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Biomedical subjects

N Yamamoto

Publications and source records attributed to N Yamamoto.

At least 127 records · Page 7Linked to original sources
PubMed2001

A dose escalation study of paclitaxel and carboplatin in untreated Japanese patients with advanced non-small cell lung cancer.

BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3-h infusion) and carboplatin (area under the curve 6) is widely used for non-small cell lung cancer in the USA. In Japan, however, the recommended dose for single-use paclitaxel in 3-h infusion is 210 mg/m(2) and the optimal dose of this agent in combination with carboplatin has not been established. This dose escalation study was designed to determine the maximum tolerated dose of paclitaxel in 3-h infusion plus carboplatin at a fixed dose of area under the curve 6 for Japanese patients with advanced, untreated non-small cell lung cancer. METHODS: Between October 1999 and May 2000, 19 patients were enrolled and 18 of these patients were evaluable for toxicity. Chemotherapy consisted of carboplatin area under the curve 6 and an escalated dose of paclitaxel on day 1 every 3-4 weeks. The initial dose of paclitaxel was 175 mg/m(2) and was increased by 25 mg/m(2) at each dose level. RESULTS: Neutropenia was the major toxicity observed, but was not dose related. Febrile neutropenia was not observed. No grade 3 or more peripheral neuropathy, myalgia or arthralgia was reported. The maximum tolerated dose was not determined even at the highest paclitaxel dose level (225 mg/m(2)) in this study. Partial responses were observed in six of the 19 patients (31.6%). CONCLUSION: We conclude that paclitaxel at 225 mg/m(2) in 3-h infusion and carboplatin area under the curve 6 can safely be given to Japanese patients with non-small cell lung cancer.

Adult↗
PubMed2001

A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer.

BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.

Adult↗
PubMed2001

Conformational change of dimerization initiation site of HIV-1 genomic RNA by NCp7 or heat treatment.

Dimerization initiation site (DIS) of the human immunodeficiency virus type 1 (HIV-1) genome has been identified as a primary sequence that can form a stem-loop structure with a self-complementary sequence in the loop and a bulge in the stem. A DIS RNA fragment spontaneously forms a kissing dimer and is converted into an extended-duplex dimer by supplement of nucleocapsid protein NCp7. This two-step dimerization reaction can be also executed by a heat treatment instead of the binding proteins. However, it has not identified whether mechanisms of the conformational conversion by two different treatments are identical or not. In the present study, we used a series of DIS RNA oligonucleotides and the conformations of two extended-duplex dimers produced by the two different treatments were compared by the analysis of NMR spectra in the imino proton region. It was found that the effects of the two kinds of treatments are quite similar and the conformations of the two extended-duplex dimers are identical. These findings suggest that the conversion mechanisms DIS RNA by NCp7 and heat treatments are similar.

Base Sequence↗
PubMed2001

The soluble interleukin 6 receptor: mechanisms of production and implications in disease.

Interleukin 6 (IL-6) performs a prominent role during disease and has been described as both a pro- and anti-inflammatory cytokine. A key feature in the regulation of IL-6 responses has been the identification of a soluble interleukin 6 receptor (sIL-6R), which forms a ligand-receptor complex with IL-6 that is capable of stimulating a variety of cellular responses including proliferation, differentiation and activation of inflammatory processes. Elevated sIL-6R levels have been documented in numerous clinical conditions indicating that its production is coordinated as part of a disease response. Thus, sIL-6R has the potential to regulate both local and systemic IL-6-mediated events. This review will outline the central role of sIL-6R in the coordination of IL-6 responses. Details relating to the mechanisms of sIL-6R production will be provided, while the potential significance of sIL-6R during the development of clinical conditions will be emphasized. We want to convey, therefore, that when thinking about the inflammatory capability of IL-6, it is essential to consider not only the action of IL-6 itself, but also the effect sIL-6R may have on cellular processes.

Alternative Splicing↗
PubMed2001

Late-onset form of lattice corneal dystrophy caused by leu527Arg mutation of the TGFBI gene.

PURPOSE: To report two Japanese patients who were clinically diagnosed with late-onset and sporadic lattice corneal dystrophy (LCD) in whom a Leu527Arg mutation in the TGFBI gene was found. METHODS: Molecular genetic analysis was performed on DNA extracted from peripheral leukocytes from the patients. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and directly sequenced. Histopathologic study was performed on the corneal tissue obtained during deep lamellar keratoplasty (DLK) from one of the patients. RESULTS: Patient 1 was a 74-year-old man who noticed a visual disturbance at the age of 72 years. Deep stromal opacities with nodular deposits and thick lattice lines were observed only in the right cornea, and DLK was performed. Patient 2 was an 82-year-old man who had LCD (similar in appearance to that in patient 1) in both eyes without visual disturbance. Neither of the patients had a family history of corneal problems and had no episode of corneal erosion. A heterozygous single base-pair transition (CTG to CGG, leucine to arginin) was detected in codon 527 of the TGFBI gene in both patients. No mutation was found in codons 124, 501, 518, 546, or 555. Histopathologically, relatively large amyloid deposits in the deep corneal stroma and ribbons of amyloid deposits just beneath the Bowman's layer were observed in the corneal tissue of patient 1. CONCLUSIONS: Clinical features and pathologic findings of the late-onset form of LCD with an L527R mutation in the TGFBI gene were made clear.

Aged↗
PubMed2001

Fungal keratitis caused by Colletotrichum gloeosporioides.

PURPOSE: To describe a case of fungal keratitis caused by a rare coelomycete pathogen, Colletotrichum gloeosporioides. METHODS: An 82-year-old man with myelodysplastic syndrome developed fungal keratitis 6 months after cataract surgery in the left eye. Because the findings of the anterior chamber deteriorated after the initiation of natamycin, additional treatment with topical and systemic fluconazole was initiated. RESULTS: The isolates of corneal scraping grew C. gloeosporioides. After antifungal treatment of 2 months, the corneal lesion resolved with no recurrence of infection over a 5-year follow-up period. CONCLUSIONS: A combination treatment of natamycin and fluconazole was effective in the treatment of C. gloeosporioides.

Aged↗
PubMed2001

Identification and characterization of the sodA genes encoding manganese superoxide dismutases in Vibrio parahaemolyticus, Vibrio mimicus, and Vibrio vulnificus.

Sequencing of Fur titration assay-positive clones obtained from genomic DNA libraries of Vibrio parahaemolyticus, V. mimicus and V. vulnificus revealed open reading frames encoding proteins of 202, 205 and 202 amino acid residues, respectively. Each open reading frame was preceded by a predicted Fur box which overlaps a likely promoter with similarity to the -10 and -35 consensus sequence of Escherichia coli. The deduced amino acid sequences shared considerable homology with bacterial Mn-containing superoxide dismutases (MnSODs). Consistent with this, these Vibrio strains produced proteins with SOD activity resistant to inhibition by H2O2 and KCN only when grown under iron-limiting conditions. Primer extension analysis of the total RNA from these vibrios revealed iron-repressible expression of the genes. Furthermore, when grown under iron-limiting conditions, E. coli carrying a plasmid with each cloned gene overexpressed protein with the same electrophoretic mobility and insensitivity of SOD activity to H2O2 and KCN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by N-terminal amino acid sequencing revealed that proteins (MnSODs) having N-terminal amino acid sequences consistent with those deduced from the corresponding genes were present in cell lysates of the vibrios grown under these iron-limited conditions. These results demonstrate that the genes cloned in this study are sodA homologs encoding MnSODs, whose expression is regulated by the iron status of the growth medium. PCR using a primer set based on the V. parahaemolyticus sodA sequence revealed the presence of homologous genes in certain other Vibrio species.

Amino Acid Sequence↗
PubMed2001

Epidemiological survey of Orientia tsutsugamushi distribution in field rodents in Saitama Prefecture, Japan, and discovery of a new type.

There are various antigenic variants of Orientia tsutsugamushi which are distinguished by immunological and molecular genetic methods targeted at the antigenic diversity of 56-kDa type-specific antigen proteins. The present study was performed to analyze 15 strains successfully isolated from rodents in Saitama Prefecture, Japan, by 56-kDa gene sequence homologies, reactivities with type-specific monoclonal antibodies and polymerase chain reaction (PCR) using type-specific primer-pairs. We demonstrated the presence of a new type of O. tsutsugamushi among the isolates. This new type, designated as the Saitama type, was located in the branch of Karp type in the phylogenetic tree based on 56-kDa gene sequences, but distant from the known Karp types, such as Karp, JP-1 and JP-2, showing less than 90% homology. Strains of this type could not be distinguished by immunological methods from Karp type strains, but a new primer-pair for PCR which specifically amplifies the DNA of this new type strain was designed. This primer-pair may serve to find this strain type in future studies.

Animals↗
PubMed2001

[Tsutsugamushi disease (scrub typhus) in Japan: epidemiological aspects].

Epidemiological aspects of tsutsugamushi disease (scrub typhus) in Japan in 1998 were analyzed using questionnaires. Four hundred and sixteen scrub typhus cases were reported in 24 prefectures in 1998. The annual number of the patients in 1998 was similar to those in the preceding three years. There was no sex difference. The patients at the age of 51 or greater accounted for 72% of the total cases. Patients engaged in farming and forestry accounted for 32% and 14% cases, respectively. Fifty-six, 21 and 19% were reported in Kyusyu, Kanto and Tohoku-Hokuriku districts, respectively, 96% of the total cases being reported in these 3 districts. Most cases were reported from April through June with some from October through December in Tohoku-Hokuriku districts, while most cases were reported from October through December in other districts, including Kyusyu and Kanto districts. Thus, there was a difference in epidemic seasons among the districts. Serotypes of scrub typhus rickettsia were analyzed by serum antibody titers in the Kyusyu district. The novel Kawasaki and Kuroki types were major strains; however, no geographical difference was seen within the Kyusyu district. Interestingly, 24 cases were diagnosed only by the new serotypes not by the classical serotypes (Kato, Karp and Gilliam) in serological tests. This result suggests that further investigations are required to determine the prevalent serotypes in each district and to improve the serological tests. This was the first comprehensive report of epidemiology of scrub typus in entire Japan. Information obtained in the present study provides deep insight into prediction, diagnosis, treatment and prevention of scrub typhus in Japan.

Adolescent↗
PubMed2001

[Tsutsugamushi disease (scrub typhus) in Japan: clinical features].

Clinical features of tsutsugamushi disease (scrub typhus) were analyzed, based on 416 cases reported in Japan in 1998. Three major clinical symptoms: eschar, fever and rash were found in 87%, 98% and 92% of the cases, respectively. Elevated levels of CRP, GOT, GPT and LDH were observed in 96%, 85%, 78% and 91%, respectively. These clinical and laboratory findings were observed in the majority of the cases and considered important for diagnosis. Disseminated intravascular coagulation developed in 21 cases, indicating that scrub typhus can be life threatening. Lymphadenopathy was observed in 51% of the cases. Enlarged lymph nodes were limited to the local sites in 75% of these lymphadenopathy cases and most of these sites were adjacent to eschars. Most eschars were scabbed and located in the abdomen and the lower half of the body, especially the feet. This suggests that these parts are frequently exposed to tsutsugamushi mites. Furthermore, the skin is soft in these parts and covered by cloth. These factors may make it possible for mites to keep biting without being noticed for several hours, long enough for rickettsial transmission. Interestingly, eschar and rash were absent in 14% and 8% of the cases, respectively. This result suggests that the cases without the unique symptoms may have been misdiagnosed as common cold or other febrile illnesses. One hundred and fifty-four suspected cases were not scrub typhus cases by the serological tests. The three major clinical symptoms were present in approximately a half of these negative cases, eschar being observed in approximately 70%. This may suggest the presence of new type of scrub typhus can not be diagnosed by the present laboratory tests. Clinical features of scrub typhus in Japan were well revealed, and information obtained in the present study is useful for improving clinical diagnosis. It should, however, be stressed that there were cases that could not be correctly diagnosed only by the clinical symptoms, suggesting that it is important to improve the serological tests.

Diagnosis, Differential↗
PubMed2001

Induction of monocyte chemoattractant protein 1 by Helicobacter pylori involves NF-kappaB.

Helicobacter pylori stimulates secretion of monocyte chemoattractant protein 1 (MCP-1) from gastric epithelial cells. Secretion of this chemokine may be instrumental in monocyte infiltration of the gastric epithelium that characterizes H. pylori gastritis. The aim of this study was to identify the mechanism by which H. pylori induces MCP-1 production. Induction of MCP-1 mRNA was assessed by reverse transcription-PCR. We used luciferase reporter assays to monitor activation of the MCP-1 gene promoter and electrophoretic mobility shift assays to explore binding of transcription factors to this promoter. H. pylori infection increased MCP-1 mRNA expression from gastric epithelial cells. Induction of MCP-1 mRNA relies on an intact cag pathogenicity island. We identified two closely spaced NF-kappaB-binding sites within the MCP-1 distal enhancer as required for H. pylori-induced MCP-1 gene transcription. H. pylori infection led to the specific activation of NF-kappaB complexes containing p50 and p65. Kinase-deficient mutants of NF-kappaB-inducing kinase (NIK) and IkappaB kinases (IKK) caused suppression of MCP-1 distal enhancer-dependent reporter activity following H. pylori infection. H. pylori infection induces the activation of NF-kappaB via the NIK-IKK signaling complex, leading to MCP-1 gene transcription in gastric epithelial cells.

Chemokine CCL2↗
PubMed2001

Immune response induced by airway sensitization after influenza A virus infection depends on timing of antigen exposure in mice.

To study which phase of viral infection promotes antigen sensitization via the airway and which type of antigen-presenting cells contributes to antigen sensitization, BALB/c mice were sensitized by inhalation of ovalbumin (OA) during the acute phase or the recovery phase of influenza A virus infection, and then 3 weeks later animals were challenged with OA. The numbers of eosinophils and lymphocytes, the amounts of interleukin-4 (IL-4) and IL-5 in the bronchoalveolar lavage fluid, and the serum levels of OA-specific immunoglobulin G1 (IgG1) and IgE increased in mice sensitized during the acute phase (acute phase group), while a high level of gamma interferon production was detected in those sensitized during the recovery phase (recovery phase group). In the acute phase group, both major histocompatibility complex class II molecules and CD11c were strongly stained on the bronchial epithelium; in the recovery phase group, however, neither molecule was detected. OA-capturing dendritic cells (DCs) migrated to the regional lymph nodes, and a small number of OA-capturing macrophages were also observed in the lymph nodes of the acute phase group. In the recovery group, however, no OA-capturing DCs were detected in either the lungs or the lymph nodes, while OA-capturing macrophages were observed in the lymph nodes. These results indicate that the timing of antigen sensitization after viral infection determines the type of immune response.

Animals↗
PubMed2001

Virological properties and nucleotide sequences of Cas-E-type endogenous ecotropic murine leukemia viruses in South Asian wild mice, Mus musculus castaneus.

Two types of endogenous ecotropic murine leukemia viruses (MuLVs), termed AKV- and Cas-E-type MuLVs, differ in nucleotide sequence and distribution in wild mouse subspecies. In contrast to AKV-type MuLV, Cas-E-type MuLV is not carried by common laboratory mice. Wild mice of Mus musculus (M. m.) castaneus carry multiple copies of Cas-E-type endogenous MuLV, including the Fv-4(r) gene that is a truncated form of integrated MuLV and functions as a host's resistance gene against ecotropic MuLV infection. Our genetic cross experiments showed that only the Fv-4(r) gene was associated with resistance to ecotropic F-MuLV infection. Because the spontaneous expression of infectious virus was not detected in M. m. castaneus, we generated mice that did not carry the Fv-4(r) gene but did carry a single or a few endogenous MuLV loci. In mice not carrying the Fv-4(r) gene, infectious MuLVs were isolated in association with three of six Cas-E-type endogenous MuLV loci. The isolated viruses showed a weak syncytium-forming activity for XC cells, an interfering property of ecotropic MuLV, and a slight antigenic variation. Two genomic DNAs containing endogenous Cas-E-type MuLV were cloned and partially sequenced. All of the Cas-E-type endogenous MuLVs were closely related, hybrid-type viruses with an ecotropic env gene and a xenotropic long terminal repeat. Duplications and a deletion were found in a restricted region of the hypervariable proline-rich region of Env glycoprotein.

Amino Acid Sequence↗
PubMed2001

OX40 stimulation by gp34/OX40 ligand enhances productive human immunodeficiency virus type 1 infection.

OX40 is a member of the tumor necrosis factor (TNF) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells. To investigate the role of costimulation of OX40 in human immunodeficiency virus type 1 (HIV-1) infection by its natural ligand, gp34, the OX40-transfected ACH-2 cell line, ACH-2/OX40, chronically infected with HIV-1, was cocultured with paraformaldehyde (PFA)-fixed gp34-transfected mouse cell line, SV-T2/gp34. The results showed that HIV-1 production was strongly induced. This was followed by apparent apoptosis, and both processes were specifically inhibited by the gp34-specific neutralizing monoclonal antibody 5A8. Endogenous TNF alpha (TNF-alpha) and TNF-beta production were not involved in the enhanced HIV-1 production. Furthermore, enhanced HIV-1 transcription in gp34-stimulated ACH-2/OX40 cells was dependent on the kappa B site of the HIV-1 long terminal repeat, and the OX40-gp34 interaction activated NF-kappa B consisting of p50 and p65 subunits. When primary activated CD4(+) T cells acutely infected with HIV-1(NL4-3) (CXCR4-using T-cell-line-tropic) were cocultured with PFA-fixed gp34(+) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/gp34 cells, HIV-1 production was also markedly enhanced. The enhancement was again significantly inhibited by 5A8. The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by gp34 may play an important role in enhancing HIV-1 production in both acutely and latently infected CD4(+) T cells in vivo.

Animals↗
PubMed2001

Unique monoclonal antibody recognizing the third extracellular loop of CXCR4 induces lymphocyte agglutination and enhances human immunodeficiency virus type 1-mediated syncytium formation and productive infection.

To increase insight into the structural basis of CXCR4 utilization in human immunodeficiency virus type 1 (HIV-1) infection, a new generation of three monoclonal antibodies (MAbs) was developed in WKA rats. The A80 MAb, which binds an epitope in the third extracellular loop (ECL3) of CXCR4, has unique biologic properties that provide novel insights into CXCR4 function. This agent enhanced syncytium formation in activated human peripheral blood mononuclear cells (PBMC) infected with X4 or R5 and CEM cells infected with X4 HIV-1 strains. Exposure to A80 increased the productive infection of activated CD4(+) T cells and CEM cells with R5 and X4 viruses, respectively. This antibody uniquely induced agglutination of PBMC and CEM cells but did not activate calcium mobilization. Agglutination induced by A80 was inhibited by stromal cell-derived factor 1, T22, and phorbol 12-myristate 13-acetate but was not significantly altered by pretreatment of cells with pertussis toxin, wortmannin, or MAbs to LFA-1, ICAM-1, ICAM-2, and ICAM-3. The binding of the A145 and A120 MAbs was mapped to the N-terminal extracellular domain and a conformational epitope involving ECL1 and ECL2, respectively. Both of these MAbs inhibited HIV-1 infection and lacked the novel properties of A80. These results suggest a new role for CXCR4 in homologous lymphocyte adhesion that is ligand independent and in HIV-1 infection.

Amino Acid Sequence↗
PubMed2001

Encoding of different aspects of afferent activities by two types of cells in the corpus glomerulosum of a teleost brain.

The corpus glomerulosum (CG) is an expansive nucleus in acanthopterigian teleosts that has been suggested to be involved in vision-related information processing and the control of the hypothalamic function. The CG has only two types of constituent cells, the large cell and the small cell, and well-defined afferent/efferent fiber connections. One of the three types of teleostean CG, type III has additional outstanding morphological characters: clearly laminated organization and giant (>50 microm in diameter) tips of postsynaptic dendrites. Although such histological architecture is potentially advantageous for the study of information processing in a brain nucleus based on the physiological properties of identified cells and synapses, previous studies on the CG have been limited to anatomy. In this study, we developed a slice preparation of the type III CG in a teleost, Stephanoplepis cirrhifer, and studied the morphology and physiology of individual cells and synaptic transmission by means of dendritic intracellular and somatic whole cell recordings. The characteristic morphology of the two types of cells was revealed by intracellular staining. While both of them received similar glutamatergic and GABAergic projections from the nucleus corticalis mediated by AMPA, N-methyl-D-aspartate, and GABA(A) receptors, they showed quite distinctive firing properties and postsynaptic responses with current injection and synaptic inputs: the large cell fired a single spike, and the small cell fired a spike train whose frequency was dependent on the stimulus intensity. Furthermore, the large cell showed low-pass temporal filtering properties with paired stimuli. These results suggest that the large cell and the small cell may encode different aspects of the corticalis activities.

Action Potentials↗