Biomedical subjects

K Mori

Publications and source records attributed to K Mori.

At least 325 records · Page 18Linked to original sources

PubMed2000

[Arterial infusion chemotherapy for liver metastases from colorectal cancer--therapeutic effects of different protocols].

The therapeutic effects of different protocols for arterial infusion chemotherapy were compared in patients with multiple liver metastases from colorectal cancer. A total of 49 patients with colorectal multiple liver metastases treated in our hospital since 1988 were the subjects. In order to compare the therapeutic effects on the regression of cancer and the survival rate, the subjects were assigned into Groups A-D, which were treated using different protocols. Group A received ADR, EPI, CDDP or 5-FU alone at first. If this drug was not effective, it was replaced with another of those mentioned here, and so on. Group B received CDDP 50 mg on day 1, 5-FU 500 mg/day from day 2 to day 7 and 5-FU 500 mg/day for 2 weeks thereafter (FP treatment). Group C received CDDP 50 mg at the time of reservoir insertion and 5-FU 1,000 mg for 5 hours thereafter (WHF treatment). Group D received 5-FU 1,000 mg for 24 hours on day 1, day 3, and day 5 of every week with combination of CDDP 5-10 mg/day from day 1 to day 5 and none on day 6 and day 7 (intermittent F + low-dose P treatment) for 3 weeks. The response rate was 33% for Group A (n = 18), 46% for Group B (n = 13), 25% for Group C (n = 8) and 80% for Group D (n = 10), showing significant differences between Group D and other groups. The 1-year survival rate was 50% for Group A, 46% for Group B, 29% for Group C and 89% for Group D. Significant differences in survival rate were found between Group B and D, and Group C and D.

Antineoplastic Agents↗

PubMed2000

[A study on resource based relative values for visiting nursing services].

PURPOSE: The purpose of this study was to investigate the resource based relative values of visiting nursing services, and to analyze the relationships between the relative values and the dimensions of nursing service(time, mental effort and physical effort). METHODS: We interviewed nurses at 20 Home-visit nursing care stations (HVNCS) in the Metropolitan area using the resource based relative value questionnaires. We asked nurses about relative values of "Total Work", and also measured relative weight of 3 dimensions of nursing services. Total Work was defined as comprehensive evaluation of nursing services, with careful consideration of intensity as well as duration. With the dependent variable as Total Work and independent variables as the 3 dimensions, multiple regression analyses were carried out. Furthermore we examined the degree of influence on Total Work by service type and individual respondent. To examine the validity of the results, we timed nursing services and compared the measured time with the answered time. RESULTS: The 107 respondents were all female and their average age was 36.6 years old. They had HVNCS experience of 2.2 years and 95.3% nurses had experience of hospital nursing. "Total Work" and 3 dimension scores were standardized using common logarithms. "Total Work" of every service significantly differed among service types. The 3 dimensions explained 54.6% of Total Work in the multiple regression analysis. Service type explained 3.3% of Total Work. Individual respondent explained 16.0% of Total Work. Answered time and measured time were not significantly different with nursing services. CONCLUSIONS: Although Total Work was somewhat influenced by individual respondent, most of variation was explained by 3 dimensions. Thus, it could be concluded that Total Work is an index of nursing resource input. A further investigation about influence of patients' condition on Total Work is necessary in the future.

Adult↗

PubMed2000

Parasitic forms of a myxosporean in the kidney of the arctic lamprey, Lampetra japonica: an ultrastructural study.

We found frequent and unique parasitism by an unidentified myxosporean in the kidney of the arctic lamprey, Lampetra japonica, living in Japan. Trophozoites (pseudoplasmodia with or without sporoblasts) existed predominantly in the lumina of proximal urinary tubules, but were rarely found in any other regions of the kidney. Since no mature spores were produced in the trophozoites, exact identification of the species was impossible. Two parasitic forms were recognized in proximal urinary tubules: one adhering to the epithelial cells of renal tubules, and the other free-floating in the lumina of tubules. Ultrastructurally, the attaching trophozoites developed microvilli-like projections towards the apical surface of epithelial cells and vigorously interdigitated with microvilli of the brush border. In contrast, the whole surface of the floating trophozoite was smooth without any cell projections. The developed projections in the former type of trophozoite may contribute to their firm attachment to the epithelial cells and/or to absorption of nutrients via the epithelial cells. Against the myxosporean infection, the lamprey as the host exhibited a local immune reaction by disposition of numerous lymphocytes and macrophages into the epithelium of urinary tubules.

Animals↗

PubMed1999

High permissivity of the fish cell line SSN-1 for piscine nodaviruses.

Seventeen isolates of piscine nodavirus from larvae or juveniles of 13 marine fish species affected with viral nervous necrosis (VNN) were examined for their infectivity to a fish cell line SSN-1. Based on cytopathic effects (CPE) and virus antigen detection by fluorescent antibody technique (FAT) after incubation at 25 degrees C, the infectivity of these virus isolates was divided into 4 groups. Group 1, including 9 virus isolates from 4 species of grouper, 2 species of sea bass, barramundi, rock porgy, and Japanese flounder showed CPE characterized by rounded, granular cells with heavy cytoplasmic vacuoles within 3 d post-incubation (p.i.), and the monolayer partially or completely disintegrated over 3 to 6 d p.i. Scattered FAT-positive cells appeared at 3 h p.i. and spread through the cell sheet with an increasing fluorescence signal over 24 h p.i. Group 2, consisting of 3 virus isolates from striped jack, induced CPE with thin or rounded, granular, refractile cells without conspicuous vacuole formation, and extensive FAT-positive reaction was observed in a time course similar to that of Group 1. Cells inoculated with Group 3 (1 isolate from tiger puffer) developed no distinct CPE but viral infection was evidenced by localized FAT-positive cells. There were no FAT-positive cells in Group 4, which included 4 isolates from Japanese flounder, Pacific cod and Atlantic halibut. However, when incubation was performed at 20 degrees C, the SSN-1 cells inoculated with the Group 3 isolate showed CPE similar to that of Group 1 and extensive FAT-positive reaction. Evidence of virus proliferation at 20 degrees C was also obtained in Group 4 isolates. The virus titers in the infected fish varied from 10(11) to 10(16) tissue culture infectious dose (TCID50) g(-1) of fish. There is a good correlation between these infectivities to the SSN-1 cells and the coat protein gene genotypes of the isolates. The present results indicate that SSN-1 cells are useful for propagating and differentiating genotypic variants of piscine nodavirus.

Animals↗

PubMed1999

Effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the survival of mice infected with influenza virus.

The antiviral effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, was investigated using mice infected with influenza virus. TJ-41 was found to increase the survival rate, prolong the mean survival days, suppress viral growth in bronchoalveolar labage fluid (BALF) and inhibit the lung index (lung consolidation) on day 4 after infection in mice infected with influenza, after the agent had been administered orally once daily from day 7 to 2 before infection and from day 0 to 4 after infection. Administration of TJ-41 decreased the BALF concentrations of IL-1alpha, IL-6 and GM-CSF, but not TNF-alpha or interferon-gamma (IFN-gamma), on day 4 after infection. In addition, TJ-41 elevated the level of IFN-alpha in BALF on day 2 after infection. Yet, TJ-41 did not show any inhibitory effect on the growth of influenza virus in vitro. These results suggest that TJ-41 exerts its inhibitory effect on influenza virus infection via enhancement of the host immune responses in this experimental murine system.

Administration, Oral↗

PubMed1999

Neuronal adhesion molecule telencephalin induces rapid cell spreading of microglia.

Telencephalin (TLCN) is a neuronal surface glycoprotein whose expression is restricted to the telencephalon, the most rostral segment of the brain. TLCN binds to lymphocyte function-associated antigen-1 (LFA-1) integrin. In the central nervous system, LFA-1 is selectively and constitutively expressed by microglia, suggesting that TLCN/LFA-1 binding may mediate cell-cell interactions between telencephalic neurons and microglia. In the present study, we investigated the effects of recombinant TLCN protein on the morphology of microglia. TLCN induced an intensive spreading of lamellipodia, causing a rapid change in microglial morphology. In contrast, TLCN induced no significant change in morphology of neuroblastoma and fibroblasts. Furthermore, the TLCN-induced spreading of microglia was accompanied by a clustering of LFA-1 on cell surface membrane. These results provide evidence that TLCN binding to the surface of microglia transduces signals into microglia that mediate or accelerate cell spreading and LFA-1 redistribution, implying that neuronal TLCN may control the state and/or function of microglia in both physiological and pathological conditions.

Animals↗

PubMed1999

Neutrophil elastase and oxygen radicals enhance monocyte chemoattractant protein- expression after ischemia/reperfusion in rat liver.

BACKGROUND: The monocyte chemoattractant protein-1 (MCP-1) is produced during reperfusion injury and induces tissue factor that is the initiator of the clotting cascade. Neutrophil elastase is a crucial mediator of inflammatory tissue damage. Activation of the coagulation system stimulates cytokine production by activated leukocytes. We investigated the effects of neutrophil elastase and oxygen radicals generated by hypoxia associated with microthrombus formation on MCP-1 expression after ischemia/reperfusion in rat liver. METHODS: In vitro MCP-1 production by macrophages after stimulation with human neutrophil elastase (HNE) or oxygen radicals generated by hypoxanthine and xanthine oxidase was examined. Liver ischemia was induced in rats by occluding the portal vein for 30 min. An inhibitor of human neutrophil elastase (ONO-5046*Na, 10 mg/kg) and antithrombin III (AT-III, 250 U/kg) were injected i.v. 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. RESULTS: Human neutrophil elastase or oxygen radicals significantly enhanced in vitro MCP-1 production by macrophage. Serum MCP-1 concentrations reached a peak at 6 hr after reperfusion and then gradually decreased. However, pretreatment of animals with AT-III or ONO-5046*Na alone resulted in significantly smaller increases in serum concentrations of MCP-1 after reperfusion. Pretreatment with both ONO-5046*Na and AT-III produced additive effects. The combined treatment with ONO-5046*Na and AT-III significantly reduced MCP-1 mRNA in liver after ischemia/reperfusion. CONCLUSIONS: MCP-1 production by macrophages is stimulated by neutrophil elastase and oxygen radicals generated by hypoxia, probably due to microthrombus formation after ischemia/reperfusion of the rat liver.

Animals↗

PubMed1999

Dose optimization and indication of Linac radiosurgery for brain metastases.

PURPOSE: The authors have examined treatment effects of linear accelerator based radiosurgery for brain metastases. Optimal doses and indications were determined in an attempt to improve the quality of life for terminal cancer patients. METHODS AND MATERIALS: Ninety-two patients with 162 lesions were treated with Linac radiosurgery for brain metastases between April 1993 and September 1998. To determine prognostic factors, risk factors for recurrence, and appearance of new lesions, univariate and multivariate analyses were performed. To compare the local control between the high-dose (minimum dose > or =25 Gy: prescribed to the 50-80% isodose line) and low-dose (minimum dose <25 Gy) irradiated groups, matched-pairs analysis was performed. RESULTS: Median survival time was 11 months. In univariate analysis, extracranial tumor activity (p<0.001) and Karnofsky Performance Status (KPS) (p = 0.036) were two significant predictors of survival. In multivariate analysis, the status of an extracranial tumor was the single significant predictor of survival (p = 0.005). Minimum dose was the single most significant predictor of local recurrence in univariate, multivariate, and matched-pairs analyses (p<0.05). As to the appearance of new lesions, activity of extracranial tumors was a significant predictor (p<0.05). Side effects due to radiosurgery were experienced in 4 of 92 cases (4.3%). CONCLUSIONS: We concluded that brain metastases patients should be irradiated with > or =25 Gy, when extracranial lesions are stable and longer survival is expected. Combined surgery and conventional radiation may have little advantage over radiosurgery alone when metastatic brain tumors are small and extracranial tumors are well controlled. When extracranial tumors are progressive, the rate of appearance of new lesions in other nonirradiated locations becomes higher. In such cases, careful follow-up is required and a combination with whole brain irradiation should be considered.

Adult↗

PubMed1999

Anesthesia with sevoflurane, but not isoflurane, prolongs bleeding time in humans.

PURPOSE: Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo. METHODS: Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5-10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1-1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values. RESULTS: Bleeding time was increased from the preanesthetic value of 2.07 +/- 0.82 min to 2.83 +/- 0.93 min (n = 15) in the sevoflurane group (P < 0.01) but was not significantly altered in the isoflurane group. CONCLUSION: Sevoflurane alters bleeding time in the clinical situation.

Clinical Trial↗

PubMed1999

The olfactory bulb: coding and processing of odor molecule information.

Olfactory sensory neurons detect a large variety of odor molecules and send information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. The axonal connection is precisely organized so that signals from 1000 different types of odorant receptors are sorted out in 1800 glomeruli in the mouse olfactory bulb. Individual glomerular modules presumably represent a single type of receptor and are thus tuned to specific molecular features of odorants. Local neuronal circuits in the bulb mediate lateral inhibition among glomerular modules to sharpen the tuning specificity of output neurons. They also mediate synchronized oscillatory discharges among specific combinations of output neurons and may contribute to the integration of signals from distinct odorant receptors in the olfactory cortex.

Action Potentials↗

PubMed1999

Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.

Endogenous serotonin (5-hydroxytryptamine, 5-HT)-mediated regulation of dopamine release in the rat prefrontal cortex was pharmacologically characterized using in vivo microdialysis. To increase synaptic 5-HT availability, a selective 5-HT uptake inhibitor fluoxetine was applied via the dialysis probe. Local perfusion of fluoxetine (30 and 100 microM) increased dopamine levels in a concentration-dependent manner. The fluoxetine (100 microM)-induced increases in dopamine release were abolished by pretreatment with the 5-HT(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide] ) (10 and 100 microM). The facilitation of dopamine release was also prevented by selective inactivation of the mRNA encoding 5-HT(6) receptors using antisense oligonucleotides techniques. These findings suggest that not only 5-HT(1B) receptors but also 5-HT(6) receptors are associated with the endogenous 5-HT-mediated facilitation of dopamine release. In other words, 5-HT(6) receptors may play, in part, a significant role in the functional interaction between the dopaminergic and serotonergic neuronal system in the rat prefrontal cortex.

Animals↗

PubMed1999

Vocal fold nodules in children: preferable therapy.

BACKGROUND: The purpose of this paper is to know the preferable treatment for vocal fold nodules in children. METHODS: Two hundred and fifty nine patients with vocal fold nodules (176 males and 83 females) were retrospectively reviewed. Age ranged from 2 to 18 years with a mean age of 9 years. In addition, questionnaire survey was carried out, asking about their present voice. RESULTS: Sixteen percent of the patients showed improvement by vocal hygiene advice. Fifty two percent of patients receiving voice therapy showed some improvement. Eighty nine percent of patients showed some improvement by endolaryngeal microsurgery. With respect to the influence of puberty upon the voice, there was no significant difference among vocal hygiene, voice therapy, and no-treatment for pre-puberty cases. Surgical treatment was the only reliable method to acquire voice improvement for pre-puberty cases. In contrast, following puberty there was no significant difference in voice improvement among treatment modalities. CONCLUSION: If the patient needs immediate improvement of voice, surgery is preferable. If they need the improvement of voice but do not hurry up, voice therapy should be carried out. If patients have no motivation, vocal hygiene is recommended.

Adolescent↗

PubMed1999

Mechanism of reactivation of coenzyme B12-dependent diol dehydratase by a molecular chaperone-like reactivating factor.

The mechanism of reactivation of diol dehydratase by its reactivating factor was investigated in vitro by using enzyme. cyanocobalamin complex as a model for inactivated holoenzyme. The factor mediated the exchange of the enzyme-bound, adenine-lacking cobalamins for free, adenine-containing cobalamins through intermediate formation of apoenzyme. The factor showed extremely low but distinct ATP-hydrolyzing activity. It formed a tight complex with apoenzyme in the presence of ADP but not at all in the presence of ATP. Incubation of the enzyme.cyanocobalamin complex with the reactivating factor in the presence of ADP brought about release of the enzyme-bound cobalamin, leaving the tight apoenzyme-reactivating factor complex. Although the resulting complex was inactive even in the presence of added adenosylcobalamin, it dissociated by incubation with ATP, forming the apoenzyme, which was reconstitutable into active holoenzyme with added coenzyme. Thus, it was established that the reactivation of the inactivated holoenzyme by the factor in the presence of ATP and Mg2+ takes place in two steps: ADP-dependent cobalamin release and ATP-dependent dissociation of the apoenzyme.factor complex. ATP plays dual roles as a precursor of ADP in the first step and as an effector to change the factor into the low-affinity form for diol dehydratase. The enzyme-bound adenosylcobalamin was also susceptible to exchange with free adeninylpentylcobalamin, although to a much lesser degree. The mechanism for discrimination of adenine-containing cobalamins from adenine-lacking cobalamins was explained in terms of formation equilibrium constants of the cobalamin.enzyme.reactivating factor ternary complexes. We propose that the reactivating factor is a new type of molecular chaperone that participates in reactivation of the inactivated enzymes.

Adenine↗

PubMed1999

Distinct roles of thioredoxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB.

Oxidative stresses such as UV irradiation to mammalian cells triggers a variety of oxistress responses including activation of transcription factors. Recently, activation of nuclear factor-kappaB (NF-kappaB) has been shown to be under oxidoreduction (redox) regulation controlled by thioredoxin (TRX), which is one of major endogenous redox-regulating molecules with thiol reducing activity. In order to elucidate where in the cellular compartment TRX participates in NF-kappaB regulation, we investigated the intracellular localization of TRX. UVB irradiation induced translocation of TRX from the cytoplasm into the nucleus. In our in vitro diamide-induced cross-linking study, we showed that TRX can associate directly with NF-kappaB p50. Overexpression of wild-type TRX suppressed induction of luciferase activity under NF-kappaB-binding sites in response to UV irradiation compared with the mock transfectant. In contrast, overexpression of nuclear-targeted TRX enhanced the luciferase activity. Thus, TRX seems to play dual and opposing roles in the regulation of NF-kappaB. In the cytoplasm, it interferes with the signals to IkappaB kinases and blocks the degradation of IkappaB. In the nucleus, however, TRX enhances NF-kappaB transcriptional activities by enhancing its ability to bind DNA. This two-step TRX-dependent regulation of the NF-kappaB complex may be a novel activation mechanism of redox-sensitive transcription factors.

Cell Line, Transformed↗

PubMed1999

Histopathological and immunohistochemical studies of membranes of deacetylated chitin derivatives implanted over rat calvaria.

Membranes made of 65, 70, 80, 94, and 100% deacetylated chitin (chitosan) were implanted subperiosteally over the calvaria of 100 rats. Reactions were studied at 1, 2, 4, and 8 weeks after implantation. Membranes prepared with 65, 70, and 80% deacetylated chitin initially elicited marked inflammatory reactions that subsided in time with granulation tissue formation and osteogenesis. Osteocalcin-positive cells were detected immunohistochemically in the granulation tissue. On the other hand, membranes made of 94% deacetylated chitin and chitosan showed mild inflammation and minimal osteogenesis. The results indicate that membranes made of 65, 70, and 80% deacetylated chitin enhance osteogenesis at the site of their implantation. However, the initially severe inflammatory reaction associated with these materials needs to be controlled before the materials would be suitable for clinical application.

Acetylation↗

PubMed1999

Anti-tumor promoting activity of polyphenols from Cowania mexicana and Coleogyne ramosissima.

Chemical investigation on polyphenol-rich fractions of Cowania mexicana and Coleogyne ramosissima (Rosaceae) which showed significant inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), has led to the characterization of 10 compounds including C-glucosidic ellagitannin monomers and dimers from the former plant, and 17 polyphenols including flavonoid glycosides from the latter. The effects of individual components and their analogues with related structures on the TPA-induced EBV-EA activation were then evaluated. Among the compounds isolated from C. mexicana, two C-glucosidic ellagitannins, alienanin B and stenophyllanin A and a nitrile glucoside (lithospermoside), and among the constituents from C. ramosissima, two flavonoid glycosides, isorhamnetin 3-0-beta-D-glucoside and narcissin were revealed to possess strong inhibitory effects on EVB-EA activation, the potencies of which were either comparable to or stronger than that of a green tea polyphenol, (-)-epigallocatechin gallate. These polyphenols except for nitrile glucoside, which was not tested owing to an insufficient amount, were also found to exhibit anti-tumor promoting activity in two-stage mouse skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and TPA.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes in cancer patients.

Genes encoding tumor epitopes that are capable of inducing CTLs against adenocarcinomas and squamous cell carcinomas, two major human cancers histologically observed in various organs, have rarely been identified. Here, we report a new gene from cDNA of esophageal cancer cells that encodes a shared tumor antigen recognized by HLA-A2402-restricted and tumor-specific CTLs. The sequence of this gene is almost identical to that of the KIAA0156 gene, which has been registered in GenBank with an unknown function. This gene encodes a Mr 140,000 protein that is expressed in the nucleus of all of the malignant tumor cell lines tested and the majority of cancer tissues with various histologies, including squamous cell carcinomas, adenocarcinomas, melanomas, and leukemia cells. However, this protein was undetectable in the nucleus of any cell lines of nonmalignant cells or normal tissues, except for the testis. Furthermore, this protein was expressed in the cytosol of all of the proliferating cells, including normal cells and malignant cells, but not in normal tissues, except for the testis and fetal liver. Two peptides of this protein were recognized by HLA-A2402-restricted CTLs and were able to induce HLA-A24-restricted and tumor-specific CTLs from peripheral blood mononuclear cells of most of HLA-A24+ cancer patients tested, but not from peripheral blood mononuclear cells of any healthy donors. These peptides may be useful in specific immunotherapy for HLA-A24+ cancer patients with various histological types.

Antigens, Neoplasm↗

PubMed1999

Induction of transcription factor interferon regulatory factor-1 by interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) in FRTL-5 cells.

While it is well known that interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) play a role in the regulation of thyroid growth and differentiated functions, the cellular and molecular mechanisms involved in mediating the effects of IFN gamma and TNF alpha on thyroid function are unknown. In the present study, we used FRTL-5 rat thyroid cells to examine the effects of IFN gamma and TNF alpha on gene expression of transcription factor interferon regulatory factor-1 (IRF-1), which is involved in mediating the effects of these cytokines in a number of cell types. Northern blot analysis of FRTL-5 mRNA showed a single IRF-1 mRNA at 2.2 Kb. In quiescent FRTL-5 cells, IRF-1 mRNA levels were low but detectable by Northern analysis. Incubation of FRTL-5 cells with IFN gamma or TNF alpha resulted in a dose- and time-dependent increase in IRF-1 mRNA levels. We have shown that TNF-alpha and IFN-gamma act synergistically to block the TSH-induced increase in type I 5'-deiodinase(5'D-I) activity and 5'D-I gene expression in FRTL-5 rat thyroid cells. Incubation of FRTL-5 cells with IFN gamma and TNF alpha in combination, however, did not synergistically increase IRF-1 mRNA levels. Electrophoretic mobility shift assay (EMSA) revealed that IFN gamma induced the formation of a single complex to a IFN gamma activation site (GAS) probe in a dose dependent manner. Several lines of evidence suggest that TNF alpha activates transcription factor nuclear factor-kappa B (NF kappa B) through activation of protein kinase C (PKC) or the hydrolysis of sphingomyelin to ceramide in a number of cell types. Here we demonstrate that hydrolysis of sphingomyelin to ceramide by sphingomyelinase (SMase), but not activation of PKC by 12-O-tetradecanoylphorbol 13-acetate (TPA), was involved in the activation of NF kappa B in FRTL-5 cells. Similarly, hydrolysis of sphingomyelin to ceramide, but not activation of PKC, resulted in an increased in IRF-1 mRNA levels in FRTL-5 cells. The present data demonstrate that IFN gamma and TNF alpha increase IRF-1 mRNA levels in FRTL-5 cells through activation of GAS and NF kappa B binding proteins, respectively. Thus, our results suggest that upregulation of IRF-1 may play a role in mediating the effects of IFN gamma and TNF alpha on thyroid function. Our results also suggest that the induction of IRF-1 mRNA by IFN gamma and TNF alpha is not the cellular mechanism involved in the synergistic effect of these cytokines on thyroid function.

Animals↗