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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 109 records · Page 6Linked to original sources
PubMed2001

Intravascular ultrasound imaging before and after angioplasty for stenosis of arteriovenous fistulae in haemodialysis patients.

BACKGROUND: Complications of haemodialysis vascular access have emerged as a major cause of patient morbidity. Intravascular ultrasound imaging is a new technical modality providing visualization of the vessel lumen and wall structure in a cross-sectional fashion. Percutaneous transluminal angioplasty has long been used in the treatment of stenoses of arteriovenous fistulae. However, there is no detailed quantitative information on the stenotic lesion and the morphological change by angioplasty. METHODS: Intravascular ultrasound studies were performed in 40 haemodialysis patients with 63 stenoses in arteriovenous fistulae who had percutaneous transluminal angioplasty. The patients were qualitatively and quantitatively evaluated for echogenic patterns and morphological changes before and after angioplasty. RESULTS: Morphological plaque features in stenotic lesions were classified as 37 soft (58%), five hard (8%), 20 mixed (32%), and one calcified sites. Plaque fractures after angioplasty were detected in 45/63 (71%) instances. The lumen cross-sectional area was found to be dilated approximately threefold (from 3.8+/-2.4 to 11.1+/-4.5 mm(2)) and the external elastic membrane cross-sectional area was dilated approximately twofold (from 11.1+/-5.3 to 19.8+/-8.1 mm(2)) after angioplasty. CONCLUSION: These results indicate that intravascular ultrasound allows both qualitative and quantitative assessments of arteriovenous fistulae in haemodialysis patients. The results further suggest that the mechanism of expansion of arteriovenous fistulae stenoses by percutaneous transluminal angioplasty involves stretching of the vessel wall as well as plaque fractures.

Adult↗
PubMed2001

Asn to Lys mutations at three sites which are N-glycosylated in the mammalian protein decrease the aggregation of Escherichia coli-derived erythropoietin.

Erythropoietin (EPO) derived from Escherichia coli is unstable to elevated temperature and tends to aggregate with time, making it unsuitable for high-resolution structure analysis. The mammalian EPO contains about 40% carbohydrate, which makes this protein more stable and less prone to aggregate than non-glycosylated E.coli-derived EPO, but makes it unsuitable for high-resolution analysis owing to its size and flexibility. In an attempt to decrease the aggregation of E.coli-derived EPO, the three asparagine residues at positions 24, 38 and 83 were mutated to lysine residues. In the native protein, these residues are the sites of N-linked glycosylation, which suggests that they should be located on the surface of the protein and should not be involved in interactions in the hydrophobic protein core. Therefore, the substitution of basic amino acids for these neutral asparagine residues is not expected to affect the protein structure, but should increase the isoelectric point of the protein and its net positive charge, decreasing its tendency to aggregate at or below neutral pH due to electrostatic interactions. No apparent alterations in receptor binding, as determined by both cell-surface receptor competition assay and in vitro receptor dimerization experiments, were observed when these mutations were introduced into the EPO sequence. However, this mutant protein displayed a significant increase in stability to heat treatment and to storage, relative to the wild-type molecule. This resulted in a greater number of observable cross peaks in the mutant EPO in 2D NOESY experiments. However, the mutant was similar to the wild-type in stability when urea was used as a denaturant. This indicates that the introduced mutations resulted in a decrease in aggregation with heating or with prolonged incubation at ambient temperature, without changing the conformational stability or the receptor binding affinity of the mutant protein. This approach of placing charged residues at sites where N-glycosylation occurs in vivo could be applied to other systems as well.

Amino Acid Substitution↗
PubMed2001

Stomach cancer-related mortality.

In Japan stomach cancer remains the leading cause of cancer-related mortality. We analysed the annual mortality rate of stomach cancer in relation to age, gender and life expectancy in Japan between 1970 and 1995. The adjusted stomach cancer-related mortality rates decreased from 88.9 in 1970 to 45.4 per 100,000 in 1995 in males and from 46.5 to 18.5 per 100,000 in females. The male-female ratio for stomach cancer-related mortality in all ages was 1.9-2.5 during this 25-year period, and the mortality rate was higher in females than in males at young age. The negative contribution to life expectancy for stomach cancer in males was 0.65 years and 0.42 years in females, which is consistent with a higher mortality rate in males. This negative contribution was 41.8% of total cancer in 1970 and 39.4% in 1995 in males and 34.4% and 16.0%, respectively, in females. Our results demonstrated the need to take into consideration the characteristics of stomach cancer in young women and the effects of ageing when designing programmes aimed at prevention and control of this malignancy.

Adult↗
PubMed2001

Models of sexual selection on a quantitative genetic trait when preference is acquired by sexual imprinting.

The evolution of a quantitative genetic trait under stabilizing viability selection and sexual selection is modeled for a polygynous species in which female mating preferences are acquired by sexual imprinting on the parents and by exposure to the surviving population at large. Stabilizing viability selection acts equally on both sexes in the case of a sexually monomorphic trait and on males only in the case of a dimorphic trait. A genetically fixed sensory or perceptual bias defines the origin of the scale on which the trait is measured, and the possibility is incorporated that female preferences may deviate asymmetrically from the familiar-either toward or away from this origin. When viability selection is strong relative to sexual selection, the models predict that the mean trait value will evolve to the viability optimum. With intermediate ratios of the strength of viability to sexual selection, a stable equilibrium can occur on either side of this viability optimum, depending on the direction of asymmetry in female preferences. When viability selection is relatively weak and certain other conditions are also satisfied, runaway selection is predicted.

Animals↗
PubMed2001

Contribution to promoting cancer epidemiology in Japan and to the activities of the UICC and others in cancer epidemiology and prevention.

On the occasion of being awarding the 5th Nagayo Mataro Prize for contributions to promoting cancer epidemiology and international involvement in the UICC (International Union against Cancer), the Monbusho Overseas Field Research (International Scientific Research)-Special Cancer Study and others, it is my pleasure to give a concise description of activities in which I have played a role. My achievements in administration and management are only a small part of the whole of what has been accomplished in cancer epidemiology and prevention, but I hope that a comprehensive coverage of the projects in which it has been my good fortune to participate may provide orientation and suggest priorities for research in the coming decades. I have taken part in many meetings that stimulated the interest of young scientists and physicians in epidemiology and prevention. It can be said that efficient administration and management are indispensable for modern scientific research in order to promote information collection and exchange. I, therefore, humbly hope that my experience may be illuminating.

Cohort Studies↗
PubMed2001

Involvement of mu-calpain in human sperm capacitation for fertilization.

PROBLEM: The distribution and physiological role of calpains in human sperm were investigated. METHOD OF STUDY: Semen collected manually from healthy donors was liquefied then centrifuged by percoll gradient centrifugation. After exposure to different concentrations of Ca2+ ionophore A23187, the samples were used for immunostaining sodium dodecyl sulfate polyacrylamide gel electrophoresis, and western blot analysis. It was speculated from the results of the study using calpain-specific inhibitors that calpain contributes to the sperm motility and acrosome reaction. RESULTS: With the anti-pro mu-calpain antibody, sperm were immunostained, whereas all were negative for anti-pro mu-calpain antibody binding. Stained sperm were classified into four types according to the staining pattern: acrosome type, equatorial segment type, whole head type, and neck and tail segments type. Western blot analysis of sperm homogenate revealed a single 80-kDa band using the anti-pro mu-calpain antibody, its dose-dependent reduction with Ca2+ ionophore A23187 suggesting activation by this treatment. In the presence of membrane permeable calpain inhibitors, sperm motility and acrosome reaction were significantly suppressed. CONCLUSION: These results indicate that mu-calpain may play pivotal roles in the process of fertilization of human sperm.

Amino Acid Sequence↗
PubMed2001

IgG anti-laminin-1 autoantibody and recurrent miscarriages.

PROBLEM: The present study assesses the clinical significance of anti-laminin-1 auto-antibodies (auto-Abs) in recurrent miscarriages. METHOD OF STUDY: A total of 207 recurrent aborters with a history of two or more consecutive first-trimester miscarriages were tested for the presence of anti-laminin-1 Abs, beta2-glycoprotein I-dependent anticardiolipin Abs, lupus anticoagulants, anti-DNA Abs, and anti-nuclear Abs, before they had conceived again. Recurrent aborters then were followed up during subsequent pregnancies and their outcomes were evaluated relative to their blood test results prior to pregnancy. RESULTS: Fifty-five (31.1%) women out of 177 recurrent aborters were positive for IgG anti-laminin-1 auto-Abs. The levels of IgG anti-laminin-1 auto-Abs in recurrent aborters were significantly higher than those in healthy pregnant women and in healthy non-pregnant women (P = 0.0043 and 0.0073, respectively). The live birth rate of subsequent pregnancies in IgG anti-laminin-1 auto-Abs-positive recurrent aborters was significantly lower than the IgG anti-laminin-1 auto-Abs-negative recurrent aborters (P = 0.0320). There were no specifically significant relationships observed between IgG anti-laminin-1 auto-Abs and other tested auto-Abs. CONCLUSION: IgG anti-laminin-1 auto-Abs are associated with recurrent miscarriages and the subsequent pregnancy outcome of recurrent aborters.

Abortion, Habitual↗
PubMed2001

Nonnoradrenergic mechanism of reflex cutaneous vasoconstriction in men.

We tested for a nonnoradrenergic mechanism of reflex cutaneous vasoconstriction with whole body progressive cooling in seven men. Forearm sites (<1 cm(2)) were pretreated with: 1) yohimbine (Yoh; 5 mM id) to antagonize alpha-adrenergic receptors, 2) Yoh plus propranolol (5 mM Yoh-1 mM PR id) to block alpha- and beta-adrenergic receptors, 3) iontophoretic application of bretylium tosylate (BT) to block all sympathetic vasoconstrictor nerve effects, or 4) intradermal saline. Skin blood flow was measured by laser Doppler flowmetry and arterial pressure by finger photoplethysmography; cutaneous vascular conductance (CVC) was indexed as the ratio of the two. Whole body skin temperature (T(SK)) was controlled at 34 degrees C (water-perfused suit) for 10 min and then lowered to 31 degrees C over 15 min. During cooling, vasoconstriction was blocked at BT sites (P > 0.05). CVC at saline sites fell significantly beginning at T(SK) of 33.4 +/- 0.01 degrees C (P <0.05). CVC at Yoh-PR sites was significantly reduced beginning at TSK of 33.0 +/- 0.01 degrees C (P < 0.05). After cooling, iontophoretic application of norepinephrine (NE) confirmed blockade of adrenergic receptors by Yoh-PR. Because the effects of NE were blocked at sites showing significant reflex vasoconstriction, a nonnoradrenergic mechanism in human skin is indicated, probably via a sympathetic cotransmitter.

Adrenergic alpha-Antagonists↗
PubMed2001

Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress.

It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (T(or)) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to T(or) was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites (P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems.

Anti-Arrhythmia Agents↗
PubMed2001

Function of human eccrine sweat glands during dynamic exercise and passive heat stress.

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

Acclimatization↗
PubMed2001

Relationship between insulin resistance and uremic toxins in the gastrointestinal tract.

The relationship between insulin resistance and local uremic toxins was examined using an oral adsorbent. Fourteen rats demonstrating a diabetic state underwent two-thirds, nephrectomy and were divided into two groups. The control group was fed standard rat chow, and the test group was fed standard rat chow containing 5% AST-120. The target level of blood glucose was achieved by controlling the dosage of exogenous insulin. All rats were sacrificed at week 6. Body weight, blood glucose level, and renal function at week 6 were not significantly different between both groups. However, the mean blood glucose level and the mean dose of exogenous insulin in the AST-120-fed group were significantly reduced as compared with the control group. The results of the present study indicate that administration of an oral adsorbent in diabetic nephropathy decreases the doses of exogenous insulin and improves insulin resistance, and that uremic toxins which exist in the gastrointestinal tract play important roles.

Adsorption↗
PubMed2001

Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs.

Even though cerebral vasospasm after subarachnoid hemorrhage (SAH) causes cerebral ischemia or infarction, the metabolic alterations in cerebrospinal fluids (CSF) after SAH have not been studied. This study was undertaken to measure the levels of glucose, lactate, pyruvate and glutamate in CSF from double hemorrhage dog models. Thirty-two mongrel dogs of either sex, weighing 18-24 kg, underwent double hemorrhage by percutaneous needle puncture of the cistema magna and injection of autologous blood on day 0 and day 2. The dogs were then sacrificed on day 3, 5 and 7, after collecting CSF. In another study, the dogs were treated with mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126, and caspase-2 and caspase-3 inhibitors from day 3 to day 6 after initial blood injection. CSF was collected on day 7 before dogs were sacrificed. The concentration of glucose, lactate, pyruvate and glutamate in CSF was measured by photometrical method. Compared with CSF collected on day 0, glucose was decreased on days 5-7, lactate was increased on days 2-7, pyruvate was increased on days 2-7, and glutamate was increased on days 3-7 (p < 0.05). In the groups treated with MAPK or caspase inhibitors, most of the metabolic alterations remained unchanged as compared with CSF from untreated dogs. Clinically, caspase inhibitors-2 and -3, and MAPK inhibitor U0126 all failed to prevent vasospasm. MAPK inhibitor PD98059 partially prevented vasospasm. Our data demonstrated a metabolic alteration of glucose, glutamate, lactate and pyruvate in CSF during cerebral vasospasm. This metabolic change in consistent with the time course of cerebral vasospasm. This study suggests that brain energy metabolites and excitative amino acids are altered during cerebral vasospasm.

Animals↗
PubMed2001

Mechanism of hemolysate-induced [Ca2+]i elevation in cultured fibroblasts.

Erythrocyte lysate (hemolysate) released from blood clot after subarachnoid hemorrhage is the causative agent for chronic cerebral vasospasm, a prolonged contraction of cerebral arteries. Fibroblasts, the outer layer cells of vessel wall that in contact with blood clot directly, may contribute to cerebral vasospasm. However, the effect of hemolysate on intracellular Ca2+ ([Ca2+]i) mobilization in fibroblasts has not been studied. We investigated hemolysate-induced [Ca2+]i mobilization in cultured neonatal human dermal and canine middle cerebral arterial fibroblasts by using fura-2 microfluorimetry. Hemolysate increased [Ca2+]i by releasing internal Ca2+ stores and promoting Ca2+ entry. Tyrosine kinase inhibitors partially but significantly reduced the effect of hemolysate. The major components of hemolysate, oxyhemoglobin (OxyHb) and adenosine triphosphate (ATP) failed to mimic the effect of hemolysate. In cultured canine middle cerebral arterial fibroblasts, hemolysate produced similar Ca2+ mobilization to that of dermal cells. OxyHb and ATP failed again to reproduce the effect of hemolysate. We conclude that hemolysate increases [Ca2+]i in fibroblasts and this effect of hemolysate is not mediated by OxyHb or ATP but by some unknown factors.

Animals↗
PubMed2001

Production of catechol from benzoate by the wild strain Ralstonia species Ba-0323 and characterization of its catechol 1,2-dioxygenase.

Ralstonia sp. Ba-0323, a wild strain isolated from soil, produced catechol from benzoate and accumulated it outside the cells. The bacterium produced a maximal amount of catechol (1.6 mg/ml) from 3 mg/ml of sodium benzoate in a 20-h growing culture. The conversion rate of benzoate to catechol was 70% on a molar basis. The catechol production by the resting cells increased in the presence of glycerol, and the maximal amount of catechol produced from 3 mg/ml of sodium benzoate reached 1.9 mg/ml at the conversion rate of 83% after 8 h of incubation. Catechol 1,2-dioxygenase, which catalyzed the ring cleavage of catechol, was purified to homogeneity from a cell extract of Ralstonia sp. Ba-0323 growing on benzoate and characterized. The specific activity of the purified enzyme was much lower than those of the dioxygenases from other microorganisms reported. The Km for catechol of the purified enzyme was much higher than those of other dioxygenases. In addition, the NH2-terminal amino acid sequence of the enzyme was less similar to the other catechol 1,2-dioxygenases than they are to each other.

Amino Acid Sequence↗
PubMed2001

Regulation by two CatR proteins that differ in binding affinity to catB promoters expressing two cat gene clusters.

We isolated the two LysR-type regulatory proteins CatR1 and CatR2, which regulate the expression of cat1 and cat2 gene clusters, respectively, required for catechol degradation in the bacterium Frateuria sp. ANA-18. In a gel mobility shift assay using CatR1 and the DNA fragment containing the catB1 promoter region, the formation of two complexes, complex 1-1 (C1-1) and complex 1-2 (C1-2), was observed in the presence of cis,cis-muconate. On the other hand, CatR2 and the DNA fragment containing the catB2 promoter region formed only complex 2-2 (C2-2) at a lower concentration of cis,cis-muconate than that at which C1-1 and C1-2 were formed. As the concentration of cis,cis-muconate decreased, the production of the muconate cycloisomerase isozyme MC II encoded by catB2 decreased as well as that of MC I encoded by catB1. However, the amount of MC II synthesized was larger than that of MC I at low concentrations. On the basis of these results, we concluded that the catB2 promoter was activated at low concentrations of cis,cis-muconate.

Bacterial Proteins↗
PubMed2001

Role of calpain in human sperm activated by progesterone for fertilization.

We evaluated the activation of mu-calpain in progesterone-activated human sperm. Semen collected from fertile donors with informed consent was liquefied and subjected to percoll gradient centrifugation. After exposure to different concentrations of progesterone, the samples were used for immunostaining, SDS-PAGE and Western blot analysis. An increase of the intracellular free calcium concentration in the sperm following the addition of progesterone was observed using fura-2 AM. Immunostaining using an antibody against active mu-calpain produced 6 distinct staining patterns: (1) the acrosome, (2) an equatorial segment, (3) the whole head, (4) the neck, (5) the neck and tail or (6) unstained sperm. After addition of progesterone, the predominant type changed from the neck type (90%) to the neck and tail type (79%). Western blot analysis using a pro-mu-calpain and a mu-calpain domain III antibody revealed autodigestion of mu-calpain, indicating activation by progesterone. Using calpain-specific inhibitors it was shown that calpain activation contributes to sperm motility as well as to the acrosome reaction. These results suggest the possibility that activation of mu-calpain in human sperm by progesterone plays an important role in fertilization.

Blotting, Western↗
PubMed2001

[Simultaneous carotid and coronary artery surgery in asymptomatic carotid artery stenosis--report of three cases].

Some patients with coronary artery disease are diagnosed as having additional carotid artery disease. This subset of patients has been identified as a high-risk group for cardiac and cerebral complications following surgical intervention. Three patients who underwent combined CEA/CABG for coexistent asymptomatic carotid occlusive disease are reported. Case 1: A 69-year-old female who suffered chest pain on exertion. Her coronary angiogram showed severe stenosis of three vessels. Her carotid angiogram showed 98% stenosis of the right internal carotid artery and poor collateral circulation. The severe stenosis of her carotid artery was considered as a risk factor for perioperative cerebral stroke. Intraoperatively, CEA preceded the CABG. Postoperative course was uneventful. Case 2: A 64-year-old male. Intermittent claudication was his initial symptom. His coronary angiogram showed stenosis in three vessels and carotid angiogram showed 75% stenosis in the right carotid artery. Simultaneous CABG and CEA was performed. His postoperative course was uneventful. Case 3: A 62-year-old male whose ECG indicated ischemic heart disease, although he had no symptoms. His coronary angiogram showed stenosis in three vessels, and 80% stenosis of his right carotid artery was observed by carotid angiogram. He underwent simultaneous surgery, and had an uneventful postoperative course. It has been reported that 1.5-8.7% of CABG patients have severe carotid artery stenosis, and perioperative cerebral stroke occurs in 0.9-16%. Simultaneous surgery was successful in our three patients who had asymptomatic carotid artery stenosis. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Aged↗