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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 487 records · Page 27Linked to original sources
PubMed1995

Functional identification of histamine H3-receptors in the human heart.

Norepinephrine release contributes to ischemic cardiac dysfunction and arrhythmias. Because activation of histamine H3-receptors inhibits norepinephrine release, we searched for the presence of H3-receptors directly in sympathetic nerve endings (cardiac synaptosomes) isolated from surgical specimens of human atria. Norepinephrine was released by depolarization with K+. The presence of H3-receptors was ascertained because the selective H3-receptor agonists (R) alpha-methylhistamine and imetit reduced norepinephrine release, and the specific H3-receptor antagonist thioperamide blocked this effect. Norepinephrine release was exocytotic, since it was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220. Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine. Also, thioperamide antagonized the effect of (R) alpha-methylhistamine. Our findings are the first demonstration that H3-receptors are present in sympathetic nerve endings in the human heart, where they modulate adrenergic responses by inhibiting norepinephrine release. Since myocardial ischemia causes intracardiac histamine release, H3-receptor-induced attenuation of sympathetic neurotransmission may be clinically relevant.

Cell Separation↗
PubMed1995

Acute myocardial infarction in a patient with primary coronary dissection and severe coronary vasospasm. A case report.

A case of myocardial infarction associated with coronary artery dissection in a thirty-five-year-old woman is reported. An emergent coronary angiogram revealed extensive dissection and thrombosis in the right coronary artery; in addition, severe vasospasm was observed in the left coronary artery on the next day. She was successfully treated with intracoronary thrombolysis and intra-aortic balloon pumping. The patient is alive and well two years after infarction.

Adult↗
PubMed1995

Lysine vasopressin stimulation of cortisol secretion in patients with adrenocorticotropin-independent macronodular adrenal hyperplasia.

We present two patients with Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia who showed marked plasma cortisol response to lysine-8-vasopressin (LVP) injection (from 930 and 731 pmol/L to 2177 and 1920 pmol/L, respectively), while plasma ACTH levels remained undetectable. The ACTH independence of cortisol secretion in the two patients was determined from the following endocrinological findings. Plasma cortisol levels were not increased by corticotropin-releasing hormone injections and were not suppressed by high dose (16 mg) dexamethasone administrations. The plasma ACTH levels, measured by two independent sensitive immunoassays, were persistently undetectable even after corticotropin-releasing hormone injection, metyrapone administration, and bilateral adrenalectomy. The particular pathological finding of the two cases, atrophic lesions in nonnodular parts of the adrenal cortexes, also indicated ACTH independence of the macronodular hyperplasia. In vitro examination revealed a direct effect of LVP on cortisol secretion from the adrenal cells of the macronodules. We also examined seven patients with Cushing's syndrome caused by adrenal adenoma and found a statistically significant plasma cortisol response to LVP injection. The direct effect of LVP was also demonstrated in cultured adenoma cells. In conclusion, we discovered a direct adrenal effect of LVP on cortisol secretion in patients with ACTH-independent macronodular hyperplasia and, to a lesser extent, in patients with cortisol-producing adrenal adenoma. The cortisol response to LVP may serve to facilitate their diagnosis and choice of therapy.

17-Hydroxycorticosteroids↗
PubMed1995

A non-alpha-like DNA polymerase from the hyperthermophilic archaeon Pyrococcus furiosus.

We identified a DNA polymerase with properties that differed from those of alpha-like DNA polymerase (Pol I), in Pyrococcus furiosus, a hyperthermophilic archaeon. The novel DNA polymerase (Pol II) was partially purified and characterized. The DNA polymerizing activity of Pol II was relatively sensitive to dideoxythymidine-triphosphate (ddTTP) and it was inhibited by N-ethylmaleimide, but not by aphidicolin. Activity staining gel electrophoresis showed that the DNA polymerizing activity was derived from a polypeptide with a molecular weight of 130000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The DNA elongation ability of Pol II using a natural DNA template was much lower than that of Pol I from this organism and DNA synthesis of Pol II seems to be non-processive.

Aphidicolin↗
PubMed1995

Cytokine gene expression after allogeneic bone marrow transplantation.

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Transplantation-related complications predicted by cytokine gene expression in the mixed lymphocyte culture in allogeneic bone marrow transplants.

In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2, IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition, this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.

Antigens, CD↗
PubMed1995

Cytokine receptor gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation.

Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL-6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation (allo BMT) and 2 patients who underwent autologous transplantation were analyzed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). There were several exceptions in some cases and IL-1R expression was found to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA tended to increase during the development of graft-versus-host disease (GVHD). In particular, IL-2R mRNA expression was increased in four patients with GVHD and graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT) patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in PBMC play an important role in the development of an allo response and GVHD. Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo BMT may provide important information concerning the immune response and the cytokine network system in marrow transplants.

Acute Disease↗
PubMed1995

Differential effects of the immunosuppressants cyclosporin A, FK506 and KM2210 on cytokine gene expression.

Cyclosporin A (CsA) inhibited interleukin 2 (IL-2), IL-3, interferon gamma (IFN gamma), GM-CSF and tumor necrosis factor alpha (TNF alpha) mRNA expression in spleen cells stimulated with concavalin A (Con A) when determined by the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. FK506 which has a similar immunosuppressive mechanism to that of CsA also showed the same inhibitory effects except for decreased IL-5 and IL-6 mRNA expression. In contrast, both CsA and FK506 enhanced transforming growth factor beta (TGF beta) and IL-1 beta mRNA expression. Another immunosuppressant KM2210 did not show any inhibitory effects on cytokine gene expression but rather enhanced IL-10, IL-6, TGF beta and IL-1 mRNA expression, thus suggesting that KM2210 has a completely different immunosuppressive mechanism from that of CsA and FK506. Anti-TFG beta 1 antibody abrogated the suppression by KM2210 of BALB/c anti-3H/He mixed lymphocyte reaction (MLR) whereas this antibody did not abrogate the suppression by CsA and FK506 of BALB/c anti-C3H/He MLR. These results indicate that TGF beta is one of the major cytokines in KM2210 immunosuppression, in addition to IL-10, but not in immunosuppression by CsA and FK506.

Animals↗
PubMed1995

[A preliminary analysis of unrelated marrow transplantations facilitated by the Japan Marrow Donor Program (JMDP)].

Between January 1993 and June 1994, the JMDP facilitated marrow donations from unrelated donors for 171 patients with malignant and non-malignant disorders. The median age of the patients was 21 years. All patients received marrow from phenotypically HLA -A, -B, -DR identical donors. About half of the patients wrer treated with total body irradiation (TBI)-containing regimens and about 80% of the patients received short-courses methotrexate and cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Eight out of 171 patients, (4.7%) had graft failure and 63 out of 144 patients (44%), who survived for more than 30 days posttransplant, developed grade II to IV acute GVHD. The incidence of chronic GVHD was 47% (extensive form; 27%); most of them were progressive/quiscent type. The incidence of moderate to severe acute GVHD was higher than that observed in sibling transplants. On the other hand, the incidence of chronic GVHD was similar to that observed in sibling transplants. Overall survival at 1.5 years posttransplant was about 50% with no significant differences between diseases. The age correlated significantly with the survival in standard risk leukemia but not in high-risk leukemia. Despite the risk of graft failure and acute GVHD, this preliminary analysis demonstrates that transplantation of marrow from unrelated donors can be an effective treatment for certain hematologic disorders.

Acute Disease↗
PubMed1995

Twenty-four hour monitoring of pH in the gastric tube replacing the resected esophagus.

BACKGROUND: Peptic ulcers in the gastric tube replacing the resected esophagus develop silently and cause serious problems. In this study, the acidity of the gastric tube was examined by 24-hour pH monitoring to determine if the acidity of the gastric tube was sufficient to cause peptic ulcers. STUDY DESIGN: The acidity of a gastric tube was evaluated by 24-hour pH monitoring of both the fundus and the antrum in 55 patients treated for carcinoma of the esophagus. The correlation between the fasting serum gastrin concentration and the intraluminal acidity of the completely vagotomized gastric tube was examined. RESULTS: In the patients with high postoperative acidity in the fundus or the antrum (46 percent of the 41 patients examined), the intraluminal pH remained consistently low, even long after operative treatment. Significant correlations existed between the percentage of time that the pH remained below 3 preoperatively and postoperatively in both the fundus and the antrum (r = 0.4777, p = 0.0386, and r = 0.7597, p = 0.0002, respectively). The percentage did not decrease significantly postoperatively. A significantly negative correlation (r = -0.783401, p < 0.0001) was found between the fasting serum gastrin level and the proportion of time that the nocturnal pH in the antrum remained below 3. CONCLUSIONS: Even long after esophagectomy, the pH of the gastric tube is low enough to cause peptic ulcers, especially in patients with high preoperative acidity. In these patients, the intraluminal pH in the antrum of the gastric tube correlates inversely with the fasting serum gastrin level.

Aged↗
PubMed1995

Value of fluorine-18-fluorodeoxyglucose and thallium-201 in the detection of pancreatic cancer.

UNLABELLED: This study compares the diagnostic value of 18F-FDG PET imaging and 201TI-SPECT imaging in patients with pancreatic cancer. METHODS: Twenty-five patients with histologically-proven pancreatic cancer were studied. Following PET transmission scanning, 3 mCi of 201TI were administered after patients had fasted overnight. Thallium-201-SPECT images were obtained 15 min later. Immediately after 201TI-SPECT imaging, 4 mCi of FDG were administered and PET images were obtained 60 min later. The PET and SPECT images were compared qualitatively and quantitatively. For quantitative analysis, 10 x 10 mm2 regions of interest (ROIs) were selected in areas of the tumor showing the highest tracer accumulation and in the normal pancreas. The tumor to nontumor activity ratio (T/N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 16 patients, PET identified eight additional patients in whom 201TI-SPECT images did not visualize any lesion. Thus, FDG-PET provided significantly higher sensitivity (96%) than 201TI-SPECT (64%). Among the patients showing increased tracer accumulation, the T/N ratio was significantly higher with FDG-PET (3.24 +/- 1.27) than with 201TI-SPECT (1.77 +/- 0.37) (p < 0.0001). CONCLUSION: We conclude that FDG-PET has a larger clinical value for noninvasive detection of pancreatic cancer than 201TI-SPECT. If a PET camera is available, FDG-PET is considered to be the method of choice for the evaluation of patients with suspected pancreatic cancer.

Adult↗
PubMed1995

Comparison of peripheral blood stem cells mobilized with granulocyte colony-stimulating factor with or without prior standard-dose chemotherapy in patients with malignancy.

We studied the effect of granulocyte colony-stimulating factor on the magnitude of peripheral blood stem cell mobilization in patients with malignancy. The leukapheresis products mobilized with granulocyte colony-stimulating factor alone at a steady state (a period of full hematopoietic recovery) (group 1) were compared with those obtained after cytotoxic chemotherapy using granulocyte colony-stimulating factor (group 2). In group 1, six patients underwent six courses of stem cell collection with a median of 20 l leukapheresis. In group 2, 10 patients underwent 12 courses of stem cell collection with a median of 10 l leukapheresis. Median yields of group 1 vs. group 2 were mononuclear cells (x 10(9)), 21.9 vs. 11.6; CD34+ cells (x 10(6)/l), 14.5 vs. 17.1; colony-forming unit for granulocyte-macrophage (/ml), 223 vs. 1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-forming unit for erythroid (/ml), 42 vs. 29; colony-forming unit for megakaryocyte (/ml), 26 vs. 59. While there were no statistically significant differences in the number of CD34+ cells between the two groups, granulocyte-macrophage-committed progenitor cells were more enriched in the apheresis products of group 2. The correlation between CD34+ cells and colony-forming unit for granulocyte-macrophage was poor. Our results demonstrate that granulocyte colony-stimulating factor can mobilize a sufficient number of progenitor cells into the peripheral blood for stem cell transplantation with or without prior chemotherapy.

Adolescent↗
PubMed1995

[Anesthetic management of a neonate with primary cardiac rhabdomyoma].

We have experienced anesthetic management for cardiac rhabdomyoma in a 21-day-old male, whose pulmonary trunk was obstructed by the tumor. He was anesthetized with fentanyl 70 micrograms.kg-1 and oxygen. The operative and post-operative courses were uneventful. Cardiac tumor, especially cardiac rhabdomyoma, in infant is rare. Anesthesia for the resection of the cardiac tumor must be carried out carefully, because sudden death due to arrhythmias as well as cardiac or respiratory failure is the most dangerous complication.

Anesthesia↗