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Biomedical subjects

T Ihara

Publications and source records attributed to T Ihara.

At least 91 records · Page 5Linked to original sources

[Four cases of hemolytic uremic syndrome (HUS) associated with serotype O165 verotoxin producing Escherichia coli (VTEC) identified by LPS-solid phase enzyme-linked immunosorbent assay (ELISA)].

Enzyme-linked immunosorbent assay using LPS derived from newly recognized serotype O165 verotoxin producing Escherichia coli (VTEC) could identify 4 cases of hemolytic uremic syndrome (HUS) associated with O165 VTEC. All 4 cases showed a typical clinical course seen in VTEC-associated HUS. We screened 33 cases of HUS whose pathogen was not identified by culture of serodiagnosis. The O165 serotype was not thought to be important not only as a VTEC but also as an enteropathogenic E. coli. However, the prevalence, 4 cases, was as high as of O111 serotype, which is the second major serotype of VTEC in Japan. We have to be careful for this serotype when we look for the pathogen of the patients with hemorrhagic colitis or with HUS.

Bacterial Toxins↗

Extraction of water-soluble vitamins from pharmaceutical preparations using AOT (sodium di-2-ethylhexyl sulfosuccinate)/pentane reversed micelles.

Reversed micelles can be used to concentrate water-soluble materials in the water pool. In this study, the extraction of water-soluble vitamins into reversed micelles was attempted, and a flow system was used to determine the time-course of the vitamin extraction. The efficiency of extraction was strongly affected by the extraction temperature and the concentration of reversed micelles, and the selectivity depended on the size of micelles. Water-soluble vitamins could be efficiently and rapidly extracted. The selective extraction of a model mixture of vitamins from pharmaceutical preparations was also attempted. Moreover, the usefulness of the proposed method for the determination of vitamins in various commercial tablets was also demonstrated. Using of this method, the surfactant remains mixed with the extracted compounds, and so we attempted to remove the surfactant from the extract by supercritical fluid extraction. Supercritical carbon dioxide containing 7.5% ethanol as entrainer was found to be the most efficient solvent for removing residual surfactant from the extract.

Ascorbic Acid↗

[Studies on SY5555 in the field of pediatrics].

SY5555, a new oral penem, in the form of dry syrup (powder which is dissolved before use) was evaluated for its pharmacokinetics and clinical efficacy in pediatric patients. Oral administration of 5 mg/kg and 10 mg/kg of SY5555 in dry syrup resulted in respective maximum plasma concentrations of 1.08 +/- 0.38 micrograms/ml (n = 4) and 2.50 +/- 1.81 micrograms/ml (n = 4), half-lives (T 1/2) of 2.72 +/- 1.86 hours (n = 3) and 1.14 +/- 0.88 hours (n = 4), and urinary excretion until 6 hours of 4.7% (n = 1) and 3.86 +/- 2.01% (n = 4). Clinical efficacy was evaluable in 22 patients, and the overall efficacy rate was 100%. As for bacteriological efficacy, all 5 strains of pathogenic organisms identified were eradicated (eradication rate, 100%). No remarkable adverse reactions or abnormal laboratory values were observed.

Administration, Oral↗

Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage disequilibrium in 24 Japanese families.

The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a 29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage analysis, together with haplotype segregation analysis, led to the conclusion that the MJD gene is located at the 6.8-cM interval between D14S256 and D14S81 (Zmax = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligate recombination with the MJD gene (Zmax = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted with D14S81 (P < .05) but not with D14S291 or D14S280. These results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81.

Adult↗

Electrochemically active DNA probes: detection of target DNA sequences at femtomole level by high-performance liquid chromatography with electrochemical detection.

Electrochemically active DNA probes were prepared by linking a ferrocene unit with 5'-aminohexyl-terminated oligonucleotides. The DNA sequences of probes 5a, 5b, and 5c were 5'-T12-3', 5'-T20-3', and 5'-TGCAG TTCCG GTGGC TGATC-3', respectively. Probe 5a could form a complex selectively with a single-strand poly(A) and a double-strand DNA fragment containing an A13 sequence and these complexes could be detected at femtomole levels by an electrochemical detector (ECD) on HPLC. The observed ECD response was proportional to the amount of the complex over the range 20-100 fmol. Probe 5c was capable of detecting femtomole levels of a restriction DNA fragment having oncogene v-myc. Moreover, probe 5b was able to detect picogram levels of mRNA taken from rat brain or yeast total cellular RNA. This proves that the electrochemically active DNA probes are useful in analyzing traces of DNA and RNA carrying the complementary sequence.

Base Sequence↗

Genetic heterogeneity of dominantly inherited olivopontocerebellar atrophy (OPCA) in the Japanese: linkage study of two pedigrees and evidence for the disease locus on chromosome 12q (SCA2).

We did a linkage study of 2 multigenerational pedigrees with dominant olivopontocerebellar atrophy (OPCA) other than SCA1, with chromosome 12q microsatellites. Multipoint linkage analysis led to the conclusion that the disease locus locates within the 6.2 cM interval between IGF1 and D12S84/D12S105. This result coincides with that of Cuban ataxia pedigrees designated as SCA2. Our study provides genetic evidence that dominant OPCA in the Japanese consists of at least two genetically different disorders; SCA1 and SCA2.

Adolescent↗

Electrocardiographic inverse solution for ectopic origin of excitation in two-dimensional propagation model.

Inverse calculations were examined that sought the origin of a cardiac ectopic excitation sequence. Cardiac anatomy and its geometric relationships to sites on the body surface were adapted from human cross-sectional images to form a two-dimensional model, which included ventricular muscle and a primitive conduction system. The surrounding volume conductor was modelled in a simplified way as unbounded, homogeneous and isotropic. In a series of tests, one ectopic origin was designated the 'true' origin. The ECG for this true origin was compared to ECGs for 197 ectopic 'trial' origins, and differences between the wave forms for true versus trial origins were determined. Core issues were the magnitudes of changes in ECG wave forms as a function of the site of origin, whether these changes were sufficient to imply uniqueness, and what spatial resolution might be expected, in the presence of realistic noise levels. For a noise level of 10 microV RMS, the origin of excitation was localised to a single region of the muscle using one wave form from the body surface, with a resolution of 10 mm. The resolution was not improved significantly with a second electrode on the body surface, but was substantially improved with an endocardial electrode.

Algorithms↗

Impaired cell-mediated immunity to cytomegalovirus (CMV) in leukemic children with prolonged CMV viruria.

To determine the role of cell-mediated immunity (CMI) to cytomegalovirus (CMV) in leukemic children after CMV infection, CMI to CMV antigen was studied using CMV-specific lymphocyte blastogenic responses (LBR) and interferon (IFN) production. Four children, who continuously secreted CMV in urine more than 2 years after symptomatic CMV infection (CMV disease) (group 1), showed impaired LBR to CMV antigen, though they had normal LBR to phytohemagglutinin (PHA) and concanavalin A (Con A). Impairment of LBR either to AD-169 strains or autologous and heterologous wild strains was observed. IFN production was not detected in three of four children. Six leukemic children, who had no viruria after cessation of CMV disease (group 2), showed good responses to CMV antigens. IFN was detected in all six children in group 2. Eight leukemic children, who were seropositive to CMV at the onset of leukemia (group 3), showed good responses to CMV antigens and IFN production. These results suggest that impaired cell-mediated immunity to CMV antigen might contribute to prolonged excretion of CMV in urine in leukemic children.

Adolescent↗

Generation of hydrogen peroxide by varicella-zoster virus-stimulated polymorphonuclear leukocytes.

BACKGROUND: In varicella-zoster virus (VZV) infections, the initial response in cutaneous lesions is predominantly polymorphonuclear leukocytes (PMN). However, interaction of VZV and PMN has not yet been fully defined. OBJECTIVES: To explore the potential role of PMN in VZV infections, we investigated the ability of PMN to generate hydrogen peroxide (H(2)O(2)) after stimulation with VZV antigen. STUDY DESIGN: H(2)O(2), one of the reactive oxygen species, was measured by cytofluorography after PMN were incubated with varicella-zoster virus (VZV) antigen in the presence of seropositive or seronegative serum. RESULTS: H(2)O(2) was detectable in unseparated PMN obtained from seropositive children and adults, while unseparated PMN of seronegative donors were not capable of generating H(2)O(2). Separated PMN obtained from either seropositive or seronegative donors were capable of generating H(2)O(2) in the presence of seropositive serum. However, H(2)O(2) was not detectable in separated PMN of seropositive donors in the presence of seronegative serum. The of H(2)O(2) generation did not correlate with concentrations of serum antibodies to VZV. CONCLUSIONS: VZV antigen-antibody complexes might induce H(2)O(2) generation by PMN.

Journal Article↗

Effects of anaesthesia and recent surgery on diastolic function.

OBJECTIVE: The aims were to determine the effects and the extent to which halothane anaesthesia affects diastolic function both immediately after and remote from surgery and to investigate whether the effect is due to alterations in loading conditions. METHODS: Eight mongrel dogs were studied under halothane anaesthesia (0.5-1.5 end tidal vol%) with the chest closed, after acute instrumentation with left ventricular pressure transducers, left atrial and aortic catheters, and left ventricular diameter and wall thickness crystals. The same dogs were then studied in the fully conscious state, 2-3 weeks later. An additional four dogs were studied in the conscious state and then again under halothane anaesthesia remote from acute instrumentation. The left ventricular isovolumetric relaxation time constant, tau, as well as myocardial and chamber stiffness constants were used as indices of diastolic function. RESULTS: Following halothane anaesthesia and recent surgery, tau was prolonged significantly compared to the conscious state, at 30(SEM 1) v 22(1) ms (p < 0.01), but there were no changes in either myocardial or chamber stiffness. While tau remained sensitive to increased heart rate and enhanced contractility and was prolonged by increasing afterload in both the anaesthetised and conscious states, it was consistently prolonged following halothane anaesthesia and recent surgery even at matched levels of contractile states, heart rates and loading conditions, compared to the conscious state, at 26(1) v 19(1) ms (p < 0.01). When the effects of halothane anaesthesia were examined after full recovery from surgery, tau was still prolonged under halothane anaesthesia, at 29(2) v 20(1) ms (p < 0.01), compared to the conscious state, but in contrast to the findings following halothane anaesthesia and recent surgery, it was fully normalised [19(1) v 19(1) ms] when contractile state and loading conditions were matched. CONCLUSIONS: Left ventricular diastolic function is influenced markedly by halothane anaesthesia and recent surgery, and to a degree comparable to many pathological states. The effects of halothane anaesthesia and recent surgery appear to prolong the isovolumetric relaxation time constant independently of heart rate, contractility, and loading conditions and are most likely to be due to the combined direct effects of anaesthetics and acute instrumentation.

Anesthesia, Inhalation↗

Cytotoxicity against varicella zoster virus infected targets in children with acute leukemia.

To eliminate the role of natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), and polymorphonuclear leukocyte (PMN)-mediated cytotoxicity in Varicella zoster virus (VZV) infections, peripheral blood mononuclear cell (PBMC)-mediated NK and ADCC, and phorbol myristate acetate-stimulated PMN-mediated cytotoxicity against VZV-infected targets were studied in children with leukemia. Natural killer and PMN-mediated cytotoxic activity was depressed for 6 months after complete remission and ADCC activity was depressed for 1 year after complete remission. The magnitude of three cytotoxic mechanisms in leukemic children gradually increased while they continued in complete remission. These results suggested that decreased cytotoxic activities of PBMC and PMN might contribute to serious VZV infections and susceptibility to herpes zoster in leukemic children.

Adolescent↗

A flow cytometric method for measurement of hydrogen peroxide generation by pediatric polymorphonuclear leukocytes stimulated by Staphylococcus aureus and Escherichia coli.

The generation of hydrogen peroxide (H2O2), one of the reactive oxygen species, by polymorphonuclear leukocytes (PMN) stimulated by Staphylococcus aureus and Escherichia coli was studied in infants by cytofluorography. After heparinized whole blood was incubated with bacteria for 60 min, generated H2O2 was measured. The positive rate of H2O2 generation of PMN and mean fluorescent intensity of positive PMN stimulated by S. aureus and E. coli were significantly reduced in infants aged < 1 year and H2O2 generation increased with advancing age. In 10-15 year old children, the level of generated H2O2 reached adult levels. When sera from 1 year old children were added to separated PMN from healthy adults, H2O2 generation was reduced. In contrast, H2O2 generation by PMN from 1 year old children was increased by the addition of adult sera. These results suggest that the ability to generate H2O2 in response to S. aureus and E. coli is lower in infants and that such reduced activity may be related to the susceptibility of such infants to S. aureus and E. coli infections.

Adolescent↗

Effect of varicella zoster virus antigen-antibody complexes on hydrogen peroxide generation by human polymorphonuclear leukocytes.

Hydrogen peroxide (H2O2) generation by human polymorphonuclear leukocytes (PMN) incubated with varicella zoster virus (VZV) antigen was studied by cytofluorography. Hydrogen peroxide generation was detected in the presence of VZV-seropositive sera. When seropositive sera were heat-inactivated, H2O2 generation was reduced. When PMN were pre-incubated with Leu-11b, a monoclonal antibody to the Fc receptor on PMN, H2O2 generation was also reduced. These results suggest that VZV antigen-antibody-complement complexes induce H2O2 generation by PMN after these complexes attach to Fc receptors on PMN.

Antibodies, Viral↗

Left ventricular systolic dysfunction precedes diastolic dysfunction during myocardial ischemia in conscious dogs.

We studied the initial effects of regional and global left ventricular (LV) ischemia induced by left circumflex and left main coronary artery occlusion (CAO), respectively, on indexes of systolic and diastolic LV function in conscious dogs to determine whether diastolic abnormalities precede systolic dysfunction or vice versa during the onset of either regional or global myocardial ischemia. With regional myocardial ischemia, within four beats after left circumflex CAO, there was a significant decrease in end-systolic wall thickness in the ischemic zone followed by significantly enhanced postsystolic wall thickening in the nonischemic zone at beat 6. Both peak negative first derivative of left ventricular pressure (LV dP/dt) and the isovolumic relaxation half-time (T 1/2) were prolonged, but later (i.e., by the 9th beat). During sustained CAO T1/2 was normalized shortly after postsystolic thickening in the nonischemic zone had disappeared despite persistent regional systolic asynchrony and shortened ejection time. Thus postsystolic thickening in the nonischemic zone played a major role in the early, transient changes in isovolumic relaxation after acute induction of regional ischemia. With global myocardial ischemia, induced by left main coronary occlusion, indexes of systolic function (e.g., LV dP/dt, ejection fraction, and velocity of circumferential endocardial fiber shortening) were also depressed significantly before (by 5-15 beats) indexes of LV diastolic function [e.g., time constant of isovolumic relaxation and LV myocardial and chamber stiffness (by 35-45 beats)]. Similar results were observed in the presence of autonomic blockade, when heart rate did not change with CAO. Thus, during the induction of either acute regional or acute global LV ischemia in conscious dogs, LV systolic dysfunction occurs before diastolic dysfunction.

Animals↗

Exercise induces cardiac dysfunction in both moderate, compensated and severe hypertrophy.

BACKGROUND: Ventricular hypertrophy begins as a physiological adaptation to cardiac overload but progresses to a pathological state. We examined whether the extent of hypertrophy influenced the response to exercise in terms of its effects on regional and global ventricular function and transmural myocardial blood flow distribution. METHODS AND RESULTS: Left ventricular (LV) hypertrophy was induced by aortic banding in puppies. The effects of treadmill exercise were compared in sham-operated control dogs (n = 7) and in dogs with moderate LV hypertrophy (47% increase in LV wt/body wt, n = 7) with normal baseline levels of LV systolic and diastolic wall stress and dogs with severe LV hypertrophy (85% increase in LV wt/body wt, n = 18), which exhibited elevated levels of LV systolic wall stress at baseline. The dogs with severe LV hypertrophy were further subdivided into those with either elevated or normal baseline levels of LV end-diastolic pressure and wall stress. The response to exercise in dogs with moderate LV hypertrophy was directionally similar to that of sham-operated control dogs for systemic hemodynamics and global and regional LV function, ie, full and subendocardial wall thickening rose, as did mean and diastolic arterial pressures, shortening fraction, and Vcf. The endocardial/epicardial blood flow ratio did not fall during exercise in these two groups. However, relations comparing either LV shortening, Vcf, or wall thickening with LV systolic wall stress during exercise demonstrated depressed myocardial function in the dogs with moderate LV hypertrophy. In contrast, in dogs with severe LV hypertrophy, exercise reduced LV shortening fraction, Vcf, mean and diastolic arterial pressures, and full and subendocardial wall thickening, and the endocardial/epicardial blood flow ratio fell to 0.73 +/- 0.07. There were no differences observed between the two subgroups with severe LV hypertrophy, but the global and regional wall function responses to exercise were more severely impaired than those in dogs with moderate LV hypertrophy. CONCLUSIONS: Responses of global and regional LV function and transmural myocardial blood flow distribution to exercise were clearly abnormal in dogs with severe LV hypertrophy with elevated baseline levels of LV systolic wall stress whether or not baseline levels of LV end-diastolic wall stress were elevated. Thus, it required more severe LV hypertrophy as well as elevated levels of LV wall stress to elicit qualitatively abnormal regional and global hemodynamic responses to exercise. However, even with moderate LV hypertrophy, which was well compensated under baseline conditions, qualitatively impaired contraction-afterload relations were observed during the stress of exercise.

Animals↗