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Biomedical subjects

A Iguchi

Publications and source records attributed to A Iguchi.

At least 55 records · Page 3Linked to original sources

Vascular endothelial growth factor (VEGF) is one of the cytokines causative and predictive of hepatic veno-occlusive disease (VOD) in stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is one of the most serious complications in patients receiving stem cell transplantation (SCT). However, the cause of VOD remained to be elucidated. Vascular endothelial growth factor (VEGF) has been reported to have various physiological effects including neovascularization and acceleration of vasopermeability. Because we postulated that VEGF could be one of the causative factors in VOD after SCT, serum VEGF levels were measured by ELISA in 50 patients receiving SCT. Six of the patients showed typical manifestations of VOD and four of them died due to VOD. The mean maximum serum VEGF level in the six patients with VOD was markedly increased compared to that in the patients without VOD (P < 0.001) and in normal controls (P < 0.001). Moreover, the mean maximum serum VEGF level in patients with VOD before conditioning chemoradiotherapy for SCT was also high compared to patients without VOD (P = 0.0012) in the same period. Similarly, serum VEGF levels were significantly higher in patients whose plasma protein C activities decreased below 40% (P < 0.001). During the clinical course of VOD after SCT, the increase of serum VEGF synchronized fairly well with the development of VOD. Since VEGF causes the expression of tissue factor on circulating monocyte/macrophages and results in hypercoagulability, our observation suggests that in the patients with VOD who showed high serum VEGF it might account for the development of VOD. Furthermore, this observation may indicate a novel therapeutic strategy for prevention of VOD.

Adolescent↗

Successful management of secondary aortoesophageal fistula with graft infection.

A 60-year-old woman was transferred to our institution after massive hematemesis and the diagnosis of secondary aortoesophageal fistula was made. Five months previously, she had undergone graft replacement from the origin of the left subclavian artery to midthoracic aorta for chonic type B dissection. After an extraanatomic bypass was performed through a sternotomy, the infected thoracic aortic graft was resected through a left thoracotomy. She remained well without evidence of infection.

Aortic Dissection↗

HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxide.

Male rabbits fed a 0.5% cholesterol diet for 8 wk were divided into three groups. Group 1 was hypercholesterolemic; group 2 was fed a regular diet for an additional 12 wk; and group 3 was fed a regular diet with simvastatin (5 mg x kg(-1) x day(-1)). Simvastatin treatment reduced the atherosclerotic area and total and esterified cholesterol concentrations in the thoracic aorta. Tone-related basal nitric oxide (NO) release was highest in group 3. Acetylcholine-induced, NO-dependent relaxation was improved in group 3 compared with group 2. Amount of endothelial nitric oxide synthase (eNOS) mRNA in vessels increased in group 1, compared with normal aorta, and decreased in group 2; however, it did not decrease in group 3. The amount of O released from vessels increased in group 1 and group 2 compared with normal rabbits; however, it decreased in group 3, especially in the endothelial cells. Peroxynitrite determined by nitrotyrosine staining decreased in group 3. Additionally, the arteries of rabbits fed a regular diet with or without simvastatin were investigated. The aorta from simvastatin-treated group showed increase of tone-related basal NO release and eNOS mRNA and decrease of O release. Taken together, upregulation of eNOS and decrease of O treatment were observed in vivo in the process of the sufficient stabilization of atheroma following simvastatin.

Animals↗

Temporal effects of 17beta-estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells.

Endothelial nitric oxide synthase (eNOS) is regulated both by caveolin-1 and 17beta-estradiol (E(2)). Temporal relationships between effects of estrogen on caveolin-1 and nitric oxide (NO) are not known. Therefore, this study was designed to determine whether estrogen regulates caveolin-1 and, if so, whether such regulation corresponds to changes in nitrite/nitrate (NO(x)) production. Bovine aortic endothelial cells (BAECs) were cultured in the absence and presence of 17beta-estradiol or 17alpha-estradiol (10(-8) and 10(-10) M) for 12, 24, and 48 h. eNOS protein expression and NO(x) production increased significantly after 24 h but not after 12-h treatment with 17beta- and not 17alpha-estradiol. Both mRNA and protein for caveolin-1 were increased significantly only after 48-h treatment with E(2), but eNOS protein and NO(x) production were decreased compared with cells treated for 24 h. These increases in caveolin-1 were inhibited by the estrogen receptor antagonist ICI-182,780 (10(-6) M). Results of this study suggest that E(2) stimulates caveolin-1 transcription and translation through estrogen receptor-mediated mechanisms. The results further suggest that estrogen may indirectly regulate NO(x) through caveolin-1 expression, which inhibits eNOS catalytic activity.

Animals↗

Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation.

Diesel exhaust particles cause an impairment of endothelium-dependent vasorelaxation and are associated with cardiopulmonary-related diseases and mortality, but the mechanistic details are poorly understood. Since we reported previously that phenanthraquinone, an environmental chemical contained in diesel exhaust particles, suppresses neuronal nitric oxide synthase (nNOS) activity by shunting electrons away from the normal catalytic pathway, it was hypothesized that phenanthraquinone inhibits endothelial NOS (eNOS) activity and affects vascular tone. Therefore, the effects of phenanthraquinone on eNOS activity, endothelium-dependent relaxation, and blood pressure were examined in the present study. Phenanthraquinone inhibited NO formation evaluated by citrulline formed by total membrane fraction of bovine aortic endothelial cells with an IC(50) value of 0.6 microM. A kinetic study revealed that phenanthraquinone is a competitive inhibitor with respect to NADPH and a noncompetitive inhibitor with respect to L-arginine. Endothelium-dependent relaxation of rat aortic rings by ACh was significantly inhibited by phenanthraquinone (5 microM), whereas the endothelium-independent relaxation by nitroglycerin was not. Furthermore, an intraperitoneal injection of phenanthraquinone (0.36 mmol/kg) to rats resulted in an elevation of blood pressure (1.4-fold, P < 0.01); under this condition, plasma levels of stable NO metabolites, nitrite/nitrate, in phenanthraquinone-treated rats was reduced to 68% of control levels. The present findings suggest that phenanthraquinone has a potent inhibitory action on eNOS activity via a similar mechanism reported for nNOS, thereby causing the suppression of NO-mediated vasorelaxation and elevation of blood pressure.

Air Pollutants↗

VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor.

Although the accumulation of vascular endothelial growth factor (VEGF) has been observed in human atherosclerotic lesions, the exact role of this growth factor in atherogenesis remains unknown. We hypothesized that VEGF in the vascular wall might have a preventive effect on endothelial cell damage during atherosclerosis. To test our hypothesis, we examined whether VEGF protects against the toxicity of oxidized low density lipoprotein (Ox-LDL) in cultured endothelial cells derived from bovine aortas (BAECs). Preincubation of BAECs with VEGF prevented Ox-LDL-induced toxicity in a preincubation time- and VEGF concentration-dependent manner. Addition of N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not reverse the protective effect of VEGF on Ox-LDL toxicity. Incubation of BAECs with VEGF increased intracellular glutathione (GSH) content in a time-dependent manner. Combined addition of VEGF and L-buthionine sulfoximine, a GSH synthesis inhibitor, reversed both GSH levels and the protective effect of VEGF on Ox-LDL-induced cytotoxicity. Placenta growth factor, which ligates to the VEGF Flt-1 receptor but not KDR/Flk-1, failed to prevent Ox-LDL toxicity and had no effect on intracellular GSH levels. An anti-KDR antibody completely blocked these beneficial activities of VEGF. These results suggest that VEGF prevents Ox-LDL-induced endothelial cell damage via an intracellular GSH-dependent mechanism through the KDR/Flk-1 receptor.

Animals↗

[A survey on how medical student consider end-if-life care in the elderly].

We examined the way medical students think about end-of-life care in the elderly by a questionnaire survey. The major variables of the evaluation instrument included the students' idea of the special nature of end-of-life care for the elderly, the necessity for disclosure of the name of disease, consideration for patient's age on disclosure, advance directives concerning their life-sustaining treatment, and communication concerning preferences for end-of-life care. The final items on the instrument asked for student comments about end-of-life care in the elderly. We analyzed this qualitative data using the process of immersion/crystallization. We received 95 responses, and of these 65 (68%) provided written commentaries that were analyzed using qualitative techniques. Fifty-nine (62%) students pointed out the special nature of end-of-life care in the elderly and most of them (96%) needed the disclosure of the name of disease. Fifty-two (55%) students agreed with advance directives for end-of-life care and 88 (93%) students pointed out the importance of communication with regard to patients' preferences. Medical students' concerns about end-of-life care in the elderly related to three major domains: 1) patient-physician relationship; 2) the procedures of end-of-life care; and 3) emotional and intuitive comments. These results suggest that in the education of geriatric medicine the patient-physician's relationship about end-of-life care is important and we may need to introduce systematic lectures and practical training.

Aged↗

[Questionnaire survey comparing first-year medical students and non-medical students with regard to their level of interest and knowledge of care and terminal care for the elderly].

To study the level of interest and knowledge about care and terminal care for the elderly of medical students in Nagoya University, we made a questionnaire for first-year medical students (about 90 students per year) each April from 1998 to 2000. To assess the differences, we also gave the same questionnaire to 75 first-year non-medical students in 1999. Only about 10% of students had experienced providing care for member(s) of their family, but about one third stated that other family member(s) such as their mother, cared for older family member(s). The introduction of long-term care insurance was known by 22%, 43.5% and 96.6% of medical students in 1998, 1999 and 2000, respectively. Moreover, 19.8%, 13.0% and 52.3% of medical students knew about the care managers, respectively. About 80% of students hoped to be informed about their disease if they had terminal-stage cancer. However, about half of students could not decide whether to tell a family member who had terminal-stage cancer. Medical students had significantly more interest in the care system (68.5% in 1999) and terminal care (72.8% in 1999) for the elderly than non-medical students (41.3% and 40.0% in 1999, respectively). There were no significant differences between medical and non-medical students with regard to experiences of care, knowledge of long-term care insurance system and the attitudes to informing about terminal-stage cancer. However, more medical students had an interest in the elderly care system and terminal care than non-medical students.

Adult↗

[Cognitive function and brain atrophy in elderly type 2 diabetic patients in comparison with non-diabetic elderly subjects].

Previous studies have suggested that type 2 diabetic mellitus could lead to learning and memory deficits. We studied cognitive function tests and brain computed tomography (CT) findings in elderly subjects with drug-treated type 2 diabetic patients (n = 9), diet-treated type 2 diabetic patients (n = 8) and nondiabetic subjects (CR, n = 21). A battery of cognitive function tests (Cog-T; WAIS-R's digit span test and symbol test, Stroop Test, ADAS's verbal memory test, and MMSE) was carried out on two occasions, separated by at least 6 months. Brain CT was analyzed by the following 5 variables; 1) Evan's Ratio, 2) Inverse Cella Media Index, 3) maximum width of the third ventricle, 4) maximum width of temporal horn tips on both sides and 5) maximum width of the Sylvian fissure at the insula, bilaterally. The scores of Cog-T did not differ significantly between the groups. On brain CT measurements, maximum width of the temporal horn tips on right side were significantly different in the three groups (ANOVA, P = 0.035). The drug-treated diabetics subjects had wider temporal horn tips on the right side than did the diet treated diabetics and nondiabetic subjects (Fisher's post hoc test, P = 0.030, P = 0.016).

Aged↗

[Factors contributing to dying at home in elderly patients who received home care service].

This study examine whether around-the-clock medical support is a contributing factor to dying at home, and also tried to identify other such factors. Visiting nursing records of 81 elderly patients who died at home or in hospital after receiving home care at two facilities, one with and one without 24-hour medical support respectively were examined retrospectively. The subjects were divided into two groups: those who died at home and those who died in a hospital or nursing home. The two groups were compared in terms of clinical and sociodemographic characteristics and preferences for dying at home, expressed by patients, families and medical staff. Those who died at home showed a significantly higher rate of total dependence (84.6% vs. 48.1%) at month before death. Dying at home was significantly more preferred by all patients, families and medical staff. The major reason for hospitalization was rapid deterioration of the patients' condition. The facility with around-the-clock medical service had a higher rate of dying at home (42% vs. 27%, p = 0.18). Also, patients, families, and medical staff associated with their facility showed a higher preference for dying at home. We concluded from the above that the contributing factors for dying at home are: 1) total dependence level of ADL at one month before the death, and 2) preference for dying at home expressed by the patient, family and medical staff. This study suggests 24-hour medical support should be a requirement for in-home terminal care. Supporting advice from the staff to the family seems to be another contributing factor.

Aged↗

[Aortic root replacement after operation for the ascending aorta and/or aortic valve].

We reviewed ten cases who underwent aortic root replacement after operation for the ascending aorta and/or aortic valve. As initial operation, aortic valve replacement (AVR) was performed in five patients, replacement of the ascending aorta in two, original Bentall operation in two, and entry closure and suspension of the aortic valve in one. At reoperation, three patients were diagnosed as aneurysm of the ascending aorta, two were annulo-aortic ectasia, and one was acute aortic dissection, chronic dissecting aneusym, pseudoaneurysm of the ascending aorta, prosthetic valve endocarditis, and massive aortic regurgitation. Aortic root replacement was performed using mechanical valved composite graft in all cases. One patient who underwent repeat aortic root replacement for prosthetic valve endocarditis was died of septemia and ventricular fibrillation. Five patients had nine complications (two low output syndrome, respiratory failure and cerebral infarction, one gastrointestinal bleeding, septemia and ventricular fibrillation). In conclusion, aortic root replacement after operation for the ascending aorta and/or aortic valve was performed with acceptable morbidity and mortality.

Adult↗

[Efficacy of modified ultrafiltration in reoperation for valvular disease].

We evaluated the efficacy of modified ultrafiltration (MUF) in reoperation for valvular disease. Fourteen patients were divide into two groups consisting of a control group (n = 6) and a MUF group (n = 8). MUF was carried out for fifteen minutes immediately after the completion of cardiopulmonary bypass. The blood flow through the ultrafilter was 300 ml/min and about 1,200 ml of water was removed. The hematocrit elevated significantly from 25% to 31% in the MUF group (p < 0.05). The percentage of the increase in body weight after the operation in the MUF group was significantly less than that in the control group (3.3 +/- 3.1% vs 8.3 +/- 4.3%, p < 0.05). The PaO2/FIO2 after the operation in the MUF group was significantly higher than that in the control group (376 +/- 125 mmHg vs 242 +/- 79 mmHg, p < 0.05). The duration of mechanical ventilation in the MUF group was significantly less than that in the control group (1.1 +/- 1.1 days vs 5.3 +/- 3.3 days, p < 0.05). In conclusion, MUF is useful to hemoconcentrate, reduce postoperative body weight gain and promote early recovery of pulmonary function in reoperation for valvular disease.

Aged↗

[Efficacy of modified ultrafiltration in coronary artery bypass grafting].

We evaluated the efficacy of modified ultrafiltration (MUF) in coronary artery bypass grafting. Twenty patients were divide into two groups consisting of a control group (n = 11) and a MUF group (n = 9). MUF was carried out for fifteen minutes immediately after the completion of cardiopulmonary bypass. The blood flow through the ultrafilter was 300 ml/min and about 1,200 ml of water was removed. The hematocrit elevated significantly from 25% to 30% in the MUF group (p < 0.01). Postoperative blood loss in the first 24 hours in the MUF group was significantly less than that in the control group (8 +/- 2 ml/kg vs 12 +/- 4 ml/kg, p < 0.01). There was no statistical difference in the percentage of the increase in body weight after the operation, inflammatory reaction and pulmonary function (A-a DO2, PaO2/FIO2 and duration of intubation) between two groups. In conclusion, MUF is useful to hemoconcentrate and reduce postoperative blood loss in coronary artery bypass grafting.

Aged↗

Noninvolvement of hypertriglyceridemia and hyperleptinemia in blood pressure increases induced by dietary lard in rats.

We investigated whether hypertriglyceridemia and hyperleptinemia are involved in the development of increases in blood pressure induced by dietary lard. Rats received either chow alone or chow in which 50% of the energy content was from substituted lard. Each group was divided into two groups according to whether the diet included bezafibrate or not. In another series of experiments, rats were fed either chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil, or sucrose. Systolic blood pressure (SBP) was measured every week during each 7-week feeding period. A steady-state plasma glucose method was used to determine insulin sensitivity after lard substitution with or without bezafibrate. After the 7-week feeding period, the plasma levels of glucose, immunoreactive insulin, triglyceride and leptin were measured. In rats fed with a high lard diet, SBP, plasma levels of immunoreactive insulin, triglyceride, leptin and steady-state plasma glucose concentrations significantly increased, compared with levels of these substances in controls. Bezafibrate treatment completely reversed these effects. In rats fed with a high safflower oil or a high sucrose diet, no significant change was seen in SBP and plasma immunoreactive insulin levels. However, the plasma triglyceride levels were increased by dietary lard or sucrose. Moreover, the plasma leptin level was also increased by dietary lard and safflower oil. Neither dietary hypertriglyceridemia nor hyperleptinemia were involved in the development of increases in blood pressure induced by dietary lard.

Adipose Tissue↗

Rise in plasma leptin levels after stimulation of hypothalamic cholinoceptive neurons by neostigmine in rats.

To investigate the role of hypothalamic cholinergic neurons in the regulation of plasma leptin levels, we injected neostigmine, a cholinesterase inhibitor, or vehicle alone into the third cerebral ventricle in free moving male Wistar rats and then measured plasma leptin levels. The administration of neostigmine (5 x 10(-9) or 5 x 10(-8) mol) increased plasma leptin levels 3-6 h after stimulation in a dose-dependent manner, while intravenous injection of neostigmine (5 x 10(-8) mol) had no effect. Atropine (5 x 10(-8) mol) concomitantly injected with neostigmine (5 x 10(-8) mol) prevented neostigmine-induced increase in plasma leptin. The expression of leptin messenger ribonucleic acid (mRNA) in epididymal white adipose tissue was significantly increased at 4 and 6 h after neostigmine injection compared with that before the injection. Plasma levels of corticosterone were significantly increased at 30 min after stimulation with neostigmine and this increase was sustained for 6 h after stimulation. Furthermore, bilateral adrenalectomized rats showed no increase in plasma leptin levels after stimulation. In conclusion, stimulation of hypothalamic cholinoceptive neurons increased plasma leptin levels in rats by increasing leptin production in adipocytes. This increase may be due to an increase in glucocorticoids from the adrenal glands. These results suggest that plasma leptin levels can be regulated by hypothalamic cholinoceptive neurons.

Adipocytes↗