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Biomedical subjects

T Takaishi

Publications and source records attributed to T Takaishi.

At least 55 records · Page 3Linked to original sources

Modulation of human basophil histamine release by insulin-like growth factors.

Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.

Basophils↗

Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma.

There is increasing evidence for the role of basophils in the pathogenesis of bronchial asthma. To examine the presence of basophils in the airways of patients with fatal asthma by immunohistochemistry, we stained lung tissues from four post-mortem cases who had died from severe asthmatic attacks and four controls with a monoclonal antibody raised against tryptase (AA-1) and anti-IgE. Mast cells and basophils were identified in the bronchioles as AA-1- and anti-IgE-positive cells, and anti-IgE-positive cells, respectively. Airway mast cells were found beneath the basement membrane, near blood vessels in the submucosa, and adjacent to the submucosal glands, and scattered throughout the muscle bundles. There was a significant increase of mast cells in the asthma group compared with the control group (203.5+/-84.6/mm2, mean+/-s.d. vs 37.7+/-8.7/mm2, P<0.05, n=4). In contrast, basophils were observed in the airway lumen, in the bronchial epithelium and in the submucosa. The number of basophils in the bronchioles was 81.8+/-55.5/mm2 (n = 4); however, basophils were not found at all in the airways of the control group. Although eosinophils, B lymphocytes and macrophages bear low affinity IgE receptors and could react with anti-IgE, the location of these cells in the close sections did not correspond closely with basophils. The presence of basophils in lung tissues obtained from fatal asthma patients supports the view that basophils play a role in the pathogenesis of bronchial asthma.

Adult↗

Determination of maximal power output at neuromuscular fatigue threshold.

The purpose of this study was to determine the maximal power output at the neuromuscular fatigue threshold (EMGFT), as estimated from electromyographic (EMG) data from representative leg muscles during cycling. The rate of rise in integrated EMG activity as a function of time (iEMG slope) was calculated at each of four constant-power-output ergometer bouts for 20 subjects. The iEMG slopes were plotted against work rates that were well described as linear functions (0.84 < R2 < 0.99). This iEMG slope vs. work rate relationship was extrapolated to zero slope to give an intercept on the power axis that was interpreted as the highest work rate sustainable without EMG evidence of neuromuscular fatigue (EMGFT). Each individual EMGFT was then expressed in terms of an O2 output (VO2) equivalent on the basis of the individual delta efficiency calculated during a linearly increasing maximal exercise test on the same bicycle ergometer. Results indicated a highly significant correlation (r = 0.92, P < 0.01) between EMGFT VO2 and anaerobic threshold VO2, as determined by conventional gas exchange criteria. The mean EMGFT VO2 (1.84 +/- 0.55 l/min) was, however, significantly greater (P < 0.01) than the anaerobic threshold VO2 (1.72 +/- 0.54 l/min). It was suggested that the EMGFT may provide an attractive alternative to the measurement of the highest work rate that can be sustained without evidence of neuromuscular fatigue.

Adult↗

Human neuroblastoma cells express alpha and beta platelet-derived growth factor receptors coupling with neurotrophic and chemotactic signaling.

Both platelet-derived growth factor (PDGF) A- and B-chains are expressed in mammalian neurons, but their precise roles still remain to be clarified. In the present studies, we examined the expression of two PDGF receptor genes in human tumor cell lines derived from neural crest. The expression of alpha and/or beta PDGF receptors was detected in a wide variety of neural crest-derived human tumor cell lines such as neuroblastoma, primitive neuroectodermal tumor, and Ewing's sarcoma by RNA blot analysis, and confirmed by immunoblot analysis. We have also demonstrated that PDGF receptors on the human neuroblastoma cell lines were biologically functional. Accordingly, chemotactic and mitogenic activities were induced by either PDGF-AA or PDGF-BB in serum-free medium. PDGF isoforms as well as nerve growth factor induced morphological changes showing neuronal cell maturation. Moreover, PDGF coordinately increased the levels of the transcript of the midsize neurofilament gene. The neuroblastoma cell lines also expressed the transcripts of PDGF A- and B-chains. These findings suggest that PDGF isoforms are involved not only in the promotion of the neuroblastoma cell growth, but also in neuronal cell migration, growth, and differentiation in human brain development.

Amino Acid Sequence↗

[The role of mast cells and basophils in the pathogenesis of bronchial asthma].

Bronchial asthma has now been recognized as an inflammatory disease. The present study was undertaken to evaluate the role of mast cells and basophils in the pathogenesis of bronchial asthma. Stem cell factor, a growth factor of mast cells, activates rat peritoneal mast cells and human lung mast cells to release histamine. We demonstrated the presence of basophils in lung tissues obtained from fatal asthma cases using immunohistochemical techniques. IL-3, GM-CSF, IL-5 and IGF-I enhanced basophil histamine release. These findings indicate that mast cells and basophils have important roles in the pathogenesis of bronchial asthma.

Animals↗

Stem cell factor has histamine releasing activity in rat connective tissue-type mast cells.

Stem cell factor (SCF) was documented to be involved in the growth of mast cells controlled by fibroblasts. We tested the effect of recombinant rat SCF on degranulation from rat peritoneal mast cells (connective tissue-type mast cells: CTMC). SCF induced histamine release (approximately 20% of total histamine content) in a dose-dependent fashion. The release response was relatively rapid and reached a maximum within 5 min. The release showed total dependence on the presence of extracellular phosphatidylserine (PTS). These results reveal that SCF has histamine releasing activity in CTMC.

Animals↗

Relationship between muscle fatigue and oxygen uptake during cycle ergometer exercise with different ramp slope increments.

The surface electromyogram (EMG) from active muscle and oxygen uptake (VO2) were studied simultaneously to examine changes of motor unit (MU) activity during exercise tests with different ramp increments. Six male subjects performed four exhausting cycle exercises with different ramp slopes of 10, 20, 30 and 40 W.min-1 on different days. The EMG signals taken from the vastus lateralis muscle were stored on a digital data recorder and converted to obtain the integrated EMG (iEMG). The VO2 was measured, with 20-s intervals, by the mixing chamber method. A non-linear increase in iEMG against work load was observed for each exercise in all subjects. The break point of the linear relationship of iEMG was determined by the crossing point of the two regression lines (iEMGbp). Significant differences were obtained in the exercise intensities corresponding to maximal oxygen uptake (VO2max) and the iEMGbp between 10 and 30, and 10 and 40 W.min-1 ramp exercises (P < 0.05). However, no significant differences were obtained in VO2max and VO2 corresponding to the iEMGbp during the four ramp exercises. With respect to the relationship between VO2 and exercise intensity during the ramp increments, the VO2-exercise intensity slope showed significant differences only for the upper half (i.e. above iEMGbp). These results demonstrated that the VO2max and VO2 at which a nonlinear increase in iEMG was observed were not varied by the change of ramp slopes but by the exercise intensity corresponding to VO2max and the iEMGbp was varied by the change of ramp slopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Haemopoietic growth factors induce human basophil migration in vitro.

Accumulation of basophils in inflammatory sites is an important aspect of the late-phase allergic reaction involving skin and upper and lower airways, suggesting the existence of mechanisms for basophil migration. Because haemopoietic growth factors have been shown to stimulate various functions of human basophils, we tested the ability of haemopoietic growth factors to migrate basophils in vitro. Both IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced migration of purified normal basophils (purity c. 80%) in a dose-dependent fashion at picomolar concentrations, while granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no effect at all. Chequerboard analyses indicate that migratory activity of both factors are chemokinetic. These results suggest that local production of both factors during allergic reactions might potentially play an initial role in the recruitment of basophils from the circulation to sites of inflammatory reactions.

Antibodies↗

Evidence for distinct neuronal localization of gamma and delta subunits of Ca2+/calmodulin-dependent protein kinase II in the rat brain.

Localization of the gamma and delta types of mRNAs for Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) was determined in the rat brain, making use of in situ hybridization histochemistry. The gamma and delta mRNAs as well as the alpha and beta mRNAs for CaM-kinase II were heterogeneously and distinctly distributed. In the Purkinje cell layer of the cerebellum, alpha, beta, and gamma mRNAs but not delta mRNA were present, whereas beta, gamma, and delta mRNAs were present in the locus coeruleus. These findings provide evidence that CaM-kinase II exists in a variety of forms in different cells composed of a variable number and type of subunits.

Animals↗

Hemopoietic growth factors regulate the survival of human basophils in vitro.

Human basophils were purified from normal peripheral blood, using density gradient followed by negative panning selection. We tested the effects of hemopoietic growth factors on the survival of these basophils in vitro. In the absence of exogenous factors, basophils (purity greater than 90%) decreased in number rapidly. At day 7 only 11% of the cells remained alive in cultures; less than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte-macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the survival; 33% of cells remained at day 7. Other growth factors including granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on the survival of basophils at all. Morphological and functional characterization of cells maintained by IL-3 revealed that they belonged to the basophil lineage. These observations indicate that normal basophils possess functional receptors for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type hypersensitivity reactions by prolonging the life span of basophils.

Basophils↗

Mouse IL-3 induces histamine release from mouse peritoneal mast cells.

In this study, we have attempted to determine whether mouse peritoneal mast cells released histamine in response to IL-3. Recombinant mouse (m)IL-3 induced histamine release from mouse peritoneal mast cells in a dose-dependent fashion. Histamine release did not occur in the absence of phosphatidyl serine (PS), and was dependent on PS concentrations. The release was 14.3 +/- 3.8 and 43.5 +/- 11.5% (mean +/- SEM, n = 5) at 1 nM IL-3 in the presence of 10 and 20 micrograms/ml of PS. Calcium was required for the response, and in the absence of calcium, significant histamine release was not observed. The kinetics were slower than those of anti-IgE-induced response. IL-3-induced histamine release reached a peak within 15 min, while that by anti-IgE reached 80% of the maximum in 3 min. Lower concentrations of IL-3, which failed to directly induce histamine release, did not enhance anti-IgE-induced histamine release. Other cytokines, including mIL-4, mIL-5, m-granulocyte-macrophage colony-stimulating factor, human (h)IL-1 alpha, hIL-1 beta and hIL-8, neither induced histamine release nor enhanced anti-IgE induced histamine release. IL-4 had no capacity to enhance IL-3-induced histamine release. These results suggest that locally produced IL-3 might modulate mast cell-related inflammation through histamine release from mast cells.

Animals↗

Differential distribution of the mRNA encoding two isoforms of the catalytic subunit of calcineurin in the rat brain.

The distribution of mRNAs encoding two distinct isoforms of the catalytic subunit of calmodulin-dependent protein phosphatase (calcineurin A), designated calcineurin A alpha and A beta, in the rat brain was examined by using Northern blots and in situ hybridization histochemistry. The mRNAs for calcineurin A alpha and A beta were both unevenly present in the brain and showed different distribution. The differential distribution between calcineurin A alpha and A beta messages suggests that the individual isoforms are involved in specialized neural functions.

Animals↗

Enhancement of human basophil histamine release by interleukin 5.

Substantial evidence indicates a close relationship between eosinophils and basophils. We examined whether interleukin 5 (IL-5), known to be eosinophilopoietic and capable of selectively regulating eosinophil functions, has an affect on basophil functions. IL-5 enhanced basophil histamine release evoked by anti-IgE, formyl-methionyl-leucyl-phenylalanine, or ionophore A23187 at picomolar concentrations. Direct action of IL-5 on human basophils was confirmed using highly purified basophil populations. These observations reveal the novel fact that IL-5 is able to modulate basophil functions as well as eosinophil functions, and suggest that normal human basophils possess functional receptors for IL-5.

Basophils↗

Enhancement of basophil histamine release by a human basophil-like cell promoting activity.

A basophil-like cell promoting activity (BaPA) is a lymphokine which has the ability to proliferate metachromatically staining cells in human bone marrow. We studied the effect of BaPA on histamine release from human peripheral basophils. BaPA did not directly induce histamine release from basophils. However BaPA ranging from 0.001 to 0.5 U/ml enhanced histamine release from basophils stimulated with anti-IgE, calcium ionophore A23187 or FMLP in a dose-dependent manner. On the basis of recent observations that in addition to their capacity for proliferating progenitor cells, colony-stimulating factors are capable of regulating functions of end-stage cells of the same lineage, this finding that BaPA is able to modulate a basophil function raises the possibility that BaPA also regulates progenitors of basophils.

Basophil Degranulation Test↗

[A case of food-dependent-exercise induced anaphylaxis possibly induced by shellfish (Sulculus Supertexta and Turbo Cornutus)].

A 17 years old girl experienced an anaphylactic reaction of urticaria, dyspnea, syncope and hypotension while riding a bicycle 55 minutes after eating shellfish Lapas shellfish which was a-like Sulculus Supertexta (SS). She recovered within several hours after the emergency treatment. Another attack occurred 3 months later while she was running with a dog 30 minutes after eating shellfish (Turbo Cornutus; TC). RAST scores were 4 for Lapas and 2 for TC. RAST inhibition test by ELISA showed a high crose-reaction between keyhole limpet hemocyanin (KLH) and Lapas, and between KLH and TC, while the cross reaction between Lapas and TC was low. Gel chromatography with sephacryl G-200 revealed that both Lapas and TC had several allergens with different molecules which were detected by ELISA. Exercise challenge produced an immediate fall of FEV1 and a significant increase in plasma histamine levels for 45 minutes.

Adolescent↗

Functional differences of human basophils with different densities.

It has been reported that blood basophils comprise two populations of different densities. In this study, we compared the responses of two populations of basophils (band-1 and 2 basophils) to several secretagogues and anti-allergic agents. Twelve patients with bronchial asthma, 3 patients with Japanese cedar pollinosis and 6 healthy subjects were included in this study. Band-2 basophils collected from the interface between Percoll of density 1.078 and 1.068 g/ml released histamine better in response to anti-IgE than band-1 basophils taken from the interface between plasma and Percoll 1.068 (band 1 vs. band 2, 13.2 +/- 2.7 vs. 21.4 +/- 3.6% at 1:10(5), p less than 0.01; 47.1 +/- 5.0 vs. 57.7 +/- 6.1% at 1:10(4), p less than 0.01). Band-2 basophils also responded better to formyl-methionyl-leucyl-phenylalanine than band-1 basophils (34.4 +/- 4.9 vs. 43.2 +/- 5.6% at 10(-6) M, p less than 0.01; 35.6 +/- 5.0 vs. 45.2 +/- 5.7% at 10(-5) M, p less than 0.01). In contrast, band-1 basophils were much more sensitive to the calcium ionophore A23187 stimulation than band-2 basophils (13.0 +/- 3.7 vs. 6.3 +/- 1.8% at 0.05 microgram/ml, p less than 0.05; 52.5 +/- 4.3 vs. 33.8 +/- 3.9% at 0.1 microgram/ml, p less than 0.01; 71.3 +/- 3.3 vs. 51.5 +/- 4.2% at 0.2 microgram/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗