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T Kanda

Publications and source records attributed to T Kanda.

At least 55 records · Page 3Linked to original sources

Ratio of factor V activities in PT and APTT assays as a new diagnostic marker of lupus anticoagulant.

Lupus anticoagulant (LA) is an antibody that interferes with phospholipid-dependent coagulation tests. We investigated the usefulness of the ratio of factor V activity determined by the Simplastin auto test (PT assay) to factor V activity determined by the Platelin Excel LS test (APTT assay) for detection of LA in plasma samples obtained from 276 patients with haematological and non-haematological disorders and 73 healthy subjects. This ratio was significantly higher in the 15 LA-positive (4.82 +/- 3.34) than in samples from healthy subjects (1.09 +/- 0.10) and was > 1.4 in 10 of the remaining 261 patient samples. The ratio was particularly low in the 54 samples from warfarin-treated patients. These findings suggest that determination of this ratio may be useful as a routine laboratory test for detection of LA. This test requires no specific antigens and can be applied in patients receiving anticoagulants such as warfarin and heparin.

Adult

Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha.

Budding yeast CDC45 encodes Cdc45p, an essential protein required to trigger initiation of DNA replication in late G1 phase. We cloned four and one species of the human Cdc45p homolog cDNA, resulting from different splicing patterns, from HeLa cell and human placenta cDNA libraries, respectively. A comparison of the cDNAs and the genomic sequence showed that the longest encoding a 610-amino acid protein was comprised of 20 exons. One species, which lacks exon 7 and contains the shorter of two exons 18, was identical with the previously reported CDC45L cDNA and constituted 24 out of 28 clones from HeLa cells. Splicing was different in HeLa cells and TIG-1 cells, a human diploid cell line. Human CDC45 protein was found to bind directly in vitro to human minichromosome maintenance 7 protein (hMCM7) and to the p70 subunit of DNA polymerase alpha. The data support a thesis that human CDC45 acts as a molecular tether to mediate loading of the DNA polymerase alpha on to the DNA replication complex through binding to hMCM7.

Alternative Splicing

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients.

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.

Antibodies, Viral

Reduction of leptin precedes fat loss from running exercise in insulin-resistant rats.

Serum concentrations of leptin, a hormone secreted into the circulation by adipocytes, correlate with body mass index. Circulating of leptin is thought to signal the brain in patients with hyperinsulinemia, a condition reported to be preventable and testable by exercise training. In the present experiments, sucrose-fed rats had reduced concentrations of leptin in portal venous blood after 4 weeks of nonforced wheel-running exercise (1.1 +/- 0.1 vs. 6.2 +/- 1.8 ng/mL, in nonexercised sucrose-fed rats, P < 0.05). Mesenteric and subcutaneous fat stores were similar between groups. After 12 weeks of exercise, portal vein levels of leptin concentrations (5.2 +/- 2.1 vs. 9.9 +/- 0.8 ng/mL, P < 0.05) and mesenteric and subcutaneous fat all were reduced in the exercise group. These results suggest that short-term running exercise reduces circulating leptin before any reduction of adipose mass, and this reduction in the concentration of leptin available to its receptors has beneficial effects on the metabolism of fat and carbohydrates.

Adipose Tissue

The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

UNLABELLED: The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. IMPLICATIONS: The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

Adrenergic alpha-Agonists

Common neutralization epitope in minor capsid protein L2 of human papillomavirus types 16 and 6.

Studies of virus neutralization by antibody are a prerequisite for development of a prophylactic vaccine strategy against human papillomaviruses (HPVs). Using HPV16 and -6 pseudovirions capable of inducing beta-galactosidase in infected monkey COS-1 cells, we examined the neutralizing activity of mouse monoclonal antibodies (MAbs) that recognize surface epitopes in HPV16 minor capsid protein L2. Two MAbs binding to a synthetic peptide with the HPV16 L2 sequence of amino acids (aa) 108 to 120 were found to inhibit pseudoinfections with HPV16 as well as HPV6. Antisera raised by immunizing BALB/c mice with the synthetic peptide had a cross-neutralizing activity similar to that of the MAb. The data indicate that HPV16 and -6 have a common cross-neutralization epitope (located within aa 108 to 120 of L2 in HPV16), suggesting that this epitope may be shared by other genital HPVs.

Animals

Nuclear transport of the major capsid protein is essential for adeno-associated virus capsid formation.

Adeno-associated virus capsids are composed of three proteins, VP1, VP2, and VP3. Although VP1 is necessary for viral infection, it is not essential for capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but the functional roles of each protein are still not well understood. By analyzing a series of deletion mutants of VP2, we identified a region necessary for nuclear transfer of VP2 and found that the efficiency of nuclear localization of the capsid proteins and the efficiency of virus-like particle (VLP) formation correlated well. To confirm the importance of the nuclear localization of the capsid proteins, we fused the nuclear localization signal of simian virus 40 large T antigen to VP3 protein. We show that this fusion protein could form VLP, indicating that the VP2-specific region located on the N-terminal side of the protein is not structurally required. This finding suggests that VP3 has sufficient information for VLP formation and that VP2 is necessary only for nuclear transfer of the capsid proteins.

Amino Acid Sequence

C-Reactive protein in dilated cardiomyopathy.

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5-8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1. 05 +/- 1.37 vs. 0.49 +/- 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.

Adult

Sudden death with malignant hemangioendothelioma originating in the pericardium--a case report.

The authors report a rare case of a malignant hemangioendothelioma (MH) originating in the pericardium. In this case, a metastatic skin lesion was found first, and subsequently the existence of a primary cardiac lesion was confirmed. Generally, primary cardiac tumors grow slowly, and the prognosis of MH is relatively good. In this case, however, the patient died suddenly during the creation of a pericardial window for drainage. An autopsy showed that the MH originated from a pericardial lesion in the right atrium.

Death, Sudden

Loculated pericardial effusion due to congestive heart failure: an unusual case of vanishing tumor--a case report.

Loculation of a pleural effusion within an interlobar fissure as a result of congestive heart failure is a well-known entity. It has been termed "vanishing" or "phantom" tumor because its roentgenographic appearance simulates a pulmonary tumor and resolves with treatment of the congestive heart failure. The authors describe an 89-year-old man with a loculated pericardial effusion on the left cardiac border on chest roentgenogram. This was initially thought to represent an occult metastatic malignancy; however, its etiology became obvious when it disappeared with therapy of heart failure. Loculated pericardial effusion should be included in the differential diagnosis of roentgenographic densities in the chest when seen on the left cardiac border.

Aged

Arterial blood gas levels and cardiovascular function during varying environmental conditions in a mudskipper, periophthalmodon schlosseri

Changes in blood gas levels, blood pressure and heart rate were studied in chronically cannulated mudskippers, Periophthalmodon schlosseri, subjected to air exposure (6 h), aquatic hypoxia with access to air (water PO2 <0.9 kPa, 6 h) and forced submersion in normoxic water (12 h) at 30 degrees C. Air exposure did not affect either blood O2 and had little effect on blood CO2 levels, but blood pH increased slightly, but significantly. Blood ammonia concentration was elevated sixfold during air exposure. Aquatic hypoxia caused no significant changes in blood gas levels. When the fish was forcibly submerged, blood O2 saturation decreased rapidly to approximately 30 %. Blood PCO2 and total CO2 also decreased, but blood pH was unaffected by forcible submersion. Air exposure did not affect blood pressure or heart rate. Aquatic hypoxia did not affect blood pressure but transiently increased heart rate. In contrast, forced submersion significantly depressed heart rate throughout the period of submersion, while blood pressure decreased only transiently. Upon emersion, the heart rate immediately increased to above the control level when the fish took its first air breath.

Journal Article

Glycyrrhizin protects mice from concanavalin A-induced hepatitis without affecting cytokine expression.

The administration of concanavalin A (Con A) to mice induces cytokine-dependent hepatitis. In the present study, the effect of glycyrrhizin on Con A-induced hepatitis was examined. Treatment of mice with Con A (0.2 mg/mouse, i.v.) induced elevation of the plasma transaminase activities at 24 h. Mice were treated with glycyrrhizin (100, 200 and 400 mg/kg, i.p.), and glycyrrhizin at the doses of 200 and 400 mg/kg inhibited the Con A-induced elevation of the plasma transaminase activities. At 1 h after Con A treatment, interferon-gamma, tumor necrosis factor-alpha, interleukin-2 and interleukin-6 proteins were released into the plasma. Although treatment with glycyrrhizin at 200 mg/kg inhibited Con A-induced hepatitis, it did not affect the release of any of these Con A-induced cytokines into the plasma. The present results clearly show that glycyrrhizin inhibited Con A-induced hepatitis without affecting cytokine expression.

Alanine Transaminase

Long lasting chronic hepatitis is accompanied by cyclin D1 gene expression in the mouse.

The interferon-gamma (IFN-gamma) transgenic mouse expresses the IFN-gamma gene strongly in the liver and develops chronic hepatitis from 6-10 weeks of age. Previously we reported the detection of hepatocyte apoptosis and the expression of the Fas system in the transgenic mouse liver. The objective of the present study was to examine the possible development of favorable conditions for predisposing cells to malignancy. The connection between the cell cycle and cancer has become evident, and the relation of cyclin D1 (CD1) with hepatocellular carcinomas has been strengthened. In the liver of transgenic mice of 48 weeks of age, c-myc and CD1 gene expression was induced, indicating progression of the cell cycles. p21 gene expression in the transgenic mouse liver might counteract cell-cycle progression promoted by c-myc and CD1. In the liver of 8-week-old transgenic mice, expression of c-myc mRNA was correlated with the levels of plasma transaminase activities. In these 8-week-old transgenic mice, however, CD1 mRNA was not induced, regardless of the progression of hepatitis. Based on these results, we conclude that long lasting hepatitis may lead to favorable conditions for predisposing cells to malignancy.

Animals

Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis.

We investigated apoptosis and Bcl-2 expression in 221 advanced gastric carcinomas in correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis, using the in situ DNA nick end labeling method and immunohistochemistry. Apoptosis was associated with high immunoreactivity of proliferating cell nuclear antigen. Bcl-2 expression correlated with a low apoptotic index and less malignant behavior of tumors. Prognostically, Bcl-2 expression was associated with a better prognosis, whereas p53 expression was the most important prognostic risk factor. Thus, apoptosis in gastric carcinomas is associated with cell proliferation, and Bcl-2 expression may have a prognostic importance as well as p53 expression.

Apoptosis

Extended radical esophagectomy for superficially invasive carcinoma of the esophagus.

BACKGROUND: The purpose of the study was to determine whether extended radical esophagectomy is both clinically and oncologically indicated for patients with superficially invasive esophageal carcinomas. METHODS: We reviewed 51 patients with this disease in whom extended radical esophagectomy was performed. RESULTS: Major morbidity developed in 80% of the patients associated with no mortality after the operation. At surgery lymph node metastases were found in 29 patients (57%). Although the number of positive nodes was 3 or less in 93% of those patients, the tumors metastasized not only to the mediastinal nodes but also to the cervical and abdominal nodes, frequently jumping the first echelon of nodes. The overall 5-year survival rate was 68%. The survival curve of the patients with positive nodes was significantly worse (P < .01) than that of patients with negative nodes: the respective 5-year survival rates were 47% and 93%. However, no significant difference was detected between the survival curves of the patients with cervical metastases and those with noncervical metastases. CONCLUSIONS: Extended radical esophagectomy is needed for complete tumor clearance and may be effective in improving the rate of cure in patients with superficially invasive esophageal carcinoma. However, patients should be selected carefully for the performance of extended radical esophagectomy because this procedure is potentially associated with high morbidity rates.

Adult

[Congestive heart failure due to a combination of atrial fibrillation and tricuspid regurgitation: clinical course and echocardiographical analysis].

The combination of atrial fibrillation (Af) and tricuspid regurgitation (TR) may induce the congestive heart failure (HF) due to insufficient output. However, these associations have not been elucidated. We examined the clinical course with echocardiographic data in 119 patients with Af and/or TR and/or HF. Their mean age was 65 +/- 14 years. The patients were classified into 6 groups as follows: Group I contained patients with Af, TR and HF(n = 13); Group II contained patients with Af and TR, without HF(n = 59); Group III contained patients with TR and HF, without Af(n = 15); Group IV contained patients with TR and without AF and HF(n = 15); Group V contained patients with Af and HF, without TR(n = 24); Group VI contained patients with Af and without TR and HF(n = 13). The fractional shortening and ejection fraction in Group I and II were significantly (p < 0.05) decreased compared to Group IV. Moreover, the fractional shortening in Group V was significantly (p < 0.05) lower than in Group IV. Among 72 cases in Group I and II, 24 cases were followed by echocardiography for 2 to 5 years. Eight cases of HF exhibited a no HF state and 1 demonstrated had the HF state. All 9 cases (38%) showed a decreased heart rate and no alternation of TR. Four of the 24 patients (17%) had developed worsened TR and a lowered ejection fraction but none developed them became HF. Therefore, tachycardia may be an accelerative factor for HF due to the combination of Af and TR, not due to the grade of TR.

Aged