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Biomedical subjects

Y Katayama

Publications and source records attributed to Y Katayama.

At least 145 records · Page 8Linked to original sources
PubMed2000

The effect of NSAIDs and a COX-2 specific inhibitor on Helicobacter pylori-induced PGE2 and HGF in human gastric fibroblasts.

BACKGROUND: There is compelling evidence for the pivotal role of Helicobacter pylori in the pathogenesis of gastrointestinal ulcer disease. However, despite the bacterium's toxicity, the majority of H. pylori infections are not accompanied by gastric ulcers. This implies the existence of a host mechanism offsetting H. pylori toxicity. AIMS: To evaluate gastric fibroblasts' expression of hepatocyte growth factor (HGF), which is known to facilitate gastric ulcer healing, in the presence of H. pylori; to compare the effect on H. pylori-induced HGF expression of a COX-2 selective inhibitor with that of nonselective nonsteroidal anti-inflammatory drugs METHODS: Human gastric fibroblasts were cultured from human gastric mucosa obtained at surgery. Prostaglandin E2 (PGE2) and HGF were measured by EIA. The expression of COX-2 mRNA was assessed by the TaqMan quantitative RT-PCR system. RESULTS: H. pylori increased PGE2 release in gastric fibroblasts. H. pylori induced expression of COX-2 mRNA, which indicates that PG induction by H. pylori is through COX-2. Sulindac sulphide, etodolac and NS 398 all inhibited H. pylori-induced PGE2 release to the same extent. These agents also inhibited H. pylori-induced HGF release. CONCLUSION: Gastric fibroblasts produce PG and HGF in response to the presence of H. pylori, which may be considered part of the human body's defensive reaction to H. pylori toxicity. This defensive mechanism is inhibited not only by COX-2 nonselective NSAIDs but also by a COX-2 selective inhibitor. These findings indicate the importance of COX-2 in chronic H. pylori infection.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Five-year follow-up of valve replacement with the Jyros bileaflet mechanical valve.

Jyros bileaflet rotating valves were implanted as a clinical trial conducted in Japan, and the 5-year results were assessed. Nineteen patients underwent implantation of the valves: 14 in the mitral and 5 in the aortic position. The mean follow-up period was 65.4+/-15.7 months. There was 1 case of late death due to fatal arrhythmia and another case of cerebral thromboembolism (1.0% per patient year). All survivors were in New York Heart Association class I. On the early postoperative cinefluorography, 8 valves (42.1%) showed rotation of the leaflets. However, in the latest assessment 6 valves (33.3%) showed rotation, some valves had stopped rotation, and others had started to rotate during the follow-up period. The Jyros valve functions effectively, similar to other bileaflet valves. However, because the correlation between thromboembolism and the rotation mechanism is not clear, further follow-up of our patients and more implant studies are necessary to elucidate this issue.

Adult↗
PubMed2000

Intraoperative electro-oculographic Monitoring for Skull Base Surgery.

During surgery on the skull base, preservation of the integrity of the ocular motor nerves is vitally important. Intraoperative electrophysiological monitoring methods for protecting such functions have been reported by several investigators. However, these methods so far have not been popularized sufficiently, due to the difficulty and complexity of the procedures involved. The authors have developed an extremely simple but far more reliable method using electro-oculography under total intravenous anesthesia with propofol to preserve the integrity of the ocular motor nerves. The ocular motor nerves were stimulated with a monopolar electrode intracranially, and the polarity of the waves was recorded using surface electrodes placed around the eyeball, yielding precise information concerning the locations of the oculomotor nerve and/or abducent nerve. In addition, by performing continuous monitoring, invasive procedures affecting the ocular motor nerves could be detected as spontaneous ocular movements. In practice at our department, this method has been applied in 12 cases with tumors close to the ocular motor nerves, and has produced excellent results.

Journal Article↗
PubMed2000

Studies on congenital protein C deficiency in Japanese: prevalence, genetic analysis, and relevance to the onset of arterial occlusive diseases.

Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. We identified 43 patients with protein C deficiency by screening approximately 26,800 patients admitted to the National Cardiovascular Center Hospital. The observed prevalence of protein C deficiency was 1 per 620. We performed genetic analyses of 57 Japanese families with protein C deficiency. Combined with the results of the other studies in 10 families, the 67 Japanese families with protein C deficiency have been examined and 39 different gene defects have been identified. Some changes were solely identified in Japanese subjects, whereas others showed no such ethnic bias. The recurrent defects of Phe139Val, Arg169Trp, Val297Met, and Met364Ile substitutions and a G8857 deletion were found in 33 Japanese families, accounting for 49% of Japanese families with protein C deficiency, Finally, we examined the relevance of protein C deficiency to the onset of arterial occlusive diseases. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference (p = 0.02) in the age at onset of acute myocardial infarction between the patients with protein C deficiency (n = 10: 49.4 +/- 14.8 years) and a group of patients with normal protein C levels (n = 42: 60.5 +/- 10.6 years). At the onset of atherothrombotic cerebral infarction, the patients with protein C deficiency were significantly (p = 0.022) younger (n = 11:57.4 +/- 12.8 years) than those with normal protein C levels (n = 48: 64.6 +/- 10.1 years). Thus, we conclude that congenital protein C deficiency hastens the onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.

Age of Onset↗
PubMed2000

Bloody cerebrospinal fluid from patients with subarachnoid hemorrhage alters intracellular calcium regulation in cultured human vascular endothelial cells.

Endothelial cell dysfunction may contribute to cerebral vasospasm and aggravation of ischemic brain damage following subarachnoid hemorrhage (SAH). It has been suggested that oxyhemoglobin derived from subarachnoid blood clots might be a prime candidate for cerebral vasospasm. In this study, cisternal bloody cerebrospinal fluid (bCSF) was collected from SAH patients four and seven days after aneurysmal rupture, and the effects of bCSF on the cell growth and intracellular calcium ion ([Ca2+]i) dynamics were investigated in cultured human umbilical vein endothelial cells. CSF collected from patients undergoing other intracranial surgeries was used as a control. Pre-treatment with bCSF4 significantly facilitated cell proliferation and DNA synthesis in the cultured endothelial cells, and significantly enhanced histamine-induced [Ca2+]i increase, while acute treatment of the bCSF elicited no [Ca2+]i change. Pre-treatment with interleukin-1 beta showed a similar significant enhancement of the histamine-induced [Ca2+]i response, while pre-treatment with high concentrations of serum or interleukin-6 did not change the [Ca2+]i response. It is concluded that bCSF collected from SAH patients contains some substances which enhance endothelial cell proliferation and sensitivity to inflammatory mediator.

Adult↗
PubMed2000

Oxygen-independent real-time monitoring of distinct biphasic glutamate release using dialysis electrode in rat striatum during anoxia: in vivo evaluation of glutamate release and reversed uptake.

Using a dialysis electrode, previous studies showed a clear biphasic release of glutamate during anoxia and ischemia. In this study, we examined two hypotheses: (1) glutamate is of vesicular origin and its release is thus Ca2+- and ATP-dependent in the first phase, while in the second phase glutamate is derived primarily from the metabolic pool, and (2) reversed glutamate uptake, due to electrogenic stoichiometry, produces the second phase during anoxic insult in the rat brain. A dialysis electrode continuously perfused with glutamate oxidase and ferrocene-conjugated bovine serum albumin (BSA) optimized the time resolution of monitoring, allowing quantitative oxygen-independent, real-time measurement of the extracellular glutamate concentration ([Glu]e) during anoxia. [Glu]e dynamics were analyzed during anoxia by combining the dialysis electrode with focal microinjection of substances inducing glutamate release. Following anoxia in the rat brain, a sharp and rapid [Glu]e elevation took place (first phase). The [Glu]e elevation then shifted, continuing a gently sloping rise throughout the anoxic period (second phase). This first phase disappeared with intracranial administration of either Co2+ or omega-conotoxin. The second phase rise increased with focal microinjection of KCl (300 mM, 1 microL) and decreased with NaCl (300 mM, 1 microL), ultimately reaching a plateau in both cases. Preloading with a novel glutamate transporter inhibitor (tPDC) decreased both the first and second phases of [Glu]e elevation. This dialysis electrode system provides data supporting in vivo evidence that the peak of the first phase of [Glu]e elevation is derived from the "neurotransmitter pool," while the second phase is derived from the neuronal and glial "metabolic pool," which is, at least, partly related to a "reversed uptake" mechanism in the anoxic rat brain.

Animals↗
PubMed2000

Rapid and widespread microglial activation induced by traumatic brain injury in rat brain slices.

In order to assess the role of circulating blood in early microglial activation after traumatic brain injury (TBI), controlled cortical impact injury was applied to adult rat brain slices (400 microm in thickness) and the microglial response was examined. The complement receptor (CR3) expression and morphological transformation of the microglia were evaluated by OX42 immunohistochemistry. At 5 min following injury, activated microglia with intense CR3 expression appeared throughout the hemisphere on the injured side. In contrast, the morphology and CR3 expression of the microglia on the contralateral side were indistinguishable from those of the resident ramified microglia seen in normal brains. At 30 min following injury, microglial activation was more pronounced on the injured side, while the microglia on the contralateral side still retained a ramified morphology. These results are consistent with our previous observations made in in vivo experiments, which indicate that, as the brain slice paradigm excludes variables arising from the circulating blood, the rapid and widespread microglial activation observed following TBI can not be attributed exclusively to the infiltration of blood-borne macrophages or molecules. Rather this activation is most likely caused by intrinsic mechanisms within the brain tissue, such as traumatic depolarization.

Animals↗
PubMed2000

Alpha-synuclein inclusions in amygdala in the brains of patients with the parkinsonism-dementia complex of Guam.

We investigated by immunohistochemistry the deposition of alpha-synuclein in the brains of deceased patients with the parkinsonism-dementia complex (PDC) of Guam. Five of 13 PDC brains showed numerous alpha-synuclein positive neuronal inclusions and abnormal neurites, chiefly in the amygdala. Similar alpha-synuclein positive lesions were observed, although to a lesser extent, in the entorhinal cortex and the dorsal vagal nucleus. No alpha-synuclein positive inclusions were observed in motor cortex or locus coeruleus, and only a small number of positive inclusions were found in the Sommer's sector, temporal cortex, or substantia nigra. Some of the alpha-synuclein positive inclusions were reminiscent of cortical Lewy bodies (LB), but many of those in the amygdala coexisted with tau-positive pretangles and/or neurofibrillary tangles (NFT) within the same neurons. In these neurons, tau-positive shells encapsulated alpha-synuclein positive central cores or irregularly shaped alpha-synuclein-positive deposition intermingled with pretangles/NFT. Thus, the present study suggests that a common mechanism may govern aggregation of alpha-synuclein and tau in the amygdala, and that aggregation of alpha-synuclein may play some role in the neurodegenerative process of a tauopathy (i.e. PDC) in which Abeta deposition is virtually absent.

Adult↗
PubMed2000

Specific accumulation of polysaccharide-linked hydroxycinnamoyl esters in the cell walls of irregularly shaped and collapsed internode parenchyma cells of the dwarf rice mutant Fukei 71.

We examined a novel rice mutant, Fukei 71 (Oryza sativa L.), for alterations in the levels of hydroxycinnamoyl esters that are linked to cell wall polysaccharides and lignin units. In this mutant, a recessive mutation at a single locus caused the collapse of parenchyma cells in the internodes. Light microscopy revealed that the abnormal walls of internode parenchyma cells of Fukei 71 were stained by the Mäule reaction, which is specific for syringyl units in phenolic compounds. These walls were not stained by Wiesner's reagent (phloroglucinol-HCl), which reacts cinnamaldehyde in lignin. Levels of p-coumaric acid (PCA) and ferulic acid (FA) were apparently elevated in the abnormal tissue of the mutant. Western blotting analysis with antibodies specific for phenylalanine ammonia-lyase (PAL) revealed higher levels of PAL in the abnormal parenchyma tissue of Fukei 71 than in the parenchyma tissue of the parent cultivar Fujiminori. These results and the observation that PAL was produced at a greatly elevated level indicated that the phenylpropanoid pathway that leads to the biosynthesis of polysaccharide-linked FA and PCA was abnormally activated in the irregularly shaped and collapsed internode parenchyma cells, in which the biosynthesis of lignin is normally repressed.

Cell Wall↗
PubMed2000

Different patterns of renal prostaglandins I2 and E2 in patients with essential hypertension with low to normal or high renin activity.

OBJECTIVE: Differences in renal synthesis between prostaglandins I2 and E2, and the relationships of the amounts synthesized to renin release were investigated in patients with essential hypertension. METHODS: Of 12 inpatients, six had low to normal plasma renin activity and six had high renin activity. Before and 30 min after intravenous injection of aspirin D,L-lysine (18 mg/kg), abdominal aortic and renal venous plasma was sampled and assayed for renin activity, 6-ketoprostaglandin F1alpha (as an index of prostaglandin I2), and prostaglandin E2. RESULTS: In patients with low to normal renin activity, mean +/- SD plasma levels of 6-keto-prostaglandin F1alpha were lower in the right and left renal veins (3.6 +/- 1.4 and 4.1 +/- 1.5 pg/ml, respectively) than in the aorta (5.5 +/- 2.0 pg/ml), but in the other patients, the levels in these veins (7.0 +/- 2.4 and 6.5 +/- 1.5 pg/ml) were higher than in the aorta (5.4 +/- 0.9 pg/ml). Plasma prostaglandin E2 levels in both veins were higher than in the aorta in both groups and, at each site, the levels were similar in the two groups. Aspirin suppressed renin release in the patients with high renin activity. CONCLUSIONS: In patients with essential hypertension with low to normal renin activity, either less prostaglandin I2 than prostaglandin E2 is produced in the kidney or else more is metabolized there, and in such patients with high renin activity, the renal synthesis of prostaglandin I2, more than that of prostaglandin E2, seems to be related to the increased renin release.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

[Pacemaker infection caused by Staphylococcus schleiferi].

Pacemaker infection is one of the severe complication of pacemaker implantation. We report a case of pacemaker infection caused by Staphylococcus schleiferi which is a coagulase-negative staphylococcus, and its relation with human infection is not well characterized. In 1994, a 80-year-old male presented with a pacemaker pocket infection, cutaneous inflammation but no fever 2 months after insertion of a pacemaker. S. schleiferi was isolated from the pus. The patient was given cefazolin for 5 days. One month later he was readmitted because of cutaneous inflammation and the extruded generator was removed. S. schleiferi was isolated from the generator. After the patient was treated with cefazolin for 3 weeks, four consecutive wound cultures were all negative. A new generator was inserted on the same side. One month after re-insertion, the patient again presented a cutaneous inflammation, and S. schleiferi was isolated from the pus as well as the generator and the leads on their removal. Twenty-six days later, a new pacing system was inserted on the other side. There was no further recurrence of the infection. Removal of the entire pacing system was necessary to cure the infection. We expect further information of human infections caused by S. schleiferi.

Aged↗
PubMed2000

A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus.

We have previously shown that the methicillin-resistance gene mecA of Staphylococcus aureus strain N315 is localized within a large (52-kb) DNA cassette (designated the staphylococcal cassette chromosome mec [SCCmec]) inserted in the chromosome. By sequence determination of the entire DNA, we identified two novel genes (designated cassette chromosome recombinase genes [ccrA and ccrB]) encoding polypeptides having a partial homology to recombinases of the invertase/resolvase family. The open reading frames were found to catalyze precise excision of the SCCmec from the methicillin-resistant S. aureus chromosome and site-specific as well as orientation-specific integration of the SCCmec into the S. aureus chromosome when introduced into the cells as a recombinant multicopy plasmid. We propose that SCCmec driven by a novel set of recombinases represents a new family of staphylococcal genomic elements.

Amino Acid Sequence↗
PubMed2000

Coexistence of two different O demethylation systems in lignin metabolism by Sphingomonas paucimobilis SYK-6: cloning and sequencing of the lignin biphenyl-specific O-demethylase (LigX) gene.

Sphingomonas paucimobilis SYK-6 can grow on several dimeric model compounds of lignin as a carbon and energy source. It has O demethylation systems on three kinds of substrates: 5, 5'-dehydrodivanillic acid (DDVA), syringate, and vanillate. We previously reported the cloning of a gene involved in the tetrahydrofolate-dependent O demethylation of syringate and vanillate. In the study reported here, we cloned the gene responsible for DDVA O demethylation. Using nitrosoguanidine mutagenesis, a mutant strain, NT-1, which could not degrade DDVA but could degrade syringate and vanillate, was isolated and was used to clone the gene responsible for the O demethylation of DDVA by complementation. Sequencing analysis showed an open reading frame (designated ligX) of 1,266 bp in this fragment. The deduced amino acid sequence of LigX had similarity to class I type oxygenases. LigX was involved in O demethylation activity on DDVA but not on vanillate and syringate. DDVA O demethylation activity in S. paucimobilis SYK-6 cell extracts was inhibited by addition of the LigX polyclonal antiserum. Thus, LigX is an essential enzyme for DDVA O demethylation in SYK-6. S. paucimobilis SYK-6 has two O demethylation systems: one is an oxygenative demethylase system, and the other is a tetrahydrofolate-dependent methyltransferase system.

Bacterial Proteins↗
PubMed2000

Genetic and biochemical characterization of 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase and its role in the protocatechuate 4,5-cleavage pathway in Sphingomonas paucimobilis SYK-6.

Protocatechuate (PCA) is the key intermediate metabolite in the lignin degradation pathway of Sphingomonas paucimobilis SYK-6 and is metabolized to pyruvate and oxaloacetate via the PCA 4,5-cleavage pathway. We characterized the 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS) dehydrogenase gene (ligC). CHMS is the 4,5-cleavage product of PCA and is converted into 2-pyrone-4,6-dicarboxylate (PDC) by LigC. We found that ligC was located 295 bp downstream of ligB, which encodes the large subunit of the PCA 4,5-dioxygenase. The ligC gene consists of a 945-bp open reading frame encoding a polypeptide with a molecular mass of 34,590 Da. The deduced amino acid sequence of ligC showed 19 to 20% identity with 3-chlorobenzoate cis-dihydrodiol dehydrogenase of Alcaligenes sp. strain BR60 and phthalate cis-dihydrodiol dehydrogenases of Pseudomonas putida NMH102-2 and Burkholderia cepacia DBO1, which are unrelated to group I, II, and III microbial alcohol dehydrogenases (M. F. Reid and C. A. Fewson, Crit. Rev. Microbiol. 20:13-56, 1994). The ligC gene was expressed in Escherichia coli and LigC was purified to near homogeneity. Production of PDC from CHMS catalyzed by LigC was confirmed in the presence of NADP(+) by electrospray ionization-mass spectrometry and gas chromatography-mass spectrometry. LigC is a homodimer. The isoelectric point, optimum pH, and optimum temperature were estimated to be 5.3, 8.0, and 25 degrees C, respectively. The K(m) for NADP(+) was estimated to be 24.6 +/- 1.5 microM, which was approximately 10 times lower than that for NAD(+) (252 +/- 3.9 microM). The K(m)s for CHMS in the presence of NADP(+) and NAD(+) are 26.0 +/- 0.5 and 20.6 +/- 1.0 microM, respectively. Disruption of ligC in S. paucimobilis SYK-6 prevented growth with vanillate. Only PCA was accumulated during the incubation of vanillate with the whole cells of the ligC insertion mutant (DLC), indicating a lack of PCA 4,5-dioxygenase activity in DLC. However, the introduction of ligC into DLC restored its ability to grow on vanillate. PDC was suggested to be an inducer for ligAB gene expression.

Aldehyde Oxidoreductases↗
PubMed2000

The 4-oxalomesaconate hydratase gene, involved in the protocatechuate 4,5-cleavage pathway, is essential to vanillate and syringate degradation in Sphingomonas paucimobilis SYK-6.

Sphingomonas paucimobilis SYK-6 is able to grow on various dimeric lignin compounds, which are converted to vanillate and syringate by the actions of unique lignin degradation enzymes in this strain. Vanillate and syringate are degraded by the O-demethylase and converted into protocatechuate (PCA) and 3-O-methylgallate (3MGA), respectively. PCA is further degraded via the PCA 4,5-cleavage pathway, while the results suggested that 3MGA is degraded through another pathway in which PCA 4,5-dioxygenase is not involved. In a 10.5-kb EcoRI fragment carrying the genes for PCA 4,5-dioxygenase (ligAB), 2-pyrone-4,6-dicarboxylate hydrolase (ligI), and a portion of 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase (ligC), we found the ligJ gene encoding 4-oxalomesaconate (OMA) hydratase, which catalyzes the conversion of OMA into 4-carboxy-4-hydroxy-2-oxoadipate. The ligJ gene is transcribed in the same direction as ligABC genes and consists of an 1,023-bp open reading frame encoding a polypeptide with a molecular mass of 38,008 Da, which is located 73-bp upstream from ligA. The ligJ gene product (LigJ), expressed in Escherichia coli, was purified to near homogeneity and was estimated to be a homodimer (69.5 kDa) by gel filtration chromatography. The isoelectric point was determined to be 4.9, and the optimal temperature is 30 degrees C. The K(m) for OMA and the V(max) were determined to be 138 microM and 440 U/mg, respectively. LigJ activity was inhibited by the addition of thiol reagents, suggesting that some cysteine residue is part of the catalytic site. The ligJ gene disruption in SYK-6 caused the growth defect on and the accumulation of common metabolites from both vanillate and syringate, indicating that the ligJ gene is essential to the degradation of these two compounds. These results indicated that syringate is converted into OMA via 3MGA, and it enters the PCA 4,5-cleavage pathway.

Amino Acid Sequence↗
PubMed2000

Prevalence of GB virus C/Hepatitis G virus infection among various populations in Surabaya, Indonesia, and identification of novel groups of sequence variants.

A molecular epidemiological study was performed to investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among various populations in Surabaya, Indonesia. The prevalence of GBV-C/HGV RNA, determined by reverse transcription-PCR for a portion of the NS3 region of the viral genome, was 2.7% (4 of 150) among randomly collected blood donor sera, which were all negative for both hepatitis B virus surface antigen and antibodies against hepatitis C virus (HCV). On the other hand, the prevalence among anti-HCV-positive blood donors was 17.8% (13 of 73), with the ratio being significantly higher than that observed with the anti-HCV-negative blood donors (P < 0.001). A high prevalence of GBV-C/HGV infection was also observed among patients with chronic liver disease, such as chronic hepatitis (5.7%), liver cirrhosis (11. 5%), and hepatocellular carcinoma (7.0%), and patients on maintenance hemodialysis (29.0%). No correlation was observed between GBV-C/HGV viremia and serum alanine aminotransferase levels in the populations tested, suggesting the possibility that GBV-C/HGV does not cause apparent liver injury. Phylogenetic analysis of sequences of a portion of the 5' untranslated region and the E1 region of the viral genome identified, in addition to a previously reported then novel group of GBV-C/HGV variants (group 4), another novel group of variants (group 5). This result suggests that GBV-C/HGV can be classified into at least five genetic groups. GBV-C/HGV isolates of group 4 and group 5 were each shown to comprise approximately 40% of the total Indonesian isolates.

5' Untranslated Regions↗
PubMed2000

Human receptor for measles virus (CD46) enhances nitric oxide production and restricts virus replication in mouse macrophages by modulating production of alpha/beta interferon.

Complement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-gamma). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-alpha/beta blocked NO production. Antibodies against IFN-alpha/beta also inhibited the augmenting effect of MV on IFN-gamma-induced NO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-gamma alone. These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-alpha/beta. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to MV. These cells produced much lower levels of NO and IFN-alpha/beta upon infection by MV, suggesting the CD46 cytoplasmic domains enhanced IFN-alpha/beta production. When mouse macrophages expressing tailless human CD46 were exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-alpha/beta abrogated these antiviral effects. Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-alpha/beta in response to MV infection, and IFN-alpha/beta synergizes with IFN-gamma to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.

Animals↗