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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 55 records · Page 3Linked to original sources

Comparative immunochemical study of lectin-binding sites and cytoskeletal filaments in static and reactive mesothelium and adenocarcinoma.

In cytological preparations, reactive mesothelial cells (RMC) in serous effusions are sometimes difficult to distinguish from adenocarcinoma cells (AC). RMC and AC can be distinguished by lectin-binding patterns, but the pattern of binding of lectins to normal mesothelium is not well defined. We investigated the expression of cytoskeletal filaments, cytokeratin (CK) and vimentin (VM), and the cell surface binding pattern of 10 lectins (HPA, SBA, ABA, DSA, PNA, RCA-I, UEA-I, LTA, WGA and ConA) in the serosa of 48 adenocarcinoma specimens. We also investigated the usefulness of six lectins (HPA, SBA, RCA-I, UEA-I, LTA and WGA) in identification of RMC and AC in 16 serous effusions. DSA reactivity was significantly higher (P < 0.05) in static mesothelial cells (SMC) than in RMC. Reactivity for LTA and ConA was significantly lower (P < 0.05) in SMC than in RMC. Anti-CK and anti-VM immunoreactivity was always positive in RMC and almost negative in SMC. In serous effusions, HPA, SBA and UEA-I binding was evident in 100, 88 and 81% of AC, respectively. Little to no binding of HPA, SBA or UEA-I was detected in RMC. Our results suggest that the morphological differences between SMC and RMC are likely to be due to differences in cytoskeletal composition, with accompanying changes in cell-surface lectin-binding patterns. HPA, SBA and UEA-I are likely to be useful markers for identification of RMC and AC in cytology.

Adenocarcinoma↗

Inhibition of Ras extracellular-signal-regulated kinase (ERK) mediated signaling promotes ciliary neurotrophic factor (CNTF) expression in Schwann cells.

Ciliary neurotrophic factor (CNTF) can prevent injury-induced motor neuron death. However, it is also evident that expression of CNTF in Schwann cells is suppressed during nerve regeneration. In this report, we have addressed the mechanism underlying the down-regulation of CNTF expression in injured nerves using a mouse Schwann cell line IMS32 and mouse sciatic nerve. In IMS32 cells, activation of the Ras extracellular-signal-regulated kinase (ERK) pathway by adenoviral vector-mediated expression of dominant active MEK1 did not alter a basal level of CNTF expression, whereas inhibition of the Ras-ERK pathway by using adenoviral vectors resulted in a marked increase in CNTF expression. This inverse relation between before and after axotomy was also observed in mouse sciatic nerve. In the axotomized sciatic nerve, the phosphorylated ERK was markedly increased; in contrast, the expression of CNTF was markedly decreased. These findings suggest that an inactive state of ERK is crucial for the CNTF expression in Schwann cells, and that activation of ERK following nerve injury critically influences the expression of CNTF. This might well explain why CNTF is highly expressed in quiescent Schwann cells in the peripheral nervous system, and also why CNTF is not abundant in axotomized nerves or cultured Schwann cells in which the proliferation signal is obviously active.

Adenoviridae↗

Glucocorticoids induce basophil apoptosis.

BACKGROUND: Induction of apoptosis represents an important mechanism by which glucocorticoids (GCCs) exert their anti-inflammatory properties. The effects of GCCs on apoptosis have been determined in various immune cells and found to vary among different cell types. On the other hand, the effects of GCCs on apoptosis of basophils, active participants in allergic inflammation, have remained obscure. OBJECTIVE: The objective of this study was to investigate the effects of GCCs on basophil apoptosis. METHODS: Basophils were highly purified (purity, >97%) by Percoll density gradient centrifugation followed by negative selection. Cell status was determined by their ability to bind annexin V and exclude propidium iodide. DNA fragmentation was determined by flow cytometry. RESULTS: Dexamethasone (DEX) significantly accelerated the decrease in live cells and increased the number of apoptotic cells in a time-dependent fashion. Light microscopy as well as DNA fragmentation assay confirmed the induction of apoptosis by DEX. A half-maximal effect was observed in a DEX concentration range from 10(-9) to 10(-8) mol/L. Sex steroids did not induce basophil apoptosis at all. DEX also induced basophil apoptosis in the presence of low doses of IL-3. CONCLUSION: GCCs exert potent apoptogenic effects on basophils. GCC-mediated apoptogenic effects on basophils might have implications with respect to the mechanism of action of this class of drugs in allergic disorders.

Apoptosis↗

Amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

We investigated the effects of i.v. amrinone on intraoperative changes of core temperature during deliberate mild hypothermia for neurosurgery. The patients in a control group (n=10) did not receive amrinone and patients in the amrinone group (n=10) received amrinone 5 microg kg(-1) min(-1) after a loading dose of 1.0 mg kg(-1). Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. After the induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were rewarmed in the operating room. Tympanic membrane temperatures between 30 and 90 min after cooling were significantly lower in the amrinone group than in the control group. During cooling, the times taken to cool to 35 degrees C and to the lowest temperature were significantly shorter in the amrinone group than in the control group. These results suggest that i.v. amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

Amrinone↗

Crystallization and preliminary X-ray analysis of (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis.

Dimeric (R)-specific enoyl-coenzyme A (CoA) hydratase from Aeromonas caviae catalyzes the hydration of trans-2-enoyl-CoAs with carbon lengths of 4-6 to yield their corresponding (R)-3-hydroxyacyl-CoAs and is essential for polyhydroxyalkanoate (PHA) biosynthesis. The enzyme has been crystallized by vapour diffusion against a reservoir solution containing 20% polyethylene glycol 4000, 5% 2-propanol and 20 mM HEPES pH 7.0 at 298 K. Crystals belong to the monoclinic space group C2, with unit-cell parameters a = 111.54 (3), b = 59.29 (1), c = 47.27 (4) A, beta = 113.04 (2) degrees and contain a dimeric molecule in the asymmetric unit. Flash-cooling of a crystal at 100 K alters its unit-cell parameters to a = 109.82 (7), b = 57.98 (6), c = 46.84 (2) A, beta = 112.71 (3) degrees. Native data to a resolution of 1.7 A have been collected with 94.5% completeness and an R(merge) of 4.0% under cryogenic (100 K) conditions using synchrotron radiation.

Aeromonas↗

The genetic factor in acute myocardial infarction with hypertension.

This study assessed the contribution of polymorphisms of angiotensin II (AngII) receptors and bradykinin B2 (BK-B2) receptor to hypertension and acute myocardial infarction (AMI) in a Japanese population: 150 subjects with essential hypertension, 150 subjects with AMI with/without hypertension, and 150 healthy, age- and sex-matched controls. Polymorphisms of the AngII type 1 receptor (1166 A/C) and type 2 receptor (3123 C/A), and the BK-B2 receptor (-58T/C, exon 1) were analyzed and significant differences of genotypes and allelic frequencies in the AngII type 2 receptor C/A and BK-B2 receptor -58T/C were found between the essential hypertension and control subjects. Further, a significantly higher incidence of the C allele of the BK-B2 receptor was seen in AMI subjects with hypertension compared with those without hypertension. Genetic variations in the AngII and BK-B2 receptors could prove to be significant pathophysiological mechanisms affecting essential hypertension and AMI, and genetic differences appear to be a new risk factor for these conditions.

Adult↗

Enhancement of epsilon-polylysine production by Streptomyces albulus strain 410 using pH control.

The enhancement of epsilon-poly-l-lysine (epsilon-PL) production by Streptomyces albulus strain no. 410 (S410) by means of a pH control strategy was investigated. S140 cells produce epsilon-PL at a high concentration if the culture pH remains at about 4.0; however, if it shifts to higher than 4.0, the accumulated epsilon-PL is depolymerized. We therefore suggest a pH control strategy for cell growth and epsilon-PL production aimed at increasing the amount of epsilon-PL produced. The cultivation was divided into two control phases. In phase I, cell growth was accelerated by maintaining the pH at higher than 5.0; in phase II, epsilon-PL production was increased by maintaining the pH at about 4.0. To avoid an increase in the pH during phase II as a result of glucose depletion, the glucose concentration was kept at around 10 g/l by glucose feeding. This control strategy enhanced the production of epsilon-PL to 48.3 g/l from 5.7 g/l in the case of batch culture.

Journal Article↗

Genetic background in patients with acute myocardial infarction.

The renin-angiotensin system is believed to play important roles in the development of acute myocardial infarction, and gene polymorphisms may also be involved. To investigate the genetic background in patients with acute myocardial infarction, we performed a case control study in a Japanese population. The study included 150 patients with acute myocardial infarction and 150 healthy, age- and sex-matched controls. We examined polymorphisms of angiotensin II type 1 receptor (1 166 A / C), type 2 receptor (3123 C / A), and bradykinin B2 receptor (-58 T / C) in these subjects. The allelic frequencies of angiotensin II type I receptor C and angiotensin II type 2 receptor A were significantly higher in the acute myocardial infarction subjects than in the control subjects, and this tendency was more significant in the younger patients. The combined ratios of angiotensin II type 1 receptor C and type 2 receptor A alleles in patients under 64 years old were significantly higher than in their older counterparts. However the total numbers of conventional coronary risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) in individual subjects were not significantly different between younger and older patients. These polymorphisms were found to be involved in the development of acute myocardial infarction, particularly in the younger patients, and it was concluded that the incidence of acute myocardial infarction might be reduced by management from the genotypes.

Aged↗

Elimination of the uninformative calibration sample subset in the modified UVE(Uninformative Variable Elimination)-PLS (Partial Least Squares) method.

In order to increase the predictive ability of the PLS (Partial Least Squares) model, we have developed a new algorithm, by which uninformative samples which cannot contribute to the model very much are eliminated from a calibration data set. In the proposed algorithm, uninformative wavelength (or independent) variables are eliminated at the first stage by using the modified UVE (Uninformative Variable Elimination)-PLS method that we reported previously. Then, if the prediction error of the ith (1 < or =i< or = n) sample is larger than 3sigma, the corresponding sample is eliminated as uninformative, where n is the total number of calibration samples and sigma is the standard deviation calculated from the other n(-1) samples. Calculation of sigma by the leave-one-out manner enhances the ability to identify the uninformative samples. The final PLS model is constructed precisely because both uninformative wavelength variables and uninformative samples are eliminated. In order to demonstrate the usefulness of the algorithm, we have applied it to two kinds of mid-infrared spectral data sets.

Journal Article↗

[An elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia].

We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.

Aged↗

Application of the piezo-micromanipulator for injection of embryonic stem cells into mouse blastocysts.

Microinjection of embryonic stem (ES) cells into mouse blastocysts is one of the most important techniques for production of knockout or transgenic mice. However, skillful manipulation techniques and tremendous effort are required for this method. To overcome this difficulty, we applied a piezo-micromanipulator (PMM), which has been used for intracytoplasmic sperm injection in mice and production of cloned mice, for the injection of ES cells into blastocysts. When ES cells were injected by using a conventional method, 91% of the blastocysts were manipulated successfully. Using the PMM significantly (P < 0.01) increased the success rate of ES injection to 97%. The number of embryos manipulated in an hour increased from 9.7 embryos with the conventional method to 27.0 embryos with the PMM method. The injected ES cells did not show any detrimental effects due to a pulse from the PMM. After embryo transfer of the manipulated blastocysts, 39% of the newborns were chimeric mice with the conventional method, whereas 42% of the neonates were chimeric after the PMM method. These results indicate that microinjection of the ES cells into blastocysts is more efficient by the PMM method than the conventional method.

Animals↗

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Amino Acid Sequence↗

Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice.

Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein that specifically binds alpha-tocopherol, is known as a product of the causative gene in patients with ataxia that is associated with vitamin E deficiency. Targeted disruption of the alpha-TTP gene revealed that alpha-tocopherol concentration in the circulation was regulated by alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile; however, placentas of pregnant alpha-TTP(-/-) females were severely impaired with marked reduction of labyrinthine trophoblasts, and the embryos died at mid-gestation even when fertilized eggs of alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients. The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653) dietary supplement by alpha-TTP(-/-) females prevented placental failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals, alpha-TTP gene expression was observed in the uterus, and its level transiently increased after implantation (4.5 days postcoitum). Our results suggest that oxidative stress in the labyrinth region of the placenta is protected by vitamin E during development and that in addition to the hepatic alpha-TTP, which governs plasma alpha-tocopherol level, the uterine alpha-TTP may also play an important role in supplying this vitamin.

Animals↗