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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 523 records · Page 29Linked to original sources

Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

Animals↗

Cell-attachment activities of surface immobilized oligopeptides RGD, RGDS, RGDV, RGDT, and YIGSR toward five cell lines.

Tetrapeptides, Arg-Gly-Asp-Ser (RGDS), Arg-Gly-Asp-Val (RGDV), and Arg-Gly-Asp-Thr (RGDT), respectively, appearing in the cell-attachment domains of fibronectin, vitronectin, and collagen, and pentapeptide Tyr-Ile-Gly-Ser-Arg (YIGSR) appearing in B1 chain of laminin, were synthesized by liquid-phase procedure. Bioactivities of RGD, RGDX (X = S, V and T), YIGSR, and YIGSR-NH2 as cell recognition determinants were investigated by cell-attachment test using these oligopeptides immobilized to ethylene-acrylic acid copolymer (PEA) film. The cell lines used were A431, NRK, CHO-K1, HeLa.S3, and RLC-16 cells. It was found that the residue X in RGDX plays an important role for cell-attachment activity of RGDX, and, regarding YIGSR, introduction of NH2 residue at the C-terminal of the pentapeptide enhances the cell-attachment activity.

Acrylic Resins↗

Characterization of mycoplasma strains isolated from house musk shrews (Suncus murinus) and their infectivity in mice and rats.

Five mycoplasma strains isolated from house musk shrews (Suncus murinus) in the Central Institute for Experimental Animals were characterized and compared with three murine mycoplasma strains, Mycoplasma pulmonis m 53, M. arthritidis PG6, and M. neurolyticum Type A, and with reference strain G3-5 previously isolated from a house musk shrew. These isolates fermented glucose, but did not hydrolyze urea and arginine, passed through membrane filters of 450 nm pore size, were sensitive to digitonin, and formed minute (115 to 231 microns in diameter) colonies on agar medium. All the five unclassified house musk shrew mycoplasma strains and strain G3-5 used as a reference constituted a homogeneous group based on (i) their antigenic properties (determined using the metabolism inhibition test), (ii) their polypeptide profiles (determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Western blotting assay), and (iii) their genomic properties (determined using DNA cleavage pattern analysis), but were quite distinct from the established murine mycoplasmas on the basis of these findings. In a survey of 56 house musk shrews aged 2 to 45 weeks in our colonies, mycoplasmas were isolated from the oral cavities of all animals examined. No gross or microscopic lesions were observed in the five animals from which the mycoplasma strains were isolated. In experimental infection, the mycoplasma was not infective for mice and rats. The results suggest that this group of mycoplasmas is a common inhabitant of house musk shrews.

Animals↗

Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETB receptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2. 1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-beta, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-alpha, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Clinical experience with expanded polytetrafluoroethylene sheet used as an artificial dura mater.

Dural repair using chemically treated cadaveric dura mater often results in atrophic and fragile change of the substitute as well as adhesion between the dura mater and brain surface at reoperation. Creutz-feldt-Jakob disease has occurred after repair using cadaveric dura mater. Expanded polytetrafluoroethylene (EPTFE) surgical sheet was used for dural repair in 34 patients. Suturing of EPTFE was easy and the incidence of cerebrospinal fluid accumulation in the epidural space was the same as when cadaveric dura mater was used. Six patients underwent reoperation, 1-15 months after the first operation. At reoperation the EPTFE sheet showed no change except for becoming transparent, and the strength was well preserved. A very thin layer of granulation tissue was formed between the EPTFE sheet and brain surface, but the EPTFE sheet was easily detached from the brain surface without adhesion even 15 months after the first operation. Our results suggest that the EPTFE sheet can be used safely and effectively as an artificial dura mater.

Brain Diseases↗

[Preoperative embolization using absolute ethanol for renal cell carcinoma--including the questionnaire survey in Japan].

The usefulness of transvascular embolization before radical nephrectomy using absolute ethanol was studied in thirty-two cases with renal cell carcinoma, among them, 30 cases received radical nephrectomy one day after transvascular embolization. And a nation wide questionnaire survey regarding the embolization was also reported. These results were as follows: 1. The infarcted areas were very extensive and among 28 cases examined, 26 cases showed more than 75% of infarct in the whole area of the cortex. 2. Among 32 cases, 22 cases complained of no pain after the embolization using absolute ethanol only by the preventive epidural administration of analgesics. 3. The questionnaire survey showed that the embolization before radical nephrectomy was performed in 62% of the hospitals as a whole, including 81 hospitals (41%) in which the embolization was performed case by case. In the whole of hospitals, 21% performed the embolization principally by evaluating the significance of the embolization. On the other hand, 19% of the hospitals did not perform by the reason of no significance of the embolization on the treatment of renal cell carcinoma. As shown in this questionnaire survey, the significance of the embolization before radical nephrectomy was still debatable in our country. 4. In 62% of the hospitals where the embolization is carried out, as a whole, the period from embolization to the nephrectomy was 3-7 days. And in 42% of the hospitals as a whole absolute ethanol was principally used as an embolizing agent. In conclusion we believe that absolute ethanol was useful and should find further application as an embolizing agent before the radical nephrectomy.

Aged↗

Possible action of human placental aminopeptidase N in feto-placental unit.

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.

Amino Acid Sequence↗

Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels.

BACKGROUND: Angiogenesis occurs within the interstitial matrix. We therefore cultured endothelial cells within collagen gels rather than on the surface of culture dishes. We measured the effect of a human glioblastoma-derived factor, and the combined effect of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), on both the proliferative and morphologic changes exhibited by endothelial cells. EXPERIMENTAL DESIGN: Bovine capillary endothelial (BCE) cells were cultured in a gel of type I collagen. Effects of growth factors were evaluated by the cell recovery from the gel and the morphologic changes of cells. The glioblastoma-derived factor was characterized by column chromatography, immunoblotting, and immunoadsorption with an anti-VEGF antibody. RESULTS: After 4 days of culture in the collagen gel with 10% calf serum Dulbecco's minimum essential medium, most of the BCE cells died. Addition of glioblastoma-conditioned medium resulted in a change in morphology from a round shape to an elongated spindle shape; moreover, the number of BCE cells was enhanced. The major activity in the conditioned medium was VEGF. In the 3-dimensional gel, we found a higher activity associated with VEGF, compared with bFGF when the growth factors were added 24 hours after seeding. In this assay, the response to bFGF diminished within 24 hours, but that to VEGF continued for 48 hours. When the two factors were added to the culture simultaneously, the cell number was greater than the sum of those stimulated with either growth factor alone. In the presence of both bFGF and VEGF, cord-like structures became prominent in the BCE cell cultures. CONCLUSIONS: A human glioblastoma cell line produced VEGF, which enhanced the proliferation of BCE cells and induced an elongated shape in collagen gels. VEGF and bFGF increased the rate of proliferation and the number of cord-like structures in a synergistic manner.

Animals↗

[Age and sex dependent distribution pattern and normal range of blood cell parameters obtained by automated blood cell analyzer].

Distribution and normal value of 23 blood cell parameters in healthy 2509 males and 1658 females (20-69 year of age) who are the visitors of our health examination clinic or workers of the hospital were studied. These parameters were obtained by automated cell analyzer (Sysmex NE-8000, Toa Med. Electronics). Distribution pattern and normal range of 23 parameters were studied in different groups of the sex and the age (decade). Distribution of the parameters in each groups was classified into 5 patterns such as Gaussian (G), log-Gaussian (L), skewed toward lower values (P1), skewed toward higher values with shorter tail than of log-Gaussian (P2), skewed toward higher values with longer tail than of log-Gaussian (P3). Normal range of parameters in each groups was calculated by mean +/- 1.96SD of normal distribution curve obtained by power transformation procedure in L, P1, P2 and P3 distribution. Parameters concerning leukocytes and platelets showed rarely G distribution in each groups. Significant sex difference was observed in leukocyte count (male > female, p < 0.001) and platelet count (female > male, p < 0.01) in each age group. Normal values of newly analysed parameters as volume distribution curve of erythrocytes and platelets, mean platelet volume and large platelet ratio were established.

Adult↗

[Blunt trauma with combined femoral arterial and venous occlusion].

Blunt trauma to common femoral artery is rare, and it is frequently unrecognized. A 61-year-old man who fell while carrying a log and struck on his right groin, presented right leg edema and intermittent claudication one month later. Both right femoral arterial and venous occlusion was suspected by Doppler flowmeter, confirmed by venography and arteriography which showed concomitant external iliac arterial occlusion. He underwent prosthetic bypass grafting from common iliac artery to common femoral artery and embolectomy of femoral vein. Circulation to the right leg was restored, but postphlebitic syndrome had remained which was ameliorated by wearing the elastic stocking.

Femoral Artery↗

[Successful surgical repair for a patient with atrial septal defect and severe pulmonary hypertension--its surgical indication and prostaglandin E1 use for postoperative pulmonary hypertensive crisis].

A 45-year-old woman with atrial septal defect and pulmonary hypertension was admitted for surgical repair. Cardiac catheterization data revealed pulmonary to systemic flow ratio (Qp/Qs) of 1.81, pulmonary artery pressure (PAP) of 82/30 mmHg and pulmonary vascular resistance (PVR) of 10.8 unit. Open lung biopsy was added to evaluate pulmonary vascular obstructive disease (PVOD) which was shown Heath-Edwards grade 3 PVOD. Following closure of the defect, PAP (systolic) exceeded momentarily systemic level after cardiopulmonary bypass. Prostaglandin E1 drip was remarkably effective to bring down PAP during early postoperative period. Although PAP has not been shown significant decrease on catheterization of one year after surgery, great symptomatic improvement has been achieved.

Alprostadil↗

[A case of radiation myelopathy with characteristic findings of thermoregulatory sweat distribution and magnetic resonance images].

A 73-year-old man had undergone resection of a lung carcinoma of the right upper lobe in 1987. Post-operative irradiation (40 Gy) was given to the right hilus. In November 1988, recurrence was detected in the trachea. Laser therapy was done in December 1988. From January 9 to February 13 in 1989, irradiation (50 Gy) was given to the mediastinum. From the beginning of 1991, the patient developed muscle weakness in the right lower extremity and pain temperature sensations were impaired below the Th12 level on the left side. On October 3, 1991, he was admitted to our hospital. Neurological examination revealed mild muscle weakness in the right lower extremity. Superficial sensations were impaired below the Th6 level bilaterally. Deep tendon reflexes were hyperactive in the lower extremities. A bilateral Babinski sign was positive. The T1 weighted MRI showed a low signal intensity in the spinal cord at the level of thoracic vertebra (TV)2-TV6. T2 weighted images revealed a high signal intensity area of the spinal cord from TV4-TV6. A gadolinium-DTPA injection revealed an enhancement on the left side of the spinal cord at the TV2-3 level, and right side of the spinal cord at the TV4-5 level on the sagittal and axial images. A thermal sweating test revealed hypohidrosis below the Th8 level on the right side, and the Th11 level on the left side. Sweating was delayed at the Th7-8 levels on the right side and Th10-11 levels on the left side. An irradiated field on the chest revealed hypohidrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Inferior branch palsy of the oculomotor nerve following clipping of basilar apex aneurysm].

A 67-year-old woman experienced a severe headache and vomiting. A computed tomographic (CT) scan showed a mild subarachnoid hemorrhage. Cerebral angiography revealed a saccular aneurysm at the apex of the basilar artery. Several days later, she noticed mild hemiparesis of the left extremities. She underwent a clipping operation on the aneurysm by approaching from the right temporal love. Postoperatively, she developed diplopia and dilatation of the left pupil. Cerebral angiography revealed an occlusion of the left posterior cerebral artery. She was admitted to another hospital in order to continue rehabilitation. General physical examination was normal. Neurological examination revealed paralysis of the left medial and left inferior rectus muscles and palsy of the left inferior oblique muscle. The pupil of the left eye was dilated, measuring 5 mm in diameter, and it did not constrict to any stimuli. The left superior rectus and levator palpebrae superioris functioned normally. Visual acuity and visual fields were normal except for the influence of a senile cataract. She had a mild left hemiparesis, slight left ataxia and slurred speech. She had numbness of the left half of the body. A CT scan showed small low density areas in the right thalamus and left cerebellar hemisphere. Her ophthalmologic findings were compatible with the inferior branch palsy of the oculomotor nerve. The ophthalmoplegia of this case seems to be due to partial damage of the oculomotor nerve induced by ischemia of vascular supply. It is supposed to be caused by a vasospasm of the left posterior cerebral artery following a clipping operation of the basilar apex aneurysm.

Aged↗

[Endothelin-1-induced vasoconstriction in retinal blood vessels in the rabbit].

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide which is synthesized in retinal vessels. In order to investigate its effect on retinal blood vessels, we injected ET-1 intravitreally (10(-12), 3 x 10(-12), 10(-11), 3 x 10(-11), 10(-10) mole) and examined the change in diameters of retinal arteries in rabbits by fundus photography. After injection of a high dose (10(-10) mole) of ET-1, fluorescein angiography was used to investigate whether complete occlusions of retinal blood vessels occurred or not. 3 x 10(-12) mole ET-1 induced contraction of retinal arteries and the contraction of those induced by 10(-10) mole ET-1 showed complete occlusion. A medium dose (10(-11) mole) of ET-1 caused repeated vasospasms and segmental vasoconstrictions of retinal blood vessels. Fluorescein angiograms revealed that retinal blood flow was interrupted transiently by injection of a high dose (10(-10) mole) of ET-1. These findings suggested that intravitreal injection of ET-1 could provide a new model of experimental transient occlusion of retinal vessels in rabbits.

Animals↗

Gene expression for endothelins and their receptors in glomeruli of diabetic rats.

The present study was designed to assess levels of messenger RNA encoding for endothelin-1, endothelin-3, and endothelin receptors A and B in glomeruli of rats with streptozotocin-induced diabetes at 4, 12, and 24 weeks of age. In addition, streptozotocin-induced rats with diabetes were either treated with 8 to 14 units neutral protamine Hagedorn insulin daily to maintain moderate hyperglycemia (approximately 200 mg/dl) or left untreated to produce severe hyperglycemia (more than 400 mg/dl) during the 4-week study period. The messenger RNA levels for endothelin-1 in glomeruli of diabetic rats increased with the progression of diabetic nephropathy (4 weeks, 2.5 times control level, p < 0.01; 12 weeks, 3.8 times, p < 0.01; and 24 weeks, 5.3 times, p < 0.001. In contrast, messenger RNA levels for endothelin receptors A and B were not altered in glomeruli from diabetic and control rats throughout the experimental period. Messenger RNA for endothelin-3 in glomeruli from diabetic and control rats was not detected until 24 weeks of age. Insulin treatment partially ameliorated the increase in messenger RNA for endothelin-1 in the glomeruli of diabetic rats (0.3 times compared with diabetic rats without insulin treatment, p < 0.01), whereas insulin treatment did not affect messenger RNA for endothelin receptors A and B in diabetic glomeruli. These findings indicate that increased endothelin-1 messenger RNA in glomeruli may be a manifestation of diabetic nephropathy, and hyperglycemia or insulin-deficiency may play a role in abnormal endothelin-1 gene regulation.

Animals↗

Diabetes mellitus-associated glycogen storage hepatomegaly: report of a case and review of the Japanese literature.

A huge hepatomegaly was seen in a 30-yr-old female diabetic who was treated with high dose of insulin for her uncontrollable food ingestion. The liver function at the peak of the hepatic enlargement showed a moderate increase of transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase. The histology of the enlarged liver revealed PAS-positive granules in enlarged hepatocytes, indicating the presence of massive glycogen storage. On admission, she was maintained under a calorie-restricted diet and received approximately 15 to 20 units per day of insulin supplement. At one month after admission, a marked shrinkage of her enlarged liver and restoration of normal liver function were observed concomitantly with the return of fair control of her blood sugar levels. One year later, she had an episode of diabetic ketoacidosis which subsequently was treated with a continuous low-dose infusion of insulin; however, she showed neither hepatomegaly nor liver dysfunction during this episode. There have been 20 cases reported of Japanese diabetics with marked hepatomegaly, in whom the vigorous treatment of diabetic ketoacidosis with insulin seemed to be a trigger of the enlarged liver. This has occurred mostly in patients with insulin-dependent diabetes mellitus. We present a case of non-insulin-dependent diabetes mellitus with glycogen storage hepatomegaly, presumably due to excessive insulin supplements. This suggests that glycogen storage hepatomegaly in diabetics may not be only due to an acute restoration from diabetic ketoacidosis, but may also be due to an overinsulinization in an attempt to maintain a euglycemic condition in spite of excess food intake.

Adult↗