months. When he stopped taking them, all laboratory data improved. He took the drugs again on his own judgment, leading to a second bout of Fanconi syndrome. This is the first case in which Chinese crude drugs have been known to cause acquired Fanconi syndrome.

Adult↗

Expression of P-glycoprotein and multidrug resistance in renal cell carcinoma.

The expression of the multidrug-resistance gene product, P-glycoprotein was examined immunohistochemically in 31 untreated human renal cell carcinomas. In 17 of these, chemosensitivity to Adriamycin and vinblastine was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and intrinsic multidrug resistance was investigated. P-glycoprotein was detected in 16 (51.6%) of the 31 carcinomas. In the chemosensitivity test, 14 (82.4%) of the 17 carcinomas were estimated to be resistant to both drugs (multidrug resistant; MDR). Eight (72.7%) of the 11 carcinomas with a positive expression of P-glycoprotein were MDR, and none of them were sensitive of both drugs. On the other hand, MDR carcinomas were not necessarily associated with the expression of P-glycoprotein. Eight (61.5%) of the 13 MDR carcinomas showed a positive expression of P-glycoprotein while the remaining 5 (38.5%) were negative. These results suggest that the expression of P-glycoprotein is an important factor responsible for the intrinsic MDR phenotype of renal cell carcinoma, however, there are probably other factors involved as well which have yet to be fully elucidated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗