[The relationship between cardiac systolic and diastolic function and the changes in cellular membrane signal transduction system and extracellular matrix].
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Biomedical subjects
Publications and source records attributed to N Miyamoto.
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It has been postulated that gravitational change from 1 g to microgravity may cause cephalad fluid shift, resulting in suppression of antidiuretic hormone (ADH) secretion and diuresis (Gauer-Henry's reflex). However, results obtained in space flights did not confirm this. Since astronauts are confined at supine position for hours before launch, this posture may abolish the reflex in space flight. To investigate this possibility, effects of head-out water immersion (WI) after 2-hour head-down tilt (HDT) on hormonal and metabolic responses were examined and compared with those after 1-hour upright posture (UP). Hematocrit decreased by WI after UP, indicating hemodilution, but it did not change by WI after HDT. Plasma ADH, renin activity and aldosterone fell and atrial natriuretic peptide (ANP) rose by WI after UP, resulting in increased urine flow. On the other hand, appreciable hormonal changes were not elicited by WI after HDT, and urine flow stayed unchanged. These results indicate that fluid shift and hormonal and metabolic responses to WI are strongly attenuated by the prior exposure to HDT. Pre-launch posture of astronauts may at least partly explain why either suppression of ADH or diuresis was not observed on arrival at space.
Tail-suspension of rats has been employed for the study of disuse atrophy of hindlimb muscles and bones. From our study, it is suggested that stress exacerbates muscle and bone atrophy; however, the determination of stress hormones has been inappropriately performed. For assessing the effect of tail suspension on stress hormone secretion, suspension was performed for 7 days in a metabolic cage. Urinary excretions of corticosterone, catecholamines and antidiuretic hormone were determined during the 7-day suspension. Urine volume was unchanged during the suspension period, whereas water consumption was decreased during suspension. Urinary excretion of corticosterone and catecholamines increased significantly during the initial 3 days of suspension. The excretion of antidiuretic hormone increased throughout the suspension period. Our results demonstrated that the determination of urinary excretion of these hormones is useful for evaluating the stress reaction.
Heart failure is basically a manifestation of mechanical disturbances of the heart, but not of electrical abnormalities and is not associated with specific ECG patterns. Several ECG findings are, however, experienced in cases with heart failure as a result of cardiac chamber enlargement and other related changes. Left atrial enlargement is known to cause characteristic P wave changes, which sometimes show parallel course with the clinical state. ECG criteria for atrial enlargement are critically reviewed. In cases with cardiac enlargement, which was improved in a relatively short period of time, R wave height often showed first increase and then decrease. Tissue edema was thought to be the major reason for the initial increase and the distance between the recording electrode and the heart for the later decrease, although other factors can contribute and modify the findings. Minor conduction disturbances due to myocardial stretch and other reasons may also contribute to changes of QRS complex. Analysis of RR intervals offers another possibility to characterise heart failure. A decrease in variability of the RR intervals and in high frequency components on frequency spectrum has been reported in cases with heart failure.
For introduction of a left atrial (LA) cannula by the transseptal puncture technique, we examined the feasibility of using biplane transesophageal echocardiography (B-TEE). A transseptal puncture was performed on 15 patients (3 male; 12 female; mean age, 48.9 +/- 11.2 years) by B-TEE guide during percutaneous transvenous mitral comissurotomy (PTMC). The entire Brocken-brough needle and the position of its tip were clearly observed in the right atrium by a longitudinal image of B-TEE in all patients (100%), and in 2 (13%) of them also by the transverse image of B-TEE. The puncture was about 1 cm caudal from the center of the fossa ovalis to avoid any large residual atrial septal defect. After transseptal puncture, a Mullin's sheath (7 Fr) and a dilator (14 Fr) were inserted into the left atrium in order, and then an Inoue's balloon catheter (12 Fr) was introduced without difficulty into the left atrium in all patients. With contrast injection, the position of the sheaths's tip was clearly confirmed by B-TEE. Left heart bypass support (left atrial-femoral artery bypass or AAB) was performed on 2 patients after percutaneous introduction of the LA cannula using this technique, and both were successfully supported and survived. With B-TEE guidance, the Brockenbrough atrial septal puncture and introduction of the LA cannula into left atrium can be performed easily. Thus, percutaneous left heart bypass can be set up quickly and safely even in an intensive care unit or outpatient emergency room without radiographic guidance.
The effect of hypoglycemic stress on the changes in water and electrolyte metabolism induced by head-down tilting (HDT) was studied. Six healthy men were subjected to postural changes (30 min standing, 2 h HDT, 1 h standing), with or without the intravenous administration of insulin at the beginning of HDT. When insulin was not given, antidiuretic hormone (ADH), cortisol, plasma renin activity (PRA), aldosterone, and catecholamine levels were decreased and atrial natriuretic polypeptide (ANP) levels increased during HDT. These changes were associated with 2.5- and 1.5-fold increases in urine flow and sodium excretion, respectively, when compared with the amounts before HDT. On the other hand, insulin-induced hypoglycemia during HDT produced increases in ADH, cortisol, PRA, aldosterone, and catecholamine levels. At the same time, an exaggerated ANP response by HDT was observed. These hormonal changes were associated with an abolishment of the increases in urine flow and sodium excretion. It is suggested that acute stress modifies the changes in fluid and electrolyte metabolism induced by HDT.
ACTH rapidly and transiently increases c-fos mRNA in the rat adrenals in vivo. The present investigation was undertaken in order to determine what kind(s) of second messenger systems is involved in this increase. Rat adrenal cells were grown in monolayers in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. After 2 days of culture, cells were treated with ACTH and various agents alone or in combination. The amount of c-fos mRNA was determined by dot blot hybridization and corticosterone levels in the media were measured by RIA. ACTH (300 pg/ml) increased c-fos mRNA transiently with a peak level after 60 min. A similar increase was observed when (Bu)2cAMP (1 mM) was substituted for ACTH. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H-89), a selective inhibitor of cAMP-dependent protein kinase, suppressed both basal and ACTH-increased c-fos mRNA. H-89 also suppressed corticosterone production. On the other hand, neither 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml) nor elevated potassium ion (50 mM) affected the amount of c-fos mRNA and corticosterone production. Furthermore, pretreatment with cycloheximide (5 micrograms/ml) increased both basal and ACTH-increased c-fos mRNA. These results indicate that ACTH increases c-fos mRNA by phosphorylation of preexisting trans-acting factor(s) via cAMP-dependent protein kinase in common with steroidogenesis.
We encountered a patient with spontaneous coronary artery dissection complicated by acute inferior myocardial infarction. A 58-year-old male was admitted to our hospital due to acute inferior myocardial infarction in 1979. Coronary angiography performed 4 weeks after the onset showed a double lumen divided by a linear intimal flap in the right coronary artery, suggesting coronary artery dissection, but no apparent occlusion. Subsequently, he had been medicated with nitrates without any recurrent infarction. In February, 1989, 10 years after the first examination, coronary angiography was again performed and showed that the dissection had remained unchanged. Acetylcholine infusion into the right coronary artery induced coronary spasm. The prognosis of this condition seems to be better than has been generally considered, particularly in patients such as ours in whom the involvement of coronary spasm in the development of coronary artery dissection and myocardial infarction is suggested. When coronary spasm in controlled by treatment with nitrates or calcium antagonists, an uneventful course may be expected.
Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals.
It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied. The effect of gonadotropin was examined in female rats whose gonadotrophs were medically ablated by GnRH agonist (TAP-144-SR). After intravenous administration of pregnant mare's serum gonadotropin (PMSG:30 IU/rat), their ovaries were dissected out at various time intervals and total RNA was extracted. Changes in the levels of c-fos, c-jun and P450scc mRNAs were determined by Northern blot analysis. The levels of c-fos and c-jun mRNAs increased rapidly and transiently with the peak levels at 15 min after PMSG administration. The levels of both mRNAs were decreased by 30 to 60 min. On the other hand, the levels of P450scc mRNA started to increase 60 min after PMSG. These results indicate that gonadotropin-induced increase in the expression of c-fos and c-jun genes may play important roles in mediating the action of gonadotropin on the ovaries.
Between Sept.1, 1989 and Feb.28, 1990, 19 patients received renal allografts, and all of them were examined by serological tests for CMV infection before and after the transplantation. Six patients who had some clinical symptoms such as fever and cough were monitored for anti-CMV antibodies by the ELISA method during the first 3 months after the transplantation. Five of the 6 patients complained of mild clinical symptoms but their condition was not serious. The other patients, a 42-year-old man developed serious CMV infection. His serological CMV antibody titer had decreased one month after the transplantation compared to that before the transplantation. By contrast, the other patients showed either elevation or no change of CMV antibody titer. Therefore, special attention should be paid to the case of decrease rather than increase in CMV antibody titer one month after the transplantation in patients with severe symptoms.
Inversion of chromosome 16 was found in a 73-year-old female with acute myeloblastic leukemia (FAB:M2). Complete remission was achieved by combined chemotherapy (DNR, Ara-C, 6-MP, Prednisolone), but she relapsed 6 months later without CNS involvement and died of respiratory failure presumably due to cerebrovascular accident during remission reinduction chemotherapy. Biphenotypic surface markers (CD2+ and CD13+) were observed on relapse. Eosinophilia was not observed throughout. Our patient and the other reported case suggest that biphenotypism and the lack of eosinophilia and monocytosis in inv (16) leukemia may be correlated with a poor prognosis.
A 41-year-old male complaining of fever and left shoulder pain was admitted to our hospital for further examination of an abnormal shadow on chest X-ray film. His laboratory data on admission showed marked leukocytosis and elevation of serum alkaline phosphatase. The diagnosis of large cell carcinoma of the lung was made by percutaneous biopsy and he was staged clinically as T3N0M0. Chemotherapy including CDDP and VDS resulted in resolution of symptoms and normal laboratory data. After three courses of chemotherapy, he underwent left upper lobectomy with chest wall resection. Pathological diagnosis of the resected tumor was large cell carcinoma with giant cells, and he was staged postoperatively as T3N0M0. Since colony stimulating activity was demonstrated in both homogenate of tumor cells and tumor conditioned medium, and preoperative serum granulocyte colony-stimulating factor (G-CSF) was 105 pg/ml, we concluded that leukocytosis in this patient was caused by G-CSF produced by tumor cells. The patient was in good health two years after surgery with no signs of recurrence.
The iliac hemophilic pseudotumor is a rare complication of hemophilia occurring in 1-2% of patients with Factor VIII or Factor IX deficiency. It is frequently disabling and life threatening. This report presents a comparative study of postoperative results of two cases of hemophilic pseudotumor of ilium. One patient undergoing partial resection showed a favorable postoperative course, whereas the patient with complete resection of the pseudotumor died of postoperative bleeding and sepsis. Studies on the postoperative results of these two cases indicate that careful preoperative consideration of tumor size and degree of infiltration is of the utmost importance in operative management. Early excision of tumors eliminates the possibility of endogenous infection. Even partial resection of huge tumors, leaving the lateral wall intact for compression, can promote recovery of functions.
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The present study was undertaken to examine whether sulfonamide-derived diuretics affect [Arg8]vasopressin (AVP)-stimulated or atrial natriuretic peptide (ANP)-stimulated cyclic nucleotide formation in cells cultured from rat or dog kidney. In rat renal cells, all four sulfonamide-derived diuretics examined significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations of 10(-4) and 10(-3) M, while basal cAMP formation was unchanged by the diuretics. When cells were stimulated with 10(-7) M AVP, low ceiling diuretics (indapamide and trichlormethiazide) did not suppress cAMP formation, while high ceiling diuretics (furosemide and azosemide) significantly suppressed cAMP formation at concentrations of 10(-4) and 10(-3) M. The suppressive effect of the diuretics on AVP-stimulated cAMP formation in vitro paralleled the reported diuretic potency of the agents in vivo. In dog renal cells, all four diuretics significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations from 10(-6) to 10(-5) M, while these diuretics did not change basal cAMP levels. High ceiling diuretics suppressed 10(-7) M AVP-stimulated cAMP formation, whereas low ceiling diuretics did not. The difference in effective doses between rats and dogs seems to be consistent with the species difference observed in vivo. None of the diuretics affected basal levels of intracellular cGMP or ANP-stimulated cGMP formation in cultured rat renal cells. In addition to the inhibition of the Na/K/Cl co-transporter, it is suggested that most sulfonamide-derived diuretics act, at least in part, by inhibiting the actions of AVP.
A rare case of a 51-year-old female with a pleomorphic adenoma, measuring 0.9 x 0.7 x 0.6 (cm3), originating from the right external auditory canal (EAC), was reported. The authors discussed the 7 reported cases of EAC pleomorphic adenoma in Japan, comparing them with pleomorphic adenomas occurring in the nasal cavity and the parotid gland. It is currently too early to conclude that pleomorphic adenoma in the EAC does not tend to recur or shows a marked tendency toward canceration. The best possible treatment for EAC pleomorphic adenoma at present seems to be, as in cases of tumors in other sites, surgical resection together with removal of a sufficient range of surrounding normal tissue, followed by careful long-term postoperative observation of the clinical course.
We measured the cord serum levels of thyroid-stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) in 922 neonates delivered by mothers who had no thyroid disorders. The T4 and T3 levels increased progressively from the 27th to the 40th week of gestation. However, the TSH levels varied widely and had no correlation with gestational age, because they were affected by the mode of delivery. The mean cord serum TSH level in neonates delivered by vacuum extraction was 16.3 +/- 10.0 microU/ml (n = 30), which was significantly higher than the level following normal vaginal delivery (9.5 +/- 6.0 microU/ml, n = 622) (p less than 0.005). The mean cord serum TSH level following elective caesarean section was 6.5 +/- 3.1 microU/ml (n = 79), and this was significantly lower than after normal vaginal delivery (p less than 0.005). TSH levels in high-risk neonates were significantly higher than in neonates without risk factors. A significant positive correlation was found between the duration of the second stage of labor and the cord serum TSH level (r = 0.45, n = 412, p less than 0.01). However, there was no correlation between the cord serum TSH level and the congenital hypothyroidism screening TSH level (r = 0.01, n = 468). We conclude that the cord serum TSH level reflects delivery stress and that an elevated level does not influence the congenital hypothyroidism screening TSH test in which blood is obtained at five days of life.