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Biomedical subjects

S Itoh

Publications and source records attributed to S Itoh.

At least 127 records · Page 7Linked to original sources

Cytokine profile of liver-infiltrating CD4+ T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reaction.

BACKGROUND AND METHODS: We have previously reported that CD4+ T cells induced primary biliary cirrhosis (PBC)-like hepatic lesions in mice with graft-versus-host reaction due to major histocompatibility complex class II disparity. To clarify the relationship between the cytokine profile produced by CD4+ T cells and the formation of hepatic lesions, we sorted CD4+ T cells from the liver by using flow cytometry and examined their cytokine mRNA expression at various times after GVHR induction. We also examined the associated changes in the serum levels of antimitochondrial antibodies (AMA). RESULTS: Histologically, the infiltration of CD4+ T cells around the bile ducts was observed from day 5, and the lesions deteriorated gradually until day 14. On day 14, CD8+, B220+ and Mac-1+ cells, as well as CD4+ T cells were seen around the bile ducts. In the liver-infiltrating CD4+ T cells, the expression level of interferon-gamma (IFN-gamma) mRNA was observed to increase at an early phase (day 3), whereas that of interleukin (IL)-10 mRNA was elevated at a later phase (day 14). The elevation of IFN-gamma mRNA expression at an early phase before the appearance of non-suppurative destructive cholangitis suggests that IFN-gamma may be related to the pathogenesis of PBC in this model. Serum levels of AMA on day 14 were significantly higher than those on day 5. Interleukin-10 was considered to stimulate antibody production, to show an inhibitory effect upon the function of T helper 1 cells, and to inhibit fibrosis. CONCLUSIONS: Interferon-gamma may play an important role in the pathogenesis of this model. Moreover, delayed expression of IL-10 mRNA may control PBC-like hepatic lesions.

Animals↗

Formation of propentdyopents and biliverdin, oxidized metabolites of bilirubin, in infants receiving oxygen therapy.

BACKGROUND: Bilirubin has antioxidative effects. When bilirubin reacts with reactive oxygen species, oxidized metabolites of bilirubin are formed, such as biliverdin and propentdyopents. A decrease in serum bilirubin concentration and an increase in serum and urinary oxidized metabolites of bilirubin may indicate the protective action of bilirubin against reactive oxygen species. METHODS: In the in vitro study, we measured the oxidative products of bilirubin formed through the action of O2- by the xanthine-xanthine oxidase system, either as free bilirubin or bilirubin-human serum albumin complex. In the clinical investigation, serum concentrations of (ZZ)-bilirubin (4Z, 15Z-bilirubin), the subfraction and biliverdin, and urinary propentdyopent absorption, were measured in blood and urine samples, respectively, collected from 30 5-day-old neonates with birth weights of 1500-3624 g who had been hospitalized at the Ehime Prefectural Hospital and who had not undergone phototherapy. RESULTS: In the in vitro study, a significant formation of propentdyopents was observed in aqueous solution. A statistically significant correlation was found between serum (ZZ)-bilirubin concentration and serum biliverdin concentration (r = 0.82, P < 0.0001), but not between serum (ZZ)-bilirubin concentration and urinary propentdyopent absorption. Serum (ZZ)- and serum (ZE)-bilirubin and biliverdin concentrations, and urinary propentdyopent absorption were compared between the groups with and without oxygen therapy. No significant differences were found in serum (ZZ)-bilirubin, serum (ZE)-bilirubin and biliverdin concentration, urinary propentdyopent absorption, serum biliverdin/serum (ZZ)-bilirubin, or urinary propentdyopent absorption/serum (ZZ)-bilirubin. Neither a decrease in serum bilirubin concentration nor an increase in serum biliverdin concentration and urinary propentdyopent absorption after oxygen therapy were demonstrated in the present study. CONCLUSIONS: In the in vitro study, we demonstrated for the first time that propentdyopents were produced from (ZZ)-bilirubin by the xanthine-xanthine oxidase system but biliverdin was not. In the in vivo study, serum biliverdin concentration and urinary propentdyopent absorption seem to have a different relationship to serum (ZZ)-bilirubin concentration in sick and early neonates.

Bilirubin↗

Dilation and reduced distensibility of carotid artery in patients with abdominal aortic aneurysms.

BACKGROUND: Although patients with abdominal aortic aneurysms (AAA) frequently have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is the opposite of the occlusion characteristic of atherosclerotic disease. It has been suggested that this dilatative disease is caused by an alteration in connective tissue metabolism in systemic arterial wall. Such a condition might alter systemic arterial diameter and wall behavior. We investigated arterial characteristics in AAA patients, including morphologic changes and wall mechanics in the carotid artery. METHODS AND RESULTS: Atherosclerotic intimal changes such as intima-media thickness (IMT), plaque formation, diameter, and wall elasticity of the carotid artery were determined ultrasonographically in patients with AAA (n = 102) and compared with age-matched patients with the atherosclerotic diseases arteriosclerosis obliterans (ASO, n = 115) and coronary artery disease (CAD, n = 123) and with age-matched healthy control patients (CTL, n = 45). Intimal disease in AAA was significantly milder than in ASO, at the same level as CAD, and more severe than in CTL. Although end-diastolic luminal diameters (mm) in AAA (7.05 +/- 1.08), ASO (6.74 +/- 0.18), and CAD (6.66 +/- 0.83) were significantly higher than in CTL (5.97 +/- 0.93), they were also excessively increased compared with the equivalent diameters seen in ASO (P <.01) and CAD (P <.01). Luminal distensibility (x 10(-6) cm(2). dyne(-1)) in AAA (0.83 +/- 0.48) was excessively decreased compared not only with CTL (1.70 +/- 1.11, P <.01) but also with ASO (1.12 +/- 0.47, P <.01) and CAD (1.18 +/- 0.59, P <. 01). These relations remained true when adjusted for blood pressure and luminal diameter. Intra-AAA group analysis showed that distensibility in ruptured cases (n = 14) was significantly lower than in nonruptured cases (n = 88) (0.58 +/- 0.24 vs 0.88 +/- 0.50, P <.05). CONCLUSIONS: Excessive arterial dilation and reduced distensibility without severe intimal disease were found in the carotid arteries of patients with AAA. This suggests that these patients may be subject to systemic arterial alterations, including structural and functional abnormalities.

Aged↗

The effects of the ALDH2*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination.

The effects of CYP2E1 genotypes on the blood ethanol and acetaldehyde levels were investigated in a pair of Japanese volunteers whose ADH2, ADH3 and ALDH2 genotypes were identical but whose CYP2E1 genotypes were different. In the same way, the effects of ALDH2 and ADH2 on the ethanol elimination kinetics were also studied. The predicting 95% confidence bounds determined on regression analysis of the data suggested that after venous injection of ethanol, the blood ethanol and acetaldehyde concentrations in a volunteer normal homozygous for ALDH2 (ALDH2*1/1) were lower than in a heterozygous one (ALDH2*1/2). Also, the blood ethanol and acetaldehyde concentrations in a volunteer with the c2 and C alleles of CYP2E1 (c1/c2 and C/D) were lower than in one without the c2 and C alleles (c1/c1 and D/D). However, there were no significant differences in the blood ethanol and acetaldehyde concentrations between volunteers with ADH2*1 (ADH2*1/1) and without ADH2*1 (ADH2*1/2).

Acetaldehyde↗

Image quality improvement using helium gas in low voltage variable pressure scanning electron microscopy.

An effective combination of the low voltage and variable pressure (VP) scanning electron microscopy (SEM) are discussed. In low voltage VP-SEM, helium gas is utilized for reducing the amount of scatter of the primary electron beam. Most samples can receive various benefits obtained from the combination of low voltage and low vacuum observation. Compared to a back-scattered electron (BSE) image in air, signal-to-noise ratio (SNR) of a BSE image taken with helium gas is 5.4 times under a pressure of 50 Pa and an accelerating voltage of 1.5 kV.

Letter↗

Selective extraction of antenna chlorophylls, carotenoids and quinones from photosystem I reaction center.

By the ether treatment of lyophilized PSI pigment-protein complexes, all the carotenoids and the secondary acceptor phylloquinone (A1), and more than 90% of the Chl were removed to yield the PSI complex with 9-11 molecules of Chl per reaction-center unit. The complexes retained the primary electron donor and acceptor (P700 and A0), in addition to three FeS clusters (F(X), F(A) and F(B)), and showed an activity of highly efficient electron transfer when phylloquinone was reconstituted. The methods for the preparation and the characterization of the ether-extracted PSI complexes are reviewed in this article. We also review the studies done with this PSI preparation on (1) the identification of the absorption and fluorescence spectra of P700, (2) the nano- and picosecond reaction of A0 and A1, (3) the energy-gap dependency of the reaction rate between A0 and the artificial quinones reconstituted at the A1 site, (4) the direct excitation of P700 followed by the ultra-fast electron transfer from P700 to A0, and (5) the de- and re-stabilization of the PSI structure by the removal and reconstitution, respectively, of antenna Chl in the presence of certain lipids.

Carotenoids↗

Energy correction for isolated impurities under periodic boundary conditions

The Coulomb energy of aperiodic systems was investigated. To treat completely isolated disorder in infinite systems, energy correction for a supercell method is presented. We discuss a definition of the correction term, and then consider a direct approach taking into account interactions between charge distribution and an indirect approach based on a multipole expansion. In test calculations for isotropic-charged, anisotropic-charged, and neutral impurities, impurity energies independent of supercell sizes were obtained. The present energy correction can be applied to arbitrary systems and is expected to realize more practical simulations for aperiodic systems.

Journal Article↗

Changes in cerebral hemoglobin concentration and oxygen saturation immediately after birth in the human neonate using full-spectrum near infrared spectroscopy.

Using full-spectrum near infrared spectroscopy (fsNIRS), we measured changes in oxy- and deoxyhemoglobin (HbO2 and Hb), total hemoglobin (T-Hb) concentration, and hemoglobin oxygen saturation (SbO2) in the brain tissue of seven neonates immediately following birth. It was found that HbO2 rose rapidly within 2-3 min after birth. During the same time, there was a transient increase in T-Hb concentration, after which it decreased together with Hb. SbO2 increased rapidly after birth, from 18% at 1.5 min to about 55% at 5-6 min, followed by a gradual increase of about 10%. Oxygenation in the brain occurred much sooner in three subjects given oxygen for a short time immediately after birth than in those who did not receive oxygen. This preliminary study indicated that dynamic changes occur in cerebral circulation and oxygenation as part of the physiological changes taking place soon after birth.

Brain↗

Synthetic modification of prostaglandin f(2alpha) indicates different structural determinants for binding to the prostaglandin F receptor versus the prostaglandin transporter.

Several principles governing the binding of E series prostaglandins to EP receptors have emerged in recent years. The C-1 carboxyl group binds electrostatically to a conserved arginine residue in the seventh transmembrane segment of the receptor. Prostaglandin E analogs involving bioisosteric replacements of the carboxyl group, such as acylsulfonamide, are also active. In addition, structurally similar esters may also exhibit similar affinity, presumably by virtue of hydrogen bonding. Other regions of the substrate molecule appear to bind to other domains of EP receptors, either via hydrophobic interactions or by hydrogen bonding. Less information is available about the structural requirements for substrate binding to FP receptors. Prostanoids also bind to the prostaglandin transporter PGT. In this case, a conserved C-1 carboxyl group is critically important, since C-1 esters exhibit little affinity. Here we examined the binding of chemically diverse PGF(2alpha) structural analogs to the FP receptor and compared these with binding by the PG transporter. PGT recognized a wide range of anionic substituents. In contrast, the carboxylic acid group was essential for optimal binding to the FP receptor, since replacement by larger moieties with a similar pK(a), such as acylsulfonamide and tetrazole, substantially decreased binding affinity. Interestingly, insertion of cyclic substituents in the omega chain increased binding to the FP receptor but reduced affinity for PGT, and substitution for the 15-hydroxyl group produced only a modest reduction in FP receptor binding, but eliminated binding by PGT. Because extracellular PGF(2alpha) may compete for binding between FP receptors and PGT, these findings have implications for designing PGF(2alpha) analogs for treating disease states.

Animals↗

Lung cancer screening: minimum tube current required for helical CT.

PURPOSE: To investigate the minimum tube current required for helical computed tomography (CT) for lung cancer screening. MATERIALS AND METHODS: Thirty helical scans of the lung were obtained at effective tube currents of 50, 30, 20, 18, 12, 10, and 6 mAs in seven healthy volunteers. Computer-generated nodules 6 mm in diameter that showed ground-glass opacity were superimposed on the images. The image quality and detectability of nodules were evaluated subjectively by six observers. The SDs of measured CT numbers were calculated. The results were analyzed according to location in the lung. RESULTS: Compared with the subjective quality of images obtained at 50 mAs, the subjective quality of images obtained at 20 mAs was not significantly different. The detectability of nodules was not significantly degraded by reducing the tube current to 20 mAs in the upper zone of the lung, to 12 mAs in the middle zone, or to 18 mAs in the lower zone. The SDs at the apex and base of the lung were larger than those at other levels, and the difference became greater as the dose was reduced. CONCLUSION: The minimum tube current required for screening helical CT differs for different locations in the lung. An ideal CT protocol for the lung should permit the tube current to be changed during helical scanning.

Adult↗

Bradykinin B(2) receptor gene polymorphism is associated with angiotensin-converting enzyme inhibitor-related cough.

The appearance of cough in association with angiotensin-converting enzyme (ACE) inhibitors is thought to be related to bradykinin, and it has been speculated that the elicitation of adverse effects is genetically predetermined. Several polymorphisms of the human bradykinin B(2) receptor gene may be involved in ACE inhibitor-related cough. To investigate this possibility, we identified the -58 thymine (T)/cytosine (C) polymorphism in subjects with ACE inhibitor-related cough. We classified the study population into 4 groups: subjects with and without cough that were treated with ACE inhibitors (n=30/30), nontreated essential hypertensive subjects (n=100), and normotensive subjects (n=100). The -58T/C was genotyped by the polymerase chain reaction single-strand conformation polymorphism method. The frequencies of the CC genotype and C allele of -58T/C were significantly higher in the nontreated hypertensive subjects than in the normotensive subjects. Conversely, the frequencies of the TT genotype and T allele were significantly higher in the subjects with cough than in the subjects without cough. These tendencies were more pronounced in females. Among the promoter assays of the human bradykinin B(2) receptor, -58T was found to have a higher transcription rate than that of -58C. This finding seems to suggest that the transcriptional activity of promoter might be involved in the appearance of ACE inhibitor-related cough. A genetic variant of the bradykinin receptor is involved in the elicitation of ACE inhibitor-related cough. It may be possible to predict the side effects of ACE inhibitors in advance.

Adult↗

Effects of bilirubin and its photoisomers on direct bilirubin measurement using bilirubin oxidase.

We examined the reactivity of human serum albumin-bound bilirubin and its photoisomers as substrates for a direct bilirubin assay using bilirubin oxidase. The reduction of (EZ)-cyclobilirubin reached 100% 5 min after addition of the enzyme at any pH tested (3.5-7.4) in 0.1 mol/L phosphate buffer, whereas the reduction of (ZE)-bilirubin or (ZZ)-bilirubin reached 100% only below pH 4.5 or 5.5, respectively. (ZZ)-Bilirubin and its photoisomers did not react in citrate-lactate buffer at pH 3.7. The circular dichroism spectrum of (ZZ)-bilirubin in this buffer did not show a positive Cotton effect. These results indicate that a three-dimensional structure surrounding the reaction site of bilirubin is important for the reactivity with bilirubin oxidase.

Bilirubin↗

Chemiluminescence because of the production of reactive oxygen species in the lungs of newborn piglets during resuscitation periods after asphyxiation load.

Reactive oxygen species are regarded as a possible cause of many diseases. However, there are few reports offering in vivo and in situ proof of the direct involvement of reactive oxygen species in the pathogenesis of disease. In the present study, the luciferin derivative 2-methyl-6-[4-methoxyphenyl]-3,7-dihydroimidazo [1,2-alpha] pyrazin-3-one (MCLA) was used to investigate the amount of reactive oxygen species produced during resuscitation after asphyxiation load in newborn piglets. The animals were first asphyxiated by stopping respiration for 4 min, and then resuscitated using 100% oxygen. When physiologic saline solution was administered, lung surface chemiluminescence had a mean value of 2, whereas with MCLA, a maximum luminescence of 580 was seen, demonstrating the possibility of measuring reactive oxygen species in vivo and in situ using MCLA. In a group in which resuscitation after acute asphyxiation was performed with 21% oxygen, the relative maximum lung surface chemiluminescence was 59.5+/-39, whereas that for a group in which resuscitation was performed using 100% oxygen had a significantly higher value of 186.1+/-72.5. Consequently, ventilation and especially resuscitation by 100% oxygen may represent a potential danger.

Animals↗

Toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome--four case reports.

Four patients, all males aged 40-64 years, presented with toxoplasmic encephalitis associated with human immunodeficiency virus (HIV) infection manifesting as nonspecific neurological deficits such as epilepsy or hemiparesis. Magnetic resonance imaging showed single or multiple lesions with ring enhancement, mimicking metastatic brain tumor or brain abscess. Marked eosinophilia was noted in three patients. Two patients who received anti-toxoplasma chemotherapy in the early stage had a good outcome. However, the other two patients suffered rapid neurological deterioration and needed decompressive surgery, resulting in a poor outcome. Toxoplasma diffusely infects the whole central nervous system from the early stage. The outcome for patients who needed emergency surgery was poor. Therefore, this rare but increasingly common infectious disease must be considered in the differential diagnosis of a patient with neuroimaging findings similar to those of metastatic tumor or brain abscess. Appropriate chemotherapy should be started immediately after HIV-positive reaction is identified in patients with single or multiple mass lesions with ring enhancement.

AIDS Serodiagnosis↗

XYY male with essential thrombocythemia in childhood.

We describe a boy with XYY male accompanied with essential thrombocythemia. This is, to our knowledge, the first complete case report of the kind in the pediatric literature. The patient was asymptomatic, but at age 5 his platelet count had increased to 145.5 x 10(4)/microL, and he was diagnosed as having essential thrombocythemia based on the diagnostic criteria of the Polycythemia Vera Study Group. At that time, it was discovered by chromosome analysis of both bone marrow and peripheral blood cells that he was XYY male. At times during the clinical course when his platelet count was 94.1 x 10(4)/microL, his serum thrombopoietin (measured by enzyme-linked immunosorbent assay) was 1.09 fmol/mL, which was normal for his age. Aspirin was administered, and he remained asymptomatic throughout the course. After 2 years, he underwent a spontaneous remission. Because of the small number of reported cases, we have been unable to determine the relation between XYY males and essential thrombocythemia.

Aspirin↗

Mutations of the WASP gene in 10 Japanese patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency, and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study, we identified mutations of the WASP gene in 10 Japanese patients from 9 unrelated families with WAS/XLT. All XLT patients (n = 3) and one WAS patient had a missense mutation at the PH domain of WASP. Two WAS patients had nonsense mutations. One WAS patient had exon 8 skipping caused by one nucleotide deletion at the acceptor site of intron 7. Three WAS patients had genomic deletions; one of the three had a large genomic deletion involving exons 3 to 7. Codons 45 and 86 seem to be the hot spots of the WASP mutation, because missense mutations in these codons have been reported previously in several WAS/XLT patients in addition to the patients in this report, and patients with the same mutation show a similar clinical phenotype. All other mutations are novel, indicating that the mutations of WASP are heterogeneous. EB virus-transformed cell lines from XLT patients expressed nearly normal amounts of WASP, whereas those from typical WAS patients expressed almost undetectable amounts of WASP. We conclude that the analysis of gene mutation and protein expression of WASP are useful together in assessing the severity of WAS.

Adult↗

Successful treatment of disseminated Fusarium infection in an infant with leukemia.

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.

Amphotericin B↗