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Biomedical subjects

K Fukushima

Publications and source records attributed to K Fukushima.

At least 235 records · Page 13Linked to original sources

Leukocyte-endothelium interaction in the rat mesenteric microcirculation during halothane or sevoflurane anesthesia .

BACKGROUND: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules. METHODS: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins. RESULTS: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29. CONCLUSIONS: Halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion: P-selectin upregulation plays a crucial role in leukocyte rolling and adhesion during sevoflurane anesthesia, whereas low-flow perfusion is likely to evoke ICAM-1-dependent leukocyte adhesion during halothane anesthesia.

Anesthetics, Inhalation↗

Quantitative analysis of cyclin D1 messenger RNA expression in head and neck squamous cell carcinomas.

Cyclin D1 is thought to play a critical role in the G1/S phase transition of the cell cycle. Amplification of this gene has been reported in several types of human neoplasms including breast, lung, esophageal, and head and neck tumors. In this study, we have analyzed the relative level of expression of cyclin D1 messenger RNA (mRNA) in fresh specimens of head and neck squamous cell carcinoma (HNSCC), and investigated the concordance of the overexpression of cyclin D1 mRNA with gene amplification. Levels of cyclin D1 mRNA were analyzed by a modified method of competitive reverse transcription-polymerase chain reaction and levels of cyclin D1 gene amplification were evaluated by Southern blot hybridization in a series of 23 matched normal mucosas and HNSCC. Overexpression of cyclin D1 mRNA was observed in 10 of 23 cases (43.5%) of HNSCC, ranging from 2 to 50-fold higher than the normal control. Twelve of 23 cases could be evaluated by Southern blot hybridization, and gene amplification was found in only 2 of 12 cases (16.7%). These findings suggest that cyclin D1 plays an important role in tumorigenesis of HNSCC, and gene amplification is not one of the major mechanisms for overexpression of cyclin D1.

Aged↗

Paracentric inversion of chromosome 9 with schizoaffective disorder.

A 36-year-old man with schizoaffective disorder was found to have a de novo 46 XY inv (9) (q31.2q34.3). Phenotypical abnormalities are short stature, depressed nasal bridge, hypertelorism and slender shoulders. Paracentric inversion of chromosome 9 is a rare chromosome aberration. This case suggests a new candidate region related to schizoaffective disorder.

Adult↗

Butyric acid-induced apoptosis of murine thymocytes, splenic T cells, and human Jurkat T cells.

The purpose of this study was to examine the effect of butyric acid, an extracellular metabolite from periodontopathic bacteria, on apoptosis induction in murine thymocytes, splenic T cells, and human Jurkat T cells. Butyric acid significantly suppressed T-cell viability in both a concentration- and time-dependent fashion. The results of DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in thymocytes (with 1.25 mM butyric acid and 6 h after treatment) and in splenic T cells and Jurkat cells (with 2.5 mM butyric acid and 16 h after treatment). Incubation of thymocytes or Jurkat cells with 5 mM butyric acid for 21 h resulted in the typical ladder pattern of DNA fragmentation. Furthermore, Jurkat cells treated with 5 mM butyric acid showed the characteristic pattern of apoptotic cells such as chromatin condensation and hypodiploid nuclei. Experiments with fractionated subpopulations of splenic T cells revealed that DNA fragmentation was predominantly observed in CD4+ T cells. Butyric acid-induced apoptosis of thymocytes was decreased by the protein kinase inhibitors H7 and staurosporine. These inhibitors were less effective with similarly treated splenic T cells and Jurkat cells. These data suggest that butyric acid, one of the volatile fatty acids produced by periodontopathic bacteria and one that easily penetrates the oral mucosa, can modulate the immunoregulatory cell population in periodontal tissue by inducing T-cell death through apoptosis.

Animals↗

Delayed improvement of autonomic nervous abnormality after the Maze procedure: time and frequency domain analysis of heart rate variability using 24 hour Holter monitoring.

OBJECTIVE: To analyse heart rate variability in patients with atrial fibrillation after the Maze procedure, to investigate whether the procedure damages the cardiac autonomic fibres supplying the sinus node. DESIGN AND PATIENTS: Time and frequency domain analyses of RR variability were performed using 24 hour Holter monitoring one month after surgery in 12 patients with atrial fibrillation who underwent the Maze procedure (Maze group) and in seven patients who underwent cardiac surgery without the Maze procedure (control group). Mean RR intervals (mRR) and the standard deviation of successive RR intervals (SDRR) were determined by time domain analysis, and high frequency (HF), low frequency (LF), and total power (TP) spectral components of RR variability were calculated by frequency domain analysis. Holter monitoring was also performed at six and 12 months after cardiac surgery in the Maze group. RESULTS: Circadian variation (mean (SD)) in mRR (daytime to night time difference: 119 (60) v 302 (143) ms), SDRR (daytime: 8.4 (3.3) v 37.0 (12.0) ms), TP (daytime: 46.7 (16.0) v 171.8 (30.4) ms), HF (daytime: 19.6 (9.9) v 36.7 (7.1) ms2), and LF/HF (daytime: 0.31 (0.07) v 1.18 (0.46)) was decreased in the Maze group at one month compared with the control group (p < 0.01), but showed improvement at six and 12 months (p < 0.05). CONCLUSIONS: Surgery combined with the Maze procedure markedly suppressed the circadian variation of heart rate over a 24 hour period within one month after surgery, mainly because of damage to the innervation of the sinus node. However, at six and 12 months there was restoration of circadian variation, probably as the result of reinnervation of the sinus node.

Analysis of Variance↗

Usher's syndrome type IC: clinical studies and fine-mapping the disease locus.

Usher's syndrome type I is a heterogeneous group of diseases characterized by severe to profound sensorineural hearing loss, absent vestibular function, and progressive pigmentary retinopathy. Other identifying clinical features have not been documented. In this study, we examined olfactory acuity, plasma levels of polyunsaturated fatty acids and sarcosine, and cilia ultrastructure in a homogeneous cohort of patients with Usher's syndrome type IC. The normal age-dependent decline in olfactory acuity was observed, and normal plasma levels of polyunsaturated fatty acids and sarcosine were found. However, the incidence of compound cilia in biopsies from the inferior turbinate was significantly higher than that reported in control populations. By reconstructing haplotypes in affected persons. D11S902 and D11S1310 were identified as flanking markers over an interval that contains a candidate gene, KCNC1. No mutations in the coding sequence of this gene could be demonstrated in affected persons.

Adolescent↗

Colocalization of 11 beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia.

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) has been shown to confer specificity on mineralocorticoid receptors (MR) by inactivating glucocorticoids. In the present study we examined the colocalization of 11 beta HSD2 and MR in various exocrine and secretory glands by immunostaining of serial mirror tissue sections with subsequent computerized image analysis. Both 11 beta HSD2 and MR proteins were expressed in the same cells in the distal convoluted tubules, Henle's loop, and collecting tubules of the kidney and the absorptive epithelia of duodenum, jejunum, ileum, colon, and excretory ducts of anal and esophageal glands. Significantly, 11 beta HSD2 and MR immunoreactivity also colocalized in the respiratory tract, in collecting ducts of the tracheal and bronchial glands, ciliated bronchial epithelial cells, and type II alveolar epithelial cells, suggesting important and unexpected roles for mineralocorticoids in the lung. In the skin, 11 beta HSD2 and MR were present only in excretory ducts of eccrine sweat glands, but not in sebaceous or apocrine glands. In eccrine glands, MR immunoreactivity was present in the basal cells of excretory ducts, while 11 beta HSD2 immunoreactivity was localized in the luminal cells. Neither 11 beta HSD2 nor MR proteins were expressed in the lacrimal gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, or ureter. These results indicate that 11 beta HSD2 protein colocalizes with MR protein in the great majority of sodium-transporting epithelia involved in serous secretion and supports the proposal that 11 beta HSD2 is a pivotal determinant of mineralocorticoid receptor occupancy in man. Furthermore, our demonstration of colocalization in discrete areas of the lung suggests that mineralocorticoid agonists or antagonists, and/or inhibitors of 11 beta HSD2, may have unexpected applications in respiratory disease.

11-beta-Hydroxysteroid Dehydrogenases↗

Relationship between the metabolic chiral inversion and chemical structure of 4-phenyl-4-oxobutanoic acids, derivatives of anti-rheumatic agent KE-298.

The relationship between metabolic chiral inversion and chemical structure of various 4-phenyl-4-oxobutanoic acids (4-OBA), derivatives of anti-rheumatic agent KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid], was investigated in rats. Chiral inversion occurred with the thio-alkyl group, whereas the thio-acyl group played no role in the inversion of 4-OBA. A 2-methylene moiety was required for the inversion. When the 4-carbonyl moiety was removed, chiral inversion was significantly decreased, which provided an affinity for the intramitochondrial medium chain fatty acid CoA ligase. In addition, the distance between the chiral center and the carbonyl moiety was also an important factor for chiral inversion. While a sulfur atom was not indispensable for the chiral inversion, the existence of the sulfur atom influenced its affinity to the long chain fatty acid CoA ligase.

Animals↗

Effects of a novel potent aldose reductase inhibitor, GP-1447, on aldose reductase activity in vitro and on diabetic neuropathy and cataract formation in rats.

GP-1447 {3-[(4,5,7-trifluorobenzothiazol-2-yl) methyl]-5-methylphenylacetic acid}, a novel aldose reductase (AR) inhibitor, exhibited highly potent and specific inhibition of AR activity from human placenta, human muscle, porcine and rat lens with IC50 values ranging from 3 to 10 nM. Lineweaver-Burk plots revealed non-competitive inhibition between DL-glyceraldehyde or beta-NADPH and inhibition of AR by GP-1447. In contrast to epalrestat, AR activity inhibited by GP-1447 did not recover after dialysis for 24 hr. Administration of GP-1447 to streptozotocin (STZ)-induced diabetic rats for 5 days beginning 1 week after STZ injection effectively inhibited the accumulation of sorbitol in the sciatic nerve, lens and retina with ED50 values of 0.25, 1.6 and 2.9 mg/kg/day, respectively. The motor nerve conduction velocity (MCV) in STZ-induced diabetic rats was significantly decreased 4 weeks after the induction of diabetes. Treatment with GP-1447 for the following 2 weeks dose-dependently restored the decreased MCV with an ED50 value of 0.28 mg/kg/day. Administration of GP-1447 (3 and 15 mg/kg/day for 12 weeks beginning 3 days after STZ injection) completely prevented cataract formation and was accompanied by marked inhibition of sorbitol accumulation in the lens. Furthermore, partial reversibility of cataract formation and morphological changes of the lens was observed in diabetic rats treated with 15 mg/kg/day of GP-1447 for 5 weeks beginning 8 weeks after the induction of diabetes. From these results, GP-1447 would be expected to exert potent ameliorating effects on some diabetic complications. Potent inhibition of cataract formation will be one of the characteristics of this compound.

Aldehyde Reductase↗

[The effect of cerebral perfusion pressure on cerebral blood flow in the rhesus monkey during sevoflurane anesthesia].

The effect of cerebral perfusion pressure on cerebral blood flow (CBF) was studied under the normocapnic condition in the rhesus monkey under sevoflurane anesthesia. CBF was measured by means of positron emission tomography technique. After the measurement of CBF at 0.5% sevoflurane as control, the measurement was repeated at 2.0% sevoflurane (1 MAC), when blood pressure was kept at a half of the control value. The measurement was also repeated at the same sevoflurane concentration, when the mean blood pressure was restored with the infusion of angiotensin II. Average CBF as well as regional CBFs were compared between two different mean blood pressures at 2.0% sevoflurane. Average CBF increased significantly (+35%), when the mean arterial pressure was increased by the angiotensin II infusion. All the regional CBFs except at frontal cortex increased significantly (+ about 30%) in response to the increase in the mean arterial pressure. The increase in occipital CBF was greatest (+52%). We conclude that CBF during sevoflurane anesthesia up to 2.0% might become dependent on the cerebral perfusion pressure, indicating the compromised autoregulation of CBF in the rhesus monkey.

Anesthesia, Inhalation↗

[Effects of halothane and sevoflurane on reversal of neuromuscular blockade induced by vecuronium in man].

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.

Adult↗

[The effect of sevoflurane on regional cerebral metabolism and cerebral blood flow in rhesus monkeys].

The effects of sevoflurane on cerebral metabolism and hemodynamics were studied in rhesus monkeys. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR O2) as well as their regional changes were measured by means of positron emission tomography technique. After the measurement of regional CBFs and CMR O2s at 1.5% sevoflurane as control, the measurement was repeated at 3.0% sevoflurane and at the same sevoflurane concentration with the infusion of angiotensin II to restore mean arterial pressure. Regional CBFs and CMR O2s were compared among three different conditions. At 3.0% sevoflurane, regional CBFs increased significantly in response to the increase in the mean arterial pressure, suggesting the inhibition of autoregulation of CBF. However, regional CBF/CMR O2 ratio was not significantly different among the cerebral regions with each condition. It could be concluded that CBF during sevoflurane anesthesia up to 3.0% might become dependent on the cerebral perfusion pressure and the changes in regional CBFs varied among the regions. On the other hand, the ratio of oxygen consumption and delivery was well maintained throughout the brain regions.

Anesthesia, Inhalation↗

[Lung volume reduction surgery for pulmonary emphysema--report of two cases].

Lung volume reduction surgery (LVR) was practiced in 2 male patients with pulmonary emphysema to improve pulmonary function. On admission, they complained of exertional dyspnea (Grade III of the Hugh-Jones dyspnea scale). Computed tomographic scan (band display) revealed emphysematous changes throughout both lung fields, especially in bilateral upper lobes. Nuclear lung perfusion scintigraphy showed markedly diminished blood flow in both upper lobes. The bilateral upper lobes of each patient were excised through median sternotomy using the linear stapling device. The staple lines were buttressed with bioabsorbable polyglycolic acid fabric. At 1 month after LVR, the forced expiratory volume in 1 second improved, respectively, from 0.51 L to 1.27 L (Case 1) and from 0.68 L to 0.85 L (case 2). In conclusion, LVR was useful to improve pulmonary function of the patients with pulmonary emphysema.

Aged↗

[Preventive use of diltiazem to suppress supraventricular tachyarrhythmia in the patients after esophagectomy].

We investigated the efficacy of preventive use of diltiazem to suppress supraventricular tachyarrhythmia such as paroxysmal atrial tachycardia (PAT) and atrial fibrillation (Af) in the patients who underwent transthoracic esophagectomy. We divided 52 patients into 2 groups; the diltiazem group (n = 26) and the control group (n = 26). In the diltiazem group continuous intravenous infusion of diltiazem (1-3mcg.kg-1.min-1) was started when the patient's heart rate remained over 110.min-1 without any predisposing factor. On the other hand, in the control group we did not use it preventively. In both groups, we did not restrict the use of antiarrhythmic agents if necessary. We recognized PAT or Af in the control group (54%) more often than in the diltiazem group (19%). PAT or Af seldom occurred after the 4th post-operative day in the both groups. Serum diltiazem concentrations of 9 patients after about 10 hours infusion showed great variation (between 30 and 250 ng.ml-1). In 7 of them the diltiazem concentration increased as the duration of infusion was prolonged. However, we did not observe bradyarrhythmia. We consider that the continuous diltiazem infusion is effective in suppressing supraventricular tachyarrhythmia after esophagectomy.

Aged↗

[Minimally invasive technique for mitral valve repair--the importance of intraoperative transesophageal echocardiography].

A 65-year-old male with mitral regurgitation was scheduled for the mitral valve repair by means of minimally invasive technique. The technique, which requires a 10-cm right parasternal incision, offers minimal discomfort, less postoperative pain, quick functional recovery and excellent cosmetic healing. However, the intraoperative monitoring by the transesophageal echocardiography was required to evaluate the mitral valve function and to confirm the complete removal of air from the apex of the left ventricle and right upper pulmonary vein due to the small operative field. In addition, the monitoring of the short-axis view of the left ventricle makes it possible to evaluate and to confirm the preload and the left ventricular contractility. We considered that the transesophageal echocardiography is essential and useful for the minimally invasive mitral valve repair.

Aged↗

[Heart rate changes in propofol anesthesia--relation with excitatory movements].

Acceleration of heart rate simultaneously with excitatory movements was observed during anesthesia with propofol in four patients. Anesthesia was induced with propofol 2.5 mg.kg-1 i.v. and maintained with propofol 10 mg.kg-1.hr-1 i.v. About ten minutes after the induction, the patients showed jerking movements such as pronation or flexion of their arms, and/or plantar flexion. These movements lasted one or two seconds and appeared two or three times a minute. Three patients received vecuronium 0.1 mg.kg-1 and even after muscular relaxation acceleration of heart rate persisted. In one of two patients who had received midazolam 0.8 mg.kg-1, heart rate acceleration ceased. In one patient acceleration of heart rate and excitatory movements stopped after reducing the infusion rate of propofol from 10 mg.kg-1.hr-1 to 3 mg.kg-1.hr-1. Another patient with no involuntary movements showed no heart rate changes. These results suggest that heart rate acceleration in four patients was closely related to excitatory movements caused by propofol. As it was not influenced by muscular relaxation, heart rate monitoring would be useful to detect latent excitatory movements under muscular relaxation.

Adult↗