PubMed Health⌕ Search

Biomedical subjects

M Fujihara

Publications and source records attributed to M Fujihara.

At least 55 records · Page 3Linked to original sources
PubMed1996

Decreased inducible expression of CD80 and CD86 in human monocytes after ultraviolet-B irradiation: its involvement in inactivation of allogenecity.

Ultraviolet-B (UV-B) irradiation of antigen presenting cells (APCs) modifies their allogenecity, resulting in inhibition of the proliferative response of T cells in mixed lymphocyte reaction (MLR). Costimulation by the CD28 ligand CD80 (B7/B7-1) and CD86 (B70/B7-2) plays an important role during T-cell proliferation by augmenting synthesis of interleukin-2 (IL-2) and other cytokines. In this study, we demonstrated induced expression of both CD80 and CD86 during allogeneic MLR, though human freshly isolated monocytes express CD86 constitutively with a much lower level of CD80. A monoclonal antibody (MoAb) against CD86, but not CD80, efficiently inhibited allogeneic T-cell proliferative responses stimulated with highly purified monocytes. UV-B exposure (0 to 1,000 J/m2) of monocytes inhibited the proliferation of T lymphocytes in MLR in a dose-dependent manner. Flow cytometric analysis showed that UV-B exposure of monocytes impaired the constitutive expression of CD54 (intercellular adhesion molecule-1) by 24 hours after irradiation, but the effect on CD86 was relatively less. The surface expression of CD80, CD86, CD54, and HLA-DR on monocytes was further augmented by interferon (IFN)-gamma; this cytokine-induced expression was dose-dependently reduced by UV-B irradiation. Similarly, the upregulation of these molecules following allogeneic MLR was downregulated by UV-B irradiation. UV-B irradiation of monocytes inhibited the expression of IL-2 mRNA in monocyte-stimulated allogeneic MLR. In contrast, the addition of anti-CD28 MoAb at the onset of MLR prevented, at least partially, the reduction of IL-2 mRNA. These results strongly suggest that the impairment of inducible expression of CD86 and CD80 may contribute to the reduced MLR response following exposure of monocytes of UV-B.

Antibodies, Monoclonal↗
PubMed1996

Pathological features of invasive oral aspergillosis in patients with hematologic malignancies.

PURPOSE: Little is known about the characteristic macroscopic and microscopic changes that take place during the progression of oral invasive aspergillosis in immunocompromised patients. The aim of this study was to determine the relationship between the oral and histopathologic findings in these patients. Such a study would aid in understanding the early development of subsequent progression of the disease. PATIENTS AND METHODS: Twelve patients with hematologic malignancies who developed invasive oral aspergillosis were studied. The condition was divided into three stages according to the oral findings at the time biopsy procedures were performed. Tissue sections from biopsy specimens were stained with hematoxylin and eosin for histopathologic study and the findings were evaluated in relation to the oral findings. Fungal cultures of biopsy specimens were also performed to confirm the causative organisms. RESULTS: The diagnosis of oral aspergillosis was established in terms of both histologic and microbiologic evidence in all 12 patients. In the early stage (three patients), isolated areas of violaceous marginal gingiva consisted of degenerated epithelium and connective tissue infiltrated by fungal hyphae. In the advanced stage (four patients), the violaceous marginal gingiva had become transformed into gray necrotic lesions that extended to the attached gingiva. The necrotic lesions showed ulceration and were covered by a pseudomembrane containing fungal hyphae. At the base of the ulcers, connective tissue was occupied by proliferating fungal hyphae, with vascular invasion being observed. In the late stage (five patients), the ulcerated lesions had progressed, showing destruction of the alveolar bone and surrounding facial muscles, with infiltration of fungal hyphae unto the tissues. No inflammatory cellular reaction was observed until the hematologic status of the patients improved. CONCLUSION: These findings indicate that invasive oral aspergillosis has three distinctive clinicopathological stages. Recognition of the different stages of invasive Aspergillus infections is helpful for correct diagnosis of the disease.

Adult↗
PubMed1996

Effects of ultraviolet B irradiation on cell-cell interaction; implication of morphological changes and actin filaments in irradiated cells.

We studied the effects of ultraviolet B (UV-B) irradiation on cell-cell interactions using mouse lymphoma RMA cells and T cell hybridoma HTB-176.10. RMA cells act as stimulators by presenting H-2Kb surface antigens to HTB-176.10 cells, inducing IL-2 production in HTB-176.10 cells. Irradiating RMA cells with 1000J/m2 UV-B suppressed cell cluster formation between RMA and HTB-176.10 cells and reduced the level of IL-2 production in HTB-176.10 cells, although H-2Kb surface antigens of RMA cells were still expressed. Electron microscopic observations of irradiated RMA cells revealed that UV-B irradiation damaged cell structures, resulting in the disappearance of microvilli on the cell surface, destruction of mitochondria, vacuolation of cytoplasm and swelling of the perinuclear cisterna space. We found that these alterations were accompanied by polymerization of filamentous actin quantified by flow cytometry after NBD-phallacidin staining. Our results suggest that a target of UV-B-induced alterations is actin filaments, which support the cell morphology as the cytoskeleton, and that modification of filamentous actin inhibits interaction between RMA and HTB-176.10 cells. This underlying mechanism may account for the impaired interaction between antigen-presenting cells and T cells after transfusion with UV-B-irradiated allogeneic blood components.

Actins↗
PubMed1996

Cyst sclerotherapy with minocycline hydrochloride in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: The enlarged cysts in autosomal dominant polycystic kidney disease (ADPKD) frequently cause abdominal discomfort. Cyst sclerotherapy with minocycline hydrochloride was performed to relieve this symptom. METHODS: Ten symptomatic ADPKD cases were recruited. As a sclerosant, minocycline hydrochloride solution (10 mg/dl) was used. This solution was instilled into the cysts under ultrasonographic control. Renal volume was calculated before therapy and at 6-month intervals thereafter. Renal function and blood pressure were regularly monitored. The effect of sclerotherapy on symptoms was also assessed at 6-month intervals. RESULTS: At 6 months, renal volume was statistically lower than the presclerotherapy, and was associated with improvement in chronic symptoms. However, such ameliorating effects were blunted at 12 months. Renal volume reduction at 6 and 12 months showed a significant positive correlation with the dose of minocycline injected. No significant influence in renal function and blood pressure was observed. CONCLUSIONS: These results suggest that cyst sclerotherapy with minocycline hydrochloride is a valid treatment regime for the relief of chronic symptoms in ADPKD cases, although repeated application of this approach may be required to obtain a more long-term effect.

Adult↗
PubMed1996

Effect of FK 506 administered topically versus intramuscularly on suppression of the corneal immune reaction in rats.

The immunosuppressive effect of FK 506 on penetrating keratoplasty in rats was evaluated following intramuscular and topical administration. Implanted corneal grafts were inspected weekly by clinical evaluation for 3 weeks. Cytotoxic T lymphocyte (CTL) activity was measured in the spleen on postoperative day 21, and the grafts were examined histologically. A dose of FK 506, 0.1 mg/kg given intramuscularly, only moderately suppressed CTL activity and the graft failed. In contrast, doses of either 0.024 mg/day topically or 0.3 mg/kg intramuscularly suppressed CTL activity and the grafts remained intact. Results suggest that FK 506 administered topically would be effective in preventing failure of human corneal grafts.

Administration, Topical↗
PubMed1996

Serum and urinary levels of insulin-like growth factor I in patients with chronic renal disease and diabetes mellitus: its clinical implication.

The aim of this study was to determine the clinical significance of serum and urinary insulin-like growth factor I (IGF-I) in renal disease and diabetes mellitus. In renal portion, we measured their concentrations in patients with chronic renal disease (serum creatinine < 2.0 mg/dl) (CRD. n = 22) and those with chronic renal failure (serum creatinine > or = 2.0 mg/dl) (CRF, n = 26) and compared with normal healthy controls (C. n = 20). Serum concentrations growth hormone (GH) and IGF-I did not differ among these groups. Urinary IGF-I level was significantly increased in CRF (4.0 +/- 0.5 ng/mg creatinine) compared with CRD (2.8 +/- 0.6 ng/mg creatinine) and C (1.8 +/- 1.0 ng/mg) creatinine). Urinary IGF-I did not correlate with either serum GH or serum IGF-I. Urinary IGF-I, but not serum IGF-I, demonstrated a significant negative correlation with creatinine clearance. In diabetic portion, 29 patients with noninsulin dependent diabetes mellitus (NIDDM), whose serum creatinine were within normal range, and age-matched 12 subjects were enrolled. Serum IGF-I in NIDDM (130 +/- 11 ng/ml) was significantly lower than that in controls (201 +/- 11 pg/ml). In contrast, urinary IGF-I level in NIDDM (1.93 +/- 0.31 ng/mg creatinine) did not differ from that in controls (2.00 +/- 0.31 ng/mg creatinine). In NIDDM, urinary IGF-I had poor correlation with both serum IGF-I and albuminuria. The data in renal patients suggest the possible participation of renal IGF-I in the progression of renal disease, while in NIDDM with normal serum creatinine the role of renal IGF-I may be less in the early diabetic nephropathy.

Adult↗
PubMed1996

Effects of low dose of recombinant human growth hormone on renal excretion of insulin-like growth factor-I (IGF-I) in humans: an inverse relation between serum and urinary IGF-I level.

To elucidate the possible physiological interaction between growth hormone (GH) and insulin-like growth factor-I (IGF-I) system in human kidney, recombinant human GH (rhGH), which reached a supranormal level of serum GH, was administered, and serum and urinary IGF-I levels were determined in 6 normal men. The first two days served as a pre-control period (preTx). At days 3 and 4 (Tx), 2 U of rhGH was subcutaneously injected twice at 8:00 AM and 8:00 PM. The following three days (days 5, 6, 7) served as a post-control period (postTx). After rhGH administration, serum level of GH increased rapidly, followed by elevation of serum IGF-I concentration. Changes in creatinine clearance during the study were not significant. The 24-hour urinary IGF-I output decreased significantly during the rhGH administration period compared with that in pre- and post-Tx. During the Tx, urine volume and urinary excretion of electrolytes decreased compared with those in preTx, and mostly returned to the preTx level during postTx. These results indicated an inverse relationship between serum and urinary IGF-I level during the supranormal elevation of serum GH, suggesting IGF-I accumulation within the kidney.

Adult↗
PubMed1995

Endotoxin antagonism by a synthetic lipid A analogue, DT-5461, with low endotoxicity in human peripheral blood monocytes.

We examined the molecular mechanism of DT-5461-induced LPS antagonism in human peripheral blood monocytes. Dose-response studies revealed that LPS-induced IL-1 and TNF-alpha production was apparently totally suppressed in a competitive manner by a 10-fold excess of DT-5461. A 10-fold excess of DT-5461 significantly blocked the binding of FITC-LPS to the monocytes. DT-5461 suppressed IL-1 and TNF-alpha mRNA expression in LPS-activated monocytes. Western blots showed that DT-5461 suppressed the LPS-induced tyrosine phosphorylation of p42mapk/ERK2. These results suggested that the competitive binding inhibition and repression of early intracellular signaling involved in DT-5461-mediated LPS antagonism.

Adjuvants, Immunologic↗
PubMed1995

Oral Fusarium infection in a granulocytopenic patient with acute myelogenous leukemia: a case report.

The fungus Fusarium moniliforme causes fusariosis, which can be invasive and fatal in immunocompromised patients. We report a case of oral Fusarium infection in a granulocytopenic patient with acute myelogenous leukemia who developed necrotic ulceration of the gingiva, extending to the alveolar bone, but was otherwise free of any active systemic lesions. Fusarium moniliforme was identified, by histopathology and culture, to be present in the lesion and was deduced to be the causative organism for this invasive oral infection.

Acute Kidney Injury↗
PubMed1995

A novel synthetic lipid A analog with low endotoxicity, DT-5461, prevents lethal endotoxemia.

Bacterial endotoxin (lipopolysaccharide [LPS]) causes severe damage to the host organism as a result of excessive release of inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), from mononuclear phagocytes during gram-negative bacterial infection. We evaluated the ability of a novel synthetic lipid A analog with low endotoxicity, DT-5461, to antagonize LPS-induced IL-1 and TNF-alpha production in cells of monocyte/macrophage lineage and examined the protective effect of DT-5461 against lethal endotoxic shock in mice. The IL-1- or TNF-alpha-inducing activity of DT-5461 is 100,000 to 10,000 times less active than that of Escherichia coli LPS (EcLPS) or synthetic lipid A. DT-5461 significantly inhibited EcLPS-induced IL-1 and TNF-alpha release when murine peritoneal macrophages were incubated with DT-5461 2 h prior to EcLPS stimulation at the same concentration (1 microgram/ml). The antagonistic effect of DT-5461 on the production of IL-1 and TNF-alpha induced by EcLPS occurred in a concentration-dependent manner. DT-5461 also inhibited IL-1 and TNF-alpha induction when murine peritoneal macrophages were stimulated by LPS from Salmonella typhimurium or synthetic lipid A, as well as by EcLPS, but not by muramyl dipeptides. This indicated that DT-5461 specifically antagonized the action of LPS. DT-5461 also antagonized EcLPS-mediated activation of human peripheral blood monocytes. DT-5461 blocked the binding of fluorescein isothiocyanate-labelled LPS to murine peritoneal macrophages as well as it did the binding of EcLPS and synthetic lipid A, i.e., in a concentration-dependent fashion. Injection of DT-5461 2 h before EcLPS challenge prevented the production of serum IL-1 and TNF-alpha in D-galactosamine-treated mice. Furthermore, this treatment modality protected mice against LPS-induced lethal toxicity. This study suggests that DT-5461 possesses a potent LPS antagonistic effect and may be useful in a protective strategy against lethal endotoxemia caused by gram-negative bacterial infection.

Animals↗
PubMed1995

Suppression of corneal graft rejection by subconjunctival injection of FK-506 in a rat model of penetrating keratoplasty.

The usefulness of the subconjunctival injection of FK-506 for suppression of allograft rejection was investigated in a rat model of orthotopic penetrating keratoplasty. Fischer rats were used as donors and Dark Agouti rats, as recipients. FK-506 was administered subconjunctivally in a dosage of 0.3 mg/kg/day for 15 consecutive days after penetrating keratoplasty was performed. Allograft rejection occurred within 8 to 10 days after keratoplasty in all untreated rats (n = 6). None of the FK-506-treated rats (n = 6) exhibited graft rejection during the 3-week observation period. Histologic examination showed marked infiltration of mononuclear cells in the stroma of corneal grafts from untreated rats 3 weeks after grafting. Inflammatory cells were only occasionally observed in grafts from FK-506-treated rats. Donor-specific cytotoxic T lymphocyte activity was completely suppressed in FK-506-treated rats 3 weeks after grafting. Our results indicated that subconjunctival injection of FK-506 effectively prevented corneal allograft rejection in a rat model of penetrating keratoplasty.

Animals↗
PubMed1995

Renal response to prostaglandin E1 infusion in polycystic kidney disease versus non-polycystic renal disease.

The effect of prostaglandin E1 (PGE1) on renal function was examined in 8 patients with autosomal dominant polycystic kidney disease (ADPKD) and 8 subjects with non-polycystic chronic renal disease (CRD). Intravenous PGE1 infusion (50 micrograms/hr, for 2 hrs) resulted in a significant fall in creatinine clearance in ADPKD, but not in CRD. Although PGE1 had no effect on urinary sodium excretion and osmolar clearance in both groups, it increased significantly free water clearance in CRD, but not in ADPKD. Nephrogenic cyclic AMP during PGE1 administration did not differ significantly from their respective baseline level in two groups. In these groups, although nephrogenic cyclic AMP correlated poorly with urine volume, osmolar clearance, and free water clearance, it demonstrated a significant negative correlation with creatinine clearance. Renal volume in ADPKD cases had no relation with the parameters of renal function examined during PGE1 infusion. These data demonstrate the different responses of polycystic kidneys to PGE1 compared with non-polycystic kidneys.

Adult↗
PubMed1995

Production of defective virus by terminally differentiated myotubes infected with Rous sarcoma virus.

The generally accepted concept that the replication of Rous sarcoma virus (RSV) is dependent on host cell DNA synthesis was reexamined. As the host we used terminally differentiated myotubes (MT), in which no cellular DNA synthesis is observed. As an extension of our previous study which indicated that RSV-infected MT produce various virus components, we examined viral particles produced by infected MT. Electron microscopy showed presence of viral particles released from infected MT. Immunoprecipitation analysis revealed that these particles contained an equal amount of the gag but a decreased amount of the env proteins as compared with the particles from infected chicken embryo fibroblasts (CEF). Consequently, viral particles from infected MT had an infectivity only 6% of that of particles from infected CEF cells. In a parallel experiment, we microinjected molecularly cloned RSV DNA into MT. In contrast to the infection mediated by viral particles, both MT and CEF cells produced the same amount of infectious particles when microinjected with viral DNA. We conclude that RSV replicates in the complete absence of host DNA synthesis, though infectivity of the progeny virus depends on the initial condition of the infection.

Animals↗
PubMed1994

Role of endogenous interferon-beta in lipopolysaccharide-triggered activation of the inducible nitric-oxide synthase gene in a mouse macrophage cell line, J774.

The role of endogenous tumor necrosis factor alpha (TNF-alpha) and interferon-beta (IFN-beta) in lipopolysaccharide (LPS)-induced activation of the inducible nitric-oxide synthase (i-NOS) gene was investigated. By Northern analysis or reverse-transcription polymerase chain reaction, the mouse macrophage cell line (J774) was found to respond to LPS treatment by increased expression of mRNAs specific for TNF-alpha, IFN-beta, and i-NOS with the kinetics unique for each gene. Bioassay of the culture supernatants showed that TNF-alpha and IFN-beta secreted by J774 cells increased from an undetectable level to about 300 and 340 units/ml, respectively, 3-6 h after LPS stimulation. Nitrite concentration was found to increase from 0 to 7.8 and 28.5 microM by 12 and 24 h, respectively, in the culture supernatant of LPS-treated J774 cells. The presence of a neutralizing dose of antibodies against IFN-beta, but not against TNF-alpha, during treatment with either 10 ng or 1 microgram of LPS/ml significantly, but not completely decreased the level of i-NOS-specific mRNA expression and NO production. The incubation of J774 cells with mouse natural IFN-beta itself (up to the level of 1,200 units/ml) did not induce i-NOS-specific mRNA and therefore did not stimulate J774 cells to produce NO. However, natural IFN-beta synergistically augmented the expression of i-NOS mRNA and the production of NO by J774 cells triggered by suboptimal concentrations of LPS (1 to 5 ng/ml). These data thus suggest that endogenous IFN-beta, but not TNF-alpha, produced by LPS-stimulated J774 cells specifically contributes, probably in an auto/paracrine fashion, to the activation of the i-NOS gene expression by LPS.

Amino Acid Oxidoreductases↗
PubMed1994

Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production.

Northern analysis of poly(A)+ RNA extracted from J774 cells (a mouse macrophage cell line) showed that this cell line constitutively expresses mRNAs specific for protein kinase C (PKC)-beta I, -beta II, -epsilon and -zeta, but not those for PKC-alpha, -gamma or -delta. Western analysis of the total cell lysate showed that J774 cells express PKC-beta II, -epsilon and -zeta isoenzymes, but failed to show the expression of PKC-beta I. The exposure of J774 cells to > 10 nM PMA led to a loss of immunoreactive PKC-beta II in 4 h. The down-regulation of immunoreactive PKC-epsilon required more than 8 h of the exposure to > 100 nM PMA. Immunoreactive PKC-zeta was most resistant to PMA treatment and was not significantly reduced after the exposure to 300 to 600 nM PMA for 24 h. PMA-mediated, persistent down-regulation of PKC-beta II is probably a result of the inhibition of PKC-beta II biosynthesis at the posttranscriptional level, because PMA-exposed cells were found to gradually increase the expression of PKC-beta II specific mRNA. PMA-pretreated cells responded to a low dose (10 ng/ml), but not to a high dose (1 microgram/ml), of LPS by significantly lower expression of mRNA specific for the inducible nitric oxide synthase (i-NOS) gene and production of nitric oxide (NO) than the control cells did. Thus, PKC could be a part of the signal transduction apparatus involved in LPS-induced inducible nitric oxide synthase gene activation.

Amino Acid Oxidoreductases↗
PubMed1994

Invasive oral aspergillosis in immunocompromised patients with leukemia.

The clinicopathologic characteristics of invasive oral aspergillosis in 16 immunocompromised patients who developed this infection during antileukemic chemotherapy are described. The primary site of the infection was the marginal gingiva, there was severe spontaneous pain, and the patients developed spiking fever and granulocytopenia. Necrotic ulceration of the gingiva rapidly extended to the contiguous mucosa, muscle, and bone. Microscopically, the necrotic tissue contained thrombotic vascular infarcts and there were hyphae that showed frequent transverse septa and dichotomous branching. The invasive organisms were not responsive to amphotericin B in the absence of remission of the leukemia and restoration of the depressed host defenses. In 15 patients who showed improvement of hematologic status, oral aspergillosis was controlled by the combination of antifungal chemotherapy and debridement of necrotic tissues.

Adult↗
PubMed1994

Tumorigenicity study of ferric citrate administered orally to mice.

Ferric citrate (FC) was orally administered at concentrations of 0.12 (maximum tolerated dose) or 0.06% in the drinking water to male and female B6C3F1 mice. Treatment was continued for 96 wk and the experiment was terminated at wk 100. There was no significant difference between treated and control groups in the tumour incidence or in the distribution of different types of tumour. Thus the long-term oral administration of FC to mice did not yield any evidence of chronic toxicity or tumorigenicity.

Administration, Oral↗