Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 307 records · Page 17Linked to original sources

PubMed1996

Age-related changes in alpha-adrenoceptor-mediated blood pressure in the rat: relationship between the potency for phenylephrine and the maximum number of binding sites.

To study the effects of aging on the blood pressure potency of phenylephrine, 6-, 10- and 40-week-old rats were used. In anesthetized rats, the potency (pD2 value) of phenylephrine on the blood pressure tended to increase with age from 6 to 10 weeks, but significantly decreased thereafter with age from 10 to 40 weeks. Similarly, in pithed rats, the potency of phenylephrine significantly increased, but decreased thereafter. In isolated rat thoracic aorta, the pD2 value of phenylephrine from the contractile responses significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. The change in the potency of phenylephrine on the blood pressure was proportional to the pD2 value of phenylephrine estimated in aortic preparations. The specific binding of [3H]prazosin to single smooth muscle cells of thoracic aorta from different aged rats was saturable. The maximum number of binding sites (Bmax) significantly increased with age from 6 to 10 weeks, but decreased thereafter from 10 to 40 weeks. However, the dissociation constant of [3H]prazosin (Kd) did not alter with age. The changes in the potencies (pD2 values) of phenylephrine on the pressure responses and on the contractile responses were proportional to the logarithm of the maximum number of binding sites. The present study suggests that age-related changes in blood pressure are due to changes in the maximum number of binding sites (receptor density) of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1996

Pharmacological characteristics of indoline derivatives in muscarinic receptor subtypes.

The present study was designed to investigate which muscarinic receptors the indoline derivatives interact with and also their pharmacological properties. Compounds I and II contracted guinea-pig ileum in a concentration-dependent manner, whereas compounds III-IX behaved as antagonists and Schild plots gave straight lines. 4-DAMP antagonized the contractile responses to compounds I and II, and the pA2 values for 4-DAMP were 8.96 +/- 0.23 and 9.09 +/- 0.06, respectively. In guinea-pig left atrium, compound I partly inhibited twitch responses, whereas compound II did not have any effect. In rabbit vas deferens, compounds I and II produced inhibitory effects on twitch responses evoked by field stimulation. Pirenzepine antagonized the inhibitory responses of compounds I and II, and the pA2 values for pirenzepine were 7.90 +/- 0.13 and 8.12 +/- 0.06, respectively. Compound I has about 150-fold higher affinity to M1 receptors than to M3 receptors, while compound II has about 360-fold higher affinity to M1 receptors. Our results indicate that compounds I and II show 7- and 16-fold higher M1 receptor selectivity than McN-A-343, respectively. Therefore, compound II is selective for M1 receptors over M2 or M3 receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1996

Relaxant responses by optical isomers of ephedrine and methylephedrine in guinea pig tracheal smooth muscle.

The effects of optical isomers of ephedrine and methylephedrine on the guinea pig tracheal smooth muscle were studied. l-Ephedrine markedly caused a graded relaxation of the guinea pig trachea where the tone had been raised spontaneously. A rightward shift of the l-ephedrine concentration-response curve was observed for propranolol and butoxamine, and the pA2 values for propranolol and butoxamine were 8.55 and 6.38, respectively. d-Methylephedrine markedly caused a graded relaxation of the guinea pig trachea contracted with histamine. Propranolol and bupranolol did not affect the relaxant response to d-methylephedrine. d-Methylephedrine competitively antagonized the contractile responses to histamine, and the pA2 value for d-methylephedrine was 5.12. These results suggest that l-ephedrine-induced relaxation of the guinea pig trachea is mediated through beta 2-adrenoceptors, whereas d-methylephedrine relaxes the guinea pig trachea by blocking histamine receptors.

Animals↗

PubMed1996

Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Cytokines play a critical role in the cascade of events that cause septic shok. One regulatory system suggested to be important in controlling inflammatory response is the neuroendocrine axis. One of the chemokines is cytokine induced neutrophil chemoattractant (CINC), which was first described as an immuno-modulator of peripheral tissue in inflammatory responses. To assess further the contribution of the chemokine to the central nervous system, we performed immunohistochemistry on rat brains and found strong CINC-like immunoreactivity in the posterior pituitary gland. Treatment with bacterial endotoxin (lipopolysaccharide; LPS) markedly enhanced CINC-like immunoreactivity in the posterior pituitary. Before the LPS challenge, signal for CINC mRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The LPS challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 15 minutes (min) and peaked at 30 min. The LPS challenge provoked no observable change in the supraoptic nucleus. These studies demonstrate the presence of an endotoxin-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly-described pathway will provide a novel information to understand another possible neuralimmune mechanism.

Animals↗

PubMed1996

Assessment of antihistaminic and antimuscarinic effects of optical isomers of ephedrine and methylephedrine by receptor binding assay in guinea pig ileal muscle.

Effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on histamine H1-receptors and muscarinic receptors in guinea pig ileal muscle were investigated by radioligand binding assay and by measuring the mechanical response to histamine and acetylcholine. EPH and MEP inhibited the specific binding of [3H]mepyramine and [3H]quinuclidinyl benzilate (QNB) to microsomal fractions prepared from this tissue. The rank order of inhibitory potency of [3H]mepyramine and [3H]QNB binding was d-->l-isomer and l-->d-isomer, respectively. Furthermore, the rank order of antagonistic potency in the mechanical response study was the same as that in the binding study. d-MEP competitively antagonized histamine-induced contraction (pA2 value; 5.14). These results suggest that each isomer of EPH and MEP has a distinct affinity for histamine H1-receptors and muscarinic receptors in guinea pig ileal muscle. The antihistaminic and antimuscarinic activity of these compounds may be largely attributed to competition at receptor sites. In addition, it is suggested that d-MEP exhibits a competitive antagonist activity for the histamine H1-receptor.

Acetylcholine↗

PubMed1996

Chronotropic effects of optical isomers of ephedrine and methylephedrine in the isolated rat right atria and in vitro assessment of direct and indirect actions on beta 1-adrenoceptors.

Effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on the spontaneous beating rate of isolated right atrium of normal and reserpinized rat were investigated to assess direct and indirect actions on beta 1-adrenoceptors. l-EPH (3 x 10(-7) - 3 x 10(-5) M) and d-EPH (10(-6) - 10(-4) M) markedly increased beating rate of rat right atrium. l-MEP (10(-5) - 3 x 10(-4) M) showed slight increase in heart rate. The potency of positive chronotropic effect is l-EPH > d-EPH "l-MEP. l-EPH was about 3 times as potent as d-EPH. In addition, d-MEP (3 x 10(-5) - 3 x 10(-4) M) caused a decrease in heart rate. Positive chronotropic effects of EPH isomers and l-MEP were attenuated by pretreatment with atenolol ( a selective beta 1-adrenoceptor antagonist) or reserpine treatment (8 mg/kg, s.c.). In reserpinized atria, the maximal increase by d-EPH was quite small, and l-MEP decreased heart rate. On the other hand, d-MEP, at 3 x 10(-4) M, did not show antagonist activity against the positive chronotropic effect of isoprenaline (10(-10) - 10(-5) M). These results suggest that l-EPH, d-EPH and l-MEP have beta 1-adrenoceptor agonist activity, while d-MEP is suggested to have only low or no affinity for beta 1-adrenoceptors. The relatively weak activity of l-MEP is believed to be mainly mediated by released noradrenaline. It is also suggested that d-EPH has very potent noradrenaline-releasing activity.

Animals↗

PubMed1996

A new cytotoxic cholestane bisdesmoside from Ornithogalum saundersiae bulbs.

Bioassay-guided fractionation of the MeOH extract of Ornithogalum saundersiae bulbs led to the isolation of a new cholestane bisdesmoside with potent cytotoxic activities toward leukemia HL-60 and MOLT-4 cells. The structure was deduced mainly from spectroscopic information.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Effects of optical isomers of ephedrine and methylephedrine on the twitch response in the isolated rat vas deferens and the involvement of alpha 2-adrenoceptors.

The effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on the twitch response to electrical stimulation (1 msec, 1 Hz) in the isolated rat vas deferens were investigated to clarify the action on alpha 2-adrenoceptors. l-EPH (10(-7) 3 x 10(-5) M) and d-EPH (10(-6)-10(-4) M) markedly inhibited the twitch response in the presence of prazosin (10(-6) M). l-MEP also inhibited the twitch response at high concentrations (3 x 10(-5)-10(-3) M). The rank order of inhibitory potency was 1-EPH > d-EPH >> l-MEP. Yohimbine (3 x 10(-7) M), a selective alpha 2-adrenoceptor antagonist, attenuated the twitch-inhibitory effects of EPH isomers and l-MEP. Furthermore, the twitch-inhibitory effects of EPH isomers and l-MEP were attenuated by reserpine treatment (8 mg/kg, s.c.). On the other hand, d-MEP showed the potentiation of twitch response, and competitively antagonized the twitch-inhibitory effect of clonidine (10(-9)-10(-6) M) with the pA2 value of 4.3 in the presence of prazosin. The results suggest that EPH isomers and l-MEP have stimulating activity for presynaptic alpha 2-adrenoceptors. In addition, the twitch-inhibitory effect of EPH isomers and l-MEP may be at least partly mediated through the release of noradrenaline. It is also suggested that d-MEP has competitive alpha 2-adrenoceptor antagonist activity.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1996

Simultaneous estimation of filtration variables in isolated rat lungs in zone 3 conditions.

Estimation of filtration variables (filtration coefficient, perimicrovascular pressure, and reflection coefficient) is important for evaluating pulmonary microvascular permeability to fluids, especially when the lungs are inflamed, injured, or being preserved for transplantation. Here we report a new method for estimating filtration variables simultaneously in isolated rat lung lobes in zone 3 conditions (pulmonary arterial pressure > pulmonary venous pressure > alveolar pressure). We used Krebs-Henseleit solution containing 6% bovine serum albumin for the perfusate and maintained perfusion using a constant-pressure circuit system. Pulmonary venous and alveolar pressures were kept at 2.5 and 2.0 cmH2O, respectively, and pulmonary arterial pressure was set so that lung weight did not change. Then we increased both pulmonary arterial and venous pressures by 3 cm H2O simultaneously, and recorded the weight gain. Next, we diluted the perfusate with Krebs-Henseleit solution to about half the original concentration, and recorded the weight gain. Using the Starling equation, the values we obtained for the filtration variables were filtration coefficient, 5.3 mg. min-1.cmH2O-1.g-1; perimicrovascular pressure, 1.1 cmH2O; reflection coefficient, 0.54. These values agree with values from previous reports. Since these 3 filtration variables are interrelated, this method for simultaneous measurement is more accurate than independent measurements are. The advantages of this method are that it does not require direct measurement of interstitial pressure or collection of lymph fluid. What we need to calculate these filtration variables are the initial filtration rates and the albumin osmotic pressures for perfusate.

Animals↗

PubMed1996

Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous leukemia in serum-free culture.

We investigated the properties of granulocyte-macrophage (GM) progenitors obtained from patients with juvenile chronic myelogenous leukemia (JCML). CD34+ bone marrow cells from a patient with JCML, unlike normal bone marrow cells, generated a large number of cells in serum-containing liquid culture without additional hematopoietic factors. In serum-deprived culture, only granulocyte colony-stimulating factor (G-CSF) had a modest stimulatory effect on GM colony growth in normal controls. In contrast, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3), as well as G-CSF, when tested individually, generated significant numbers of GM colonies in some JCML patients. All two-factor combinations generated significantly more GM colonies in JCML compared with normal controls. In particular, GM-CSF plus SCF exerted an interaction equivalent to the all-factor combination in most patients. Significant differences in the size and constituent cells of GM colonies stimulated by GM-CSF plus SCF were also observed. These results suggest that one possible mechanism for the excessive cell production in JCML is the strong proliferation of GM progenitors induced by hematopoietic factors, especially SCF. According to immunofluorescent analysis, however, it is unlikely that this multiplication is due to an increase in the cell surface expression of c-kit receptors on JCML progenitors.

Antigens, CD34↗

PubMed1996

[Assessment of Japanese patients receiving heart transplants overseas].

No heart transplants have been performed in Japan due to various obstacles since the only operation performed in 1968. Since 1981, a number of patients requiring heart transplants have been accepted by foreign transplantation centers in England, the U.S.A., and Germany. This report describes an investigation of the postoperative course of these Japanese heart transplant patients and discusses the problems regarding transplantation in Japan. Of the 21 transplant patients, the diagnosis was dilated cardiomyopathy in 17, restrictive cardiomyopathy in 1, hypertrophic cardiomyopathy in 2, and congenital muscle dystrophy in 1. All patients survived surgery but three died in the long-term period. The causes of death were acute rejection (after 3 months), chronic rejection (after 50 months) and infection (after 30 months). The actuarial survival curve of these patients was 95.0% for one-year survival and 86.4% for three-year survival. The postoperative functional class was NYHA classification I in all patients (100%). Ninety-three percent of patients returned to work. Immunosuppressive therapies included triple drug therapy in 14 patients (66.7%), double drug therapy in 4 (19.0%), ciclosporin alone in 2 (9.5%) and FK506 in 2 (5.0%). The incidence of acute rejection was 1.56 episodes per patient per year within 3 months and 2.9 episodes per patient per year within 1 year. The postoperative courses of Japanese patients who underwent heart transplantation at foreign transplantation centers were satisfactory. These results will encourage heart transplantation in Japan.

Adolescent↗

PubMed1996

[Effects of subacute hypoxia on alveolar epithelial ion transport in rats].

To study the effects of subacute hypoxia on alveolar epithelial ion transport, alveolar fluid clearance was measured in isolated fluid-filled rat lungs. After instillation of a solution containing about 5% bovine albumin, an increase in alveolar fluid clearance was measured over 2 hours. Alveolar fluid clearance was lower when rats were kept in hypoxic conditions (FiO2 = 0.1) for 48 hours. Neither 10(-5) M amiloride (a Na(+)-channel blocker) nor 10(-3) M ouabain (an inhibitor of Na(+)-K(+)-ATPase) inhibited fluid clearance in the hypoxia group, but they did in the normoxia group. These results indicate that subacute hypoxia may down-regulate both the Na(+)-channl and Na(+)-K(+)-ATPase, and thus decrease the absorption of excess alveolar fluid.

Animals↗

PubMed1996

[Effect of time in culture on modulation of Na(+)-K(+)-ATPase activity in rat alveolar type II cells].

To determine the effect of time in culture on epithelial cell function, we evaluated the modulation of Na(+)-K(+)-ATPase activity in rat alveolar type II cells in culture. Ouabain sensitivity testing revealed that the alpha-1 predominance in the enzyme's isoforms was maintained over the 120 hours in culture. Basal Na(+)-K(+)-ATPase activity in the whole cell homogenate did not differ significantly between cells cultured for 48 hours and those cultured for 120 hours. Terbutaline (10 mM) did not activate Na(+)-K(+)-ATPase in the cells cultured for 48 hours, but, it significantly increased the activity of this enzyme in the cells cultured for 120 hours cells cultured for 48 hours, produced intracellular cyclic AMP after exposure to 10 mM of terbutaline. These results indicate that the coupling between Na(+)-K(+)-ATPase and the beta-adrenergic pathway in alveolar type II cells can be influenced by the time in cell culture.

Adrenergic beta-Agonists↗

PubMed1996

[Long-term effect of a beta-adrenergic agonist on sodium uptake into cultured rat alveolar type II cells].

To evaluate the long-term effect of a beta-adrenergic agonist on Na(+)-channel function in cultured rat alveolar type II cells, we measured 22Na+ uptake into type II cells cultured in the presence and absence of 0.1 mM terbutaline for up to 5 days. Terbutaline did not influence the growth, morphology, or protein content of the cells. Terbutaline increased amiloride-inhibitable 22Na+ uptake into the cells at day 2 in culture, but there was no significant difference at day 5. Because amiloride-inhibitable 22Na+ uptake reflects Na(+)-channel function, these data indicate that terbutaline may transiently upregulate Na(+)-channel function. This study provides direct evidence of a long-term effect of a beta-adrenergic agonist on Na(+)-channel function in alveolar type II cells.

Adrenergic beta-Agonists↗

PubMed1996

[CD7, HLA-DR, CD38 positive acute undifferentiated leukemia with subcutaneous tumor and thymoma].

A case of acute undifferentiated leukemia (AUL), accompanied by subcutaneous tumor and thymoma is reported. The analysis of immunophenotype showed that the leukemic blasts were positive for CD7, HLA-DR, CD38 and CD34 in 17.5% but negative results were obtained for other lymphoid and myeloid antigens. The leukemic blasts had a rearranged immunoglobulin heavy chain (IgH) gene and T cell receptor delta (TCR-delta) chain gene chromosomal abnormality, 47, XY, +8, t(13; 17) (q12; q21), -17, +M was observed. In general, the CR rate is low and prognosis is poor in patients with AUL. In our case, CR was not achieved by the therapy with JALSG-ALL87 protocol, but was achieved by subsequent treatment with high dose ara-C therapy and combination chemotherapy including intermediate-dose ara-C, mitoxantrone, etoposide and prednisolone.

ADP-ribosyl Cyclase↗

PubMed1996

[Hemophagocytosis in a child with paroxysmal cold hemoglobinuria].

A 2-year and 5-month-old boy was admitted to Okaya municipal hospital because of low grade fever and reddish-brown urine soon after an outside walk in November, 1994. Direct Coombs test was negative, but indirect Coombs test positive. Both sugar water test and Ham test were negative. A diagnosis of paroxysmal cold hemoglobinuria (PCH) was made by Donath-Landsteiner (D-L) test which showed the presence of a high amount of anti-P specific IgG and IgM of D-L antibody. Serological tests for syphilis were negative. Cold agglutinin titer and mycoplasma antibody titer was X 128 and X 80, respectively. A bone marrow specimen exhibited pronounced hemophagocytosis. Serum INF-gamma and M-CSF level were normal (less than 5 pg/ml and 1007 units/ml, respectively). These results suggest that hemophagocytosis in this case is not due to hemophagocytic syndrome.

Bone Marrow↗

PubMed1996

A killing defect of natural killer cells as an underlying immunologic abnormality in childhood systemic lupus erythematosus.

OBJECTIVE: To elucidate the nature of the natural killer (NK) cell system in children with systemic lupus erythematosus (SLE), we performed phenotypic and functional studies of circulating NK cells during the course of childhood SLE. For comparison, similar examinations were undertaken in juvenile rheumatoid arthritis (JRA). METHODS: Twenty-five children with SLE and 27 children with JRA were studied; 5 of these children with SLE were examined 6 to 67 months before the overt progression to SLE. The number and cytolytic function of NK cells were determined, using flow cytometry, 51Cr release, and single-cell cytotoxicity assays. RESULTS: At the diagnosis of SLE, a decrease in NK cells defined as CD16+ or CD56+ was the most prominent of the numerical changes in lymphocyte subsets. In regard to cytolytic function, NK activity in children with SLE was greatly reduced at diagnosis: at the single cell level, their NK cells were defective in killing and recycling abilities. Although the relative number of NK cells and their recycling capacity returned to normal with the improvement of active SLE, the killing defect persisted during the inactive phase; there was no persistent NK cell abnormality in JRA. Reduced NK activity due to a killing defect was demonstrable early in the course of SLE: the NK activity and killing capacity values were profoundly decreased in 5 children before the overt progression to SLE. CONCLUSION: It would appear that NK cell functional abnormality, characterized by a killing defect, is an underlying immunological abnormality during the course of childhood SLE.

Adolescent↗

PubMed1996

[Role of Na(+)-glucose cotransport in fluid absorption across alveolar epithelium in isolated rat lungs].

To evaluate the role of Na(+)-glucose cotransport in fluid absorption across alveolar epithelial walls in isolated rat lungs, we measured the inhibitory effects of amiloride (a Na+ channel blocker) and phlorizin (a Na(+)-glucose cotrasport blocker) on the fluid absorption rate in fluid-filled lungs. Amiloride (10(-5)-10(-4) M) reduced alveolar fluid absorption by 30%. This value was similar to that obtained in the presence of 10(-3) M phlorizin. The coefficient of Na(+)-glucose cotransport was estimated to be 2.5. The strong correlation between Na+ escape and fluid absorption (r = 0.907) was not affected by phlorizin. These findings suggest that the impact of Na(+)-glucose cotransport was similar to that of Na+ transport alone, and that glucose molecules transported by Na(+)-glucose cotransport do not play an important role in alveolar fluid absorption across rat alveolar epithelium.

Absorption↗