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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 73 records · Page 4Linked to original sources

Analysis of class II genes of human leukocyte antigen in patients with moyamoya disease.

Moyamoya disease is a progressive steno-occlusive disease at the terminal portion of the bilateral internal carotid arteries. An unusual vascular network is formed as a result of ischemic change of cerebrovascular system. Although some investigations suggested possible etiological factors of Moyamoya disease, the etiology is still unknown. To elucidate the genetic factors of Moyamoya disease, class II genes of human leukocyte antigen (HLA) were analyzed at the DNA level. The DNA typing of HLA was performed in the unrelated Japanese patients with definite Moyamoya disease using extracted genomic DNA from the leukocyte. The genotype was confirmed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) technique. The class II genotypes were analyzed in 71 samples. As a result, several alleles of class II genes showed significant association with Moyamoya disease. DQB1*0502 had positive association with the disease. On the other hand DRB1*0405 and DQB1*0401 had negative association. Moyamoya disease seems to have a genetic background in its etiology because certain alleles of HLA are associated with Moyamoya disease.

Alleles

'Angiographic moyamoya' its definition, classification, and therapy.

Are there any differences between probable Moyamoya disease and unilateral Moyamoya disease? What kinds of differences exist between definite and probable Moyamoya disease? Furthermore, according to the diagnostic criteria of Moyamoya disease, patients with systemic disorders and angiographic features similar to those of Moyamoya disease can not be diagnosed as Moyamoya disease. How should we call these? Such patients have been reported as 'Moyamoya syndrome,' 'quasi-Moyamoya disease', 'akin-Moyamoya disease'. etc. These variations of terminology including unilateral or probable Moyamoya disease have thus led to as state of confusion. In this study the previously reported cases in the literature were surveyed to clarify how these terms have been used and how we should use them correctly in the future. Since the diagnostic criteria of this disease are mainly based on angiographic findings, the term Moyamoya 'syndrome' should not be used. A unilateral involvement without any known cause should be called 'probable.' Because some systemic diseases commonly associated with Moyamoya disease might be genetically linked, it is better to avoid using such vague expressions as 'quasi', 'akin', or 'pseudo.' There might be a coexistence of two diseases. It is therefore better to simply state that the angiographic findings are similar to Moyamoya disease, or a systemic disease with 'angiographic Moyamoya' until the etiology of the Moyamoya disease is clarified.

Cerebral Angiography

Clinical features of probable moyamoya disease in Japan.

To clarify the current clinical features of probable Moyamoya disease in Japan, 180 cases were analyzed based on the cases collected by the Research Committee on Spontaneous Occlusion of the Circle of Willis of the Ministry of Health and Welfare, Japan. Although the age distribution patterns of probable Moyamoya disease showed two peaks similar to that of definite cases, the pattern shifted to the right thus indicating a reversed children versus adult ratio. The female/male ratio was 1.65, which was not significantly different from that observed in definite cases. The family occurrence rate was 6.7%. The incidence of cerebral infarction and bleeding in probable cases was higher than that in definite cases. The incidence of hemorrhage was higher in females than in males. Angiographically probable cases were at earlier stages in comparison to definite cases. The rebuild-up phenomenon in electroencephalograms was less detectable than in definite cases. Surgical procedures were performed in 63.3% of all cases and approximately 81% of them underwent bypass surgery. Single encephalo-duro-arterio-synangiosis, direct bypass and combined bypass procedures were performed in 35, 40 and 25% of all surgical cases, respectively. Although the incidence of bleeding was higher in the probable cases, the outcomes of the patients were similar to that of the definite cases except for mortality. Approximately 7% of the probable cases developed into definite type within an average 6.6 year follow-up period. The majority of probable Moyamoya disease cases thus seems to have somewhat different clinical characteristics from the definite disease cases.

Adolescent

Cerebral hemodynamics and metabolism in moyamoya disease--a positron emission tomography study.

We studied the cerebral blood flow (CBF), cerebrovascular response to hypercapnia, oxygen extraction fraction (OEF), metabolic rate for oxygen (CMRO2), blood volume (CBV) and transit time (TT: CBV/CBF) in Moyamoya disease using positron emission tomography (PET). The subjects consisted of 23 patients with Moyamoya disease, including eight pediatric and 15 adult patients. Among them, ten patients were examined both before and after surgery. The pediatric patients showed a marked increase in the CBV and a prolonged TT, especially in the striatum. The adult patients also showed a prolonged TT, but it was less prominent than that observed in pediatric patients, while the CBF remained at the level of the normal controls. The cerebrovascular response to hypercapnia was markedly impaired in both the pediatric and adult patients, which thus indicates a decrease in the hemodynamic reserve capacity. After surgery, the CBV, TT and cerebrovascular response to hypercapnia all improved, mainly in the temporal cortex where extracranial-intracranial (EC-IC) bypass surgery had been performed. In the striatum, the CBV also decreased, while the TT was shortened after surgery. A PET study was thus found to be useful for evaluating the cerebral hemodynamics in Moyamoya disease and monitoring the effect of surgery.

Adolescent

Surgical techniques and the results of a fronto-temporo-parietal combined indirect bypass procedure for children with moyamoya disease: a comparison with the results of encephalo-duro-arterio-synangiosis alone.

We recently treated children with Moyamoya disease using a fronto-temporo-parietal combined indirect bypass procedure. Three different indirect bypass procedures (frontal EMAS, EDAS, EMS) were simultaneously carried out at three different sites. We thus treated 16 sides in 12 pediatric patients with Moyamoya disease using this method. Both the collateral formation and the improvement in the clinical symptoms were evaluated postoperatively. These results were then compared with those of the patients treated by EDAS alone. The postoperative collateral formation was more extensively seen in the patients treated with the combined bypass procedure than in those treated by EDAS alone. The improvement in ischemic symptoms was also better in the patients treated by the combined indirect bypass procedure. We therefore conclude that the combined indirect bypass procedure is more effective than EDAS alone.

Cerebral Angiography

The current status of the treatment for hemorrhagic type moyamoya disease based on a 1995 nationwide survey in Japan.

The optimal treatment regimen for hemorrhagic type Moyamoya disease has yet to be clearly established. Furthermore, it remains unclear as to whether or not bypass surgery can help prevent future intracranial hemorrhaging in Moyamoya patients. In Japan, several treatment options, such as conservative, medical, and surgical intervention, have been employed for the treatment of hemorrhagic type of Moyamoya disease. In this study, 282 hemispheres with hemorrhagic onset were analyzed based on a 1995 nationwide survey by the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare Japan to clarify the current status of treatment for hemorrhagic type Moyamoya disease. Questionnaires were distributed to the departments of neurology, neurosurgery, and pediatrics all over Japan asking about both treatment and rebleeding. As a result, 12.5% of the affected hemispheres were treated conservatively while 32.3% were medically treated. Ventricular drainage and/or hematoma removal was performed in 15.8%, and revascularization surgery in 38.3% of all hemorrhagic sides. Among the revascularization procedures used, 45.7% of the hemispheres underwent single indirect bypass surgery, such as EDAS while 22.2% of them received a direct (superficial temporal artery--middle cerebral artery: STA-MCA) bypass surgery. A combination of direct and indirect bypass surgery or a combination of different kinds of indirect procedures comprised 32.1%. Forty-nine out of 282 hemorrhagic hemispheres demonstrated rebleeding. An intracranial hemorrhage occurred in 15 hemispheres with ischemic onset even though nine of them had undergone bypass surgery prior to hemorrhaging. Nearly 18% of the patients with hemorrhagic type disease experienced rebleeding regardless of the treatment modalities. Based on these findings, there remains no clearly superior treatment plan for hemorrhagic Moyamoya disease to prevent rebleeding at this time. However, the selection of patients, treatment modalities, and the timing of the surgery might all play an important role in controlling rebleeding. The final outcome of the patients are therefore mainly considered to correlate with the initial severity of the clinical features.

Cerebral Hemorrhage

The efficacy of bypass surgery for the patients with hemorrhagic moyamoya disease.

The efficacy of bypass surgery for the patients with hemorrhagic Moyamoya disease were studied by multi-center retrospective questionnaire study. The rebleeding rate was 28.3% (39/138 patients) in conservative treatment group and 19.1% (29/152 patients) in bypass surgery group with no significant statistical difference. It is still difficult to clarify the efficacy of bypass surgery for prevention of hemorrhagic attack.

Adolescent

Improvement of the pulmonary absorption of (Asu1,7)-eel calcitonin by various absorption enhancers and their pulmonary toxicity in rats.

The effects of absorption enhancers on the pulmonary absorption of (Asu1,7)-eel calcitonin (ECT) and their pulmonary toxicity were examined by means of in situ pulmonary experiments. The absorption of ECT from the lungs was estimated by its hypocalcemic effect. The pulmonary membrane toxicity of absorption enhancers was evaluated by the leakage of Evans Blue from the plasma into the lungs. In the absence of absorption enhancers, a slight hypocalcemic effect was obtained following intrapulmonary administration of ECT. However, we found significant hypocalcemic effects after the ECT administration with 10 mM n-lauryl beta-D-maltopyranoside (LM), 10 mM sodium glycocholate (NaGC), and 10 mM linoleic acid-HCO60 (hydrogenated caster oil) mixed micelle (MM). The plasma calcium levels decreased as the amount of LM coadministered with ECT increased. In contrast, 10 mM EDTA did not improve the pulmonary absorption of ECT. Overall, a correlation between the pulmonary absorption of ECT and local toxicity was observed in the presence of these additives. However, 1 mM LM, 10 mM NaGC, and 10 mM MM improve the pulmonary absorption of ECT with low pulmonary toxicity. These findings suggest that the use of these adjuvants would be a useful approach for improving the pulmonary absorption of ECT.

Absorption

Electroresponsive pulsatile depot delivery of insulin from poly(dimethylaminopropylacrylamide) gel in rats.

We describe a model for pulsatile drug delivery with an electroresponsive polymer that is stimulated by an externally applied electrical field. Insulin loaded in an electroresponsive poly(dimethylaminopropylacrylamide) (PDMAPAA) gel was administered as a subcutaneous depot in rats. The gel induced a pulsatile plasma glucose decrease in correspondence to stimulation with a constant current of 1.0 mA (0.36 mA/cm2). The first drop occurred at 0.5 h after a 1-min application of current at 0 h and the second drop occurred at 3 h after a 10-min application of current at 2 h. Calculation of pharmacological bioavailability showed that the gel released 0.12% of the loaded insulin after these two stimuli. This in vivo study demonstrates the feasibility of this pulsatile delivery system. The mechanism of insulin release from the electroresponsive PDMAPAA gel is associated with electrokinetic flow of solvated insulin with water; that is, transportation process of counterions (electrophoresis) and water molecules (electroosmosis) in the crosslinked polyelectrolyte gel network.

Acrylic Resins

Effects of antihypertensive drugs on antioxidant enzyme activities and renal function in stroke-prone spontaneously hypertensive rats.

The reactive oxygen species has been proposed as a key mediator of the progression of renal injury associated with essential hypertension. Among the defense systems operating against the reactive oxygen species, superoxide dismutase, glutathione peroxidase, and catalase are the most important antioxidant enzymes (AOEs). In the present study, systolic blood pressure, renal function (creatinine clearance, urinary albumin, and N-acetyl-beta D-glucosaminidase excretion), renal intrinsic AOE activities, and renal histopathology were determined in stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. The effects of a 20-week treatment using three antihypertensive drug regimens--captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor; temocapril, a potent, non-sulfhydryl-containing angiotensin-converting enzyme inhibitor prodrug; and a conventional triple drug combination that includes a vasodilator (hydralazine, hydrochlorothiazide and reserpine)--on renal function, renal tissue, AOE activities, and renal histopathologic abnormalities were evaluated in stroke-prone spontaneously hypertensive rats. Renal function and AOE activities were lower in the stroke-prone spontaneously hypertensive rats than in the Wistar Kyoto rats. Normalization of systolic blood pressure using the antihypertensive drugs improved renal function and produced a nonuniform alteration in renal AOEs; only glutathione peroxidase activity increased significantly with the use of all three drug regimens. The mild renal histopathologic abnormality in stroke-prone spontaneously hypertensive rats was not altered by drug treatment. The improvement in renal function may be related to an increase in glutathione peroxidase activity, but no correlation was seen between renal function changes and alteration in activities of superoxide dismutase or catalase.

Acetylglucosaminidase

Resting load and modulation of the myofilament Ca2+ sensitivity in rabbit cerebral arteries.

The effect of preload on myofilament Ca2+ sensitivity was examined using alpha-toxin permeabilization and fura-2 fluorometry in rabbit cerebral arteries. The [Ca2+]i-force curves shifted leftward at a high preload, with a decrease in median effective concentration of Ca2+ in the permeabilized artery. In the fura-2-loaded artery, the preload modulated the force without affecting [Ca2+]i levels during K+ depolarization, and a high preload moved the [Ca2+]i-force curve upward and to the left. It is thus concluded that the preload regulates the Ca2+ sensitivity of the myofilament and, therefore, may play a role in the regulation of cerebral arterial tonus and blood flow.

Actin Cytoskeleton

Histopathological aspects of dural arteriovenous fistulas in the transverse-sigmoid sinus region in nine patients.

OBJECTIVE: In recent years, dural arteriovenous fistulas (DAVFs) have been primarily thought to be acquired lesions, formed after sinus thrombosis. The pathogenesis of DAVF, however, is still controversial. We have studied histopathological aspects of DAVFs in resected specimens obtained from nine patients, to obtain clues to the pathogenesis of DAVFs. METHODS: Histological comparison was made among nine DAVF cases and five control cases without venous sinus disease. In addition, the relationship between the clinical course and histological aspects was investigated. RESULTS: The essential abnormality found was a connection between the dural arteries and the dural veins within the venous sinus wall, through small vessels averaging approximately 30 microns in diameter. By using several staining methods, we confirmed that the vessels were part of the venous system; we named these dilated venules "crack-like vessels." CONCLUSIONS: The development of abnormal communications between dural arteries and dural veins (crack-like vessels) is regarded as the essential part of the pathogenesis of DAVFs, and sinus thrombus is not thought to be an essential lesion of DAVFs. It might be postulated that sinus hypertension caused by stenocclusive disease of the venous sinuses triggers the development of fistulous connections between arteries and veins in the dural wall, which may result in increasingly dilated venules and the formation of DAVFs.

Adult

Plasma volume estimation using indocyanine green with biexponential regression analysis of the decay curves.

We studied seven analytical methods of estimating the plasma volume from the decay curves of indocyanine green. Fifteen volunteers received 1.0 mg.kg-1 of the dye by intravenous injection and the plasma concentration was measured continuously using spectrophotometry. Plasma volumes were calculated using three single-regression methods (1-a, 1-b, 1-c) and four biexponential regression methods (2-a, 2-b, 2-c, 2-d). The means (SD) of 1-a, 1-b and 1-c were 39 (5.0), 44 (5.7) and 54 (11.5) ml.kg-1, respectively, and these were significantly different from each other (p < 0.05). The values for methods 2-b, 2-c and 2-d were similar to each other: 39 (4.6), 40 (4.1) and 40 (4.0) ml.kg-1, respectively. These required more than 3 min circulation or mixing time. When the time allowed for mixing was less than 3 min (method 2-a) the plasma volume was underestimated. We conclude that plasma volume estimation using indocyanine green and spectrophotometry is most accurate when the mixing time is adequate (3-5 min) and the decay curves are analysed using biexponential regression.

Adult

Effects of antihypertensive drugs or glycemic control on antioxidant enzyme activities in spontaneously hypertensive rats with diabetes.

The activities of glomerular intrinsic antioxidant enzymes (AOEs) were measured in a diabetic spontaneously hypertensive rat (SHR) model. The effects of antihypertensive drugs, i.e. captopril or triple therapy (hydralazine, reserpine, and hydrochlorothiazide), on glomerular intrinsic AOE activities in this model were evaluated. The effects of blood glucose control on the AOE activities were also determined. The aim of the present study was to determine whether activities of glomerular intrinsic AOEs might correlate with disease activity in diabetic SHR. This study showed a decrease of glomerular intrinsic AOE, i.e. Cu/Zn-SOD and Mn-SOD (SOD = superoxide dismutase), glutathione peroxidase, and catalase, activities in diabetic SHR. Glomerular Cu/Zn-SOD or Mn-SOD, glutathione peroxidase, and catalase activities in nondiabetic SHR were slightly lower than those in nondiabetic WKY rats. These activities in diabetic SHR were significantly improved after captopril or triple therapy or blood glucose control. The levels of urinary albumin excretion, creatinine clearance, and glomerular tuft areas in diabetic SHR were also improved after the therapy. It appears that hypertension and hyperglycemia may influence the glomerular intrinsic AOE activities, albuminuria, creatinine clearance, and glomerular tuft areas in diabetic SHR. Thus, it is indicated that control of blood pressure or blood glucose is a very important factor for preventing renal injuries in the diabetic SHR model.

Animals

A clinical comparison of definite moyamoya disease between South Korea and Japan.

BACKGROUND AND PURPOSE: The goal of the present study was to clarify whether South Korean patients with moyamoya disease have clinical features similar to those of Japanese patients. METHODS: From 26 South Korean neurosurgical institutes, 296 definite cases were collected and analyzed statistically. These cases were then compared with 731 Japanese definite cases registered to the Research Committee on Moyamoya Disease of the Ministry of Health and Welfare, Japan. RESULTS: The Korean age distribution patterns showed two peaks that were similar to those seen in Japanese patients. The incidence of adult moyamoya disease in South Korea, however, was 20% higher than that in Japanese patients. The family occurrence rate was 1.8% in Koreans. The incidence of cerebral infarction and bleeding in Koreans was statistically higher, whereas transient ischemic attack and seizure were less than those in Japanese subjects. The incidence of infarction in children and that of hemorrhage in both children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Although most Japanese patients underwent direct bypass surgery and/or combined indirect bypass procedures, single encephaloduroar-teriosynangiosis was performed on 87.6% of all surgical cases in Koreans. Despite the higher incidence of hemorrhagic type in South Korea, the outcomes of the patients were similar to those of the Japanese patients. CONCLUSIONS: This study suggests that the clinical background of moyamoya disease in South Korea is essentially similar to that in Japan.

Adolescent

Response to hypercapnia in moyamoya disease. Cerebrovascular response to hypercapnia in pediatric and adult patients with moyamoya disease.

BACKGROUND AND PURPOSE: We have previously reported that cerebral blood flow decreased and oxygen extraction fraction and cerebral blood volume increased in pediatric patients with moyamoya disease, whereas these values did not change significantly in adult patients. In this study, we measured the cerebrovascular response to hypercapnia using 15O H2O positron emission tomography (PET) in each group of patients. These data were also compared with the oxygen extraction fraction and transit time (cerebral blood volume/cerebral blood flow) measured by 15O PET. METHODS: The subjects consisted of 20 patients with moyamoya disease (7 pediatric and 13 adult patients). Cerebral blood flow was measured by the 15O H2O bolus injection method at the resting state and during the inhalation of 5% CO2. Cerebrovascular CO2 response was estimated as the percentage change of cerebral blood flow per 1 mm Hg change of PaCO2. Oxygen extraction fraction and transit time were measured by the 15O steady-state method. RESULTS: Cerebrovascular response to hypercapnia severely decreased over the cerebral cortices in both pediatric and adult patients with moyamoya disease when compared with those of normal control subjects, and there was no significant difference between pediatric and adult patients. A significant correlation was observed between the CO2 response and transit time, whereas no significant correlation was seen between the CO2 response and oxygen extraction fraction. CONCLUSIONS: Our study revealed that the cerebral hemodynamic reserve capacity decreased to an equal degree in both pediatric and adult patients with moyamoya disease. This finding may thus help to explain the occurrence of transient ischemic attack in adult patients.

Administration, Inhalation

Degradation of a novel tripeptide, tert-butoxycarbonyl-Tyr-Leu-Val-CH2Cl, with inhibitory effect on human leukocyte elastase in aqueous solution and in biological fluids.

The stability of tert-butoxycarbonyl-Tyr-Leu-Val-CH2Cl (YLV) with inhibitory effect on human leukocyte elastase was investigated in aqueous solution, alpha-chymotrypsin solution and biological media. In all cases studied here, the degradation was observed as a pseudo-first order reaction. The half-life for the degradation of YLV in an aqueous solution of pH 7.4 at 37 degrees C was 35.9 h. YLV was most stable at about pH 3.8-5.8 and the effect of temperature was explained by the Arrhenius equation. The activation energies of the degradation in aqueous solutions at pH 2.0, 4.8, and 7.4 were 24.6, 22.1 and 23.4 kcal/mol, respectively. The degradation products in aqueous solution were analyzed by HPLC-MS and were estimated as Boc-Tyr-Leu-Val-CH2OH at pH 7.4 and H2N-Tyr-Leu-Val-CH2Cl at pH 2.0. In a bovine pancreas alpha-chymotrypsin solution at 37 degrees C, the half-life of YLV was 15 min at 25.6 micrograms/ml of alpha-chymotrypsin solution. In the rat plasma, the half-life of YLV was 42.4 min (YLV 26.7 micrograms/ml plasma), and in rat liver, lung and spleen homogenates, the degradation rate constants of YLV were 37.6, 10.3 and 23.5 times larger than that in plasma solution, respectively (all fluids containing 5 mg protein/ml). YLV was less stable than nafarelin acetate, secretin, adrenocorticotropic hormone (ACTH) and gonadorelin in an aqueous solution of pH 7.4.

Animals

Changes in the arterial PCO2 during a single night's sleep in patients with obstructive sleep apnea.

To investigate the relationship between hypercapnia during sleep and its influence on the PaCO2 during the morning after sleep in patients with obstructive sleep apnea syndrome (OSAS), the transcutaneous PCO2 (PtcCO2) was measured throughout the night, and the arterial blood gases (ABG) were also measured while awake before and after polysomnography in 30 OSAS patients with (n=13, hypercapnic group: HC) and without (n=17, normocapnic group: NC) hypercapnia. Significant differences were observed in the body mass index (p=0.03), the difference between the highest PtcCO2 during sleep and the PtcCO2 during awake before sleep (D-PtcCO2), (HC: 11.l+/-1.7 mmHg; NC: 6.3+/-0.5 mmHg; p=0.0057) and the lowest SaO2 during sleep (p=0.0007). In the HC, the PaCO2 on the morning after sleep (50.0+/-0.14 mmHg) was significantly increased (p=0.0029) compared with the PaCO2 on the night before sleep (47.4+/-1.1 mmHg). In the NC, this phenomenon was not observed. Severe hypercapnia (high D-PtcCO2) during a single night's sleep has a significant effect on the waking PaCO2 immediately following sleep in the HC.

Body Mass Index