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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 163 records · Page 9Linked to original sources

Abnormal neurohumoral responses to exercise in patients with heart disease: inhibition of an increase in endothelin-1 production during exercise.

We have reported that the plasma endothelin-1 (ET-1) level is significantly increased by exercise in healthy athletes and that it is elevated in the circulation of the non-working leg but not the working leg, suggesting that ET-1 plays an important role in redistribution of blood during exercise. This study was designed to compare alterations of neurohumoral substances by exercise in normal subjects and patients with heart disease. Study patients comprised three groups: eight patients with congestive heart failure (CHF) due to Ebstein's anomaly or single-ventricle heart after Fontan operation; six patients with complete transposition of the great arteries (TGA) after an anatomic surgical correction who may be candidates for ischemic heart disease; and five age-matched normal subjects. All patients were in New York Heart Association functional class I. All subjects performed symptom-limited treadmill exercise. It is suggested that patients with CHF or TGA have a manifest or latent exercise intolerance, respectively. In failed to increase plasma ET-1 level, although it caused a greater increase in norepinephrine, angiotensin II, and arginine vasopressin than in the controls. Exercise also caused a delay in the increased response of plasma ET-1 levels in patients with TGA after an anatomic surgical repair. On the other hand, plasma brain natriuretic peptide (BNP) level was augmented by exercise in patients with CHF and patients with TGA but not in the controls. The present results suggest that an increase in ET-1 production during exercise is absent in patients with heart disease. The mechanisms of inhibition of ET-1 production during exercise in patients with heart disease remain to be elucidated. However, the present study suggests that ET-1 plays an important role in redistribution of blood during exercise, and proposes the possibility that failure of an increase in ET-1 production results in exercise intolerance in patients with heart disease.

Child↗

Endothelin-1 expression in hearts of transgenic hypertensive mice overexpressing angiotensin II.

Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which has potent hypertrophic effects on cardiac myocytes. Although in cultured cardiomyocytes, angiotensin II (Ang II) was reported to enhance ET-1 production in vitro, it is not known whether ET-1 production is enhanced by Ang II in vivo. We investigated the production and pathophysiologic roles of ET-1 in 20-week-old male transgenic hypertensive mice (THM), in which the renin-angiotensin system (RAS) was markedly activated because of the presence of both human renin and angiotensinogen genes. Systolic blood pressure and the ratio of left ventricular weight to body weight were significantly higher in the THM than in control mice, indicating that THM developed cardiac hypertrophy. ET-1 production was significantly increased in the heart of THM because both ET-1 mRNA expression and peptide levels were significantly higher than in controls. However, circulating plasma ET-1 levels did not differ between the groups, and blood pressure did not change after i.v. injection with a high dose (3 mg/kg) of the ETA/B-nonselective receptor antagonist SB209670. These findings suggest that increased cardiac ET-1 production may contribute to the progression of cardiac hypertrophy and that endogenous ET-1 may not be involved in the short-term modulation of blood pressure in THM of this age.

Angiotensin II↗

Endothelin-converting enzyme and angiotensin-converting enzyme in failing hearts of rats with myocardial infarction.

We have previously reported that production of endothelin (ET)-1 is markedly increased in failing hearts of rats with chronic heart failure (CHF). It was also reported that the production of angiotensin II (Ang II) is increased in the failing heart. In this study we investigated both converting enzymes of the ET-1 system and the angiotensin system. We used left coronary artery-ligated rats as a model of CHF. The peptide level of ET-1 in the left ventricle (LV) was markedly higher in CHF rats than in control rats. In the LV, expression of preproET-1 mRNA was also markedly higher in CHF rats than in controls. The expression of endothelin-converting enzyme (ECE)-1 mRNA in the rats with CHF was similar to that in controls. Therefore, we believed that the increase in ET-1 production in the failing heart originated from an increase in preproET-1 production rather than increase in ECE. The expression of angiotensin-converting enzyme (ACE) mRNA in failing hearts of CHF rats was significantly higher than that of the sham-operated rats. The expression of angiotensinogen mRNA in failing hearts of these CHF rats was slightly higher than that of the sham-operated rats. This study suggests that there is a difference in the role of peptide synthesis between the ECE system and the ACE system in rats with CHF.

Angiotensinogen↗

Prolonged exercise causes an increase in endothelin-1 production in the heart in rats.

Cardiac myocytes produce endothelin-1 (ET-1). ET-1 has potent positive inotropic and chronotropic effects. We investigated whether production of ET-1 in the heart is altered by prolonged exercise in rats. Rats ran on a treadmill for 45 min. Immediately after this exercise the heart and lungs were quickly removed. Control rats remained at rest during this 45-min period. Expression of preproET-1 mRNA in the heart was markedly higher in the exercised than in the control rats. The peptide level of ET-1 in the heart was also markedly higher in the exercised rats. Expression of endothelin type A- and type B-receptor mRNA and endothelin-converting enzyme mRNA in the heart did not differ between the groups. The peptide level of ET-1 and the preproET-1 mRNA level in the lungs of the exercised rats did not differ from those in the control rats. The present results show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelin receptor expression. The present study suggests that myocardial ET-1 may participate in modulation of cardiac function during exercise.

Animals↗

Requiring higher doses of erythropoietin suggests pregnancy in hemodialysis patients.

BACKGROUND/AIMS: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. METHODS: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. RESULTS: The mean duration of HD was 6 years, the mean duration of the patients' marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. CONCLUSIONS: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.

Adult↗

Co-expression of transforming growth factor beta and interferon tau during peri-implantation period in the ewe.

The transforming growth factor beta (TGFbeta) family is known to control cell migration, growth, differentiation, function and regulation of extracellular matrix, all of which are required for the process of implantation. Expression of TGFbeta by the conceptus and endometrium was studied during the period of implantation in the ewe. A total of thirty-four ewes were hysterectomized on day 12, 14, 16, 18 or 20 of pregnancy (day 0 = day of estrus). Conceptus (200 mg wet weight) and endometrial (300 mg wet weight) tissues were cultured in vitro in 7 and 10 ml Eagle's minimal essential medium, respectively. The culture media were subjected to a bioassay to determine concentrations of TGFbeta. Conceptus culture media (CCM) were also analyzed for contents of ovine interferon-tau (oIFNr), low molecular weight acidic protein, produced by the trophectoderm between days 8 and 21 of pregnancy. Whole uteri including conceptus(es) and conceptuses (day 16) only were fixed and subjected to immunohistochemical and in situ hybridization studies. Levels of oIFNr produced by conceptuses were the highest on day 16 at 4.4 microg/ml. Concentrations of TGFbeta in day 12, 14, 16, 18 and 20 CCM were 38+/-19, 102+/-56, 862+/-152, 728+/-191 and 336+/-106 pg/ml, respectively, and approximately 90% of TGFbeta activity in CCM was due to TGFbeta1 whereas less than 10% was due to TGFbeta3 based on neutralization with TGFbeta subtype-specific antibodies. Immunohistochemical studies revealed that day 16 conceptuses displayed major staining for TGFbeta1, no beta2 staining and minor staining for beta3. In situ hybridization studies also revealed that day 16 trophectoderm possessed most TGFbeta1 mRNA while day 14 trophectoderm and day 20 chorion/amnion displayed weaker staining for TGFbeta1 mRNA. TGFbeta in day 12, 14, 16, 18 and day 20 endometrial culture media was 156+/-37, 129+/-33, 49+/-22, 62+/-23 and 179+/-40 pg/ml, respectively, and approximately 65% and 35% of the activities were due to TGFbeta1 and beta2, respectively. These results indicate that TGFbeta production by the conceptus coincides with the time when oIFNtau production starts to decline. These observations support the postulate that TGFbeta may play an important role in implantation in the ovine species.

Animals↗

Hypotensive effects of an angiotensin II type 1 receptor antagonist differ between exercised and sedentary rats aged from 4 to 19 weeks.

The hypotensive effects of an angiotensin II type 1 receptor antagonist TCV-116 were accelerated by swimming training in the early period of chronic administration in young rats. In the latter period, however, a severe decrease in blood pressure that appeared during long-term administration of TCV-116 was prevented by swimming training. Therefore exercise may contribute to the stabilization of blood pressure in young rats treated with TCV-116.

Angiotensin Receptor Antagonists↗

[Changes in blood polyamine levels following chemotherapy in patients with invasive urinary bladder carcinoma].

BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to determine whether blood polyamines are useful biochemical makers for monitoring the efficacy of the chemotherapy on bladder tumors. METHODS: The blood concentrations of three polyamines, diamine, spermidine and spermine, were determined in 31 patients with invasive urinary bladder carcinoma, following chemotherapy with cisplatin, methotrexate and pirarubicin. Clinical response was evaluated by CT after 3 weeks. In 26 patients who underwent subsequent surgical therapy, the effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. RESULTS: Mean regression rate in the size of the tumor after the chemotherapy was 40.8%. Of 31 patients, clinical CR was observed in 2, PR in 11, and NC in 18. Of 26 patients who were histopathologically evaluated, grade 3 was observed in 5, grade 2 in 4, grade 1b in 4, grade 1a in 12, and grade 0 in 1. One week after chemotherapy, the levels of spermine and total polyamine in the patients with CR and PR were significantly lower than those in the patients with NC. Similarly one week after chemotherapy, the levels of spermine and total polyamine in the patients with grade 3 and grade 2 were significantly lower than those in the patients with grade 1b, grade 1a and grade 0. CONCLUSION: The study suggested that the levels of blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy on bladder tumors.

Adenocarcinoma↗

[Thermal effect on alpha 1-adrenoceptors in the guinea-pig vas deferens: histological and binding studies].

OBJECTIVE: To study the mechanism of thermotherapy on benign prostatic hyperplasia, we examined thermal effects on alpha 1-adrenoceptors in the guinea-pig vas deferens. The histological changes in the muscle cells after thermal exposure were also examined by electron microscopy. METHODS: The guinea-pig vasa deferentia were pretreated at 4 degrees C (control group), 43 degrees C, 50 degrees C, and 55 degrees C (heated group) for 1 hour and returned to 37 degrees C for 1 hour or 2 hours. Radioligand binding assay for alpha 1-adrenoceptors was performed by an incubation of [3H]prazosin with the crude membrane fraction from vasa deferentia. The dissociation constant (Kd) and the number of binding sites (NBS) of alpha 1-adrenoceptors were calculated from Scatchard analysis. The histological changes in the muscle cells were also examined at 4 degrees C, 40 degrees C, 50 degrees C, and 55 degrees C for 1 hour by electron microscopy. RESULTS: Kd and NBS did not change at 43 degrees C, but declined significantly above 50 degrees C for 1 hour. The changes in Kd and NBS above 50 degrees C for 1 hour did not recover after returning to 37 degrees C for 1 hour or 2 hours. Electron microscopic observations revealed a loss of myofilaments and dark staining of nuclear chromatin of the smooth muscle cells after thermal exposure above 50 degrees C. CONCLUSION: The binding ability of [3H]prazosin to alpha 1-adrenoceptors declined after thermal exposure above 50 degrees C. Also, the muscular damages were observed histologically after thermal exposure above 50 degrees C. These results indicated that the irreversible decrease in NBS and the disruption of smooth muscle fibers were associated with the thermotherapy.

Animals↗

[Anesthetic management of a patient with antiphospholipid syndrome].

A 46-year-old woman with antiphospholipid syndrome (APS) underwent an emergent laparotomy. The symptoms and signs of APS are reported to be thrombosis, habitual abortion, thrombocytopenia and biological false positive (BFP) for syphilis' tests. Clinical symptoms are based on hypercoagulation of blood, while prothrombin time (PT) activity and activated partial thromboplastin time (APTT) are prolonged. Although we have selected general endotracheal anesthesia without epidural catheterization, we recommend that the regional analgesia is suitable for those APS patients with abnormality of coagulation. If PT and APTT differ from clinical symptoms, we have to think about APS and manage the patients carefully as APS.

Anesthesia, General↗

LDL adsorption improves the response of focal glomerulosclerosis to corticosteroid therapy.

We investigated the therapeutic effect of low density lipoprotein adsorption (LDL-A) in 14 patients who had focal glomerulosclerosis (FGS) with the nephrotic syndrome resistant to steroids. Patients received a total of 6 sessions (2 times a week for 3 weeks). The levels of total cholesterol, triglycerides and low-density lipoprotein were decreased significantly after treatment (by approximately 50%) in all patients (p<0.01). There also seemed to be a possibility that LDL-A improved the response to steroid therapy. The glomerular filtration rate (GFR) increased from 54.4 +/-27.4 ml/min to 70.0+/-30.2 ml/min (p <0.05) and daily urinary protein excretion (Up/day) decreased from 7.24+/-3.58 g/day to 2.56 + 2.00 g/day (p<0.01). Up/day was significantly higher in patients who showed more than 30% improvement of GFR (n = 6) than in patients who showed less than 30% improvement of GFR (n = 7) (9.50+/-3.41 g/day vs 4.59+/-1.17 g/day, p<0.05). The decrease of urinary protein excretion was more marked in younger patients (29.4+/-11.9 vs 49.7+/-14.8, p <0.05). Only electron microscopy was able to detect histological recovery in the patients who showed a decrease of proteinuria after LDL-A therapy and light microscopy was not able to verify or accurately identify the histological response. In conclusion, LDL-A seems to be effective for FGS associated with nephrotic syndrome resistant to steroids, especially in younger patients. Histological assessment of the effect of this treatment requires electron microscopic examination.

Adrenal Cortex Hormones↗

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

[Recent surgical treatment of hemorrhagic diseases in the gastrointestinal tracts].

With an advent of conservative therapy for hemorrhagic gastroenterological diseases, the candidates for surgical treatment have been tremendously decreased. As to the treatment of ruptured esophagogastric varices, endoscopic injection sclerotherapy, endoscopic variceal ligation, TIPS have been practiced as a procedure of choice. Although these conservative treatments are effective and less invasive, the high incidence of rebleeding has been reported in the literature. Therefore the optimal choice is still controversial. It includes esophageal transection, selective distal splenorenal shunt. They should be considered as candidates for surgery if tests suggested that the patient could tolerate for surgical stress. On the other hand liver transplantation is considered to be an important therapeutic option in the United State for the patients with severe liver cirrhosis. Another recent advances in this field are laparoscopically assisted surgery. When bleeding is caused by divericulum or tumor of the gastrointestinal tracts, laparoscopic approach is another method of choice before laparotomy.

Esophageal and Gastric Varices↗

Effects of major Class II occlusal corrections on temporomandibular signs and symptoms.

This study explored the relationship between malocclusion and signs and symptoms of temporomandibular disorders (TMD) in 124 patients with severe Class II malocclusion, before and 2 years after bilateral sagittal split osteotomy (BSSO). Patients were evaluated with the Craniomandibular Index (CMI), the Peer Assessment Rating Index (PAR Index, to assess gross changes in the occlusion), and symptom questionnaires. The results showed a significant improvement in occlusion; PAR Index scores dropped from a mean of 18.1 before surgery to a mean of 6.1 at 2 years postsurgery (P < 0.001). The CMI and masticatory index (MI) for muscle pain indicated clinically small but statistically significant improvement (P = 0.0001) from before surgery (mean CMI = 0.14, mean MI = 0.15) to after surgery (mean CMI = 0.10, mean MI = 0.08). The number of patients with clicking upon opening decreased significantly from 33 (26.6%) to 13 (10.5%) (P = 0.001). However, the number of patients with fine crepitus increased from 5 (4.0%) before surgery to 16 (12.9%) at 2 years postsurgery (P = 0.005). Significant reductions in subjective pain and discomfort were also found 2 years after surgery. The magnitude of change in muscular pain was not related to the severity of the pretreatment malocclusion, a finding that suggests that factors other than malocclusion may be responsible for the change in TMD.

Adolescent↗

Corticosterone is required for the prolactin receptor gene expression in the late pregnant mouse mammary gland.

In order to clarify the prolactin receptor (PRL-R) gene expression at lactogenesis, the levels of the long and short forms of PRL-R mRNA were determined by the competitive RT-PCR in the pregnant, lactating and ovariectomized midpregnant mouse mammary gland. Plasma concentrations of corticosterone and progesterone were determined by RIA. The long form of PRL-R mRNA level was low until 10:00 on day 18, increased 3.3-fold at 22:00 on day 18 of pregnancy and further increased to 4.6-fold at 10:00 on day 0 of lactation. The short form of PRL-R mRNA level remained unchanged during this time period. The corticosterone:progesterone ratio increased 15.5-fold during the last 1.5 days of pregnancy. Corticosterone increased the long form of PRL-R mRNA level when the tissues on day 17 were cultured. On day 12 of pregnancy and following ovariectomy, corticosterone was exceedingly high from 2 h to 8 h and the corticosterone:progesterone ratio changed prior to the increase in the long form of PRL-R mRNA level. We conclude that corticosterone increases the PRL-R gene expression in the mammary gland before the onset of parturition.

Animals↗