A case of huge gastric varices successfully treated with endoscopic injection sclerotherapy with occlusion of both supplying and draining veins with balloons.
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Publications and source records attributed to K Ando.
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OBJECTIVES: Restoration of coronary blood flow by angiogenesis may offer a new approach to intractable ischemic heart disease. In the present study, we investigated the angiogenic effects of gene transfer of vascular endothelial growth factor 165 on microvascular myocardial ischemia. METHODS: A rabbit model of microvascular myocardial ischemia was created by plugging coronary microvessels with microspheres (15 microm in diameter, 2.8 x 10(5)/kg, n = 29). Gene transfer was performed by semi-selective intracoronary injection of recombinant adenovirus expressing vascular endothelial growth factor 165 forty minutes after microsphere injection (n = 9). RESULTS: Microsphere injection reduced myocardial perfusion (78% +/- 9% of baseline tissue flow) and diminished myocardial contraction (61% +/- 12% of the baseline ejection fraction) and cardiac performance (elevated left ventricular end-diastolic pressure and decreased systemic flow) in the acute phase. At 17 +/- 3 days, gene transfer of vascular endothelial growth factor 165 had had the following effects: (1) promoted coronary angiogenesis as evidenced by myocardial flow above the baseline (121% +/- 24%), (2) increased vascular density revealed by synchrotron radiation microangiography and histologic analysis, (3) ameliorated the degree of myocardial ischemia as evidenced by myocardial lactate content and the extent of histologic necrosis, and (4) restored heart function as evidenced by increased ejection fraction (95% +/- 10%), reduced left ventricular end-diastolic pressure, and restored body weight. CONCLUSIONS: In vivo vascular endothelial growth factor 165 gene transfer promoted angiogenesis and was an effective approach to treating microvascular myocardial ischemia.
PURPOSE: To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein. MATERIALS AND METHODS: RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression. RESULTS: The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly induced VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF protein levels, detected in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. CONCLUSION: Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.
PURPOSE: To examine the relationship between cell killing and residual chromatin breaks after irradiation with qualitatively different types of radiation in six human cell lines. MATERIALS AND METHODS: Six human tumour cell lines and normal human cells were irradiated with 200 kV X-rays and two carbon-ion beams accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) differing in LET. At the sample position the carbon-ion beams had LET infinity values of 13.1 and 77.5 +/- 0.4 keV/microm. Cell inactivation was documented by a colony assay. Residual chromatin breaks were measured by counting the number of residual chromatin fragments at 24h, detected by the premature chromosome condensation (PCC) technique. RESULTS: The cell lines covered a broad range of radiosensitivity. D10 values ranged from 3.53 to 8.12 Gy for X-rays, 2.56 to 7.41 Gy for the lower LET carbon ions and 1.17 to 3.85 Gy for the higher LET carbon ions. The results for residual chromatin breaks indicate that the more radiosensitive cell lines showed a greater induction of residual chromatin breaks either by X-rays or carbon-ions, and that an X-ray resistant cell line also showed resistance to carbon-ions. Cellular radiosensitivity correlated with the frequency of residual chromatin breaks. CONCLUSION: The detection of residual chromatin breaks by the PCC technique could be used to predict cellular radiosensitivity among qualitatively different types of radiation.
Erythrocytes oxidized or aged in the circulation undergo membrane protein aggregation and anti-band 3 autoantibody binding to the cell surface. When human erythrocytes were mildly oxidized in vitro with 0.1 mM Fe(III) at 37 degrees C for 3 h, the aggregation of nonionic detergent C(12)E(8)-insoluble membrane protein and the binding of anti-band 3 IgG to the cell surface were increased. Incubation of membranes isolated from the oxidized cells increased the amount of protein aggregates by 5-fold after 6 h, while incubation for a further 12 h sharply decreased the amount of aggregates. In the presence of diisopropyl fluorophosphate (DFP), however, the increased amount of aggregates was maintained in the subsequent incubation. Western blot analysis of the aggregates using rabbit anti-band 3 showed that band 3 protein aggregates increased in the initial stage of incubation and decreased upon subsequent incubation, whereas the increased band 3 protein aggregates did not subsequently decrease when membranes were incubated in the presence of DFP. Incubation of the oxidized cells at 37 degrees C for 18 h caused reduction of the membrane protein aggregates and the (125)I-anti-band 3 IgG binding to the cell surface, while incubation in the presence of DFP did not cause these reductions. The results suggest that the oxidation-induced cell membrane protein aggregates were probably removed by 80-kDa serine protease, namely, oxidized protein hydrolase (OPH), in the oxidized cell membranes [Fujino et al. (1998) Biochim. Biophys. Acta 1374, 47-54; (1998) J. Biochem. 124, 1077-1085; (2000) Biochim. Biophys. Acta 1478, 102-112], and as a result the increased anti-band 3 binding to the cell surface was reduced.
We present the case of a 72-year-old woman with successful control of repeated episodes of bleeding from diffuse antral vascular ectasia (DAVE) by laser coagulation therapy. In addition to DAVE, the patient also suffered from severe iron deficiency anaemia (due to recurrent bleeding), liver cirrhosis, and huge tumours of hepatocellular carcinoma (HCC). She was referred from another hospital after failure to stop her bleeding episodes. Endoscopic examination revealed diffuse speckled telangiectasia over most of the stomach (from antrum to the upper portion of the body) and large numbers of blood clots. The patient had received repeated blood transfusions, haemostatic drugs, and H2 receptor antagonists at the other hospital, without improvement of the repeated bleeding. She underwent three sessions of endoscopic laser coagulation therapy for the lesions at our hospital after the final diagnosis of DAVE had been made based on the characteristic histological findings of biopsied specimens. This treatment improved her general condition and stopped the bleeding from the gastrointestinal tract even without fasting. Unfortunately, however, her liver function gradually worsened due to HCC and previous massive bleeding, and she finally died of liver failure three months after the last laser session. Autopsied specimens obtained from the patient's stomach revealed that macroscopic diffuse speckled telangiectasia and microscopic typical vasodilatation in mucosal and submucosal layers of gastric tissue had disappeared in the treated areas but not all portions of the DAVE lesion. These histological findings for the treated areas, in addition to the clinical improvement of bleeding, suggest that endoscopic laser coagulation therapy may be useful and one of the first choices in treatment for DAVE.
OBJECTIVES: The incidence of poor neurologic outcomes was studied in term newborns who had suffered severe asphyxia at birth. METHODS: Subjects were 152 newborns admitted to the NICU with a low Apgar score at 1 or 5 minutes. A 1-year prospective follow-up of neurological outcomes was carried out by a questionnaire survey concluded between April 1, 1996 and March 31, 1998. RESULTS: 1) The incidence of a poor neurologic outcome, including 15 neurologic sequelae and 6 deaths, was 13.8% among the subjects. 2) The risk of a poor outcome was increased by 13-fold in neonates with adverse neurological signs and 31-fold in those with hypoxic ischemic encephalopathy. CONCLUSION: The incidence of poor neurologic outcome was very high among term infants with low Apgar scores. These infants were 10 times to 20 times more likely to die, or to survive with permanent disabilities, than were infants without low Apgar scores.
The aim of this study was to assess how the administration of prostaglandin E(1) incorporated in lipid microspheres (Lipo PGE(1)) affects liver injury and regeneration after massive hepatectomy in rats. Two hundred and eight male Wistar rats underwent 90% partial hepatectomy. Lipo PGE(1) of 1, 10 or 30 microg/kg were administered intraperitoneally at 6 h prior to and 0 and 6 h after hepatectomy. Postoperative increases in serum GOT, total bilirubin, IL-6 and plasma endotoxin levels were significantly suppressed by Lipo PGE(1). The depressed phagocytic index and arterial ketone body ratio and hepatic DNA synthesis after 90% partial hepatectomy were significantly enhanced by Lipo PGE(1), which resulted in the improvement of survival. Lipo PGE(1) might bring about a protective effect on liver injury and an enhancement of liver regeneration after massive hepatectomy.
AIM: The objective of this study was to examine the effects of perioperative administration of ulinastatin, or urinary trypsin inhibitor (UTI), on inflammatory cytokines and acute-phase proteins induced by inflammatory cytokines in patients who had undergone hepatic resection. METHOD: Twenty patients admitted to the hospital for hepatic resection were equally randomized to one of two groups: the UTI group, those who were administered perioperative UTI, and the control group. RESULTS: The UTI group had no adverse effects from using UTI. Production of serum interleukin-6 (IL-6) tended to be attenuated in the UTI group when compared with the control group. Moreover, the UTI group had significantly decreased positive acute-phase C-reactive protein (p < 0.05) and significantly increased negative acute-phase protein prealbumin and retinol-binding protein (p < 0.05). Serum IL-6 levels significantly correlated with serum C-reactive protein levels on postoperative day 1 (r = 0.70, p < 0.01). CONCLUSION: These results suggest that perioperative administration of UTI might deserve further assessment for use in modulating acute-phase responses without adverse effects in patients who have undergone hepatic resection.
The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63. 6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.
The influence of sesamol, an antioxidant in processed sesame oil, on oxidative modification of human erythrocyte membrane proteins was investigated. Human erythrocytes were incubated with sesamol at various concentrations up to 10 mM at 37 degrees C for 1 h. The amounts of hemoglobin bound to the membranes and detergent C12E8-insoluble membrane protein aggregates were increased as the concentration of sesamol increased. Western blot analysis indicated that aggregates of band 3 protein were increased by the treatment. Binding of anti-band 3 antibody to the erythrocytes was increased by the treatment. Isolated cell membranes were incubated with sesamol similarly. Aggregates of band 3 protein were also increased, indicating that the band 3 protein aggregation was little affected by hemoglobin bound to the membranes. Aggregation of band 3 protein in the treatment of isolated cell membranes was partially prevented when the treatment was conducted under anaerobic conditions, suggesting that augmentation of the protein aggregation by sesamol involved both oxygen-dependent and oxygen-independent pathways. Among phenolics, sesamol showed a distinctive feature to increase band 3 protein aggregation in erythrocyte membranes and to enhance anti-band 3 binding to erythrocytes.
Nitrotyrosine is considered a stable biomarker of reactive nitrogen species, including nitrogen dioxide (NO2) and peroxynitrous acid (ONOOH) in biomaterials. There are inconsistent observations on the detection of free and protein-associated nitrotyrosine in normal human plasma. Human erythrocytes, differentiated from erythrocyte precursor cells in the bone marrow, circulating in the body for an average of 120 d, and finally removed by spleen macrophages, may be exposed to reactive nitrogen species. In the present study, membrane proteins and hemoglobin from the senescent erythrocyte population were compared with those from young erythrocytes separated from the same individuals in their nitrotyrosine presence using newly prepared rabbit polyclonal anti-nitrotyrosine-ribonuclease A and anti-nitro(N-butoxycarbonyl)tyrosine-bovine serum albumin antibodies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the membranes and hemoglobin, and subsequent Western blot analysis, showed that these antibodies only slightly bind to the bands of the proteins from both young and senescent erythrocytes, whereas these antibodies definitely bind to the protein bands of membranes and hemoglobin nitrated by NO2 or ONOOH in vitro. This result indicates that nitrotyrosine is not detected in the membrane proteins and hemoglobin in human normal erythrocytes in circulation. However, this does not conclude that erythrocytes are not exposed to reactive nitrogen species in the circulation.
4-Hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF) is representative of the Maillard reaction-derived reductones found in many foodstuffs. Influence of HEMF on iron ion-induced oxidative modification of human erythrocyte membranes and low density lipoprotein (LDL) under aerobic conditions was investigated. When human erythrocytes were incubated at 37 degrees C for 24 h with HEMF alone, levels of thiobarbituric acid-reactive substances (TBARS) and non-ionic detergent C12E8-insoluble membrane protein aggregates in the membranes were unchanged. Levels of TBARS and protein aggregates in the membranes increased on treatment of the cells with Fe(III) ion at 37 degrees C for 3 h were lowered in the presence of HEMF. Western blot analysis indicated that aggregates of band 3 protein induced by Fe (III) ion were decreased in the presence of HEMF, and the level of TBARS in LDL increased on treatment with Fe(II) or Fe(II) ion at 37 degrees C for 24 h was also lowered in the presence of HEMF. The results indicate that HEMF protected the iron ion-induced oxidative modification of human erythrocyte membranes and LDL.
Adrenomedullin (AM) is a potent vasodilating peptide secreted from the vasculature of various organs. It is biologically active when its C-terminus is amidated. Recently, an RIA method was developed for measurement of the active form of AM, or mature AM. We here employed this method to investigate the significance of amidation of AM in controlling cardiovascular function. Thirty-six patients under hemodialysis were recruited and divided into hypertensive (n = 25; 157/86 mmHg) and normotensive (n= 11; 116/66 mmHg) groups. Mature AM, immature AM and blood pressure were monitored during hemodialysis in all patients. There was a significant reduction in blood pressure during hemodialysis in both groups, although after hemodialysis blood pressure was still higher in hypertensives than in normotensives (139 +/-14.8/76 +/- 2.5 mmHg vs. 110 +/- 5.1/66.7 +/- 3.1 mmHg). Mature AM before hemodialysis were lower in hypertensives than normotensives and it decreased in both groups. Although mature AM decreased more in normotensives than in hypertensives (-27 +/- 8% vs. -17 +/- 5%), at the end point, its level was still higher in normotensives. The ratio of mature AM/immature AM decreased only in normotensives (-11.4 8.7%), whereas it remained stable in hypertensives (0.2 +/- 5.6%). Both groups showed similar changes in ANP, endothelin, catecholamines, cGMP, and NOx. The low level in mature AM level in hypertensives may have contributed to the higher blood pressure in this group. The attenuation of AM amidation in normotensives indicates that an unspecified amidative enzyme of AM was regulated in order to normalize blood pressure.
The pattern of cerebrovascular substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) innervation was investigated in the quail. SP- and CGRP-IR nerves were relatively a few in the rostral part of the anterior circulation, and very scanty or lacking in its caudal part and the whole of the posterior circulation. A significant finding was that the anterior circulation in the majority of individuals is furnished with a varying proportion of SP-IR nerves with or without CGRP immunoreactivity. There was a good correlation in the expression of CGRP immunoreactivity between SP-IR cells in the ophthalmic division of the trigeminal ganglion and SP-IR nerves supplying the major cerebral arteries. In the quail, SP- and CGRP-IR fiber bundles are usually present in the internal ethmoidal artery (IEA). From these and other findings, it is most probable that cerebral perivascular SP- and CGRP-IR nerves are mainly derived from the same categories of neurons in the primary sensory ganglion via the IEA. The close association of varicose SP-IR axons to the nerve cells in the pial arteries suggests that these intrinsic neurons may play some vasocontrolling roles through the modulatory effect of their pericellular SP-IR axons.
Human bone marrow (BM) or mobilized peripheral blood (mPB) CD34(+) cells have been shown to loose their stem cell quality during culture period more easily than those from cord blood (CB). We previously reported that human umbilical CB stem cells could effectively be expanded in the presence of human recombinant cytokines and a newly established murine bone marrow stromal cell line HESS-5. In this study we assessed the efficacy of this xenogeneic coculture system using human BM and mPB CD34(+) cells as materials. We measured the generation of CD34(+)CD38(-) cells and colony-forming units, and assessed severe-combined immunodeficient mouse-repopulating cell (SRC) activity using cells five days after serum-free cytokine-containing culture in the presence or the absence of a direct contact with HESS-5 cells. As compared with the stroma-free culture, the xenogeneic coculture was significantly superior on expansion of CD34(+)CD38(-) cells and colony-forming cells and on maintenance of SRC activity. The PKH26 study demonstrated that cell division was promoted faster in cells cocultured with HESS-5 cells than in cells cultured without HESS-5 cells. These results indicate that HESS-5 supports rapid generation of primitive progenitor cells (PPC) and maintains reconstituting ability of newly generated stem cells during ex vivo culture irrespective of the source of samples. This xenogeneic coculture system will be useful for ex vivo manipulation such as gene transduction to promote cell division and the generation of PPC and to prevent loss of stem cell quality.
Balb/c mice were examined to determine whether or not they transmitted rodent malaria, Plasmodium berghei, to their fetuses. On the 15th day of pregnancy, mice were inoculated with approximately 3 x 10(6) P. berghei-infected erythrocytes by peritoneal injection. The blood from 27 adult females and 196 neonates was examined using a sensitive polymerase chain reaction (PCR) method with a detection level of approximately 1 parasite/microl blood. The average parasitemia of females at delivery was 8.1%, ranging from nondetectable to 37.1%. In 12 females, nested PCR established the presence of blood parasite DNA. Malaria parasites were microscopically confirmed in 2 of the 12 neonates. Maternal parasitemia at the time of delivery was not correlated with the incidence of vertical infection (6.1%), which was higher in this study than that found in previous studies. Although the combination of balb/c mice and P. berghei has not been used to examine vertical transmission of malaria, our report showed that this model may be used for this purpose.
The LET-RBE spectra for cell killing for cultured mammalian cells exposed to accelerated heavy ions were investigated to design a spread-out Bragg peak beam for cancer therapy at HIMAC, National Institute of Radiological Sciences, Chiba, prior to clinical trials. Cells that originated from a human salivary gland tumor (HSG cells) as well as V79 and T1 cells were exposed to (3)He-, (12)C- and (20)Ne-ion beams with an LET ranging from approximately 20-600 keV/micrometer under both aerobic and hypoxic conditions. Cell survival curves were fitted by equations from the linear-quadratic model and the target model to obtain survival parameters. RBE, OER, alpha and D(0) were analyzed as a function of LET. The RBE increased with LET, reaching a maximum at around 200 keV/micrometer, then decreased with a further increase in LET. Clear splits of the LET-RBE or -OER spectra were found among ion species and/or cell lines. At a given LET, the RBE value for (3)He ions was higher than that for the other ions. The position of the maximum RBE shifts to higher LET values for heavier ions. The OER value was 3 for X rays but started to decrease at an LET of around 50 keV/micrometer, passed below 2 at around 100 keV/micrometer, and then reached a minimum above 300 keV/micrometer, but the values remained greater than 1. The OER was significantly lower for (3)He ions than the others.