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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 541 records · Page 30Linked to original sources

What are parents of obese children concerned about in their children?

We retrospectively examined the issues that concern parents of obese children to determine the most effective means of motivating them to seek treatment for obesity in their children. Children with an obesity index > or = 40%, aged six to 12 years, were screened in Kagoshima City in 1992. Parents were notified if their children needed an evaluation that included a family history and measurements of the blood pressure, total cholesterol, high density lipoprotein (HDL)-cholesterol, atherogenic index (ASI), triglycerides, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Parents were informed of the results of the evaluation and invited to attend a lecture on the treatment of obesity in children. A total of 378 obese children were evaluated. However, the parents of only 39 children attended the lecture. Children whose parents attended had higher mean total levels of cholesterol (190 +/- 25 vs 175 +/- 28, P < 0.01) and ASI values (3.2 +/- 0.9 vs 2.7 +/- 0.9, P < 0.02) than those whose parents did not attend. There were no significant differences in other factors. Only 4.2% of parents whose children showed no abnormal values, except for obesity, attended the lecture, compared with 20.3% (P < 0.01) or 16.9% (P < 0.05) of parents whose children had abnormal levels of cholesterol or abnormal ASI. Parents may be more concerned about hypercholesterolemia or arteriosclerosis than obesity per se. We should perhaps use the total cholesterol or ASI values, not just the severity of obesity, to motivate parents to enter their children into treatment programs for obesity.

Adult↗

Plasma membrane fluidity during regeneration and atrophy of the rat liver following portal branch ligation.

Dynamic changes in liver plasma membrane fluidity caused by regeneration and atrophy were assessed in rats following portal branch ligation (PBL). The portal branch, which perfuses 70% of the liver, was ligated with 5-0 prolene, and liver plasma membranes were isolated by ultracentrifugation. The membrane fluorescence polarization was measured as an index of membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe dye. In nonligated lobes, a significant decrease in fluorescence polarization was observed 12 and 24 h after PBL (0.171 +/- 0.004, p < 0.01 and 0.165 +/- 0.005, p < 0.001, respectively) as compared to the controls (0.181 +/- 0.002). The fluorescence polarization values then gradually returned to near control levels. In contrast, in the ligated lobes, the fluorescence polarization had increased by 12 hours after PBL (0.196 +/- 0.002, p < 0.01), and remained significantly elevated (p < 0.01) for up to 1 week after PBL, gradually returning to control levels within 3 weeks. The membrane composition was also evaluated by analyzing the cholesterol/phospholipid (C/P) ratio. A significant increase in the C/P ratio was detected in the ligated lobes 12 h and 3 days after PBL, but there was no significant difference in fluorescence polarization values between nonligated lobes and controls. These results suggest that alterations in membrane fluidity play an important role in the regenerative and atrophic processes of the liver following portal branch ligation.

Animals↗

Pancreatic exocrine secretion in short-term pancreatic duct obstruction induced acute pancreatitis in rats: an in vivo and in vitro study.

We investigated digestive enzyme release following a short-term pancreatic duct obstruction in rats. An in vivo experiment demonstrated that a 6-hour pancreatic duct obstruction reduced digestive enzyme release evoked both by endogenously released cholecystokinin (CCK) due to pancreaticobiliary diversion and by exogenous administration of CCK8. In vitro experiments also showed that pancreatic duct obstruction reduced the maximal CCK8-evoked amylase secretion. Amylase secretion evoked by the calcium ionophore A23187 and by phorbol myristate acetate was also markedly decreased. These data suggest that pancreatic duct obstruction probably interferes with the secretory process downstream of hormone receptor binding, intracellular Ca2+ release and protein kinase C activation.

Acute Disease↗

Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors.

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.

Adrenal Gland Neoplasms↗

Significance of the proportion of binucleate cells in the micronucleus assay: a methodological study.

Using treatment with cytochalasin-B (Cyt-B) for the induction of a cytokinetic block, the significance of the proportion of binucleate cells (BNC) in the micronucleus (MN) assay was investigated in a methodological study. A Chinese hamster cell line V79 was used in which MN were induced by radiation. In complementary tests the radiation effect in inducing MN was enhanced by depletion of the cellular glutathione content with buthionine sulfoximine (BSO). The data indicated that the concentration of Cyt-B is the major factor which determines the proportion of BNC. This proportion was shown to be independent of radiation dose and of BSO. Furthermore, the MN frequency was not related to the percentage of BNC. Therefore, a high proportion of BNC may be practical for the MN assay, but may not make the technique more accurate.

Animals↗

Effect of dietary fats on cholesterol metabolism and eicosanoid production in hamsters fed undigested fraction of soybean protein.

The undigested fraction of soybean protein (UDF) exerts a markedly greater hypocholesterolemic effect than soybean protein itself in rats. The present study was undertaken to confirm the effect in hamsters, a more appropriate animal model for human cholesterol metabolism. Hamsters were given diets containing UDF at a nitrogen level equivalent to the 20% casein diet. Dietary fats, at the 10% level, were perilla oil and safflower oil. There was apparently no increase in the serum and liver cholesterol levels in both groups of animals cholesterol-enriched diets that had been fed for 38 days. Fecal excretion of neutral and acidic steroid tended to be higher in the perilla oil group than in the safflower oil group. The perilla oil group significantly increased 20:5n-3 in liver phosphatidylcholine and phosphatidylethanolamine accompanying a decrease in 20: 4n-6. Such changes were not so evident in liver phosphatidylinositol. The production of leukotriene B4 and the concentration of prostaglandin E2 in the spleen were higher in the safflower oil group than in the perilla oil group. Thus, the hypocholesterolemic effect of the undigested fraction of soybean protein was apparently reproduced even in hamsters. Dietary fat-induced changes in lipid parameters in hamsters resembled those observed in rats.

Animals↗

Unmasking of activated histamine H3-receptors in myocardial ischemia: their role as regulators of exocytotic norepinephrine release.

We had previously found that histamine H3- receptors are negatively coupled to norepinephrine exocytosis in atrial tissue. We report here that in the presence of H1- and H2- receptor blockers, histamine significantly inhibits the tachycardia and norepinephrine release elicited by sympathetic nerve stimulation is isolated guinea pig hearts, an effect prevented by the H3 antagonist, thioperamide. Sympathetic nerve stimulation also caused a 1.5-fold increase in histamine overflow, which was insufficient to activate H3 receptors because thioperamide affected neither the tachycardia nor the norepinephrine release. Hence. We questioned whether H3 receptors become activated when adrenergic activity is greatly enhanced, as in myocardial ischemia. Guinea pig hearts underwent 10-min global ischemia. At reperfusion, norepinephrine exocytosis was markedly augmented and was associated with a 3.5-fold increase in histamine overflow. (R)alpha-methylhistamine, an H3 agonist, did not modify norepinephrine release, whereas thioperamide doubled it. Thus, in physiologic conditions, cardiac H3 receptors are quiescent, yet available for activation by exogenous ligands. In contrast, in the ischemic myocardium, H3 receptors appear to be fully activated by an endogenous ligand, probably histamine. Hence, cardiac H3 receptors may play an important role by negatively modulating exocytotic norepinephrine release associated with ischemic states.

Animals↗

Cytokines involved in graft-versus-host disease.

Graft-versus-host disease (GVHD) is one of the major complications which should be resolved to improve the survival rates in allogeneic bone marrow transplantation (BMT). Recently, several cytokines have been identified, suggesting that they form a cytokine network and play an important role in immune system and hematopoiesis. Among several cytokines, it has been reported that tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are mainly involved in GVHD. In the present report, we analyzed the role of cytokines in GVHD. When we measured serum cytokine levels, IL-6, interferon gamma (IFN gamma), and TNF alpha levels were increased prior to the onset of acute GVHD. For chronic GVHD, a similar pattern of cytokine increment was observed. Interestingly, these cytokines appeared to interact synergistically to induce clinical GVHD, suggesting that none of those cytokines does not function solely. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that increased IL-1 beta mRNA expression was also observed in acute GVHD in addition to increased IL-6 and TNF alpha mRNA expressions. Unexpectedly, no increased IL-2 levels were observed in both assays. In hyperacute GVHD, only IL-6 level was increased. However, in vivo administration of IL-6 into allogeneic bone marrow chimeras did not induce severe GVHD. Therefore, some other factors also appeared to be involved in inducing hyperacute GVHD. Furthermore, it is important to consider the role of inhibitory cytokines such as transforming growth factor beta (TGF beta) or IL-10.

Animals↗

[Use of Bullard intubating laryngoscope in emergency room].

A sixty-year-old male patient with caries of the cervical spine suffered from cardio-respiratory arrest outside the hospital. Laryngeal mask was inserted into his pharynx and he was brought to the emergency department of our hospital under CPR by emergency paramedical staffs. Endotracheal intubation was tried three times with a Macintosh laryngoscope but was unsuccessful. His neck was difficult to extend and his epiglottis was not visible at all (X-ray photograph showed the fusion and the significant backward protrusion of his cervical spine). EGTA and Combitube were tried but in vain. At last Bullard intubating laryngoscope with videocamera system was operated. An endotracheal tube was easily inserted into his trachea with it and effective cardiopulmonary resuscitation was managed under reliable airway maintenance. These facts indicate that Bullard intubating laryngoscope is valuable at the emergency department and it should be always available there.

Cardiopulmonary Resuscitation↗

Cytokine gene expression by concanavalin A-stimulated peripheral mononuclear cells after bone marrow transplantation: an indicator of immunological abnormality due to chronic graft-versus-host disease.

The response of IFN-gamma, IL-2 and IL-5 mRNA expression to the stimulation of concanavalin A (Con A) in peripheral blood mononuclear cells (PBMC) after bone marrow transplantation (BMT) was analyzed using reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the recovery of T cell function. The subjects were 23 patients undergoing allogeneic BMT, 1 syngeneic BMT, 1 autologous BMT and 2 normal individuals. IFN-gamma mRNA expression increased after Con A stimulation in 6 patients who had limited chronic graft versus host disease (GVHD), 14 patients who did not have chronic GVHD, each one patient receiving syngeneic and autologous BMT and 2 normal individuals. On the other hand, IFN-gamma mRNA expression was not increased by Con A stimulation in 4 patients who had extensive chronic GVHD. Also, the concentration of IFN-gamma in cultured medium in a patient with extensive chronic GVHD was not detectable. A similar low response of IL-2 and IL-5 mRNA expression to Con A was observed in these patients with extensive chronic GVHD. These findings indicate that the cytokine productive capacity of T cell (IFN-gamma and IL-2 could be produced by type 1 T helper (Th1) cells and IL-5 could be produced by type 2 T helper (Th2) cells) was suppressed in patients who had extensive chronic GVHD, while that capacity was almost normal in patients without chronic GVHD and with limited chronic GVHD. Therefore, the analysis of cytokine gene response to Con A stimulation may provide useful information regarding immune reconstitution after BMT.

Adolescent↗

Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels.

Hyperacute graft-versus-host disease (GVHD), which progresses severely and rapidly, was observed in three patients with acute leukemia transplanted with bone marrow cells from human leukocyte antigens (HLA)-identical and mixed leukocyte reactions (MLR)-negative siblings. Hyperacute GVHD developed in these patients within 7 days after bone marrow transplantation (BMT) and was rapidly aggravated inspite of cyclosporin A (CyA) and short-term methotrexate (MTX) prophylaxis and treatment with bolus methylprednisolone (mPSL). These patients showed markedly increased serum interleukin-6 (IL-6) levels after BMT, whereas other cytokines such as interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and IL-2 were not increased compared with pretreatment levels. These findings suggest that markedly increased IL-6 levels may be related to hyperacute GVHD.

Acute Disease↗

Serum cytokine levels in bone marrow transplantation: synergistic interaction of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha in graft-versus-host disease.

In patients with acute graft-versus-host disease (GVHD), IL-6 gradually increased > 14 days before clinical onset of acute GVHD and decreased when acute GVHD disappeared. Interferon-gamma (IFN gamma) levels increased < 14 days before clinical acute GVHD and decreased at the disappearance of acute GVHD. Tumor necrosis factor-alpha (TNF alpha) levels increased almost simultaneously with the onset of acute GVHD and also decreased when it disappeared. However, these results do not necessarily mean that the increased levels of IL-6, IFN gamma and TNF alpha induced acute GVHD; they merely show that acute GVHD is observed more frequently in patients with increased IL-6, IFN gamma and TNF alpha levels than in those with normal levels. Although increased IL-6 levels were also observed in patients without acute GVHD, concomitant increase of IFN gamma and TNF alpha was not detected in such cases, showing that IL-6 can be increased by even graft-versus-host reaction (GVHR) which may not develop into clinical acute GVHD. Taken together, acute GVHD appeared to be induced by synergistic interaction of IL-6, IFN gamma and TNF alpha, consistent with a cytokine cascade. A similar interaction of IL-6 and TNF alpha was also observed in chronic GVHD. Although IFN gamma levels were slightly increased in chronic GVHD and sometimes aggravated the disease status, IL-6 and TNF alpha appeared to be more closely involved in the induction of chronic GVHD. In autologous BMT, increased cytokine levels were not observed unless IL-2 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[A case of dissecting aortic aneurysm and presence of anti-Jr(a) antibody].

A 66-year-old woman was diagnosed as a DeBakey type II dissecting aortic aneurysm with angiography and CT. Antibody screening revealed circulating anti-Jr(a) antibody. Preoperatively, erythropoietin was administered twice a week. Over 24 days, a total of 1200 ml of her blood was removed and stored for autologous transfusion. The dissecting ascending aorta was replaced with the aid of cardiopulmonary bypass. The post operative course was uneventful. By using erythropoietin, pre-donated autologous blood, cell saver, aprotinin and transfusion of fresh autologous blood, it was possible to perform cardiovascular surgery on this patient who had an abnormal antibody. This patient is the first case of repair or dissecting aortic aneurysm with anti-Jr(a) antibody in Japan.

Aged↗

Massive apoptosis in infantile myofibromatosis. A putative mechanism of tumor regression.

Two cases of solitary infantile myofibromatosis (IM) are presented. Solitary IM are tumors prone to spontaneous regression. Histopathologically, several tumor lobules in our IM cases had central areas of massive cell death, with nuclear pyknosis, cytoplasmic hyalinization and nuclear fragmentation but without lymphoid or neutrophilic cell infiltration. These central cell death areas consisted of about 40% in case 2 and 50% in case 1 of the entire tumor tissues, respectively. Electron microscopy revealed that the condensed nuclei and cytoplasm were fragmented into "apoptotic bodies", with or without phagocytosis by histiocytes. DNA fragmentation, as evidenced by the terminal deoxy transferase-mediated uptake of biotinylated dUTP, was identified at massive cell death areas on paraffin sections from both cases. A characteristic 180- to 190-bp nucleosomal ladder was detected in DNA obtained from the tumor cells in case 1. The collective evidence suggested that these tumors underwent a central, massive apoptosis. As massive cell death similar to that seen in the present cases has been described in other documented cases of IM, we propose that the spontaneous regression that frequently occurs with this type of tumor may be mediated by massive apoptotic cell death.

Actins↗

[Reversal of myelofibrosis is an important pre-transplant factor for bone marrow grafting--a successful case of allogeneic bone marrow transplantation for an acute megakaryoblastic leukemia].

We report a successful ereated case of acute megakaryoblastic leukemia (AMKL) with myelofibrosis (MF), which achieved a disease free condition, with disappearance of MF, for over 24 months after allogeneic bone marrow transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM aspiration resulted in a dry tap and MF and cells stained positive with anti-GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete remission was achieved by multi-drug chemotherapy including behenoylcytosine arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After preconditioning with little BU+CY, BMT was performed from an HLA-identical brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host disease (grade 1) was observed, which was controlled by 60 mg/day of PSL. Engraftment was achieved on day 12. Although cystitis developed, he was discharged on Apr. 5, 1992 and remains disease free. Including the present case, seven allogeneic BMT patient with MF have been reported so far in Japan. Four cases in whom MF recovered before BMT showed better results than other three cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre-transplant factor for successful BMT in patients with MF.

Adult↗

[Clinical application of gene technology to monitor bone marrow transplantation].

We assessed the origin of peripheral blood cells and bone marrow cells obtained from 15 patients after allogeneic bone marrow transplantation (allo BMT) by sensitive two-step polymerase chain reaction (PCR) amplification of MCT118, a variable number of tandem repeats regions (VNTR), that can be used to detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism(MC) was detected in the haematopoietic cells of 3 patients. Two patients developed relapse of leukaemia after the detection of MC and one patient died of bone marrow hypoplasia 7 months after BMT. These findings indicate the clinical usefulness of this method to monitor patients with MC. Also, we analyzed cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allo BMT using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin(IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. These findings suggest that IL-1 beta, IL-6, and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Therefore, analysis of MC and cytokine mRNA expression using the PCR technique after allogeneic bone marrow transplantation provide important information for treatment and monitoring of marrow transplant patients.

Adolescent↗

[A case of a huge malignant lymphoma in the lesser omentum showing a long-term survival after combined treatment of surgery and VEP-THP chemotherapy].

A 33-year-old house wife with malignant lymphoma in the lesser omentum was treated with a combination of surgery and VEP-THP chemotherapy (consisting of pirarubicin, cyclophosphamide, fildesin and predonine). Complete remission has been observed by reduction surgery and subsequent chemotherapy of VEP-THP. Although mild bone marrow suppression was seen during the chemotherapy, gastrointestinal toxicity and alopecia were minimal, which led to 10 complete courses of VEP-THP regimen. The patient has been in good health 5 years after the operation with no sign of recurrence. This case indicates that even advanced malignant lymphoma may be successfully treated with a combination of surgery and proper chemotherapy.

Adult↗