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Biomedical subjects

S Sugiyama

Publications and source records attributed to S Sugiyama.

At least 19 recordsLinked to original sources

Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy.

DNA repair enzymes repair DNA damaged by platinum agents and ionising radiation. Single nucleotide polymorphisms (SNPs) in DNA repair genes modulate the repair capacity and might affect response and prognosis following platinum-based chemoradiotherapy (CRT). We investigated associations between the functional SNPs in DNA repair genes and response and survival in muscle-invasive bladder cancer patients treated with CRT to determine the predictive value of the SNPs in patient selection for bladder conservation therapy. The study group comprised 78 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms in xeroderma pigmentosum complementation groups C (Lys939Gln, A/C), D (XPD; Lys751Gln, A/C), and G (Asp1104His, G/C), and X-ray repair cross-complementing groups 1 (XRCC1; Arg399Gln, G/A) and 3 (Thr241Met, T/C) genes were genotyped. Combined genotypes with at least one variant allele in XPD or XRCC1 were significantly associated with improved cancer-specific survival compared with remaining groups (P=0.009). In multivariate analysis, only the combined XPD and XRCC1 genotypes were independently associated with cancer-specific survival (P=0.04). The association was stronger in stage T3/T4 patients (P=0.0008). These results suggest that combined XPD and XRCC1 genotypes might be prognostic factors in muscle-invasive bladder cancer patients treated with CRT.

Aged↗

[Thoracic surgical approach for traumatic diaphragmatic hernia].

Four patients with traumatic diaphragmatic hernias are reported and are discussed from the view point of surgical approach for the repair of diaphragm. All hernias were caused by car accidents and the diagnoses were made by routine radiography, computed tomography (CT) and magnetic resonance imaging (MRI) examinations. All patients were diagnosed clinically and radiologically. There was no associated intraabdominal trauma and the surgical approach was through the chest in all cases. All but 1 of the patients survived. Abdominal approach at surgery has been considered preferable because associated injuries to intra-abdominal organs have frequently been encountered in the United States. The outcomes in our series indicate that the surgical approach should be based on the clinical and radiographic findings in each indicated patient.

Accidents, Traffic↗

Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis.

OBJECTIVE: To investigate the prognostic value of procollagen type II carboxy-terminal propeptide (PIICP) level in synovial fluid in relation to early tibiofemoral joint osteoarthritis (OA). METHODS: Data were collected on 172 women (age 40 to 59 years) who had knee pain and tibiofemoral joint OA in the early stage. Standing semiflexed knee radiographs were obtained by fluoroscopy at baseline and at four year follow up and a computerised, magnification corrected measurement system was applied to measurement of minimal joint space width in the tibiofemoral compartment. Synovial fluid sampling was performed at baseline and at the four year follow up. Levels of PIICP in the synovial fluid were measured by enzyme immunoassay. The outcome measures were assessed by radiographic joint space narrowing (JSN) in the tibiofemoral joints over four years. Multiple linear regression analyses were used to examine the relation between radiographic JSN and synovial fluid level of PIICP. RESULTS: The number of women available at both baseline and at four year follow up was 110. The average of radiographic JSN over four years was 0.53 mm (range 0.00-2.01). Body mass index showed a slightly positive association with baseline PIICP level. In multiple linear regression analyses adjusted for age and body mass index, radiographic JSN over four years had a direct positive correlation with baseline PIICP level (r=0.395; 95% confidence interval (95% CI) 0.231 to 0.529; p<0.001). CONCLUSION: In a four year prospective study of women, quantification of synovial fluid PIICP was able to predict subsequent radiographic progression in early tibiofemoral joint OA.

Adult↗

[Traumatic diaphragmatic hernia repaired by video-assisted thoracic surgery; report of two cases].

Two cases of traumatic diaphragmatic hernia treated by video-assisted thoracic surgery (VATS) were experienced. Both a 67-year-old female (left side) and a 44-year-old female (right side) was admitted to our hospital in a traffic accident. These patients were diagnosed as diaphragmatic hernia by chest magnetic resonance imaging (MRI). We tried VATS to this trauma, but the combined mini-thoracotomy for 7 cm in length was necessary to replace sliding organs for both cases. The rupture of diaphragm was repaired by direct suture of 2-0 viclyl. VATS will be recommended in the hernia of the diaphragm.

Accidents, Traffic↗

Comparison of remnant-like lipoprotein particles in postmenopausal women with and without coronary artery disease and in men with coronary artery disease.

It is known that hypertriglyceridemia is a risk factor of coronary artery disease (CAD) in postmenopausal women. This study prospectively examined whether remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, may have a significant risk and prognostic values in postmenopausal women with angiographically verified CAD. Remnant-like lipoprotein particles cholesterol (RLP cholesterol) levels in fasting serum were measured in 134 consecutive postmenopausal women with (n = 56) or without (n = 78) CAD by an immunoseparation method. The women with CAD were followed for < or =24 months until occurrence of the following clinical coronary events: readmission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, and cardiac death. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>5.7 mg/dl cholesterol; 90th percentile of the distribution of RLP cholesterol levels in controls) were a significant risk factor for the presence of CAD independent of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and other traditional risk factors. Kaplan-Meier analysis demonstrated that women with CAD and higher RLP cholesterol levels had a significantly higher probability of developing coronary events (p <0.001). In multivariate Cox hazard analysis, high RLP cholesterol levels as well as diabetes and hypercholesterolemia were a significant predictor of future coronary events independent of other risk factors in women with CAD (odds ratio 9.7, 95% confidence intervals 1.3 to 20.3, p = 0.02). In conclusion, increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in postmenopausal women with CAD.

Aged↗

Simultaneous topographic and fluorescence imaging of single DNA molecules for DNA analysis with a scanning near-field optical/atomic force microscope.

High-resolution fluorescence imaging of lambda-phage DNA molecules, intercalated with the dye YOYO-1, has been performed by a SNOM/AFM based on a bent-type optical fiber probe. A modified design of the optical probe has been made, and successful near-field optical resolution has been obtained for the strongly stretched lambda-phage DNA molecules. The best optical resolution was estimated at 45 nm for the dye-intercalated single lambda-DNA molecules by a mean width evaluation. In our comparison between the far-field fluorescence and high-resolution near-field fluorescence images for the DNA, it has been found that the near-field images much better defined the intercalation state of the dye. Finally, the relation between the DNA shapes and the dye distribution states, and the discrimination between the double-stranded and single-stranded DNA molecules, are discussed by comparing the topography and fluorescence images of the SNOM/AFM.

Benzoxazoles↗

Bacterial swimming speed and rotation rate of bundled flagella.

Swimming speed (v) and flagellar-bundle rotation rate (f) of Salmonella typhimurium, which has peritrichous flagella, were simultaneously measured by laser dark-field microscopy (LDM). Clear periodic changes in the LDM signals from a rotating bundle indicated in-phase rotation of the flagella in the bundle. A roughly linear relation between v and f was observed, though the data points were widely distributed. The ratio of v to f (v-f ratio), which indicates the propulsive distance during one flagellar rotation, was 0.27 microm (11% of the flagellar pitch) on average. The experimental v-f ratio was twice as large as the calculated one on the assumption that a cell had a single flagellum. A flagellar bundle was considered to propel a cell more efficiently than a single flagellum.

Flagella↗

Increase in plasma levels of oxidized low-density lipoproteins in patients with coronary spastic angina.

Oxidized low-density lipoproteins (LDL) impair endothelium-dependent dilation and constrict arteries. This study examined possible relation of the circulating plasma levels of Ox-LDL to coronary spastic angina (CSA). The plasma levels of Ox-LDL were measured by ELISA in 37 consecutive patients with CSA and normal coronary angiograms and in 79 consecutive control patients. The Ox-LDL levels in patients with CSA were significantly higher than those in controls. In multivariate analysis, higher levels of Ox-LDL were a risk factor for CSA independently of other traditional risk factors. The Ox-LDL levels had a significant and positive correlation with constrictor response of coronary arteries to the intracoronary acetylcholine infusion. Thus, Ox-LDL may play a possible role in pathogenesis of coronary spasm.

Acetylcholine↗

An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro.

BACKGROUND: Unstable atherosclerotic plaques that cause acute coronary events usually contain abundant macrophages expressing matrix metalloproteinases (MMPs) and tissue factor (TF), molecules that probably contribute to plaque rupture and subsequent thrombus formation. Lipid lowering with HMG-CoA reductase inhibitors reduces acute coronary events. METHODS AND RESULTS: To test whether lipid lowering with an HMG-CoA reductase inhibitor retards macrophage accumulation in rabbit atheroma, we administered cerivastatin to immature Watanabe heritable hyperlipidemic rabbits (cerivastatin group, n=10, cerivastatin 0.6 mg x kg(-1) x d(-1); control group, n=9, saline 0.6 mL x kg(-1) x d(-1)) for 32 weeks and measured macrophage accumulation and expression of MMPs and TF. Serum cholesterol levels after 32 weeks were 809+/-40 mg/dL (control group) and 481+/-24 mg/dL (treated group). Cerivastatin diminished accumulation of macrophages in aortic atheroma. Macrophage expression of MMP-1, MMP-3, MMP-9, and TF also decreased with cerivastatin treatment. Cerivastatin reduced the number of macrophages expressing histone mRNA (a sensitive marker of cell proliferation) detected by in situ hybridization but did not alter macrophages bearing a marker of death (TUNEL staining). Cerivastatin treatment (>or=0.01 micromol/L) also reduced growth, proteolytic activity due to MMP-9, and TF expression in cultured human monocyte/macrophages. CONCLUSIONS: These results suggest that lipid lowering with HMG-CoA reductase inhibitors alters plaque biology by reducing proliferation and activation of macrophages, prominent sources of molecules responsible for plaque instability and thrombogenicity.

Animals↗

Morphologic changes in the aorta during elastase infusion in the rat aneurysm model.

BACKGROUND: The morphologic changes in the aorta during elastase infusion, which have not previously been investigated, were examined in the rat abdominal aortic aneurysm model. MATERIALS AND METHODS: A total of 80 Wistar rats were divided into five groups. A 1.0-cm segment of infra-renal abdominal aorta was infused with 25 U of elastase in 1 mL saline for 10 (n = 14), 20 (n = 14), 30 (n = 14), 60 (n = 19), or 120 min (n = 19). In the 120-min group, transparency and aortic diameter were recorded every 10 min. In each group, 7 rats were killed immediately after infusion. The aortas were excised for histologic examination. The aortic diameters were measured 7 days after infusion in the remaining rats. RESULTS: The infused aorta became transparent within 50 min of elastase infusion. The aortic diameter increased rapidly for the first 30 min of infusion. Histologically, the elastic tissue was completely absent after 60 min of infusion. The aortic diameters in the 60- and 120-min groups were not significantly different 7 days after infusion. CONCLUSIONS: Morphologic changes in the infused aorta are complete after 60 min of elastase infusion. It may be possible to shorten the elastase infusion time from 120 to 60 min in this model.

Animals↗

Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes.

Inflammation and oxidative stress contribute to the pathogenesis of many human diseases including atherosclerosis. Advanced human atheroma contains high levels of the enzyme myeloperoxidase that produces the pro-oxidant species, hypochlorous acid (HOCl). This study documents increased numbers of myeloperoxidase-expressing macrophages in eroded or ruptured plaques causing acute coronary syndromes. In contrast, macrophages in human fatty streaks contain little or no myeloperoxidase. Granulocyte macrophage colony-stimulating factor, but not macrophage colony-stimulating factor, selectively regulates the ability of macrophages to express myeloperoxidase and produce HOCl in vitro. Moreover, myeloperoxidase-positive macrophages in plaques co-localized with granulocyte macrophage colony-stimulating factor. Pro-inflammatory stimuli known to be present in human atherosclerotic plaque, including CD40 ligand, lysophosphatidylcholine, or cholesterol crystals, could induce release of myeloperoxidase from HOCl production by macrophages in vitro. HOCl-modified proteins accumulated at ruptured or eroded sites of human coronary atheroma. These results identify granulocyte macrophage colony-stimulating factor as an endogenous regulator of macrophage myeloperoxidase expression in human atherosclerosis and support a particular role for the myeloperoxidase-expressing macrophages in atheroma complication and the acute coronary syndromes.

Arteriosclerosis↗

The importance of glycolytically-derived ATP for the Na+/H+ exchange activity in guinea pig ventricular myocytes.

The cardiac subtype of Na+/H+ exchanger (NHE-1) plays an important role in the regulation of intracellular pH (pHi) and also can be a major route for Na+ influx. Although intracellular ATP is required for the optimal function of NHE-1, the regulation of the exchanger by ATP is less well characterized. This study was designed to investigate which intracellular ATP generated by oxidative phosphorylation or by glycolysis is dominant for the activation of NHE-1 in intact cardiac myocytes. Isolated guinea pig ventricular myocytes were loaded with the pHi-sensitive fluorescent indicator, 2'-7'-bis(carboxyl)-5',6'-carboxy fluorescein (BCECF), and exposed to 20 mM 2-deoxyglucose (2-DG) or 2 mM sodium cyanide (CN) to inhibit glycolysis or oxidative phosphorylation, respectively. The activity of NHE-1 was estimated with pHi recovery following transient application of 15 mM NH4Cl (NH4Cl prepulse). After the NH4Cl prepulse, pHi decreased from 7.00 +/- 0.03 (mean +/- S.E.) to 6.60 +/- 0.06 and recovered to 6.94 +/- 0.13 at 10 min (n = 7). The pHi recovery was suppressed in the presence of 2-DG (6.67 +/- 0.05, p < 0.01, n = 7), but was not changed in the presence of CN (6.88 +/- 0.18, n = 6). Since there was no difference in the intrinsic H+ buffering power, the estimation of the net acid efflux demonstrated that the activity of NHE-1 was significantly depressed in 2-DG. The inhibitory effect of 2-DG was not due to more extensive depletion of global intracellular ATP or secondary to the change in either intracellular Na+ or Ca2+ concentration. We concluded that ATP generated by glycolysis rather than by oxidative phosphorylation is essential to activate NHE-1 in ventricular myocytes.

Adenosine Triphosphate↗

Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy.

Long-term solid-organ allografts typically develop diffuse arterial intimal lesions (graft arterial disease; GAD), consisting of smooth-muscle cells (SMC), extracellular matrix and admixed mononuclear leukocytes. GAD eventually culminates in vascular stenosis and ischemic graft failure. Although the exact mechanisms are unknown, chronic low-level alloresponses likely induce inflammatory cells and/or dysfunctional vascular wall cells to secrete growth factors that promote SMC intimal recruitment, proliferation and matrix synthesis. Although prior work demonstrated that the endothelium and medial SMCs lining GAD lesions in cardiac allografts are donor-derived, the intimal SMC origin could not be determined. They are generally presumed to originate from the donor media, leading to interventions that target donor medial SMC proliferation, with limited efficacy. However, other reports indicate that allograft vessels may contain host-derived endothelium and SMCs (refs. 8,9). Moreover, subpopulations of bone-marrow and circulating cells can differentiate into endothelium, and implanted synthetic vascular grafts are seeded by host SMCs and endothelium. Here we used murine aortic transplants to formally identify the source of SMCs in GAD lesions. Allografts in beta-galactosidase transgenic recipients showed that intimal SMCs derived almost exclusively from host cells. Bone-marrow transplantation of beta-galactosidase--expressing cells into aortic allograft recipients demonstrated that intimal cells included those of marrow origin. Thus, smooth-muscle--like cells in GAD lesions can originate from circulating bone--marrow-derived precursors.

Animals↗

Reactive carbonyl compounds related uremic toxicity ("carbonyl stress").

Many studies on uremic toxins have focused on enzymatic biochemistry. Recently, attention has turned to nonenzymatic biochemistry, especially progressive and irreversible modifications of proteins. Two different approaches opened the field of irreversible nonenzymatic modifications of proteins in uremia: the advanced glycation end products (AGEs) derived from the Maillard reaction and the advanced lipoxidation end products (ALEs) derived from lipid peroxidation. They have revealed the accumulation of reactive carbonyl compounds (RCOs) derived from carbohydrates and lipids and the subsequent carbonyl modifications of proteins ("carbonyl stress"). In this article, we describe the causal role of various RCOs and AGEs/ALEs accumulating in uremia, the clinical consequences of carbonyl stress in uremia, and finally, the therapeutic perspectives. We propose carbonyl stress as a new uremic toxicity.

Amyloidosis↗

Feeding dried purple laver (nori) to vitamin B12-deficient rats significantly improves vitamin B12 status.

To clarify the bioavailability of vitamin B12 in lyophylized purple laver (nori; Porphyra yezoensis), total vitamin B12 and vitamin B12 analogue contents in the laver were determined, and the effects of feeding the laver to vitamin B12-deficient rats were investigated. The amount of total vitamin B12 in the dried purple laver was estimated to be 54.5 and 58.6 (se 5.3 and 7.5 respectively) microg/100 g dry weight by Lactobacillus bioassay and chemiluminescent assay with hog intrinsic factor respectively. The purple laver contained five types of biologically active vitamin B12 compounds (cyano-, hydroxo-, sulfito-, adenosyl- and methylcobalamin), in which the vitamin B12 coezymes (adenosyl- and methylcobalamin) comprised about 60 % of the total vitamin B12. When 9-week-old vitamin B12-deficient rats, which excreted substantial amounts of methylmalonic acid (71.7(se 20.2) micromol/d) in urine, were fed the diet supplemented with dried purple laver (10 microg/kg diet) for 20 d, urinary methylmalonic acid excretion (as an index of vitamin B12 deficiency) became undetectable and hepatic vitamin B12 (especially adenosylcobalamin) levels were significantly increased. These results indicate that vitamin B12 in dried purple laver is bioavailable to rats.

Animals↗

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina.

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.

Acetylcholine↗

Experimental study of materials for patch graft on right ventricular outflow tract under extracorporeal circulation in dogs--comparison between Denacol EX-313-treated bovine jugular vein graft and expanded polytetrafluoroethylene (EPTFE) graft.

A comparison between a bovine jugular vein treated with a hydrophilic polyepoxy compound cross-linker (Denacol), and expanded polytetrafluoroethylene (EPTFE), an artificial material, as a patch graft for the reconstruction of the right ventricular outflow tract under extracorporeal circulation in dogs, as if they had pulmonic stenosis, was made. Hemodynamic and histological examinations were conducted two weeks after the transplantation. Hemodynamic problems were not observed in either the Denacol or EPTFE groups. Macroscopically, organization of new tissue on the graft surface was more marked in the EPTFE group than in the Denacol group, and newly-formed tissue was seen surrounding the border of the graft and burying it in the EPTFE group. In the Denacol group, microscopic findings revealed the presence of inflammatory cells and fibroblasts, and an invasion of the graft by collagen fibers and elastic fibers. In the EPTFE group, there was minimal cellular infiltration of the graft and a thick layer consisting of collagen fibers and fibroblasts was observed around the graft. These results indicated that two weeks after transplantation the graft was better assimilated and organized with blood vasculature in the patch graft in the Denacol group than in the EPTFE group.

Animals↗