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Biomedical subjects

H Katano

Publications and source records attributed to H Katano.

At least 19 recordsLinked to original sources
PubMed2006

Effusion and solid lymphomas have distinctive gene and protein expression profiles in an animal model of primary effusion lymphoma.

Lymphoma usually forms solid tumours in patients, and high expression levels of adhesion molecules are observed in these tumours. However, Kaposi's sarcoma-associated herpesvirus (KSHV)-related primary effusion lymphoma (PEL) does not form solid tumours and adhesion molecule expression is suppressed in the cells. Inoculation of a KSHV-associated PEL cell line into the peritoneal cavity of severe combined immunodeficiency mice resulted in the formation of effusion and solid lymphomas in the peritoneal cavity. Proteomics using two-dimensional difference gel electrophoresis and DNA microarray analyses identified 14 proteins and 105 genes, respectively, whose expression differed significantly between effusion and solid lymphomas. Five genes were identified as having similar expression profiles to that of lymphocyte function-associated antigen 1, an important adhesion molecule in leukocytes. Among these, coronin 1A, an actin-binding protein, was identified as a molecule showing high expression in solid lymphoma by both DNA microarray and proteomics analyses. Western and northern blotting showed that coronin 1A was predominantly expressed in solid lymphomas. Moreover, KSHV-encoded lytic proteins, including viral interleukin-6, were highly expressed in effusion lymphoma compared with solid lymphoma. These data demonstrate that effusion and solid lymphomas possess distinctive gene and protein expression profiles in our mouse model, and suggest that differences in gene and protein expression between effusion and solid lymphomas may be associated with the formation of effusion lymphoma or invasive features of solid lymphoma. Furthermore, the results obtained using this combination of proteomics and DNA microarray analyses indicate that protein synthesis partly reflects, but does not correlate strictly with, mRNA production.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Enhanced transduction of mouse salivary glands with AAV5-based vectors.

We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct from rAAV2 and from each other, suggesting that they may direct binding and entry into different cell types. In the present study, we investigated the tropisms, transduction efficiencies, and antibody response to AAV vectors based on AAV serotypes 2, 4, and 5. Administration of rAAV2beta-galactosidase (betagal), rAAV4betagal, or rAAV5betagal to murine submandibular salivary glands by retrograde ductal instillation resulted in efficient transduction of salivary epithelial cells, with AAV4 and AAV5 producing 2.3 and 7.3 times more betagal activity compared with AAV2. Improved transduction with AAV5 was confirmed by QPCR of DNA extracted from glands and immunohistochemical staining for transgene expression. Like AAV2, AAV5 primarily transduced striated and intercalated ductal cells. AAV4 transduction was evident in striated, intercalated, and excretory ductal cells, as well as in convoluted granular tubules. In keeping with the encapsulated nature of the salivary gland, the majority of persistent viral genomes were found in the gland and not in other tissues. Neutralizing antibodies (NABs) found in the serum of virus-infused animals were serotype specific and there was no crossreactivity between serotypes. No NABs were detected in saliva but sialic acid conjugates present in saliva could neutralize AAV4 at low dilutions. Together our data suggest that because of differences in receptor binding and transduction pathways, other serotypes may have improved utility as gene transfer vectors in the salivary gland and these differences could be exploited in gene therapy applications.

Animals↗
PubMed2006

Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps.

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.

Adolescent↗
PubMed2006

Novel real-time monitoring system for human cytomegalovirus-infected cells in vitro that uses a green fluorescent protein-PML-expressing cell line.

Promyelocytic leukemia (PML) bodies are discrete nuclear foci that are intimately associated with many DNA viruses. In human cytomegalovirus (HCMV) infection, the IE1 (for "immediate-early 1") protein has a marked effect on PML bodies via de-SUMOylation of PML protein. Here, we report a novel real-time monitoring system for HCMV-infected cells using a newly established cell line (SE/15) that stably expresses green fluorescent protein (GFP)-PML protein. In SE/15 cells, HCMV infection causes specific and efficient dispersion of GFP-PML bodies in an IE1-dependent manner, allowing the infected cells to be monitored by fluorescence microscopy without immunostaining. Since a specific change in the detergent solubility of GFP-PML occurs upon infection, the infected cells can be quantified by GFP fluorescence measurement after extraction. With this assay, the inhibitory effects of heparin and neutralizing antibodies were determined in small-scale cultures, indicating its usefulness for screening inhibitory reagents for laboratory virus strains. Furthermore, we established a sensitive imaging assay by counting the number of nuclei containing dispersed GFP-PML, which is applicable for titration of slow-growing clinical isolates. In all strains tested, the virus titers estimated by the GFP-PML imaging assay were well correlated with the plaque-forming cell numbers determined in human embryonic lung cells. Coculture of SE/15 cells and HCMV-infected fibroblasts permitted a rapid and reliable method for estimating the 50% inhibitory concentration values of drugs for clinical isolates in susceptibility testing. Taken together, these results demonstrate the development of a rapid, sensitive, quantitative, and specific detection system for HCMV-infected cells involving a simple procedure that can be used for titration of low-titer clinical isolates.

Anticoagulants↗
PubMed2005

Eosinophil chemoattractants in the middle ear of patients with eosinophilic otitis media.

BACKGROUND: Patients with intractable otitis media associated with bronchial asthma have an extensive accumulation of eosinophils in the effusion and mucosa of the middle ear; this condition is called eosinophilic otitis media (EOM). It remained to be determined how eosinophils accumulate in the middle ear. OBJECTIVES: To clarify the pathogenesis of middle ear diseases, we measured the concentration of eosinophil chemoattractants in middle ear effusion (MEE), and carried out immunohistochemical studies of middle ear mucosa specimens to demonstrate the expression of eosinophil chemoattractants. METHODS: Middle ear effusion samples were obtained from 15 EOM patients with bronchial asthma and from six controls for the measurement of eosinophil cationic protein (ECP), IL-5, eotaxin and regulated on activation, normal T expressed and secreted concentrations. Middle ear mucosa samples were also taken from 14 EOM patients and 16 controls for immunohistochemical study. In 10 EOM patients, the numbers of immunoreactive cells as well as apoptotic cells were determined before and after the topical application of triamcinolone acetonide into the middle ear. RESULTS: In EOM, significantly higher ECP and IL-5 concentrations were detected in MEE than in serum, and ECP, IL-5 and eotaxin concentrations in MEE were higher in the EOM patients than in the controls. ECP concentration positively correlated with that of IL-5. Immunohistochemically, the numbers of cells positive for EG2 and ecalectin were significantly higher in the EOM patients than in the controls. After the topical application of triamcinolone acetonide, the numbers of infiltrating cells and immunoreactive cells distinctly decreased, whereas the number of apoptotic cells significantly increased. CONCLUSION: In EOM, locally produced IL-5 may play a crucial role in the accumulation of eosinophils in the middle ear. Chemokines such as ecalectin and eotaxin are also produced in the middle ear, and help activate and enhance the survival of eosinophils to induce the intractable condition in the middle ear. The topical application of triamcinolone acetonide induces the apoptosis of not only eosinophils but also eosinophil chemoattractant-producing cells, thereby improving the middle ear condition.

Adult↗
PubMed2004

Perioperative evaluation of carotid endarterectomy by 3D-CT angiography with refined reconstruction: preliminary experience of CEA without conventional angiography.

Three-dimensional CT angiography (3D-CTA) was employed for perioperative evaluation of carotid endarterectomy (CEA) as an alternative to conventional angiography. A total of 62 carotid arteries were examined before and after CEA, 26 with an early 3D-CT system and 36 with multidetector helical CT allowing sophisticated reconstruction by a personal workstation. In addition to patients who had undergone conventional angiography at other institutes, 10 subjects underwent CEA on the basis of 3D-CTA findings alone. The findings provided detailed information with an excellent view of carotid stenoses. Volume rendering images comprehensively visualized lesions and surrounding structures as well as calcifications, which were also well depicted by maximum intensity projection images. Evaluation of the cerebral circulation is one problem that still requires solution, although cerebral vessels were delineated by 3D-CTA. One patient experienced transient hemiparesis, but no significant permanent deficit. We conclude that 3D-CTA is a safe and accurate modality that is a practical alternative to conventional perioperative angiography.

Aged↗
PubMed2002

An endoplasmic reticulum protein, p180, is highly expressed in human cytomegalovirus-permissive cells and interacts with the tegument protein encoded by UL48.

We have used a virus overlay assay to detect cellular proteins associated with human cytomegalovirus (HCMV) particles. The radiolabeled HCMV particles specifically bound to two host proteins with molecular sizes of 150 and 180 kDa. By a micro-amino-acid sequencing technique, the 180-kDa protein was identified as a human homologue of the ES130/p180 ribosome receptor (p180), which is an integral endoplasmic reticulum (ER) membrane protein possessing a very unique tandem repeat domain at its N-terminal region. The virus overlay assay using truncated p180 polypeptides revealed that HCMV binding to human p180 occurred through the N-terminal region. In HCMV-permissive cells the high level of expression of the human p180 protein was clearly observed regardless of cell type. Furthermore, we showed that p180 binds to the UL48 gene product, which is one of the predominant tegument proteins of HCMV and which is considered to be tightly associated with the capsid. The interaction between the two proteins was assumed to be specific and was observed both in vitro and in vivo. During the late phase of infection, the unique relocation of human p180 was observed, that is, to the juxtanuclear region, which appeared to be in the vicinity of the area where naked virions were frequently observed in an electron-microscopic study. Thus our data suggest that p180 interacts with the HCMV tegument, at least through pUL48, during the HCMV replication process. We discuss the possible role of the interaction between p180 and pUL48 in the intracellular transport of HCMV virions.

Amino Acid Sequence↗
PubMed2001

Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies.

BACKGROUND: Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) cells express human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen (LANA) (open reading frame [ORF] 73 protein), suggesting that LANA plays an important role in the pathogenesis of HHV-8-associated malignancies. Recently, the binding of LANA to p53 was demonstrated in vitro. In the current study, the authors investigated the association between p53 and LANA expression with apoptosis in HHV-8-associated malignancies in vivo. METHODS: Twenty-six cases of KS, 1 case of HHV-8-associated solid lymphoma, 2 PEL cell lines, and an HHV-8-associated lymphoma engrafted in severe combined immunodeficiency (SCID) mice were examined. Immunohistochemistry using the catalyzed signal amplification system was employed to detect LANA and p53 on paraffin embedded tissues and the immunofluorescence technique was used on cell lines. To detect apoptosis, the TdT-mediated dUTP nick end labeling (TUNEL) method was used. For mutation analysis of p53, exons 5-9 of the p53 gene were amplified by polymerase chain reaction and examined by direct sequencing. RESULTS: Immunohistochemistry revealed that LANA and p53 were expressed in the tumor cells of all these specimens, and apoptotic cells were rarely detected in them using the TUNEL method. Immunofluorescence assay revealed that LANA colocalized with p53 in the nuclei of PEL cells. Sequencing analysis indicated that there was no mutation in the deduced amino acid sequences of p53 in KS tissues. CONCLUSIONS: These data suggest colocalization of p53 and LANA and the inhibition of apoptosis in HHV-8-associated malignancies in vivo, supporting the results found in vitro that p53 inhibition by LANA suppresses cell death, as reported previously. These results also suggest that the p53 pathway is crucial in the pathogenesis of HHV-8-associated malignancies.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Human-herpesvirus-8-encoded K8 protein colocalizes with the promyelocytic leukemia protein (PML) bodies and recruits p53 to the PML bodies.

Promyelocytic leukemia protein (PML) bodies are nuclear sites for both input viral genome deposition and immediate-early (IE) gene transcription during infection with certain human DNA viruses, such as human cytomegalovirus (HCMV), herpes simplex virus type 1, and adenovirus. In this study, we showed that the K8 (K-bZIP) protein, an early protein encoded by the human herpesvirus 8 (HHV-8), colocalized with the PML bodies in HHV-8-infected primary effusion lymphoma cells. Cotransfection of two plasmids expressing the K8 protein and green-fluorescence protein (GFP)-PML fusion protein into 293T cells revealed that the K8 protein colocalized with PML in cells with high PML expression. Overexpression of the K8 protein in Chinese hamster ovary (CHO) cells with stable GFP-PML expression did not induce the dispersion of the PML bodies, unlike the IE1 protein of HCMV. Transfection of a truncated K8 gene revealed that the leucine zipper domain of the K8 protein was required for the colocalization with PML. We also demonstrated that the K8 protein bound to p53 in vivo and in vitro, and that high expression of the K8 protein caused the accumulation of p53 to the PML bodies in CHO cells, suggesting that the K8 protein functions in the recruitment of p53 to the PML bodies. These data suggest that the K8 protein may be associated with the functional modulation of p53 in the nucleus during the lytic phase of HHV-8.

Animals↗
PubMed2001

A metabotropic glutamate receptor antagonist, alpha-methyl-4-carboxyphenylglycine, attenuates immediate early gene mRNA expression following traumatic injury in cultured rat cortical glial cells.

The effects of three glutamate receptor antagonists, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801) for the N-methyl-D-aspartate receptor, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f] quinoxaline-7-sulfonamide (NBQX) for the alpha-amino-3-hydroxy-5methyl-4-isoxazole propionate /kinate receptor and (S)-alpha-methyl-4-carboxyphenylglycine (MCPG) for the metabotropic receptor, on c-fos and c-jun mRNA expression were investigated in cultured cortical glial cells following traumatic scratch injury. Expression of the two genes along the edges of wounds detected by in situ hybridization was not affected by MK-801 and NBQX. However, 100 and 500 microM of MCPG remarkably reduced the hybridization signals for both c-fos and c-jun mRNAs. The present results suggest that group I metabotropic glutamate receptors might have some association with immediate early gene induction after in vitro traumatic injury in glial cells.

Animals↗
PubMed2001

Injection of human herpesvirus-8 in human skin engrafted on SCID mice induces Kaposi's sarcoma-like lesions.

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) has been implicated in the development of Kaposi's sarcoma (KS) and several B-cell lymphoproliferative diseases. Serologic and molecular genetic association data has implicated HHV-8 as the causal agent of KS, but its role in the development of KS lesions is not understood. To examine the etiology of KS, HHV-8 was injected into normal human skin transplanted onto SCID mice. Injection of HHV-8 induced lesion formation that is morphologically and phenotypically consistent with KS, including the presence of angiogenesis and spindle-shaped cells latently infected with HHV-8. These findings suggest that HHV-8 is indeed the etiologic agent of KS, and that the virus plays an important role in initiation of this disease.

Animals↗
PubMed2001

Serological and immunohistochemical detection of human herpesvirus 8 in Kaposi's sarcoma after immunosuppressive therapy for bullous pemphigoid.

Kaposi's sarcoma (KS) developed in an 87-year-old human immunodeficiency virus-negative woman from Hokkaido island 4 months after oral administration of prednisolone for the treatment of bullous pemphigoid (BP), and rapidly disseminated to almost the entire body within 2 months. The open reading frame (ORF) 59 and ORF73 proteins encoded by human herpesvirus 8 (HHV-8) were detected immunohistochemically in the nuclei of the tumour cells of KS. The protein coded by ORF73, latent protein, was detected in most of the nuclei of the tumour cells, but only a few tumour nuclei were positive for the ORF59 protein, a lytic protein expressed during active infection. The antibodies against both lytic and latent proteins of HHV-8 were detected retrospectively in the serum 4 months before the appearance of KS and before prednisolone therapy had been started. Immunosuppression associated with the treatment for BP possibly activated latent HHV-8 infection and induced the development of KS.

Aged↗
PubMed2001

HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype.

Primary effusion lymphoma (PEL) has been recognized as a body-cavity-based lymphoma that was originally reported to be associated with human herpes virus 8 (HHV8) infection, and was frequently found in human immunodeficiency virus-positive (HIV) patients. Here we describe an autopsy case of PEL of the peritoneal cavity in an immunocompetent patient. Cytological analysis of tumor cells within ascites revealed immunocytochemical features of keratin positivity and CD45 negativity. At autopsy, the presence of a massive volume of ascites as well as diffuse tumor cell infiltrates within the serosa of the intestine and mesenterium were observed. Tumor cells were morphologically similar to anaplastic large-cell lymphoma, but were immunohistochemically positive for keratin and epithelial membrane antigen (EMA). They also showed no reactivity to representative lymphocyte surface markers including CD45, in addition to being negative for CD30 and p80NPM/ALK. Molecular analysis of the tumor cells revealed monoclonality of the immunoglobulin heavy-chain gene rearrangement which demonstrated a lymphoma of the B-cell lineage. Furthermore, HHV8 was not detected by immunohistochemical analysis, PCR or nested PCR technique. Based on these results, we consider the present case to be an HHV8-negative PEL with keratin and EMA positivity.

Adult↗
PubMed2001

HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman's disease.

Multicentric Castleman's disease (MCD) is a clinicopathologically defined entity characterized by systemic lymphadenopathy with unique pathomorphology such as angiosclerosis, blood vessel proliferation in and around follicles, and plasmacytosis. While its pathogenesis has remained unclarified for many years, identification of the human herpesvirus 8 (HHV-8) in at least some MCD cases has opened new perspectives in this field. Because previous reports have described many inconsistencies regarding HHV-8 positivity in MCD, we intended to clarify this issue by the introduction of more convincing methodologies. For this investigation, we introduced two antibodies produced in our laboratories that recognize a latent gene product ORF73 and a lytic gene product ORF59, together with two well-recognized methods, in situ hybridization for the detection of lytic phase transcript T1.1/nut-1, and genomic polymerase chain reaction (PCR). Eighty-two cases of MCD were collected from Japan (n = 75) and France (n = 7). In three cases, the patients were suffering from acquired immunodeficiency syndrome (AIDS). Immunohistochemistry and in situ hybridization showed identical results: only three out of 82 cases were positively stained, and all the positive cases were found to be the patients with AIDS. Genomic PCR was done in 43 cases, and only one case produced positive results: the only AIDS case among the 43 cases studied by genomic PCR. Histopathologically, the HHV-8-positive cases showed the highest intensity of angiosclerosis and germinal center / perifollicular vascular proliferation, while plasmacytosis was not severe in the HHV-8-positive cases. Some of the HHV-8-negative MCD cases displayed similar histopathology, but at a far less intense level, except for the plasmacytosis. These results suggest that: (i) all three of the HHV-8-positive MCD patients in the present group are the patients with AIDS; and (ii) HHV-8-positive MCD patients develop typical but marked angiosclerosis and vascular proliferation that might be differentiated from HHV-8-negative MCD patients, who showed far less intense changes.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, China.

We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is located in the north-western area of China surrounded by Mongolia in the east, Russia in the north and Kazakhstan in the west. Fifteen of the patients were of the Uygur people. All patients were male and did not have acquired immunodeficiency syndrome. Most of the lesions were found in the lower and/or upper extremities, with 16 patients showing multiple lesions. Immunohistochemical examination of the lesions revealed that human herpesvirus 8 (HHV-8)-encoded latency-associated nuclear antigen was expressed in the nuclei of spindle-shaped tumor cells. HHV-8 DNA was detected by polymerase chain reaction in all seven cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV-8-encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype C that was common in the Mediterranean, the Middle East and East Asian countries. In addition, using immunofluorescence we investigated the seroprevalence of HHV-8 in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the serological study revealed that 34 of the patients (46.6%) were positive for antibodies against HHV-8, suggesting that HHV-8 infection is widespread in Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high seropositivity rate implies that Xinjiang is the most endemic area for HHV-8 infection in the world known to date. Considering that Xinjiang is located at the middle point of the Silk Road that used to extend from Rome to China, these data imply that the virus may have been in circulation in this area due to the migration of the people via the Silk Road.

Adolescent↗