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J Nishimura

Publications and source records attributed to J Nishimura.

At least 145 records · Page 8Linked to original sources
PubMed1996

The effects of calcitonin gene-related peptide on the cytosolic calcium concentration and force in the porcine coronary artery.

Using front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, we simultaneously monitored the cytosolic Ca++ concentration ([Ca++]i) and force development to investigate the mechanisms of vasorelaxation induced by calcitonin gene-related peptide (CGRP). CGRP actively decreased [Ca++]i of the strips at rest both in the presence and in the absence of extracellular Ca++. In the presence of extracellular Ca++, CGRP inhibited concentration-dependently the steady-state elevations of [Ca++]i and force induced by high-K+ depolarization and by histamine (HIS). The extent of the inhibition of force was much greater than the extent of reductions of [Ca++]i would lead one to expect. The [Ca++]i (abscissa)-force (ordinate) relationship at the peak levels of force during HIS-induced contractions shifted to the left of that observed with high-K+ depolarization. The [Ca++]i-force relationships of the contractions induced by high-K+ depolarization and by HIS shifted to the right as a result of the treatment with CGRP. In the absence of extracellular Ca++, CGRP inhibited the transient elevations of [Ca++]i induced by HIS but not by caffeine. Our results suggest that CGRP relaxes the porcine coronary artery by the following mechanisms: 1) the inhibition of Ca++ influx stimulated by HIS and by high-K+ depolarization, 2) the reduction of HIS-induced release of intracellular Ca++, without affecting a caffeine-sensitive mechanism, 3) an active decrease in the resting levels of [Ca++]i and 4) a decrease in the Ca(++)-sensitivity of the contractile apparatus.

Animals↗
PubMed1996

[Primary macroglobulinemia with t(11;18) (q21;q21)].

This is the first case of primary macroglobulinemia with t(11;18) (q21;q21) reported in the literature. A 77-year-old man was admitted to a hospital in December, 1994, with acute renal failure and pleural effusion. He was treated with prednisolone pulse therapy and his symptoms improved. He was referred to our hospital for further examination. Analysis of blood chemistry revealed macroglobulinemia (IgM-kappa). There were no other findings that would indicate a diagnosis of malignant lymphoma. A complete blood count revealed a hemoglobin level of 8.7 g/dl and a white blood cell count of 5,300/microliters with 11% abnormal lymphoid cells. Immunologic and karyotype analyses revealed that these abnormal cells were positive for IgM-kappa, CD19, and CD20, negative for CD5, and CD10, and had t(11;18) (q21;q21). The bone marrow had also been infiltrated by 8.6% abnormal lymphoid cells. Six other cases with t(11;18) (q21;q21) have been reported including 5 of small lymphocytic lymphoma and 1 of mucosa-associated lymphoid tissue-type lymphoma. The tumor cells in these cases were the same as in our case. Therefore, our report is in agreement with the finding that t(11;18) (q21;q21) might be one of the characteristic chromosomal abnormalities in mature B-lymphoid neoplasms.

Aged↗
PubMed1996

Clinical evaluation of histamine release test: a novel method for identifying allergens from the whole blood of allergic patients.

Identification of allergens is necessary for proper treatment of allergic diseases. We have so far mainly used two types of allergen identifying tests, one type based on the quantification of specific serum IgE (e.g. radioallergosorbent test (RAST)), the other on allergen challenging (e.g. prick test, provocation test) for an estimation of immediate allergic reaction. However, with the former test, a high level of serum specific IgE does not necessarily indicate evidence of allergy; the latter type causes itching on the challenged focus and may, in some cases, cause anaphylaxis. The histamine release test using the glass-fiber method (HRT) is based on the measurement of an immediate allergic reaction but can be performed safely in vitro. In this investigation, we measured the reaction of samples taken against 10 allergens simultaneously using HRT with a small amount of peripheral whole blood. HRT showed a high correlation and concordance with the CAP-RAST system. HRT also had a significant correlation with the nasal provocation test, and had good specificity and positive predictive value. With these advantages, HRT is considered to be clinically useful and especially suitable for screening of allergens because of its high specificity and positive predictive value, and also because of its safety and ease of performance.

Adolescent↗
PubMed1996

Differential effects of diltiazem and nitroglycerin on cytosolic Ca2+ concentration and on force in the bovine ophthalmic artery.

PURPOSE: To determine the mechanisms of inhibition by diltiazem (Dil) and nitroglycerin (NG) of the contraction induced by serotonin (5-HT) in the ophthalmic artery. METHODS: Using front-surface fluorometry of fura-2 and the medial strips of the bovine ophthalmic artery, [Ca2+]i and force were monitored simultaneously. Changes in the force at a constant [Ca2+]i were determined by use of receptor-coupled membrane permeabilization with alpha-toxin. RESULTS: In the presence of extracellular Ca2+, 5-HT (10(-5) M) induced an initial transient and subsequently lower steady state elevation of [Ca2+]i. The transient elevation of [Ca2+]i was dependent on both intracellular and extracellular [Ca2+]i, whereas the steady state elevation was dependent on only extracellular Ca2+. For a given level of elevation of [Ca2+]i, 5-HT produced a greater force than the depolarization with high external K+ (118 mM) solution. In the permeabilized ophthalmic artery smooth muscle, 5-HT enhanced the contractile response to constant cytosolic Ca2+ (pCa 6.5) in the presence of guanosine triphosphate (GTP, 10 microM), but not in its absence. Therefore, 5-HT induces [Ca2+]i elevation, depending on both extracellular (Ca2+ influx) and intracellular Ca2+ (Ca2+ release), and it potentiates the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins. 5-HT-induced release of Ca2+ from the store was inhibited by NG, but not by Dil, in a concentration-dependent manner. However, neither NG nor Dil inhibited caffeine (20 mM)-induced release of Ca2+ from the store. Dil (10 microM) and NG (10 microM) inhibited in a concentration-dependent manner the steady state elevations of [Ca2+]i (Ca2+ influx) and force induced by 5-HT (10 microM) in the presence of extracellular Ca2+. Dil equally inhibited the steady state elevations of [Ca2+]i and force induced by 5-HT, whereas NG inhibited the force to a greater extent than expected from the reduction in [Ca2+]i. In the permeabilized ophthalmic artery smooth muscle, NG (10 microM), but not Dil (10 microM), decreased the force development induced by GTP (10 microM) and 5-HT (10 microM) at constant [Ca2+]i (pCa 6.5). These results indicate that NG, but not Dil, decreases the Ca2+ sensitivity of contractile apparatus. CONCLUSIONS: The authors found that 5-HT contracts the ophthalmic artery smooth muscle by the elevation of [Ca2+]i mediated by the release of intracellular Ca2+ and the influx of extracellular Ca2+, as well as by an increase in the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins, and that Dil relaxes 5-HT-mediated contraction of ophthalmic artery primarily by inhibiting the Ca2+ influx and, hence, by decreasing [Ca2+]i without having any effect on the Ca2+ sensitivity of the contractile apparatus. Nitroglycerin relaxes the ophthalmic artery not only by decreasing [Ca2+]i (inhibition of both the Ca2+ release and Ca2+ influx) but also by decreasing the Ca2+ sensitivity of the contractile apparatus.

Animals↗
PubMed1996

[Successful treatment with combination of all-trans retinoic acid (ATRA) and rhG-CSF a relapsed acute promyelocytic leukemia with umbilical tumor].

A 48-year-old female was admitted to our hospital because of pancytopenia and pneumonia in February, 1993. The increase of abnormal promyelocytes with t (15; 17) and PML-RAR mRNA was detected in bone marrow aspirate and a diagnosis of acute promyelocytic leukemia was made. She obtained complete remission after the administration of all-trans retinoic acid (ATRA) and following chemotherapy. Then she received peripheral blood stem cell transplantation in September, 1993. However she noticed a umbilical tumor in June, 1995. Abnormal promyelocytes were demonstrated not only in bone marrow aspirate but also in the umbilical tumor. Because of the poor response to ATRA and development of fever, a side effect of ATRA, G-CSF and prednisolone were administrated together with ATRA. After the combined therapy, umbilical tumor disappeared and she obtained complete remission again. These findings suggest that combined therapy of ATRA and G-CSF is effective to the low responder to ATRA and that combined use of ATRA and prednisolone reduces the side effect of ATRA without diminishing the favorable effect on differentiation.

Drug Therapy, Combination↗
PubMed1996

[Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders].

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

Adolescent↗
PubMed1995

Autocrine regulation of the renal arterial tone by adrenomedullin.

We tested the hypothesis that adrenomedullin (ADM), a recently isolated hypotensive peptide, is an autocrine transmitter in renal arterial smooth muscle cells (RASMCs). Fura-2 fluorometry revealed that ADM decreases both the cytosolic Ca2+ concentration ([Ca2+]i) and tension induced by 0.3 microM phenylephrine (PE) in porcine RASMCs. The expression of ADM mRNA in RASMCs was assessed by the reverse transcription polymerase chain reaction (RT-PCR), using the total RNA from the RASMCs and the specific primers for the porcine ADM mRNA. A band with an expected size could be detected only when the reverse transcriptase was added, thus indicating that the porcine RASMCs express ADM mRNA. These results therefore suggested that ADM plays an important role in the regulation of the renal vascular tone, not only as a circulating hormone, but also as an autocrine transmitter.

Adrenomedullin↗
PubMed1995

Adrenomedullin decreases both cytosolic Ca2+ concentration and Ca(2+)-sensitivity in pig coronary arterial smooth muscle.

Adrenomedullin (AM) is a newly identified vasorelaxant peptide which circulates in human plasma. We investigated the cellular mechanisms of AM-induced relaxation in the pig coronary artery, using fura-2 fluorometry and receptor-coupled membrane permeabilization by alpha-toxin. AM inhibited both the elevations of cytosolic Ca2+ concentration ([Ca2+]i) and the tension induced by high K(+)-depolarization and by U46619. The extent of the tension inhibition was much greater than expected based on the extent of reductions of [Ca2+]i. Thus, the [Ca2+]i (abscissa)-tension (ordinate) relation shifted to the right by AM. In alpha-toxin-permeabilized strips, AM decreased the tension development at constant [Ca2+]i (pCA 6.5) in the presence of GTP, whereas GDP beta S antagonized this effect. We thus conclude that AM relaxes the coronary artery not only by decreasing [Ca2]i but also by decreasing the Ca(2+)-sensitivity of the contractile apparatus, as mediated by G-protein.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.

Amino Acid Sequence↗
PubMed1995

High D-glucose stimulates the cell cycle from the G1 to the S and M phases, but has no competent effect on the G0 phase, in vascular smooth muscle cells.

The effects of high (28mM) D-glucose (HG) on the cell cycle progression were investigated in rat aorta vascular smooth muscle cells (VSMCs) in primary culture, using an immunocytochemical analysis of cell-cycle-specific nuclear antigens. HG had no effect on the cell cycle of the serum-deprived G0 cells, whereas platelet-derived growth factor (PDGF) stimulated the entry of the G0 cells to the G1 phase without a further progression to the S and M phases. HG, but neither mannitol nor L-glucose, stimulated the progression of the PDGF-pretreated G1 cells to the S and M phases, which was blocked by calphostin-C, a protein kinase C (PKC) blocker. HG did not affect the cytosolic Ca2+ concentration ([Ca2+]i). These data suggest that HG has no competent effect on the G0 cells and acts as a progression growth factor (to stimulate the cell cycle from the G1 to the S/M) in VSMCs through the mechanism, which may be insensitive to [Ca2+]i and mediated by PKC.

Animals↗
PubMed1995

Resting load regulates cytosolic calcium-force relationship of the contraction of bovine cerebrovascular smooth muscle.

1. We determined the effects of a change in preload, or resting load, on the development of force and on cytosolic calcium concentration ([Ca2+]i) during the contraction induced by high K+ depolarization and by the stable analogue of thromboxane A2, U-46619, using front-surface fluorometry and medial strips of bovine middle cerebral artery loaded with fura-2. 2. Increase in resting load of strips from 0.495 mN (low load; 0.85L(max)) to 1.98 mN (optimal load; L(max)) elevated resting levels of [Ca2+]i slightly, and, significantly, after a delay of a few seconds. The force developed by high K+ depolarization at resting load of 1.98 mN was much greater than that at a resting load of 0.495 mN (191.8% of that at 0.495 mN); however, there was no difference in [Ca2+]i elevation induced by high K+ depolarization between resting loads of 0.495 and 1.98 mN. 3. Both in the presence and absence of extracellular Ca2+, the force developed by U-46619 (0.1 microM) at resting load of 1.98 mN was also much greater than that at a resting load of 0.495 mN. Both in the presence and absence of extracellular Ca2+, there was no difference in the [Ca2+]i transients induced by U-46619 between two different resting loads. 4. The [Ca2+]i-force relationship during the contraction induced by high K+ depolarization was shifted to the left when the resting load was increased from 0.495 to 1.98 mN. At 0.495 mN resting load, this Ca(2+)-force relationship was shifted to the left by U-46619. This left-side shift of the curve by U-46619 was further enhanced by the increase in resting load from 0.495 to 1.98 mN. 5. The augmentation of force development induced by the change in resting load (from 0.495 to 1.98 mN) was not affected by a relatively specific inhibitor of protein kinase C, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydro-chloride (H-7; 10 microM). 6. We conclude that (1) at a given degree of [Ca2+]i elevation, the developed force induced by U-46619 was greater than that induced by high K+ depolarization, and (2) preload, or resting load (below optimal load), regulates contractile responsiveness of cerebrovascular smooth muscle to various stimulations, mainly by modulating the [Ca2+]i-force relationship, without affecting the extent of [Ca2+]i elevation. The results suggest the possibility that Ca(2+)-insensitive pathways may be involved in the stretch-dependent regulation of Ca2+ sensitivity of the contractile apparatus in smooth muscle.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Proximal subtotal gastrectomy for the treatment of carcinoma of the upper third of the stomach: its indications based on lymph node metastasis and perigastric lymphatic flow.

To clarify the indications for a proximal subtotal gastrectomy in the treatment of carcinoma in the upper third of the stomach based on lymph node metastases, 1055 patients in whom either a D2 or greater lymph node removal was performed were reviewed. In the patients in which the lesion was confined to the upper stomach and did not invade beyond the muscularis propria of the stomach wall, no metastases to either the lymph nodes above and below the pylorus or the lymph nodes along the greater curvature were observed. A lymphatic flow study revealed a minimal flow to these nodes from the upper stomach in patients without lymph node metastasis, but in cases with lymph node metastases the lymphatic flow changed. The indications for a proximal subtotal gastrectomy for a carcinoma of upper third of the stomach therefore must fulfill the following two conditions: (1) The deepest layer of cancerous invasion does not extend beyond the muscularis propria of the stomach wall, and (2) No macroscopic evidence of lymph node metastasis can be detected during surgery.

Case-Control Studies↗
PubMed1995

Natural killing activity is associated with progression of gastric cancer.

Previously, we proposed a new analysis of natural killing activity, in which an individual effector/target cell ratio was employed for comparison according to the peripheral number of effector cells. In 51 patients with gastric cancer, the activity was studied using that modified analysis. Natural killing activity was activated in patients with early cancer, where tumor-cell invasion was restricted to the mucosa or the submucosa, even though in well-differentiated adenocarcinoma with invasion of the mucosa alone, the activity remained at the level of controls. In contrast, the activity in advanced cancer, where tumor cells infiltrated beyond the submucosa, came to be inactivated as the cancer progressed. These facts suggest that natural killing activity in patients with gastric cancer is closely associated with tumor invasion and that reactive activation of the activity against tumor is induced, at least, in some patients with early stage.

Adenocarcinoma↗
PubMed1995

Effects of U46619 on intracellular Ca++ concentration and tension in human umbilical artery.

OBJECTIVE: The aim was to examine the effects of U46619, a thromboxane A2 analog, on intracellular Ca++ concentration and tension in human umbilical artery. STUDY DESIGN: By means of front-surface fluorometry and human umbilical arterial strips loaded with fura-2 we simultaneously measured intracellular Ca++ concentration and tension. RESULTS: In the presence of extracellular Ca++ (1.25 mmol/L), U46619 elevated intracellular Ca++ concentration and tension in a concentration-dependent manner. Oscillations of both intracellular Ca++ concentration and tension were evident in many cases. In the absence of extracellular Ca++ U46619 induced a transient elevation of intracellular Ca++ concentration that was associated with a transient increase and a sustained tension. At any given intracellular Ca++ concentration level the tension induced by the cumulative application of extracellular Ca++ during depolarization with high external K+ in the presence of U46619 was greater than that in the absence of this drug; thus the intracellular Ca++ concentration-tension relationship in the presence of U46619 shifted to the left. CONCLUSION: The tension developed by U46619 depends both on an influx of Ca++ from the extracellular space and on release of intracellular Ca++, and U46619 increased Ca++ sensitivity of the contractile apparatus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Effects of midazolam on intracellular Ca2+ and tension in airway smooth muscles.

BACKGROUND: It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscles. To determine the underlying mechanisms of this phenomenon, the effects of midazolam on the intracellular Ca2+ concentration ([Ca2+]i) and tension in airway smooth muscles were investigated. METHODS: Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, both [Ca2+]i and isometric tension developments were simultaneously recorded. RESULTS: When the tracheal strips were exposed to a high external K(+)-solution (40 mM) or 10(-7) M carbachol containing 1.25 mM Ca2+, both [Ca2+]i and tension increased rapidly until they reached a plateau (the steady state). During steady-state contraction induced by K(+)-depolarization or carbachol, the cumulative application of midazolam (10(-7) approximately 10(-4) M) caused decreases in both [Ca2+]i and tension, in a concentration-dependent manner. During 40 mM K(+)-induced depolarization, the stepwise increases in the extracellular Ca2+ concentration induced the stepwise increases in [Ca2+]i and tension. Midazolam (3 x 10(-5) M) inhibited these increases in [Ca2+]i and tension, but had no effect on the [Ca2+]i-tension relationship. In the presence of 3 x 10(-3) M NiCl2 (a nonselective cation channel blocker), midazolam (3 x 10(-5) M) did not cause any additional reduction of [Ca2+]i or tension during the contraction induced by carbachol (10(-7) M). In the absence of extracellular Ca2+, midazolam (3 x 10(-5) M) had no effect on the transient increases in either [Ca2+]i or the tension induced by carbachol (10(-7) M) or caffeine (20 mM). Pretreatment with both 10(-5) M flumazenil (a specific central antagonist of benzodiazepines) and 10(-5) M PK11195 (a specific peripheral antagonist of benzodiazepines) did not influence the effect of 10(-5) M midazolam on [Ca2+]i or tension during the contractions induced by carbachol. CONCLUSIONS: Midazolam directly relaxes airway smooth muscles by decreasing [Ca2+]i; this can be attributed to the inhibition of the influx of extracellular Ca2+. Midazolam has no effect on the release of stored Ca2+. In addition, midazolam has no effect on Ca2+ sensitivity of the contractile apparatus. Finally, benzodiazepine antagonists, flumazenil and PK11195, have no effect on this mechanism of direct action of midazolam on airway smooth muscles.

Animals↗
PubMed1995

Causative allergens of allergic rhinitis in Japan with special reference to silkworm moth allergen.

To determine the importance of silkworm moth allergens, we tested 267 patients with allergic rhinitis with CAP-RAST, a new assay system for detecting specific IgE in sera. We used the following allergen sources: house-dust mite, Candida, Alternaria, cat dander, orchard grass, ragweed, mugwort, Japanese hops, Japanese cedar, Japanese cypress, cotton, silk, larval chironomid midge, adult chironomid midge, and silkworm moth. As expected, the highest positive rate of reaction, as determined by CAP-RAST, was 73.8% for Japanese cedar, followed by 53.2% for mite and 50.6% for Japanese cypress. Although the positive rate for silkworm moth was not as high as for cedar pollen, one-third of patients had specific IgE against silkworm moth. The positive rate of reaction to silkworm moth was much higher than that to chironomid. It was interesting to note that the patients reported had not been documented as having frequent contact with silkworm moth allergen. Correlations between silkworm moth and silk, and silkworm moth and chironomid midge were found to be significant (P < 0.001). Silkworm moth allergen showed the third highest reaction rate in patients with severe symptoms. These results suggest that silkworm moth allergen should be considered to be important in patients with allergic rhinitis in Japan.

Adolescent↗