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J Nishimura

Publications and source records attributed to J Nishimura.

At least 19 recordsLinked to original sources
PubMed2001

Ca(2+) influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery.

1. To determine the mechanism of bradykinin-induced production of endothelium-derived contracting factors, we monitored the changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca(2+)](i) of smooth muscle cells and force in porcine interlobar renal arterial strips using front-surface fluorometry of fura-2. 2. In the presence of N(omega)-nitro-L-arginine methyl ester, bradykinin caused an endothelium-dependent transient elevation of [Ca(2+)](i) and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H(2)/thromboxane A(2) receptor antagonist. 3. In the absence of extracellular Ca(2+), bradykinin failed to induce contraction. However, replenishing extracellular Ca(2+) to 0.75 mM and higher induced an instantaneous contraction. However, replenishing Ca(2+) per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10(-5) M 1-(beta-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365) or 0.2 mM Ni(2+) abolished the contraction induced by bradykinin in the presence of extracellular Ca(2+). 4. Treatment with 10(-5) M indomethacin completely inhibited the contractile response induced by Ca(2+) replenishment, regardless of the timing of its application, before or after the application of bradykinin. 5. In endothelial cells in the valvular strips, bradykinin caused a transient [Ca(2+)](i) elevation in the presence of 1.25 mM extracellular Ca(2+), but [Ca(2+)](i) returned to the resting level within 10 min. Neither 10(-5) M SKF96365 nor 0.2 mM Ni(2+) had any effect on the peak [Ca(2+)](i) elevation, but decreased [Ca(2+)](i) in the declining phase. In the absence of extracellular Ca(2+), bradykinin induced a transient [Ca(2+)](i) elevation to a level similar to that seen in the presence of 1.25 mM extracellular Ca(2+). However, [Ca(2+)](i) then rapidly returned to the prestimulation level within 5 min. Subsequent Ca(2+) replenishment to 0.75 mM and higher in the presence of bradykinin elevated [Ca(2+)](i) to significantly higher levels than the resting level seen in the media containing 1.25 mM Ca(2+). 6. In conclusion, Ca(2+) influx in the endothelial cells is essential for bradykinin to induce endothelium-dependent contraction in the porcine interlobar renal artery.

Animals↗
PubMed2001

Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells.

To better understand the control of apoptosis during erythropoiesis, this study investigated the role of a novel tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells), with regard to the regulation of apoptosis of erythroid progenitor cells. Erythroid colony-forming cells (ECFCs) purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone marrow cells was analyzed, RCAS1R was evident on cells with an immature erythroid phenotype (transferrin receptor(+)/glycophorin A(-)) but not with a mature phenotype (transferrin receptor(-)/glycophorin A(+)). Histochemical staining revealed the expression of RCAS1 in the cytoplasm of bone marrow macrophages. These findings indicate that RCAS1, which is mainly produced by macrophages in hematopoietic tissue, may have a crucial role in controlling erythropoiesis by modulating apoptosis of erythroid progenitor cells via a Fas-independent mechanism.

Adenocarcinoma↗
PubMed2001

Cloning and functional expression of a degradation-resistant novel isoform of p27Kip1.

p27(Kip1) is an inhibitor of cyclin-dependent kinases. It has been implicated as having a role in the induction of growth arrest at the G(1) phase of the cell cycle in response to anti-mitogenic signals such as cell contact and serum starvation. Proteasome-mediated degradation plays an important role in the rapid inactivation of p27(Kip1), causing quiescent cells to re-enter the cell cycle. Although the existence of a second isoform has been suggested, no such isoform was isolated. Through screening of a cDNA library derived from growth-arrested confluent porcine endothelial cells, we obtained clones for a novel isoform of p27(Kip1) in addition to the original isoform. The novel isoform differed from the original isoform at the C-terminus. The tissue-specific expression of the original and novel isoforms was demonstrated at the mRNA and protein levels. An in vitro degradation assay demonstrated this novel isoform to be resistant to proteasome-mediated destruction. The expression as a fusion protein with green fluorescent protein revealed this isoform to be targeted to the nucleus by a bipartite nuclear-localization signal with a C-terminal part different from that of the original isoform. The expression of the novel isoform caused the growth arrest of HeLa cells and an accumulation of cells in the G(0)/G(1) phase, and this effect was similar to that seen with the original isoform. The present study suggests that the novel isoform functions as a negative regulator of the cell cycle, and may play a distinct role. The novel isoform was named p27(Kip1R) because of its resistance to degradation.

Alternative Splicing↗
PubMed2001

Autoimmune neutropenia with cyclic oscillation of neutrophil count after steroid administration.

A 16-year-old female patient was evaluated for pancytopenia. She had a white blood cell count of 1.6 x 10(9)/L with 0.02 neutrophils and a platelet count of 19 x 10(9)/L. In the bone marrow, mature granulocytes were markedly decreased in number, but no atypical cells were present. Antineutrophil antibody was demonstrated by flow cytometry, and the level of platelet-associated immunoglobulin G was increased. A diagnosis of autoimmune neutropenia and thrombocytopenia was made. Interestingly, neutrophil and platelet counts fluctuated cyclically after the initiation of prednisolone therapy. The neutrophil count fluctuated between 0.1 x 10(9)/L and 7 x 10(9)/L, and the platelet count fluctuated between 19 x 10(9)/L and 175 x 10(9)/L, in 4-week cycles. Following splenectomy, neutrophil and platelet counts normalized. We believe the immune mechanism of recurrent neutropenia in this patient differs from that in other patients with cyclic neutropenia reported with stem cell disorders.

Adolescent↗
PubMed2001

Leukotriene C(4) enhances the contraction of porcine tracheal smooth muscle through the activation of Y-27632, a rho kinase inhibitor, sensitive pathway.

1. An unsaturated fatty acid, leukotriene C(4) (LTC(4)), has a potent contractile effect on human airway smooth muscle, and has been implicated in the pathogenesis of human asthma. Using front-surface fluorometry with fura-PE3, the effect of LTC(4) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were investigated in porcine tracheal smooth muscle strips. 2. The application of LTC(4) induced little or no contraction despite a small and transient increase in [Ca(2+)](i). In the presence of LTC(4), however, the contractions evoked by high K(+) depolarization or a low concentration of carbachol (CCh) were markedly enhanced without inducing any changes in the [Ca(2+)](i) levels, thus indicating that LTC(4) increases the Ca(2+) responsiveness of the contractile apparatus. This LTC(4)-induced increase in Ca(2+) responsiveness could partly be reproduced in the permeabilized preparation of tracheal smooth muscle strips. 3. The LTC(4)-induced enhancement of contraction was accompanied by an increase in myosin light chain (MLC) phosphorylation and was blocked by a rho kinase inhibitor (Y-27632), but not by either a PKC inhibitor (calphostin C) or a tyrosine kinase inhibitor (genistein). 4. These results indicated that, in porcine tracheal smooth muscle, LTC(4) enhances the contraction by increasing the Ca(2+) responsiveness of the contractile apparatus in a MLC phosphorylation dependent manner, possibly through the activation of the rho-rho kinase pathway.

Amides↗
PubMed2001

The mechanism for the contraction induced by leukotriene C4 in guinea-pig taenia coli.

The mechanism underlying the LTC(4)-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca(2+)](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which was induced by a typical G-protein mediated agonist, carbachol was also characterized. LTC(4) induced a contraction in the guinea-pig taenia coli in a concentration-dependent manner. The maximal response was obtained at 100 nM and the EC(50) value was 5.4+/-1.9 nM. Both LTC(4) and carbachol induced increases in [Ca(2+)](i) and force. The maximum force induced by 100 nM LTC(4) was significantly smaller than that induced by 10 microM carbachol, although an increase in [Ca(2+)](i) produced by both agonists was similar. In the permeabilized preparations, carbachol, but not LTC(4), induced an additional force development at a fixed Ca(2+) concentration. LTC(4) induced no increase in [Ca(2+)](i) and force in the Ca(2+)-free solution, while carbachol induced transient increases in both [Ca(2+)](i) and force in a Ca(2+)-free solution. Both diltiazem and SK&F 96365 significantly inhibited the LTC(4)- and carbachol-induced increases in [Ca(2+)](i) and force in normal PSS. The inhibitory pattern of [Ca(2+)](i) by these drugs was also similar. We thus conclude that LTC(4) induces the contraction of the guinea-pig taenia coli mainly through Ca(2+) influx via both the diltiazem-sensitive and SK&F 96365-sensitive Ca(2+) channels, without affecting either the Ca(2+)-sensitivity or the intracellular Ca(2+) release. These results indicated that the mechanism underlying the LTC(4)-induced contraction differs greatly from that for conventional G-protein mediated agonists, such as carbachol.

Animals↗
PubMed2001

Mechanism of trypsin-induced contraction in the rat myometrium: the possible involvement of a novel member of protease-activated receptor.

1. The mechanism of trypsin-induced contraction in the rat myometrium was investigated using front-surface fluorimetry on fura-PE3-loaded strips. The expression of protease-activated receptors (PARs) in the rat myometrium was determined by reverse transcription polymerase chain reaction (RT - PCR). 2. In non-pregnant rats, 10 microM trypsin developed a force of up to 30.5 +/- 5.1% of that obtained during the 40 mM K(+)-depolarization-induced contraction. In pregnant rats, the maximal level of the cytosolic Ca(2+) concentration and tension obtained with 3 microM trypsin was 143.2 +/- 6.0% and 63.2 +/- 7.9%, respectively. The depletion of the extracellular Ca2+ abolished the trypsin-induced contraction. 3. Trypsin-induced contraction was abolished by the pre-treatment of a serine protease inhibitor. PAR1-activating peptide (PAR1-AP) caused a potent contraction of the myometrium, while neither PAR2-AP nor PAR4-AP induced any contraction. 4. RT - PCR analysis detected the expression of PAR1 mRNA. However, neither PAR2 nor PAR4 mRNA was detected in the rat myometrium. 5. Once the strips were stimulated with thrombin, the subsequent application of thrombin failed to induce any contraction, while trypsin induced a contraction similar to that observed without the pre-stimulation with thrombin. Once the strip was stimulated with trypsin, neither trypsin nor thrombin induced any contraction. The response to PAR1-AP remained after the pre-stimulation with thrombin and trypsin. 6. In conclusion, PAR1 was the only known receptor for trypsin expressed in the rat myometrium, but it was suggested to be cleaved and inactivated by trypsin. Trypsin was thus suggested to contract the rat myometrium via a novel type of PAR, which might be upregulated during pregnancy.

Animals↗
PubMed2001

Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin-induced hyperpolarization-mediated relaxation in the porcine coronary artery.

1. To elucidate the mechanism of the relaxation mediated by endothelium-derived hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport blocker, on cytosolic Ca(2+) concentration ([Ca(2+)]i) and tension was determined in the porcine coronary arterial strips. We also examined the effect of brefeldin A on [Ca(2+)]i in the endothelial cells of the porcine aortic valve. 2. In the presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NOARG), both bradykinin and substance P induced a transient decrease in [Ca(2+)]i and tension in arterial strips contracted with 100 nM U46619 (thromboxane A2 analogue). A 6 h pre-treatment with 20 microg ml(-1) brefeldin A abolished the bradykinin-induced relaxation, while it had no effect on the substance P-induced relaxation. 3. In the absence of indomethacin and L-NOARG, brefeldin A had no effect on the bradykinin-induced relaxation during the contraction induced by U46619 or 118 mM K(+). 4. The indomethacin/L-NOARG-resistant relaxation induced by bradykinin was completely inhibited by 3 mM tetrabutylammonium (non-specific Ca(2+)-activated K(+) channel blocker), while that induced by substance P was not inhibited by 3 mM tetrabutylammonium or 1 mM 4-aminopyridine (voltage-dependent K(+) channels blocker) alone, but completely inhibited by their combination. 5. Brefeldin A had no effect on the [Ca(2+)]i elevation in endothelial cells induced by bradykinin or substance P. 6. In conclusion, bradykinin produce EDHF in a brefeldin A-sensitive mechanism in the porcine coronary artery. However, this mechanism is not active in a substance P-induced production of EDHF, which thus suggests EDHF to be more than a single entity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Mechanism of trypsin-induced endothelium-dependent vasorelaxation in the porcine coronary artery.

1. To investigate the mechanism underlying the trypsin-induced endothelium-dependent relaxation, cytosolic Ca(2+) concentration ([Ca(2+)](i)) and tension development of smooth muscle were simultaneously monitored in the porcine coronary artery, and [Ca(2+)](i) of in situ endothelial cells were monitored in the porcine aortic valvular strips, using fura-2 fluorometry. 2. During the contraction induced by 30 nM U46619, a thromboxane A(2) analogue, 100 nM trypsin induced a rapid transient significant decrease in both [Ca(2+)](i) (from 67.9+/-5.1 to 15.7+/-4.4%) and tension (from 97.5+/-9.2 to 16.8+/-3.5%) of smooth muscle only in the presence of endothelium (100% level was assigned to the level obtained with the 118 mM K(+)-induced contraction). [Ca(2+)](i) and the tension thus returned to the levels prior to the application of trypsin by 5 and 10 min, respectively. 3. The initial phase of this relaxation was partly inhibited by 100 microM N(omega)-nitro-L-arginine (L-NOARG), and was completely inhibited by L-NOARG plus 40 mM K(+) or L-NOARG plus 100 nM charybdotoxin and 100 nM apamin, while the late phase of the relaxation was inhibited by L-NOARG alone. 4. Trypsin induced a transient [Ca(2+)](i) elevation in the endothelial cells mainly due to the Ca(2+) release from the intracellular stores, at the concentrations (1 - 100 nM) similar to those required to induce relaxation. 5. In conclusion, trypsin induced an elevation in [Ca(2+)](i) mainly due to Ca(2+) release in endothelial cells, and thereby caused endothelium-dependent relaxation. The early phase of relaxation was due to nitric oxide and hyperpolarizing factors, while the late phase was mainly due to nitric oxide in the porcine coronary artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma.

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.

Adult↗
PubMed2001

Hydroxyfasudil, an active metabolite of fasudil hydrochloride, relaxes the rabbit basilar artery by disinhibition of myosin light chain phosphatase.

Fasudil hydrochloride (AT877, hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, identical to HA1077) inhibits cerebral vasospasm after subarachnoid hemorrhage in experimental animals and humans. In the current study, the vasorelaxing mechanism of hydroxyfasudil, a hydroxylated metabolite of fasudil hydrochloride, was determined in the rabbit basilar artery. The effects of hydroxyfasudil on tension, intracellular Ca2+ concentration ([Ca2+]i), and phosphorylation of the myosin light chain were examined using the isolated and intact or permeabilized rabbit basilar artery without endothelium in vitro. In the intact rabbit basilar artery, hydroxyfasudil elicited a concentration-dependent relaxation of the artery precontracted with 1 nmol/L endothelin-1 (ET-1) plus 20 mmol/L KCl without any significant decrease in [Ca2+]i as determined by fura-2 microfluorometry (IC50: 5.1 +/- 4.6 micromol/L). The relaxation induced by hydroxyfasudil was accompanied with dephosphorylation of the myosin light chain. In the permeabilized preparation, hydroxyfasudil inhibited the contraction induced by ET-1, guanosine 5'-O-(3-thiotriphosphate), or the catalytic subunit of rho-associated kinase, but it did not inhibit Ca2+-induced contraction under the condition of inhibited myosin light chain phosphatase. Hydroxyfasudil showed a greater relaxant effect under decreased adenosine triphosphate (ATP) levels. The present study indicated that hydroxyfasudil relaxes the rabbit basilar artery mainly by disinhibiting myosin light chain phosphatase through the inhibition of rho-associated kinase and that this effect depends on the intracellular ATP concentration.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Clonal analysis of B cells in the osteoarthritis synovium.

OBJECTIVES: Cellular and humoral immunity to collagen and cartilage proteoglycan were shown in patients with osteoarthritis (OA). Inflammatory infiltration containing T and B lymphocytes and macrophages, which are HLA-DR positive, is often seen in the synovial membrane of patients with OA. An analysis of the DNA restriction enzyme patterns of T lymphocytes from the OA synovium showed an oligoclonal pattern of T cell receptor beta chain gene rearrangements. No similar studies of B cell clonality have previously been performed. This study aimed at determining the clonal characteristics of the B cells in the OA synovium. METHODS: A reverse transcriptase-polymerase chain reaction of the immunoglobulin transcripts of B cells in the synovial membranes from six patients with OA was performed and the products were analysed by a single strand conformation polymorphism analysis. RESULTS: Several dominant bands were seen in all samples and some of the dominant bands were common among the two or three separate regions of each synovial sample. CONCLUSION: Infiltrated B cells are oligoclonal, and an antigen driven immune response may play a part in the progression of the disease process in OA.

B-Lymphocytes↗
PubMed2001

Aberrant BCR-ABL transcript with intronic insertion in a patient with philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression.

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript with an intronic sequence insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.

Adult↗
PubMed2001

[Two cases of B cell lymphoma associated with hemophagocytic syndrome].

B cell lymphoma-associated hemophagocytic syndrome (B-LAHS) is clinically characterized by hepatosplenomegaly and bone marrow invasion without lymphadenopathy and skin lesions. Several cases of B-LAHS have been reported to demonstrate histopathologic findings of intravascular lymphomatosis (IVL), which in Western countries is characterized by a high rate of skin involvement and, rarely, bone marrow involvement and hemophagocytosis. Here we describe two interesting cases of B-LAHS. One patient was a 52-year-old woman whose bone marrow showed proliferation of large CD20-positive cells and hemophagocytosis at presentation. Combination chemotherapy was not effective, and the patient died of progressive disease. At autopsy, the lymphoma cells showed extravascular proliferation in many organs such as the bone marrow and liver, whereas in the adrenal glands, the lymphoma cells showed intravascular proliferation. The other patient was a 50-year-old man who had swellings of the bilateral kidneys and adrenal glands at presentation. Skin involvement by large lymphoma cells, a rare complication of B-LAHS, was observed. At autopsy, there was no evidence of IVL. Both of these patients showed high fever and cytopenia, and the disease took an aggressive clinical course, as in other reported cases of B-LAHS.

Female↗
PubMed2000

Differential effects of progesterone and 17beta-estradiol on the Ca(2+) entry induced by thapsigargin and endothelin-1 in in situ endothelial cells.

The effects of progesterone and 17beta-estradiol on Ca(2+) signaling in in situ endothelial cells were investigated using front-surface fluorometry of fura-2-loaded strips of porcine aortic valve. Progesterone inhibited the thapsigargin-induced sustained [Ca(2+)](i) elevation (IC(50)=33.9 microM, n=4), while 17beta-estradiol added a transient [Ca(2+)](i) elevation. Progesterone and 17beta-estradiol had no significant effect on the thapsigargin-induced [Ca(2+)](i) elevations in the absence of extracellular Ca(2+). A Mn(2+)-induced decline of fluorescent intensity at 360 nm excitation was accelerated by thapsigargin. This acceleration was completely reversed by progesterone, but not by 17beta-estradiol. Progesterone inhibited, and 17beta-estradiol enhanced the endothelin-1 (ET-1)-induced [Ca(2+)](i) elevation, while both had no effect on the ET-1-induced Ca(2+) release observed in the absence of extracellular Ca(2+) or in the pertussis toxin-treated strips. Progesterone and 17beta-estradiol thus had different effects on Ca(2+) signaling, especially on Ca(2+) influx, in endothelial cells.

Animals↗