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Biomedical subjects

Takuya Iwasaki

Publications and source records attributed to Takuya Iwasaki.

At least 37 records · Page 2Linked to original sources
PubMed2004

A partial hepatectomy results in altered expression of clock-related and cyclic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes.

The liver is among the peripheral organs that display a clear circadian rhythmicity. To investigate whether specific pathological conditions affect circadian rhythms in the liver, we examined the expression profiles of the clock-related and glyceraldehyde 3-phosphate dehydrogenase (GADPH) genes following a partial hepatectomy in the mouse. This surgical procedure causes dynamic proliferation of residual hepatocytes and within one day of the operation the hepatectomized mice demonstrated higher expression of both mPer1 and mPer2 genes in the remaining liver tissue when compared to control mice that had undergone a Sham-operation. In contrast, the mCry1 gene in hepatectomized mice displayed a circadian gene expression profile that was similar to the control group. In addition, GAPDH levels, that demonstrated no oscillations in Sham-hepatectomized mice, underwent daily alterations following a partial hepatectomy. These findings suggest that the regenerative state of the liver affects the expression not only of clock-related genes but also of genes that are constitutively expressed under steady state conditions.

Animals↗
PubMed2004

A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21.

Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 10(6) cell culture infectious dose (CCID50), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 10(6) CCID50, resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains.

Administration, Intranasal↗
PubMed2004

The miniature pig: a unique experimental model for Schistosoma japonicum infection.

As part of a search for good animal models for human schistosomiasis, two miniature pigs of the CLAWN strain (C-1, C-2) were inoculated percutaneously with 200 Schistosoma japonicum cercariae of the Chinese strain, and the subsequent infection was monitored parasitologically, pathologically and serologically. Egg excretion into feces began at 5 weeks post-infection (p.i.) and became pronounced from 8 weeks to 17-20 weeks p.i. The average number of eggs in 1 g feces of each pig at the peak period between 8 and 20 weeks were 288 and 277, respectively. C-1 and C-2 were killed and perfused at 27 and 47 weeks p.i. and adult worm numbers recovered were 35 and 15, respectively. C-2 had at least four pairs of viable mature worms but no detectable fecal eggs for a month before perfusion, suggesting that any produced eggs were not excreted into the feces during this period. Egg deposits associated with inflammatory reactions were observed by histological examination of the liver, spleen, pancreas, mesenteric lymph nodes, lung, and small intestine. This suggests that reduced fecal excretion of eggs into the feces did not correlate to reduced parasite numbers in the chronic phase of schistosomiasis. This is the first report showing the miniature pig to be a potential model for human S. japonicum infection.

Animals↗
PubMed2004

BCL-6-positive human herpesvirus 8-associated solid lymphoma arising from liver and spleen as multiple nodular lesions.

We report a case of BCL-6-positive B cell lymphoma with human herpesvirus 8 (HHV-8) infection. A human immunodeficiency virus-infected patient developed a diffuse large B cell lymphoma, which was found exclusively in the liver and spleen with the absence of lymphadenopathy and effusion in any body cavities. The lymphoma cells were composed of medium to large-sized cells positive for CD20, CD45, and BCL-6, and negative for epithelial cell membrane antigen, CD30, CD45RO, and CD138/syndecan-1, suggesting a germinal center B cell origin. The patient was serologically positive for HHV-8, and HHV-8 was detected in the liver biopsy tissue both by polymerase chain reaction and by immunohistochemistry for HHV-8-encoded latency-associated nuclear antigen. Other HHV-8-associated diseases, such as Kaposi's sarcoma, primary effusion lymphoma, or multicentric Castleman's disease were not detected in the patient. Chemotherapy was effective and reduced the size of the lymphoma dramatically. This is the first case report of a germinal center B cell-originating lymphoma with HHV-8 infection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephalitis virus.

A stable full-length infectious cDNA clone of the Oshima strain of Tick-borne encephalitis virus (Far-Eastern subtype) was developed by a long high-fidelity RT-PCR and one-step cloning procedure. The infectious clone (O-IC) had four amino acid substitutions and produced smaller plaques when compared with the parent Oshima 5-10 strain. Using site-directed mutagenesis, the substitutions were reverted to restore the parent virus sequence (O-IC-pt). Although genetically identical, parent virus Oshima 5-10 and virus recovered from O-IC-pt demonstrated some biological differences that are possibly explained by the presence of quasispecies with differing virulence characteristics within the original virus population. These observations may have implications for vaccines based on modified infectious clones. It was also demonstrated that the amino acid substitution E-S(40)-->P at position 40 in the envelope (E) glycoprotein was responsible for plaque size reduction, reduced infectious virus yields in cell culture and reduced mouse neurovirulence. Additionally, two amino acid substitutions in the non-structural (NS)5 protein (virus RNA-dependent RNA polymerase) NS5-V(378)-->A and NS5-R(674)-->K also contributed to attenuation of virulence in mice, but did not demonstrate a noticeable biological effect in baby hamster kidney cell culture. Comparative neurovirulence tests revealed how the accumulation of individual mutations (E-S(40)-->P, NS5-V(378)-->A and NS5-R(674)-->K) can result in the attenuation of a virus.

Amino Acid Sequence↗
PubMed2004

Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation.

Poliovirus and enterovirus 71 (EV71) are both neurotropic enteroviruses that cause serious neurological diseases, such as poliomyelitis and encephalitis. The neurovirulence of EV71 in cynomolgus monkeys was demonstrated previously by intraspinal inoculation. In this study, an improved simian model of EV71 infection was established by using intravenous inoculation, which revealed clinical and neuropathological similarities between this model and human cases of encephalitis. Experimental EV71 infection induced direct neurological manifestations, such as tremor, ataxia and brain oedema, but not non-neurological complications, such as pulmonary oedema and cardiac failure. Using this model of EV71 infection, the neurotropic characteristics of the prototype strains of EV71 and poliovirus type 1 (PV1) were compared. Three monkeys were inoculated intravenously with 10(5.5) TCID50 EV71 and all developed neurological disease signs within 4-6 days of inoculation. However, after inoculation with 10(5.5) TCID50 PV1 strain OM1 (PV1-OM1), the major manifestation was flaccid paralysis, starting from the lower limbs 6-9 days post-inoculation. Histopathological and virological analyses of moribund monkeys revealed that disseminated EV71 infection was characterized by severe panencephalitis involving both the pyramidal and extrapyramidal systems. In contrast, the lesions induced by PV1-OM1 were mainly restricted to the pyramidal tract, particularly the spinal motor neurons, thalamus and motor cortex. In conclusion, neuropathological involvement in this model correlated well with the apparent differences in neurological disease induced by EV71 and PV1-OM1. Thus, intravenous inoculation with EV71 is an excellent model to study the neuropathology of EV71 and to evaluate candidate vaccines and potential antiviral agents.

Animals↗
PubMed2004

Epizootiological and epidemiological study of hantavirus infection in Japan.

Epizootiological surveys on hantavirus infections in rodents were carried out in various areas of Japan, including the four major islands of Hokkaido, Honshu, Shikoku, and Kyushu from 2000 to 2003. A total of 1,221 rodents and insectivores were captured. Seropositive animals were found in Apodemus (A.) speciosus (5/482, 1.0%), Rattus (R.) norvegicus (4/364, 1.1%), R. rattus (3/45, 6.7%), and Clethrionomys (C.) rufocanus (7/197, 3.6%). The partial S segment was amplified from one seropositive R. rattus captured at Hakodate. The nucleotide sequence showed 96% identity with the Seoul virus (SEOV) prototype strain SR-11. In addition, we conducted an epidemiological survey on human hantavirus infection in a high-risk population, the personnel of the Japan Ground Self-defense Force on Hokkaido. One out of 207 human blood samples was positive for anti-hantavirus antibody by IFA, ELISA, and WB analysis. The result of the serotype specific ELISA indicates that this individual acquired SEOV infection. This study indicates that A. speciosus, R. norvegicus, R. rattus, and C. rufocanus carry hantaviruses as the reservoir animals in Japan. Infected R. rattus and R. norvegicus in port areas could be the sources of human SEOV infection and a threat to travelers and individuals working in seaports.

Animals↗
PubMed2004

Spontaneous regression of malignant lymphoma of the breast.

A complete spontaneous regression of diffuse large B cell lymphoma involving the right breast, confirmed by aspiration cytology, is reported. The patient visited a hospital due to the rapid growth of a tumor in the right breast. Five years previously she underwent a craniotomy for a brain tumor, diagnosed as B-cell malignant lymphoma, and received several courses of irradiation to the brain. Analysis of the breast tumor cells obtained by aspiration revealed lymphoma cells morphologically, which were similar to the tumor cells in the brain expressing CD20. While waiting for further examination, the tumor regressed rapidly and was not palpable after 20 days. An excisional biopsy of the breast exhibited no definite malignant lymphoma cells among a diffuse population of CD45RO and CD8-positive small lymphocytes. Nucleotide sequencing of HCDR3s of the brain tumor and breast tumor cells showed a completely matched sequence, revealing the breast mass to be a metastatic lesion from the tumor of the brain. Although there was no tumorous lesion, the patient received additional chemotherapy and has shown no sign of recurrence in the breast for 7 years. We were able to confirm that the breast lymphoma shown in the aspiration cytology was a metastatic one, which was not proven histologically prior to chemotherapy, and regard the present case as a malignant lymphoma of the breast showing spontaneous regression. The present case shows a rare occurrence of spontaneous regression of diffuse large B cell malignant lymphoma after aspiration and suggests that CD8-positive T cells might be related to the regression.

Base Sequence↗
PubMed2004

Naturally acquired Plasmodium knowlesi malaria in human, Thailand.

We describe a case of naturally acquired infection with Plasmodium knowlesi in Thailand. Diagnosis was confirmed by the small subunit ribosomal RNA and the mitochondrial cytochrome b sequences. The occurrence of simian malaria in human has signified the roles of wild primate populations in disease transmission in some malaria-endemic areas.

Adult↗
PubMed2004

[Advance and perspective of clinical nutrition].

Although nutritional support using nutrient enemas was recorded almost 3,500 years ago, the modern era of clinical dietetics commenced with the development of intravenous hyperalimentation by Dudrick et al. and the development of the chemically defined diet by Greenstein et al. Thereafter, clinical nutritional support became widely accepted as one of the basic tools of patient care, and knowledge of the metabolism of nutrients has been extended. In particular, the significance of micronutrients in systemic function, importance of gut function on the systemic metabolism and immune system, and involvement of amino acids and fat elements in the development and amelioration of specific disease status such as renal and hepatic failure have been recognized, and specific nutritional support has been created as a treatment strategy. In addition to knowledge of renal and hepatic failure or metabolic disorders, accumulated information on tumor metabolism and pathophysiology in cancer cachexia has also enabled cancer treatment using a nutritional approach. An enteral diet containing certain amino acids such as arginine or glutamate, omega-3 unsaturated fatty acids, and nucleic acids has been developed, and its clinical application under the new concept of "immunonutrition" has demonstrated reduction of the incidence of infection and shortening of hospital stay. Many questions on Immunonutrition remain to be answered such as its mechanism or optimal composition, although it is a promising field for future evolution. Currently, the assessment of nutritional status and gut function is required through lifelong education of medical doctors as well as the popularization of nutritional support teams. In the near future, tailor-made nutritional support will be required based on gene polymorphisms.

Adjuvants, Immunologic↗
PubMed2004

Comparison of virulence of various hantaviruses related to hemorrhagic fever with renal syndrome in newborn mouse model.

The virulence of hantaviruses that are antigenically related but have different genetic characteristics from the prototype of hantavirus, Hantaan (HTN) virus, was examined in newborn mice. The H5 and B78 strains of the Amur (AMR) genotype, the Bao14 strain of the Far East (FE) genotype, and the 76-118 strain of HTN virus were inoculated subcutaneously (1focus-forming unit; FFU) into newborn mice. All of the AMR and FE genotype viruses inoculated mice were died by 16 days post-infection (dpi) and 21 dpi, respectively, while 50% of the HTN virus inoculated mice survived until 30 dpi. The AMR and FE genotype viruses inoculated mice had high viral titers in the lung (1.3x10(6) to 1.3x10(8) FFU/gram [g] tissue) , brain (2.1x10(7) to 1.2x10(9) FFU/g tissue), and kidney(2.5x10(5) to 1.6x10(7) FFU/g tissue), and showed a detectable level of antibodies (titers 1:16-1:32) at 14 dpi. In contrast, the HTN virus infected mice had viruses only in the lungs at low titers (1.1-5.3x10(5) FFU/g tissue). Observations of body-weight changes revealed that the AMR and FE genotype viruses inoculated mice had lower growth rates than the HTN virus inoculated mice. These data suggest that the AMR and FE genotype viruses are more virulent than the HTN virus in newborn mice.

Animals↗
PubMed2004

[Histopathological findings in cytomegalovirus retinitis].

PURPOSE: We examined eyeballs collected from autopsied acquired immunodeficiency syndrome patients with cytomegalovirus (CMV) retinitis, and analyzed the precise pathogenesis of CMV retinitis. MATERIAL AND METHODS: Eyeballs were fixed with 10% buffered formalin embedded in paraffin. CMV antigens were investigated by histopathological and immunohistochemical analyses. Histopathological findings were compared with funduscopic images. RESULTS: CMV antigens remained in the necrotic area of the retina and many CMV immediate early antigens existed in intact parts of the inner retina showing almost intact structure, and around retinal vessels. CONCLUSIONS: The results suggest that CMV infects the inner retina first via the retinal vessels, although funduscopic examination may appear normal. It extends through the neuronal cells and glial cells horizontally and Muller cells vertically. CMV severely damages the retinal structure.

AIDS-Related Opportunistic Infections↗
PubMed2003

Human herpesvirus 6 infection of human epidermal cell line: pathogenesis of skin manifestations.

In order to elucidate the pathogenesis of variant B human herpesvirus 6 (HHV-6) infection in skin tissues, an A431 cell line was inoculated with variant B HHV-6. HHV-6 causes abortive infection in the A431 cells, because neither late antigen (OHV-3 antigen) nor progeny virus is produced. Maximum levels of HHV-6 antigen (IEA/ex3 antigen)-positive cells (36.4%) were observed 48 hr after viral infection. Cocultivation of HHV-6-infected cord blood mononuclear cells with A431 cells was necessary for the establishment of a sufficient level of viral infection. Cell-to-cell contact between the infected cord blood mononuclear cells and A431 cells was crucial for increasing infection efficiency. To determine the biological effect of HHV-6 infection, flow cytometric analysis was carried out in HHV-6- and mock-infected A431 cells. Although no alteration was observed in VCAM-1 and ELAM-1 expression, that of HLA-ABC, HLA-DR, and ICAM-1 was upregulated after infection with HHV-6.

Cell Line↗
PubMed2003

Cross-reactive antigenicity of nucleoproteins of lyssaviruses recognized by a monospecific antirabies virus nucleoprotein antiserum on paraffin sections of formalin-fixed tissues.

Diagnosis of rabies is routinely confirmed by detection of rabies virus antigens in acetone-fixed frozen brain tissues or imprint smears using an immunofluorescence method with commercial antirabies virus antibodies. Since recent molecular analyses disclosed wide heterogeneity in the genome sequences of rabies virus strains and related lyssaviruses, it is necessary to confirm the presence of common epitopes in these lyssaviruses. In this study we confirmed the presence of cross-reactive antigens of various lyssaviruses in paraffin sections of formalin-fixed tissue using a monospecific rabbit antiserum prepared by immunization with a recombinant nucleoprotein of rabies virus. By immunohistochemical application, the antigen was detected predominantly in the cytoplasm of neurons in the brains of mice infected with rabies virus, Duvenhage virus, Mokola virus and European bat lyssavirus-1, while no cross-reaction was observed in uninfected humans and animals including dogs, bats, and raccoons. In addition, we examined one autopsy case that was infected in a rabies-endemic nation and developed the clinical manifestation of rabies after returning to Japan in 1970, and found that the antigen was well preserved in paraffin sections of formalin-fixed tissues. Thus, this suggests that the lyssavirus-specific antigen is recognized by the monospecific antibody against rabies virus nucleoprotein, and that this cross-reactive antigen is detectable on formalin-fixed paraffin-embedded tissues by immunohistochemical analysis.

Amino Acid Sequence↗
PubMed2003

[Glutamate and gamma-aminobutylic acid release into the vitreous during cataract surgery].

OBJECTIVE: In cataract surgery, transient retinal ischemia and photostimulation-induced retinal damage occurs, even though only for a short duration. We suspected the possibility of excessive release of glutamate under these conditions, and therefore analyzed the amino acid contents in the vitreous body. MATERIALS AND METHODS: The vitreous bodies of 32 eyes with disease of the macular area necessitating retinovitreous surgery were used as samples for amino acid analysis. Ischemic diseases such as diabetic retinopathy, venous occlusion, and retinal detachment were excluded. The vitreous amino acid contents were compared between 18 eyes that underwent combined cataract and vitreous surgery and 14 eyes that had vitreous surgery alone. RESULTS: An approximately 3-fold increase of glutamate, 6-fold increase of gamma-aminobutylic acid (GABA), and 2-fold increase of alanine were observed in combined cataract and vitreous surgery compared to vitreous surgery alone. CONCLUSION: Even in human eyes, acute pressure overload or photostimulation for a short duration cause excessive release of glutamate. A simultaneous increase of GABA suggests the possibility that when glutamate is over-released, the retina physiologically reduced the concentration of glutamate via GABA, in an attempt to suppress the neurotoxin action.

Aged↗
PubMed2002

Processing of the HTLV-II envelope precursor glycoprotein gp63 by furin is essential for cell fusion activity.

To investigate the relationship between the fusogenic properties of HTLV-II and the processing of the envelope precursor glycoprotein gp63, recombinant cowpox virus expressing this protein was used to infect a range of cell lines derived from different species. Syncytium formation and gp63 processing were observed in all cells with the exception of LoVo cells, which are known to have a dysfunctional form of the endoprotease, furin. Furin has been shown to be necessary for the processing of a number of viral envelope glycoproteins, and gp63 contains a consensus sequence (305)Arg-Arg-Arg-Arg, which is a furin substrate motif. Pulse-chase studies demonstrated gp63 processing in Vero but not in LoVo cells. In addition it could be shown that expression of recombinant furin restored the processing of gp63 to gp46 in LoVo cells, and this resulted in syncytium formation. Our findings suggest that furin plays a pivotal role in cleavage of the HTLV-II envelope gp63, which in turn is a prerequisite for the fusogenic properties of the virus.

Animals↗