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Biomedical subjects

H Shigematsu

Publications and source records attributed to H Shigematsu.

At least 37 records · Page 2Linked to original sources

Oxygen saturation measurement of calf muscle during exercise in intermittent claudication.

OBJECTIVES: to evaluate the oxygen saturation of the calf muscle measured by means of spatially resolved spectroscopy (SRS) in claudicants. METHODS: a total of 150 legs in 84 consecutive patients with calf claudication were studied by SRS. Oxygen saturation (SmO(2)) and the relative changes in oxygenated haemoglobin (HbO(2)) and deoxygenated haemoglobin (Hb) of the gastrocnemius muscle were measured during a treadmill walking test (2.4 km/h, 12%, 5 min). RESULTS: exercise was associated with a decrease in HbO(2) and an increase in Hb. There was no difference in SmO(2) at rest among all groups. The decrease oxygen saturation correlated well with the severity of symptoms of IC. CONCLUSION: muscle oxygen saturation measurement by SRS can be used clinically to provide objective information regarding the severity of IC.

Adult↗

A case of mixed membranous nephropathy and purpura nephritis.

We report the case of a 71-year-old man with mixed glomerular lesions, membranous and necrotizing changes. The patient had abdominal pain and purpurat on the extremities and trunk, followed by melena, and after admission to hospital, proteinuria and occult blood were noted. Laboratory findings were negative for autoimmune disease and viral hepatitis. Renal biopsy showed segmental necrotizing changes and mesangial proliferation with spike formation. Immunofluorescence revealed a granular deposition of IgA predominantly in the mesangial area in contrast to the granular IgG deposition along the glomerular capillary loops. Moreover, electron-microscopically, mesangial as well as subepithelial electron-dense deposits were observed. These data suggest that the patient had 2 distinct types of glomerulonephritis simultaneously: idiopathic membranous nephropathy and purpura nephritis.

Aged↗

Structural fragility of blood vessels and peritoneum in calponin h1-deficient mice, resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells.

We have observed weak expression of calponin h1, which stabilizes the actin filament system, in blood vessels within human malignant tumors. This observation suggested that because of a deficiency in stabilization by calponin h1, the structure of blood vessels in malignant tumors is fragile compared with blood vessels in normal tissues. We therefore generated calponin h1-deficient (CN(-/-)) mice to examine the effect of calponin h1 on the integrity of the barrier system in blood vessels against cancer metastasis. The CN(-/-) mice exhibited morphological fragility of the tissues, including the uterus and blood vessels. In particular, we frequently observed bleeding into the surrounding tissue from blood vessels of the ocular fundus in CN(-/-) mice. In addition, mesothelial cells, which usually express calponin h1 in normal (CN(+/+)) mice, were retracted in the CN(-/-) mice. When fluorescein was injected i.v. into mice, the CN(-/-) mice exhibited a greater and more rapid leakage of fluorescein from the blood vessels of the ocular fundus compared with the CN(+/+) mice. In the CN(-/-) mice receiving i.v. inoculations of B16 melanoma cells, significantly more metastatic nodules were formed in the lung than in the CN(+/+) mice. When B16 melanoma cells were injected i.p., the severity of peritonitis carcinomatosa was greater in CN(-/-) than in CN(+/+) mice. These results indicate that calponin h1 plays an important role in the regulation of the integrity of the blood vessels and peritoneum, which in turn is an important factor influencing the frequency of cancer metastasis. The CN(-/-) mice, which exhibit fragile blood vessels and peritoneum, could serve as sensitive and useful host models to investigate cancer metastasis.

Actins↗

Surgical treatment for popliteal artery entrapment syndrome.

PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period. METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings varied, showing medial deviation in two limbs, poststenotic dilatation in four limbs and occlusion of the popliteal artery in five limbs. In addition, computed tomographic (CT) scanning showed positive findings of PAES in all the limbs. RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch angioplasty with or without thromboendarterectomy in three limbs, and MTS alone in one limb. All the ASV grafts were found to be patent during the postoperative follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to be the most sensitive diagnostic modality for PAES, and MTS with or without ASV grafting method was considered to be the best surgical procedure for PAES.

Adolescent↗

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia.

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF), a new strategy for the treatment of chronic vascular occlusive disease, was examined in a rabbit model of hind limb ischemia. The left femoral artery was completely excised to induce an ischemic state in the hind limb of male rabbits. Simultaneously, a skin section was resected from the wound, and host fibroblasts were cultured. The cultured fibroblasts were infected with adenovirus vector containing modified human bFGF cDNA with the secretory signal sequence (AxCAMAssbFGF) or LacZ cDNA (AxCALacZ). At 21 days after femoral artery excision, the gene-transduced fibroblasts were administered through the left internal iliac artery. The fibroblasts significantly accumulated in the ischemic hind limb, and the AxCAMAssbFGF-treated cells secreted bFGF for less than 14 days without elevation of systemic bFGF level. At 28 days after cell administration, calf blood pressure ratio, angiographic score, capillary density of muscle tissue and blood flow of the left internal iliac artery were determined, and animals with AxCAMAssbFGF-treated cells showed significantly greater development of collateral vessels, as compared with those with AxCALacZ-treated cells. These findings suggest that adenovirus-mediated ex vivo gene transfer of bFGF was effective for improvement of chronic limb ischemia.

Adenoviridae↗

Participation of endothelial cells and transformed mesangial cells in remodeling of glomerular capillary loops in Thy-1 nephritis.

The relationship between mesangial cells (MC) and endothelial cells (EC) in the remodeling of glomerular capillary loops was investigated in a rat model of anti-Thy-1 antibody (Ab)-induced glomerulonephritis. Immunohistochemical analysis showed that cells positive for alpha-smooth muscle actin (alpha-SMA) appeared in the mesangial stalks at day three, and had increased in number at day seven, after injection of Thy-1 Ab. Double staining for alpha-SMA and proliferating cell nuclear antigen (PCNA) showed that some MC expressing PCNA were negative for alpha-SMA at day three, but by day seven almost all PCNA-positive MC expressed alpha-SMA. Western blotting for alpha-SMA from isolated glomeruli was negative at day one after injection of Thy-1 Ab, but positive at day seven. Type III collagen appeared at day seven, followed by an increase of EC in the capillary loops, as determined by double immunofluorescent staining for rat endothelial cell antigen-1 (RECA-1) and type III collagen. RECA-1-positive cells increased rapidly in number after day seven and eventually showed the same distribution pattern as that in control rats. Both type I and type III collagens were expressed in the mesangial and the ballooning area of the glomerulus at day seven. Electron microscopy revealed that immature MC and EC forming small capillary lumina appeared in the enlarged mesangial area at day seven. In accordance with the increase of capillaries and the enlargement of the lumina, the number of MC and the amount of mesangial matrix decreased gradually, and most of the glomeruli returned to a normal structure by week 4. These data show that type I and type III collagen produced by transformed MC may be of benefit to proliferation of EC and remodeling of the capillary in Thy-1-induced nephritis.

Animals↗

Glomerular expression of alpha-smooth muscle actin reflects disease activity of IgA nephropathy.

To elucidate the relationship between histological disease states and clinicopathological features in immunoglobulin A nephropathy (IgAN), 90 needle-biopsy specimens diagnosed as IgAN were analyzed. The specimens were divided into four groups according to histological grade and stage index. Immunohistochemical features of alpha-smooth muscle actin (alpha-SMA), macrophages positive for myeloid/histiocyte antigen (MAC387), and expression of type I, III and IV collagens were all examined. Glomerular expression scores of alpha-SMA and the degree of intraglomerular macrophage infiltration were highest in the active and non-sclerotic groups. Type I and IV collagens were significantly more abundant in the sclerotic groups than in the active groups. Type III collagen was strongly expressed in both the active and sclerotic groups. Double immunolabeling of alpha-SMA and intercellular adhesion molecule (ICAM)-1 revealed that ICAM-1 was expressed around the alpha-SMA-positive mesangial area. In multivariate analysis, the glomerular expression score of alpha-SMA was mostly correlated with histological grading in the 10 clinicopathological parameters. Type IV collagen score was mostly correlated with histological staging. These results suggest that glomerular alpha-SMA expression reflects the histological activity of IgAN. Immunohistological staining of alpha-SMA is valuable to estimate the degree of disease activity in IgAN.

Actins↗

Topical application of antiangiogenic agent AGM-1470 suppresses anastomotic intimal hyperplasia after ePTFE grafting in a rabbit model.

BACKGROUND: Anastomotic intimal hyperplasia (AIH) remains an unsolved problem. Angiogenesis around the anastomosis is one of the important mechanisms accelerating AIH. In this study, we investigated the effects of an antiangiogenic agent AGM-1470 (O-[chloroacetyl-carbamoyl] fumagillol: AGM) on the thickness of AIH after expanded polytetrafluoroethylene grafting. METHODS: Study 1: Smooth muscle cells (SMCs) were cultured to form 3-mm-side square colonies by using 4 kinds of culture medium, containing AGM at concentrations of 0, 0.1, 1.0, and 10 ng/mL. The SMC colony spreading distance in each group was measured as an index of mitogenic activity. The isolated proliferative activity of SMCs was also assessed. Study 2: Male New Zealand white rabbits underwent inlay expanded polytetrafluoroethylene grafting of the carotid arteries. They were divided in 4 groups (control, vehicle, AGM [0.5], and AGM [5]) in which no topical application, Vaseline ointment, Vaseline ointment containing 0.5 mg AGM, or Vaseline ointment containing 5 mg AGM was applied to the anastomoses, respectively. Rabbits were fed a high-cholesterol diet for 2 weeks before and 8 weeks after the operation. AIH thickness was measured and capillary formation and SMC accumulation around the anastomoses were examined with immunohistochemical staining. RESULTS: Study 1: AGM suppressed SMC migratory activity in a cytostatic, but not cytotoxic, manner. Study 2: AGM ointment inhibited AIH in proportion to its concentration and also suppressed new capillary formation around the anastomoses and SMC accumulation in AIH. CONCLUSIONS: Topical application of the antiangiogenic agent AGM may become an important strategy for preventing AIH.

Angiogenesis Inhibitors↗

Risk factors for rupture of abdominal aortic aneurysm based on three-dimensional study.

PURPOSE: Factors influencing the development or rupture of abdominal aortic aneurysms (AAAs) have not yet been confirmed. This study delineated the risk factors for rupture of AAAs as evaluated by means of a combination of three-dimensional (3D) reconstruction and clinical data analysis. METHODS: The study population comprised Japanese patients in whom an atherosclerotic AAA had been diagnosed between January 1980 and December 1997. We obtained 3D-based data by means of computer-aided 3D reconstruction from computed tomography studies of AAAs. The data included the tortuosity of the aneurysm, maximum transverse diameter, length of the aneurysm, aneurysmal volume, aneurysmal surface area, largest aneurysmal cross-sectional area, ratio of transverse aneurysmal diameter to the length of the aneurysm (T/L), and amount of mural thrombus. Clinical data were collected from patient files. All data were assessed by means of multivariate analysis for their predictive value for expansion or rupture of AAA. RESULTS: The most efficient predictor of annual expansion rate of maximum transverse diameter (EX-D) was a combination of largest aneurysmal cross-sectional area, tobacco use, and tortuosity. The most efficient predictor of annual expansion rate of aneurysmal volume (EX-V) was a combination of aneurysmal volume and blood urea nitrogen level. The most efficient predictors of aneurysmal rupture was a combination of EX-D, diastolic blood pressure, and T/L. CONCLUSION: Three-dimensional-based data on aneurysmal morphology, including T/L, largest aneurysmal crosssectional area, and aneurysmal volume, had strong predictive value for expansion and rupture of AAAs.

Aged↗

Extracranial carotid aneurysm in Takayasu's arteritis.

Extracranial carotid aneurysm caused by Takayasu's arteritis is extremely rare. We have experienced six cases of extracranial carotid aneurysm among 106 cases of Takayasu's arteritis that were treated surgically in the past 50 years. We herein review these cases and discuss the surgical indications and postoperative course of this rare disease. We report original observations about extracranial carotid aneurysm in Takayasu's arteritis.

Adult↗

Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.

Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NO(x) and Glu. L-NAME abolished the increases in the levels of NO(x) and Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.

Animals↗

Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt.

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

Angiotensin II↗

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Adult↗

Prostacyclin inhibits the production of MMP-9 induced by phorbol ester through protein kinase A activation, but does not affect the production of MMP-2 in Human cultured mesangial cells.

BACKGROUND/AIMS: The imbalance between degradation and synthesis of the glomerular extracellular matrix (ECM) causes glomerular sclerosis in various types of glomerulonephritis. We investigated the effect of prostacyclin, which is an inflammatory mediator, on the production of matrix metalloproteinase (MMP)-9 and MMP-2 in human cultured mesangial cells. The synthesis of Jun proteins and Ets-1 proteins, which are related with MMP-9 gene, was also studied. METHODS: The production of MMP-9 and MMP-2 was investigated by gelatin zymography. Western blotting was undertaken to analyze the protein synthesis of Jun and Ets-1. RESULTS: Prostacyclin inhibited the production of MMP-9 induced by phorbol ester. The inhibitory effect by prostacyclin was reversed in part by the pretreatment with an inhibitor of protein kinase A, such as H-89. Forskolin also inhibited the production of MMP-9. The production of MMP-2 was constitutionally seen and was not influenced by prostacyclin and forskolin. The synthesis of Jun protein augmented by phorbol ester was suppressed by prostacyclin. Ets-1 protein was constitutionally synthesized and was not affected by phorbol ester and prostacyclin. CONCLUSION: Prostacyclin plays an important role in inflammatory glomerular disorders by regulating the metabolism of ECM. The production of MMP-9 and MMP-2 may be under the different control pathways.

Carcinogens↗

Coronary revascularization in Japan. Part 1: survey of facilities during 1997.

Coronary artery disease is one of the major causes of morbidity and mortality in industrialized countries, including Japan. Increasing numbers of patients have been treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), but there is little information in Japan concerning the use of revascularization therapy and the facilities. The Japanese Coronary Intervention Study (JCIS) Group conducted a nationwide survey on coronary revascularization procedures and facilities during 1997. A questionnaire was mailed to the presidents or designated delegates of 8,253 laboratories in 7,986 hospitals that had departments of internal medicine and/or cardiovascular medicine and to 578 facilities in 558 hospitals identified by the PCI survey as performing CABG and/or registered in the annual survey carried out by the Japanese Association for Thoracic Surgery. A total of 109,788 PCIs were performed at 1,023 laboratories, and 17,667 CABGs at 477 facilities. PCI and CABG numbers per 10(6) population were 870 and 140, respectively. The ratio of PCI to CABG was 6.2. The numbers of PCI laboratories and CABG facilities per 10(6) population were 8.1 and 3.8, respectively. The majority of PCI laboratories and CABG facilities had a small annual volume: 44% of PCI laboratories and 77% of CABG facilities had annual volumes of 50 or less. Only half of the PCI laboratories had surgical backup on-site. Despite the small volume for each facility, coronary revascularization, especially PCI, is highly utilized in Japan.

Angioplasty, Balloon, Coronary↗

Coronary revascularization in Japan. Part 2: comparison of facilities between 1997 and 1999.

A nation-wide survey on the procedures and facilities of coronary revascularization, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) conducted by the Japanese Coronary Intervention Study (JCIS) group during 1997 revealed that PCI is more often used than CABG and is mainly carried out in low-volume facilities without surgical backup. The present study aimed to investigate the temporal changes in the usage of revascularization therapies and facilities from 1997 to 1999. A questionnaire was mailed in 1998 to the delegates of 1,086 PCI and 582 CABG facilities identified by the previous survey, and 89% of PCIs surveyed and 94% of CABGs surveyed reported back. The number of PCI procedures had increased by 19% from 97,831 to 116,479 and that of CABG procedures also increased by 21% from 16,374 to 19,846. The ratio of PCI to CABG was 5.9 in 1999, showing no significant change from 6.0 in 1997. In parallel, the number of PCI and CABG facilities increased from 888 to 941 and from 442 to 453, respectively. The use of coronary stents and other interventional devices increased during these 2 years. Coronary stents were used regardless of the annual procedural volume of the facilities, whereas other interventional devices, directional and rotational coronary atherectomy, were used mainly in the high-volume laboratories (p<0.01). Beating-heart, off-pump CABG had increased from 2% to 11% of total cases. Continued monitoring of trends in PCI and CABG facilities and procedures will be needed for nation-wide assessment of the use of new technology.

Angioplasty, Balloon, Coronary↗

Rare complication of saccular aneurysm and histological dissection: an autopsy study of 5865 elderly cases.

The purpose of this study was to examine complicated lesions of saccular aneurysm and dissection. We investigated the ascending aortae in 5865 consecutive elderly autopsy cases, and 5 cases (0.085%) of aortic saccular aneurysms associated with dissection at the edges were selected. Their edges characteristically protruded like a shelf, which histologically consisted of an inner part of the dissected media. All patients were female and their mean age was 76.8 (67-89) years. The aneurysmal walls at the center showed severe fragmentation and disappearance of the elastic lamellae of the remaining outer media. Thus, partial sections of these lesions were not sufficient but cross-sections of the whole diseased regions including the edges were essential for diagnosis. One patient had 3 saccular aneurysms and an adjacent shallow depression, which we called "healed microscopic dissection". Histologically, it showed disappearance of the inner media and was replaced by fibrosis in continuation from the intima. This lesion showed no findings of intramural hemorrhage or thrombus, and thus it will differ from organized thrombi in the dissected false lumen. Another patient presented had an aneurysmal rupture which resulted in cardiac tamponade. This case implies the need for surgical treatment of this entity.

Aged↗