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Biomedical subjects

T Hosono

Publications and source records attributed to T Hosono.

At least 19 recordsLinked to original sources

The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.

Allyl sulfides, e.g., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), are principal constituents of garlic oil. In the present study, we investigated the in vivo effect of these sulfides on the phase I and phase II drug-metabolizing enzymes, and elucidated their structure-function relationship. A highly purified form of each sulfide (more than 99% purity) was administered i.p. as a bolus to rats at a concentration of 10 or 100 micromol/kg body weight for 14 consecutive days. As to the phase I enzymes, DAS (100 micromol/kg) slightly but significantly increased cytochrome P-450 (CYP) 2E1 activity (1.6-fold vs. control), whereas DADS and DATS did not affect it or the hepatic total CYP level or CYP1A1/2 activity. With respect to the phase II enzymes, DATS (10 micromol/kg) and DADS at a 10-fold higher dose (100 micromol/kg) significantly increased the activities of glutathione S-transferase, quinone reductase, and antioxidative enzyme glutathione peroxidase; whereas DAS did not. In the carbon tetrachloride (CCl4)-induced acute liver injury model of rats, either DATS (10 micromol/kg) or DADS (100 micromol/kg) significantly reduced the injury caused by the induction of phase II enzymes with CCl4. In conclusion, the sulfides affected both phase I and phase II enzymes, the former being stimulated by the monosulfide only and the latter, strongly by the trisulfide and weakly by the disulfide. Therefore, the polysulfide DATS may be one of the important factors in garlic oil that protects our body against the injury caused by radical molecules encountered in daily life.

Allyl Compounds↗

Classifying cases of fetal Wolff-Parkinson-White syndrome by estimating the accessory pathway from fetal magnetocardiograms.

The paper presents an evaluation of the possibility of using fetal magnetocardiogram (FMCG) signals to estimate and classify the accessory pathway in fetal Wolff-Parkinson-White (WPW) syndrome. The FMCG signals of two fetuses with WPW syndrome (type A) were detected using a 64-channel superconducting quantum-interference device system. An average across the cycles of these signals was taken to obtain clear WPW signals. To determine the direction and position of the accessory pathway in a fetal heart accurately, the accessory pathway and activated pathway at the peak of the QRS complex thus obtained were estimated for each fetus, using a single-dipole model. The phase angle (about 90 degrees) between the equivalent current dipoles (ECDs) was the same for both fetuses. This angle suggested that the accessory pathway is in the left side of the heart, i.e. that the pathway exists in the left ventricle, which indicates type A WPW syndrome. Identification of the position of the accessory pathway in a fetus with WPW syndrome from the angle between the ECD of the accessory pathway and the ECD of the peak in the QRS complex was thus demonstrated.

Electrocardiography↗

Detection of atrial-flutter and atrial-fibrillation waveforms by fetal magnetocardiogram.

Two cases of fetal tachycardia are reported: atrial flutter and fibrillation. The waveforms from each case were detected by fetal magnetocardiograms (FMCGs) using a 64-channel superconducting quantum interference device (SQUID) system. Because the magnitude of supraventricular arrhythmia signals is very weak, two subtraction methods were used to detect the fetal MCG waveforms: subtraction of the maternal MCG signal, and subtraction of the fetal ORS complex signal. It was found that atrial-flutter waveforms showed a cyclic pattern and that atrial-fibrillation waveforms showed f-waves with a random atrial rhythm. Fast Fourier transform analysis determined the main frequency of the atrial flutter to be about 7Hz, and the frequency distribution of atrial fibrillation consisted of small, broad peaks. To visualise the current pattern, current-arrow maps, which simplify the observation of pseudo-current patterns in fetal hearts, of the averaged atrial flutter and fibrillation waveforms were produced. The map of the atrial flutter had a circular pattern, indicating a re-entry circuit, and the map of the atrial fibrillation indicated one wavelet, which was produced by a micro-re-entry circuit. It is thus concluded that an FMCG can detect supraventricular arrhythmia, which can be characterised by re-entry circuits, in fetuses.

Atrial Fibrillation↗

CAR- or alphav integrin-binding ablated adenovirus vectors, but not fiber-modified vectors containing RGD peptide, do not change the systemic gene transfer properties in mice.

Targeted gene delivery to the tissue of interest by recombinant adenovirus (Ad) vectors is limited by the relatively broad expression of the primary receptor, the coxsackievirus and adenovirus receptor (CAR), and the secondary receptor, alphav integrin. This problem could be overcome by mutating the fiber and penton base, which bind with CAR and alphav integrin, respectively. In this study, we constructed CAR-binding ablated Ad vectors and alphav integrin-binding ablated Ad vectors by mutation in the FG loop of fiber knob and in the RGD motif of penton base, respectively, and compared the gene transfer properties of their vectors into various types of cultured cells and mice with conventional Ad vectors. We also generated Ad vectors containing RGD peptide in the HI loop of the fiber knob. CAR-binding ablated Ad vectors mediated about 1% of gene transfer activity into CAR-positive cultured cells, compared with conventional Ad vectors, while alphav integrin-binding ablated Ad vectors maintained at least 76% of gene transfer activity into cultured CAR-positive cells. Inclusion of the RGD peptide into the HI loop of the fiber knob of CAR-binding ablated Ad vectors restored gene transfer activity in vitro. On the other hand, systemically administered CAR-binding ablated Ad vectors, as well as alphav integrin-binding ablated Ad vectors mediated similar levels of gene transfer into mouse liver with the conventional Ad vectors. These results suggest that continued interaction of either the fiber with CAR or the penton base with alphav integrin offers an effective route of virus entry into mouse liver in vivo. Inhibition of the interaction of both the fiber with CAR and the penton base with alphav integrin is likely to be crucial to the development of targeted Ad vectors.

Adenoviridae↗

Initial experiences of tissue harmonic imaging in the diagnosis of fetal cardiac tumors.

The usefulness of tissue harmonic imaging in prenatal diagnosis is illustrated in two fetuses with a cardiac tumor. Tissue harmonic imaging provided more informative images than conventional B-mode imaging, enabling the detection of the site of attachment of the cardiac tumor and estimation of intracardiac blood flow. The advantages of tissue harmonic imaging over conventional B-mode imaging in prenatal diagnosis are discussed.

Blood Flow Velocity↗

Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans.

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.

Acetaldehyde↗

Efficient gene transfer by fiber-mutant adenoviral vectors containing RGD peptide.

One of the hurdles to adenovirus (Ad)-mediated gene transfer is that Ad vectors mediate inefficient gene transfer into cells lacking in the primary receptors, Coxsackievirus and adenovirus receptor (CAR). We previously developed a fiber-mutant Ad vector containing the Arg-Gly-Asp (RGD)-containing peptide motif on the HI loop of the fiber knob, and showed that the mutant vector had enhanced gene transfer activity to human glioma cells, which showed little CAR expression, compared to the vector containing wild type fiber. In this study, the feasibility of the Ad vector containing RGD peptide on the fiber knob was examined in a wide variety of cell types: CAR-positive or -negative human tumor cells, mouse cells, and leukemia cells. The mutant vector infected the cells, which lacked CAR expression but showed alpha(v) integrin expression, about 10-1000 times more efficiently than the vector containing wild type fiber via an RGD-integrin (alpha(v)beta3 and alpha(v)beta5)-dependent, CAR-independent cell entry pathway. The results of this study indicate that Ad vector containing RGD peptide on the fiber knob could be of great utility for gene therapy and gene transfer experiments.

Adenoviridae↗

Optical detection of neuromodulatory effects of conditioned taste aversion in the pond snail Lymnaea stagnalis.

Multiple site optical recording was used to analyze the neural activity changes caused by conditioned taste aversion (CTA) training in the pond snail Lymnaea stagnalis. In response to electrical stimulation of the median lip nerve, which transmits chemosensory signals of appetitive taste to the central nervous system, we optically detected large numbers of spikes in several parts of the buccal ganglion. The effects of CTA training on the spike responses were examined in two areas of the ganglion where the most active neural responses occurred. In one area (termed Area I) that included the N1 medial (N1M) cells, a class of central pattern generator interneurons involved in feeding behavior, the number of spikes in a period 1500-2000 ms after median lip nerve stimulation was significantly reduced in conditioned animals compared to control animals. In another area (termed Area II) positioned between buccal motoneurons, the B3 and B4CL (cluster) cells, the evoked spike responses were unaffected by CTA training. These results, taken together with our previous results indicating an enhancement of an inhibitory input to the N1M cells during CTA, suggest that an appetitive taste signal transmitted to the N1M cells through the median lip nerves is suppressed during CTA, resulting in a decrease of the feeding response.

Action Potentials↗

PKCtheta II, a new isoform of protein kinase C specifically expressed in the seminiferous tubules of mouse testis.

Protein kinase C (PKC) theta, a Ca(2+)-independent isoform of PKC, has been known to be expressed in skeletal muscle and T cells. In the present study, we isolated and characterized a smaller transcript expressed in the mouse testis, the cDNA of which is referred hereafter as PKCthetaII and the original PKCtheta as PKCthetaI. The cDNA clone of PKCthetaII has 2184 base pairs and 464 amino acids in the possible open reading frame, consisting of the 5' unique sequence of 20 amino acids and the PKCthetaI sequence of 444 amino acids. Genomic DNA analysis revealed that transcription of PKCthetaII is initiated from the PKCthetaII-specific exon, which is located between exons 7 and 8 of the PKCtheta gene, indicating that alternative splicing is the mechanism by which PKCthetaII is generated. PKCthetaII is expressed exclusively in the testis in an age-dependent manner with sexual maturation. In situ hybridization and reverse transcription-polymerase chain reaction of microdissected tissues clearly demonstrated that PKCthetaII is expressed in the seminiferous tubules of the mouse testis. Consistent with its molecular structure lacking the C1 regulatory domain, PKCthetaII is constitutively active as determined by an in vitro kinase assay, being independent of PKC activators, e.g. phosphatidylserine and phorbol ester. PKCthetaII may play a crucial role in spermatogenesis or some related function of the testis.

Alternative Splicing↗

Transgenic mice expressing mutant caveolin-3 show severe myopathy associated with increased nNOS activity.

Caveolin-3 is the muscle-specific isoform of the caveolin protein family, which is a major component of caveolae, small membrane invaginations found in most cell types. Caveolins play important roles in the formation of caveola membranes, acting as scaffolding proteins to organize and concentrate lipid-modified signaling molecules, and modulate a signaling pathway. For instance, caveolin-3 interacts with neuronal nitric oxide synthase (nNOS) and inhibits its catalytic activity. Recently, specific mutations in the caveolin-3 gene, including the Pro104Leu missense mutation, have been shown to cause an autosomal dominant limb-girdle muscular dystrophy (LGMD1C), which is characterized by the deficiency of caveolin-3 in the sarcolemma. However, the molecular mechanism by which these mutations cause the deficiency of caveolin-3 and muscle cell degeneration remains elusive. Here we generated transgenic mice expressing the Pro104Leu mutant caveolin-3. They showed severe myopathy accompanied by the deficiency of caveolin-3 in the sarcolemma, indicating a dominant negative effect of mutant caveolin-3. Interestingly, we also found a great increase of nNOS activity in their skeletal muscle, which, we propose, may play a role in muscle fiber degeneration in caveolin-3 deficiency.

Animals↗

A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob.

The use of recombinant adenovirus (Ad) vectors containing genetically modified capsid proteins is an attractive strategy for achieving targeted gene transfer. The HI loop of the fiber knob is a promising candidate location for the incorporation of foreign ligands for achieving this goal. However, the method of constructing an Ad vector containing a foreign ligand in the HI loop of the fiber knob has proved difficult. In this study, we developed a simple system to construct fiber-modified vectors. To do this, a vector plasmid containing a complete E1/E3-deleted Ad type 5 genome and a unique Csp45I and/or ClaI site between positions 32679 and 32680 of the Ad genome (residues threonine-546 and proline-547 of the fiber protein) was constructed. Oligonucleotides corresponding to the Arg-Gly-Asp (RGD) or Asn-Gly-Arg (NGR)-containing peptide motif (as a model) and containing a Csp45I and/or ClaI recognition site, were ligated into the Csp45I and/or ClaI-digested plasmid. The foreign transgene expression cassette was inserted into the E1 deletion site of the vector plasmid and the fiber-mutant Ad vector was produced by transfection of the PacI-digested plasmid into 293 cells. The virus containing the RGD or NGR peptide on the fiber knob was able to infect human glioma cells, which do not express coxsackievirus and adenovirus receptor (CAR), one of the Ad virus receptors, about 100-1000 times more efficient than the virus containing wild-type fiber. This suggested that the mutant virus mediated CAR-independent cell entry pathway. The simplicity of this method allows not only for easy construction of fiber-mutant Ad vectors, but also for screening of the peptides that target the vector to the desired cells and tissues.

Adenoviridae↗

Indomethacin induced bulky lymphadenopathy and eosinophilic pneumonia.

Indomethacin is one of the most popular non-steroidal anti-inflammatory drugs (NSAID). Although NSAID occasionally provoke bronchospasm and hypersensitivity pneumonia, they seldom cause lymphadenopathy. This is the first report in which NSAID induced both eosinophilic pneumonia and bulky intrathoracic lymphadenopathy simultaneously. A 76-year-old Japanese man experienced high fever and dyspnoea after using an indomethacin suppository. Computed tomography scan of his chest revealed massive mediastinal and hilar lymphadenopathy along with diffuse infiltration in both lungs. He was diagnosed to have eosinophilic pneumonia because of eosinophilia in his peripheral blood and bronchoalveolar lavage fluid (BALF). Without using glucocorticoids, the pulmonary infiltration and lymphadenopathy subsided spontaneously. As the blastoid transformation test using the lymphocytes in his BALF was positive to indomethacin, we judged that both his eosinophilic pneumonia and mediastinal lymphadenopathy were due to a hypersensitivity reaction to indomethacin. An allergic reaction to NSAID should be considered as a rare cause of mediastinal lymphadenopathy.

Aged↗

Contraindication of magnesium sulfate in a pregnancy complicated with late-onset diabetes mellitus and sensory deafness due to mitochondrial myopathy.

A primipara affected by late-onset diabetes and sensory deafness because of mitochondrial myopathy was hospitalized for threatened preterm delivery. Magnesium sulfate was started for tocolysis, resulting in general muscle damage, although the mitochondrial myopathy did not deteriorate during pregnancy. Magnesium sulfate may be contraindicated in pregnancy with mitochondrial myopathy.

Adult↗

Prenatal diagnosis of QT prolongation by fetal magnetocardiogram--use of QRS and T-wave current-arrow maps.

To determine the T wave of a fetal magnetocardiogram (FMCG), we have evaluated the T/QRS ratio and obtained current-arrow maps that indicate weak currents. We measured FMCG signals for 52 normal fetuses and two abnormal fetuses with prolonged QT waves by using three superconducting quantum interference device (SQUID) systems: a nine-channel system, a 12-channel vector system and a 64-channel system. The T/QRS ratio was calculated for all the normal fetuses from the maximum magnitudes of the QRS complex and the T wave. Current-arrow maps of the QRS complex (R wave) and T wave were obtained by using the 64-channel system, and the phase differences of the total-current vectors were calculated by using the current-arrow maps. The results showed that the T/QRS ratio had a wide variability of 0.35 for the normal fetuses. However, the magnitude of the prolonged T wave was as weak as the detection limit of the SQUID magnetometer. Although the T/QRS ratios for the fetuses with QT prolongation were within the normal range (< 0.35), the weak magnitude of the prolonged T wave could be evaluated. On the other hand, by comparing the current-arrow maps of the R and T waves for the normal fetuses, we found that the maximum-current arrows were indicated as either in the same direction or in opposite directions. These patterns could be identified clearly by the phase differences. Very weak prolonged T waves for the two abnormal fetuses could be determined by using these current-arrow maps and phase differences. Consequently, although the T/QRS ratios of FMCG signals have a wide distribution, we have concluded that the current-arrow map and phase difference can be used to determine the T wave of an FMCG signal.

Adult↗

Pulmonary intravascular lymphoma complicated with Pneumocystis carinii pneumonia: a case report.

We report a case of intravascular lymphoma (IVL) complicated with Pneumocystis carinii pneumonia (PCP). A 65-year-old male complaining of dyspnea and dementia was diagnosed to have pulmonary IVL by transbronchial lung biopsy. Concomitantly, deoxyribonucleic acid sequence specific to Pneumocystis carinii was detected in bronchoalveolar lavage fluid by polymerase chain reaction. Differential responses to the sequential treatments for PCP and IVL implied that increased serum lactate dehydrogenase (LDH) was due to PCP, whereas hypoxemia and dementia were due to IVL. Although pulmonary IVL and PCP share many clinical presentations, exact diagnosis is essential for their successful treatment.

Aged↗

Effects of estrogen on thermoregulatory tail vasomotion and heat-escape behavior in freely moving female rats.

Effects of estrogen on thermoregulatory vasomotion and heat-escape behavior were investigated in ovariectomized female rats supplemented with estrogen (replaced estrogen rats) or control saline (low estrogen rats). First, we measured tail temperature of freely moving rats at ambient temperatures (T(a)) between 13 and 31 degrees C. Tail temperature of the low estrogen rats was higher than that of the replaced estrogen rats at T(a) between 19 and 25 degrees C, indicating that the low estrogen rats exhibit more skin vasodilation than the replaced estrogen rats. There was no significant difference in oxygen consumption and core temperature between the two groups. Second, we analyzed heat-escape behaviors in a hot chamber where rats could obtain cold air by moving in and out of a reward area. The low estrogen rats kept T(a) at a lower level than did the replaced estrogen rats. These results imply that the lack of estrogen facilitates heat dissipation both by skin vasodilation and by heat-escape behavior. Ovariectomized rats may mimic climacteric hot flushes not only for autonomic skin vasomotor activity but also for thermoregulatory behavior.

Animals↗

Sarcomere lengths of thick skeletal muscle specimens measured under an epi-illumination-type polarization microscope.

The purpose of this study was to measure sarcomere lengths of thick muscle fiber bundles at resting and at isometric tetanic contractions. We developed a novel measurement system using an epi-illumination-type polarization microscope and an image processing algorithm using an ellipse-type Gabor filter. Images with striation patterns of frog skeletal muscle were obtained by the microscope and the image processing algorithm. Individual lengths of 10 consecutive sarcomeres of a single muscle fiber were measured by gauging each width of the striation pattern, which was proved to be derived from striation structures of the single fiber by performing experiments using different polarization lights and different focus depths. At the resting state, each sarcomere length was identical at the fixed muscle length and in proportion to the length ranging over 91-123% of the natural length. Each sarcomere length was unchanged at the steady state during isometric tetanic contractions. Individual sarcomere lengths in the central part of the skeletal muscle were identical at resting and at isometric tetanic contractions even in the thick muscle fiber specimen.

Algorithms↗