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Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 145 records · Page 8Linked to original sources

The protective effect of a leucocyte removal filter on the lung in open-heart surgery for ventricular septal defect.

We elucidated the protective effect of a leucocyte removal filter on cardiopulmonary bypass (CPB)-induced lung dysfunction during open-heart surgery for ventricular septal defect (VSD). Forty-six VSD patients were divided into two groups: (a) a control group of 22 patients in whom the banked blood was used to prime the CPB circuit, and (b) a leucocyte removal group of 24 patients in whom a leucocyte removal filter was used for priming and every supplement of banked blood during and after the operation. The respiratory index immediately after the CPB was significantly lower in the leucocyte removal group than in the control group (2.23 +/- 0.22 vs 3.90 +/- 0.68; p < 0.05). The duration of stay in the intensive care unit was significantly shorter in the leucocyte removal group (3.0 +/- 0.4 vs 4.1 +/- 0.4 days; p < 0.05). These data suggest that the use of a leucocyte removal filter for blood added to the CPB prime or administered after CPB may have protective effects on lung function after open heart surgery for VSD patients.

Child↗

Plasma adrenomedullin level after cardiopulmonary bypass.

Adrenomedullin is an intrinsic vasodilator which is metabolized mainly in the pulmonary circulation. We measured plasma levels of adrenomedullin in children with congenital cyanotic heart disease (CY group, n = 6), children with high pulmonary blood flow due to congenital heart disease (PH group, n = 8), and in adults with mitral valve disease (MV group, n = 7) before and 3 h after cardiopulmonary bypass (CPB). Before CPB, the adrenomedullin level was the highest in the MV group, possibly due to chronic heart failure. Three hours after CPB, the plasma adrenomedullin level (pg/ml) increased to 1712.7 +/- 498.4 in the CY group, 167.6 +/- 26.4 in the PH group, and 1404.3 +/- 313.7 in the MV group, the level in the PH group being significantly lower than the rest. In the PH group, there was statistically significant negative correlation between the mean pulmonary arterial pressure at the preoperative catheter study, and the adrenomedullin level 3 h after CPB. These results illustrate that the adrenomedullin level increased after CPB, but that the increase was less marked in the PH group, implying that where the pulmonary vasculature was damaged most, this results in increased vasoconstriction.

Adrenomedullin↗

Combined carotid endarterectomy and coronary artery bypass graft.

Atherosclerosis is a generalized disease which afflicts a considerable number of patients in both the carotid and coronary arteries. Although the risk of stroke or death use to combined carotid endarterectomy (CEA) and coronary artery bypass graft (CABG) is thought to be higher than that of each individual operation, the combined procedure is generally preferred over staged operations to treat such patients. We performed the combined procedure safely with the aid of intraoperative portable digital subtraction angiography (DSA). This report describes our experience with the operative strategy of simultaneous CEA and CABG. Ninety CEA and 404 CABG were carried out between January 1989 and December 1997. A total of six patients received the combined procedure with the aid of intraoperative DSA; they were studied retrospectively. Postoperative mortality and morbidity after the combined procedure was 0%. In the combined procedure, neurological complications are difficult to detect after CEA because the patient must be maintained under general anesthesia and extracorporeal circulation during the subsequent CABG. However, intraoperative DSA can confirm patency of the internal carotid artery and absence of flap formation after CEA, and the CABG can be performed safely. Intraoperative portable DSA between CEA and CABG is helpful in preventing perioperative stroke in the combined procedure.

Aged↗

Geranylgeranylpyrophosphate plays a key role for the G1 to S transition in vascular smooth muscle cells.

Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression, suggesting the importance of mevalonate itself and/or its metabolites in VSMC proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP), farnesyl pyrophosphate (FPP) and IPP (isopentenyl pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP, FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest were examined. Only GGPP restored the pravastatin-induced inhibition of DNA synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase from cytosol to membrane. By the addition of GGPP, Rho small GTPase are geranylgeranylated and translocated to membranes during G1/S transition. These data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among mevalonic acid metabolites for VSMC proliferation and the G1/S transition.

Animals↗

Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage.

Expression of facilitative glucose transporter (Glut) isoforms was studied immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61 lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1 staining was seen in normal lung epithelium surrounding the tumors. In squamous cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in the central area of tumor cell nests corresponding to the hypoperfused region. Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining was correlated to lesser differentiation, larger tumor size, and positive lymph node metastasis. Glut-2 was detected in normal airway epithelium, but no positive staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively stained in normal lung epithelia, but a few lung carcinoma samples showed positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression was seen in regenerating alveolar and bronchiolar epithelia around and in cancer tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed the expression revealed by immunohistochemical analysis. Overexpression of Glut could enhance uptake of glucose into lung carcinoma cells, and the increased glucose influx could be involved in cell biologic activities.

Adenocarcinoma↗

[The long-term result of an adult case of transposition of the great arteries corrected with Rastelli operation at the age of thirty-two years].

A 32-year-old woman with transposition of the great arteries was referred to us for corrective surgery. She had severe cyanosis, dyspnea, and hemoptysis. The cardiac catheter study and echocardiography revealed that she had transposition of the great arteries, associated with atrial septal defect, ventricular septal defect, patent ductus arteriosus, and pulmonary stenosis. Rastelli operation was performed using equine pericardial roll with three valves made from autologous pericardium. After the operation she gave birth to two children without any symptom. Ventricular tachycardia occurred several times but was controlled by the drug. Eight years after the operation she underwent catheter study. Although the right ventricular pressure was 80 mmHg and the pressure gradient through the conduit was 38 mmHg, her general clinical condition was fairly good. We think the late postoperative result of this patient is satisfactory as an adult case of transposition of the great arteries.

Adult↗

[A case of corneal abscess with impetigo contagiosa].

Impetigo contagiosa often occurs on the face of children. Although the eyelid and conjunctiva are frequently affected, no corneal involvement has been reported in Japan. We encountered a case of impetigo contagiosa with corneal abscess. The patient, an 8-year-old boy, complained of pain and presented with corneal abscess and iritis in the right eye as well as eruptions in the inferior eyelid and around the anterior nostrils. He was diagnosed as having impetigo contagiosa with corneal abscess. Because the corneal abscess and eruptions occurred at the same time and coagulase-positive Staphylococcus with identical drug sensitivity was isolated from both lesions, we considered the corneal lesion as a part of the impetigo contagiosa. When impetigo contagiosa occurs around the eye, especially on the eyelids, a careful examination of the anterior segment of the eye is needed.

Abscess↗

[Combined coronary artery bypass with right nephrectomy in a patient with left main lesion, calcified ascending aorta, pelvic carcinoma and liver cirrhosis].

A 66-year-old female had ischemic heart disease due to left main lesion complicated with calcified ascending aorta, right pelvic carcinoma and liver cirrhosis. The combined operations with coronary artery bypass by left internal thoracic artery under the hypothermic ventricular fibrillation with cardiopulmonary bypass and right nephrectomy were performed successfully. Postoperatively Treadmill exercise test and scintigram revealed no ischemihc change. She is doing well. The aortocoronary bypass to left anterior descending artery using a left internal thoracic artery under hypothermic ventricular fibrillation with cardiopulmonary bypass might be one of surgical options for high risk patient.

Aged↗

[Bone metastasis of primary lung cancer].

To improve the treatment of patients with bone metastasis from lung cancer, 178 (23.8%) of 748 patients with primary lung cancer admitted to our hospital during an 11-year period were studied. The 178 patients were mainly women. The frequency of bone metastasis was significantly higher among patients with adenocarcinoma than among those with small cell or squamous cell cancer. The concentration of carcinoembryonic antigen in serum was significantly higher in patients with bone metastasis than in those with stage IV lung cancer without bone metastasis. The bone lesions were symptomatic in 116 patients (65%) and were treated in 67. Symptomatic improvement was achieved in 50 patients (74%) and pain was alleviated in 94%. However, neurological disorders improved in only 41%. Differences in survival did not depend on the presence or absence of symptomatic bone metastasis or no whether the metastases were treated. The median survival time of patients who responded to treatment tended to be longer than that of patients in whom treatment was not effective. The median survival time calculated from the start of treatment was 5 months for patients with bone metastasis and 7.3 months for patients with stage IV disease without bone metastasis. Aggressive local treatment may be effective for painful bone metastasis.

Biomarkers, Tumor↗

[Clinical significance of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in peripheral blood of patients with gastric carcinoma].

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in peripheral blood were measured in 54 patients with gastric carcinoma; 46 were primary and 8 were recurrent cases. There were no significant associations between MMP-9 concentrations and clinicopathological factors. TIMP-1 levels were significantly increased in advanced and recurrent cases, and in cases with peritoneal dissemination and lymph node metastasis, suggesting that TIMP-1 concentration in the peripheral blood could be a new tumor marker for the recurrence of gastric carcinoma.

Biomarkers, Tumor↗

Application of locoregional chemotherapy using lymph-directed substances in a canine transhiatal esophagectomy model.

We investigated whether lymph-directed substances injected into the mediastinal connective tissue of dogs reached the regional lymph nodes of the esophagus. In 46 dogs, 1.5 mL of cuttlefish particles or activated carbon particles containing 15 mg of bleomycin (CH-BLM) was injected at two sites: into the connective tissue between the trachea and the aorta via mediastinoscopy in 23 dogs (16 with cuttlefish particles and 7 with CH-BLM: mediastinal group), and into the crura of the diaphragm by means of laparotomy in 23 dogs (16 with cuttlefish particles and 7 with CH-BLM: crural group). Cuttlefish particles, distinguished by decolorization with melanin bleaching, showed selective affinity for lymphatics. When cuttlefish particles were injected into mediastinal connective tissue, the rate of staining (# of black-stain positive nodes/# of examined nodes) was higher in the crural group than in the mediastinal group. In the crural group, bleomycin activity in lymph nodes was higher in the regions from the neck to the abdominal para-aortic region than at the injection site, excluding the peri-gastric region. If the topography of lymphatics and lymph flow kinetics in man are similar to that of the dog, then the crura of the diaphragm appears to be a potentially effective site for applying loco-regional chemotherapy for carcinoma of the esophagus in patients undergoing transhiatal esophagectomy.

Animals↗

Neural Network Computer Analysis of Fetal Heart Rate.

> Objective: A nonsubjective evaluation of intrapartum fetal heart rate (FHR) with a neural network (NNW) computer system and its clinical application. Methods: Eight simple FHR data were input into the NNW computer after 16-step normalizations. The computer was composed of 40 units in the input layer, 30 in intermediate layer, and 3 in the output layer, and the probabilities to be normal, suspicious, and pathological were obtained at the output. Before use, the computer was trained 10,000 times by 50-min teacher FHR data of 20 cases with known outcomes. The trained NNW computer was tested by FHRs of another 29 cases. The outcome probabilities in 15 min were calculated every 5 min in another 10 cases, and the bar graphs of the probabilities were displayed in sequence in the trendgrams. Results: The trained NNW computer was 100% accurate in the internal check; in the external check 86% of the results were evaluated correctly with the cardiotocogram, Apgar score, and umbilical arterial pH of the 29 test cases. The FHR scores of our conventional computer FHR analysis were higher in the suspicious and pathological groups than the normal group, and the fetal distress index was high in the pathological group. The trendgrams were simply accurate in typically normal or abnormal cases, transitory abnormal probabilities were shown in intermediate cases, and mixed suspicious and pathological probabilities suggested pathological outcome. Conclusions: The outcome probabilities and their trendgrams in the NNW FHR analysis are promising in objective decision making in the intrapartum stage.

Journal Article↗

T cell functions in granulocyte/macrophage colony-stimulating factor deficient mice.

Immunological functions were analyzed in mice lacking granulocyte/macrophage colony-stimulating factor (GM-CSF). The response of splenic T cells to allo-antigens, anti-mouse CD3 mAb, interleukin 2 (IL-2), or concanavalin A was comparable in GM-CSF +/+ and GM-CSF -/- mice. To investigate the responses of CD8(+) and CD4+ T cells against exogenous antigens, mice were immunized with ovalbumin peptide or with keyhole limpet hemocyanin (KLH). Cytotoxic CD8+ T cells with specificity for ovalbumin peptide could not be induced in GM-CSF -/- mice. After immunization with KLH, there was a delay in IgG generation, particularly IgG2a, in GM-CSF -/- mice. Purified CD4+ T cells from GM-CSF -/- mice immunized with KLH showed impaired proliferative responses and produced low amounts of interferon-gamma (IFN-gamma) and IL-4 when KLH-pulsed B cells or spleen cells were used as antigen presenting cells (APC). When enriched dendritic cells (DC) were used as APC, CD4+ T cells from GM-CSF -/- mice proliferated as well as those from GM-CSF +/+ mice and produced high amounts of IFN-gamma and IL-4. To analyze the rescue effect of DC on CD4(+) T cells, supernatants from (i) CD4(+) T cells cultured with KLH-pulsed DC or (ii) DC cultured with recombinant GM-CSF were transferred to cultures of CD4(+) T cells and KLH-pulsed spleen cells from GM-CSF -/- mice. Supernatants from both DC sources contained a factor or factors that restored proliferative responses and IFN-gamma production of CD4(+) T cells from GM-CSF -/- mice.

Animals↗

Characterization of tumor necrosis factor-deficient mice.

Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and duration of an inflammatory process-i.e., an anti-inflammatory function. (iii) In contrast to the expectation that TNF+/+ mice and TNF+/- mice would have identical phenotypes, TNF+/- mice showed increased susceptibility to high-dose LPS lethality, increased susceptibility to Candida challenge, and delayed resolution of the C. parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF.

Animals↗

Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells.

Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of the cell cycle. Elimination of Cdk inhibitor protein p27Kip1 during the G1 to S phase is required for the activation process. An inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase prevents its elimination and leads to G1 arrest. Mevalonate and its metabolite, geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, restore the inhibitory effect of pravastatin on the degradation of p27 and allow Cdk2 activation. By the addition of geranylgeranyl pyrophosphate, Rho small GTPase(s) are geranylgeranylated and translocated to membranes during G1/S progression. The restoring effect of geranylgeranyl pyrophosphate is abolished with botulinum C3 exoenzyme, which specifically inactivates Rho. These results indicate (i) among mevalonate metabolites, geranylgeranyl pyrophosphate is absolutely required for the elimination of p27 followed by Cdk2 activation; (ii) geranylgeranylated Rho small GTPase(s) promote the degradation of p27 during G1/S transition in FRTL-5 cells.

Animals↗

Effect of hemorrhagic toxin produced by Clostridium sporogenes on rabbit ligated intestinal loop.

In order to characterize the toxicity of the hemorrhagic toxin of Clostridium sporogenes isolated from the rabbit with antibiotic-associated hemorrhagic diarrhoea, we studied the toxin productivity of C. sporogenes cultured in various media and the toxic effect of the partially purified preparation of the culture supernatant in rabbit intestinal loops. The hemorrhagic activity, which was determined by rabbit skin test for assessment of the toxin production, of culture supernatant of C. sporogenes reached maximum in the early stationary phase of the bacterial growth in GAM or Trypticase soy broth that contained rich glucose, ammonia and peptide. The partially purified toxin prepared by hydroxyapatite, phenyl Toyopearl and Superdex 200 columns caused marked hemorrhage in rabbit ligated intestinal loops. Histological examination of the intestinal loops injected with the toxin revealed noticeable pathological alterations which seemed to be a characteristic of this toxin. Marked hemorrhage could be observed in the mucosa, submucosa, muscular layer and subserous spaces. There were various degrees of infiltration of inflammatory cells such as polymorphonuclear leukocytes and granulated leukocytes throughout the intestinal wall, but it was not associated with any necrotic changes of the tissue. These findings indicate that hemorrhagic toxin produced by C. sporogenes induces vascular changes in the intestine without any direct effects on the parenchymal cells.

Ammonia↗

Activated eosinophils stimulate endothelin-1 release from airway epithelial cells by direct adherence via adhesion molecules.

Endothelin-1 (ET-1), synthesized in airway epithelial cells, has a potent constrictive action on airway smooth muscle. In this study, we investigated the effect of eosinophils on ET-1 release from guinea pig cultured tracheal epithelial cells. Eosinophils with or without the activation were directly co-cultured with tracheal epithelial cells. Eosinophils activated by GM/CSF or IL-5 potentiated ET-1 release, but non-activated ones did not. Treatment of activated eosinophils with antibodies against macrophage-1 (Mac-1) and/or very late antigen-4 (VLA-4) suppressed the potentiated ET-1 release. However, inhibition of lipid mediators derived from activated eosinophils could not suppress the potentiated ET-1 release. Moreover, separated co-culture of activated eosinophils with tracheal epithelial cells using Millicell-CM had no effect on ET-1 release. These observations suggest that adherence of activated eosinophils to epithelial cells via adhesion molecules such as Mac-1 and VLA-4 was essential for potentiation of ET-1 release. Since presence of eosinophils in the epithelial layer has been commonly demonstrated in bronchial biopsies and autopsy specimens from patients with asthma, epithelial cells would be activated by adherence of eosinophils via adhesion molecules and potentiate ET-1 release in vivo.

Animals↗