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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 451 records · Page 25Linked to original sources
PubMed1997

Lysyl-tRNA synthetase from Bacillus stearothermophilus. Formation and isolation of an enzyme-lysyladenylate complex and its analogue.

The formation of an enzyme.lysyladenylate complex was studied with a highly purified lysyl-tRNA synthetase [L-lysine:tRNALYS ligase (AMP-forming); EC 6.1.1.6] from Bacillus stearothermophilus. The apparent dissociation equilibrium constants of the enzyme with L-lysine and ATP in the process of the complex formation were estimated to be 50.9 and 15.5 microM, respectively, at pH 8.0, 30 degrees C, by fluorometric measurement. The isolated enzyme.lysyladenylate complex was relatively stable with a rate constant of decomposition of 1.7 x 10(-5) s-1 at pH 8.5 and 0 degree C. The rate constant of transfer of L-lysine from the complex to Escherichia coli tRNA was 1.2 x 10(-2) S-1 at pH 8.5 and 0 degree C. The effects of replacing L-lysine by several analogues on the complex formation were examined. L-Lysine hydroxamate, a strong inhibitor of the L-lysine dependent ATP-PPi exchange reaction, produced a stable complex with the enzyme and ATP, enzyme.lysinehydroxamate-AMP probably being formed. The binding stoichiometry of the assumed L-lysinehydroxamate-AMP per mol of the dimer enzyme was 1:1.

Adenosine Monophosphate↗
PubMed1997

Peptidyl aldehyde inhibitors of proteasome induce apoptosis rapidly in mouse lymphoma RVC cells.

Proteases play an important role in regulation of apoptosis. To elucidate the role of proteasome in apoptosis, we examined the effects of the proteasome inhibitors, carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal and carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal on RVC lymphoma cells. Cells exposed to the proteasome inhibitors arrested at G2/M phase followed by internucleosomal DNA cleavage, chromatin condensation, and formation of apoptotic bodies dose- and time-dependently. Ubiquitinated histone H2A levels decreased in the exposed cells, suggesting a relationship between deubiquitination of histone H2A and the chromatin disarray seen in apoptosis. Northern blots showed an increase in expression of polyubiquitin genes early in the incubation. These findings suggest that the ubiquitin-mediated proteasome-proteolytic system is involved in regulating the cell cycle and apoptosis in RVC cells.

Animals↗
PubMed1997

Diversity in the renal hemodynamic effects of dihydropyridine calcium blockers in spontaneously hypertensive rats.

Effects of dihydropyridine (DHP) Ca2+ channel blocker (CaB) on glomerular hemodynamics are controversial. We examined the effects of two DHP derivatives, benidipine hydrochloride (BDP) and nifedipine (NDP), on glomerular hemodynamics by an in vivo micropuncture method by using spontaneously hypertensive rats (SHRs). Systemic bolus infusion of BDP (4 microg/kg) or NDP (250 microg/kg) elicited comparable decreases in mean arterial blood pressure (MAP). The proximal stop-flow pressure (Psf), an indicator of glomerular capillary pressure, revealed significant decreases in BDP but nonsignificant increases in NDP. To minimize the influence of MAP or other systemic events, we monitored Psf during perinephron infusion of CaB and observed significant increases in Psf during 10(-3) M NDP perfusion and nonsignificant changes with 10(-3) M BDP. Moreover, the stability of Psf during alteration of renal perfusion pressure was significantly impaired in the nephron treated with topical NDP. These findings support the notion that CaB has diverse effects on glomerular hemodynamics, and such effects may in part be the result of different pharmacologic actions on the renal microvasculature.

Animals↗
PubMed1997

N-acetylcysteine attenuates TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII expression in human monocytes.

We have previously shown that tumor necrosis factor-alpha (TNF-alpha) reduces interleukin-4 (IL-4)-induced Fc epsilon RII expression in human monocytes. It has been shown that TNF-alpha activates nuclear transcriptional factors through the generation of reactive oxygen intermediates (ROIs), and antioxidant N-acetylcysteine (NAC) inhibits TNF-alpha-induced activation of nuclear transcriptional factors. Therefore, we hypothesized that TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII expression in monocytes might be mediated through the ROIs-activated mechanism. In the present study, to test our hypothesis, we examined the effect of NAC on TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII expression in human monocytes. NAC attenuated TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII expression by attenuating TNF-alpha-dependent reduction of Fc epsilon RII mRNA expression. Similarly, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC), also effectively attenuated this-reduction. These results indicate that an ROIs-activated and antioxidant-sensitive mechanism might be involved in TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII expression in monocytes.

Acetylcysteine↗
PubMed1997

Free-running circadian rhythm of melatonin in a sighted man despite a 24-hour sleep pattern: a non-24-hour circadian syndrome.

Sleep and plasma melatonin rhythms were measured longitudinally in a sighted young man (21 years old) under a day-right environment. At each measurement, the responsiveness of the melatonin rhythm to a single light pulse was examined in addition to the 24-hour profile. In experiment 1, the timing of sleep was decided by the subject himself. Although most sleep episodes were observed between 21:02 h and 10:55 h, the plasma melatonin rhythm free-ran for a period of 24.18 h. In experiment 2, the sleep-wake schedule of the subject was strictly fixed. The subject was instructed to go do bed at 24:00 h and wake up, at the latest, before 8:00 h for 40 days. The melatonin rhythm, however, continued to free-run for a period of 24.12 h. Nocturnal melatonin level could not be suppressed by a 3-hour light pulse of 500 lx, but was suppressed by a pulse of 1000 lx. It is concluded that internal desynchronization occurred in this particular sighted subject where the sleep-wake rhythm was entrained by the 24-hour day-night environment, whereas the plasma melatonin rhythm free ran, and that a forced sleep schedule did not act as a strong zeitgeber.

Adult↗
PubMed1997

A sighted man with non-24-hour sleep-wake syndrome shows damped plasma melatonin rhythm.

Twenty-four-hour profiles of plasma melatonin, cortisol and rectal temperature were measured longitudinally in a sighted man who has been suffering from sleep disorders for more than 10 years. The sleep-wake rhythm of this subject free-ran, despite his routine life, and occasionally showed a sign of internal desynchronization, where sleep was lengthened up to 30 h. These states were classified into the non-24-hour sleep-wake syndrome. Plasma melatonin concentrations in the subjective night remained at a low level and showed a damped circadian rhythm. At the same time, robust circadian rhythms were detected in plasma cortisol and rectal temperature, indicating that the circadian pacemaker was intact. The causal relationship between the damping of nocturnal melatonin rise and a failure of entrainment of the sleep-wake cycle is discussed.

Adult↗
PubMed1997

Daily melatonin intake resets circadian rhythms of a sighted man with non-24-hour sleep-wake syndrome who lacks the nocturnal melatonin rise.

Effects of daily melatonin intake on the circadian rhythms of sleep and wakefulness, rectal temperature and plasma cortisol were examined in a sighted man who had suffered from the non-24-hour sleep-wake syndrome. The subject lacked the nocturnal melatonin rise in plasma, but showed robust circadian rhythms in rectal temperature and plasma cortisol. The sleep-wake rhythm free-ran with a period longer than 24 hours. Daily melatonin intake at 21:00 h concentrated sleep episodes in the nocturnal period (24:00-8:00 h), and increased the length of the episodes. A single oral dose (3 mg) of melatonin increased plasma melatonin levels to about 1300 pg/mL within one hour and remained at pharmacological levels for approximately 6 hours. The trough of rectal temperature and the circadian rise of plasma cortisol were fixed to the early morning. A higher dose of melatonin (6 mg) did not improve the general feature. After the cessation of melatonin intake, the sleep-wake rhythm began to free-run together with the circadian rhythms in rectal temperature and plasma cortisol. It is concluded that daily intake of melatonin at early night time resets the circadian rhythms in a sighted man who lacked the nocturnal melatonin rise and showed free-running circadian rhythms in routine life.

Administration, Oral↗
PubMed1997

Nemaline bodies of skeletal muscle fibers of the neck in a case of pharyngeal cancer.

Nemaline bodies were found in the regenerating muscle fibers of the neck of a 74-year-old Japanese male with pharyngeal cancer. Histologically, the nemaline bodies were needle-shaped structures and hematoxophilic with phosphotungstic acid-hematoxylin stain. Electron microscopic examination suggested that they arise as extensions of the Z bands. Although nemaline bodies occur in a variety of pathological conditions other than nemaline myopathy, their occurrence in regenerating skeletal muscle fibers invaded by cancer has not been reported previously. The pathogenesis of the nemaline body formation in the present case is discussed.

Aged↗
PubMed1997

Beta-lactoglobulin suppresses melanogenesis in cultured human melanocytes.

The effects of whey proteins from bovine milk on melanogenesis in cultured human melanocytes were examined. Among the major protein components of milk whey including beta-lactoglobulin (BLG), alpha-lactalbumin, serum albumin, and IgG, only BLG exhibited the depigmenting effect at a concentration of 1 mg/ml. Also, BLG suppressed the activity of tyrosinase in these cells. Retinol, to which BLG is known to bind, slightly increased the pigmentation of the cells at concentrations in the range of 1-100 nM, and retinoic acid, a metabolite of retinol, exhibited a strong pigmentation-promoting effect within the same concentration range. Treatment of the cells with 1 mg/ml BLG completely abrogated the pigmentation induced by these A vitamins. These results demonstrate a novel biological activity of BLG and suggest that this activity is dependent on its ability to bind retinol.

Animals↗
PubMed1997

Prevention of onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei.

The effect of Lactobacillus casei (LC) on the onset of diabetes in an insulin-dependent diabetes mellitus model, nonobese diabetic (NOD) mice, were examined. From the age of 4 weeks, female NOD mice were fed a diet of either standard laboratory chow (n = 12) or the same chow containing 0.05% weight heat-killed cells of LC (n = 12), and the onset of diabetes was thereafter recorded. The incidence of diabetes in the control group (10/12) was significantly higher than that in the LC-treated group (3/12) (p < 0.01). Pathological analysis in the LC-treated group revealed strong inhibition of the disappearance of insulin-secreting beta cells in Langerhans islets caused by autoimmune disease. The proportion of CD45R+ B-cells in the spleen was increased and that of CD8+ T-cells in spleen cells was decreased in the LC-treated group. Analysis of cytokine production revealed lower interferon-gamma production in the LC-treated group compared to the control group, while the interleukin (IL)-2 production was higher. The levels of IL-4, IL-5, IL-6 and IL-10 in the LC-treated group were somewhat higher than in the control group. Taken together, these findings clearly demonstrated that oral feeding of LC to NOD mice effectively inhibited the occurrence of diabetes and regulated the host immune response.

Animals↗
PubMed1997

[Levels of thermostable direct hemolysin production by Vibrio parahaemolyticus strains carrying both tdh and trh genes].

One hundred and twenty-five strains of Vibrio parahaemolyticus carrying both the tdh and trh genes were selected from the strains isolated from the travelers with diarrhea by an hybridization test using polynucleotide probes. The levels of TDH produced by these strains and the association between the TDH levels and related characteristics in these strains were analyzed. The TDH level varied greatly from strain to strain, but none of the levels was as high as that of the typical Kanagawa phenomenon-positive strains. The strains were classified into "TDH producer" (18 strains), "Low-level TDH producer" (85 strains), and "No TDH producer" (22 strains) based on the results of a modified Elek test and the hemolysis assay on Wagatsuma agar. The highest TDH level achieved by the "TDH producer" was twofold lower than that of the Kanagawa phenomenon-positive strains as assayed by the RPLA method. All strains possessed the toxR gene. The trh1 and trh2 genes were detected in, respectively, 105 and 20 strains, and no correlation existed between the type of the trh gene and the levels of TDH produced. Considerable restriction fragment length polymorphism was observed with the tdh gene-bearing HindIII DNA fragment in different strains, but it was not related with the TDH level.

Bacterial Toxins↗
PubMed1997

Successful treatment for active cytomegalovirus infection by cytomegalovirus antibody-enriched immunoglobulin in a renal transplant recipient.

Active cytomegalovirus (CMV) infection was treated successfully by only CMV antibody-enriched immunoglobulin (CMV-IG) in a renal transplant recipient. CMV-IG was injected at 86 mg/kg i.v. twice a day for a total of 16 days (4 plus 12 days, interrupted by a pause of 4 days), followed by weekly i.v. injection of 86 mg/kg (7 weeks). Active CMV infection was diagnosed on the basis of DNAemia in plasma, by a newly developed CMV polymerase chain reaction (PCR) test (AMPLICOR CMV). The disappearance of CMV from plasma was confirmed by this PCR test. It seems that single CMV-IG therapy is worth consideration for the treatment of CMV infection.

Antibodies, Viral↗
PubMed1997

[Incidence of Kanagawa phenomenon-positive and -negative Vibrio parahaemolyticus strains isolated from traveller's diarrhea and their relation to tdh and trh genes].

A total of 1,319 strains of Vibrio parahaemolyticus isolated from traveller's diarrhea were analysed for Kanagawa phenomenon (KP) with the Wagatsuma blood agar test and the results were also compared with those of analyses of tdh and trh genes which encode thermostable direct hemolysin (tdh) and TDH-related hemolysin (trh). The majority of the strains (1,152 strains) counting 87.3% had positive KP, among which 1,049 and 103 strains were only tdh and both tdh and trh-positive ones, respectively. However, 167 strains counting 12.7%, which is quite high compared to the previous report, were found to have negative KP, among which 94 and 24 strains were only trh and both tdh and trh-positive ones, respectively.

Bacterial Toxins↗
PubMed1997

Fluorodopa and raclopride PET analysis of patients with Machado-Joseph disease.

We performed [18F]6-fluoro-L-dopa (6-FD) and [11C]raclopride (RAC) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAC-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD.

Adolescent↗
PubMed1997

[Statistical analysis of pharmacological data: problem of multiple comparison].

Problems of multiple comparison were discussed without assuming technical knowledge of statistics. For the first question concerning why to use multiple comparison procedures, theoretical bases of statistical inference and multiple comparison (including type I error rate and familywise error rate) were briefly outlined. For the second question concerning how to properly use multiple comparison procedures, multiple comparison procedures were introduced, and their characteristics were compared. Families of comparisons are different among Dunnett's, Tukey's and Scheffe's tests. Assumptions of dose-response relationship are different among Dunnett's, Williams' tests and linear regression analysis. Duncan's test does not control familywise error rate at a fixed level. For the last question concerning what is remarked for multiple comparison, approaches to several problems such as abnormality and heteroscedasticity were provided. Philosophy and strategy to multiple comparison problems were discussed.

Data Interpretation, Statistical↗
PubMed1997

Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice.

Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) was investigated for its effect on the impaired learning of a passive avoidance task by mice induced by scopolamine or cycloheximide. SB-tPS (240, 360, 480 mg/kg) administered orally significantly prolonged the step-through latency shortened by scopolamine. SB-tPS (240 mg/kg) administered orally also prolonged the step-through latency shortened by cycloheximide. These results suggest that the effect of SB-tPS on the impaired learning behavior may be related not only to the cholinergic system but also the serotonergic system.

Administration, Oral↗