Biomedical subjects

S Sugiyama

Publications and source records attributed to S Sugiyama.

At least 73 records · Page 4Linked to original sources

PubMed1999

Increased carbonyl modification by lipids and carbohydrates in diabetic nephropathy.

BACKGROUND: In diabetic nephropathy (DN), possible mediators of untoward effects of hyperglycemia include the advanced glycation end products (AGEs). Indeed, an AGE, carboxymethyllysine (CML), accumulates in expanded mesangial matrix and nodular lesions. An advanced lipoxidation end product (ALE), malondialdehyde-lysine (MDA-lysine), generated on proteins during lipid peroxidation also accumulates in these lesions. As both ALEs and AGEs are formed by carbonyl amine chemistry between protein and carbonyl compounds derived from autoxidation of lipids and carbohydrates, their colocalization suggests an increased carbonyl modification of proteins. METHODS: To address this hypothesis, human diabetic renal tissues were examined to characterize carbonyl modification of proteins by lipids and carbohydrates: (a) ALEs, MDA-lysine and 4-hydroxynonenal (HNE) protein adduct, derived from lipids, and (b) AGEs, pentosidine and CML, derived from carbohydrates. Furthermore, to elucidate the biological effect of carbonyl modification on primary cultured human and rat mesangial cells, the intracellular protein phosphorylation was examined in the presence of various kinds of carbonyl compounds. RESULTS: The ALE and AGE adducts examined were identified in expanded mesangial matrix and nodular lesions. The exposure of cultured mesangial cells to carbonyl compounds resulted in phosphorylation of tyrosine residues of a number of intracellular proteins. CONCLUSIONS: These data suggest a broad derangement in nonenzymatic biochemistry involving both lipids and carbohydrates exists in diabetic glomerular lesions ("carbonyl stress").

Animals↗

PubMed1999

Identification and selective perfusion of the spinal cord-feeding arteries by intrathecal pO2 monitoring for spinal cord protection.

OBJECTIVES: to study whether spinal cord-feeding arteries could be identified by the changes in the intrathecal pO2 (I-pO2), and to examine whether selective perfusion of feeding arteries identified by this method could protect the spinal cord against ischaemia. DESIGN: controlled animal experiments. MATERIALS AND METHODS: in experiment 1, using 16 mongrel dogs, 18 segmental arteries were cannulated through which oxygenated saline was injected and the I-pO2 change was observed. When the I-pO2 increase was more than 0.5 mmHg, the artery was considered to be a spinal cord-feeding artery. In experiment 2, involving 10 dogs, the segmental arteries identified as spinal cord-feeding arteries were perfused with arterial blood and the recovery of I-pO2 and evoked spinal potentials (ESP) was examined. RESULTS: of 208 segmental arteries examined, 176 (84.6%) arteries were correctly judged and 32 (15.4%) were not. It was observed that the I-pO2 recovered from 13.9 to 30.5 mmHg and the ESP recovered from 20.9% and 8.2% to 66.5% and 44.7% of each control for the first negative (N1) and second negative (N2) components, respectively. CONCLUSION: spinal cord-feeding arteries were successfully identified using the I-pO2 monitoring method. Perfusion of these arteries with arterial blood improved the I-pO2 and ESP, which were significantly depressed by ischaemia.

Animals↗

PubMed1999

Enhancement of constrictor response of spastic coronary arteries to acetylcholine but not to phenylephrine in patients with coronary spastic angina.

This study examined the direct response of smooth muscle of coronary spasm sites to alpha1-adrenergic stimulation in patients with coronary spastic angina. Phenylephrine (1 microM in the coronary circulation, for 5 min), a stimulator of alpha1-adrenoreceptors, was directly infused into coronary arteries with spasm in 10 patients with coronary spastic angina and into normal coronary arteries in 10 control patients. The luminal diameter of epicardial coronary arteries was determined by computer-assisted quantitative angiography. The constrictor response to intracoronary injection of acetylcholine (ACh; 50 microg) was greater in spastic arteries than in control arteries (decrease from baseline, 48+/-2% vs. 12+/-2%, respectively; p<0.001). ACh (50 or 100 microg) induced coronary spasm associated with myocardial ischemia in all of patients with coronary spastic angina but not in any control patients. On the other hand, phenylephrine infusion did not induce coronary spasm in any of patients with coronary spastic angina or in control subjects. The constrictor response to phenylephrine infusion was comparable between spasm and control coronary arteries (decrease from baseline, 11+/-2% vs. 9+/-2%, respectively; p = NS). The results indicate that smooth muscle of spastic coronary arteries does not exhibit enhancement of constrictor response to direct stimulation of alpha1-adrenoreceptor on coronary smooth muscle. There may be receptor-specific enhancement of constrictor response to agonists in smooth muscle of spastic coronary arteries in patients with coronary spastic angina.

Acetylcholine↗

PubMed1999

Optic glioma with characteristic bilateral optic atrophy in a 3-year-old girl.

We report a case of optic glioma with bilateral optic atrophy. A 3-year-old girl presented with vomiting and left hemiparesis. She had hypothalamic dysfunction, right ptosis, right monocular nystagmus, left facial palsy, left hemiparesis, and left pes adductus. Neuroimaging studies showed obstructive hydrocephalus with a large suprasellar calcified tumor with a ring-like enhancement mimicking craniopharyngioma. Visual-evoked potentials showed delayed latency of N75 in the right occipital lead. The tumor, a pilocytic astrocytoma in the right optic tract and chiasma, was partially removed via a right frontotemporal craniotomy. The right optic nerve had shrunk to half the normal diameter and became twisted downwardly. Intracranial pressure (ICP) increased to 40 cm H2O. The fundus had bilateral optic atrophy without disc swelling. To our knowledge, this is the first report of a lamina/dot sign of the optic disc in a small child with a brain tumor and a normal neuroretinal fiber layer. These ocular findings may result from possible interruption of the axonal flow caused by the tumor and not increased ICP.

Child, Preschool↗

PubMed1999

Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasorelaxation.

We have recently found that remnant lipoproteins (RLPs) and their lipid fractions impair endothelium-dependent vasorelaxation (EDR). This study was aimed at clarifying mechanisms responsible for RLP-induced endothelial dysfunction in isolated rabbit aortas. RLPs were isolated from plasma in hyperlipidemic subjects by use of the immunoaffinity gel mixture of anti-ApoA1 and anti-ApoB100 monoclonal antibodies and ultracentrifugation. Organ chamber experiments showed that EDR impairment was restored by addition of reduced glutathione (GSH) or N-acetylcysteine, antioxidants, into the incubation buffer containing isolated rabbit aortas and RLPs (0.75 mg of triglyceride/mL). Furthermore, the incubation of isolated human red blood cells (RBCs) with RLP and its lipids converted the normal shape of RBCs to echinocytes, but coincubation with antioxidants suppressed the RLP-induced RBC transformation, suggesting that they exerted oxidative damage on RBC surface membranes. Studies with HPLC and the postcolumn chemiluminescence method showed that RLPs contain a substantial amount of phosphatidylcholine hydroperoxides. Peroxidized phosphatidylcholine also impaired EDR and had echinocytogenic action, both of which were suppressed by N-acetylcysteine. RLPs isolated from the plasma of patients under treatment with alpha-tocopherol, an antioxidant, had a lower level of phosphatidylcholine hydroperoxides (15% of the amount in nontreated patients), which was associated with a lack of the inhibitory action on EDR and with lesser effect on RBC transformation. Oxidative damage caused by lipid components in RLPs, especially peroxidized phospholipids, deteriorates cell surface membrane and may be at least partly responsible for RLP-induced impairment of EDR.

Animals↗

PubMed1999

Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney.

Lipid abnormalities are associated with various disorders ranging from generalized atherosclerosis to renal diseases, including lipoprotein glomerulopathy that is characterized by glomerular lipoprotein thrombi and causes type III hyperlipoproteinemia, proteinuria, and renal failure. This study examines lipoprotein glomerulopathy, which recurred in a transplanted kidney. Molecular biologic analysis of the patient's apolipoprotein (apo) E gene demonstrated E2/E5 type variants. Immunohistochemical analysis of the diseased kidney demonstrated various lipid peroxidation-specific protein adducts, suggesting a potential role of oxidative stress in this disorder. Recurrence in the transplanted kidney suggested a pathogenic role of extraglomerular humoral component(s) resulting from abnormal lipoprotein metabolism, presumably linked to apo E and other genetic or acquired factor(s). Furthermore, the finding that the patient showed pathologic abnormalities in the transplanted kidney with no clinical signs or symptoms of renal disease indicated that lipoprotein glomerular damage progresses early before any clinical manifestations.

Adult↗

PubMed1999

In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

AIM: The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. METHODS: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. RESULTS: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). CONCLUSION: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Adenocarcinoma↗

PubMed1999

[New operative technique to resect of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor].

We report the new operative technique for resection of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor and hook suspender. Standard muscle sparing thoracotomy cannot obtain the adequate operative field in the posterior chest wall under the scapula because of sparing the latissimus dorsi muscle. To obtain a sufficient operative field at the operation for en bloc chest wall resection, especially with the area of the posterior chest wall under the scapula, resection of the trapezius muscle, rhomboideus major muscle, and latissimus dorsi muscle has been added to muscle-sparing thoracotomy. Through our new technique using Kent's retractor and hook suspender that has been used in the abdominal surgery, assistant surgeon can be eliminated in favor of hanging up the scapula, which is able to be performed much easier to obtain a good operative field. To use the Kent's retractor and hook suspender, the scapula is lifted upward and cranially. With these procedures, the proximal portion of the first, second and third ribs in the posterior chest wall covering by the scapula is able to resect from vertebrocostal junction with muscle-sparing thoracotomy. We examined the apparatus for a case of the right upper lung carcinoma with invasion to the posterior chest wall. We performed right upper lobectomy with chest wall in the area of the second, third and forth ribs with suspending the scapula by Kent's retractor after muscle-sparing thoracotomy.

Adenocarcinoma↗

PubMed1999

[Cases of sternal metastasis except from breast cancer].

Surgical resection is the option for sternal metastasis from breast cancer. But surgical treatment is the subject of controversy for sternal metastasis except from breast cancer. Four cases of secondary malignant tumors of the sternum except from breast cancer were reported. Primary lesions included thyroid cancer, gastric cancer, malignant fibrous histiocytoma of the chest wall and multiple myeloma. In 3 cases, operation were done and they survived 11 months, 13 months and 3 years respectively. In case of secondary malignant tumor of the sternum except from breast cancer, surgical treatment should be considered.

Aged↗

PubMed1998

Expression of tissue inhibitor of metalloproteinases-3 in human atheroma and regulation in lesion-associated cells: a potential protective mechanism in plaque stability.

Atherosclerotic plaque stability depends on the structural integrity of its extracellular matrix skeleton. The balance between degradation by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may regulate plaque stability. Although MMP expression in atheroma is well documented, localization and control of expression of TIMPs in these lesions is incomplete. Extracts of atheroma (n= 14) had 5-fold higher levels of TIMP-3 than nonatherosclerotic tissue (n= 10). Plaques (n=24) contained abundant TIMP-1, -2, and -3 in macrophages in plaque shoulders, intimal-medial borders, and areas overlying the lipid core, as well as in medial smooth muscle cells, albeit in lesser amounts. These observations suggested that macrophages, a cell type not heretofore known to express TIMP-3, did so in atheroma in vivo. Further studies in vitro established the human macrophage as a novel source of TIMP-3 mRNA and protein. Human smooth muscle cells constitutively expressed TIMP-1, -2 and -3 proteins; platelet-derived growth factor and transforming growth factor-beta augmented levels of TIMP-1 and TIMP-3 but not TIMP-2. These findings suggest that regulated expression of TIMP-3, in addition to the presence of TIMP-1 and TIMP-2, counteracts MMP activity in atheroma and hence influences plaque stability.

Arteriosclerosis↗

PubMed1998

Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries.

BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50 micromol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

Acetylcholine↗

PubMed1998

Direct fractionation of proteins in particle-containing feedstocks by a filter paper pieces-based DEAE-cellulose column chromatography. Rapid, robust and low-cost capturing procedure for protein.

Filter paper pieces-based (FPB) DEAE-celluloses was prepared for direct fractionation of proteins in particle-containing feedstocks. FPB DEAE-cellulose has a protein binding capacity equivalent to that of commercially available DEAE-cellulose. Crude extracts from porcine intestine and kiwi fruit pulp, which were unmanageable by commercially available chromatographic media due to rapid clothing, could be directly fractionated with FPB DEAE-cellulose column. In addition, effluents from an FPB DEAE-cellulose column were extensively clarified. The present approach can be used as a rapid, robust and low-cost capturing step for protein from particle-containing feedstocks.

Animals↗

PubMed1998

Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation.

BACKGROUND: Oxygen free radicals have been shown to cause endothelial vasomotor dysfunction. This study examined the effect of reduced glutathione (GSH), an antioxidant, on human coronary circulation. METHODS AND RESULTS: Responses of epicardial diameter and blood flow of the left anterior descending coronary artery to intracoronary infusion of acetylcholine (ACh, 50 microg/min) were measured by quantitative coronary angiography and Doppler flow-wire technique, respectively, before and during combined intracoronary infusion of GSH (50 mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH infusion suppressed the constrictor response of epicardial diameter to ACh and enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the epicardial diameter response to ACh was observed in a subgroup of subjects with > or = 1 coronary risk factors but not in a subgroup without risk factors. Saline infusion did not have any effects. CONCLUSIONS: The results indicate that GSH improved coronary endothelial vasomotor function, particularly in subjects with coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin in human coronary arteries.

Acetylcholine↗

PubMed1998

The operation of a superconducting wiggler at TERAS.

A superconducting wiggler has been successfully installed at the ETL 800 MeV electron storage ring facility (TERAS). The operation of the wiggler at magnetic field strengths of 5 T with electron beam energy of 750 MeV has been accomplished. The wiggler has been designed and constructed to produce synchrotron radiation with critical photon energy around 3 keV for scientific, industrial and medical applications. We report here experiments that demonstrate the possibility of stable operation of a superconducting wiggler in a small storage ring.

Journal Article↗

PubMed1998

Increases in the mitochondrial DNA replication and transcription in the remnant liver of rats.

We studied mitochondrial DNA (mtDNA) replication and transcription in association with major hepatectomy. Changes in nuclear respiratory factor 1 (NRF-1) mRNA and RNA moiety of mitochondrial RNA-processing endoribonuclease (MRP-RNase RNA) were followed at 0, 3, 6, 12, and 24 h after hepatectomy. Contents of mtDNA, cytochrome b mRNA, and beta-actin mRNA were also measured. Contents of NRF-1 mRNA and MRP-RNase RNA increased to maximum or sub-maximum level 1 h after hepatectomy. mtDNA and cytochrome b mRNA increased to maximum level 3 h after. On the contrary, content of beta-actin mRNA increased to maximum level 12 h after. From these results, mtDNA replication and transcription occurred in the initial phase of liver regeneration, which might lead to an increase in mitochondrial respiratory function in the remnant liver, and cytoskeleton proteins such as beta-actin were followed thereafter.

Actins↗

PubMed1998

A Dumon stent inserted for bronchial stenosis causing a left bronchopericardial fistula: report of a case.

We present herein the case of a 59-year-old man in whom a Dumon stent, inserted as treatment for stenosis of the left main bronchus, caused a left bronchopericardial fistula. The patient initially presented with severe dyspnea caused by main bronchial stenosis of unknown origin for which a Dumon stent was inserted at a local hospital. The Dumon stent migrated to the endobronchus through the stenosis of the left main bronchus a few days later, and his dyspnea remained unresolved. He was subsequently referred to our department 6 months later, where a left pneumonectomy under supportive cardiopulmonary bypass through the femoral artery and vein was performed, and a postoperative pathological diagnosis of bronchial leiomyosarcoma was made. For this rare group of malignant tumors, early diagnosis permits complete surgical resection of the mass and offers the best prognosis. Excision of the tumor should be performed under cardiopulmonary bypass through the femoral vessels when a risk of sudden rupture of the pulmonary artery or vein exists for any reason.

Bronchi↗

PubMed1998

Antibody-dependent difference in biodistribution of monoclonal antibodies in animal models and humans.

The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and humans, and to elucidate the applicability of animal models. 99mTc-labeled murine mAb -- against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150) -- and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb (not 99mTc-BW431/26) differed clearly in mice and patients. 99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination showed increased uptake in the liver with rapid blood clearance (mean alpha half-life = 31.1 min) compared with 99mTc-BW431/26 (28.4 h). 99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in tumors. Clinical examination showed rapid blood clearance (mean alpha half-life = 6.4 min) and increased uptake in the liver. High-performance liquid chromatographic analysis of 99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb and interacting substances.

Animals↗

PubMed1998

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese.

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial-derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm.

Adult↗