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Biomedical subjects

M Soma

Publications and source records attributed to M Soma.

At least 91 records · Page 5Linked to original sources

Distinct expression of transforming growth factor-beta receptor subtypes on vascular smooth muscle cells from spontaneously hypertensive rats and Wistar-Kyoto rats.

1. We investigated the characteristics and expression of transforming growth factor-beta (TGFbeta) receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. TGFbeta binding assays revealed that VSMC from SHR showed higher number and affinity of TGFbeta receptors than cells from WKY rats. 3. The affinity labelling with [125I]-TGFbeta1 revealed the presence of TGFbeta receptor subtypes with molecular sizes of 280, 85, 70 and 60kDa on VSMC from both strains at high cell density. The abundance of the 85kDa receptor subtype was greater in VSMC from SHR than cells from WKY rats. The 85kDa receptor subtype was not detected on VSMC from both strains at low cell density. 4. These results suggest distinct expression of TGFbeta receptor subtypes on VSMC from SHR and WKY rats, which may account for the exaggerated proliferative response of VSMC from SHR to TGFbeta.

Affinity Labels↗

[Studies on the mechanism of hyperfibrinolysis in liver cirrhosis--changes of plasma t-PA, PAI-1 and active PAI-1 levels in liver cirrhosis].

Liver cirrhosis is known to have abnormal fibrinolysis. In order to investigate the changes of fibrinolytic system in liver cirrhosis, plasma levels of various fibrinolytic molecular markers were measured in patients with different stages of liver cirrhosis, 20 compensated liver cirrhosis (c-LC) and 14 decompensated liver cirrhosis (d-LC) and were compared with those in normal subjects. Both the plasma levels of plasmin alpha 2-plasmin inhibitor complex (PIC) and the plasma levels of total fibrin/fibrinogen degradation products (T-FDP) were significantly elevated in patients with both c-LC and d-LC as compared with normal controls. Moreover, both factors in d-LC were significantly higher than those in c-LC. These findings indicate that patients with liver cirrhosis have hyperfibrinolysis. Then, in order to investigate the mechanisms of hyperfibrinolysis in liver cirrhosis, plasma levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were determined in these patients. The plasma levels of t-PA significantly increased in both c-LC and d-LC as compared with normal controls. Its levels were higher in patients with LC at their decompensated stage than at their compensated stage. In patients with LC, plasma PAI-1 levels showed significantly higher values than those in normal controls. However, the plasma levels of active PAI-1 in patients with LC were similar to those in normal controls. These results suggest that hyperfibrinolysis in patients with LC is mainly due to increased concentrations of t-PA, without increased active PAI-1 levels.

Fibrinolysis↗

Eicosapentaenoic acid enhances myo-inositol uptake in cultured human aortic smooth muscle cells.

The effects of elevated glucose and Eicosapentaenoic acid (EPA, 20:5) on myoinositol uptake in human aortic smooth muscle cells (HASMC) were evaluated. Myo-inositol incorporation into HASMC was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and Ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. In addition, EPA potentiated Na(+)-K+ ATPase activity of HASMC. Since EPA decrease glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate aortic smooth muscle cell function associated with diabetes.

Adult↗

Effects of high-dose chemotherapy with syngeneic bone marrow transplantation in experimental brain tumor in rats.

BACKGROUND: The clinical dose of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitro- sourea hydrochloride (ACNU) is limited by the bone marrow suppression it produces. The authors investigated whether bone marrow transplantation (BMT) associated with a high dose of ACNU could alleviate marrow toxicity and achieve greater antitumor effects in Fischer rats. METHODS AND RESULTS: High doses of ACNU (20, 25, and 30 mg/kg) were administered on day 1, followed by injection of syngeneic bone marrow cells on day 3. Patterns of leukocyte recovery were compared in BMT and non-BMT groups. There was a significant benefit in leukocyte recovery in the BMT groups. A 9L glioma that was sensitive to ACNU was transplanted into the brain tissue of rats. Seven days later, the animals were divided into three groups based on the dose of ACNU (2, 10, and 25 mg/kg). The median survival time increased with larger ACNU doses. CONCLUSIONS: This suggested that high-dose ACNU chemotherapy with BMT could achieve greater antitumor effects and less bone marrow suppression than high-dose ACNU alone.

Animals↗

Compensatory adrenal growth and steroidogenesis after unilateral adrenalectomy.

To examine the effect of unilateral adrenalectomy on compensatory growth and steroidogenesis in the remaining adrenal gland, we determined the tissue concentrations of protein, DNA and corticosterone in the remaining adrenal gland and the circulating corticosterone and ACTH concentrations at 1, 3, 5, 7 and 14 days after unilateral adrenalectomy in male rats. The remaining adrenal weight and total protein content increased steadily over the 14 days after the operation, while the plasma ACTH increased transiently on the 1st day. The adrenal total DNA level was not significantly changed after unilateral adrenalectomy, whereas the protein/DNA ratio was significantly increased by the 14th day. These findings suggest that compensatory growth is not induced by an increase in ACTH and that hypertrophy may occur rather than hyperplasia in the remaining gland. The serum corticosterone levels and corticosterone concentration in the remaining gland were significantly increased by the 3rd day, when the plasma ACTH levels returned to normal. The aldosterone/corticosterone ratio in the remaining gland did not change during the experiment. These results indicate that steroidogenesis stimulating factors other than ACTH may be present and stimulate rather the early stages than the late stages of steroidogenesis under conditions of unilateral adrenalectomy.

Adrenal Glands↗

[Pregnancy in Cushing's syndrome].

Pregnancy in cases of Cushing's syndrome is rare. A pregnant patient with Cushing's syndrome due to an adrenal adenoma who was diagnosed in the third trimester is described. She underwent conservative treatment for Cushing's syndrome and delivered a normal infant by Caesarean section. Currently, 121 pregnancies in 97 patients have been reported, but a principle for the treatment of the mother and fetus has not yet been established. We reviewed pregnancy in Cushing's syndrome based on the world literature and evaluated the choice of treatment to take. In the first trimester of pregnancy, therapeutic abortion or surgical treatment, such as adrenalectomy or resection of the pituitary tumor in Cushing's syndrome, is recommended for patients with severe hypercorticism (plasma cortisol > or = 30 micrograms/dl, urinary 17-OHCS > or = 15 mg/day, urinary free cortisol > or = 1000 micrograms/day), while conservative treatment is recommended for patients with mild hypercorticism (plasma cortisol < 30 micrograms/dl, urinary 17-OHCS < 15 mg/day, urinary free cortisol < 1000 micrograms/day). In the second trimester of pregnancy, surgical treatment is recommended for patients with severe hypercorticism, while conservative treatment is recommended for patients with mild hypercorticism. In the third trimester of pregnancy, Caesarean section is recommended for most cases. Drug treatments such as with metyrapone should be limited to patients showing severe hypercorticism or a maternal high risk who have contraindications to surgical treatment.

Adenoma↗

[Relationship between types of hypertension and patterns of urinary catecholamine excretion in Sipple's syndrome].

We report here a case of Sipple's syndrome, and we also analyze the relationship between the type of hypertension and urinary excretion of catecholamines in Sipple's syndrome based on the literature in Japan. One hundred and fourteen cases of Sipple's syndrome have been reported in Japan. The hypertension of patients with Sipple's syndrome shows a ratio of fitfull hypertension to continual hypertension of 6 to 1, whereas the ratio is 1 to 1.5 in patients whose pheochromocytoma is not accompanied by Sipple's syndrome. The patients with Sipple's syndrome, being pheochromocytoma can be classified into the adrenaline (U-AD) dominant type and noradrenaline (U-NA) dominant type based on the catecholamine excretion in the urine. The U-AD predominant (U-AD/U-NA greater than 0.4) patients mostly reveal fitfull hypertension, while patients with continual hypertension hardly show U-AD predominant.

Adrenal Gland Neoplasms↗

Effects of L-NG-monomethyl arginine on the cyclic GMP formations in rat mesenteric arteries.

To evaluate the contribution of L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF) on vascular cyclic GMP formation, we examined the effects of L-NG-monomethyl arginine (L-NMMA), and analog of L-arginine, on basal and acetylcholine (ACh)-, sodium nitroprusside (SNP)- and atrial natriuretic peptide (ANP)-induced cyclic GMP formations in rat mesenteric arteries. The mesenteric arteries were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the arteries were collected before and after infusions of graded doses of ACh, SNP or ANP in the absence or presence of 100 microM L-NMMA, and the levels of cyclic GMP were measured. Basal and ACh-induced cyclic GMP formations in the mesenteric arteries were significantly inhibited in the presence of L-NMMA, whereas a concomitant infusion of 300 microM L-arginine restored the inhibition of basal as well as ACh-induced cyclic GMP formations. L-NMMA did not affect SNP- and ANP-stimulated cyclic GMP formations, respectively. These results suggest that L-arginine is necessary for not only the stimulated cyclic GMP formation but also the basal cyclic GMP formation in the mesenteric arteries, whereas the SNP- and ANP-stimulated cyclic GMP formations in the arteries are independent of L-arginine.

Animals↗

N-myc gene amplification and neuron specific enolase production in immature teratomas.

The primary tumour tissues from 13 teratomas were investigated, 3 cases of immature teratoma (1 of pure type and 2 of mixed type), 5 cases of dermoid cyst, and 5 cases of mature solid teratoma, with special reference to N-myc gene amplification, productivity of neuron specific enolase (NSE), and the presence of double minutes (DMs). The possible relationship between these variables and malignancy of the tumours was also examined. N-myc gene amplification and NSE production were recognized in the primary tumour tissues and the first and the third passage cultured cells of all of the 3 cases of immature teratoma containing immature neural tissues. In 2 cases DMs were recognized. In dermoid cysts and mature teratoma, neither N-myc gene amplification nor NSE production were recognized in either the primary tumour tissues or cultured cells. The chromosomes were normal. Malignancy of teratoma is generally decided by the clinical stage and histological grade, but a more securely based decision is necessary where an immature teratoma contains immature neural tissues. The presence of N-myc gene amplification, NSE productivity and the presence of DMs may be valuable.

Adult↗

Carcinoembryonic proteins produced by Wilms' tumor cells in vitro and in vivo.

A Wilms' tumor cell line (HFWT) was established after tissue culture of the Wilms' tumor which had developed in the left kidney of a five-month-old boy. The HFWT line has the following cyto-biological characteristics: 1. The cells have a spindle, round or polygonal shape with neoplastic and pleomorphic features that grew in multilayers without contact inhibition. 2. The cells show a stable proliferation, giving 95 passages within 4 years. 3. The chromosomes show a wide aneuploidy distribution, and the modal number was found in diploid range. The stem cells have a normal karyotyping, 46, XY. 4. Heterotransplantation into nude mice can be easily made, and anaplastic Wilms' tumor resembling the original tumor forms. 5. The principal tumor markers produced by the cells in large amounts in the conditioned culture media were carbohydrate antigen 125 (CA 125) and tissue polypeptide antigen (TPA). 6. A good correlation was found between enlargement of the tumor formed by heterotransplantation into nude mice and the levels of CA 125 and TPA in the serum of the nude mouse. No report on the study of tumor markers widely used in clinical treatment of Wilms' tumor has been available to us, but CA 125 and TPA are considered to be useful in the diagnosis and treatment of Wilms' tumor.

Animals↗

Simvastatin but not pravastatin inhibits the proliferation of rat aorta myocytes.

The in vitro effect of simvastatin and pravastatin, two competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on the proliferation of rat aortic smooth muscle cells was investigated. Simvastatin, but not pravastatin, inhibited the replication of arterial myocytes in concentrations ranging between 0.01 microM and 10 microM. The inhibition, evaluated as cell number and nuclear incorporation of [3H]thymidine, was dose-dependent and completely prevented by addition of mevalonate (100 microM), confirming the role of mevalonate or its products in regulating cell division and growth. The present results provide evidence that simvastatin, in addition to its effect on cholesterol biosynthesis, interferes in vitro with other processes involved in atherogenesis.

Animals↗

Low doses of endothelin-3 elicit endothelium dependent vasodilation which accompanies with elevation of cyclic GMP.

Low doses (10(-16)-10(-10) M) of endothelin-3 (ET-3) elicited continuous vasodilations of mesenteric arteries preconstricted with norepinephrine (NE) but not with KCl. In arteries perfused with Ca2+ free solution, ET-3 did not affect the perfusion pressure. In endothelium-denuded arteries preconstricted with NE, ET-3 significantly elevated the perfusion pressure in a dose-related manner. The levels of cyclic GMP and cyclic AMP from the intact arteries were significantly elevated by ET-3; the cyclic GMP elevasion disappeared with methylene blue. Following endothelium-denudation, cyclic GMP elevation was abolished, but cyclic AMP elevation was unaffected. Levels of 6-Keto-PGF1 alpha in the arteries were not changed appreciably by ET-3. These data indicate that the vasodilating effects of ET-3 depend on the presence of extracellular Ca2+ and the existence of endothelium. They are accompanied by elevations of cyclic nucleotides and the elevation of cyclic GMP depends on the endothelium. It is possible that the vasodilating effects of low doses of ET-3 are associated with endothelium-derived relaxing factor.

Animals↗

Cyclic GMP formation of resistance vessel in the development of hypertension in spontaneously hypertensive rats.

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the mesenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to infusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated release of EDRF is not associated with the development of hypertension.

Acetylcholine↗

Effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine on the vasoactive effects of endothelin-3.

To clarify the mechanisms underlying the vasoactive effects of endothelin-3 (ET-3), we examined the effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine (L-NMMA) on the perfusion pressures of isolated rat mesenteric arteries infused with ET-3. ET-3 at 10(-15)-10(-8) M elicited significant vasodilations in a dose-related manner, in which 10(-9) and 10(-8) M ET-3 caused biphasic pressure changes involving a transient dilation and subsequent vasoconstriction. Five micromolar indomethacin did not affect the vasodilations and vasoconstrictions induced by ET-3. In endothelium-denuded arteries, 10(-13)-10(-8) M ET-3 elicited significant vasoconstriction in a dose-related manner without any vasodilation. In the presence of 30 microM methylene blue, the vasodilations induced by ET-3 disappeared. In the presence of 100 microM L-NMMA, 10(-15)-10(-8) M ET-3 elicited significant vasoconstrictions in a dose-related manner, and the vasodilation by ET-3 existed only at 10(-8) M ET-3. These data suggest that the vasodilating effects of low doses of ET-3 through the endothelium overcome the vasoconstricting effects, and that the vasodilating effects of ET-3 are associated with an endothelium-derived relaxing factor as an endothelium-derived nitric oxide.

Animals↗

Effect of endothelin-3 (ET-3) on renal function in rat perfused kidney.

We examined the effect of endothelin-3 (ET-3) at a high dose (pressor dose) and a low dose (non-pressor dose) in rat perfused kidney (PK), since ET-3 has recently been reported to exert a vasodilator action especially at a low dose. Kidneys were perfused with Krebs-Henseleit buffer at a fixed flow rate (6 ml/min) in situ. After collection of the renal venous effluent and urine for 20 min, vehicle (saline; n = 6), 10(-13)M ET-3 (low dose; n = 6) or 10(-8) M ET-3 (high dose; n = 6) was added to the perfusate, and sample collection was performed for the same period with each. The high dose of ET-3 significantly increased the perfusion pressure, fractional sodium excretion and synthesis of prostaglandins (PGs) consistently with a significant reduction in the glomerular filtration rate (GFR). On the other hand, the low dose of ET-3 significantly increased the GFR, urine volume and free-water clearance with no change in the perfusion pressure or synthesis of PGs. These findings suggest that a low dose of ET-3 can increase the glomerular capillary ultrafiltration coefficient and that ET-3 exerts an influence on sodium and water handing in the rat PK.

Animals↗

Presence of human papillomavirus genome in human tumor cell lines and cultured cells.

A series of 47 human carcinoma cell lines and their cultured cells were examined for human papillomavirus (HPV) genomes with the use of an HPV detection kit (DNA-RNA hybridization, mixed HPV DNA probe of types 6, 11, 16, 18, 31, 33 and 35). Four of 8 cases of mild dysplasia, 3 of 9 cases of severe dysplasia, 3 of 7 cases of carcinoma in situ, 3 of 15 cases of uterine carcinoma and 5 of 6 cases of condyloma acuminatum were shown to contain the HPV DNA genome in primary cultured cells, while HPV was not detected in the third-passage cells except for the three cases of large cell, nonkeratinizing squamous cell carcinoma. HPV was also not detected in such normal tissues as uterine cervical squamous epithelium, uterine cervical columnar epithelium and endometrium. The presence of HPV DNA genomes was detected consistently in the passages of three lines (SKG-II, HKMUS and HKTUS; large cell nonkeratinizing squamous cell carcinomas of the uterine cervix) with the use of the Southern Blot method (DNA-DNA hybridization, mixed HPV probe of types 6, 11, 16 and 18). HPV type 16 DNA was detected in HKTUS, and HPV type 18 DNA was found in SKG-II and HKMUS. The other 44 cell lines, including ovarian carcinoma, endometrial carcinoma, sarcoma, gastric cancer, pancreatic cancer and rectal cancer, were negative for the HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33 and HPV-35 genomes under stringent hybridization conditions.

Adenocarcinoma↗