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Biomedical subjects

A Iguchi

Publications and source records attributed to A Iguchi.

At least 127 records · Page 7Linked to original sources

Assessment of the Björk-Shiley prosthetic valve orifice area in the aortic position.

The actual orifice area of a valve is still considered to be a valuable index for assessing prosthetic valve function. Valve orifice area as calculated by Gorlin's formula is, however, not constant but changes in proportion to the transvalvular flow rate. The purpose of the present study was to examine the relationship between orifice area and flow rate across the Björk-Shiley prosthetic valve as calculated by Gorlin's formula, and to modify the formula in a series of patients with the Björk-Shiley prosthetic valve in the aortic position. Fifty-six patients who had received aortic valve replacement with a Björk-Shiley prosthetic valve underwent cardiac catheterization. Prosthetic valve orifice area was calculated by Gorlin's formula and then plotted against flow rate across the valve with respect to valve size. The relationship between orifice area and flow was linear. The discharge coefficient of Gorlin's formula was plotted against flow rate, and a linear correlation was obtained. By substituting Gorlin's formula for an empiric coefficient into the function for transvalvular flow rate, a modified formula that can predict the actual orifice area of the prosthetic valve is obtained.

Aortic Valve↗

[Usefulness and problems of percutaneous endoscopic gastrostomy in a geriatric hospital].

Usefulness and problems of percutaneous endoscopic gastrostomy (PEG) placement in a geriatric hospital where most patients were severely demented or bed-ridden were evaluated. The variables examined were acute complications, chronic complications, restraint of patients before and after PEG placement, change in physical activity, and ability of oral intake. Results showed that both acute and chronic complications were not rare, but these problems are not peculiar to geriatric hospitals. Quality of life (QOL) was clearly improved. Restraint could be reduced or stopped in 65.2% of restrained patients after PEG tube placement, activity was improved in 55.5% of patients, and oral intake became possible in 14.0% of patients. There were also some improvements in the management of PEG, as the incidence of self-extubation decreased, and tube exchange became easier. In conclusion, it is possible to insert and manage the PEG tubes even in geriatric hospitals, and PEG tubes are quite useful in managing patients with chronic disease and in improving QOL.

Aged↗

[Brain damage following aortic arch repair with regard to techniques of selective cerebral perfusion and preoperative cerebral lesions].

One hundred and twenty-nine aortic aneurysm patients (true 68 and dissection 61) underwent aortic arch repair from January 1987 to December 1995. Postoperative brain damage was evaluated regarding both preoperative brain lesions and techniques of selective cerebral perfusion (SCP) in that one pump for SCP until April 1992, then two pumps were employed, one for right and the other for left hemisphere of the brain. Overall hospital mortalities were 21% in true and 13% in dissecting aneurysms. Ten patients were complicated with postoperative brain damages (coma 8 and hemiplegia 2), registering 7.8% of total patients. Both history of stroke and silent cerebral infarction (SCI) detected by CT and/or MRI were considered to be positive in the mean of having preoperative brain lesions. Although there was no significant difference between incidences of postoperative brain damage in true and dissecting aneurysms, registering 11% and 4% respectively, preoperative brain lesions in true aneurysm (68%) was significantly greater than dissecting aneurysm (32%). Furthermore, the incidence of postoperative brain damage was 22% in one-pump SCP which was significantly greater than 3% in two-pumps SCP in the patients with a true aneurysm. But there was no postoperative brain complication in patients with SCI even using either one two pumps for SCP. The present data suggest two-pumps SCP is better technique for cerebral protection compared to one-pump SCP for aortic arch repair.

Adult↗

Identification of heparin-binding sites in midkine and their role in neurite-promotion.

Midkine (MK) is a heparin-binding growth factor, which promotes neurite outgrowth in embryonic neurons and enhances their survival. The three dimensional structure of MK clarified by NMR spectroscopy indicates that several basic amino acids are exposed on the surface of the C-terminal half domain, which retains heparin-binding and neurite-promoting activity. We performed site-directed mutagenesis of these amino acids, and found that mutation of arginine78 reduced the heparin-binding activity. Mutation of either lysine83 or lysine84 scarcely affected heparin-binding activity, while the double mutant involving both lysine residues showed reduction in the activity. Neurite-promoting activity of mutant MKs always correlated with their heparin-binding activity, illustrating the close relationship of the two activities. Thus, the present result verifies the occurrence of two distinct heparin-binding sites involved in neurite-promoting activity of MK molecule.

Animals↗

Expression of inducible nitric oxide synthase in T lymphocytes and macrophages of cholesterol-fed rabbits.

While endothelial nitric oxide synthase has been reported to be expressed in the endothelial cells of normal and atherosclerotic vessels, there are few reports about inducible nitric oxide synthase (iNOS). We investigated the expression of iNOS and its relation to inflammatory cells in atheroma. New Zealand White rabbits were fed 1 of 4 diets: (i) normal diet for 9 weeks; (ii) normal plus 1% cholesterol diet (atherogenic diet) for 9 weeks; (iii) atherogenic diet for 9 weeks, then normal diet for 9 weeks; (iv) atherogenic diet for 9 weeks, then the normal diet for 36 weeks. The aortas were examined by immunohistochemical staining for anti-iNOS antibody, as well as antibodies for macrophages, T lymphocytes, and muscle actin. No iNOS was detected in normal aortas, intimal thickenings, or fatty streaks. Although iNOS was detected in necrotic cores of advanced plaque, it was not seen in smooth muscle-derived cells or endothelial cells but was found in some macrophage-derived cells and in T lymphocytes. In regressive atherosclerotic aortas, iNOS was detected only in necrotic cores, not in macrophage-derived cells but in T lymphocytes. These findings suggest that T lymphocytes and some macrophages induce iNOS through cytokine production in atheroma. This is the first report of iNOS expression in atheromatous plaque.

Animals↗

Characteristics of macrophage-derived foam cells isolated from atherosclerotic lesions of rabbits.

It is generally accepted that the foam cells in atherosclerotic lesions are derived mainly from monocytes/macrophages. We investigated whether the macrophage-derived foam cells, isolated from the atherosclerotic lesions of cholesterol-fed rabbits, would exhibit properties similar to those of blood monocytes in vitro and whether the cholesterol concentration of the macrophage-derived foam cells would decrease in the presence of an appropriate cholesterol acceptor in culture. We found that most (> 98%) of the foam cells isolated from atherosclerotic lesions were positive for anti-monocyte-macrophage antibody and nonspecific esterase. While almost all (> 98%) of the foam cells exhibited NaF-resistant, nonspecific esterase activity, the blood monocytes exhibited no such activity. Macrophage-derived foam cells contained larger amounts of cholesterol, most of it esterified, than the blood monocytes. Although blood monocytes exhibited a substantial amount of lysozyme, the freshly isolated, macrophage-derived foam cells showed no detectable lysozyme activity. The production of superoxide by macrophage-derived foam cells stimulated by PMA or opsonized zymosan was lower than that of stimulated monocytes. The cholesterol concentration of macrophage-derived foam cells decreased during five days of culture in the presence of an appropriate acceptor, such as normal and hypercholesterolemic rabbit serum and high density lipoprotein, although the rate of decrease was slow. Results suggest that macrophage-derived foam cells may be involved in both the progression and the regression of early atherosclerotic lesions.

Animals↗

Role of central neural mechanisms in the regulation of hepatic glucose metabolism.

Central monoamine neurotransmitters affect blood glucose homeostasis. Activation of central cholinergic, noradrenergic histaminergic, and serotonergic neurons rapidly increase hepatic glucose output via the sympathetic nervous system. Acute hyperglycemia is mediated by three distinct pathways: the action of epinephrine on the liver, the action of glucagon on the liver, and the direct innervation of the liver. The relative contribution of these factors to hyperglycemia can be altered by diet and the kinds of neurotransmitters evoked in the central nervous system, but the magnitude of epinephrine secretion is closely related to the magnitude of hyperglycemia. On the other hand, neuropharmacological stimulation of central cholinergic muscarinic receptors, histaminergic H1 receptors, and serotonergic 5-HT2 receptors increases hypothalamic noradrenergic neuronal activity, which is associated with hyperglycemia. In contrast, central GABAA receptors play an inhibitory role in the regulation of hepatic glucose metabolism. Thus, central monoaminergic neurons could be linked together, and play a homeostatic role in the regulation of hepatic glucose metabolism.

Animals↗

The beta adrenoreceptor antagonist, nipradilol, preserves the endothelial nitric oxide response in atherosclerotic vessels of rabbit.

We evaluated the effects of nipradilol, a beta-adrenoreceptor antagonist which contains a nitroxy residue, for vascular response in atherosclerosis of rabbits. Four groups of rabbits received different diets (standard diet; standard diet plus 10 mg/kg/day nipradilol; atherogenic diet [standard diet plus 1% cholesterol]; atherogenic diet plus 10 mg/kg/day nipradilol) for 9 weeks. Plasma lipids, blood pressure, vascular function, nitric oxide (NO), activity of NO synthase, cGMP, and histological atherosclerotic changes were evaluated. Neither the atherogenic diet nor nipradilol treatment affected significantly the animals' body weight, blood pressure, or heart rate. The atherogenic diet increased total cholesterol and triglycerides, which were not altered by nipradilol. The atherogenic diet diminished the acetylcholine-induced NO mediated relaxation. Nipradilol treatment restored this relaxation. Analyses using a NO-sensitive selective electrode showed that nipradilol released NO in the presence of cells and that NO release was greater in atherosclerotic aorta with than without nipradilol treatment. Nipradilol treatment increased the basal NO release as evaluated by the aortic tissue cyclic GMP (cGMP) levels in atherosclerotic vessel, and reduced the esterified cholesterol levels in atherosclerotic vessel. Conclusively, NO released by nipradilol may protect endothelium derived relaxation in atherosclerotic vessels, and may partially inhibit the accumulation of cholesterol in the atherosclerotic lesions.

Adrenergic beta-Antagonists↗

Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease.

The clinical pharmacokinetics of the cognitive enhancer, aniracetam (200 mg), was studied in elderly patients with cerebrovascular disease (CVD) and compared with those of young healthy volunteers. Six female hospitalized patients (mean age 84.5 years) were used in this study. The serum level of anisic acid and p-methoxyhippuric acid, major metabolites of aniracetam, reached a peak at 2 h after oral administration, and returned to basal level by 6 h. Mean creatinine clearance was 20-30 ml/min. The t1/2 of metabolites was increased by 4- to 7-fold in the elderly patients compared with young volunteers. This study showed that tmax, t1/2, and AUC were enlarged in the elderly; however, no clinical side effects were observed.

Adult↗

Possible involvement of catalase in the protective effect of interleukin-6 against 6-hydroxydopamine toxicity in PC12 cells.

We examined the effects of various neurotrophic factors and cytokines on 6-hydroxydopamine (6-OHDA)-induced toxicity in PC12 cells. Exposure of PC12 cells to 6-OHDA resulted in a concentration- and time-dependent cell death, as evidenced by the release of lactate dehydrogenase into the culture medium. Addition of catalase, but not superoxide dismutase, to the culture medium protected PC12 cells from the 6-OHDA-induced toxicity. Interleukin (IL)-6 provided a dose-dependent protection against the 6-OHDA toxicity, as did nerve growth factor (NGF). In addition, basic fibroblast growth factor and dibutyryl cyclic AMP partially protected PC12 cells from 6-OHDA toxicity. Neither IL-1alpha, IL-2, IL-4, transforming growth factor-beta, nor leukemia inhibitory factor had any effect. The protective effect of IL-6 was attenuated by 3-amino-1,2,4-triazole, an inhibitor of catalase. These results suggest that IL-6 may protect PC12 cells against the 6-OHDA toxicity by activating free radical detoxifying mechanisms, such as catalase activity.

Animals↗

Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group.

BACKGROUND: Radical nephrectomy is the standard therapy for low-stage renal cell carcinoma. However, recurrence sometimes develops even in patients who are considered to have undergone a curative resection of the primary tumor. The purpose of this study was to evaluate the usefulness of UFT (a 1:4 mixture of tegafur and uracil) adjuvant and the risk factors for recurrence in renal cell carcinoma. METHODS: A prospective randomized trial was conducted to compare the use of long-term oral UFT adjuvant with nonadjuvant therapy after a radical nephrectomy for Robson stage I or II renal cell carcinoma. A multivariate analysis was also performed to estimate the risk factors for recurrence. RESULTS: A total of 71 patients were entered into this study, and 66 were evaluable (33 for each group). There was no significant difference in patient characteristics between the 2 groups. The nonrecurrence rate at 5 years after a radical nephrectomy was 80.5% and 77.1% in the UFT adjuvant group and the nonadjuvant group, respectively, with a median follow-up of 112.9 months; the difference was not significant. The toxicity of UFT was generally mild and tolerable. The tumor grade was found to be an important factor influencing recurrence. CONCLUSION: UFT cannot be universally recommended as an adjuvant therapy for radical nephrectomy in all patients with low-stage renal cell carcinoma.

Antimetabolites, Antineoplastic↗

Significance of the preoperative intravesical instillation of doxorubicin and the oral administration of 5-fluorouracil in preventing recurrence after a transurethral resection of superficial bladder cancer. Kyushu University Urological Oncology Group.

BACKGROUND: The postoperative intravesical instillation of doxorubicin (ADM) has a preventative effect on recurrence after a transurethral resection (TUR) of superficial bladder cancer. However, the significance of preoperative ADM instillation remains unclear. Although the oral administration of 5-fluorouracil (5-FU) has been observed to show some clinical response against bladder cancer, its preventative effect on the recurrence of superficial bladder cancer after TUR is unknown. METHODS: Patients were randomized into 4 groups. All 4 groups received postoperative ADM instillation. In addition, patients in groups C and D received preoperative ADM instillation, whereas patients in groups B and D additionally received oral 5-FU postoperatively. The nonrecurrence rate and side effects were both compared among the 4 groups. RESULTS: Of the 282 patients registered, 200 were evaluable, with a median follow-up period of 21.4 months. There were no significant differences in the characteristics of the patients among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly longer disease-free interval than group A (postoperative ADM alone). However, there was no significant difference in the disease-free interval between groups A and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and postoperative ADM plus 5-FU). Bladder irritation symptoms were the most frequently noted side effect encountered in all groups, but the severity was generally mild. CONCLUSIONS: Preoperative ADM instillation was found to prevent recurrence to a greater extent than the usual postoperative instillation alone, whereas oral 5-FU was found to have no additional beneficial effect on the disease-free interval in patients with superficial bladder cancer.

Administration, Intravesical↗

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, affects the central nervous system to produce peripheral hyperglycemia in conscious rats.

To determine whether the nitric oxide (NO) system in the central nervous system (CNS) is involved in the peripheral metabolism of carbohydrate we injected NG-methyl-L-arginine (L-NMA), an inhibitor of NO synthase, into the third cerebral ventricle of unanesthetized, unrestrained rats and determined the plasma level of glucose. This intracerebroventricular (i.c.v.) injection of the drug increased the plasma level of glucose dose-dependently, whereas an intravenous (i.v.) injection had no effect. The hyperglycemia thus induced was suppressed by concomitant i.c.v. or prior i.v. administration of L-arginine. Concomitant administration of D-arginine did not affect hyperglycemia by L-NMA. The i.c.v. injection of 5 x 10(-6) mol L-NMA increased plasma levels of glucose, epinephrine and norepinephrine, and serum levels of glucagon. However, plasma levels of insulin were unchanged, despite the presence of hyperglycemia. The hyperglycemia produced by L-NMA was completely inhibited by bilateral adrenalectomy. It was also inhibited by prior intraperitoneal injection of phentolamine, but not of propranolol or naloxone. Results suggest that L-NMA acts on the CNS to stimulate adrenal secretion of epinephrine and, subsequently, to elevate glucose levels in the peripheral blood. The NO system thus seems to be involved in the neural regulation of the adrenal by the GNS, which in turn regulates peripheral blood glucose levels.

Adrenalectomy↗

Effect of estrogen on isoforms of nitric oxide synthase: possible mechanism of anti-atherosclerotic effect of estrogen.

While estrogen is known to prevent the development of atherosclerosis, the mechanism is not completely understood. We investigated the effects of superoxide dismutase, acetylcholine, and other compounds on the release of nitric oxide (NO) by measuring the relaxation responses of aortic rings, with and without intact endothelium, taken from rabbits under various experimental conditions. The aorta of female rabbits released a greater amount of NO than did that of oophorectomized females and male rabbits. The greater basal release of NO in female rabbits was decreased in animals with atherosclerosis induced by a high cholesterol diet. We also investigated the effect of estrogen on endothelial, neuronal and inducible NO synthase (NOS), NOS-3, NOS-1 and NOS-2, respectively. Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12) to 10(-8) M) over 8 h significantly enhanced the activity of NOS-3 in the endothelial cells of cultured human umbilical vein and bovine aortas. 17 beta-Estradiol also enhanced the release of NO from endothelial cells as measured by an NO selective meter and NO2-/N/3-, metabolites of NO. Western blot showed a similar effect of 17 beta-estradiol on NO. Estrogen increased NOS-3 via a receptor-mediated system. Low concentrations of 17 beta-estradiol (10(-10) to 10(-8) M) enhanced the activity of crude NOS-1 in the cytosolic fraction of rabbit cerebella. Partially purified NOS-1, obtained from the cytosolic fraction by DEAE column chromatography, had a similar response to estrogen. Estrogen at a low dose enhanced the fluorescence of dansyl calmodulin and augmented it in high doses. We also investigated the effect of estrogen on NOS-2. When J774 cells, a murine macrophage cell line, were incubated with interferon-r and lipopolysaccharide, NOS-2 was induced and a large amount of NO was released. Pre- or co-incubation of 17 beta-estradiol inhibited the induction of NOS-2 protein and NO release. The estrogen receptor antagonists, tamoxifen and ICI 182780, inhibited that effect of 17 beta-estradiol. 17 beta-Estradiol inhibited the induction of NOS-2 by a receptor-mediated system. These results may offer a new mechanism for the anti-atherosclerotic effect of 17 beta-estradiol.

Animals↗

Selective stimulation of granulopoiesis in vitro by established bone marrow stromal cells.

Bone marrow is a major granulopoietic organ whose hematopoietic microenvironment is comprised of stromal cells. In the present work, we examined the regulation of in vitro granulopoiesis with an established line of bone marrow stromal cells. In coculture of the progenitor cells on the particular stromal cell lines from bone marrow, large granulocyte (G) colonies consisting of over 200 cells were formed without G-CSF for 5 days. Stromal cells supported development of Gr-1 (granulocyte specific surface marker)-negative progenitors into Gr-1 and myeloperoxidase positive granulocytes. Seventy percent of the large G-colonies were formed on the stromal layers even in the presence of anti-G-CSF antibody, which indicates the G-CSF independent pathway of granulopoiesis. Inhibition of the large G-colony formation by the addition of anti-adhesion molecules, such as very late activation antigen-4 (VLA-4) and CD31 (PECAM-1), suggested the role of cell-to-cell adhesion in stroma-supported granulopoiesis.

Animals↗

Preoperative autologous blood donation and plateletpheresis in patients undergoing elective cardiac operations--factors that influence the need for homologous blood transfusion.

An increased awareness of the adverse effects of homologous blood transfusion prompted us to initiate a blood conservation program consisting of preoperative autologous blood donation and platelet-rich plasma-pheresis. We studied 120 patients who underwent elective cardiac surgery at Aomori General Hospital between January 1991 and September 1994. If their hemoglobin values exceeded 12 g/ml, 400 g of whole blood was drawn 3 times before the operation. Platelet-poor plasma was collected 10 days before the operation and platelet-rich plasma was collected the day before the operation. However, despite participation in this program, 42 of 120 patients (35%) required homologous blood transfusion perioperatively. Factors that influenced the need for homologous blood transfusion were identified retrospectively, with the following found to be significant by univariate analysis: operative procedures performed, cardiopulmonary bypass time, and the amount of autologous blood and autologous plasma donated. Although the effectiveness of our blood conservation procedure remains to be verified, it reduced the need for the transfusion of homologous blood. Thus, additional units of autologous blood are required to obviate the need for homologous transfusion in patients undergoing long cardiopulmonary bypass procedures.

Aged↗

The pressor response induced by repeated injections of neostigmine into the central nervous system is desensitized in adrenalectomized, but not in intact rats.

To investigate whether or not pressor responses to repeated stimulation of central cholinoceptive neurons are desensitized, mean arterial blood pressure (MAP) and heart rate (HR) were measured following repeated injections of neostigmine, an acetylcholinesterase inhibitor, into the third cerebral ventricle in conscious, unrestrained intact or adrenalectomized (ADX) rats. Neostigmine (5 x 10(-9) or 5 x 10(-8) mol) in 1 milliliter saline increased MAP dose-dependently and increased HR in intact rats. The peak values in MAP and HR after three repeated injections at 4 hour intervals did not wane. Neostigmine (5 x 10(-8) mol) also increased MAP in ADX rats, and the peak values after the first injection were higher in the ADX rats than in the intact rats. The pressor responses to the second and third injection, however, were less than to the first injection in the ADX rats. HR responses to the repeated injections in the ADX rats were identical to those in the intact rats. These findings suggest that the adrenal gland plays a role in antagonizing the development of desensitization in the neostigmine-induced pressor response.

Adrenalectomy↗