PubMed Health⌕ Search

Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 55 records · Page 3Linked to original sources
PubMed1999

Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice.

Several lines of evidence show the importance of angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the renin-angiotensin system (RAS) was observed in both groups of mice at around day 1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was transiently induced at six hours in both groups, which was then downregulated at day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed, and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I increased, resulting in severe glomerulosclerosis and interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria, and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this amelioration is likely due to the lack of AT1a, we can conclude that AII action, mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may contribute to the exacerbation of glomerular MCP-1 expression. These results suggest the involvement of AII in immune-mediated renal injuries.

Angiotensin II↗
PubMed1998

Involvement of angiotensin II in development of spontaneous nephrosis in Dahl salt-sensitive rats.

We investigated the effect of angiotensin-converting enzyme inhibition on spontaneous nephrosis in Dahl salt-sensitive (Dahl/S) rats. Dahl/S rats fed on a normal sodium diet spontaneously developed nephrosis and mild hypertension from a young age. In young Dahl/S rats, an angiotensin-converting enzyme inhibitor, imidapril, attenuated the development of proteinuria accompanied by a decrease in blood pressure. Methylprednisolone, a potent therapeutic agent for proteinuria, did not affect the development of nephrosis. An angiotensin AT1 receptor antagonist, losartan, but not a Ca2+ channel blocker, verapamil, inhibited the development of nephrosis while both agents decreased blood pressure to a similar extent as imidapril. In mature Dahl/S rats, imidapril suppressed not only the development of proteinuria but also the glomerular lesions. It is concluded that the development of spontaneous nephrosis in Dahl/S rats is mediated by angiotensin II.

Aging↗
PubMed1998

Diagnostic value of plasma thrombin-antithrombin III complex and D-dimer concentration in patients with varicose veins for exclusion of deep-vein thrombosis.

The aim of this study was to evaluate the usefulness of determining plasma D-dimer (DD) and thrombin-antithrombin III complex (TAT) levels in the diagnostic workup for the screening of deep-venous thrombosis (DVT) among varicose vein patients. One hundred forty consecutive patients being treated for DVT or varicose veins underwent color-flow duplex scanning, and 25 patients had DVT and the remaining 115 had primary varicose veins. When DD and TAT were analyzed statistically in combination, it was determined that the combination of either positive DD (cutoff level 1.0 microg/ml) or positive TAT (cutoff level 3.0 microg/l) had a sensitivity of 100% for DVT with a specificity, positive predictive value, and negative predictive value of 79%, 51%, and 100%, respectively. This study demonstrates plasma levels of DD (less than 1.0 microg/ml) and TAT (less than 3.0 microg/l) in combination to be useful for the exclusion of DVT among patients with varicose veins. Patients with negative hematological data may safely undergo surgical treatment for varicose veins without further evaluation such as duplex scanning or contrast venography.

Antithrombin III↗
PubMed1998

A case of Kearns-Sayre syndrome showing a constant proportion of deleted mitochondrial DNA in blood cells during 6 years of follow-up.

Kearns-Sayre syndrome (KSS) and Pearson syndrome (PS) show quite different phenotypes despite the same underlying genetic defect, i.e. a large deletion of one population of mitochondrial (mt) DNA. The main feature of KSS is progressive encephalomyopathy; on the other hand, PS shows fatal hematological problems in early infancy. Through Southern blot analysis of mtDNA of blood cells, deletion has been consistently found in patients with PS but usually undetectable in KSS patients. Therefore, their different clinical phenotypes have been explained by the different tissue distribution of mutant mtDNA. Recently, a few cases were reported which had features of PS in infancy and later developed KSS. These observations suggest that phenotypes may also be modified by the selection process involving mtDNA within different tissues. We found a case of KSS, who initially presented endocrinological dysfunction such as insulin-dependent diabetes mellitus (IDDM) and growth hormone (GH) deficiency, and had not developed external ophthalmoplegia until the age of 17. Although he did not show any symptoms of PS, a marked proportion of mtDNA was deleted not only in muscle but also in blood cells. Analysis of his blood cells showed an unchanged proportion of deleted mtDNA at three estimations within 6 years of the follow-up period. This case provides evidence that deleted mtDNA in blood cells also has a stable replicative capacity and that a large proportion of deleted mtDNA in blood cells may not accompany hematological problems.

Anemia, Sideroblastic↗
PubMed1998

Regional differences in alpha1-adrenoceptor subtypes and mechanisms in rabbit arteries.

Contractility mediated through alpha1-adrenoceptor subtypes and the maximum binding site (Bmax value) and the dissociation constant (Kd value) for [125I]HEAT ([125I]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca2+-free physiological saline solution (Ca2+-free PSS), the pA2 values for 5-methylurapidil were also similar except for the renal artery, in which there were no stable contractions. In normal PSS, the concentration-response curves for norepinephrine with chloroethylclonidine-pretreatment were shifted to the right (pD2 values of 5.58, 5.70, 5.74, 5.98 and 6.38 for thoracic and abdominal aorta, mesenteric, renal and iliac arteries, respectively). In the [125I]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the Bmax values (33.2-105.2 fmol/mg protein) for [125I]HEAT varied considerably among arteries, while the Kd values (0.20-0.26 nM) were identical. The logarithm of Bmax values is proportional to the pD2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (pD2 value) of the alpha1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha1-adrenoceptor subtypes in rabbit arteries.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1998

Molecular cloning of Saccharomyces cerevisiae MLF4/SSH4 gene which confers the immunosuppressant leflunomide resistance.

Immunosuppressant leflunomide inhibits the growth of cytokine-stimulated lymphoid cells in vitro and also inhibits the growth of eukaryotic microorganism Saccharomyces cerevisiae. To elucidate the molecular mechanism of the action of the drug, a yeast gene which suppresses the anti-proliferative effect when in increased copy number was cloned and designated MLF4 for multicopy suppressor of leflunomide sensitivity. DNA sequencing analysis indicates that the MLF4 gene is identical to the SSH4 gene which suppresses the shr3 mutation. Excess of amino acids overcame the anti-proliferative activity of leflunomide. Thus, leflunomide is suggested to affect amino acid transport by interacting with Shr3 chaperon-like protein.

Amino Acids↗
PubMed1998

Three novel missense mutations in unrelated Japanese patients with type I and type II protein S deficiency and venous thrombosis.

A molecular analysis of protein S deficiency in three unrelated Japanese patients was performed. An approximately 50% reduction in both functional and immunologic levels of protein S was detected in the plasmas from two unrelated patients, designated protein S Osaka 1 and protein S Osaka 2. An approximately 50% reduction in the functional level, but a normal immunologic level of protein S, was detected in plasma from a third patient, designated protein S Osaka 3. All of the exons and exon/intron junctions of the protein S gene were studied using a strategy combining polymerase chain reaction amplification and rapid non-radioactive single-strand conformational polymorphism analysis. We identified a G-to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation resulted in the substitution of Gly for Ser at position 295 in the sex hormone-binding globulin-like region. In protein S Osaka 2, a G-to-C change at the position of the 3' end of exon III was identified, leading to the amino acid substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3, an A-to-G change in exon II was identified, leading to the substitution of Lys9 by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu mutation causes type II deficiency.

Adult↗
PubMed1998

Severe motor-dominant neuropathy with IgM M-protein binding to the NeuAcalpha2-3Galbeta- moiety.

We report the occurrence of a relapsing, severe predominantly motor neuropathy in a 75-year-old man with an IGM-K M-protein binding to gangliosides GM2, GM3, GM4, GD1a, GT1b and LM1. Motor nerve conduction velocities were slowed with conduction block. A superficial peroneal nerve biopsy specimen revealed segmental demyelination and remyelination. The patient improved after repeated plasma exchanges, and the antibody titer decreased in association with clinical recovery. This IgM M-protein has a unique, previously unreported binding specificity for terminal NeuAcalpha2-3Galbeta- moiety in common to all gangliosides bound by the antibody except GM2. M-proteins with this affinity may be involved in the pathogenesis of this and other cases of motor-dominant demyelinating neuropathy.

Aged↗
PubMed1998

The fluid-attenuated inversion-recovery pulse sequence in assessment of central nervous system involvement in myotonic dystrophy.

We compared the fluid-attenuated inversion recovery (FLAIR) sequence with conventional spin-echo (SE) imaging for detection of involvement of the central nervous system in five patients with myotonic dystrophy (MD). The diagnosis was made based on clinical features and DNA analysis. All patients showed abnormal high-intensity lesions in the white matter on T2-weighted images, although these were more clearly visible using FLAIR.

Adult↗
PubMed1998

Growth inhibition of Saccharomyces cerevisiae by the immunosuppressant leflunomide is due to the inhibition of uracil uptake via Fur4p.

The immunosuppressant leflunomide inhibits cytokine-stimulated proliferation of lymphoid cells in vitro and also inhibits the growth of the eukaryotic microorganism Saccharomyces cerevisiae. To elucidate the molecular mechanism of action of the drug, two yeast genes which suppress the anti-proliferative effect when present in multiple copies were cloned and designated MLF1 and MLF2 for multicopy suppressor of leflunomide sensitivity. DNA sequencing analysis revealed that the MLF1 gene is identical to the FUR4 gene, which encodes a uracil permease and functions to import uracil efficiently. The MLF2 was found to be identical to the URA3 gene. Excess exogenous uracil also overcomes the anti-proliferative effect of leflunomide on yeast cells. Uracil prototrophy also conferred resistance to leflunomide. Uracil uptake was inhibited by leflunomide. Thus, the growth inhibition by leflunomide seen in a S. cerevisiae ura3 auxotroph is due to the inhibition of the entry of exogenous uracil via the Fur4 uracil permease.

Biological Transport↗
PubMed1998

Fas has a crucial role in the progression of experimental autoimmune encephalomyelitis.

To investigate the role of Fas in experimental autoimmune encephalomyelitis (EAE) in mice, we examined the susceptibility of EAE in C57BL/6 (B6).lpr mice lacking Fas. The frequency of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in B6.lpr mice was significantly lower than that in B6 mice (19% vs 94%). However, no significant difference was observed between them in either the lymphocyte proliferation response or antibody reactivity to MOG. In addition, the histological examination and semiquantitative reverse transcriptase polymerase chain reaction analysis revealed that the infiltration of inflammatory cells and the up-regulation of gene expression for inflammatory cytokines occurred in the central nervous system (CNS) of B6.lpr mice immunized with MOG, even if they showed no clinical sign. These results indicate that Fas may contribute to the pathogenesis of EAE and may play a crucial role in the expansion of inflammation and/or myelin destruction in the CNS rather than in the activation of encephalitogenic T cells in the periphery and/or the breakdown of blood brain barrier.

Animals↗
PubMed1998

Aminoguanidine, a selective inhibitor of the inducible nitric oxide synthase, has different effects on experimental allergic encephalomyelitis in the induction and progression phase.

To elucidate the role of excessive nitric oxide (NO) via the inducible nitric oxide synthase (iNOS) in experimental allergic encephalomyelitis (EAE), the effect of a selective iNOS inhibitor, aminoguanidine, was investigated using mice with actively induced EAE. Administration of aminoguanidine by intraperitoneal or intracisternal injection from day 2 to day 12 after immunization produced a significant delay in the onset of EAE. On the other hand, administration of aminoguanidine by intraperitoneal or intracisternal injection for 10 days after the onset of EAE enhanced the clinical severity and mortality rate and hastened the onset of relapse significantly. The histological study at day 11 after the onset revealed that more inflammatory cells were present in the central nervous system of mice treated with aminoguanidine as compared with mice without aminoguanidine treatment. These results suggested that NO via iNOS was a pathogenetic factor in the induction phase of EAE, but had an inhibitory role in the progression phase of EAE. Although the effect of NO synthase inhibitors on EAE has been controversial, the present study suggested that the timing of administration might be an important consideration and might explain the previous contradictory reports.

Acute Disease↗
PubMed1998

IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein.

The role of IL-6 in experimental autoimmune encephalomyelitis (EAE) provoked by myelin oligodendrocyte glycoprotein (MOG) was investigated using IL-6-deficient mice. We show here that IL-6-deficient mice were resistant to the MOG-induced EAE as compared to wild-type mice (one out of 18 versus 17 out of 20). The delayed-type hypersensitivity response, lymphocyte proliferation response and antibody reactivity to MOG in IL-6-deficient mice were significantly lower than those in wild-type mice. Furthermore, the histological examination revealed that no infiltration of inflammatory cells was observed in the central nervous system of IL-6-deficient mice. These results indicate that IL-6 may play a crucial role in the induction phase of EAE. Given the potential relevance of this animal model for multiple sclerosis (MS), it is possible that anti-IL-6 therapy may be useful in the prevention of relapses of MS.

Animals↗
PubMed1998

[The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract].

The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C-radioactivity may be excreted into the expired air. The results suggest that Car-Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption.

Administration, Oral↗
PubMed1998

[An autopsy case of Degos' disease with ascending thoracic myelopathy].

Degos' disease is a rare multisystem vasculopathy of unknown etiology. We report a 44-year-old man who presented himself with gait and sensory disturbances mainly due to thoracic transverse myelopathy four years after the appearance of many characteristic umbilicated papules over the trunk and extremities. He did not complain of abdominal pain or discomfort. Laboratory, electrophysiological and imaging studies did not show any characteristic change, except for the increase of protein contents and cell counts in the cerebrospinal fluid. We tried methylprednisolone pulse-dose therapy (1,000 mg/day x 3 days) five times, but this patient's neurological condition worsened stepwise after it, although the appearance of new skin lesion was suppressed. Intravenous infusion of ozagrel sodium and cyclophosphamide (1,000 mg/day) were also ineffective, and this patient died of respiratory failure after showing oculomotor paresis and comatose state. Necropsy revealed Degos' disease-specific vasculopathy in the central nervous system and the gastrointestinal tract, where occlusions of small-sized arteries and veins due to the intimal thickening were evident. The tissue necrosis was macroscopically remarkable in the brainstem and the thoracic spinal cord. The efficacy of steroid therapy for this disease should be investigated more carefully.

Adult↗