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Biomedical subjects

T Kawashima

Publications and source records attributed to T Kawashima.

At least 109 records · Page 6Linked to original sources

Histamine release induced by human natriuretic peptide from rat peritoneal mast cells.

We have been interested in the effects of some popular peptides on tracheal smooth muscle. Previously, we reported that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) had dose-dependent relaxant effects on guinea pig tracheal smooth muscle. In this study, we compared the effects of ANP, BNP and CNP on histamine release from rat peritoneal mast cells. ANP and BNP were more potent than CNP, dose-dependently increasing histamine release at a concentration of 10(-7) M or higher. CNP induced histamine release at a concentration of 10(-6) M or higher. Extracellular calcium inhibited the histamine release induced by all 3 peptides. In conclusion, the effects of these 3 peptides in rat peritoneal mast cells demonstrated adverse reactions for respiratory diseases, although our previous results showed that these peptides caused relaxation of guinea pig tracheal smooth muscle. We should note that the drugs have different actions in each organ.

Amino Acid Sequence↗

Successful coronary artery bypass grafting for a patient with myelodysplastic syndrome: report of a case.

We report herein the case of a 61-year-old man with myelodysplastic syndrome causing pancytopenia who underwent successful coronary artery bypass grafting (CABG). Preoperatively, his hemoglobin (Hb) value was 10.4 g/dl while receiving transfusions of 1 or 2 units of red blood cells (RBC) every 2 weeks, his white blood cell (WBC) count was 8200/microliter with injections of 100 micrograms granulocyte colony-stimulating factor (G-SCF) every 5 days, and his platelet count was 4.5 x 10(4)/ microliter without platelet transfusion. From the time the pancytopenia was diagnosed in his peripheral blood, he had received a total of 104 units of RBC and 472 units of platelets, following which he developed an antiplatelet antibody, not for a platelet-specific antigen, but for an HLA antigen. Thus, HLA-matched platelets were prepared to prevent bleeding caused by thrombocytopenia, and the WBC count was elevated preoperatively by G-CSF injections. Thereafter, CABG was performed on three vessels. The HLA-matched platelets were transfused as the patient was weaned from the extracorporeal circulation. As a result of these preparations, we were able to protect the patient against bleeding and infection.

Antibodies↗

GABAergic characteristics of transcallosal activity of cat motor cortical neurons.

GABAergic characteristics of transcallosal activity of cat pyramidal tract neurons (PTNs) and non-PTNs (nPTNs) were studied with stressing on GABAB receptors. PTNs and nPTNs were further classified into group 1 (< 10 ms) and group 2 (> 10 ms) based on the latency upon transcallosal stimulation. However, mainly the results of group 1 neurons were presented here, due to the small number of group 2 neurons. GABA, bicuculline, CGP 35348 and phaclofen were iontophoretically applied. The spike number to 20 trials of transcallosal stimulation was 8.9 +/- 4.3 (mean +/- S.D.) for group 1 PTNs (n = 14) and 10.4 +/- 4.5 for group 1 nPTNs (n = 38) under the control conditions. CGP 35348, phaclofen and bicuculline significantly increased the spike numbers in both cases. The increase was greater for nPTNs than for PTNs. GABA decreased them. The transcallosal latency was 3.9 +/- 1.1 ms for PTNs under the control conditions. CGP 35348, phaclofen and bicuculline significantly shortened the latency, and GABA elongated it. The transcallosal latency for nPTNs under the control conditions was 2.7 +/- 1.2 ms. This was significantly shortened by application of CGP 35348, phaclofen or bicuculline. GABA restored it. In conclusion, CGP 35348, phaclofen and bicuculline increased spike discharge and shortened the latency upon transcallosal stimulation for both group 1 PTNs and nPTNs.

Animals↗

Determination of ultratrace amounts of copper (II) by its catalytic effect on the oxidative coupling reaction of 3-methyl-2-benzothiazolinone hydrazone with N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline.

A spectrophotometric method was developed for the determination of ultratrace amounts of copper(II) based on its catalytic effect on the oxidative coupling reaction of 3-methyl-2-benzothiazolinone hydrazone with N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline to produce an intensely coloured dye (lambda(max) = 525 nm) in the presence of hydrogen peroxide. In this reaction, pyridine acted as an effective activator for the catalysis of copper(II). By measuring the absorbance of the dye, copper(II) can be determined at the 0.002-0.1 ng cm(-3) (3.1 x 10(-11)-1.6 x 10(-9) mol dm(-3) level. The relative standard deviation for ten determinations of 0.06 ng cm(0-3) of copper(II) was 2.6%. The proposed method was successfully applied to the determination of copper(II) in tap water and biological material.

Aniline Compounds↗

Phenotypic change and proliferation of murine Kupffer cells by colony-stimulating factors.

Kupffer cells were isolated from C57BL/6 mice by collagenase perfusion and assessed for response to colony-stimulating factors (CSFs) in terms of their phenotypic change and proliferation. Kupffer cells expressed F4/80, but not Mac-1, CD71, or asialo-GM1 initially. This phenotype pattern was different from that of alveolar and peritoneal macrophages. After stimulation with recombinant human macrophage CSF (M-CSF) or mouse granulocyte-macrophage CSF (GM-CSF), Kupffer cells expressed Mac-1 and a low level of CD71 in addition to F4/80 and increased in phagocytotic activity in association with the expression of CR3. Both M-CSF and GM-CSF, but not human IL-3, induced the proliferation of Kupffer cells in a dose-dependent manner, and after 7 days, the number of the cells increased to about four to six times the initial number. The relatively high dose of GM-CSF downmodulated the M-CSF receptor on Kupffer cells and inhibited the cell proliferation induced by the optimal dose of M-CSF. These data indicated that murine Kupffer cells have a different phenotype from other macrophages and that they respond to M-CSF and GM-CSF, leading to functional maturation and proliferation.

Animals↗

Identification of mRNA-rich keratinocytes in the basal/suprabasal layers of psoriatic skin.

In this study, we examined the relative amounts of mRNA expressed in normal versus psoriatic epidermis, using in situ hybridization with a biotinylated oligonucleotide poly d(T) probe. The hybridization image was analyzed by Laser Scanning Confocal Microscopy (LSCM). In normal human skin, hybridization signals were detected homogeneously throughout the epidermis, mostly in nucleus. These signals disappeared following RNase T2 or RNase A treatment, indicating that the target for this probe is RNA; by implication, mRNA. In psoriatic lesions, the overall signal intensity was significantly elevated, especially in the basal/suprabasal layers. Moreover, those signals were most prominent in the cytoplasm, not in the nucleus. In contrast, the signals of uninvolved epidermis adjacent to the psoriatic lesions were indistinguishable from those of normal skin in both signal intensity and hybridization profile. Our data are consistent with the notion that one of the characteristic features of psoriasis is an elevated (or uncontrolled) synthesis of mRNA and proteins.

Biopsy, Needle↗

Isolation and structural analysis of polysaccharide containing galactofuranose from the cell walls of Bifidobacterium infantis.

We isolated cell wall polysaccharides (PS-1 and PS-2) from Bifidobacterium infantis Reuter ATCC 15697 and found that the backbone of PS-2 is-->3)-beta-D-Galf-(1-->3)-alpha-D-Galp- (1-->in which beta-D-Galf and alpha-D-Galp are partially substituted at O-6 with beta-D-Glcp. This is the first report of the presence of this disaccharide backbone in a gram-positive bacterium; it resembles the O antigen of some bacteria.

Bifidobacterium↗

Expression of high-affinity IgE receptor (Fc epsilon RI) on human alveolar macrophages from atopic and non-atopic patients.

The expression of high-affinity IgE receptor (Fc epsilon RI) on alveolar macrophages was examined in order to determine the association of alveolar macrophages with IgE-dependent inflammation. Immunostaining showed that a 15-1 monoclonal antibody against Fc epsilon RI alpha chain reacted with alveolar macrophages from both atopic and non-atopic patients by immunostaining. In addition, preincubation of 15-1 monoclonal antibody specifically blocked monomeric IgE binding to alveolar macrophages. Reverse transcription polymerase chain reaction showed that CD14+ alveolar macrophages expressed Fc epsilon RI alpha, beta and gamma chain mRNA. These results show that alveolar macrophages express Fc epsilon RI and may participate in IgE-dependent inflammation mediated by Fc epsilon RI.

Bronchoalveolar Lavage Fluid↗

Macrophage colony-stimulating factor induces interleukin-8 production in human monocytes.

We have investigated the stimulatory effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on interleukin-8 (IL-8) production by human peripheral blood monocytes. When monocytes were prepared from peripheral blood and cultured for 24 hours, the average amount of IL-8 in the culture medium was about 8.9 +/- 3.2 ng/2 x 10(5) cells. In contrast, the production of IL-8 by monocytes increased to a level of 19.2 +/- 4.7 ng/2 x 10(5) cells in response to rhM-CSF. This induction by rhM-CSF was dose-dependent. Northern blot analysis showed that expression of IL-8 at the pretranslational level was enhanced after M-CSF treatment. Kinetic studies showed that secretion of IL-8 from monocytes was enhanced within 2 hours after exposure to rhM-CSF, and a saturation level, which was reached around 48 hours, was two-fold higher than that of cells without M-CSF treatment. In addition, conditioned medium of M-CSF-stimulated monocytes activated the chemotaxis of human neutrophils, and this activity was significantly inhibited by anti-IL-8 antibody. These results, taken together, suggest that M-CSF can affect many cellular functions through regulation of IL-8 expression in monocytes.

Animals↗

GABAB receptor antagonist CGP 35348 shortens transcallosal response latency of pyramidal tract neurons.

The effects of a specific GABAB receptor antagonist, p-(3-aminopropyl)-p-diethoxymethyl-phosphonic acid (CGP 35348), on pyramidal tract neuron responses to transcallosal stimulation were investigated in the cat motor cortex in vivo. Iontophoretic application of CGP 35348 significantly increased the number of spikes from 10.3 +/- 4.4 (control; n = 27; mean +/- S.D.) to 16.7 +/- 7.2 (CGP 35348) for 20 transcallosal stimulation trials, while the latency of neuronal activity was significantly shortened from 4.4 +/- 2.1 ms (control; n = 27; mean +/- S.D.) to 3.8 +/- 1.7 ms (CGP 35348). In conclusion, CGP 35348 facilitated transcallosal synaptic transmission between pyramidal tract neurons by removal of GABAB inhibition.

Action Potentials↗

Increased susceptibility of angiographically smooth left anterior descending coronary artery to an impairment of vasoresponse to acetylcholine, and the relation between impaired vasoresponse and low-density lipoprotein cholesterol level.

In the present study, we demonstrated that the angiographically smooth LAD is more susceptible than the LC to an impairment of vasoresponse to acetylcholine, suggesting the more severe endothelial dysfunction in the LAD. We also showed that levels of LDL play a partial but important role on endothelial dysfunction.

Acetylcholine↗

Radioactive 2-DG incorporation patterns in the mesial frontal cortex of task-performing monkeys.

The pattern of radioactive 2-deoxy-D-glucose (2-DG) uptake in the rostral mesial cortex was investigated in seven hemispheres of four task-performing monkeys (a delayed-response task performed with a forelimb). A two-dimensional 2-DG map was constructed from frontal sections. Blob-like 2-DG incorporation sites (2-DG active sites) were observed in single frontal sections, e.g., in the anterior cingulate gyrus (CiG) and supplementary and primary motor cortices in the mesial surface, and around the superior precentral sulcus in the premotor area. Blob-like 2-DG incorporation sites were also observed in the medial part of the dorsal frontal cortex near the midline. However, most of these blob-like 2-DG active sites were revealed in fact not to be blobs. They formed rostrocaudally continuous streaks when they were constructed in a two-dimensional map. Streaks fused with one another in some areas, and gave off branches in other areas. These 2-DG uptake patterns were similar between the paired left and right hemispheres of three brains. It is highly probable that these 2-DG active streaks (or blobs) reflected neuronal activity related to somatomotor and/or eye movements, because the 2-DG-labeled areas included motor, premotor, supplementary motor, and possibly part of the supplementary eye fields. It is also probable that this 2-DG incorporation was related to cognitive or memory functions, because neuronal activity related to performance of a delayed-response was reported in the rostral mesial cortex and in the CiG.

Animals↗

The effects of cyclosporin A and FK506 on proliferation and IL-8 production of cultured human keratinocytes.

The present study was conducted to determine whether cyclosporin A (CsA) and FK506 could be effective in inhibiting the proliferation and cytokine secretion of normal human epidermal keratinocytes (NHEK). NHEK proliferation in the presence of CsA and FK506 at the concentrations 10(-9) to 10(-5) M at 24 and 48 h time points was measured colorimetrically by the MTS assay. CsA had inhibitory effects from 10(-6) to 10(-5) M, while FK506 had no effect, except for toxicity at the very highest concentrations (5 x 10(-6) M and higher). NHEK cells spontaneously secrete IL-8 (243.4 +/- 55.5 pg/ml), and this baseline level was augmented by TNF-alpha alone, or synergistically by TNF-alpha and IFN-gamma, which are thought to be secreted by T cells. Neither CsA nor FK506 had any significant effect on either spontaneous or cytokine-stimulated keratinocyte IL-8 production. Therefore, it is most likely that the two drugs indirectly inhibit the keratinocyte inflammatory response through their actions on T cells or other immunocompetent cells.

Cell Division↗

Augmentation of cancer chemotherapy by preinjection of human macrophage colony-stimulating factor in L1210 leukemic cell-inoculated mice.

Human macrophage colony-stimulating factor (hM-CSF) is a potent stimulator of the effector functions of monocytes/macrophages. We investigated the antitumor effects of this factor in CDF1 male mice inoculated with L1210 cells, a mouse B-cell leukemia line. Mice preinoculated with various numbers of L1210 cells on day 0 were given intravenous injections of vehicle (human serum albumin; HSA) (100 micrograms/kg/day) or hM-CSF (20 micrograms/kg/day) for 3 days from day 1. In mice preinoculated with 10(2) L1210 cells but not with 10(3) or more L1210 cells, a marked increment in survival rate was observed with hM-CSF treatment. We next examined the effect of hM-CSF treatment combined with chemotherapy on the survival of mice that had been preinoculated with 10(5) L1210 cells. In our system, the administration of 4.9 mg/kg adriamycin (ADM) alone slightly prolonged survival of the tumor-bearing mice, but all of the mice died within 20 days. When hM-CSF was injected for 3 days before this ADM treatment, the invasion and proliferation of tumor cells in the liver and spleen were markedly inhibited and 50% of the mice were still alive at day 50. We detected inhibitory activity toward L1210 growth in serum of mice administered with hM-CSF, and the degree of the inhibitory activity was correlated with the level of nitrite (NO2-) in the serum. When L1210 cells were co-cultured with peritoneal macrophages from mice intraperitoneally injected with hM-CSF, the uptake of [3H]thymidine in L1210 cells was inhibited. The inhibition was abolished by the addition of NG-monomethyl-L-arginine, an inhibitor of NO2- synthesis, suggesting that the reactive nitrogen oxide intermediate is involved in hM-CSF-induced inhibition of L1210 growth.

Amino Acid Oxidoreductases↗

Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis.

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.

Animals↗

[Metabolism of lomerizine hydrochloride (KB-2796) in rats].

The metabolism of lomerizine was investigated after the oral administration of [methine-14C] or [benzyl-14C]lomerizine hydrochloride in rats. 1. Urinary, fecal and biliary excretions of the unchanged drug were less than 1% of dose, showing that lomerizine was eliminated by the extensive biotransformation after the oral administration. 2. The main metabolites were 1-(2,3,4-trimethoxybenzyl)piperazine (M7) and 2,3-dimethoxy-4-hydroxybenzylpiperazine in the urine, and 1-[bis(4-fuluorophenyl)methyl]-4-(2,3-dimethoxy-4-hydroxybenzyl)pi perazine in the feces and bile. 3. The radioactive substances in the plasma, liver and brain mainly existed as unconjugated forms, of which the intact drug showed the highest concentration. 4. The main metabolites in the plasma, and in the liver and brain were 1-[bis(4-fuluorophenyl)methyl]-4-(3,4-dimethoxy-2-hydroxybenzyl)pi perazine and bis(4-fluorophenyl)methylpiperazine (M6), respectively. 5. The plasma level of M7 and the biliary excretion of bis(4-fluorophenyl)-methanol in male rats were higher than those in female rats, suggesting the sex difference in the N-dealkylation at the 4-position of piperazine ring of the drug.

Administration, Oral↗

Geographical distribution of the Hbb haplotypes in the Mus musculus subspecies in eastern Asia.

We surveyed the geographical distribution of Hbb haplotypes of the house mouse, Mus musculus, in the former USSR and the northern part of China. Mice with the w1 haplotype were distributed from the coastal area of the Black Sea to the Maritime Province of Siberia in the former USSR and in the area north of the Yangtze River in China. Mice with the p haplotype were found in the areas surrounding those populated with the w1 haplotype mice. In the Maritime Province and the southern part of Siberia, the d haplotype was predominant. The correlation between the geographical variation of the Hbb haplotypes and the distribution of the Mus musculus subspecies in the eastern part of the Eurasian Continent, is discussed.

Animals↗