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Biomedical subjects

K Nakamura

Publications and source records attributed to K Nakamura.

At least 91 records · Page 5Linked to original sources

Drug-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and increase in serum IgE level.

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with multiorgan failure. Recently, the association of the human herpesvirus (HHV) family, particularly of HHV-6, with DIHS has been reported. We report a 43-year-old female diagnosed as having DIHS based on the clinical course and laboratory examinations. The HHV-6 reactivation was demonstrated by significantly increased levels of the specific antibody in her paired sera and by polymerase chain reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in the early stage of the disease, which was associated with the disease activity. By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks later. In addition, serum levels of interferon gamma, interleukin (IL)-4 and soluble IL-2 receptor, which were increased in the early phase of the disease, decreased gradually after the corticosteroid therapy.

Adult↗

Molecular mechanisms for vascular injury in the metabolic syndrome.

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes and dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been shown to be associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. In the present article we review the molecular mechanisms by which the metabolic syndrome causes endothelial dysfunction and subsequently promotes atherosclerosis. We also discuss promising therapeutic strategies that specifically target the mechanisms responsible for vascular alterations in the metabolic syndrome.

Animals↗

Effects of high calcium intake on bone metabolism in magnesium-deficient rats.

We examined the effects of high calcium (Ca) intake on bone metabolism in magnesium (Mg)-deficient rats. Male Wistar rats were divided into three groups, with each group having a similar mean body weight, and fed a control diet (control group), a Mg-deficient diet (Mg-deficient group) or a Mg-deficient Ca-supplemented diet (Mg-deficient Ca-supplemented group) for 14 d. Femoral Ca content was significantly lower in the Mg-deficient Ca-supplemented group than in the control group and Mg-deficient group. Femoral Mg content was significantly lower in the Mg-deficient group and Mg-deficient Ca-supplemented group than in the control group. Furthermore, femoral Mg content was significantly lower in the Mg-deficient Ca-supplemented group than in the Mg-deficient group. Serum osteocalcin levels (a biochemical marker of bone formation) were significantly lower in the two Mg-deficient groups than in the control group. As a biochemical marker of bone resorption, urinary deoxypyridinoline excretion was significantly higher in the Mg-deficient Ca-supplemented group than in the control group and Mg-deficient group. The results in the present study suggest that high Ca intake had no preventive effect on alteration of bone metabolism in Mg-deficient rats.

Absorption↗

Loss of basement membrane heparan sulfate expression is associated with tumor progression in endometrial cancer.

Perlecan is a major heparan sulfate proteoglycan (HPSG) of the basement membrane (BM) and binds to various cytokines and growth factors via its heparan sulfate glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS-GAG expression in endometrial cancers. We investigated the expression of BM HS-GAG by immunohistochemistry in 109 endometrial cancers and analyzed correlations with various clinicopathological features. The HS-GAG expression index was significantly lower in cases of advanced stage, high-grade, deep myometrial invasion, positive peritoneal cytology, lymph vascular space invasion and lymph node metastasis. There was no association between HS-GAG expression status and patient outcome. Decreased HS-GAG expression of BM is associated with tumor progression, but is not be a useful prognostic factor in patients presenting with endometrial cancer.

Adult↗

Acarbose, an alpha-glucosidase inhibitor, improves insulin resistance in fructose-fed rats.

Insulin resistance is one of the determinants of postprandial hyperglycemia. Acarbose is an alpha-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, thereby suppressing postprandial hyperglycemia. Recently, acarbose has been found to reduce the incidence of cardiovascular disease (CVD) in patients with diabetes. These observations suggest that intervention of postprandial hyperglycemia with acarbose is a promising strategy for the prevention of CVD in diabetic patients. However, the effects of acarbose on insulin sensitivity are not fully understood. In this study, we examined whether oral administration of acarbose could improve insulin sensitivity in fructose-fed rats, a widely used insulin-resistant animal model. Although plasma glucose levels remained unchanged during the experiments, serum insulin levels were significantly increased in fructose-fed rats, which were suppressed by 4 weeks of treatment with acarbose. Acarbose treatment also increased high-density lipoprotein levels in fructose-fed rats. Furthermore, treatment of acarbose inhibited the elevation of systolic blood pressure levels in fructose-fed rats. These results indicate that oral administration of acarbose improves insulin sensitivity in fructose-fed rats. Our present study suggests that the cardioprotecive effects of acarbose could be ascribed, at least in part, to its insulin-sensitizing property.

Acarbose↗

[Off-pump coronary artery bypasssurgery in patients with mitral regurgitation].

Introduction of off-pump coronary artery bypass grafting (off-pump CABG : OPCAB) makes it possible to shorten the bypass time and cardiac arrest time in patients with both ischemic heart disease and valvular disease. This may be beneficial in patients with poor cardiac function and renal dysfunction. However, it is unclear whether such patients can tolerate the changes of hemodynamics during vertical displacement of the heart. In 3 patients who had ischemic heart disease with non-ischemic mitral regurgitation, we performed OPCAB prior to mitral valve plasty. The changes of mitral regurgitation observed by transesophageal echocardiography and several hemodynamic parameters were monitored as the heart was moved to various positions during OPCAB. When a heart positioner (Starfish) was used, hemodynamic deterioration was not observed, and there was also no aggravation of mitral regurgitation. Based on these results, we conclude that it may be possible to carry out OPCAB safely in patients with associated mitral regurgitation.

Adult↗

Azelnidipine, a dihydropyridine-based calcium antagonist, inhibits angiotensin II-induced oxidative stress generation and downregulation of pigment epithelium-derived factor mRNA levels in microvascular endothelial cells.

We have previously shown that azelnidipine, a long-acting dihydropyridine-based calcium antagonist (DHP), inhibited tumor necrosis factor-alpha-induced endothelial cell (EC) activation through its antioxidative properties. However whether azelnidipine could also block the angiotensin II (Ang II)-signaling in ECs remains to be elucidated. Since Ang II-type 1 receptor interaction could contribute to exacerbation of diabetic retinopathy by downregulating pigment epithelium-derived factor (PEDF) gene expression in ECs, we examined here whether azelnidipine inhibited the Ang II-induced reactive oxygen species (ROS) generation and subsequent PEDF gene suppression in microvascular ECs. Azelnidipine, but not nitrendipine, the other popular DHFP completely inhibited the Ang II-induced ROS generation in ECs. Furthermore, azelnidipine, but not nitrendipine, was found to partially restore decreased PEDF mRNA levels in Ang II-exposed ECs. The present study suggests that azelnidipine could inhibit the Ang II-induced decrease in PEDF mRNA levels in ECs through its antioxidative properties. Upregulation of PEDF by azelnidipine may become a therapeutic target for the treatment of diabetic retinopathy associated with hypertension.

Angiotensin II↗

Minodronate, a nitrogen-containing bisphosphonate, inhibits advanced glycation end product-induced vascular cell adhesion molecule-1 expression in endothelial cells by suppressing reactive oxygen species generation.

Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative stress generation in vascular wall cells through an interaction with their receptor (RAGE), thus playing an important role in vascular inflammation and altered gene expression of growth factors and cytokines. We have previously shown that minodronate, a nitrogen-containing bisphosphonate, blocked the angiogenic signaling of vascular endothelial growth factor in ECs through its antioxidative properties. However, the effects of minodronate on AGE-exposed ECs remain to be elucidated. In this study, we investigated whether and how minodronate could inhibit AGE-induced reactive oxygen species (ROS) generation and subsequent vascular cell adhesion molecule-1 (VCAM-1) gene expression in human umbilical vein endothelial cells (HUVEC). Minodronate or an NADPH oxidase inhibitor, diphenylene iodonium, completely inhibited the AGE-induced ROS generation in HUVEC. Geranylgeranyl pyrophosphate reversed the antioxidative properties of minodronate in AGE-exposed ECs. Furthermore, minodronate was found to prevent AGE-induced nuclear factor--KB activation and subsequently suppress VCAM-1 gene expression in HUVEC. These results demonstrate that minodronate could inhibit VCAM- 1 expression in AGE-exposed ECs by suppressing NADPH oxidase-derived ROS generation, probably via inhibition of geranylgeranylation of Rac, a component of endothelial NADPH oxidase. Our present study suggests that minodronate may have a therapeutic potential in the treatment of patients with diabetic vascular complications.

Antioxidants↗

Pigment epithelium-derived factor is a pericyte mitogen secreted by microvascular endothelial cells: possible participation of angiotensin II-elicited PEDF downregulation in diabetic retinopathy.

Pigment epithelium-derived factor (PEDF) is a natural extracellular component of the retina with neuronal differentiating activity. Decreased levels of PEDF in the mammalian eye have been shown to participate in proliferative diabetic retinopathy. In addition, we have recently found in in vitro experiments that PEDF protected against pericyte apoptosis, the earliest histopathological hallmark of diabetic retinopathy. These observations suggest that the loss of PEDF in the mammalian eye plays an important role in the development and progression of diabetic retinopathy. However, the functional role of endothelial cell (EC)-derived PEDF in pericyte survival and the regulation of PEDF gene expression remain to be elucidated. In this study, we examined the effects of anti-PEDF antibody (Ab) on the viable cell number of cocultured pericytes with microvascular ECs. We further studied the effects of angiotensin II (Ang II) on PEDF gene expression in ECs. Anti-PEDF Ab significantly inhibited the growth-stimulating effects of cocultured ECs on pericytes. Furthermore, Ang II significantly decreased PEDF mRNA levels in ECs, which was completely reversed by an Ang II type 1 receptor blocker, telmisartan. Our present results suggest that PEDF is an EC-derived mitogen or survival factor for retinal pericytes. Suppression by Ang II of the EC-derived PEDF may be involved in exacerbation of diabetic retinopathy in patients with hypertension.

Adult↗

Chiari malformation type I associated with familial spastic paraplegia: report of a surgically treated case.

CASE REPORT: We describe the case of a 7-year-old girl with Chiari malformation type I (CMI) and concomitant familial spastic paraplegia (FSP), who exhibited spastic gait disturbance. She also showed poor results on the standing tolerance test using thermography, which evaluates autonomic nerve function. The patient was subjected to posterior fossa decompression and cervical 1 (C1) laminectomy for CMI based on the result of the standing tolerance test. After the operation her gait disturbance and autonomic nerve dysfunction improved. DISCUSSION: Although no cases of CMI and concomitant FSP have been reported, due to the fact that autonomic nerve dysfunction is one of CMI symptoms but never FSP, the diagnosis of autonomic nerve dysfunction of CMI using the standing tolerance test played an important role in selecting the surgical procedure for this case.

Arnold-Chiari Malformation↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

The interaction of oxygen with TiC(001): photoemission and first-principles studies.

High-resolution photoemission and first-principles density-functional slab calculations were used to study the interaction of oxygen with a TiC(001) surface. Atomic oxygen is present on the TiC(001) substrate after small doses of O(2) at room temperature. A big positive shift (1.5-1.8 eV) was detected for the C 1s core level. These photoemission studies suggest the existence of strong O<-->C interactions. A phenomenon corroborated by the results of first-principles calculations, which show a CTiTi hollow as the most stable site for the adsorption of O. Ti and C atoms are involved in the adsorption and dissociation of the O(2) molecule. In general, the bond between O and the TiC(001) surface contains a large degree of ionic character. The carbide-->O charge transfer is substantial even at high coverages (>0.5 ML) of oxygen. At 500 K and large doses of O(2), oxidation of the carbide surface occurs with the removal of C and formation of titanium oxides. There is an activation barrier for the exchange of Ti-C and Ti-O bonds which is overcome only by the formation of C-C or C-O bonds on the surface. The mechanism for the removal of a C atom as CO gas involves a minimum of two O adatoms, and three O adatoms are required for the formation of CO(2) gas. Due to the high stability of TiC, an O adatom alone cannot induce the generation of a C vacancy in a flat TiC(001) surface.

Journal Article↗

High sensitivity search for nu;e's from the sun and other sources at KamLAND.

Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3<E(nu;(e))<14.8 MeV. No candidates were found for an expected background of 1.1+/-0.4 events. This result can be used to obtain a limit on nu;(e) fluxes of any origin. Assuming that all nu;(e) flux has its origin in the Sun and has the characteristic 8B solar nu(e) energy spectrum, we obtain an upper limit of 3.7 x 10(2) cm(-2) s(-1) (90% C.L.) on the nu;(e) flux. We interpret this limit, corresponding to 2.8 x 10(-4) of the standard solar model 8B nu(e) flux, in the framework of spin-flavor precession and neutrino decay models.

Journal Article↗

Formation of advanced tokamak plasmas without the use of an ohmic-heating solenoid.

A new operational scenario of advanced tokamak formation was demonstrated in the JT-60U tokamak. This was accomplished by electron cyclotron and lower hybrid waves, neutral beam injection, and the loop voltage supplied by the vertical field and shaping coils. The Ohmic heating (OH) solenoid was not used but a small inboard coil (part of the shaping coil), providing less than 20% of total poloidal flux, was used. The plasma thus obtained had both internal and edge transport barriers, with an energy confinement time of 1.6 times H-mode scaling, a poloidal beta of 3.6, and a normalized beta of 1.6, and a large bootstrap current fraction (>90%). This result opens up a possibility to reduce, and eventually eliminate, the OH solenoid from a tokamak reactor, which will greatly improve its economic competitiveness.

Journal Article↗

Treatment results of oral verrucous carcinoma and its biological behavior.

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.

Adult↗