Control of Japanese encephalitis in Japan: immunization of humans and animals, and vector control.
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Animals↗
Biomedical subjects
A Igarashi
Publications and source records attributed to A Igarashi.
Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc.
The characterization of protein components produced from bone tissues with fracture healing was investigated. Weanling rats were sacrificed between 1 and 7 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that many protein molecules were released from the diaphyseal tissues with fracture healing. Especially, a protein molecule of approximately 66 kDa was markedly increased by fracture healing. This protein molecule was significantly increased, when the diaphyseal tissues with fracture healing were cultured in the presence of zinc acexamate (10(-6)-10(-4) M). Zinc acexamate (10(-4) M)-induced increase in medium 66 kDa protein molecule was significantly inhibited in the presence of actinomycin D (10(-7) M) or cycloheximide (10(-6) M). The zinc effect was completely blocked in the presence of PD98059 (10(-5) M), an inhibitor of MAPK kinase, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The medium 66 kDa protein molecule was significantly elevated in the presence of parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or transforming growth factor-beta (10(-11) M), while 17beta-estradiol (10(-9) M) did not have an effect. The effect of these bone-stimulating factors was equal to the zinc effect. Zinc did not significantly enhance the effect of insulin-like growth factor-I in increasing medium 66 kDa protein molecule. The present study demonstrates that fracture healing increases production of the approximately 66 kDa protein molecule which is a major component produced from femoral-diaphyseal tissues of weanling rats, and that this elevation is enhanced by zinc treatment.
Animals↗
Transport properties and efficiency of elastically coupled Brownian motors.
As models for biological molecular motors, Brownian motors have been studied recently by many workers, and their physical properties such as velocity, efficiency, and so on, have been investigated. They have also attracted much interest in an application to nanoscale technology. It is significant to study more complex systems, that is, coupled Brownian motors, in detail, since Brownian motors with a single particle have been mainly studied until now. In this paper, we consider Brownian motors coupled mutually with elastic springs, and investigate the dynamics of the model and the efficiency of energy conversion. In particular, we find that the center of the mass of the elastically coupled particles moves faster than the corresponding single-particle model, and also that the efficiency of the coupled-particle model is larger than that of the single-particle model.
Journal Article↗
Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta ); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity.
We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid beta-peptide (A beta) in vitro. Surprisingly, ACE was found to significantly inhibit A beta aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A beta fibril formation with electron microscopy. ACE inhibited A beta deposits on a synthaloid plate, which was used to monitor A beta deposition on autopsied brain tissue. ACE also significantly inhibited A beta cytotoxicity on PC12 h. The most striking fact was that ACE degraded A beta by cleaving A beta-(1-40) at the site Asp(7)-Ser(8). This was proven with reverse-phase HPLC, amino acid sequence analysis, and MALDI-TOF/MS. Compared with A beta-(1-40), aggregation and cytotoxic effects of the degradation products A beta-(1-7) and A beta-(8-40) peptides were reduced or virtually absent. These findings led to the hypothesis that ACE may affect susceptibility to AD by degrading A beta and preventing the accumulation of amyloid plaques in vivo.
Alzheimer Disease↗
Locus of a virus neutralization epitope on the Japanese encephalitis virus envelope protein determined by use of long PCR-based region-specific random mutagenesis.
We prepared recombinant Japanese encephalitis (JE) virus populations possessing random mutations at the envelope (E) protein region by a long PCR-based method. Neutralization-resistant mutants were selected from these populations by application of JE-specific virus neutralizing monoclonal antibody (mAb) 503, which possessed a 51,200-fold neutralization titer. We classified the mutants into three groups, each bearing two amino acid alterations at the E protein region: 52, Gln-Arg, and 136, Lys-Glu; 136, Lys-Glu, and 275, Ser-Pro; and 126, Ile-Thr, and 136, Lys-Glu, respectively. Three different genetically engineered variants, each bearing a single mutation, 126, Ile-Thr; 136, Lys-Glu; and 275, Ser-Pro, respectively, showed partial but not complete recovery of reactivity to mAb 503. Our results indicate that the amino acid substitutions at amino acid positions 52, 126, 136, and 275 altered the structure of the neutralization epitope for mAb 503 on the E protein. All these mutations were clustered at the junction of domains I and II of the E protein and it is likely that the epitope for mAb 503 is composed of at least E(0)-e, D(0)-a, and k strands of the E protein. We also demonstrated the efficacy of the long PCR-based recombinant virus technique as a useful tool for the creation of a variety of mutants bearing random mutations at targeted areas of the virus genome.
Animals↗
West Nile virus-induced bax-dependent apoptosis.
The mechanism of cell death induced by West Nile virus (WNV), a causative agent of human febrile syndrome and encephalitis, was investigated. WNV-infected K562 and Neuro-2a cells manifested the typical features of apoptosis, including cell shrinkage, chromatin condensation and subdiploid DNA content by flow cytometry. DNA fragmentation into nucleosomal size and changes in outer cell membrane phospholipid composition were also observed in K562 cells. UV-inactivated virus failed to induce the above-mentioned characteristics, suggesting that viral replication may be required for the induction of apoptosis by WNV. Additionally, signals involved in WNV-induced apoptosis are associated with the up-regulation of bax gene expression.
Aedes↗
Igarashi and lin reply:.
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Journal Article↗
Huge cystic lymphangioma of the pancreas: report of a case.
We report herein the case of a 33-year-old woman who presented with palpable abdominal swelling found to be caused by a huge lymphangioma of the pancreas. An abdominal computed tomographic (CT) scan showed a large multilocular cystic mass with water-dense contents, which was derived from the pancreatic head. A pancreaticoduodenectomy (PD) was performed because the tumor had invaded the duodenum. The resected tumor, which was 23 x 12 x 23 cm in size with 21 of serous fluid, was pathologically diagnosed as a cystic lymphangioma. The endothelial cells lining the internal surface of the cystic spaces were immunohistochemically positive for factor VIII-R antigen and CD31. Our review of the literature revealed 45 reports of lymphangioma of the pancreas, including this one, but to the best of our knowledge this is only the fifth case that required a PD. Nevertheless, we recommend that a complete resection be performed to reduce the risk of recurrence.
Adult↗
Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.
Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.
Animals↗
Ultrasonographic features of parathyroid carcinoma.
Although several authors have reported single cases illustrative of some ultrasonographic characteristic of parathyroid carcinoma, the value of ultrasonography for diagnosing this entity remains to be determined. The purpose of our study was to investigate the ultrasonographic features of parathyroid carcinoma in a large number of cases. We assessed the shape, contour, echogenicity, and depth-width (DW) ratio of 16 parathyroid carcinomas and 61 parathyroid adenomas. Ultrasonography showed that parathyroid carcinomas tend to be large, inhomogeneous, hypoechoic masses with lobulated contours. In contrast, parathyroid adenomas were small, homogeneous, hypoechoic masses with smooth borders. The mean (range) DW ratios for parathyroid carcinomas were 1.21 (0.91-2.5) and 0.64 (0.33-1.47) for adenomas; the difference was statistically significant (p<0.0001). The DW ratio was > or =1 in 15 (94%) of the 16 cases of carcinoma, whereas only 3 (5%) of the 61 adenomas had a similar ratio. Ultrasonographic examination is useful not only for preoperative localization but also for differentiating parathyroid carcinoma from adenoma. Parathyroid tumors with irregular margins, inhomogeneous echogenicity, and a DW ratio > or =1 are likely to be malignant.
Adenoma↗
Angiotensinogen gene variation and hypertension in a cohort study in Japanese.
Many recent case-control studies have suggested a significant relationship between M235T (the substitution of threonine for methionine at position 235 codon) polymorphism of the angiotensinogen (AGT) gene and hypertension. To investigate whether the M235T polymorphism of AGT gene affects the incidence of hypertension, a retrospective cohort study was performed among Japanese workers. The subjects were Japanese workers at an occupational site in Shimane Prefecture in Japan. The baseline data were set at the received regular health examination in 1992, and a retrospective cohort study was performed for analyzing the incidence of hypertension in 1998. The rates of M235M (MM), M235T (MT) and T235T (TT) genotypes were 4%, 32% and 64%, respectively. The relative risks of MT and TT against MM for the incidence of hypertension by single variance analysis were 1.47 [95% confidence interval (CI) 0.50 - 4.33] and 1.35 (95% CI 0.47 - 3.90), respectively. The relative risks of MT and TT against MM for the incidence of hypertension, adjusted for sex, age, body mass index, fasting glucose and cigarette smoking, drinking and exercise in 1992, were 1.49 (95% CI 0.49 - 4.53) and 1.25 (95% CI 0.42 3.74), respectively. The data from this study suggest that the M235T polymorphism of AGT gene has a weak role in the manifestation of hypertension. Further comprehensive studies are needed to resolve this issue.
Adult↗
Increase in bone growth factors with healing rat fractures: the enhancing effect of zinc.
The effect of zinc, a stimulator of bone formation, on bone protein components in the femoral-diaphyseal tissues with fracture healing was investigated. Rats were sacrificed between 1 and 7 days after the femoral fracture, and the diaphyseal tissues were cultured in a serum-free Dulbecco's modified Eagle's medium for 24 h. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. The amount of protein in the medium cultured with the diaphyseal tissues obtained from fracture healing rats was markedly elevated as compared with that of normal rats, indicating that bone protein components were secreted into culture medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel elecrophoresis (SDS-PAGE) showed that many protein molecules were secreted from the diaphyseal tissues with fracture healing. Especially, protein molecule of about 66 kDa was markedly secreted by fracture healing. The presence of zinc acexamate (10(-5) and 10(-4) M) in culture medium induced a significant elevation of medium protein content; the zinc effect was enhanced by culture with the diaphyseal tissues of fracture healing rats. Also, the culture of diaphyseal tissues with fracture healing caused a significant increase in insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in culture medium. The production of IGF-I and TGF-beta1 from bone tissues with fracture healing was significantly enhanced in the presence of zinc acexamate (10(-6)-10(-4) M). Moreover, the addition of IGF-I (10(-8) M) or TGF-beta1 (10(-10) M) in a culture medium caused a significant elevation of protein content in the medium cultured with the femoral-diaphyseal tissues from normal and fracture healing rats. The effect of IGF-I or TGF-beta1 was significantly enhanced in the presence of zinc acexamate (10(-4) M). Also, deoxyribonucleic acid (DNA) content in the diaphyseal tissues from normal and fracture healing rats was significantly raised by the culture with IGF-I or TGF-beta1. The effect of IGF-I was significantly enhanced by zinc. The present study demonstrates that fracture healing increases production of bone IGF-I and TGF-beta1, and that this elevation is enhanced by zinc treatment.
Aminocaproates↗
[Effective combination chemotherapy for a recurrent case of carcinoma of the remnant stomach].
A 69-year-old-man underwent distal gastrectomy for gastric carcinoma in 1988. Another gastric carcinoma was discovered in the remnant stomach in March 1995. Total gastrectomy and lymph node dissection were performed. CEA was up and we detected a big left suprarenal mass by abdominal CT. Suprarenalectomy was performed in June 1997. The swelling of lymph nodes was detected by CT and CEA was up to 1,000. Combination chemotherapy with intermittent 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) was performed. CEA suddenly decreased and lymph node swelling was reduced.
Adenocarcinoma↗
Identification of the putrescine recognition site on polyamine transport protein PotE.
The PotE protein can catalyze both uptake and excretion of putrescine. The K(m) values of putrescine for uptake and excretion are 1.8 and 73 microm, respectively. Uptake of putrescine is dependent on the membrane potential, whereas excretion involves putrescine-ornithine antiporter activity. Amino acids involved in both activities were identified using mutated PotE proteins. It was found that Cys(62), Trp(201), Trp(292), and Tyr(425) were strongly involved in both activities, and that Tyr(92), Cys(210), Cys(285), and Cys(286) were moderately involved in the activities. Mutations of Tyr(78), Trp(90), and Trp(422) mainly affected uptake activity, and the K(m) values for putrescine uptake by these PotE mutants increased greatly, indicating that these amino acids are involved in the high affinity uptake of putrescine by PotE. Mutations of Lys(301) and Tyr(308) mainly affected excretion activity (putrescine-ornithine antiporter activity), and excretion by these mutants was not stimulated by ornithine, indicating that these amino acids are involved in the recognition of ornithine. It was found that the putrescine and ornithine recognition site on PotE is located at the cytoplasmic surface and the vestibule of the pore consisting of 12 transmembrane segments. Based on the results of competition experiments with various putrescine analogues and the disulfide cross-linking of PotE between cytoplasmic loops and the COOH terminus, a model of the putrescine recognition site on PotE consisting of the identified amino acids is presented.
Amino Acid Sequence↗
Role of the DExH motif of the Japanese encephalitis virus and hepatitis C virus NS3 proteins in the ATPase and RNA helicase activities.
The role of the conserved DExH motif of the Japanese encephalitis virus (JEV) NS3 protein in the ATPase and RNA helicase activities was compared with that of the hepatitis C virus (HCV) NS3 protein. In the DExH motif of JEV NS3, Asp-285 and Glu-286 were essential for both ATPase and RNA helicase activities. Cys-287 was critical for the RNA helicase activity of JEV NS3 but not for ATPase activity. A His-288-to-Ala substitution in the DExH motif of HCV NS3 resulted in an increase in ATPase activity which was suppressed by poly(U). In contrast, alanine substitution at the same site in JEV NS3 did not increase basal ATPase activity which remained to be stimulated by poly(U). Thus, the mutational effect at His in motif II was different in the HCV and JEV NS3 proteins. Mutagenesis at His-288 of JEV NS3 revealed that His was the most preferable amino acid for ATPase activity and Ala, Gly, Asn, Gln, Ser, or Arg could partly substitute for it. However, any other mutation at His-288 completely disrupted the RNA helicase activity of JEV NS3. The results suggest that Cys-287 and His-288 are essential residues especially for the RNA helicase activity of JEV NS3 and the ATPase and helicase activities are separable enzymatic functions.
Adenosine Triphosphatases↗
Identification and characterization of the RNA helicase activity of Japanese encephalitis virus NS3 protein.
The NS3 protein of Japanese encephalitis virus (JEV) contains motifs typical of RNA helicase/NTPase but no RNA helicase activity has been reported for this protein. To identify and characterize the RNA helicase activity of JEV NS3, a truncated form of the protein with a His-tag was expressed in Escherichia coli and purified. The purified JEV NS3 protein showed an RNA helicase activity, which was dependent on divalent cations and ATP. An Asp-285-to-Ala substitution in motif II of the JEV NS3 protein abolished the ATPase and RNA helicase activities. These results indicate that the C-terminal 457 residues are sufficient to exhibit the RNA helicase activity of JEV NS3.
Adenosine Triphosphatases↗
Interventricular methotrexate therapy for carcinomatous meningitis due to breast cancer: a case with leukoencephalopathy.
A 46-year-old woman presented with paraplegia and severe lumbago. She had had a radical mastectomy for left breast cancer 10 years earlier, and 6 months prior to presentation she completed CMF chemotherapy for treatment of retroperitoneal metastasis. CT and MRI to identify potential causes of the paraplegia and lumbago showed leptomeningeal carcinomatosis due to dissemination from invasive recurrence of the retroperitoneal tumor. An Ommaya reservoir was inserted, and infusion of intrathecal methotrexate (MTX; 5 mg twice weekly) began. Her clinical symptoms improved after receiving 53 mg MTX. However, after receiving 83 mg MTX, the patient became dizzy from leukoencephalopathy. Although administration of prednisolone mostly resolved her symptom, the patient died 9 months after the diagnosis of carcinomatous meningitis.
Antimetabolites, Antineoplastic↗
Eosinophilic fasciitis following exposure to trichloroethylene: successful treatment with cyclosporin.
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Cyclosporine↗