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Y Wada

Publications and source records attributed to Y Wada.

At least 685 records · Page 38Linked to original sources
PubMed1993

Retroviral gene expression as a possible biomarker of aging.

We examined effects of aging on endogenous retrovirus gene expression of mouse lymphocytes with a hypothesis that it may be a useful biomarker of aging. Mice have endogenous murine leukemia viruses (MuLVs) in their chromosomes. We detected the gene expression of long terminal repeats (LTRs) of MuLVs. Brains, livers and spleens were taken from young (3 months old) and old (27 months old) male C57BL/6 mice. In addition to these control (C) mice, we also determined gene expression in dietary restricted (DR) mice, in which rates of aging are known to be slowed. RNA was extracted from the tissues and converted into cDNA. The MuLV-LTR portion of cDNA was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by agarose gel electrophoresis. Gene expressions of young mice were found to be tissue-specific. Expressed LTRs from brains, livers and spleens were that of 370 base-pairs (bp), those of 370 and 620 bp, and those of 370, 400 and 620 bp, respectively. Old mice of C group, however, decreased tissue specificity: expressed LTRs became those of 370-400 bp in any tissues. In contrast the tissue specific gene expression was conserved in old DR mice which had to get prolonged life span and decreased lymphoma incidence. Thereby, gene expression of endogenous retroviruses appears to change during aging and to be modifiable by life-prolonging DR. It may be therefore used as a biomarker of aging in mice. Humans are known to have similar gene elements like MuLV. The present findings demonstrate a possibility of application of endogenous gene expressions to the epidemiology of aging.

Aging↗
PubMed1993

Decreased blood coagulation activities in carbohydrate-deficient glycoprotein syndrome.

The carbohydrate-deficient glycoprotein (CDG) syndromes are a newly recognized group of inherited metabolic diseases. We report a Japanese brother and sister with a CDG syndrome. Both patients showed decreased activities of blood coagulation Factor XI and of the coagulation inhibitor protein C. In one of them there was also a somewhat decreased activity of Factor IX and of antithrombin III. Isoelectric focusing of antithrombin III revealed a decrease of negatively charged fractions and an increase of more cathodal bands. Furthermore, there was a discrepancy between activity and antigen level of Factor VIII and protein C. The patients had an incidental deficiency of factor XII. This is the first detailed report on blood coagulation systems in the CDG syndromes. These blood coagulation abnormalities may explain at least in part the thrombotic or haemorrhagic complications of the CDG syndromes.

Antithrombin III↗
PubMed1993

O,O,S-Trimethyl phosphorothioate induces hypothermia in Fischer 344 rats in a manner dependent on both doses and housing temperatures.

We explored the effects of O,O,S-trimethyl phosphorothioate (OOS-TMP) on body temperatures in Fischer 344 female rats. The 7-day LD50 p.o. for Fischer 344 female rats was found to be 11.8 mg/kg. OOS-TMP induced long-lasting (more than 48 h) and extensive hypothermia at doses > or = 14 mg/kg at a typical laboratory temperature (22 degrees C) while it produced typical symptoms at 10 mg/kg without hypothermia. In contrast, pair-fed (to 20 mg/kg rats) rats (n = 4) did not become hypothermic, negating any role of hypophagia in OOS-TMP associated hypothermia. We next investigated the effects of housing temperatures on toxicities at a LD50 dose (12 mg/kg). At 30 degrees C (n = 11) and 22 degrees C (n = 13), rats did not have hypothermic bouts but at 15 degrees C, eight out of ten rats had. Evidence that changes of housing temperatures neither modified clinical symptoms nor changed mortality rates discards a possibility of hypothermia being involved in delayed toxicity. A novel result of the present study suggests that thermoregulation may be heavily impaired by a special class of organophosphorus compounds.

Animals↗
PubMed1993

Energy restriction suppresses microsomal Ca(2+)-ATPase activities in various organs in C57BL/6 female mice in both euthermic and torpor states.

C57BL/6 female mice were fed a daily control diet (n = 5, 3.9 g/day, 95 kcal/week) or ER diet (n = 5, 2.3 g/day, 48 kcal/week) at 1800 h from 6 weeks of age. Telemetry, conducted at 6 months of age, confirmed that all ER mice entered daily torpor (core body temperature less than 31 degrees C) for 6.63 +/- 2.34 h/day while control mice were euthermic (> 35 degrees C). In vitro activities of microsomal Ca(2+)-ATPase were determined in the brain, liver, salivary gland and kidney from these mice at 6 months of age. Assays were performed at three incubation temperatures of 37 degrees C, 31 degrees C and 25 degrees C. In assays at 37 degrees C, the activities of Ca(2+)-ATPase in the brain and salivary gland from ER mice were lower than those in corresponding organs from control mice. The suppression became profound as the incubation temperature decreased. On the other hand, at 37 degrees C Ca(2+)-ATPase activities in the liver and kidney from ER mice were not lower than those in corresponding organs from control mice, but decreased significantly at low temperatures. Microsomal Ca(2+)-ATPase activities thus appeared to be reduced in ER mice, although it remains unknown whether the present results represent reduced in vivo capacities to regulate cytosolic Ca2+ concentrations.

Animals↗
PubMed1993

Enhancement of autoimmune disease using recombinant vaccinia virus encoding myelin proteolipid protein.

Viral infections have been associated with the initiation and exacerbations often observed with autoimmune disease. Mechanisms by which viruses may play a role in the development of autoreactive immune responses include polyclonal activation of B and T cells, molecular mimicry, viral infection of immune cells, exposure of sequestered antigens, or altered host cell expression (neoantigen or altered self) in virus infected host cells. We have been studying the immune response generated to self proteins in association with viral infection. Here we evaluate the effects of viral infection on the development of an autoimmune disease of the central nervous system, experimental allergic encephalomyelitis. A vaccinia virus construct, VVplp was made containing the coding region for rat myelin proteolipid protein (PLP). Cells infected with VVplp were found to express PLP protein in vitro. Central nervous system disease was not detectable in mice vaccinated with VVplp. However, mice vaccinated with VVplp and later challenged with encephalitogenic peptides derived from PLP were found to have enhanced disease with earlier onset of symptoms when compared to mice treated with a control vaccinia virus construct. This enhancement of disease was found to peak at 10 days post challenge with the encephalitogenic PLP peptide. Clinical disease and an inflammatory response in the central nervous system was evident in mice previously vaccinated with VVplp but not in control vaccinated mice at this time. These results indicate that prior infection with a virus capable of coding for self protein can predispose the host to an accentuated autoimmune response.

Animals↗
PubMed1993

Velocity profiles and phasic flow patterns in the non-stenotic human left anterior descending coronary artery during cardiac surgery.

OBJECTIVE: The aim was to investigate the phasic characteristics of normal human left coronary artery flow and velocity profiles across the vessel. METHODS: The phasic characteristics of flow in the human left anterior descending coronary artery, the centreline flow velocities, and the velocity profiles were measured in 10 patients during corrective surgery for atrial septal defect after closure of the defect. None of these patients had any detectable coronary artery stenosis or left ventricular hypertrophy. Measurements were made with a 20 MHz 80 channel pulsed Doppler velocimeter. RESULTS: The velocity waveform displayed a diastolic-predominant pattern with a systolic to diastolic velocity ratio of 0.29(SD 0.17). Reverse flow was observed in early systole in five patients and in mid to late systole in six patients. The values of peak Reynolds number, unsteadiness parameter, and pulsatility index were 504(198), 2.5(0.6), and 5.9(4.4) respectively. The velocity profiles during diastole showed considerable variability in shape, ranging from symmetrical to skewed to M shaped patterns. The peak wall shear rate was 765(250) s-1 on the epicardial wall of the vessel and 712(301) s-1 on the myocardial wall; the difference was not statistically significant. CONCLUSIONS: The velocity waveform displayed a diastolic-predominant pattern. Considerable variability in shape of the velocity profile was found and was perhaps due to the time evolution of the velocity profile within the diastolic time period.

Adolescent↗
PubMed1993

Cellular stress- and transformation-associated cell surface antigens expressed on human and rodent tumor cells.

Stress-induced proteins may have significant roles in anti-tumor resistance. To clarify the immunobiological roles of these proteins, we first developed monoclonal antibody (mAb) H1A that detects the HeLa cell-surface antigens whose expression was enhanced by treatment of the cells with physico-chemical stressors, such as heat, H2O2 and tumor necrosis factor. H1A (IgM) detects several molecules with mol. wt. 30, 43, 75, 90, 100, 120 and 150 kDa in Western blot analysis of HeLa cell lysates. Although the antigen was constitutively expressed on the HeLa cell surface, the cell-surface expression of H1A-defined antigen was rapidly enhanced (within 1 h) after heat treatment of HeLa cells. H1A antigens were also transformation-associated, since 1) the activated oncogene-transformed fibroblasts expressed the antigens, but parental nontransformed cells did not, and 2) certain human neoplastic but not normal cells strongly expressed the antigens. Furthermore, H1A mAb also partly blocked the cytotoxicity of purified protein derivatives-stimulated human T cell receptor gamma delta-type T cells towards HeLa cells. Taken together, these data indicate that H1A-defined stress-inducible proteins may play a vital role in anti-tumor resistance by cytotoxic T cells.

Adenosine Triphosphate↗
PubMed1993

Brefeldin A blocks the cytotoxicity of T cell receptor alpha/beta and gamma/delta cytotoxic T lymphocyte clones reacting against human autologous cancer cells.

We studied the effector mechanism of T cell receptor (TCR) alpha/beta- and gamma/delta-type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells. Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8+ TCR alpha/beta-type CTL, TcHST-2. Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity. The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment. Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells. Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove. Consequently, target tumor cells were protected from killing by CTL. Moreover, we obtained a CD4-, 8-, TCR gamma/delta-type (V delta 1+) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT. BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gamma/delta-type CTL. These studies suggest that both TCR alpha/beta- and gamma/delta-type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.

Brefeldin A↗
PubMed1993

Increased type III/I collagen and alpha 1(I)/alpha 2(I) chain in a bronchopulmonary dysplastic lung.

The type ratio of collagen III/I and molecule ratio of alpha 1(I)/alpha 2(I) were analysed in lungs from five infants with bronchopulmonary dysplasia (BPD) and seven control infants. All five BPD lungs showed typical characteristics, with pulmonary fibrosis and irregular cystic formation at postmortem examination. A pepsin digestion technique followed by interrupted gel electrophoresis was performed for the determination and molecular analysis of collagens III and I. The ratio of collagen types III and I were significantly increased in BPD lung (P < 0.005). The ratio of alpha 1(I) and alpha 2(I) were also significantly increased in BPD lung (P < 0.05). It is likely that collagen III is predominantly increased and that the alpha 1(I) trimer is formed in the active stage of BPD lungs.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Influence of composition of l-menthol-ethanol-water ternary solvent system on the transdermal delivery of morphine hydrochloride.

The influence of concentration of each component in l-menthol-ethanol-water ternary solvent system (MEW system) on the skin permeation of morphine hydrochloride (MPH) was investigated in hairless rats. The cumulative amount of MPH permeated through the excised abdominal skin over 8 h (Q-8) was selected as an index of skin permeability. With changing MPH concentration over a wide range from 0.01 to 10% in a MEW system (5% l-menthol and 40% ethanol), the values of Q-8 were proportional to MPH concentration. The concentration was fixed at 1% for the following experiments. For the effect of the concentration of l-menthol at 40% ethanol, the maximum Q-8 was observed at 5% l-menthol, and no greater enhancement of Q-8 was obtained by increasing l-menthol concentration above that. In the ethanol effect at 5% l-menthol, the maximum Q-8 was observed at 45% ethanol. When 2-propanol and methanol, which are more lipophilic and hydrophilic than ethanol, respectively, were used instead of ethanol, the maximum values of Q-8 were observed at 40 and 55%. The maximum values for Q-8 were obtained in the vicinity of the solubility of l-menthol in the MEW system in all cases, suggesting that the skin permeation enhancing effect of the system is dependent on the thermodynamic activity of l-menthol.

1-Propanol↗
PubMed1993

Caloric nystagmus after plugging of the horizontal semicircular canal in pigeons.

The mechanism of caloric nystagmus has been attributed to endolymphatic thermoconvection flow of the horizontal semicircular canal in the inner ear. It has recently become difficult, however, to explain caloric nystagmus provoked in the space experiment by employing the convection theory only because the convection phenomenon does not exist under the conditions of microgravity (0G). Although several hypotheses concerning the mechanism of caloric nystagmus have been proposed which exclude the convection theory, opinions remain divided among investigators as to the mechanism governing caloric nystagmus under conditions of normal gravity (1G) and 0G. In this study, we confirmed that the convection theory represents the mechanism of caloric nystagmus under 1G using pigeons (Columba livia). The direction of caloric nystagmus was dependent upon the head position and the stimulus site of calorization in the semicircular canal. But after the plugging of the semicircular canal, however, caloric nystagmus disappeared. These results strongly support the theory that the primary mechanisms of caloric nystagmus under 1G are controlled by the convection phenomenon of the endolymph in the semicircular canal.

Animals↗
PubMed1993

[A case of papillary fibroelastoma of the heart found 13 years after open mitral commissurotomy].

A patient, 68-year-old female, underwent open mitral commissurotomy (OMC) for rheumatic mitral stenosis in April, 1979. In July of 1992, during the postoperative follow-up echocardiogram showed 8 x 7 mm mitral subvalvular tumor mass and mitral restenosis. Then, mitral valve replacement was performed using prosthetic valve (Carbomedics #25 mm). The tumor was located on the top of postero-medial papillary muscle and its chordae, and histologically was diagnosed as benign papillary fibroelastoma. Based on the findings of periodic echocardiogram, the tumor doubling time was estimated to be 283 days. The postoperative course was uncomplicated and she was discharged on the 34th post operative day. Papillary fibroelastoma is a rare benign cardiac tumor. Pathological origin of this tumor is still unknown. However, Lambl's excrescence, long-term inflammatory stimulation and/or thrombi are supposed to be etiologic factors. This tumor is generally found incidentally at the time of autopsy or operation because the patients are often asymptomatic. However, because the tumor causes embolism at times, periodic examination by echocardiogram after operation preserving valves is recommended, and surgical resection is required when the diagnosis is established.

Aged↗
PubMed1993

Relationship between alpha-aminolevulinic acid dehydratase activity, free erythrocyte protoporphyrin concentration and blood lead in calves from lead contaminated farm.

In order to investigate useful indicators of lead contamination, 108 Japanese Black calves from a lead-contaminated farm were used. The lead concentrations in blood (Ph-B), delta-aminolevulinic acid dehydratase (ALA-D) activities, and free erythrocyte protoporphyrin (FEP) concentrations were examined. A significant negative correlation was obtained between Pb-B concentrations and ALA-D activities (r = -0.621, p < 0.01). A significant positive correlation was obtained between Ph-B concentrations and FEP concentrations (r = 0.850, p < 0.01). The calves were divided by Pb-B concentrations (micrograms/100 ml) into 5 groups (A = < or = 30, B = 31 approximately 90, C = 91 approximately 150, D = 151 approximately 210, E = > or = 211) to observe the relation of ALA-D activities, FEP concentrations and ALA-D activities in group B (r = -0.706, p < 0.05). A significant positive correlation was obtained between Pb-B concentrations and FEP concentrations in groups A, B and D (A = r = 0.496, p < 0.01; B = r = 0.686, p < 0.01; D = r = 0.529, p < 0.05). These results indicate that FEP concentrations were good indicators of lead contamination.

Animals↗
PubMed1993

[Serotonergic mechanisms of hippocampal kindled seizures in cats--effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and ketanserin].

Based on our previous findings that a serotonin (5-HT) precursor L-5-hydroxytryptophan and a 5-HT1 a receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin can suppress seizures kindled from the feline hippocampus (HIP), we have suggested that 5-HT1 a receptors play an inhibitory role in HIP seizure generation. In order to clarify the role of 5-HT2 receptors in epilepsy, the present study examined the effects of a 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane(DOI) and a 5-HT2 receptor antagonist ketanserin on HIP-kindled seizures. Following the completion of HIP kindling, five cats received intravenous injections of 0.9% saline, DOI (1.0mg/kg) or ketanserin (1.0mg/kg). Electrical stimulation at the generalized seizure triggering threshold was delivered to the kindled HIP 15 min after drug administration. The anticonvulsant effects were assessed by the behavioral seizure stage, afterdischarge duration, latency to the onset of stages 4 and 6, and duration of a generalized tonic-clonic convulsion (GTC). Although no significant change was found in the seizure stage following the administration of either drug, both DOI and ketanserin significantly altered the latency for seizure generalization. DOI significantly reduced the latency to the onset of stage 6 GTC as compared with saline, with a significant reduction in the afterdischarge duration. In contrast, ketanserin significantly increased the latency to the GTC onset as compared with saline. Neither the latency of the stage 4 onset nor the GTC duration was significantly affected by these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗
PubMed1993

[A case of mitral valve re-replacement with radical correction of Bland-White-Garland syndrome].

A case of an 8-year-old girl with Bland-White-Garland syndrome (BWG) who successfully underwent a second mitral valve replacement is reported. The patient had a past history of mitral valve replacement under the diagnosis of mitral regurgitation and pulmonary hypertension at one year and 3 months of age. Cardiac catheterization at 6 years and 3 months of age revealed an anomalous origin of the left coronary artery from the pulmonary artery but she was asymptomatic. One year and 7 months later, she was admitted to our institution with a sudden onset of chest pain and respiratory distress. Right heart pressure study using a Swan-Ganz catheter showed severe pulmonary hypertension and elevated mean pulmonary wedge pressure (38 mmHg). Echocardiogram revealed severe mitral stenosis and moderate regurgitation. She was diagnosed under fluoroscopy as acute left cardiac failure due to stuck valve and suspected having myocardial damage due to BWG, thus, emergency surgery was performed. Under cardiopulmonary bypass, aorto-left coronary arterial continuity was established by intrapulmonary arterial tunnel using Hamilton's technique. After resection of the prosthetic valve, of which one of two leaflets had been fixed in pannus, re-MVR was done with a St. Jude. Medical valve (25 mm). Postoperative angiogram demonstrated satisfactorily reconstructed two coronary artery systems. Postoperatively, she has been doing well without complaint for the last eighteen months.

Child↗