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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 235 records · Page 13Linked to original sources
PubMed1994

Effect of interferon-gamma on nitric oxide hemoglobin production in endotoxin-treated rats and its synergism with interleukin 1 or tumor necrosis factor.

We studied the in vivo effect of interferon-gamma (IFN-gamma) on nitric oxide (NO) generation. ESR spectra of nitric oxide hemoglobin (HbNO) appeared after a lag time of 2h in the blood of rats treated with Escherichia coli lipopolysaccharide (LPS). IFN-gamma enhanced LPS-induced HbNO formation in rats without modifying the time lag, although IFN-gamma alone did not induce HbNO formation. The plasma nitrate concentration was approximately one order of magnitude higher than the HbNO concentration. On treatment with LPS alone, the amount of tumor necrosis factor (TNF) released decreased after 2 h. Simultaneous addition of IFN-gamma and LPS increased TNF release for at least 8 h. Interleukin 1 (IL-1) release was detected only at 2 h in both groups. We also investigated the in vivo interactions of these cytokines. TNF plus IL-1 induced the greatest HbNO generation, followed by TNF plus IFN-gamma, and then IL-1 plus IFN-gamma. These results suggest that increase of TNF release by IFN-gamma plays a key role in NO generation in LPS-treated rats.

Animals↗
PubMed1994

Interleukin-4 expression in mesangial proliferative glomerulonephritis.

Several cytokines are known to play roles in the pathogenesis of human glomerulonephritis. Recently, some studies proposed a possible relationship between interleukin-4 (IL-4) and glomerulonephritis. To investigate the involvement of IL-4 in human glomerulonephritis, we evaluated renal biopsy specimens using immunohistochemical procedures. Our study revealed that the glomeruli in immunoglobulin A nephropathy and lupus nephritis (World Health Organization grades II and IV) contained IL-4-positive cells, which were CD-3- and CD-4-positive T lymphocytes. CD-8-, CD-14-, CD-19-, or CD-56-positive cells did not react with anti-IL-4. CD-23-positive cells were not observed in the sections used in this study. Interleukin-4-positive cells were not found in the normal control kidney tissues. The degree of the glomerular IL-4-positive cell index correlated well with the glomerular hypercellularity index, but not with any other clinical or histopathologic parameters. Therefore, the present study offers more reliable evidence concerning the association between IL-4 and human glomerulonephritis.

Adult↗
PubMed1994

Subtype switching of natriuretic peptide receptors in rat chondrocytes during in vitro culture.

Subtype switching of natriuretic peptide receptor (NPR) during in vitro culture of rat chondrocytes was demonstrated by polymerase chain reaction (PCR) analysis, receptor binding assay, and the cGMP formation method. NPR-B was the predominant form in the receptor guanylate cyclase family (i.e. NPR-A and NPR-B) in both rat xiphoid cartilage and in its cultured cells. However, the chondrocytes began to express NPR-C at high levels when cultured in vitro and NPR-C became the major form (maximal binding capacity: 450 fmol/mg of protein) of NPR in the cultured cells. The abundantly expressed NPR-C had no effect on adenylate cyclase activity or proliferation of chondrocytes.

Animals↗
PubMed1994

Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases.

The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells.

Adult↗
PubMed1994

ESR spectral transition by arteriovenous cycle in nitric oxide hemoglobin of cytokine-treated rats.

Nitric oxide (NO) generation was induced in rats by Escherichia coli lipopolysaccharide (LPS) as detected by electron spin resonance (ESR) signals of NO hemoglobin (HbNO). However, there were inconsistencies in ESR spectral shape among them. We have therefore carried out a systematic study to clarify the in vivo spectral changes. First, the spectra of the alpha-NO heme species had the distinct three-line hyperfine structure in venous blood but not in arterial blood in all rats treated with tumor necrosis factor, interleukin-1, and/or LPS, and methemoglobin was not detected at the g = 6 (high-spin methemoglobin) region. Second, when the treated rats died, the three-line hyperfine structure was very distinct even in arterial blood. Third, even if HbNO was formed by injection of nitrite to rats, the three-line hyperfine structure of HbNO in venous blood was more marked than that in arterial blood, independent of the appearance of the methemoglobin signal. Fourth, an ex vivo study using whole blood demonstrated that the three-line hyperfine structure intensified lineally when O2 saturation of hemoglobin decreased but disappeared on reoxygenation of hemoglobin. These results directly demonstrate in vivo quaternary structural transition of the hemoglobin tetramer from the high-affinity state in the arterial cycle to the low-affinity state in the venous cycle. The transition makes the diverse ESR spectra of HbNO in vivo.

Animals↗
PubMed1994

Treatment strategies for hepatic metastases from pancreatic cancer in patients previously treated with radical resection combined with intraoperative radiation therapy.

Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed.

Adenocarcinoma↗
PubMed1994

Mechanisms of the enhanced contractile response to phenylephrine in thoracic aorta isolated from rats with dietary magnesium deficiency.

The mechanisms underlying the enhanced contractile response to phenylephrine (PE) and increased susceptibility to nifedipine of de-endothelialized thoracic aorta isolated from rats with dietary magnesium deficiency (Mg-deficient rats) were examined by functional and radioligand binding studies. Enhanced PE-induced contractions and increased susceptibility to nifedipine in Mg-deficient rats were not observed in the presence of 10 microM H7. PE significantly decreased the KD value without changing Bmax in the binding of [3H]PN200-110 to de-endothelialized aortic strips. The KD value obtained in the Mg-deficient rats was significantly smaller than that in the controls. Nifedipine displaced the binding of [3H]PN200-110 concentration-dependently, and the pKi value in Mg-deficient rats was significantly larger than that in the controls. A combination of PE and H7 abolished this difference. These results indicate that the modulation of L-type Ca2+ channels via the stimulation of alpha 1-adrenoceptors may be involved in the enhancement of vasoconstriction and increased susceptibility to nifedipine in aortas isolated from Mg-deficient rats. The H7-sensitive mechanisms may play an important role in these phenomena.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Enhanced contractile response to phenylephrine and increased density of [3H]PN200-110 binding sites in thoracic aorta isolated from dietary magnesium-deficient rats.

The present study was undertaken to examine whether the enhanced contractile response to phenylephrine observed in thoracic aorta isolated from dietary magnesium-deficient rats depends on an increased density of alpha 1-adrenoceptor or calcium channels. Adult male Wistar rats were fed with a magnesium-deficient diet (0.001 per cent magnesium) for 30 days with control groups (0.07 per cent magnesium). The contractile response to phenylephrine was significantly inhibited by nifedipine in both aortas without endothelium, and the degree of the inhibition was significantly greater in magnesium-deficient rats than in controls. Membranes were isolated from both thoracic aortas without endothelium, and the binding of [3H]PN200-110 or [3H]prazosin to the membranes was studied. A single binding site for [3H]PN200-110 or [3H]prazosin was evident for both membranes with high affinity. Dietary magnesium-deficiency increased significantly the maximal number (Bmax) of [3H]PN200-110 binding sites, but not Bmax of [3H]prazosin, and did not alter the binding affinity of both ligands. These results suggest that increased density of calcium channels participates in the enhanced contractile response to phenylephrine in thoracic aortas isolated from dietary magnesium-deficient rats.

Animals↗
PubMed1994

[Reoperative coronary artery bypass grafting in patients with patent internal thoracic artery grafts].

The incidence of reoperative coronary artery bypass grafting (reCABG) is recently increasing. However, there has been no report of reCABG in patients with patent internal thoracic artery (ITA) grafts in Japan. We performed reCABG in three such patients with patent ITA grafts. The first patient was a 49-year-old male who had undergone a 2 CABG (left ITA-LAD, SVG-DX 1), 8 years and 7 months prior to the 2nd operation, he received a re 2 CABG (GEA-RCA, RITA-SVG-DX 1) with a patent prior LITA-LAD graft. The second patient was a 65-year-old female who had undergone CABG in which the LITA had been erroneously anastomosed to the DX 2 in place of the LAD. Three year later, the reCABG (RITA-LAD) was performed with a patent prior LITA-DX 2 graft. The third patient was a 51-year-old male who had undergone 3-CABG (RITA-LAD, LITA-DX, SVG-RCA). The RITA was closed most probably due to technical errors and his angina recurred. Tree year after the first operation, he received a re 3-CABG (GEA-LAD, SVG-RCA, SVG-OM) with a patent prior LITA-DX graft. In each patient, PTCA had been tried twice, twice and once prior to redo operations. Their post-redo courses were uneventful, and they were discharged free from angina. In such cases it is important to manage with care the patent ITA grafts at reoperation. Biplane ITA angiograms are quite helpful to evaluate the course of grafts in relation to the sternum. To cover the ITA graft with a GORE-TEX membrane may also be useful for easy identification of the graft at redo operations.

Aged↗
PubMed1994

[Percutaneous renal cyst puncture with CO2 instillation therapy].

Ultrasound-guided percutaneous puncture of renal cysts replaced by CO2 was performed on 9 renal cysts of 6 patients from May 1993 through September 1993. Puncture and aspiration of cysts was performed using a 5.5 Fr one-step fluid drain kit (pig tail stent) under ultrasonography inspection. Aspirated volume of cyst contents was 15-292ml (mean 115 ml), and the instilled CO2 volume was 15-150 ml (mean 73 ml). All patients were checked by CT scan. In one month, the reduction rate of cyst volume was 46-84% (mean 69%) and lumbago, their chief complaint, was improved in all patients. No complications were observed in patients treated by CO2 instillation. Although long-term followup is needed to draw a definite conclusion, this therapy may be useful for benign renal cystic lesions.

Aged↗
PubMed1994

Idiopathic progressive glomerulopathy with extensive subendothelial and mesangial immune deposit formation.

A 32-year-old Japanese male presented with abundant proteinuria, and renal biopsy revealed diffuse subendothelial and mesangial deposits in the glomeruli without hypercellularity or mesangial interposition. There was no clinical or laboratory evidence of systemic conditions such as collagen-vascular disease, paraproteinemia, or infection. Treatment with corticosteroid was ineffective and the patient eventually went into end-stage renal failure. To our knowledge, this is the first report of an idiopathic progressive glomerulopathy characterized by diffuse, global subendothelial and mesangial deposits, which suggests to us a novel insight into glomerular subendothelial/mesangial deposition.

Adult↗
PubMed1994

[Myocardial protection during multiple coronary artery bypass grafting--a comparison of antegrade and combined antegrade-retrograde cardioplegia].

We compared the effectiveness of antegrade cardioplegia (A group, 100 cases) and combined antegrade-retrograde cardioplegia (A + R group, 66 cases) on myocardial protection in patients undergoing coronary artery bypass grafting for more than 3 vessels. The two groups were similar in patients' age, the extent of coronary artery diseases and preoperative risk factors, cardiac output and ejection fractions. The mean number of grafts was 3.3 in A group and 3.6 in A + R group (p < 0.05). The mean number of ITA grafts used was 1.2 in A group and 1.4 in A + R group (p < 0.05). Aortic cross-clamp time was 114 minutes in A group and 138 minutes in A + group (p < 0.01). The serum CK-MB concentration on postoperative day 1 was 38 IU/L in A group and 25 IU/L in A + R group (p < 0.05). The left ventricular stroke work index 3 hours after reperfusion was 33 gm min/m2 in A group and 43 gm min/m2 in A + R group (p < 0.05). The maximum dose of catecholamine required was similar in two groups. Intra-aortic balloon pump was used in 11 patients (11%) in A group and in 2 patients (3.6%) in A + R group (p < 0.05). We conclude that the combined method of intermittent antegrade and continuous retrograde perfusion of cardioplegic solution provides better myocardial protection than intermittent antegrade cardioplegia alone for multivessel coronary artery bypass surgery.

Aged↗
PubMed1994

Ultrastructural location of human hepatocyte growth factor in human liver.

Human hepatocyte growth factor has been purified from the plasma of patients with fulminant liver failure, but where this factor is produced in organs or cells of subjects with liver diseases is unknown. Therefore, we used a monoclonal antibody to human hepatocyte growth factor to stain cells in three normal and 29 diseased liver tissues by immunohistochemical techniques. By light microscopy, the immunostained cells seemed to be polymorphonuclear leukocytes because of their segmented nuclei. Some biliary epithelial cells also were stained. Electron microscopy confirmed that the immunostained cells with segmented nuclei were polymorphonuclear leukocytes and that the stained grains were on the membranes of rough endoplasmic reticulum, around specific or azurophilic granules and in the cell sap. Stained grains in the biliary epithelial cells were found sporadically on the inside and outside of the membranes of rough endoplasmic reticulum near the nuclei. Human hepatocyte growth factor is now known to be the same protein as scatter factor and tumor cytotoxic factor, both of which are produced by human fibroblasts in culture, but our results suggest that polymorphonuclear leukocytes in diseased livers are one cellular source of circulating human hepatocyte growth factor. The immunostaining properties of biliary epithelial cells in diseased livers also suggest that the cells produce and secrete human hepatocyte growth factor.

Adult↗
PubMed1994

[Allograft (homograft) valve surgery: current status in Japan].

The advance of cryopreservation techniques has dramatically increased the durability of human allograft valves, resulting in the wide-spread use of allograft valves in many western countries except Japan. The superiority of the allograft valve to other prosthetic valves has become apparent in some specific situations such as active endocarditis, small aortic root and hemorrhagic conditions. In this manuscript, we described the setting-up of the cryopreservation laboratory, quality control and the clinical use of allograft valves in our institute. The authors believe that surgeons should have an option of utilizing allograft valves in selected patients in Japan.

Adult↗
PubMed1994

[Coronary artery bypass surgery-redo operation particularly in patients with a functioning ITA graft or with a patent atheromatous vein graft].

An experience with redo-CABG in 20 patients is described. The incidence of reoperation in patients undergoing primary CABG in our hospital was 1.4%, relatively low even in Japanese population. The low incidence of redo-CABG in our hospital depends on the relatively short period of follow-up of 14 years, the prevalence of interventional cardiology and the early routine use of ITA grafts. The main cause of reoperation was the failure of a SVG to the LAD in 70 to 80% of the cases. The most important and difficult decision-making in redo-CABG is the selection of surgical approaches and cardioprotective methods in patients with a patent functioning ITA graft, and the management of an atherosclerotic patent SVG. Surgical strategies in these situations are discussed.

Adult↗
PubMed1993

[CO2US via an implantable port--drug distribution in intraarterial chemotherapy for hepatic tumors and evaluation of effect].

The distribution of blood flow was determined from the distribution of CO2 by US performed during the infusion of CO2 microbubbles via an implantable port (IP-CO2US) in intraarterial chemotherapy for hepatic tumor, and the usefulness of this method in determining tumor vascularity and evaluating the effects of therapy was investigated. A total of 16 patients, 12 of whom had metastatic liver tumor, two hepatocellular carcinoma, one gall bladder carcinoma, and one cholangiocellular carcinoma were studied. The enhanced areas in the liver in 16 patients in whom IP-CO2US was performed a total of 24 times were consistent in all cases with the enhanced areas demonstrated by IP-RI angiography performed a total of 10 times within 10 days, and were also consistent with one exception with the enhanced areas demonstrated by IP-CTA performed 14 times. The tumor detection rate was markedly higher with IP-CO2US than with plain US or IP-DSA, and was similar to that of IP-CTA. Evaluation of the vascularity of individual nodules by IP-CO2US surpassed that by IP-DSA, and was similar to that of IP-CTA. It was demonstrated that blood flow distribution (intrahepatic drug distribution) can be equally well grasped with IP-CO2US, which is a simple and convenient method, as with IP-RI angiography. It was also suggested that IP-CO2US is useful in the evaluation of tumor vascularity and the effect of therapy.

Antineoplastic Agents↗
PubMed1993

[Study on the evaluation of recurrence of HCC and the effect after transcatheter hepatic arterial embolization--fluctuations in AFP values].

To determine the usefulness of alpha-fetoprotein (AFP) in determining recurrence of HCC after interventional angiography (IVA) and to define the relation between AFP and the imaging diagnosis of HCC recurrence, changes in AFP values in 160 patients with hepatocellular carcinoma who were treated by IVA > or = two times were classified into four patterns: A: the AFP value was decreased after the first IVA, increased at recurrence and decreased again after the second IVA; B: the AFP value was unchanged after the first IVA, but increased at recurrence and decreased after the second IVA; C: the AFP value was decreased after the first IVA, but was not increased at recurrence; D: the AFP value showed no change. The frequency of each AFP pattern and the diagnosis of recurrence by AFP were determined. The relation between tumor type and AFP was defined. Pattern A was the most frequently detected. In 62.6%, AFP was increased at recurrence (A and B), and there was a positive correlation between changes in the AFP value and the findings of imaging diagnosis. In another 37.5%, AFP was not increased at recurrence (C and D), and therefore, the diagnosis of HCC recurrence by imaging methods was very important.

Aged↗