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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 469 records · Page 26Linked to original sources

Neutrophil-independent myocardial dysfunction during an early stage of global ischemia and reperfusion of isolated hearts.

The effect of global ischemia and reperfusion on the expression of cytokine genes and cell adhesion molecules by myocardial tissues and neutrophils was studied by using the Langendorff model. Although cardiac function deteriorated after reperfusion of ischemic hearts, there was no evidence of inflammation and myocardial degeneration, which is in contrast to previous findings that neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion injury in regional ischemia. Flow cytometry analysis demonstrated that the global ischemia and reperfusion did not affect the expression of adhesion molecules on neutrophils. We also examined the expression of various cytokines which are involved in inflammatory responses. Only interleukin 1 alpha was induced after the reperfusion of the ischemic hearts. These results suggest that neutrophils barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in post-ischemic myocardial dysfunction during the early stage of reperfusion.

Animals↗

Characteristic difference of hepatocellular carcinoma between hepatitis B- and C- viral infection in Japan.

Characteristics of 205 consecutive patients with hepatocellular carcinoma (HCC) admitted during 1990 to 1993 have been analyzed from the standpoint of hepatitis viral infection in Japan. Among 205 HCC patients, 71% of the patients showed positivity for hepatic C virus (HCV) antibody alone, 13% showed positivity both for HCV and HBV (HCV/HBV) antibody, 11% demonstrated HBsAg alone, and negativity of both HCV and HBV antibody in 4% only. Positivity to both HCV antibody and HBsAg was demonstrated in 1% only. Mean detection age of HCVAb-positive HCC as well as both HCV/HBV antibody-positive HCC was 62 +/- 7 years, in contrast to 52 +/- 13 years in HCC with HBsAg (P < .05). Male-to-female ratio among HCVAb-positive HCC was 3.3:1, in contrast to 5.5:1 among the HCV/HBVAb-positive HCC and 7:1 among HBsAg-positive HCC, but there was no significant difference in the gender distribution between these groups. More than 60% of HCVAb-positive HCC and HCV/HBVAb-positive HCC were classified into the stage of Child B and C, whereas 65% of HBsAg-positive HCC was at the stage of Child A. The severity of liver disease was confirmed by liver histology, indicating that more than 70% of the HCVAb-positive HCC and the HCV/HBVAb-positive HCC showed cirrhosis, in contrast to 50% among the HBsAg-positive HCC. Three-year survival rate of HCV Ab-positive HCC and HBV/HCVAb-positive HCC was 68% and 56%, respectively, in contrast to 47% in HBsAg-positive HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Balloon angioplasty before Wheat's operation in a patient with Turner's syndrome.

The case of a 19-year-old woman with Turner's syndrome, dissecting aneurysm of the ascending aorta, coarctation of the aorta and bicuspid aortic valve stenosis is presented. Balloon angioplasty was performed before surgery to relieve the pressure gradient caused by coarctation of the aorta. Successful surgical treatment was carried out using Wheat's method. Four-year follow-up has revealed no signs of complications such as restenosis or aneurysm formation.

Adult↗

The amino acid sequence required for 5' --> 3' exonuclease activity of Bacillus caldotenax DNA polymerase.

We studied the 5' --> 3' exonuclease activity of Bacillus caldotenax DNA polymerase by site-directed mutagenesis. Among seven mutants constructed, two mutant DNA polymerases with an amino acid substitution of Gly184 --> Asp or Gly192 --> Asp were confirmed to be deficient in this exonuclease. The two positions corresponded to those of the Escherichia coli DNA polymerase I mutants defective in 5' --> 3' exonuclease, polA480ex and polA214. These results provide experimental support for the proposed amino acid sequence essential for the 5' --> 3' exonuclease activity associated with eubacterial polymerase I-like DNA polymerases (family A), including E.coli and Thermus aquaticus.

Bacillus↗

Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay.

OBJECTIVE: The authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses. SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied. METHODS: Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion. RESULTS: In 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean +/- SD, 7.7 +/- 5.5). The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered. The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)--a streptococcal preparation, OK-432, or interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions. Responses were seen only when the patients were treated with a combination of chemotherapy and BRM. CONCLUSION: There may be a notable differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusion versus solid recurrences. Various approaches, including a combination of chemotherapy and BRM, therefore, may have to be applied to overcome these drug resistances in practical chemotherapies for recurrent tumors.

Antineoplastic Agents↗

Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells.

Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. To study the loci where nicotine might exert its effect, we examined interactions between nicotine and rat pancreatic acini. When pancreatic acini were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were increased in time-and dose-dependent manners, and the t1/2 for dissociation of [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was 33% of the association at 37 degrees C. Unlabeled nicotine had no significant effect on the accumulation of [3H]nicotine. In addition, surface-bound [3H]nicotine was not detected when acini were washed in a low-pH solution or when they were trypsinized. These results suggest that the accumulation of nicotine may be a biological phenomenon and that [3H]nicotine does not bind to surface receptors of acinar cells, but accumulates intracellularly. The addition of verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10 mM) significantly increased the accumulation of [3H]nicotine. Carbachol and cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose-dependent manner. Taken together, the increasing effects of carbachol and cholecystokinin on the accumulation of nicotine may explain, at least in part, the mechanisms involved in the multiplicative effects of the combination of two risk factors, smoking habit and high-fat or high-protein diets, on human pancreatic diseases.

Animals↗

Effect of a new bombesin receptor antagonist, (E)-alkene bombesin isostere, on amylase release from rat pancreatic acini.

The short-chain pseudopeptide, [D-Phe6, Leu13 psi (CH2NH)Leu14]bombesin(6-14) (RDI), is reported to be a potent antagonist of bombesin, and development of this type of compound has greatly contributed to the investigation of biological actions of bombesin and its related peptides. We recently synthesized (E)-alkene bombesin isostere by replacing the peptide bond with an (E)-double bond: [D-Phe6, Leu13 psi [(E)CH = CH]Leu14] bombesin(6-14) (EABI). The present study examined the effect of EABI on amylase release from rat pancreatic acini. EABI showed no agonistic activity at concentrations up to 1 microM, and RBI showed slight agonistic activity at concentrations > 10 nM. EABI caused a dose-dependent inhibition of amylase release stimulated by 0.1 nM bombesin, with an IC50 of 6.7 +/- 1.7 nM, and induced almost-complete inhibition at 0.3 microM. RDI caused a dose-dependent inhibition of amylase release, with an IC50 of 68.7 +/- 16 nM. EABI caused a parallel and rightward shift of the entire dose-response curve of bombesin-stimulated amylase release, and the degree of the shift was dependent on the concentrations of EABI. EABI (100 nM) and RDI (100 nM) inhibited amylase releases stimulated by gastrin-releasing peptide (1 nM) and neuromedin-C (1 nM). In contrast, amylase release stimulated by cholecystokinin octapeptide (0.1 nM), carbachol (10 microM), vasoactive intestinal peptide (1 nM), and gastrin-17 (10 nM) was not inhibited by EABI and RDI. The results indicate that EABI is a potent and specific bombesin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Quantitative analysis of collagen and collagen subtypes I, III, and V in human pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic pancreatitis.

The collagen content in human pancreatic cancer tissue, tissue of tumor-associated chronic pancreatitis (TACP), and normal pancreatic tissue was determined in 14 patients with pancreatic cancer by measuring the amount of 4-hydroxyproline. Four patients with alcoholic chronic pancreatitis (AlCP) were also analyzed. The mean collagen content in both pancreatic cancer tissue and TACP tissue was approximately threefold higher than in normal pancreatic tissue. Cyanogen bromide peptides of type I, III, and V collagens from invasive ductal carcinomatous tissue of the pancreas and from TACP tissue of eight patients were analyzed sequentially using high-performance liquid chromatography with ion-exchange and gel-permeation columns. No difference in the proportion of type I, III, and V collagens was detected between pancreatic cancer tissue and TACP tissue. The mean collagen content in AlCP tissue was significantly lower than that in TACP tissue, but no difference in the proportion of type I, III, and V collagens was detected between these two tissues. These results indicate a similar quantity and distribution pattern of fibrillar collagen in human pancreatic cancer and TACP.

Alcoholism↗

A possible role of 92 kDa type IV collagenase in the extramedullary tumor formation in leukemia.

Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.

Collagenases↗

Soluble c-kit levels in acute GVHD after allogeneic bone marrow transplantation.

Serum soluble c-kit concentrations were measured in 11 patients with or without acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The serum soluble c-kit levels in the patients with moderate to severe acute GVHD (grade II-IV) were significantly lower than those in the patients with no or mild acute GVHD (grade 0-I) following the onset. The data from this study indicate that measurement of serum soluble c-kit concentration is a useful indicator of severe acute GVHD.

Adolescent↗

Epidemiological investigation of insulin resistance syndrome (syndrome X) in a city in Japan.

1. In order to study the prevalence of insulin resistance syndrome (syndrome X) in Japanese subjects, inhabitants aged above 40 years living in Osaka-Sayama city from September 1992 through December 1993 were investigated. The population-based study was performed on 2498 subjects (661 males and 1837 females) constituting 10.9% of the total population aged above 40 years. 2. The prevalence of glucose intolerance was 8.7% (n = 218) in 2498 subjects. The prevalence of hypertension was 36.9% (n = 923) and that of hypertriglyceridaemia was 19.0% (n = 475). The prevalence of syndrome X as characterized by an association of glucose intolerance, hypertension and hypertriglyceridaemia was 1.6% (n = 39) in all subjects examined and 17.4% in subjects showing glucose intolerance. 3. Fasting serum insulin levels were significantly higher in patients with syndrome X than in normal subjects. Furthermore, the levels were significantly correlated with blood levels of frucutosamine, fasting glucose and triglyceride, and with body mass index as well. 4. In conclusion, insulin resistance syndrome (syndrome X) is also found among the larger Japanese population, and fasting serum insulin levels can be a useful marker of this metabolic disorder.

Adult↗

Liver transplantation and hepatic sinusoidal cells.

Primary graft non-function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non-function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)alpha, and then increased ICAM-1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti-TNF alpha antibody and anti-ICAM-1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2-thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM-1, cytokines and prostanoids.

Cold Temperature↗

Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: possible involvement of G proteins.

1. The effects of fluoroaluminate complexes (NaF plus AlCl3) on force of contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were examined in rabbit left atrial muscles. 2. Fluoroaluminates (1-10 mM NaF + 10 microM AlCl3) produced a biphasic inotropic response which was composed of an early small decline and subsequent increase in force of contraction. In the presence of the Al3+ chelator, deferoxamine (100 microM), the positive inotropic response was completely abolished and a sustained negative inotropic response appeared, suggesting that only the positive inotropic response is due to the action of fluoroaluminates. 3. The positive inotropic effect of fluoroaluminates was associated with a significant increase in the total duration of a single contraction; the time to peak tension and relaxation time were prolonged. In contrast, these parameters were substantially abbreviated by isoprenaline or histamine. 4. When force of contraction was increased by isoprenaline or histamine, the addition of fluoroaluminates caused a marked negative inotropic effect, which was eliminated by pretreatment with pertussis toxin. 5. Fluoroaluminates did not cause a significant increase in cyclic AMP content at concentrations of NaF in the range of 1-10 mM. However, the content of cyclic AMP was greatly elevated by fluoroaluminates when the atrial muscles were pretreated with pertussis toxin. 6. Accumulation of [3H]-inositol monophosphate in atrial muscle strips prelabelled with myo-[3H]-inositol was significantly increased by fluoroaluminates at concentrations of NaF over 1 mM. The phosphoinositide response to fluoroaluminates remained unchanged with pertussis toxin pretreatment. 7.These results indicate that, in rabbit left atrial muscles, fluoroaluminates produce a positive inotropic effect which may be mediated by Gq but not by Gs proteins; they produce a negative inotropic effect possibly through Gi only when Gs is activated with other agents.

Aluminum↗

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US.

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.

Adenocarcinoma↗

Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis induced by a choline-deficient, ethionine-supplemented diet in mice.

In order to approach impaired stimulus-secretion coupling in acute pancreatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini. The in vitro amylase secretion analysis of the CDE groups demonstrated a poor dose-response curve which was significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was administered. Both in CDE and control groups, the application of a physiological dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amplitude of the oscillations in the CDE groups were not significantly different. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of stimulation both in CDE and control groups. The peak Ca2+ level was lower in the CDE groups, but this was not statistically significant. In conclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+ release are likely to be involved in the inhibition of enzyme secretion.

Acute Disease↗

bcr-abl hybrid messenger RNA in a patient with Philadelphia-negative essential thrombocythemia.

We describe a case of Philadelphia-negative essential thrombocythemia in whom bcr-abl hybrid messenger RNA was detected. The patient suffered from frequent splenic infarctions and myelofibrosis. Interestingly, a transformation to acute leukemia which was commonly seen in patients with bcr-abl-positive chronic myelogenous leukemia did not occur until he died from heart failure due to severe anemia 8 years after the diagnosis. The heterogeneity of bcr-abl-positive thrombocythemia is emphasized.

Fusion Proteins, bcr-abl↗