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Biomedical subjects

Y Numaguchi

Publications and source records attributed to Y Numaguchi.

At least 37 records · Page 2Linked to original sources

Relationship between the apolipoprotein E and angiotensin-converting enzyme genotypes and LDL particle size in Japanese subjects.

We investigated whether the apolipoprotein E (apoE) and the angiotensin-converting enzyme (ACE) genotypes contribute to the variance in low-density lipoprotein (LDL) particle size in Japanese subjects (n = 136; M/F= 106/30). ACE polymorphism was associated with neither LDL size nor individual lipid levels. In contrast, the subjects with the epsilon2 allele of the apoE genotype had significantly lower levels of total cholesterol (P = 0.002) and LDL cholesterol (P = 0.004) compared with those without the epsilon2 allele. The subjects with the epsilon4 allele had a significantly smaller LDL particle size than those without the epsilon4 allele (P = 0.012). Separate analyses of the male subjects showed similar associations. A stepwise regression analysis revealed the epsilon4 allele to be an independent contributing variable that could affect LDL particle size. Our results suggest that the apoE genotype is associated with the development of atherosclerotic disease, since the epsilon2 and epsilon4 alleles relate to a decrease in LDL cholesterol levels and a decrease in LDL particle size, respectively.

Adult↗

Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats.

Carvedilol (CAR) is a vasodilating beta-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg/kg) was administered intraperitoneally, and CAR (30 mg/kg daily) or ATN (150 mg/kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104+/-4 vs. 120+/-4 mmHg, P<0.05) and left ventricular fractional shortening (38.8+/-3.1 vs. 55.4+/-1.3%, P<0.01), and resulted in a significant accumulation of ascites (14.4+/-4.9 vs. 0 ml, P<0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4+/-7.1 vs. 51.5+/-1.2 nmol/g heart, p<0.01). CAR prevented the increase in TBARS content (48.8+/-3.0 nmol/g heart, P<0.01 vs. DOX group), whereas ATN had no significant effect (74.3+/-5.2 nmol/g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its beta-blocking property.

Animals↗

Disseminated coagulopathy associated with transtorcular embolization of vein of Galen aneurysm in a neonate.

We describe in this report the development of disseminated intravascular coagulopathy in a neonate after transtorcular embolization of an unusual vein of Galen aneurysm. This rare but potentially fatal complication associated with transtorcular embolization should be considered in decision-making and prognostic evaluation processes, especially in neonates with severe heart failure.

Cerebral Angiography↗

Zinc accumulation in adriamycin-induced cardiomyopathy in rats: effects of melatonin, a cardioprotective antioxidant.

We have recently reported that melatonin protects against adriamycin-induced cardiomyopathy whose pathogenesis may involve free radicals and lipid peroxidation. Melatonin has also been shown to affect zinc turnover. Since zinc may act as an antioxidant, we investigated the role of zinc in the pathogenesis of adriamycin-induced cardiomyopathy as well as in the treatment of melatonin against this disorder. Sprague-Dawley rats were given adriamycin (cumulative dose, 15 mg/kg); melatonin (cumulative dose, 84 mg/kg); adriamycin plus melatonin; adriamycin plus probucol, another antioxidant (cumulative dose, 90 mg/kg); or vehicle alone, according to previously-used regimens. Cardioprotective effects of both antioxidants (melatonin and probucol) were confirmed by the parameters of fractional shortening, heart weight, heart/body weight ratio, ascites volume, and mortality. Adriamycin increased both the myocardial and plasma levels of thiobarbituric acid reactive substances (TBARS) and myocardial zinc levels, and decreased plasma zinc levels. The significant negative correlation observed between the myocardial and plasma zinc levels (r = 0.73, P < 0.01) among the samples of adriamycin-treated and control rats suggested an internal redistribution of zinc. Melatonin and probucol were equally effective in inhibiting the increase in myocardial TBARS as well as zinc levels, suggesting that myocardial zinc accumulation might be a protective response against adriamycin-induced oxidative stress. Melatonin also inhibited the adriamycin-induced decrease in plasma zinc levels; probucol was not as effective in doing so. In addition to melatonin's antioxidative effect, it may have the effect of maintaining the plasma zinc levels.

Animals↗

Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury.

Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87. 1+/-6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7. 5+/-0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50. 7+/-9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF1alpha, the main metabolite of PGI2, compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and 2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.

6-Ketoprostaglandin F1 alpha↗

Modulation of LDL particle size after an oral glucose load is associated with insulin levels.

Individuals with a predominance of small low-density lipoprotein (LDL) particles appear to be at increased risk for coronary artery disease. The purpose of this study was to determine whether the LDL particle size was modulated in response to a 75-g oral glucose load. Overall, there were no significant changes in the LDL particle size after glucose load. However, the difference in LDL particle size (deltaLDL size) between the fasting and 2-h post-load states was inversely correlated with the fasting LDL particle size. Also, deltaLDL size was positively correlated with BMI and the post-load glucose levels. Forward stepwise regression analysis revealed three parameters as independent factors capable of modulating LDL particle size: BMI, fasting insulin, and post-load glucose levels. After adjustment for BMI and glucose levels, the levels of fasting and 2-h post-load insulin remain independent determinants of deltaLDL size. These results suggest that plasma insulin levels during glucose load modulate LDL particle size.

Adult↗

A case of subacute combined degeneration: MRI findings.

The specific spinal cord lesion caused by vitamin B12 deficiency is known as subacute combined degeneration (SCD). Neuropathological studies of SCD show lesions mainly in the posterior and lateral columns, involving the cortico-spinal and spino-cerebellar tracts. We report a case of SCD in a 19-year-old man who presented with 4 weeks history of gradually progressing tingling in both hands. MRI of the cervical spine demonstrated symmetrical areas of T2 signal abnormality involving the dorsal columns of the cervical cord from the C2 through C5 levels associated with spinal cord expansion. He was treated with vitamin B12 supplements and experienced gradual improvement in his clinical symptoms. Repeat MRI of the cervical spine after 2 months revealed slight decrease in the area of abnormal signal.

Adult↗

Nitroglycerin-induced aortic relaxation mediated by calcium-activated potassium channel is markedly diminished in hypertensive rats.

Nitroglycerin (NTG), a nitric oxide (NO) donor, is considered to relax vascular smooth muscle by stimulating soluble guanylate cyclase, which in turn increases cyclic GMP (cGMP) level. Recently it became evident that NO-induced vasodilatation is also mediated by stimulating Ca-activated K (K(Ca)) channels directly and/or indirectly through cGMP. We, therefore, tried to investigate the possible involvement or the alteration of K(Ca) channels in the mechanism of vasodilation induced by NTG in physiological and pathological conditions. Using rings prepared from thoracic aortas of spontaneously hypertensive rats (SHR) and those of age-matched Wistar-Kyoto rats (WKY), we studied changes in isometric tension of the rings in response to NTG to evaluate effects of a soluble guanylate cyclase inhibitor methylene blue (MB), and a specific blocker of K(Ca) channel charybdotoxin (CTX). Rings from WKY and SHR precontracted with norepinephrine showed similar aortic relaxation to NTG. MB markedly suppressed the NTG-induced relaxation in both strains, leaving about 30% of MB-resistant relaxation. CTX nearly completely eliminated this MB-resistant relaxation in WHY but did not affect this relaxation in SHR. These results suggest that NTG-induced vasorelaxation is mediated through i) cGMP-dependent and ii) cGM P-independent K(Ca) channel involving mechanisms, the latter may be diminished or virtually eliminated in hypertensive state.

Animals↗

Short-term treatment with prostaglandin E1 analogue has long-term preventive effects on intimal thickening in balloon-injured rat carotid arteries.

We examined effects of a prostaglandin E1 analogue alprostadil on intimal thickening and arterial remodeling in balloon-injured rat carotid arteries. Right common carotid arteries were balloon-injured, and their left counterparts were sham-operated (uninjured). Rats were given alprostadil (0.3 microgram/kg/min, continuous subcutaneous (s.c.) infusion) or vehicle for 1 week after the injury and sacrificed at 4 weeks or 8 weeks. Segments of common carotid arteries corresponding to balloon-injured and uninjured sites were excised and subjected to elastica van Gieson staining. Cross-sectional areas were measured by computed planimetry. Alprostadil prevented intimal thickening at both 4 and 8 weeks. In addition, alprostadil prevented the increase in intimal area/area surrounded by external elastic lamina at both 4 and 8 weeks. Alprostadil had no effects on body weight, heart rate, or systolic blood pressure. Our study demonstrated that alprostadil administered only for the initial 1 week had long-term (up to 8 weeks) preventive effects on intimal thickening. Alprostadil may be useful to prevent restenosis after balloon angioplasty.

Alprostadil↗

Quality assurance in linac-based stereotactic radiosurgery and radiotherapy.

Stereotactic Radiosurgery demands extraordinary attention to quality assurance issues. This is related to the high accuracy needed to perform a successful procedure, accuracy demanded by the proximity of the target lesion to neighboring fragile and eloquent structures in the head and large doses delivered. The nature of the linac-based radiosurgery procedure is that of a series of steps, each linked together and requiring quality control, for if one step is faulty the final result will be equally faulty. The salient points associated with the quality assurance of each step are laid out in this article. Implementation of a linac-based radiosurgery program in an institution must be well thought out and must be a team effort, involving expertise in medical physics, radiological imaging, radiation oncology, and specially trained radiation therapists in order to be successful and safe.

Brain Neoplasms↗

Nonadhesive liquid embolic agent: role of its components in histologic changes in embolized arteries.

RATIONALE AND OBJECTIVES: The authors evaluated the safety and efficacy of a nonadhesive liquid embolic material and the role of its components in histologic changes in embolized arteries. MATERIALS AND METHODS: A Eudragit-E mixture (Rohm Chemische Fabrik, Darmstadt, Germany) was made of a cationic copolymer (Eudragit-E) dissolved in an equal volume of absolute ethanol and iopamidol. The Eudragit-E mixture, an ethanol-iopamidol mixture, and an iopamidol-saline mixture were injected into 12 rabbit renal arteries each. Three rabbits from each group were followed up for 1 day, 1 week, 1 month, and 3 months, at which time they were sacrificed. Kidneys were removed for histologic examination. RESULTS: The Eudragit-E mixture occluded all renal arteries without difficulty: the arteries did not recanalize. Histologically, acute vasculitis was caused by both the Eudragit-E and ethanol-iopamidol mixtures, but not by the iopamidol-saline mixture. Small infarctions were elicited with the ethanol-iopamidol mixture but not with the iopamidol-saline mixture. CONCLUSION: The Eudragit-E mixture is effective and easy to handle. Fifty percent ethanol may play a role in vessel occlusion with Eudragit-E mixture and in acute vasculitis.

Animals↗

Perirolandic cortex in infants: signal intensity on MR images as a landmark of the sensorimotor cortex.

PURPOSE: To correlate the perirolandic low signal intensity seen on T2-weighted magnetic resonance (MR) images in neonates and infants with the anatomically located sensorimotor cortex. MATERIALS AND METHODS: Axial T2-weighted MR images of 146 consecutive patients less than 6 months old were reviewed. The sensorimotor cortex was located by identifying the central sulcus. Two independent readers attempted to identify the central sulcus using two anatomic methods independently and in combination. The location of the central sulcus was compared with that of the perirolandic low signal intensity. RESULTS: Seventy-two normal hemispheres in 36 patients and 91 abnormal hemispheres in 47 patients showed clear perirolandic low signal intensity. The central sulcus was located anatomically in 70 and 72 normal hemispheres (97% and 100%, respectively) and 90 and 91 abnormal hemispheres (99% and 100%, respectively). In all normal hemispheres, the identified central sulcus correlated with the perirolandic low signal intensity. In contrast, an apparent mismatch was found in two hemispheres in a patient with Dandy-Walker syndrome. CONCLUSION: The perirolandic low signal intensity seen on T2-weighted MR images is located exactly in the anatomic sensorimotor cortex in normal brains, whereas a mismatch can occur in abnormal brains.

Bacterial Infections↗

MR imaging of the mamillothalamic tract.

PURPOSE: To demonstrate the normal and abnormal appearance of the mamillothalamic tract (MTT) on cranial magnetic resonance (MR) images. MATERIALS AND METHODS: Two formalin-fixed normal human brain specimens sectioned in axial and coronal planes were used to demonstrate the normal anatomy of the MTT. MR images were obtained in 32 volunteers. Proton-density-weighted coronal and axial pulse sequences were used. The images were evaluated for visualization quality and size and signal intensity of the MTTs in correlation with the specimens. Abnormal MTTs were identified on cranial MR images in two patients, and the imaging findings were analyzed. The clinical history of the patients was also reviewed to determine the effect of these findings on patient care. RESULTS: Normal MTTs were easily identified on MR studies of cadaveric brains and of the brains of the human volunteers. On MR images, normal MTTs were commonly symmetric in appearance, with signal intensity equal to that of other normal fiber tracts. The abnormal MTTs showed high signal intensity on images obtained with a long repetition time or asymmetric volume loss and were associated with atrophy of the ipsilateral mamillary body. CONCLUSION: Normal MTTs are readily visible on conventional MR images. Abnormality of the MTT is a very subtle finding but may be a marker of a limbic system abnormality.

Adult↗

Low density lipoprotein particle size is associated with glycosylated hemoglobin levels regardless of plasma lipid levels.

We evaluated the influence of the levels of glycosylated hemoglobin (HbA1C) and fasting plasma glucose on the variation in low density lipoprotein (LDL) peak particle size in 210 subjects who were undergoing an annual check-up. Univariate analysis showed that LDL particle size was significantly and positively correlated with high density lipoprotein (HDL) cholesterol levels, and was inversely correlated with the levels of total plasma cholesterol, triglycerides, fasting glucose, fasting insulin, HbA1C, and body mass index (BMI). Stepwise regression analysis selected four independent contributing variables that could affect LDL particle size; triglyceride levels, HDL cholesterol levels, LDL cholesterol levels, and HbA1C levels. Similar regression analysis performed for men and for normotensive subjects showed that HbA1C levels also independently influenced LDL particle size. The results indicate that HbA1C levels have a significant effect on LDL particle size. This suggests that small LDL particles would be present in subjects with non-insulin-dependent diabetes mellitus regardless of plasma lipid concentrations.

Adult↗

Intra-arterial papaverine treatment for cerebral vasospasm: our experience and review of the literature.

We described the techniques and efficacy of intra-arterial papaverine hydrochloride infusion (IA-PAP) for symptomatic vasospasm due to aneurysmal subarachnoid hemorrhage based on our experience and review of the literature. Angiographic improvement occurred almost always, but only 50% of patients who presented with acute symptoms showed remarkable clinical improvement after the first, second, or third IA-PAP. Recurrent vasospasm after IA-PAP frequently occurred and this seems to be an apparent source of controversy regarding its efficacy. Review of the literature indicates that IA-PAP may be most effective in combination with percutaneous transluminal angioplasty. Further controlled studies should be conducted regarding papaverine's true efficacy including most effective papaverine concentration and rate of infusion, maximum total dose, site of infusion, timing of treatment, and selection of patients.

Cerebral Angiography↗

Systemic sarcoidosis with bilateral orbital involvement: MR findings.

A 43-year-old woman with diplopia had a disconjugate gaze on physical examination. MR images revealed enlarged, abnormally enhancing extraocular muscles and lacrimal glands bilaterally. Biopsy results were consistent with sarcoidosis. Chest radiographs and CT scans were normal. Clinical and MR findings improved after appropriate medical therapy.

Adult↗