Search PubMed⌕ Search

Biomedical subjects

F Numano

Publications and source records attributed to F Numano.

At least 73 records · Page 4Linked to original sources

Increased levels of soluble forms of adhesion molecules in Takayasu arteritis.

The present series of experiments were designed to determine if soluble forms of vascular cell adhesion molecule-1 and inter cellular adhesion molecule-1 are elevated in the setting of Takayasu arteritis. Plasma levels of these soluble adhesion molecules were measured by enzyme-linked immunosorbent assay in 73 Takayasu arteritis and 36 age-matched normal controls and examined with respect to the age of patients. Soluble vascular cell adhesion molecule-1 levels were significantly higher in Takayasu arteritis (mean 871.4 ng/ml, P<0.01) compared with controls (mean 607.9 ng/ml). No difference was found in soluble inter cellular adhesion molecule-1 levels between these two groups. Comparison of soluble vascular cell adhesion molecule-1 and inter cellular adhesion molecule-1 in these patients subdivided by age into three groups indicated significantly higher levels of these molecules in individuals over 50 years old compared to those under 39 years old (P<0.05). These data suggest that the measurement of soluble vascular cell adhesion molecule-1 may be clinically important in Takayasu arteritis. The correlation of soluble vascular cell adhesion molecule-1 and inter cellular adhesion molecule-1 levels with age may indicate some relationship with progression of this disease.

Adolescent↗

MICA gene polymorphism in Takayasu's arteritis and Buerger's disease.

To further clarify the HLA-linked genes susceptible to arterio-vasculitis of unknown etiology, Takayasu's arteritis and Buerger's disease, polymorphism in the MICA gene, a newly identified gene near the HLA-B gene and expressed in epithelial cell lineage, was investigated. Polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis and subsequent sequencing of the MICA gene have revealed that there are 5 MICA alleles which are different in the number of a GCT repeat in exon 5: MICA alleles MICA-1.1, -1.2, -1.3 and -1.4 have 9, 6, 5 and 4 GCT repeats, respectively, and MICA-1.5 has 5 GCT repeats with a 1 bp frameshift insertion in the repeat. MICA genotyping data in 81 Japanese patients with Takayasu's arteritis, 38 Japanese patients with Buerger's disease, and 160 healthy Japanese controls showed that MICA-1.2 and -1.4 were significantly associated with Takayasu's arteritis and Buerger's disease, respectively. Because MICA-1.2 and -1.4 were in strong linkage disequilibria with HLA-B52 and -B54 in the Japanese populations, respectively, we have compared the odds ratio (OR) of the risk to the diseases for individuals having both or each of the disease-associated MICA and HLA-B alleles. It was found that MICA-1.2 gave a significantly high OR of risk to Takayasu's arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasu's arteritis is mapped near the MICA gene. In contrast, MICA-1.4 gave a significantly high OR of risk to Buerger's disease only in the presence of HLA-B54, suggesting that the HLA-linked gene susceptible to Buerger's disease is linked to the HLA-B54-MICA-1.4 haplotype, and may be differently mapped from that to Takayasu's arteritis.

Amino Acid Sequence↗

Association of clinical manifestations with HLA-B alleles in Takayasu arteritis.

HLA-DNA typing using PCR-SSOP and PCR-DCP methods was performed in 85 patients with Takayasu arteritis and 492 healthy controls who had been typed for HLA by serological method. Frequencies of HLA-B52 (B*5201) and B39 (B*3901 and B*3902) were significantly increased in the patients. Frequency of HLA-DRB1*1502 was also increased but it was suggested to be a reflection of its linkage disequilibrium with B52. Association of HLA-B52 and B39 with seven clinical manifestations--pulmonary infarction, ischemic heart disease, aortic regurgitation, systemic hypertension, renal artery stenosis, cerebrovascular disease, and visual disturbance--in 132 HLA-typed patients with Takayasu arteritis was studied. In HLA-B52 positive TA patients, aortic regurgitation (vs B52(-)-B39(+), OR=3.8, P<0.05, vs B52(-)-B39(-), OR=5.49, P<0.001), ischemic heart disease (vs B52(-)-B39(+), OR=12.05, P<0.05, vs B52(-)-B39(-), OR=2.85, P<0.05), and pulmonary infarction (vs B52(-)-B39(+), OR=5.74, P<0.03) were found to be significantly prevalent. On the other hand, in HLA-B39 positive TA patients, frequency of renal artery stenosis was significantly increased (vs B52(+)-B39(-), OR=12.14, P<0.001, vs B52(-)-B39(-), OR=5.21, P<0.03). These observations have suggested that HLA-B52 molecule and B39 molecule would contribute to different clinical manifestations by binding different antigenic peptides to cause inflammations. Thus HLA-B molecule may play an important role in pathogenesis or determining clinical manifestations of Takayasu arteritis.

Alleles↗

Subclavian steal syndrome secondary to Takayasu arteritis.

We present a case of 'subclavian steal syndrome' secondary to Takayasu arteritis, in a 32-year-old, Japanese woman, whose clinical manifestations result from severe ocular and brain ischemia, refractory to high dose systemic corticosteroids. Surgical management using two bypass-grafts was carried out. The first one, a GoreTex, 8 mm in diameter, thin wall, stretch type with ring-bypass graft, from the left external iliac artery to the ipsilateral axillary artery. The second one, an autologous reverse saphenous vein graft from the left subclavian artery to the ipsilateral common carotid artery. The result was a remarkable improvement of the patient's general condition and symptoms. Patency of the extra-anatomic conduits was established by digital subtraction angiography (DSA), and transcranial Doppler evaluation, as well as flow velocity assessment revealed an objective improvement of the blood supply to the ischemic areas. The present surgical approach was justified since the inflammatory process extended to the aortic arch. The development of new and efficient operatory techniques, and continuous improvement of the graft-materials provide better expectations for the long-term outcome of refractory syndromes.

Adult↗

Takayasu arteritis, Buerger disease and inflammatory abdominal aortic aneurysms: is there a common pathway in their pathogenesis?

Takayasu arteritis, Bueger disease and IAAA are non-specific vasculitis involving mainly large vessels, the etiology of which are all still in the mist. Our recent HLA analysis on Takayasu arteritis and Buerger disease revealed a close association with some HLA antigens which made us suppose the common pathological pathway to cause these morbid conditions. International survey on Takayasu arteritis also revealed cases involving abdominal aorta only (Type IV, International Classification) in Asian countries, very similar to clinical and pathological features of IAAA. These ongoing survey suggest the common mechanism in the pathophysiology of these morbid conditions.

Aortic Aneurysm, Abdominal↗

Increased QT dispersion in patients with vasospastic angina.

BACKGROUND: The risk factors for ventricular arrhythmias in patients with coronary vasospasm have not been identified. We evaluated QT dispersion in patients with vasospastic angina and its relation to susceptibility to ventricular arrhythmias during myocardial ischemia and reperfusion. METHODS AND RESULTS: We assessed the corrected QT (QTc) dispersion before induction of coronary artery spasm by intracoronary injection of acetylcholine (baseline) and 30 minutes after administration of isosorbide dinitrate in 50 patients with vasospastic angina and 50 patients with atypical chest pain. The baseline QTc dispersion was significantly greater in patients with vasospastic angina than in patients with atypical chest pain (mean+/-SD: 69+/-24 versus 44+/-19 ms, 95% confidence interval of mean difference [CI]: 16 to 33 ms; P<0.001). QTc dispersion decreased significantly, to 48+/-15 ms (CI: 15 to 26 ms; P<0.001 versus baseline), after administration of isosorbide dinitrate in patients with vasospastic angina but did not change significantly in patients with atypical chest pain (mean+/-SD: 41+/-17 ms, CI: -3 to 9 ms). During the provocation test, 24 of 50 patients with vasospastic angina experienced ventricular arrhythmias. The baseline QTc dispersion was significantly greater in patients with than without ventricular arrhythmias (mean+/-SD: 77+/-23 versus 61+/-19 ms, CI: 4 to 26 ms; P<0.05). CONCLUSIONS: Patients with vasospastic angina exhibited an increased baseline QTc dispersion compared with patients with atypical chest pain, which suggests that inhomogeneity of repolarization and susceptibility to ventricular arrhythmias are increased in patients with vasospastic angina, even when asymptomatic. The association between increased QTc dispersion and ventricular arrhythmias during the provocation test suggests that measurement of QT dispersion may help predict which patients with vasospastic angina are at high risk for ventricular arrhythmias during ischemia.

Acetylcholine↗

Measurement of postprandial remnant-like particles (RLPs) following a fat-loading test.

To assess the usefulness of remnant-like particles (RLPs), which represent potentially atherogenic lipoprotein remnants, as an index of postprandial hyperlipidemia, RLPs and other lipids were measured in 19 healthy adults (23-44 years old) after ingestion of a test meal (fat content, 32.9%). The lipoprotein derivatives, with a marked increase after fat-loading, were triglycerides, retinyl palmitate and RLPs. The retinyl palmitate peak lagged behind the RLP and triglyceride peaks, indicating that it may have different kinetics than RLP and triglyceride. While triglycerides are considered as an index of atherosclerotic risk factor, RLPs also may be a suitable index for evaluating postprandial hyperlipidemia. RLPs remained high even 8 h after fat-loading, suggesting that the postprandial state persists for almost the whole day. Accordingly, it may be important to assess postprandial remnant concentrations.

Adult↗

Takayasu arteritis: evaluation of the thoracic aorta with CT angiography.

PURPOSE: To determine the diagnostic accuracy of computed tomographic (CT) angiography in the evaluation of Takayasu arteritis. MATERIALS AND METHODS: Twenty-five patients with clinical symptoms suggestive of Takayasu arteritis underwent CT angiography and conventional angiography. Takayasu arteritis was diagnosed in 20 patients on the basis of conventional angiography. CT angiography was performed with a helical CT scanner after injection of a bolus of contrast material, and images were generated for three-dimensional display, multiplanar reformation, and maximum intensity projection. For vascular assessment, all images from CT angiography were used, and the results were compared with those from conventional angiography. RESULTS: CT angiography clearly depicted various luminal changes, including stenosis, occlusion, dilatation, and aneurysm, in the thoracic aorta and its major branches. CT angiography accurately depicted 190 (95%) of 200 arteries, although the extent of the steno-occlusive lesions was overestimated in five (2%) and underestimated in five (2%). Furthermore, CT angiography depicted mural changes, including wall thickening, calcification, and mural thrombi, not seen with conventional angiography. The sensitivity and specificity of CT angiography in the diagnosis of Takayasu arteritis were 95% and 100%, respectively. CONCLUSION: CT angiography clearly depicts both luminal and mural changes in the thoracic aorta and its major branches and has a high accuracy in the diagnosis of Takayasu arteritis.

Adolescent↗

Arterial remodeling at the reference site after angioplasty in the atherosclerotic rabbit model.

Recent studies suggest that arterial remodeling plays an important role in restenosis and that remodeling at the reference site may also occur. To assess the chronic effect of the reference site remodeling on angioplasty results, we evaluated reference site remodeling in an experimental atherosclerotic restenosis model. Histological sections of iliac stenoses and their associated proximal reference segments from 50 atherosclerotic rabbits killed 4 weeks after angioplasty were analyzed. Lumen area (LA), external elastic lamina area (EEL), and intimal plus medial areas (I+M) were measured at the lesion (L) and reference (R) sites. Angiography was performed preangioplasty, immediately postangioplasty, and 4 weeks postangioplasty. Restenosis was defined as an angiographic loss/gain ratio of greater than 50% at follow-up angiography. Twenty-three lesions were restenotic (R+) and 32 were not (R-). There was no difference in reference site diameters (RD) between these two groups at the time of angioplasty. However, RDs were significantly smaller in the R+ group than in the R- group (1.24+/-0.18 versus 1.52+/-0.28 mm, n=55, P<.01) at 4-week follow-up. Morphometric analysis also showed a smaller LA(R) in the R+ group (0.85+/-0.27 versus 1.06+/-0.37 mm2, n=55, P<.02), whereas there was no difference in I+M(R) between the two groups. EEL(R) significantly correlated with EEL(L), LA(R), and I+M(R) in both groups combined (r=.53, n=55, P<.0001; r=.62, n = 55, P < .0001; and r = .86, n = 55, P < .0001, respectively). Remodeling can favorably and unfavorably affect both the lesion and the reference sites and appears to occur in parallel and proportionately at both sites. These data suggest that angiographic measurement of late percent stenosis using reference site diameters may lead to an underestimation of the percent luminal narrowing in restenotic lesions because unfavorable remodeling occurs in both the lesion and reference sites in restenotic vessels.

Angiography↗

Long-term patency of an aorta-aortic graft bypass in a patient with Takayasu arteritis.

A 39-year-old woman was diagnosed by means of angiography as Takayasu arteritis complicated with severe systemic hypertension due to atypical coarctation of the aorta. Aorta-aortic bypass graft surgery was carried out successfully and hypertension remarkably improved. An evaluation of the graft 23 years later confirmed an almost perfect condition with a very satisfactory clinical status. Extensive long-term follow-up studies have been conducted among young people after surgical repair of aortic coarctation showing encouraging results, however the situation seems to be different for the atypical coarctation in Takayasu patients, since not only the age at the time of intervention affects the outcome, but the different circumstances mainly related to the natural history of the disease. We evaluated the long-term outcome based on similar cases with particular consideration to the extremely rare coexistence of familiar hypercholesterolemia.

Adult↗

[Use of platelet glycoprotein IIb/IIIa receptor inhibitors in acute coronary syndrome and coronary intervention].

New strategies in the treatment of acute coronary syndromes have focused on the potential for blocking platelet aggregation through the use of platelet surface membrane glycoprotein (GP) IIb/IIIa receptor inhibitors. The benefits of GPIIb/IIIa inhibition in preventing ischemic complications of interventional treatment have been well defined in patients with unstable angina. In the future, major therapeutic applications for this class of agents may include the stabilization of patients with unstable angina and potentially as single medical therapy, as several recently completed trials have suggested. This article attempts to review recently published clinical trials regarding the use of GPIIb/IIIa receptor inhibitors, and clarify current problems in the use of this agent and directions for future investigation.

Acute Disease↗

Vitamin E prevents apoptosis in cortical neurons during hypoxia and oxygen reperfusion.

Cerebral ischemia followed by oxygen reperfusion induces apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). The overproduction of oxygen-free radicals that occurs in the tissues of SHRSP is implicated in reoxygenation injury after hypoxia. Antioxidants inhibit reoxygenation injury in hippocampal slices, and temporal cortices in Alzheimer's disease increase sensitivity to oxygen-free radicals. Because this sensitivity may contribute to the development of the disease, we have studied hypoxia and oxygen reperfusion using cortical neurons isolated from WKY and SHRSP (at 15 days of gestation). We have tried to determine whether cortical neurons are damaged under these conditions, and whether neurons from SHRSP are more vulnerable than those from WKY. We have tried also to verify whether neuronal damage is minimized by vitamin E using the following techniques: (a) Trypan blue staining, (b) in situ staining of apoptosis, (c) ultrastructural examination, and (d) measurement of lactic dehydrogenase (LDH) activity in the bathing medium. Furthermore, we have examined the mechanisms involved in the development of neuronal damage and have studied ways of minimizing it. We demonstrated that 36 hours of hypoxia significantly increased the rate of cell death in SHRSP (p < 0.01), although 12 to 24 hours of hypoxia did not increase cell death in either WKY or SHRSP. In addition, 6 to 36 hours of hypoxia and 1.5 to 5 hours of oxygen reperfusion heavily damaged cells of both WKY and SHRSP, and most became apoptotic or necrotic. In contrast, cells incubated with 50 to 300 microg/ml of vitamin E remained intact, although 10 to 20 microg/ml of vitamin E did not totally preserve the cells. Moreover, vitamin E protected the neurons from high concentrations of sodium nitroprusside (nitric oxide donor) in a dose-dependent manner. Vitamin E, when added to the cells, increased in concentration in a time-dependent manner over a 24-hour period and in a dose-dependent manner below 200 microg/ml, and it was detected mostly in the mitochondria. We also demonstrated that serial treatments with allopurinol (a xanthine oxidase inhibitor) or superoxide dismutase preserved neurons during hypoxia and oxygen reperfusion. These data indicate that SHRSP neurons are weaker than WKY neurons in long-term hypoxia; oxygen radical generation occurs in the early minutes after reperfusion, and then the oxygen-free radicals cause heavy damage to the cells; and antioxidants including vitamin E react with the radicals, thereby preventing apoptosis and necrosis. Therefore, antioxidants appear to be the most important agents in lowering oxygen-free radical damage in cortical neurons.

Animals↗

Acute vigorous exercise attenuates sensitivity of platelets to nitric oxide.

We tested whether inhibition of platelet activation by nitric oxide (NO) might be altered by strenuous exercise. Sixteen healthy male non-smokers, aged 20-26 years, underwent treadmill testing. All subjects reached Bruce stage IV without chest pain or abnormal ST-T wave changes. Platelet aggregation by Born's method and cyclic GMP accumulation in the washed platelets were determined before and immediately after exercise. Dose-response curves for platelet aggregation by collagen were constructed both in the absence and presence of 2 microM SIN-1, an NO donor, to quantify the antiaggregation effects of NO. After exercise, platelet aggregation by collagen was modestly enhanced and inhibition of platelet aggregation by SIN-1 was significantly attenuated by exercise. This attention was accompanied by a blunted cyclic GMP response of the platelets to the NO donor. We conclude that impaired sensitivity of the platelets to NO, in addition to the enhancement of platelet aggregation, may partially explain the epidemiological evidence that acute strenuous exercise precipitates coronary events.

Adult↗

New assay for glycated lipoproteins by high-performance liquid chromatography.

We developed an automated analytic system for glycated lipoprotein using high-performance liquid chromatography (HPLC) with an affinity boronate column and a gel permeation column. This system can measure glycated lipoprotein (glycated LDL and glycated HDL) in a small (5 microliters) sample of serum in a short time (40 min/sample). Recovery with this system was 92.1%. Therefore a large number of samples can be measured in clinical use. The system should contribute to an elucidation of the role of glycated lipoprotein in atherosclerosis.

Chromatography, High Pressure Liquid↗