Biomedical subjects

M Sagara

Publications and source records attributed to M Sagara.

At least 37 records · Page 2Linked to original sources

PubMed1997

Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.

It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Peripheral neuropathy in allergic granulomatous angiitis.

A 61-year-old woman began to suffer bronchial asthma in 1985. She then developed low back pain and numbness along the lower extremities, eventually leading to bilateral drop foot in 1990. At that time, she was diagnosed as having lumbar disc hernia, and extirpation of the discs at the L3-4 and L4-5 was performed. However, her clinical condition showed little improvement. Six months later, she was emaciated and bedridden with distal dominant muscular atrophy in all four limbs, purpura in the left leg and hypereosinophils. Motor conduction velocity (MCV) was not detected in the peroneal nerves. The toes gradually became cyanotic, and a skin biopsy from the cyanotic region revealed necrosis in the vessels surrounded by infiltration of a large number of neutrocytes and lymphocytes. She was diagnosed as having mononeuritis multiplex due to allergic granulomatous angiitis (AGA), which is characterized by bronchial asthma, hypereosinophilia and necrotizing vasculitis. Thirty mg/day prednisolone was then administered. However, the toes and calcaneal areas gradually became necrosed. Finally, amputation of both feet was necessary. We concluded that an early diagnosis of this syndrome is most important, and corticosteroids should be administered early.

Adrenal Cortex Hormones↗

PubMed1996

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Acetylcysteine↗

PubMed1996

Improvement of glucose tolerance with immunomodulators on type 2 diabetic animals.

Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal models. We extend this therapy to non-insulin-dependent diabetes mellitus (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM, was recovered by allogenic bone-marrow transplantation that also prevented IDDM in animal models. An i.p. or i.v. injection of streptococcal preparation (OK-432) lowered fasting blood glucose (FBG) levels and markedly improved glucose tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose loading routes (oral, i.v. or i.p.), while an i.v. injection of BCG improved FBG and GTT for more than 4 wks without body weight loss. The improvement of FBG and GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar fatty rats. Among various cytokines possibly induced by OK-432 and BCG, IL-1 alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay mice, whereas IL-2 and IFN gamma did not. There were no differences between the OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of insulin-induced decrease in blood glucose levels, and muscle glycogen synthase activities. As to insulin secretion, there is a tendency that the OK-432-treatment less that 1 week did not affect insulin levels during GTT, whereas the treatment more than 2 weeks increased the insulin levels. Thus, cytokine-inducers improved FBG and glucose tolerance of NIDDM animals probably via cytokines. The results imply a role of the cytokines in glucose tolerance of NIDDM, although precise immune and metabolic mechanisms remain to be elucidated.

Adjuvants, Immunologic↗

PubMed1996

N-acetylcysteine inhibits loss of diaphragm function in streptozotocin-treated rats.

We examined whether streptozotocin (STZ)-induced diabetic rats have an impairment in diaphragm contractility, and if so, whether N-acetylcysteine (NAC), a nonspecific antioxidant, prevents this impairment. First, diaphragm contractility, assessed by tension-frequency relationships and twitch kinetics in in vitro diaphragm strip preparations of Wistar rats, was obtained on Days 3 and 7 after administration of STZ of 30 or 60 mg/kg body weight, and compared with that of the control group. Second, NAC at 500 mg/kg body weight or vehicle solution was administered orally every day in rats treated with STZ at 60 mg/kg body weight, and diaphragm function on Day 7 after starting NAC treatment was compared between vehicle control and STZ-treated groups. We found that diaphragm function in STZ-treated rats, which had hyperglycemia, decreased in a dose- and time-dependent manner. NAC inhibited the decrease in diaphragm contractility in STZ-treated rats without reducing blood glucose. These findings suggest that the loss of diaphragm function in STZ-induced diabetic rats is not directly related to hyperglycemia. The data are consistent with secondary alterations of normal cytokine signaling or changes in the redox state of the cell, both of which could be affected by NAC treatment.

Acetylcysteine↗

PubMed1996

[Usefullness of transesophageal echocardiography in early detection of coronary spasm].

Intraoperative transesophageal echocardiography (TEE) was performed on a 62-year-old man who underwent abdominal aortic replacement for abdominal aortic aneurysm under general anesthesia combined with epidural anesthesia. Coronary artery spasm occurred after unexpected massive hemorrhage, and TEE showed hypokinesis in the posterior-inferior left ventricular wall. The changes in TEE preceded the ST elevation in the ECG. Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin alleviated these changes. TEE enabled us to detect and evaluate coronary spasm before the appearance of ST changes in ECG.

Anesthesia, Epidural↗

PubMed1996

[Myocardial ischemia induced by air bubbles].

Intraoperative transesophagial echocardiography (TEE) was performed in a 27-year-old man who underwent direct suture for atrial septal defect (ASD) under general anesthesia. Myocardial ischemia occurred about five minutes after weaning from cardiopulmonary bypass, and at that time TEE showed that anteroseptal wall, lateral septal wall and lateral wall are severely hypokinetic and another wall is diffusely hypokinetic in the left ventricle after detecting air bubbles in the left ventricle by TEE. The changes in TEE preceded the ST elevation in the ECG. Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin showed no effects on these changes. Ten minutes after the onset of myocardial ischemia, these changes were alleviated. TEE enabled us to detect air bubbles and evaluates myocardial ischemia before the appearance of ST changes in ECG.

Adult↗

PubMed1996

[Changes in bone mineral content and bone metabolism during pregnancy and puerperium].

In order to clarify the bone metabolism of women during both pregnancy and puerperium, we studied the changes in bone mineral content and bone biochemical parameters. Bone mineral content was measured by ultrasound bone densitometry, and serum calcium (Ca), ionized calcium (i-Ca), intact parathyroid hormone (i-PTH), intact osteocalcine (i-OC), urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) were measured concomitantly. 1. In the 3rd trimester bone stiffness was decreased (p < 0.05) compared the 1st and 2nd trimesters, but was slightly increased in the puerperal group. 2. Serum i-OC was decreased during pregnancy but significantly increased (p < 0.01) in the puerperium. The Pyr/Creatinine (Cre) and D-Pyr/Cre ratios were both increased in pregnant and puerperal women. 3. Serum Ca, i-Ca and i-PTH were within the normal range during pregnancy and the puerperium. These results suggest that in the 2nd and 3rd trimesters bone resorption would be increased, and in the puerperium bone formation would be increased. In pregnant and puerperal women serum Ca, i-Ca and i-PTH are within the normal range, but the turnover rate for Ca metabolism would be relatively increased.

Adult↗

PubMed1996

[A comparison of various ways of cardiac output measurement by thermodilution methods].

We compared cardiac output values obtained by the following 3 methods: 1. Iced bolus injectate method, using the injectate temperature actually measured for computation [bolus cardiac output with flow-through temperature probe: BCO (p)]. 2. Continuous cardiac output measurement, using Vigilance system (continuous cardiac output: CCO). 3. Iced bolus injectate method, assuming injectate temperature to be 0 degrees C (bolus cardiac output without flow-through temperature probe: BCO). Only the subject receiving cardiovascular surgeries using cardiopulmonary bypass (CPB), and requiring a thermodilution catheter for hemodynamic monitoring during anesthesia were selected for the study. The total cases consisted of 15 patients (10 males), in which 60 measurement were made. Following the anesthetic induction with fentanyl, midazolam, vecuronium bromide, and intubation, a Baxter Swan-Ganz CCO thermodilution catheter was inserted through the right internal jugular vein. Compared to BCO(p), CCO showed excellent precision and bias; (r2 = 0.935, P < 0.0001, bias = -0.19 l.min-1, SD = 0.36 l.min-1). Although BCO correlated well with BCO(p), the bias was much greater (r2 = 0.919, P < 0.0001, bias = -1.25 l.min-1, SD = 0.45 l.min-1) than BCO(p). In conclusion, the values obtained by BCO(p) and CCO methods were very accurate. On the other hand, a considerable overestimation was found with BCO since the compensation for actual injectate temperature was not performed

Cardiac Output↗

PubMed1996

[Anesthesia for a patient with pheochromocytoma associated with chronic renal failure].

A case of a 53-year-old man with left pheochromocytoma associated with chronic renal failure is described. He had been on regular hemodialysis for 15 years. Also, because of right renal carcinoma, he underwent right nephrectomy at the same time. For preoperative preparation, we kept the patient's dry weight. Anesthesia was induced with isoflurane 1.0% in oxygen, and fentanyl 0.3 mg and midazolam 5 mg, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with isoflurane 0.5% in oxygen 50-100%, fentanyl and midazolam. Intraoperative hypertension during the manipulation of the tumor and hypotension after removal of the tumor were controlled by continuous or bolus infusion of phentolamine and norepinephrine respectively. For intraoperative fluid management, we administered crystalloid solution 4 ml.kg-1.hr-1. Careful preoperative management was carried out to prevent severe intraoperative and postoperative cardiovascular or respiratory complications.

Adrenal Gland Neoplasms↗

PubMed1995

Expression of thrombomodulin in esophageal squamous cell carcinoma and its relationship to lymph node metastasis.

Thrombomodulin (TM) is thrombin receptor that was identified originally on the endothelium and acts as a natural anticoagulant. However, we reported previously that TM was also expressed in the squamous epithelium mainly at the intercellular bridges. In this study, we examined TM expression in the primary lesions of 106 patients with esophageal squamous cell carcinomas and in the lymph node metastatic lesions of 59 patients using immunohistochemical methods. The carcinoma tissues expressed TM mainly at the cell-cell boundaries and in the cytoplasm. When TM expression was compared between the primary and metastatic lesions in the 59 patients who had lymph node metastasis, 41 (69%) showed decreased TM expression, 18 (31%) showed no change, and none (0%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells that were positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.0001). This result indicates that the decrease in TM expression is associated with metastasis of the carcinoma cells. This phenomenon is very similar to that of E-cadherin, although the structures of both molecules are quite different. The reduction of TM expression seems to play an important role in the metastatic process of esophageal cancer.

Adult↗

PubMed1995

Heritable formation of neuroectodermal tumor in transgenic mice carrying the combined E1 region gene of adenovirus type 12 with the deregulated human renin promoter.

Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transcriptional regulation of viral and cellular promoters in infected and transfected culture cells and for transformation of primary rodent cells. Here, we established a line of transgenic mice carrying the E1 region gene of human adenovirus type 12 under the control of the human renin promoter, in which a neuroectodermal tumor derived from retroperitoneal, olfactory, and/or pelvic regions was heritably developed with varying degrees of incidence and the phenotype was successfully passed through six generations. The transgenes were located in the region E2-E3 bands of chromosome 7 with which no genetic linkage to neuroectodermal tumors was previously demonstrated, and expressed only in the tumors but not in another tissue examined. Notably, in addition to the expression of a neural marker gene N-CAM, the three nuclear oncogenes, c-, L-, and N-myc, were coexpressed in the tumors. These results suggest that E1A and E1B are cooperatively involved in the heritable formation of neuroectodermal tumors associated with co-expression of the three sets of myc family genes.

Adenovirus E1 Proteins↗

PubMed1995

Reduced expression of c-Fos in female NOD mouse thymocytes and up-regulation with human lymphotoxin.

Previously we reported that the administration of human (h) lymphotoxin (h-LT) markedly protected NOD mice from insulin-dependent diabetes mellitus (IDDM) partly by affecting the generation phase of anti-islet effector cells, probably in the thymus. In this study, we investigated the effect of h-LT on the signal transduction of the mouse thymocytes by observing c-Fos expression in the thymocytes by using a flow cytometer. The intensity of c-Fos expression in whole thymocytes was significantly lower in the female NOD with a high incidence of diabetes than that in the male NOD mice with a low incidence of diabetes and than that in normal mice (P < 0.0001). The low c-Fos expression in the female NOD thymocytes was most prominent in CD3low thymocytes. c-Jun expression of the CD3low thymocytes was also lower in the female NOD mice. Administrations of h-LT, h-TNF, and h-IL-2, which has been reported to prevent IDDM in NOD mice by systemic administration, significantly up-regulated c-Fos expression in CD3low thymocytes. From these results, it is assumed that a relationship may exist between the high diabetes incidence and the defective c-Fos expression in female NOD mice and between the prevention of IDDM and the amelioration of the defective c-Fos expression with h-LT in female NOD mice.

Animals↗

PubMed1995

Analysis of action mechanism of lymphotoxin in prevention of cyclophosphamide-induced diabetes in NOD mice.

Recently we reported that lymphotoxin (LT) administration protected non-obese diabetic (NOD) mice and BB rats from insulin-dependent diabetes mellitus. In this study we analysed the protection mechanism of LT by using cyclophosphamide (CY)-induced autoimmune diabetes in NOD mice. Pre-administration of 500 or 1000 U of LT three times a week between the age of 4 and 11-13 weeks before CY-treatment strongly inhibited CY-induced diabetes. This inhibition was reproduced by LT pre-administration at an earlier age (4 to 7 weeks) but not at a later age (8 to 11 or 10 to 12 wks). LT post-administration (100 U daily or 500 U twice a week) after CY-treatment at 14 weeks of age also strongly inhibited CY-induced diabetes. Spleen cell transfer was carried out using various combinations of donors and recipients. Spleen cell transfer from the non-diabetic mice, which were LT pre-administered between the age of 4 and 13 wks, to CY-treated mice did not significantly inhibit CY-induced diabetes, while transfer of the cells from the similarly treated mice to irradiated recipients did induce diabetes although the onset of diabetes was significantly delayed. Diabetes was not transferred by spleen cells from diabetic mice to LT pre-administered and CY-treated mice. LT administration did not change subpopulations and adhesion molecule expressions of the spleen lymphocyte. Taken together, these results suggest that LT protects NOD mice from CY-induced diabetes by making the mice resistant to autoimmune diabetes and possibly by suppressing anti-islet effector cells, but not by inducing adoptively transferable suppressor cells, although the precise mechanisms still remain to be elucidated.

Animals↗

PubMed1995

Lymph node metastasis and the recurrence of esophageal carcinoma with emphasis on lymphadenectomy in the neck and superior mediastinum.

A series of 335 patients with squamous cell carcinoma of the thoracic esophagus undergoing resection and reconstruction via a right thoracotomy and laparotomy with cervical anastomosis between 1973 and 1990, were reviewed. Prior to 1982, the removal of lymph nodes was limited to the nodes in the mediastinum below the tracheal bifurcation and upper abdomen (142 patients). Nodal metastases were found in 89 of these patients at operation. The upper abdominal nodes were the most frequent sites of metastasis (47.2%). None of the 38 patients with positive nodes sampled from the neck and superior mediastinum survived for more than 45 months. In the 50 patients with recurrences, 30 were in the neck and/or superior mediastinum. During or after 1983, the superior mediastinal nodes, particularly the bilateral recurrent nerve nodal chains, were routinely removed (193 patients). Nodal metastasis was proven in 131 of the 193 patients, in whom 87 (45.1%) had metastasis in the neck and superior mediastinum. Eleven of these 87 patients survived for 45 months or more. In the 61 patients with recurrences, 20 were in the neck and/or superior mediastinum. These data suggest that recurrent nerve nodal chains should be removed to improve survival in patients with esophageal carcinoma.

Aged↗

PubMed1995

D-glucose transport and glycolytic enzyme activities in erythrocytes of dogs, pigs, cats, horses, cattle and sheep.

The activities of D-glucose transport (D-GT) and the glycolytic enzymes hexokinase (HK) and pyruvate kinase (PK), were measured in the erythrocytes of dogs, pigs, cats, horses, cattle and sheep. The erythrocytes of dogs had the highest activities of D-GT, HK and PK, significantly higher than the activities in the erythrocytes of the herbivores. The activities of D-GT and HK in cat erythrocytes were significantly lower than in those of dogs. The differences between the activities of D-GT in the erythrocytes of the different species followed the differences in activities of HK but not those in the activities of PK or in the blood glucose concentrations. It is considered that the activity of HK provides a convenient measurement of the relative rates of glucose oxidation in erythrocytes.

Animals↗

PubMed1995

Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene.

The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.

Adenovirus E1 Proteins↗

PubMed1995

Filtration of human seminal specimens using LeukoSorb leukocyte-retention medium.

OBJECTIVE: To compare LeukoSorb filtration with Percoll centrifugation in preparing sperm. METHODS: Each of 26 human seminal specimens were analyzed before and after two preparation methods. RESULTS: In normospermic specimens (n = 11), LeukoSorb produced higher results than Percoll did with regard to mean percentage of motility (72.7% vs 59.2%), total swollen sperm in a hypo-osmotic swelling test (84.8% vs 59.0%), (g)-type swollen sperm (37.8% vs 23.4%) and tail abnormality (20.4% vs 10.1%). In asthenospermic specimens (n = 15), LeukoSorb produced higher results than Percoll did with regard to mean percentage of motile sperm recovery (22.2% vs 10.1%), motility (46.9% vs 23.2%), viability (75.6% vs 54.7%), total swollen sperm (84.8% vs 59.0%) and tail abnormality (42.2% vs 24.3%), although the mean percentage of head abnormality was lower with LeukoSorb than with Percoll (30.6% vs 40.2%) vs 40.2%). In pyospermic specimens (n = 10), the mean concentration of round cells after LeukoSorb decreased significantly more than with Percoll (p = 0.029). The filtration time correlated with the total sperm concentration. CONCLUSION: LeukoSorb filtration is useful for preparing asthenospermic and pyospermic seminal specimens.

Centrifugation↗