Left ventricular hypertrophy demonstrated by four-dimensional myocardiography by helical computed tomography.
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Cardiomyopathy, Hypertrophic↗
Biomedical subjects
H Shinohara
Publications and source records attributed to H Shinohara.
Mitoses of existing corticotrophs contribute to their proliferation in the rat pituitary during the late fetal period.
We studied the proliferation of pituitary corticotrophs quantitatively by labeling the proliferating cells with bromodeoxyuridine (BrdU) and carrying out immunocytochemistry for ACTH in rat fetuses at 19.5 days of gestation. In addition to labeling proliferating cells with a single injection of BrdU, we used double BrdU administrations at 9:00 and 19:00 for a more sensitive detection of proliferating cells. With this double administration, the number of cells labeled with either BrdU or both BrdU and ACTH increased by 1.75 and 2.3 times, respectively, compared with the single BrdU injection. The labeled cells further increased when the sections were stained for the proliferating cell nuclear antigen (PCNA) instead of BrdU. The number of cells labeled with PCNA or both PCNA and ACTH was 1.37 and 1.68 times that of the cells labeled with either BrdU or both BrdU and ACTH, respectively. The ratio of BrdU/ACTH-labeled cells or PCNA/ACTH-labeled cells to all corticotrophs was 13.6% and 24.3%, respectively, much higher than the ratios in fetuses having a single BrdU injection (6.6%). These results indicate that the mitosis of existing corticotrophs contributes greatly to their increase during the late fetal period.
Adrenocorticotropic Hormone↗
Complications associated with pulmonary resection in lung cancer patients on dialysis.
BACKGROUND: There are few studies available investigating the perioperative problems experienced by lung cancer patients on dialysis undergoing pulmonary resection. METHODS: A retrospective review of 7 patients on dialysis undergoing pulmonary resection for lung cancer was performed. RESULTS: The patient population consisted of 7 men, with a mean age of 59.9 years. The underlying kidney disease was glomerulonephritis in 5 patients and nephrosclerosis in 2. The mean levels of blood urea nitrogen and serum creatinine were 70.7 mg/dL and 9.4 mg/dL, respectively. Histologic diagnoses were adenocarcinoma in 2 patients and squamous cell carcinoma in 5. Standard lobectomy with lymph node dissection was performed in all cases. There was one operation related death due to pulmonary edema and subsequent development of pneumonia. There were two cases of sputum retention and four of hyperkalemia. One patient died of cerebral bleeding that occurred during dialysis 2 months postoperatively. CONCLUSIONS: In patients on dialysis who undergo pulmonary resection, there is a high incidence of pulmonary complications, in addition to hyperkalemia, hemodynamic instability, and a tendency for postoperative dialysis-associated bleeding.
Adenocarcinoma↗
Enhanced production of macrophage inflammatory protein 2 (MIP-2) by in vitro and in vivo infections with encephalomyocarditis virus and modulation of myocarditis with an antibody against MIP-2.
Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and lymphocytes. Macrophage inflammatory protein 2 (MIP-2) is a murine counterpart of IL-8. The present study was performed to determine whether MIP-2 aggravates murine myocarditis. We examined (i) the MIP-2-producing activity of encephalomyocarditis (EMC) virus-infected cultured macrophages, (ii) serial plasma MIP-2 levels in EMC virus-induced mice by enzyme-linked immunosorbent assay, and (iii) the effects of antimouse MIP-2 monoclonal antibody (MAb) in vivo upon myocarditis. The production of MIP-2 increased in an infection dose- and time-dependent manner in virus-infected RAW 264. 7 macrophages. Five-week-old C(3)H/He mice were inoculated with EMC virus. Plasma MIP-2 levels were significantly elevated in mice on days 7 and 14 postinfection. Mice were injected subcutaneously with anti-MIP-2 MAb at 10 microg/day (group 2) or 100 microg/day (group 3) on days 0 to 5 and were observed until day 21. Uninfected control mice (group 1) were prepared. The survival rate was higher in the anti-MIP-2-treated group (group 3), but not in group 2, than in the control group. Histopathological analysis revealed that cellular infiltration and myocardial necrosis with macrophage and T-cell accumulation were less prominent in the anti-MIP-2 MAb-treated group, but not in group 2, compared to the level in the controls. MIP-2 is an important naturally occurring inflammatory cytokine in myocarditis, and anti-MIP-2 MAb treatment may prevent the inflammatory response.
Animals↗
[Clinical significance of coronary flow reserve in hypertrophied heart: comparison with Doppler index, hemodynamics and plasma natriuretic peptide concentrations].
OBJECTIVES: The relationship was investigated between coronary flow reserve and Doppler echocardiographic parameters, hemodynamic parameters and plasma natriuretic peptide concentrations in the hypertrophied heart. METHODS: The subjects were 19 patients with hypertrophied heart due to various etiologies and no significant coronary artery stenosis. All patients were in sinus rhythm. The left ventricular wall thickness, the E/A ratio in transmitral flow velocity pattern and the Doppler index were determined by Doppler echocardiography, and the plasma atrial and brain natriuretic peptide concentrations were measured. At cardiac catheterization, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure were measured, and the coronary flow reserve was obtained by injecting intracoronary adenosine triphosphate into the left anterior descending artery using a Doppler guidewire. RESULTS: Coronary flow reserve in the patients was significantly lower than in 11 normal control subjects (2.50 +/- 0.76 vs 3.90 +/- 0.64, p < 0.001). There were no significant correlations between coronary flow reserve and the left ventricular wall thickness or the E/A ratio. The mean value of the Doppler index in the patients was 0.48 +/- 0.10 and there was a significant negative correlation between coronary flow reserve and the Doppler index (r = -0.73, p < 0.001). The correlation between coronary flow reserve and left ventricular end-diastolic pressure was not significant, but there was a significant negative correlation between coronary flow reserve and pulmonary capillary wedge pressure (r = -0.64, p < 0.01). There were significant negative correlations between coronary flow reserve and atrial (r = -0.62, p < 0.01), or brain natriuretic peptide concentrations (r = -0.56, p < 0.05). CONCLUSIONS: Coronary flow reserve may reflect overall cardiac performance evaluated by the Doppler index and plasma natriuretic peptide concentrations in the hypertrophied heart, and the measurement of coronary flow reserve may be useful for evaluating disease severity in patients with hypertrophied heart.
Aged↗
[A case of stage IV gastric cancer with multiple liver metastases and carcinomatous ascites responding to TS-1 for six months before progression].
We report the case of a 72-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases and carcinomatous ascites which responded to chemotherapy using TS-1. Treatment of the patient with daily oral administration of 120 mg TS-1 for 4 weeks resulted in complete regression of the liver metastases and ascites, as well as a 35% reduction in the size of the primary lesion. After 2 cycles, the primary tumor size was reduced to 55% and serum CA19-9 and CA125 levels were decreased to the normal ranges. This regimen was effective without any adverse effects, and improved the patient's QOL, for 6 months before progression of liver lesions. The patient received chemotherapy at our outpatient clinic for 10 months after the first treatment, after which he died of peritonitis carcinomatosa. The current case suggests that TS-1 may have a potent therapeutic efficacy in advanced gastric cancer patients.
Aged↗
Transforming growth factor-alpha delays gastric emptying and small intestinal transit in suckling rats.
Transforming growth factor-alpha (TGF-alpha) is a biologically potent polypeptide detected in the gastrointestinal tract in suckling rats. The major goal of the present study was to test the hypothesis that the administration of TGF-alpha affects gastric emptying and small intestinal transit in suckling rats. Suckling (12-day-old) rats fasted 16 h received rat TGF-alpha subcutaneously (s.c.) or orogastrically in varying doses (0, 0.5, 1.0 microg/rat in 0.1% BSA). Control animals received 0.1% BSA only. Poly R-478 dye was used as a motility marker. Rats were decapitated 45 min after marker administration and the amount of dye in the stomach and the small intestine was measured by spectrophotometry. Subcutaneous administration of TGF-alpha significantly delayed stomach evacuation. In controls, the stomach contained 21.4 +/- 1.4% (mean +/- s(x)) of the Poly R-478 marker, whereas in TGF-alpha treated rats the stomach contained 37.2 +/- 2.8% of the total Poly R-478 dye given to animals. The delaying effect of TGF-alpha was time- and dose-dependent. Small intestinal transit was also significantly delayed. The proximal jejunum of TGF-alpha treated rats contained a 1.4-fold higher amount of marker in comparison with control rats. Orogastrically administered rTGF-alpha did not affect gastric emptying or intestinal transit. In conclusion, s.c. administration of rat TGF-alpha significantly delayed the gastrointestinal motility in vivo in suckling rats.
Analysis of Variance↗
Element-selective single atom imaging.
Electron energy-loss spectroscopy (EELS) is widely used to identify elemental compositions of materials studied by microscopy. We demonstrate that the sensitivity and spatial resolution of EELS can be extended to the single-atom limit. A chemical map for gadolinium (Gd) clearly reveals the distribution of Gd atoms inside a single chain of metallofullerene molecules (Gd@C82) generated within a single-wall carbon nanotube. This characterization technique thus provides the "eyes" to see and identify individual atoms in nanostructures. It is likely to find broad application in nanoscale science and technology research.
Journal Article↗
One-dimensional metallofullerene crystal generated inside single-walled carbon nanotubes.
Electron microscope imaging for gadolinium metallofullerenes encapsulating in single-wall carbon nanotubes [(Gd@C82)n@SWNTs] identifies the single Gd atom encaged in each. The intermolecular distance between Gd@C82 is extremely regular, regarding the chains of Gd@C82 as novel one-dimensional crystals. Chemical state analysis of Gd atoms suggests evidence for charge transfer from Gd to either a fullerene cage or a nanotube. The slopes of the temperature dependence of electric resistance for the mat-like films of (Gd@C82)n@SWNTs and (C60)n@SWNTs are much steeper than that for empty SWNTs, suggesting the electron scattering due to the electrostatic potential from inside fullerenes playing an important role.
Journal Article↗
Dissociation and recombination between ligands and heme in a CO-sensing transcriptional activator CooA. A flash photolysis study.
CooA from Rhodospirillum rubrum is a transcriptional activator in which a heme prosthetic group acts as a CO sensor and regulates the activity of the protein. In this study, the electronic relaxation of the heme, and the concurrent recombination between ligands and the heme at approximately 280 K were examined in an effort to understand the environment around the heme and the dynamics of the ligands. Upon photoexcitation of the reduced CooA at 400 nm, electronic relaxation of the heme occurred with time constants of 0.8 and 1.7 ps. The ligand rebinding was substantially completed with a time constant of 6.5 ps, followed by a slow relaxation process with a time constant of 173 ps. In the case of CO-bound CooA, relaxation of the excited heme occurred with two time constants, 1.1 and 2.4 ps, which were largely similar to those with reduced CooA. The subsequent CO recombination process was remarkably fast compared with that of other CO-bound heme proteins. It was well described as a biphasic geminate recombination process with time constants of 78 ps (60%) and 386 ps (30%). About 10% of the excited heme remained unligated at 1.9 ns. The dynamics of rebinding of CO thus will help us to understand how the physiologically relevant diatomic molecule approaches the heme binding site in CooA with picosecond resolution.
Bacterial Proteins↗
C66 fullerene encaging a scandium dimer.
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Journal Article↗
Organic chemistry with heterofullerenes: photosensitized oxygenation of alkenes
Heterofullerenes C(59)HN and (C(59)N)(2) sensitize the reaction of olefins with molecular oxygen under photolytic conditions. 2-Methyl-2-butene and alpha-terpinene undergo ene and Diels-Alder photooxygenation reactions, respectively, even in the presence of minute amounts of azafullerenes to produce the corresponding peroxides.
Journal Article↗
Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change.
OBJECTIVES: We examined effects of immunoglobulin on murine myocarditis induced by encephalomyocarditis virus, not pathogenic to humans, and analyzed the plasma cytokine and catecholamine levels and the changes of the extracellular matrix with or without the treatment. BACKGROUND: We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis by an antiviral effect. However, it is not yet determined whether beneficial effects of immunoglobulin for myocarditis are due to antiviral effects or to other unknown effects. METHODS: Antiviral activity of human immunoglobulin (Polyglobin-N) against encephalomyocarditis virus was determined in vitro. Immunoglobulin (1 g/kg/day) was administered intraperitoneally to the virus-infected mice daily for two weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II. RESULTS: Antiviral activity of immunoglobulin could not be detected in the assay of a plaque-reduction method in vitro. The in vivo study showed that immunoglobulin administration ameliorated both myocardial necrosis with interstitial fibrin deposition in experiment I and interstitial fibrosis with the improvement of ventricular remodeling in experiment II by the reduction of plasma catecholamines, interferon-alpha, and soluble intercellular adhesion molecule-1. CONCLUSIONS: Immunoglobulin therapy could suppress myocarditis associated with the improvement of extracellular matrix changes by the reduction of neurohumoral activity.
Animals↗
Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target.
Animals↗
Disrupted transforming growth factor-beta signaling and deregulated growth in human biliary tract cancer cells.
Biliary tract carcinoma is a common neoplasm in Japan, and its treatment is difficult because it tends to promote fibrosis and easily invades surrounding tissues. To better characterize the biological features of this carcinoma, we investigated abnormalities in the transforming growth factor-beta (TGF-beta) signaling pathway in five human biliary tract cancer cell lines: RBE, KMBC, SK-ChA-1, Mz-ChA-1, and Mz-ChA-2. We stably transfected into these cells the luciferase reporter plasmid carrying promoter of the plasminogen activator inhibitor-1 gene, the expression of which is stimulated by TGF-beta1. Treating the KMBC and Mz-ChA-1 cells with TGF-beta1 neither inhibited cell growth nor stimulated luciferase activity. In contrast, the RBE and Mz-ChA-2 cells responded well to TGF-beta1 treatment. TGF-beta1-treated SK-ChA-1 cells exhibited attenuated luciferase activity and their growth was not inhibited. Smad4 mRNA was not detected in SK-ChA-1 and Mz-ChA-1 cells by Northern blot analysis. Genetic analysis disclosed a nonsense mutation in the Mad homologue 2a domain of the Smad4 gene in the SK-ChA-1 cells and a heterozygous deletion in the TGF-beta type II receptor gene in the KMBC cells. Expression of the exogenous Smad4 gene in the Mz-ChA-1 cells by transient transfection restored their luciferase activity. When these TGF-beta1-insensitive and less-TGF-beta1-sensitive cell lines were xenografted into nude mice, they developed tumors that had more prominent, intervening fibrosis (desmoplasia) than the tumors caused by TGF-beta1-sensitive cells. Thus, a tight correlation between disruption of the TGF-beta signaling pathway and deregulated growth of cancer cells has been demonstrated in biliary tract carcinoma. This seems to be a critical event in this carcinoma and may also be correlated with stromal cell reaction in cancer invasion.
Animals↗
Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase activation.
Recent studies have revealed that a variety of malignant tumors express Fas and/or its ligand FasL. However, tumor cells expressing Fas are not always susceptible to Fas-mediated cell death, and the biological significance of simultaneous expression of Fas and FasL in the same tumor is not known. In the present study, we addressed this question in three glioma cells lines, A-172, T98G, and YKG-1, which express both Fas and FasL endogenously and their Fas transfectants. We report here that: (a) in gliomas, [3H]TdR incorporation was enhanced by anti-Fas IgM monoclonal antibody CH-11 and conversely inhibited by anti-FasL monoclonal antibody NOK-2; (b) cross-linking of Fas with CH-11 drove both cell cycle progression and apoptosis as demonstrated by the induction of the S-G2 phase of DNA and RNA and fragmented nuclei; (c) phosphorylation of extracellular signal-regulated kinase (ERK), but not of c-Jun NH2-terminal kinase or p38, was induced by cross-linking of Fas; (d) a mitogen-activated protein kinase/ERK kinase 1 (MEK1) inhibitor PD98059 completely blocked CH-11-induced ERK phosphorylation as well as cell cycle progression without affecting induction of apoptosis; and (e) a broad-spectrum caspase inhibitor Z-Asp-CH2-DCB inhibited CH-11-induced ERK phosphorylation, cell cycle progression, and apoptosis. These results indicate that Fas-mediated caspase activation elicits two independent cellular responses; one is to induce apoptosis and another is to promote cell cycle progression; the latter is closely linked to the MEK-ERK pathway. Together, our data strongly suggest that FasL may play a role as an autocrine growth factor in gliomas.
Animals↗
Induction of chemokine secretion and enhancement of contact-dependent macrophage cytotoxicity by engineered expression of granulocyte-macrophage colony-stimulating factor in human colon cancer cells.
We investigated the role of tumor cell-derived GM-CSF in recruitment and tumoricidal activation of tissue macrophages. Transfection of the murine GM-CSF gene into KM12SM human colon cancer cells decreased the tumorigenicity of transfected cells and nontransfected bystander colon cancer cells in nude mice. Sequential tissue sections from sites injected with high GM-CSF-producing tumor cells (but not from nontransfected or low GM-CSF-producing cells) demonstrated a dense infiltration of polymorphonuclear cells (PMN), followed by infiltration of macrophages, which correlated with expression of the macrophage-inflammatory protein-1alpha and the monocyte chemoattractant protein-1 (MCP-1) in mouse PMN and macrophages. GM-CSF-producing KM12SM cells were highly sensitive to lysis by mouse macrophages and also increased macrophage-mediated lysis of bystander nontransfected KM12SM cells. The incubation of macrophages with GM-CSF induced expression of the CD11b surface adhesion molecule, which was associated with increased attachment to tumor cells. All KM12SM cells were sensitive to macrophage-mediated lysis in the presence of rGM-CSF and recombinant MCP-1. Collectively, the results demonstrate that tumor cell-derived GM-CSF stimulates PMN and macrophages to secrete macrophage-inflammatory protein-1alpha and MCP-1, which triggers recruitment of mononuclear cells, induces expression of adhesion molecules on macrophages, and enhances contact-dependent cytolysis of tumor cells.
Animals↗
Therapy of human pancreatic carcinoma implants by irinotecan and the oral immunomodulator JBT 3002 is associated with enhanced expression of inducible nitric oxide synthase in tumor-infiltrating macrophages.
We determined the therapeutic effect of irinotecan (CPT-11) combined with the immunomodulator JBT 3002, a synthetic bacterial lipopeptide (N-acylated derivative of psi-amino-C1-C3-alkane-sulfonic acid), against highly metastatic human pancreatic carcinoma cells injected into the pancreas of athymic nude mice. Mice received four courses consisting of three daily oral doses of JBT 3002, followed by once weekly i.p. injection of CPT-11. Control mice were treated with CPT-11 alone, JBT 3002 alone, or saline. Tumor growth and metastasis were assessed by gross pathology and confirmed by histological examination. Treatment with CPT-11 alone significantly decreased the median volume of pancreatic tumors and the incidence of metastasis, whereas treatment with only JBT 3002 did not. The combination therapy of CPT-11 plus JBT 3002 decreased tumor volume and incidence of metastasis significantly more than CPT-11 alone. The number of apoptotic cells (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), the number of scavenger-receptor-positive macrophages, and expression level of inducible nitric oxide synthase (iNOS) within lesions directly correlated with therapeutic effects. Indeed, the in vitro incubation of tumor cells with macrophages activated by JBT 3002 plus IFN-gamma produced a significant lysis of tumor cells that could be blocked by a specific inhibitor of iNOS. Collectively, these data demonstrate that the oral administration of the immunomodulator JBT 3002 combined with i.p. injection of CPT-11 can decrease the growth of human pancreatic carcinoma and the incidence of metastasis in nude mice by both a direct antitumor effect and the activation of iNOS in infiltrating macrophages.
Adjuvants, Immunologic↗