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Biomedical subjects

M Eto

Publications and source records attributed to M Eto.

At least 91 records · Page 5Linked to original sources

Identification of arginine vasopressin mRNA in rat aortic smooth muscle cells.

We investigated the expression of mRNA for arginine vasopressin in vascular smooth muscle cells and A10 cells using reverse transcription-polymerase chain reaction and Northern blot analysis. Arginine vasopressin mRNA was identified both in rat aortic smooth muscle cells and A10 cells, suggesting that arginine vasopressin is locally produced in vascular smooth muscle cells. Arginine vasopressin, a potent vasoconstrictor, may modulate vascular function in an autocrine or paracrine fashion.

Animals↗

Central vasopressin is required for the complete development of deoxycorticosterone-salt hypertension in rats with hereditary diabetes insipidus.

It has been shown that vasopressin receptors are upregulated in the brain and that the central vasopressin pathway is involved in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear whether central vasopressin, in itself, is essential for this type of hypertension. To clarify this issue, the effect of centrally administered vasopressin on the development of DOCA-salt hypertension was studied in homozygous Brattleboro rats which genetically lack vasopressin. In homozygous Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on systolic blood pressure (SBP). On the other hand, hypertension was partially restored in homozygous Brattleboro rats treated with intracerebroventricular infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the magnitude of elevation of SBP was one-third of that in Long Evans rats treated with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats showed an increase in fluid intake and urinary sodium excretion, as observed in DOCA-salt hypertensive Long Evans rats. These results suggest that central vasopressin is required for the complete development of DOCA-salt hypertension and the mechanism is, in part, due to enhanced sodium intake through the additive effect of central vasopressin and DOCA-salt.

Animals↗

Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells.

The present study was performed to elucidate the mechanism underlying the anti-atherogenic action of estrogen. We investigated the effect of estrogen on intimal thickening of the rat femoral artery induced by cuff placement and further examined the effect of estrogen on migration and proliferation of vascular smooth muscle cells (VSMCs) in culture. Intimal thickening was significantly greater in males than in control females. Intimal thickening in females was increased to the level in males by ovariectomy. Estrogen replacement to ovariectomized rats reversed this effect. Proliferating cell nuclear antigen immunohistochemistry showed that in vivo proliferation of VSMCs contributed to the difference in intimal thickening. There was no difference in blood pressure and serum lipids, suggesting that estrogen directly acted on artery and inhibited intimal thickening. 17 beta-Estradiol (E2, 1-100 nmol/l) inhibited migration of cultured rat VSMCs, assayed using a microchemotaxis chamber, in a concentration-dependent manner. E2 (0.01-100 nmol/l), but not progesterone or testosterone, also inhibited [3H]thymidine incorporation in rat VSMCs in a concentration-dependent manner. Indomethacin, NG-monomethyl-L-arginine and methylene blue did not influence the inhibitory action of E2 on [3H]thymidine incorporation, suggesting that prostanoids and nitric oxide are not involved in the action of E2. E2 did not provoke VSMC injury, as measured by the release of incorporated [3H]2-deoxy-D-glucose. These results suggest that the inhibition of migration and proliferation of VSMCs contributes to the inhibitory effect of estrogen on intimal thickening.

Animals↗

Augmented Ca2+ influx is involved in the mechanism of enhanced proliferation of cultured vascular smooth muscle cells from spontaneously diabetic Goto-Kakizaki rats.

To investigate whether augmented calcium influx is involved in the mechanism of the enhanced proliferation of vascular smooth muscle cells (VSMCs) in diabetes, we studied the association between proliferation and cytosolic free calcium concentration ([Ca2+]i) in cultured aortic VSMCs from spontaneously diabetic Goto-Kakizaki (GK) and Wistar rats. Serum, angiotensin II and Bay K 8644, a voltage-dependent Ca2+ channel (VDC) agonist, stimulated the proliferation of VSMCs; the magnitude was greater in VSMCs from GK than Wistar rats. VDC blockers, verapamil and nicardipine, inhibited Bay K 8644-induced cell proliferation, and the difference in the proliferation of VSMCs between GK and Wistar rats disappeared. Angiotensin II-induced proliferation was only partially inhibited by VDC blockers, and enhanced proliferation of GK-VSMCs was still observed. Bay K 8644 and angiotensin II increased [Ca2+]i, and the increase was augmented in GK-VSMCs. Bay K 8644-induced [Ca2+]i increase was completely inhibited by pretreatment with verapamil or removal of extracellular Ca2+, suggesting that VDC is associated with this increase. Although angiotensin II-induced [Ca2+]i increase was not affected by verapamil, removal of extracellular Ca2+ slightly but significantly attenuated angiotensin II-induced [Ca2+]i increase, suggesting that VDC blocker-insensitive receptor-activated Ca2+ influx is involved. These results indicate that augmented Ca2+ influx via VDC and a receptor-activated pathway may be involved in the mechanism of the enhanced proliferation of VSMCs from GK rats.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Quantitative structure-activity studies of octopaminergic 2-(arylimino)thiazolidines and oxazolidines against the nervous system of Periplaneta americana L.

The quantitative structure-activity relationship (QSAR) of octopaminergic 2-(arylimino)thiazolidines (AITs) and 2-(arylimino)oxazolidines (AIOs) against the thoracic nerve cord of the American cockroach, Periplaneta americana L., was analysed using reported physicochemical parameters and regression analysis. The more electron-donating, the less bulky at m-position, and the more hydrophobic the substituent, the greater the activity. The plots of observed log Vmax values against calculated log Vmax values having substituents on the m-position deviated downwards from those of compounds having substituents at the 0- and/or p-positions. The more hydrophobic and the more electron-withdrawing the substituent, the greater the activity. AIO with a 2, 3, 4-trichlorophenyl group (58) was more active than its thiazolidine derivative, 2-(2,3,4-trichlorophenylimino)thiazolidine (38) in terms of Vmax:Vmax of 58 was 30% relative to octopamine (OA), whereas that of 38 has been 9% relative to OA, respectively. Superimposition of energy-minimized OA and 58 revealed structural and conformational similarities that might account for the high activity of 58.

Animals↗

Role of activin-A and follistatin in foam cell formation of THP-1 macrophages.

Macrophage (M phi) foam cell formation is a characteristic event that occurs in the early stage of atherosclerosis. To examine the roles of activin-A, a member of the transforming growth factor-beta superfamily, and follistatin, the binding protein for activin-A, in M phi function, we investigated their effects on foam cell formation of THP-1 M phi s. When THP-1 M phi s were treated with activin-A (5 nmol/L), foam cell formation and cellular cholesteryl ester accumulation were decreased. This downregulation was paralleled by a reduction in cell association and degradation of acetylated LDL. The inhibitory effect of activin-A on cell association and degradation was dose dependent, and the effect was blocked by concomitant addition of follistatin. Activin-A (5 nmol/L) also decreased the Bmax for acetylated LDL and scavenger receptor mRNA expression. Follistatin showed an effect opposite to that of activin-A and promoted M phi foam cell formation and cellular cholesteryl ester accumulation. It increased binding, cell association, and degradation of acetylated LDL and upregulated scavenger receptor mRNA expression. Because follistatin is the binding protein for activin-A, follistatin's effect is considered to be mediated by blocking the inhibitory effect of intrinsic activin-A. These results indicate that activin-A inhibits and follistatin promotes M phi foam cell formation by regulating scavenger receptor mRNA expression. We conclude that activin-A and follistatin play important roles in the process of atherosclerosis by regulating M phi foam cell formation.

Activins↗

[Hyperventilation syndrome in a very old woman].

A 92-year-old woman was admitted to our hospital due to hypertension, nausea, pain in the anterior part of the chest, epigastralgia, and tachypnea. During the initial examination of the patient in the emergency ward, she was very excited, howled, and both her hands were numb. Arterial blood gas analysis revealed a marked alkalemia (pH greater than 7.55) and hypocapnia (Pco2 24.1 mmHg). After paper bag re-breathing, the pH and Pco2 were within normal limits. Because there was no lesion in the lungs or the brain that would account for hyperventilation and convulsions, the attack was considered to be a manifestation of hyperventilation syndrome should be carefully considered in the differential diagnosis of disturbance of consciousness even in elderly patients.

Aged↗

[Swallowing rehabilitation in an elderly patient with Wallenberg's syndrome--role of videofluorography and the swallowing provocation test].

A 65-year-old man was admitted to our department due to severe dysphagia, dysarthria, and aspiration pneumonia. Dysphagia and dysarthria were caused by lateral medullary infarction (Wallenberg' s syndrome). After the patient recovered from pneumonia, the abnormality of swallowing was assessed by a swallowing provocation test and videofluorography. Two months after the start of swallowing training, a swallowing provocation test showed that the swallowing reflex had improved and videofluorography showed that the magnitude of aspiration to the trachea had decreased. The patient began taking food by mouth. These tests are useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.

Aged↗

[Two elderly patients with Rhabdomyolysis and respiratory infection with Streptococcus pneumoniae].

Rhabdomyolysis is not common in the elderly. Two elderly patients with rhabdomyolysis and respiratory infection with Streptococcus pneumoniae. The first patient was a 71-year-old woman with bronchiectasis who admitted to our hospital due to pneumonia. The second patient was an 84-year-old man who was admitted because of appetite loss, fever, and a cough producing of yellowish sputum. In both patients, sputum cultures were positive for S. pneumoniae, but blood cultures were not. The serum creatine kinase levels peaked on the day of admission at levels ten to thirty times higher than fold above the upper limit of normal; the serum lactate dehydrogenase levels were 1.5 times higher than the upper limit of normal. The creatine kinase levels returned to normal 5 to 7 days after admission, treated with antibiotics and recovered from pneumonia. The cases of these two patients, along with those described in previous reports of rhabdomyolysis associated with pneumococcal pneumonia indicate that measuring the serum creatine kinase level is important in detecting rhabdomyolysis, especially in elderly patients with respiratory infection caused by S. pneumoniae, and detection may help to prevent renal failure.

Aged↗

[Randomized prospective trial of gentian violet with dibutyryl cAMP and povidone-iodine with sugar as treatment for pressure sores infected with methicillin-resistant Staphylococcus aureus in elderly patients].

A randomized prospective study was done to evaluate the two treatments for pressure sores infected with methicillin-resistant Staphylococcus aureus in elderly patients: Gentian violet plus dibutyryl cAMP (GVcAMP, n = 8) and povidone-iodine plus sugar (IS, n = 11). Age, underlying diseases, and nutritional status did not differ between the two groups. Specimens were obtained biweekly from the pressure sores and were cultured. The percentage of culture dishes with no methicillin-resistant S. aureus was 93% for the patients given GVcAMP, but only 74% for those given IS (p < 0.01). By the 14th week after the start of treatment, the mean area of the pressure sores in the GVcAMP group had decreased to 45% of the area at the start of treatment. In the IS group, the decrease was smaller to 56% of the area before treatment. No local or systemic adverse effects occurred in either group. GVcAMP is useful to treat pressure sores infected with methicillin-resistant S. aureus.

Aged↗

Three-dimensional structural analysis of avian-teratogenic pyrimidine dialkyl phosphate esters and their analogs by molecular orbital calculations.

The most stable structures of avian-teratogenic pyrimidinyl dialkyl phosphates and phosphorothionates at semi-empirical molecular orbital (MO) AM1 method level were obtained to get net charges of nitrogen (N) and phosphorus (P), distances between 1-N and P, and twist angles between plane of the heterocycle and that made by C-O-P. These geometries of typical compounds were optimized by ab initio MO calculations at level of HF/6-31 G*. In the most potent teratogens, distances between 1-N and P were 4.3-5.4 A. Compounds of about 3 A has no teratogenicity.

Animals↗

Regulatory T cells in maintenance and reversal of peripheral tolerance in vivo.

Whether regulatory T cells could suppress the immune responses to an unrelated Ag and could induce tolerance to that Ag was investigated. In female B6 (I-Ab) mice tolerized to MHC class II I-Abm12 (bm12) alloantigen by cyclophosphamide-induced system, regulatory T cells specific for bm12 Ag were induced. These regulatory T cells suppressed in vivo immune responses to an unrelated Ag (male Ag) that was co-expressed with bm12 Ag on the same graft. However, the immune responses to male Ag suppressed by regulatory T cells were reverted by immunization with male Ag alone, indicating regulatory T cells suppressed the induction of immune responses to the unrelated Ag co-expressed with suppressogenic determinant, but did not inactivate T cells specific for that third Ag, such as clonal anergy or deletion. These results provided that minor Ag adjacent to major Ag, even if they were expressed on the professional APC, could be suppressed in the periphery, and the responses to those minor Ag could be activated when the suppression mechanism was abrogated or ineffective.

Animals↗

Estrogen inhibits endothelin-1 production and c-fos gene expression in rat aorta.

In order to clarify the mechanism underlying the preventive effect of estrogen on atherogenesis, we investigated the role of estrogen in the regulation of endothelin-1 (ET-1) production and c-fos mRNA expression, which may contribute to atherogenesis. Plasma ET-1 concentration in ovariectomized rats (OVX) was twice as high as that in sham-operated female rats (Sham). Estradiol replacement in OVX rats (OVX + E) decreased plasma ET-1 to the level in Sham (Sham, 0.68 +/- 0.14; OVX, 1.32 +/- 0.14; OVX + E, 0.85 +/- 0.12 pg/ml). Metabolic clearance rate of ET-1 was similar in these three groups of rats, suggesting that the difference in plasma ET-1 was due to production rather than degradation. Measurement of immunoreactive ET-1 in tissue extract and immunohistochemical examination showed that expression of ET-1 in the aortic smooth muscle cells of OVX was increased. The expression of c-fos mRNA in the aorta was also increased in OVX compared with Sham and OVX + E. Intravenous infusion of ET-1 to Sham induced c-fos expression in the aorta, suggesting the contribution of ET-1 to c-fos expression. Tissue culture study revealed that DNA synthesis was increased in the aorta and femoral artery of OVX. These results suggest that inhibition of ET-1 and c-fos expression is involved in the anti-atherogenic action of estrogen.

Animals↗

Apolipoprotein E polymorphism and susceptibility to early- and late-onset sporadic Alzheimer's disease in Hokkaido, the northern part of Japan.

Apolipoprotein E (ApoE) phenotypes and corresponding allele frequencies were examined in 72 patients (50-90 years of age) with sporadic Alzheimer's disease (AD) and 83 elderly controls (61-96 years of age) in Hokkaido, the northern part of Japan. The frequency of the ApoE-epsilon 4 allele was significantly higher in the patients with either early-onset (age < 65 years) AD (0.40) or late-onset AD (0.26) than in controls (0.07), while the patients developing AD before 50 years of age had no epsilon 4 allele. The mean age at onset of AD was significantly lower in the ApoE-epsilon 4 homozygotes compared to that in the patients with either one or no epsilon 4 allele (60.2, 71.3 and 70.3 years, respectively). Our results indicate that the ApoE-epsilon 4 allele is associated with susceptibility to Japanese sporadic AD developing after 50 years of age and homozygosity for the epsilon 4 allele shifts the onset to earlier age.

Age of Onset↗

Role of the transversus perinei profundus muscle on voiding: the meaning of UPmax in patients with paralyzed urethral sphincter.

Urodynamic study of 66 patients with caudal injury and of 7 patients who underwent saddle block was evaluated by putting emphasis on the maximal pressure of the urethra (UPmax). The static pressure of 49.7 +/- 10.8 cm H2O in the membranous urethra of the patients with completely paralyzed sphincter raised the question that some active muscle that functions to open the membranous urethra must have been working during physiological urination. Urodynamic findings of detrusor sphincter relationship, monitored by pressure and electromyogram (EMG) measurement, suggested that the combined reflections of the pelvic floor muscle and urethral sphincter are present. We concluded that this would be induced by the transversus perinei profundus muscle contraction and the urodynamic interpretation would be re-integrated on the role of this muscle on active urethral opening mechanism.

Anesthesia, Obstetrical↗

Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation.

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-alpha beta mAb-treated ATX mice, as shown in the present study, most of TCR-alpha beta+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-alpha beta- Thy-1+ cells remained at that time. These TCR-alpha beta- Thy-1+ cells which have downmodulated their TCR-alpha beta expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-alpha beta on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-alpha beta mAb treatment are long-lived and re-express their TCR-alpha beta at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.

Animals↗

[Use of a micturition-monitoring device in elderly inpatients].

More than 100,000 people suffer from functional urinary incontinence in Japan. To improve the quality of life of these people, we tested a device for monitoring micturition by means of a thin-layer membrane sensor in a diaper. The device was tested in elderly inpatients, and associated changes in the wordload of the nursing staff were also recorded. The device was beneficial because the precise micturition time was easily obtained and thus the daily pattern of micturition became obvious. With the use of this device, the time during which the patients wore wet diapers was shorter than with the conventional system of scheduled changes. However, the increase in the frequency of diaper changed doubled the workload of the nursing staff. In conclusion, improving the quality of life with regard to urinary incontinence entails an increase in the workload of the nursing staff; efficient distribution of that work may require some staff members to devote all their time to changing diapers.

Aged↗