Search PubMed⌕ Search

Biomedical subjects

K Nakatani

Publications and source records attributed to K Nakatani.

At least 37 records · Page 2Linked to original sources
PubMed2001

Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.

Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.

Animals↗
PubMed2001

Semi-quantitative analysis of cytokine mRNA expression induced by the herbal medicine Sho-saiko-to (TJ-9) using a Gel Doc system.

The RT-PCR method was employed to determine the cytokine mRNA expression of human peripheral lymphocytes induced by the Japanese herbal medicine Sho-saiko-to (TJ-9). The results showed that the mRNA expression of IL-12, IL-1beta, IL-10, TNF-alpha, G-CSF, and IFN-gamma increased after 6 hr in culture. This is the first reported finding that TJ-9 is an IFN-gamma inducer. Next, cytokine mRNA expression was semi-quantitatively measured using the Gel Doc system with a CCD camera and then statistically analyzed in order to determine which component of TJ-9 was the true cytokine inducer. The results showed that the scutellaria root is the main component inducing the cytokines, while the glycyrrhiza root is the secondary component. When the cytokine concentrations in the supernatants of cell cultures were measured by ELISA, the levels of IL-12, IL-1beta, IL-10, TNF-alpha, and G-CSF reflected mRNA expression levels in the cell fraction. However, the level of IFN-gamma was below the detectable limit. The effects of various reagents on many different kinds of cytokine mRNA expression could be analyzed objectively in a short time using the Gel Doc system. Many important findings could be demonstrated by this simple, easy, sensitive, and cheap method. After the clinical significance of cytokine analysis is confirmed, this method may become a useful clinical examination tool.

Cells, Cultured↗
PubMed2001

Improved selectivity for the binding of naphthyridine dimer to guanine-guanine mismatch.

Naphthyridine dimer composed of two 2-amino-1,8-naphthyridines and a connecting linker strongly binds to guanine-guanine (G-G) mismatch in duplex DNA. In order to improve G-G selectivity for the binding, we have examined structure modification of the linker. A new naphthyridine dimer possessing 3,6-diazaoctanedioic acid linker binds to G-G mismatch with an association constant of 1.18 x 10(7) M(-1), which is somewhat weaker than that of the original naphthyridine dimer having a shorter connecting linker. However, the binding of the modified naphthyridine dimer to G-A mismatch was almost negligible as compared to that of the original. This results in a net increase of the selectivity for the binding to G-G mismatch by 4-folds.

Base Pair Mismatch↗
PubMed2001

Scanning of guanine-guanine mismatches in DNA by synthetic ligands using surface plasmon resonance.

Here we have designed and synthesized ligands that specifically bind with high affinity (K(d) = 53 nM) to the guanine (G)-guanine mismatch, one of four types of single-nucleotide polymorphism (SNP). Detection of the G-G mismatch was performed by a surface plasmon resonance (SPR) assay using a sensor chip carrying the G-G specific ligand on its surface. The accuracy of the G-G mismatch detection by the SPR sensor was demonstrated by a marked SPR response obtained only for the DNA containing the G-G mismatch. DNAs containing G-A and G-T mismatches, as well as a fully matched duplex, produced only a weak response. Furthermore, this assay was found applicable for the detection of SNP existing in PCR amplification products of a 652-nucleotide sequence of the HSP70-2 gene.

Base Pair Mismatch↗
PubMed2001

Elevated serum levels of matrix metalloproteinase-9 (MMP-9) in Kawasaki disease.

Matrix metalloproteinases (MMPs) play an important role in the progression of tumour cells and the invasion of inflammatory cells by degrading the extracellular matrix. In the MMP family, MMP-9 gelatinase is thought to contribute to the pathogenesis of inflammatory arteritis by disrupting the elastic lamina. The aim of the present study is to investigate the potential role of MMP-9 in Kawasaki disease (KD), an acute type of systemic vasculitis in children. We studied the total levels of MMP-9 (free proMMP-9 and free MMP-9) in the sera using a new assay system and the expression of MMP-9 mRNA in the leucocytes using reverse transcription-polymerase chain reaction in 18 patients with KD, 10 patients with sepsis and 10 healthy children (HC). The serum MMP-9 levels were significantly higher (P < 0.01) in the acute phase of KD than in the acute phase of sepsis and HC. In the time course of KD, the serum MMP-9 levels decreased significantly (P < 0.01) from the subacute through the convalescent phases. In the acute phase of KD, the serum MMP-9 levels showed a significantly positive correlation (P < 0.05) with the circulating leucocyte counts, especially the neutrophil counts. Furthermore, the expression of MMP-9 mRNA in the circulating leucocytes increased in the acute phase of KD and decreased from the subacute through the convalescent phases. These findings indicate that an excessive amount of MMP-9 is present in the plasma during the acute phase of KD, thus suggesting that circulating leucocytes may be a source of the MMP-9 secreted into the circulation.

Acute Disease↗
PubMed2001

Delayed apoptosis of circulating neutrophils in Kawasaki disease.

Circulating polymorphonuclear neutrophils (PMNs) are known to increase in number and are functionally activated in the acute phase of Kawasaki disease (KD). In the present study, we investigated whether the apoptosis of PMNs is deregulated in KD. When the isolated PMNs were cultured in vitro, the proportions of spontaneous apoptotic PMNs (annexin V+ cells and cells with fragmented DNA) were found to be significantly lower (P < 0.01) in the patients with KD (n = 25) than in the patients with a bacterial infection (n = 20) or a viral infection (n = 20), or in healthy children (n = 20). The proportion of circulating Fas-positive PMNs was also significantly lower (P < 0.01) in the acute KD patients than in the other groups. In the acute phase of KD, the proportion of spontaneous apoptotic PMNs showed a significant positive correlation (P < 0.01) with the proportions of circulating Fas-positive PMNs. Furthermore, the agonistic anti-Fas MoAb (CH-11) induced a significant increase in the proportion of apoptotic PMNs in the patients with a viral infection and healthy children, but not in either the patients with KD or the patients with a bacterial infection. In the intracellular expression of anti- and pro-apoptotic proteins, the A1/Bax ratio was significantly higher in acute KD than in the other groups. These findings indicate that PMN apoptosis is inhibited during the acute phase of KD and also suggest that both the resistance against the Fas-mediated death signal and the down-regulation of the mitochondrial apoptotic signalling pathway due to an altered balance of Bcl-2 protein expression are responsible for the delayed PMN apoptosis.

Acute Disease↗
PubMed2001

Cardiac tamponade caused by spontaneous rupture of mediastinal lymph node metastasis of hepatocellular carcinoma.

Rupture of a hepatocellular carcinoma (HCC) is a well-known cause of death in patients with HCC. This report describes a rare case of HCC presenting as cardiac tamponade caused by a spontaneous rupture of mediastinal lymph node metastasis into the pericardial space. A transcatheter arterial embolization (TAE) of internal thoracic artery successfully controlled the bleeding, and the patient was rescued from cardiac tamponade. Although there was no rebleeding, the patient died from liver failure 2 months later. An autopsy revealed a poorly differentiated HCC in the liver, lung and mediastinal lymph nodes.

Carcinoma, Hepatocellular↗
PubMed2001

Odorant-induced hyperpolarization and suppression of cAMP-activated current in newt olfactory receptor neurons.

Although many studies have reported that odorants can elicit inhibitory responses as well as excitatory responses in vertebrate olfactory receptor neurons, the cellular mechanisms that underlie this inhibition are unclear. Here we examine the inhibitory effect of odorants on newt olfactory receptor neurons using whole cell patch clamp recording. At high concentrations, odorant stimulation decreased the membrane conductance and inhibited depolarization. Various odorants (anisole, isoamyl acetate, cineole, limonene and isovaleric acid) suppressed the depolarizing current in a dose-dependent manner. Furthermore, one odorant could suppress the depolarization caused by another odorant. The depolarization caused by isoamyl acetate was inhibited by anisole in cells that were excited by isoamyl acetate but not by anisole. Odorants were able to hyperpolarize cells that were depolarized by cAMP-induced conductance. Given that this inhibitory effect of odorants can affect excitation caused by other odorants, we suggest that it might play a role in coding odorants in olfactory receptor neurons.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Modulation of DNA-mediated hole transport efficiency by DNA-protein complex formation.

To investigate how protein interactions to DNA affects DNA-mediated hole transport, hole transport through the DNA bound to restriction endonuclease BamHI was examined. The DNA bound to BamHI retains a regular B-DNA type of conformation, but have a number of hydrogen bonding interaction. These hydrogen bondings in BamHI-DNA complex suppressed the guanine oxidation and the hole transport in sequence selective manner.

Base Sequence↗
PubMed2001

Echocardiographic diagnosis of extrapericardial tamponade due to dilated gastric roll following oesophagectomy.

A complication of lower thoracic oesophagectomy for oesophageal carcinoma is reported. Extrapericardial tamponade was caused by a dilated retrosternal gastric roll. Echocardiography was useful for diagnosis. Diagnosis, investigation and management of this unusual but life-threatening complication are discussed. Transthoracic echocardiography is a useful and practical investigation for the evaluation of complications of oesophagectomy.

Cardiac Tamponade↗
PubMed2001

Plasma levels of agouti-related protein are increased in obese men.

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.

Adult↗
PubMed2001

Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury.

To investigate the inhibitory effect of serine protease inhibitors (SPI) on neutrophil-mediated endothelial cell (EC) injury, we analyzed the in vitro cytotoxicity of radiolabeled human umbilical vein EC (HUVEC) mediated by neutrophils in the presence of SPI. The EC injury was inhibited dose-dependently by urinary trypsin inhibitor (ulinastatin, UTI) and ONO-5046, which have the ability to inactivate neutrophil elastase, but not by gabexate mesilate, nafamostat mesilate, aprotinin, and argatroban, which have no ability to inactivate neutrophil elastase. In addition, when UTI and ONO-5046 were added to the tumor necrosis factor alpha-primed neutrophils alone, they showed a dose-dependent inhibition of the intracellular elastase activity, but the other SPI did not, for either flow cytometry or confocal microscopy. Therefore, UTI and ONO-5046 may protect EC against the neutrophil-mediated injury not only by inactivating the extracellular elastase secreted by neutrophils, but also by acting directly on neutrophils and suppressing the production and secretion of activated elastase from them.

Cells, Cultured↗
PubMed2001

[A case of a persistent primitive proatlantal intersegmental artery with a ruptured basilar bifurcation aneurysm].

A case of persistent primitive proatlantal intersegmental artery (PPPIA) associated with a ruptured basilar bifurcation aneurysm was reported. A 44-year-old male with sudden headache was admitted to our hospital. CT scan revealed subarachnoid hemorrhage. Cerebral angiography revealed anomalous anastomosis between the internal carotid artery and the vertebral artery at the proatlantal region. This anastomosis branched off from the left internal carotid artery at the C4 level and joined the horizontal portion of the left vertebral artery. It was thought to be PPPIA. Angiography also revealed an aneurysm of the basilar bifurcation which was responsible for the patient's subarachnoid hemorrhage. The aneurysm was successfully treated by endovascular embolization with Guglielmi detachable coils in an acute stage, and resulted in good outcome. PPPIA with basilar bifurcation aneurysm has not been presented or reported in the literature to date. To our knowledge, this is the first report of such an association of vascular anomalies. The frequency of PPPIA combined with the intracranial aneurysm is relatively high, whereas the occurrence of PPPIA is extremely rare. Therefore, it was suggested that some congenital and/or hemodynamic factors changed by PPPIA may affect the pathogenesis of intracranial aneurysms.

Adult↗
PubMed2001

Cellular prion protein expression in non-ciliated epithelial cells (Clara cells) of proliferating bronchioles during bleomycin-induced pulmonary fibrosis in hamster.

The cellular isoform of prion protein (PrPc) is a membrane glycoprotein with unknown roles. This study aimed to immunohistochemically demonstrate PrPc expression in normal and fibrotic hamster lungs. In untreated lungs, Clara cells, which were preferentially distributed in small bronchioles and characterized by globule granules, were positively stained. Reaction products were diffuse in the cytoplasm outside the granules and nuclei. In bleomycin-induced pulmonary fibrosis, bronchiolar proliferation was induced in the thickened fibrous tissue around terminal bronchioles. This event was characterized by accumulation of ductular structures which were predominantly lined by PrPc positive cells representative of Clara cells. Furthermore, PrPc positive cells were occasionally populated in the epithelium of alveolar ducts and reepithelialized alveoli. These findings suggest that Clara cells might undergo proliferation and migration into acini from terminal bronchioles. The fibrous tissue contained many alpha-smooth muscle actin positive myofibroblasts. The present study indicates that PrPc is expressed in Clara cells in normal and fibrotic hamster lungs and suggests that Clara cells may proliferate as pulmonary stem cells and repair the damaged epithelium after alveolar injuries.

Animals↗
PubMed2000

Detection of circulating lipopolysaccharide-bound monocytes in children with gram-negative sepsis.

The possibility that gram-negative sepsis can be diagnosed by detection of lipopolysaccharide (LPS) bound on the surface of monocytes in the circulation of patients with gram-negative sepsis was investigated. Peripheral monocytes were analyzed by flow cytometer and an anti-LPS monoclonal antibody in 3 groups: children with gram-negative sepsis, children with gram-positive sepsis, and healthy children. LPS-bound monocytes were found in all patients with gram-negative sepsis but not in children with gram-positive sepsis or in healthy children. Therefore, the flow cytometry method developed for this study may be a novel method for diagnosing gram-negative sepsis.

Adult↗
PubMed2000

Azo-azulene derivatives as second-order nonlinear optical chromophores

The molecular and solid state nonlinear optical (NLO) properties of several (phenylazo)-azulenes are investigated. In particular, (4-nitrophenylazo)-azulene (2b) exhibits a quadratic hyperpolarizability (beta(vec)) of 80 x 10(-30) cm5esu recorded at 1.907 microm by the electric field-induced second-harmonic (EFISH) technique. This molecular material, which crystallizes in the monoclinic noncentrosymmetric space group Pc, exhibits an efficiency 420 times that of urea in second-harmonic generation. The origin of the optical nonlinearity in azo-azulene is discussed in relation with crystal structures and semiempirical calculations within the INDO/SOS formalism, and compared with that of the well known disperse red one (DR1) organic dye.

Journal Article↗