Biomedical subjects

M Kurosawa

Publications and source records attributed to M Kurosawa.

At least 145 records · Page 8Linked to original sources

PubMed1992

Cutaneous mechanical sensory stimulation increases extracellular acetylcholine release in cerebral cortex in anesthetized rats.

The effects of noxious and innocuous mechanical stimulation of various segmental skin areas (face, forelimb and paw, back, hindlimb and paw) on extracellular acetylcholine release in the cerebral cortex in the parietal lobe were examined in halothane-anesthetized rats, by means of the microdialysis technique. Pinching of a forepaw or hindpaw and brushing of a hindlimb for 10 min produced significant increases in extracellular acetylcholine release, whereas pinching of the face or back and brushing of the face, forelimb or back produced no significant changes. These results demonstrate that cutaneous sensory stimulation can regulate extracellular acetylcholine release in the cerebral cortex, and that the efficacy of the stimulation on cortical acetylcholine release is dependent on the sensory modality and the region of skin stimulated.

Acetylcholine↗

PubMed1992

Elevated levels of peripheral-blood, naturally occurring aliphatic polyamines in bronchial asthmatic patients with active symptoms.

The levels of peripheral-blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high-performance liquid chromatography analysis. None of the patients, except the 44-year-old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44-year-old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma.

Adult↗

PubMed1992

Effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine release from rat peritoneal mast cells.

Rat peritoneal mast cells purified on a Percoll gradient were challenged with substance P (SP) and the effect of phospholipase A2 inhibitor ONO-RS-082 on SP-induced histamine release from the cells was investigated. 10(-5) mol/l SP caused a significant histamine release and the amount of histamine release reached maximum at 1 min after the challenge. ONO-RS-082 inhibited the SP-induced histamine release in a concentration-dependent manner at the concentration from 10(-6) to 10(-4) mol/l, suggesting possible involvement of phospholipase A2 in SP-induced histamine release from rat peritoneal mast cells.

Aminobenzoates↗

PubMed1992

Human peripheral blood hypodense eosinophil proteins are more labeled with 32P than the normodense eosinophil proteins.

Peripheral blood eosinophils from patients with atopic dermatitis and normal healthy controls were isolated on a Percoll gradient and were incubated with [32P]orthophosphoric acid. After stopping the reaction, SDS/PAGE was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 14 protein bands below 66.2 kDa by SDS/PAGE and the differences of the protein staining patterns between hypodense and normodense eosinophils were present. In the autoradiographs five distinct radioactive bands were observed below 31 kDa. 32P incorporation into the bands of hypodense eosinophils was stronger than that of normodense eosinophils, suggesting possible involvement of protein phosphorylation in the activation process of human eosinophils.

Adult↗

PubMed1992

[Bronchial hyperresponsiveness to histamine induced by intravenous administration of prostaglandin D2 (PGD2) in guinea pigs].

Prostaglandin D2 (PGD2) and thromboxane A2 (TXA2) have been suggested to play important roles in the pathogenesis of bronchial asthma. In the present study, effects of i.v.-administration of PGD2 on bronchial hyperresponsiveness in guinea pigs were investigated by the measurement of dynamic compliance and dynamic respiratory resistance with formulae which can exclude the effects of changes of the airway wall thickness. With these formulae, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of PGD2 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was enhanced with the administration of PGD2. Moreover, TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the effect of PGD2 administration.

Airway Resistance↗

PubMed1992

Inhibitory effects of organotin compounds on histamine release from rat serosal mast cells.

Tributyltin inhibited compound 48/80-induced histamine release from rat serosal mast cells in a dose-related manner. Triphenyltin and tripropyltin also showed a strong inhibitory effect on the histamine release and the degree of the inhibition was the same as that of tributyltin. The inhibitory effects of other organometals were much smaller than those of the organotins. Tributyltin and triphenyltin also showed a tendency to inhibit histamine release induced by concanavalin A + phosphatidylserine and calcium ionophore A 23187. The present results suggest that certain triorganotin compounds may have a specific inhibitory effect on histamine release by acting on the same process in each of the three stimulus responses.

Animals↗

PubMed1992

[Protein phosphorylations in granulocyte/macrophage colony-stimulating factor-stimulated human peripheral blood eosinophils].

Peripheral blood eosinophils from normal healthy subjects were isolated on a Percoll gradient and were incubated with [32P] orthophosphoric acid. 32P-labeled eosinophils were washed and stimulated with GM-CSF under different conditions. After reaction was stopped, SDS/PAG electrophoresis was performed along with autoradiographs to determine the incorporation of 32P into proteins. GM-CSF-stimulated eosinophils produced an increase of 32P incorporation into the bands in the 31 kDa and 35 kDa areas after 30 sec and 1 min of stimulation. The increase of 32P incorporation was dependent on Mg2+ concentration and temperature, suggesting that proteins in the eosinophils with apparent molecular weights of 31 kDa and 35 kDa can be phosphorylated with the stimulation of GM-CSF.

Adult↗

PubMed1992

[Inhibitory effects of vasoactive intestinal peptide on superoxide anion generation from stimulated human inflammatory cells].

Vasoactive intestinal peptide (VIP) is suspected to be a neurotransmitter of nonadrenergic and noncholinergic inhibitory nerves in human respiratory tracts. Although VIP affects T lymphocytes through its specific receptor, the effects of VIP on inflammatory cells except T lymphocytes are obscure. We investigated the effects of VIP on superoxide anion (O2-) generation from five kinds of human cells; neutrophils, eosinophils and mononuclear cells isolated from peripheral blood, alveolar macrophages obtained from the bronchoalveolar lavage, and human monocyte cell line, U937, the capacity of which for O2- generation was induced by interferon-gamma. O2- generation from human cells stimulated by 10(-5) M fMLP was measured by the cypridina luciferin analog, MCLA, -dependent chemiluminescence method. VIP inhibited O2- generation from fMLP-stimulated neutrophils, mononuclear cells and U937 in a dose-dependent manner. 3 x 10(-6) M VIP inhibited O2- generation from fMLP-stimulated eosinophils and alveolar macrophages significantly. These results indicate that VIP might inhibit the activation of inflammatory cells and act as an antiinflammatory agent.

Cells, Cultured↗

PubMed1992

[Inhibitory effect of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) on bronchoconstriction in guinea pigs].

The present studies were conducted to investigate whether or not VIP and PHI have a bronchodilator effect in vivo. VIP or PHI was administered intravenously in guinea pigs, and dynamic respiratory resistance was measured. Intravenous administration of VIP and PHI reduced dynamic respiratory resistance; however, the effect was significantly less than that of isoprenaline. VIP and PHI inhibited the increase in dynamic respiratory resistance by intravenous administration of histamine in a dose-dependent manner, suggesting that VIP and PHI may be involved in the pathogenesis of airway hyperresponsiveness through inhibiting the effect of mediators on the airway.

Airway Resistance↗

PubMed1992

[Bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C4 (LTC4) and LTD4 in guinea pigs].

Leukotriene (LT) has been suggested to play an important role in the pathogenesis of bronchial asthma. In the present study, the effects of intravenous administration of LTC4 and LTD4 on bronchial smooth muscle in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance using a formula that excludes the effect of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of LTC4 and LTD4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of LTC4 and LTD4. Moreover, the LT antagonist ONO-1078 inhibited the effect of LTC4 and LTD4 administration. These results suggest that LTC4 and LTD4 can be important mediators affecting bronchial hyperresponsiveness.

Airway Resistance↗

PubMed1991

Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells.

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.

Cytokines↗

PubMed1991

Changes in cerebral blood flow do not directly affect in vivo recovery of extracellular lactate through microdialysis probe.

Influence of striatal blood flow changes on recovery of extracellular lactate in vivo through a microdialysis probe implanted into the neostriatum was investigated in halothane anesthetized rats. Relative radioactivity loss of [14C]lactate from perfusate medium through a microdialysis probe was continuously measured in vivo as an indicator of relative recovery of extracellular lactate through the probe because both the relative recovery of lactate and the relative hot loss of [14C]lactate through a microdialysis probe were similar to each other in vitro. The relative hot loss of [14C]lactate decreased in parallel with decreases in the striatal blood flow, while it did not significantly change in response to increases in the blood flow up to 200% of control. These results demonstrate that recovery of extracellular lactate in vivo through the microdialysis probe is not directly influenced by changes in the cerebral blood flow.

Animals↗

PubMed1991

Reflex changes in thermogenesis in the interscapular brown adipose tissue in response to thermal stimulation of the skin via sympathetic efferent nerves in anesthetized rats.

Reflex responses of both temperature in the interscapular brown adipose tissue (IBAT) and activity of the sympathetic efferent nerves innervating the IBAT to cutaneous thermal stimulation were examined in anesthetized rats. Thermal stimulation of the ear at 4 degrees C for 20 s produced a transient decrease in the temperature of the IBAT during this period, followed by a prolonged increase (lasting 7 min). This response was completely abolished in animals whose IBAT sympathetic nerves were bilaterally sectioned. Direct recording of IBAT sympathetic efferent activity revealed that thermal stimulation of the ear at 4 degrees C for 20 s increased activity for 80 s after the onset of stimulation. The threshold temperature of the cold stimulation for eliciting increased nerve activity was around 22 degrees C. However, warm stimulation up to 49 degrees C had no significant effect on activity. In addition to stimulation of the ear, cold stimulation of the face and neck at 4 degrees C also increased nerve activity, while warm stimulation at 49 degrees C of any skin area had no influence. The present results demonstrate that excitation of cutaneous cold receptors, but not warm or heat receptors, reflexly increases thermogenesis in the IBAT via excitation of sympathetic nerve activity, and that cold receptor afferents to cranial and cervical segments effectively increase nerve activity in the IBAT.

Adipose Tissue, Brown↗

PubMed1991

Noxious and innocuous mechanical cutaneous stimulation increase the sympathetic efferent nerve activity innervating the interscapular brown adipose tissue in anesthetized rats.

Effects of pinching and brushing of the various segmental skin areas (face, ear, neck, forelimb, chest, abdomen, hindlimb) on the activities of the sympathetic efferent nerve innervating the interscapular brown adipose tissue (IBAT) and contributing to its thermogenesis were examined in anesthetized rats. Pinching the face, ear, neck, or forelimb produced significant reflex increases in the efferent nerve activities, whereas pinching the chest, abdomen, or hindlimb did not produce any significant responses. In the case of brushing stimulation, only the stimulation of the ear produced significant increases. These results demonstrated that cutaneous mechanical stimulations at cranial, cervical, and upper thoracic segments were effective in producing reflex increases in the activities of the IBAT sympathetic nerve and that noxious stimulation was more dominant for eliciting the reflex responses.

Adipose Tissue, Brown↗

PubMed1991

HTLV-I associated myelopathy (HAM) after blood transfusion in a patient with CD2+ hairy cell leukemia.

Hairy cell leukemia complicating hemolytic anemia developed in a 46-year-old woman. Morphologically and cytochemically typical hairy cells were found to express both CD20 and CD2 antigens. Expression of surface IgG of kappa-chain type and the rearrangement of Ig but not T-cell receptor beta genes confirmed a B-cell origin of the leukemia. Blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia. However, the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having HTLV-I associated myelopathy (HAM) by the demonstration of HTLV-I antibodies in serum and cerebrospinal fluid. HTLV-I infection via the transfusion may have been involved in the hematologic improvement seen in this patient. Autopsy showed demyelination, vacuolar degeneration, gliosis, and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration.

Anemia, Hemolytic↗

PubMed1991

Responses of blood flow, extracellular lactate, and dopamine in the striatum to intrastriatal injection of endothelin-1 in anesthetized rats.

Recently a histological study has demonstrated that intrastriatally injected endothelin-1 (ET-1) produced ischemia-like lesions in the neostriatum. The present study was undertaken to investigate whether intrastriatally injected ET-1 produces ischemic responses such as a decrease in the striatal blood flow and increases in extracellular lactate and dopamine levels in the neostriatum as seen in other models of ischemia. A small needle (for injection of ET-1), a microdialysis probe (for collecting extracellular substances), and a probe of a laser Doppler flowmeter (for measuring local cerebral blood flow) were implanted with their tips close to each other in the neostriatum of halothane-anesthetized rats. Focal administration of ET-1 (430 pmol) into the neostriatum resulted in a marked decrease in striatal blood flow without any change in systemic blood pressure. It also markedly increased extracellular lactate and dopamine levels, whereas it decreased pyruvate and dopamine metabolite levels. These changes agreed well with those known to be produced by ischemia. Intracerebral injection of ET-1 will therefore provide a new model for production of local ischemia in experimental animals.

Anesthesia↗

PubMed1991

Failure of inhibitory effects by platelets on super-oxide anion generation from stimulated neutrophils in a severe bronchial asthmatic.

Blood was drawn from healthy human volunteers and a 30-year-old woman with severe bronchial asthma (atopic and perennial type), whose peripheral blood platelets counts were continuously higher than 60 x 10(4)/mm3. Neutrophils were purified on a Conray-Ficoll gradient and platelets were isolated by a gel filtration method with Sepharose 2B. Superoxide anion (O2-) generation from the cells was measured by 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]purazin-3-one (MCLA)-dependent luminescence. Addition of 0.5 microM MCLA and 10(-8) M N-formyl-methionyl-leucyl-phenylalanine (fMLP) or 10 ng/ml phorbol myristate acetate (PMA) to a suspension of platelets obtained from the healthy controls and the patient caused no significant MCLA-dependent luminescence, 02- generation by neutrophils from healthy human volunteers, activated by 10(-8) M fMLP or 10 ng/ml PMA, was inhibited by their platelets in a concentration-dependent manner. Platelets from the patient failed to inhibit O2- generation from neutrophils activated by 10(-8)M fMLP. Cu-Zn superoxide dismutase concentrations in platelets from healthy human volunteers were not higher than the patient's. These data suggest that the absence of inhibition of superoxide generation from activated neutrophils by platelets might be involved in the pathogenesis of bronchial asthma.

Adult↗

PubMed1991

Naturally occurring aliphatic polyamines-induced histamine release from rat peritoneal mast cells.

Rat peritoneal mast cells were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1-10 mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose-dependent manner. The effect of 10 mM spermine and spermidine was as much as that of 0.5 microgram/ml compound 48/80. The histamine release from the cells incubated with each polyamine was rapid and the amount of histamine release into the supernatant solutions reached a maximum at 1 min with the incubations. 0.1 mM spermine, which in itself could not cause a significant histamine release, showed a tendency to enhance anti-IgE-induced histamine release from the mast cells.

Animals↗