Nocturnal wheeze in asthmatic patients.
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Asthma↗
Biomedical subjects
A Kanda
Publications and source records attributed to A Kanda.
Chemotherapy for older people with non-small cell lung cancer.
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Aged↗
p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring.
Activation of p85/p110-type phosphatidylinositol (PI) kinase has been implicated in various cellular activities. This PI kinase phosphorylates the D-4 position with a similar or higher efficiency than the D-3 position when trichloroacetic acid-treated cell membrane is used as a substrate, although it phosphorylates almost exclusively the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate. Furthermore, the lipid kinase activities of p110 for both the D-3 and D-4 positions were completely abolished by introducing kinase-dead point mutations in their lipid kinase domains (DeltaKinalpha and DeltaKinbeta, respectively). In addition, both PI 3- and PI 4-kinase activities of p110alpha and p110beta immunoprecipitates were similarly inhibited by either wortmannin or LY294002, specific inhibitors of p110. Insulin induced phosphorylation of not only the D-3 position, but also the D-4 position. Indeed, overexpression of p110 in Sf9 or 3T3-L1 cells induced marked phosphorylation of the D-4 position to a level comparable to or much greater than that of D-3, whereas inhibition of endogenous p85/p110-type PI kinase via overexpression of dominant-negative p85alpha (Deltap85alpha) in 3T3-L1 adipocytes abolished insulin-induced synthesis of both. Thus, p85/p110-type PI kinase phosphorylates the D-4 position of phosphoinositides more efficiently than the D-3 position in vivo, and each of the D-3- or D-4-phosphorylated phosphoinositides may transmit signals downstream.
1-Phosphatidylinositol 4-Kinase↗
Imidapril, an angiotensin-converting enzyme inhibitor, improves insulin sensitivity by enhancing signal transduction via insulin receptor substrate proteins and improving vascular resistance in the Zucker fatty rat.
Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive agents, that inhibit the conversion of angiotensin I to angiotensin II, resulting in smooth-muscle relaxation and a reduction of vascular resistance. Recently, it has been suggested that ACE inhibitors improve insulin resistance in diabetic patients. To investigate the effect of an ACE inhibitor on insulin sensitivity, insulin signaling, and circulation, imidapril was administered orally or intraduodenally to Zucker fatty rats. Oral administration of imidapril improved insulin sensitivity based on the results of an oral glucose tolerance test (OGTT) and a decrease in urinary glucose secretion. Phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with hepatic insulin receptor substrate-1 (IRS-1) in the insulin-stimulated condition was significantly enhanced 110% without a significant alteration in tyrosine phosphorylation of IRS-1 in the imidapril-treated group. In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. In contrast, an alteration of the IRS-2 pathway was observed only in liver; a significant insulin-induced increase in the IRS-2-associated PI 3-kinase over the basal level was observed in the imidapril-treated group but not in the control. In addition, treatment with imidapril was shown to significantly reduce blood pressure and increase blood flow in the liver and muscle. These results suggest that the ACE inhibitor imidapril may improve insulin sensitivity not only by acting directly on the insulin signaling pathway but also by increasing blood flow in tissues via normalization of vascular resistance, a major cause of hypertension.
Angiotensin-Converting Enzyme Inhibitors↗
Two cases of gigantic dystrophic calcinosis cutis caused by subcutaneous and/or intramuscular injections.
We describe two female patients with gigantic dystrophic calcinosis cutis caused by a large number of subcutaneous and/or intramuscular injections which they received when they were much younger. Laboratory data and physical examinations were generally within normal limits, and we detected no disease which might induce cutaneous calcification. There are many reports of dystrophic calcinosis cutis caused by injection of several kinds of drugs. However, we found no previous report describing a patient with calcinosis cutis induced by local tissue injury from a large number of injections and with extraordinarily widespread calcification at the injection sites. Because we do not know the exact drugs injected, it is difficult to say if a specific ingredient in the injections was related to this condition. We do know that a large number of subcutaneous or intramuscular injections were frequently administered to patients who had difficulty in maintaining venous infusions in the past, so there may be similar cases of dystrophic calcinosis cutis which have not been reported.
Aged↗
Intracellular elasticity and viscosity in the body, leading, and trailing regions of locomoting neutrophils.
To investigate the mechanisms underlying pseudopod protrusion in locomoting neutrophils, we measured the intracellular stiffness and viscosity in the leading region, main body, and trailing region from displacements of oscillating intracellular granules driven with an optical trap. Experiments were done in control conditions and after treatment with cytochalasin D or nocodazole. We found 1) in the body and trailing region, the granules divided into a "fixed" population (too stiff to measure) and a "free" population (easily oscillated; fixed fraction 65%, free fraction 35%). By contrast, the fixed fraction in the leading region was <5%. 2) In the body and trailing region, there was no difference in stiffness or viscosity, but both were sharply lower in the leading region (respectively, 20-fold and 5-fold). 3) Neither cytochalasin D nor nocodazole caused a decrease in stiffness, but both treatments markedly reduced the fixed fraction in the body and trailing region to <20% and <40%, respectively. These observations suggest a discrete lattice structure in the body and trailing region and suggest that the developing pseudopod has a core that is more fluidlike, in the sense of a much lower viscosity and an almost total loss of stiffness. This is consistent with the contraction/solation hypothesis of pseudopodial formation.
Cell Movement↗
Association of lifestyle parameters with the prevention of hypertension in elderly Japanese men and women: a four-year follow-up of normotensive subjects.
To study the association of lifestyle parameters with the future risk of hypertension in normotensive subjects, a baseline questionnaire and a four-year follow-up were performed in 445 normotensive Japanese at 35 to 89 years of age. In 60 to 69 year old subjects, the changes of blood pressure during four years were negatively correlated with the amount of boiled rice intake in men and with Japanese tea intake in women. Multiple logistic regression analysis revealed that miso-soup intake at two bowls per day or over was protective against hypertension during follow-up (p < 0.05). These results indicate that food intake is important in the prevention of hypertension in the elderly.
Adult↗
Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats.
Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles in insulin-induced translocation of GLUT4 and in glycogen synthesis. In this study, we investigated the process of PI 3-kinase activation via binding with IRS-1 and -2 in liver, muscle, and fat of high-fat-fed rats, a model of insulin-resistant diabetes. In the liver of high-fat-fed rats, insulin increased the PI 3-kinase regulatory subunit p85alpha and the PI 3-kinase activities associated with IRS-1 3.6- and 2.4-fold, and with IRS-2, 4.7- and 3.0-fold, respectively, compared with those in control rats. The tyrosine phosphorylation levels of IRS-1 and IRS-2 were not significantly altered, however. In contrast with the liver, tyrosine phosphorylation levels and associated PI 3-kinase proteins and activities were decreased in the muscle and adipose tissue of high-fat-fed rats. Thus, high-fat feeding appears to cause insulin resistance in the liver by a mechanism different from the impaired PI 3-kinase activation observed in muscle and adipose tissue. Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system. This is the first report to show increased PI 3-kinase activation by insulin in an insulin-resistant diabetic animal model. These findings may be important for understanding the mechanism of insulin resistance in human NIDDM, since a high-fat diet is considered to be one of the major factors exacerbating insulin insensitivity in humans.
Adipose Tissue↗
Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.
The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.
Administration, Oral↗
[Blood products use and related factors in Japan].
PURPOSES: To examine the use of blood products in Japan by prefectures and to determine the factors associated with the amount of blood products used. METHODS: The amounts of blood products used in November 1995 were surveyed in 8,723 hospitals throughout Japan. The survey also included whether the blood products in hospitals were stored and managed based on the guidelines for appropriate use of blood products. RESULTS: 1. 4,675(90.9%) of the 5,141 respondents used blood products in 1995. 2. The amount of use of each blood product was considerably different among the prefectures. Larger amounts of red blood products and plasma products were used in urban areas. 3. The amounts of use of red blood cell products, plasma products and platelet concentrates showed similar geographical distributions at a significant correlation (r > or = 0.6) each other. The amount of use of albumin products correlated significantly (r = 0.69) with that of immunoglobulin products. 4. Among the various blood products surveyed in this study, the amount of use of only red blood cell products was comparatively larger in the prefectures where blood products were appropriately stored and managed. 5. The number of surgical operations performed under general anesthetization correlated positively with the amount of use of red blood cell products, plasma products and platelet concentrates; a similar correlation was observed between the number of operations for malignant neoplasm and cardiac diseases. CONCLUSION: The amounts of use of blood products used were significantly different among the prefectures in Japan. The amount of use of red blood cell products possibly reflects demand and consumption of blood products as a whole.
Anesthesia, General↗
Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.
BACKGROUND: The efflux of potassium (K) through the ATP-sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e. METHODS AND RESULTS: We studied the effects of 10 and 25 mumol/L pinacidil, and ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 mumol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 mumol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage. CONCLUSIONS: Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.
Adenosine Triphosphate↗
p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin.
Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by association with a variety of tyrosine kinase receptors and intracellular tyrosine-phosphorylated substrates. We isolated a cDNA that encodes a 50-kDa regulatory subunit of PI 3-kinase with an expression cloning method using 32P-labeled insulin receptor substrate-1 (IRS-1). This 50-kDa protein contains two SH2 domains and an inter-SH2 domain of p85alpha, but the SH3 and bcr homology domains of p85alpha were replaced by a unique 6-amino acid sequence. Thus, this protein appears to be generated by alternative splicing of the p85alpha gene product. We suggest that this protein be called p50alpha. Northern blotting using a specific DNA probe corresponding to p50alpha revealed 6.0- and 2.8-kb bands in hepatic, brain, and renal tissues. The expression of p50alpha protein and its associated PI 3-kinase were detected in lysates prepared from the liver, brain, and muscle using a specific antibody against p50alpha. Taken together, these observations indicate that the p85alpha gene actually generates three protein products of 85, 55, and 50 kDa. The distributions of the three proteins (p85alpha, p55alpha, and p50alpha), in various rat tissues and also in various brain compartments, were found to be different. Interestingly, p50alpha forms a heterodimer with p110 that can as well as cannot be labeled with wortmannin, whereas p85alpha and p55alpha associate only with p110 that can be wortmannin-labeled. Furthermore, p50alpha exhibits a markedly higher capacity for activation of associated PI 3-kinase via insulin stimulation and has a higher affinity for tyrosine-phosphorylated IRS-1 than the other isoforms. Considering the high level of p50alpha expression in the liver and its marked responsiveness to insulin, p50alpha appears to play an important role in the activation of hepatic PI 3-kinase. Each of the three alpha isoforms has a different function and may have specific roles in various tissues.
Amino Acid Sequence↗
Estimation of obesity in schoolchildren by measuring skinfold thickness.
To determine whether skinfold thickness is correlated with degree of overweight, serum levels of cholesterol, and blood pressure in children, 161 boys and 167 girls aged 9 and 10 y underwent physical examinations at three elementary schools in Japan. Triceps skinfold thickness was positively correlated with degree of overweight, atherosclerosis index, and systolic blood pressure, and was negatively correlated with levels of high-density lipoprotein (HDL) cholesterol. Among children who were highly overweight (> or = 30%), those with low triceps skinfold thickness (< 11.2 mm) have lower levels of HDL cholesterol, a higher atherosclerosis index, and higher systolic blood pressure than those with greater triceps skinfold thickness (> or = 11.2 mm). The ratio of degree of overweight to triceps skinfold thickness was significantly correlated with levels of HDL cholesterol in girls but not in boys. These results suggest that, in overweight schoolchildren, skinfold thickness may reflect the risk of future hypercholesterolemia and hypertension. Measurement of triceps skinfold thickness and determination of degree of overweight may be useful for the estimation of obesity in children.
Blood Pressure↗
Comparison of the effects of regional ischemia and hyperkalemia on the membrane action potentials of the in situ pig heart. Experimental Cardiology Group, University of North Carolina at Chapel Hill.
INTRODUCTION: This study was designed to determine the role of increased extracellular potassium [K+]e on action potential duration (APD) in the in situ porcine heart during acute regional no-flow ischemia. METHODS AND RESULTS: In open chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise [K+]e. Myocardial [K+]e was determined by potassium-sensitive electrodes, and transmembrane action potential was recorded by floating glass microelectrode. During the first 2 minutes of ischemia, APD at 90% repolarization (APD90) lengthened by 31.2 +/- 1.1 msec (P < 0.05). The comparable increase in [K+]e alone shortened APD90. During the next 6 minutes of ischemia, [K+]e rose to 11.3 +/- 0.3 mM and APD90 showed a decrease. However, the comparable increase in [K+]e by infusion of KCl caused further shortening of APD90 at similar levels of [K+]e. CONCLUSIONS: Acutely ischemic myocardium showed a brief increase in APD90 during the first 2 minutes of ischemia, followed by a fall in APD90 after 2 minutes of ischemia, but the shortening is less than anticipated by the rise in [K+]e. Thus, we hypothesize that other component(s) of ischemia may inhibit action potential repolarization.
Action Potentials↗
Systemic lupus erythematosus in a patient whose younger sister had allergic granulomatous angitis.
A 37-year-old woman visited to our hospital due to general edema. The patient was diagnosed as having systemic lupus erythematosus (SLE) associated with chronic glomerulonephritis, which developed into chronic renal failure and was treated with regular hemodialysis. The patient's younger sister had been followed in our outpatient's clinic because of allergic granulomatous angitis (AGA). The sibling's common histocompatibility leukocyte antigens (HLA) were A24(9), B52(5), and DR2.
Adult↗
[The significance of surgical treatment for T4 lung cancer].
A total of 114 pT4 patients underwent pulmonary resection from January 1980 to December 1993 at our hospital. The overall five-year survival rate of the 114 cases was 17%. There was no significance between the five-year survival rate of squamous cell carcinoma and that of adenocarcinoma. Five-year survival rates of 17 patients with N0 disease, 29 patients with N1 disease, 51 patients with N2 disease, 1 patients with N3 disease, and 16 patients with NX disease were 40%, 21%, 21%, 0%, and 0%, respectively. Five-year survival rate of 89 cases with single factor of T4 was 24% and that of 25 cases with more than one factor was 4% (0.05 < P < 0.1). In the patients with only single factor of T4, five-year survival rates of 6 patients with left atrium invasion, 13 patients with major vessel invasion, 9 patients with trachea/carina invasion, and 18 patients with vertebral body, were 50%, 38%, 22%, and 0%, respectively. Furthermore, in 38 pT4 patients with involvement only to single adjacent structure, five-year survival rates were 47% in curative operation (n = 17) and 10% in non-curative operation (n = 21) (P < 0.05). We conclude that surgical treatment for T4 lung cancer should be performed to patients with single structure invasion which is expected to have a curative operation. N0 disease is more favorable than N1 or N2 disease.
Adenocarcinoma↗
[A case of myasthenia gravis associated with systemic lupus erythematosus and pemphigus erythematosus].
A 34-year-old woman was admitted to our hospital because of ptosis, dysarthria, muscle weakness of upper limbs and skin lesions. At the age of 22 years, she was diagnosed as having systemic lupus erythematosus (SLE) due to the presence of arthritis and high titer of antinuclear antibody. On admission, the high antiacetylcholine receptor antibody titer, along with the positive tensilon test and electromyography established a diagnosis of myasthenia gravis (MG). The demonstration of anti-intercellular antibodies both in cutaneous tissue and blood confirmed the diagnosis of pemphigus. MRI showed hypertrophic thymus. After thymectomy, the myasthenic symptoms aggravated and SLE and pemphigus erythematosus relapsed despite anti-cholinesterase treatment with plasmapheresis. She was then placed on corticosteroid therapy with an improvement of her all symptoms. This very rare case of MG associated with SLE and pemphigus erythematosus suggests that these diseases share common immunological abnormalities.
Adult↗
[Successful two-stage approach to treating excessive hemorrhage from pulmonary arterial stump in post-lobectomy bronchopleural fistula].
A 62-year-old man underwent right lower lobectomy for adenocarcinoma (pT2N0M0) and nine days later, a bronchopleural fistula with empyema was evident. Six weeks following the lobectomy, excessive hemorrhage from the site of chest drainage and hemoptysis were noted. The bleeding and empyema were controlled by a two-stage approach. Anterior transpericardial approach was first made through the median sternotomy to clamp the right main pulmonary artery and then postero-lateral thoracotomy was conducted for the bronchopleural fistula with empyema. The right bronchial stump was covered with a pedicled muscle flap and pseudomonas aeruginosa, always positive in drainage effusion, consequently disappeared. The patient was discharged with a closed bronchus 4 months following the operation.
Bronchial Fistula↗