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Biomedical subjects

N Fujiwara

Publications and source records attributed to N Fujiwara.

At least 19 recordsLinked to original sources
PubMed2001

Dioxin and fly ash free incineration by ash pelletization and reburning.

Dioxins (DXNs) in municipal waste incinerator fly ash were effectively reduced by pelletizing the mixture of ash, cement, and sodium phosphate and reburning the pellets in a laboratory scale bubbling fluidized bed (BFB) furnace. Three types of pellets--A, B and C, of various sizes and compositions were used in the experiments. The efficiency of DXN reduction in the pellet matrix was proportional to the incineration time, temperature, and degree of pellet incineration. At 700 degrees C and incineration time sufficient for a complete burnout, the efficiency of DXN reduction in the pellets of type A and C was found to be 99.9% and 99.7%, respectively. Correspondingly, the DXN concentration in the pellets decreased from 862 ng TEQ/kg to 0.9 ng TEQ/kg for pellets A and 2.2 ng TEQ/kg for pellets C. The residual concentration of coplanar polychlorinated biphenyls (coplanar PCBs) was below 0.2 ng TEQ/kg and 0.4 ng TEQ/kg, respectively. Assuming a tortuosity factor of tau = 3 and the reaction rate constants of 0.013 m/s (at 700 degrees C) and 0.025 m/s (at 800 degrees C), the experimental pellet incineration times were reasonably predicted by using the shrinking core model. Possible DXN evaporation from the pellets was also studied. The amount of DXNs in the flue gas captured by an impinger trap was less than 3% when the reactor was operated at 700 and 800 degrees C. The described method of fly ash pelletization and reburning seems to be a relatively easy and inexpensive way to reduce both the emission of DXNs and the amount of fly ash.

Air Pollutants↗
PubMed2001

Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306.

Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 6-monomycolate. The length of carbon chains and number of double bonds of mycolic acids were C(34), C(36)and C(38)saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C(78-88)monoenoic and dienoic). Among them, only TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity.

Actinomycetales Infections↗
PubMed2001

Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and upregulation of CD1d1 on murine macrophages.

Trehalose 6,6'-dimycolate (TDM, cord factor) has frequently been used as an adjuvant to stimulate antibody production. Although it also induces cellular immunity, detailed studies about the underlying events do not exist. To determine the kinetics of TDM-specific changes promoting a T helper 1 (Th1) response, we injected mice with TDM or 2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL, sulfolipid), another mycobacterial trehalose-containing glycolipid without mycolic acid. TDM, but not SL, caused a strong increase in serum interferon-gamma (IFN-gamma) levels 2 days later, accompanied by expansion of natural killer (NK) cells. Subsequent TDM effects included depletion of normal-density CD4(+) NK1.1(+) TCRalpha/beta(intermediate) cells from day 7 on, upregulation of MHC class II and CD1d1 on macrophages (peaking on day 21), and an increased proportion of Th1 cells evident after 3 weeks. TDM, but not a similar glycolipid without mycolic acid, can therefore initiate a cascade of events starting with strong release of IFN-gamma and NK cell expansion, resulting in the appearance of macrophages activated for antigen presentation. Our data therefore provide the basis for optimized immunization schedules with TDM as the adjuvant component of a Th1 vaccine.

Adjuvants, Immunologic↗
PubMed2001

Relative validity of a semi-quantitative food frequency questionnaire versus 28 day weighed diet records in Japanese female dietitians.

OBJECTIVE: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). SUBJECTS AND METHODS: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996-1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. RESULTS: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum-median-maximum) ranged from 0.17 (beverages)-0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)-0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)-0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)-0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. CONCLUSIONS: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. SPONSORSHIP: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242).

Adult↗
PubMed2001

Effects of lifestyle factors on ultrasonographically determined bone health in Japanese women.

The objective of this study was to determine by ultrasonographic measurements, an inexpensive and radiation-free technique, the association between bone health and lifestyle factors among a large population of Japanese women. Two hundred and fifty-six pre-menopausal women and 585 post-menopausal women who underwent a voluntary medical check-up for osteoporosis in 1996-1997 were analyzed. There were significant positive correlations between the bone density (designated as the stiffness value) vs the weight, the height and the body mass index of the subjects only in the post-menopausal group. Negative correlations were also found between the bone density vs the age and the years since menopause. Our data using ultrasonographic technique agree well with previous studies using other devices. In both groups, subjects with current or past exercise habits had higher stiffness values. Dietary habits had no effects on the stiffness value. Smoking habits had a trend towards negative effects and alcohol consumption seemed to have a trend towards positive effects on the stiffness value in post-menopausal women, but these effects did not reach statistical significance. Positive effects of current exercise on bone density were maintained after adjustment for past exercise habits. These results support the effectiveness of exercise begun in adulthood. Having a good exercise habit is one of the most effective ways of maintaining good bone health.

Adult↗
PubMed2001

Roles of N-terminal active cysteines and C-terminal cysteine-selenocysteine in the catalytic mechanism of mammalian thioredoxin reductase.

Mammalian thioredoxin reductase [EC 1.6.4.5], a homodimeric flavoprotein, has a marked similarity to glutathione reductase. The two cysteines in the N-terminal FAD domain (-Cys59-x-x-x-x-Cys64-) and histidine (His472) are conserved between them at corresponding positions, but the mammalian thioredoxin reductase contains a C-terminal extension of selenocysteine (Sec or U) at the penultimate position and a preceding cysteine (-Gly-Cys497-Sec498-Gly). Introduction of mutations into the cloned rat thioredoxin reductase gene revealed that residues Cys59, Cys64, His472, Cys497, and Sec498, as well as the sequence of Cys497 and Sec498 were essential for thioredoxin-reducing activity. To analyze the catalytic mechanism of the mammalian thioredoxin reductase, the wild-type, U498C, U498S, C59S, and C64S were overproduced in a baculovirus/insect cell system and purified. The wild-type thioredoxin reductase produced in this system, designated as WT, was found to lack the Sec residue and to terminate at Cys497. A Sec-containing thioredoxin reductase, which was purified from COS-1 cells transfected with the wild-type cDNA, was designated as SecWT and was used as an authentic enzyme. Among mutant enzymes, only U498C retained a slight thioredoxin-reducing activity at about three orders magnitude lower than SecWT. WT, U498C, and U498S showed some 5,5'-dithiobis(2-nitrobenzoic acid)-reducing activity and transhydrogenase activity, and C59S and C64S had substantially no such activities. These data and spectral analyses of these enzymes suggest that Cys59 and Cys64 at the N-terminus, in conjunction with His472, function as primary acceptors for electrons from NADPH via FAD, and that the electrons are then transferred to Cys497-Sec498 at the C-terminus for the reduction of oxidized thioredoxin in the mammalian thioredoxin reductase.

Animals↗
PubMed2001

Proposal of Sphingomonas wittichii sp. nov. for strain RW1T, known as a dibenzo-p-dioxin metabolizer.

A polyphasic taxonomic study was performed on Sphingomonas sp. strain RW1T. The organism was isolated from water of the River Elbe and has been known as a potent metabolizer of dibenzo-p-dioxin and its relatives. TLC of a mild alkaline hydrolysate of extractable cellular lipids of strain RW1T and type strains of 21 Sphingomonas species gave a spot of sphingoglycolipid (SGL)-1 (glucuronosyl ceramide), which is characteristic of sphingomonads. In addition, strain RW1T and type strains of three Sphingomonas species (Sphingomonas yanoikuyae, Sphingomonas terrae and Sphingomonas macrogoltabidus) showed a second spot of SGL (SGL-1') identified as galacturonosyl ceramide. The presence of SGL-1 in cellular lipids suggested that strain RW1T is a member of the genus Sphingomonas. DNA-DNA reassociation rates between strain RW1T and each type strain of 14 Sphingomonas species including Sphingomonas paucimobilis, type species for the genus, revealed that strain RW1T is independent from these species. Results of phylogenetic analysis of 16S rDNA sequences of strain RW1T and type strains of 21 named Sphingomonas species verified that strain RW1T belongs to the genus Sphingomonas. Strain RW1T could be differentiated from named species of the genus by phenotypic characteristics and has been assigned to a new species, Sphingomonas wittichii sp. nov. The type strain is DSM 6014T (= JCM 10273T = EY 4224T). DNA G+C content is 67 mol %.

Bacterial Typing Techniques↗
PubMed2001

Trehalose 6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis induces foreign-body- and hypersensitivity-type granulomas in mice.

Granulomatous inflammation is characterized morphologically by a compact organized collection of macrophages and their derivatives. It is classified as either a hypersensitivity type or a foreign-body type. Lipid components of the Mycobacterium tuberculosis cell wall participate in the pathogenesis of infection. Strains of M. tuberculosis have cord factor (trehalose 6,6'-dimycolate [TDM]) on their surface. To clarify host responses to TDM, including immunogenicity and pathogenicity, we have analyzed the footpad reaction, histopathology, and cytokine profiles of experimental granulomatous lesions in immunized and unimmunized mice challenged with TDM. In the present study, we have demonstrated for the first time that TDM can induce both foreign-body-type (nonimmune) and hypersensitivity-type (immune) granulomas by acting as a nonspecific irritant and T-cell-dependent antigen. Immunized mice challenged with TDM developed more severe lesions than unimmunized mice. At the active lesion, we found monocyte chemotactic, proinflammatory, and immunoregulatory cytokines. The level was enhanced in immunized mice challenged with TDM. This result implies that both nonimmune and immune mechanisms participate in granulomatous inflammation induced by mycobacterial infection. Taken together with a previous report, this study shows that TDM is a pleiotropic molecule against the host and plays an important role in the pathogenesis of tuberculosis.

Animals↗
PubMed2000

Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells.

Although estrogen is known to activate endothelial nitric oxide synthase (eNOS) in the vascular endothelium, the molecular mechanism responsible for this effect remains to be elucidated. In studies of both human umbilical vein endothelial cells (HUVECs) and simian virus 40-transformed rat lung vascular endothelial cells (TRLECs), 17beta-estradiol (E2), but not 17alpha-E2, caused acute activation of eNOS that was unaffected by actinomycin D and was specifically blocked by the pure estrogen receptor antagonist ICI-182,780. Treatment of both TRLECs and HUVECs with 17beta-E2 stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the 17beta-E2-induced activation of Akt. 17beta-E2-induced Akt activation was also inhibited by ICI-182,780, but not by actinomycin D. Either treatment with wortmannin or exogenous expression of a dominant negative Akt in TRLECs decreased the 17beta-E2-induced eNOS activation. Moreover, 17beta-E2-induced Akt activation actually enhances the phosphorylation of eNOS. 17beta-E2-induced Akt activation was dependent on both extracellular and intracellular Ca(2+). We further examined the 17beta-E2-induced Akt activity in Chinese hamster ovary (CHO) cells transiently transfected with cDNAs for estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta). 17beta-E2 stimulated the activation of Akt in CHO cells expressing ERalpha but not in CHO cells expressing ERbeta. Our findings suggest that 17beta-E2 induced eNOS activation through an Akt-dependent mechanism, which is mediated by ERalpha via a nongenomic mechanism.

Animals↗
PubMed2000

Ischemic tolerance preserves propagation of membrane depolarization.

The functional integrity of the synaptic connections within the hippocampus in gerbils that had acquired ischemic tolerance was investigated. The propagation of membrane depolarization across the hippocampus in response to electrical stimulation of CA1 was monitored with the use of a high speed optical recording technique. In comparison to control slices, propagation was significantly depressed and depolarization was shortened in slices from gerbils subjected to 5 min of ischemia. Hippocampal slices from gerbils who were preconditioned with prior sublethal ischemia demonstrated only a slight reduction in propagation. The duration of depolarization was longer than that of ischemia group. These findings suggest that ischemia induces a functional disturbance of synaptic transmission and membrane depolarization. Ischemic preconditioning significantly reduced the extent of this functional disturbance.

Animals↗
PubMed2000

A potent inhibitor of inducible nitric oxide synthase, ONO-1714, a cyclic amidine derivative.

(1S,5S,6R,7R)-7-Chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride (ONO-1714), a novel cyclic amidine analogue, inhibits human inducible nitric oxide (iNOS) with a K(i) of 1.88 nM and rodent iNOS with similar potency in vitro. ONO-1714 was found to be 10-fold selective for human iNOS over human endothelial NOS (ecNOS). When the inhibitory activity of ONO-1714 was compared for iNOS, it was found to be 451-fold and >20,000-fold more potent than L-NMMA and aminoguanidine (AG), respectively. In terms of human iNOS selectivity, ONO-1714 was approximately 34- and 2-fold more selective for iNOS than L-NMMA and AG, respectively. ONO-1714 inhibited the LPS-induced elevation of plasma nitrate/nitrite in mice with an ID(50) value of 0.010 mg/kg, s.c. The maximum tolerated dose of ONO-1714 was 30 mg/kg, i.v. Thus, ONO-1714 represents one of the most potent iNOS inhibitors in vitro and in vivo to date and has great potentials for use as an inhibitor for clarifying the pathophysiological roles of iNOS and for use as a therapeutic agent.

Amidines↗
PubMed2000

Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension : modulation of nitric oxide synthesis by salt intake.

BACKGROUND: High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. METHODS AND RESULTS: Inpatients with essential hypertension (n=24) were maintained on a normal-salt diet (12 g/d NaCl) for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (n=16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by >5% by salt loading were assigned to group 1 (n=8) and the others to group 2 (n=16). Nitrate plus nitrite (NO(x)) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NO(x) level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NO(x) level was decreased and reversed after the second salt restriction. Plasma ADMA level was increased after salt loading and decreased after salt restriction. The change in plasma NO(x) level was correlated inversely with those in blood pressure (r=-0.59, P=0.0007) and plasma ADMA level (r=-0.64, P=0.003) after salt loading and restriction. CONCLUSIONS: Modulation of NO synthesis by salt intake may be involved in a mechanism for salt sensitivity in human hypertension, presumably via the change in ADMA.

Adult↗
PubMed2000

Primary somatosensory cortex is actively involved in pain processing in human.

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.

Adult↗
PubMed2000

Monitoring of human herpesvirus-6 and -7 genomes in saliva samples of healthy adults by competitive quantitative PCR.

Human herpesviruses-6 and -7 (HHV-6 and HHV-7) are thought to be transmitted during early infancy through saliva. However, the kinetics of the virus shedding in saliva of healthy adults, from whom children are assumed to acquire the viruses, is mostly unknown. This study was conducted to determine how many copies of the genome are secreted in saliva of healthy adults and to clarify the relationship between viral DNA load and virus isolation of HHV-6 and HHV-7. Competitive PCR was performed using primer sets in the U42 gene of each viral genome. In saliva samples from 29 healthy adults, HHV-6 and HHV-7 DNA was detected in 41.4% and 89.7%, respectively. The average copy number of the HHV-7 genome in the positive samples was higher than that of the HHV-6 genome. Follow-up studies of six seropositive individuals for 3 months showed that the amount of HHV-7 DNA was constant in each individual and that "high producers" and "low producers" could be distinguished. By contrast, the amount of HHV-6 DNA varied drastically over time in each individual. Although HHV-6 was never isolated from the saliva of any of the six individuals during the follow-up period, HHV-7 was isolated from each individual several times. The amount of HHV-7 DNA tended to be higher at the times when the virus was isolated than at the times when the virus was not isolated. These data demonstrate a striking contrast between HHV-6 and HHV-7 in the kinetics of genome and virus shedding.

Adult↗
PubMed2000

Postnatal differentiation of Merkel cells in the rat palatine mucosa, with special reference to the timing of peripheral nerve development and the potency of cell mitosis.

The origin and mechanism of the differentiation and proliferation of Merkel cells are enigmatic. A preliminary study in our laboratory showed that Merkel cells in the rat palatine mucosa emerge after birth. This is in contrast to the case of similar cells in the skin that differentiate during the embryonic period prior to the establishment of peripheral nerve innervation. We studied immunohistochemically the developmental timings of Merkel cells and peripheral nerves in the rat palatine mucosa using antibodies to cytokeratins 18 and 20, PGP 9.5, and CGRP using developing palates of prenatal and postnatal rats. We also studied the potency of mitosis in Merkel cells by immunohistochemistry using antibodies for a cell proliferation marker Ki67 and cyclin D-kinase inhibitors p16, p21 and p27. It was shown that Merkel cells in the rat palatine mucosa differentiate postnatally, after the development of peripheral nerve fiber terminals was almost established. The emergence and increase in number of Merkel cells progressed in an anterior-to-posterior wave. Newly appearing Merkel cells were usually negative for anti-cytokeratin 20 antibody but gained affinity for the antibody with progress of maturation. All Merkel cells in the palatine mucosa were negative for anti-Ki67 antibody but positive for anti-p27 antibody. These results indicate that Merkel cells in the rat palatine mucosa are not responsible for the development of peripheral nerve fiber terminals and that these cells differentiate in situ from intraepithelial stem cells.

Animals↗
PubMed2000

Salt-induced exacerbation of morning surge in blood pressure in patients with essential hypertension.

The morning surge in blood pressure (BP) is related to the morning occurrence of lethal cardiovascular events. We tested the hypothesis that salt intake may be associated with the morning surge in BP in essential hypertension. Seventy-six patients were admitted and placed on a low salt diet (2 g/day) for 7 days followed by a high salt diet (20-23 g/day) for another 7 days. At the end of each salt diet, 24-h ambulatory BP and heart rate monitorings and head-up tilt (HUT) test were performed. Patients whose average mean BP (MBP) was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 37); the remaining patients, whose MBP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 39). The increase in ambulatory MBP during 6.30-8.00 am above the baseline (2.00-4.00 am) was significantly enhanced by salt loading in the NSS group (P < 0.05), but not in the SS group. The coefficient of variation of 24-h MBP and heart rate was increased by salt loading only in the NSS group. The significant elevation of plasma noradrenaline concentration after awakening, which was noted during the low salt diet period, was unchanged during the high salt diet period in the NSS group, but abolished in the SS group. Salt loading enhanced HUT-induced decrease in systolic BP without affecting the heart rate response only in the NSS group. We conclude that the morning surge in BP is enhanced by salt loading in the NSS type of essential hyper- tension, presumably by the excessive activation of the sympathetic nervous system. Journal of Human Hypertension (2000) 14, 57-64.

17-Hydroxycorticosteroids↗