Search PubMed⌕ Search

Biomedical subjects

T Noda

Publications and source records attributed to T Noda.

At least 163 records · Page 9Linked to original sources
PubMed1998

Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Amphotericin B↗
PubMed1998

Moesin is not a receptor for measles virus entry into mouse embryonic stem cells.

The involvement of moesin in measles virus (MV) entry was investigated with moesin-positive and -negative mouse embryonic stem (ES) cells. MV infection of these cells was very ineffective and was independent of moesin expression. Furthermore, when these cells were transfected to express human CD46, a 100-fold increase in syncytium formation was observed with these cells and was independent of the expression of moesin. The only obvious difference between moesin-positive and -negative ES cells was the shape of the syncytia formed. Moesin-negative ES cells expressing or not expressing human CD46 formed separate pieces of fragmented syncytia which were torn apart during spreading, whereas ES cells expressing moesin exhibited typical syncytia. In addition, moesin was not detected on the surface of any murine cells or cell lines that we have tested by a flow cytometric assay with moesin-specific antibodies. These findings indicate that murine moesin is neither a receptor nor a CD46 coreceptor for MV entry into mouse ES cells. Moesin is involved in actin filament-plasma membrane interactions as a cross-linker, and it affects only the spreading and shape of MV-mediated syncytia.

Animals↗
PubMed1998

Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa.

Apoptosis after ischemia-reperfusion (I/R) was characterized in rat small intestine. Under halothane anesthesia, the superior mesenteric artery in the rat was occluded for 15 or 60 min, followed by reperfusion. Ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after I/R. Some rats were pretreated with alpha-difluoromethylornithine (DFMO) to examine the relationship between intestinal apoptosis and ornithine decarboxylase (ODC) activity. The percentage of fragmented DNA significantly increased just after ischemia and peaked at 1 h after reperfusion in the jejunum and ileum. These increases were significantly higher in the 60-min ischemia group compared with the 15-min ischemia group. This increase decreased 6 h after reperfusion. The results were corroborated by histological evaluations of the intestine under the same conditions. DFMO completely abolished elevation of ODC activity 6 h after reperfusion but did not change the percentage of fragmented DNA. Apoptosis in rat small intestine was induced by ischemia of the gut, and this process was exacerbated by reperfusion. The changes in apoptosis were independent of ODC activity.

Animals↗
PubMed1998

Defect in the induction of nitric oxide synthase by lipopolysaccharide (LPS) in an LPS-resistant mutant of a murine macrophage-like cell line, J774.1.

Nitric oxide (.NO)-generating activity was examined in a lipopolysaccharide (LPS)-resistant mutant of a murine macrophage-like cell line, J774.1, treated with LPS or LPS and interferon-gamma (IFN-gamma). This mutant, an LPS1916 cell line, showed no NO2- accumulation in the culture medium, and no expression of NOS activity in the cell extract, .NO synthase (NOS(II)) protein or NOS(II) mRNA on treatment with up to 10(4) ng/ml LPS, although the parental cell line, JA-4, showed significant .NO production. The addition of 10 U/ml IFN-gamma, together with more than 1 ng/ml LPS to JA-4 cells, increased .NO production remarkably, while IFN-gamma did not reverse the defect of .NO production in LPS1916 cells when they were treated with less than 10 ng/ml LPS; however, it induced .NO production by the mutant cells with more than 100 ng/ml LPS. Analysis of NOS activity, NOS(II) protein and NOS(II) mRNA revealed that LPS1916 cells are not devoid of the NOS(II) gene, but are rather defective in transcription of the gene in response to LPS, and this defect is partly reversed by IFN-gamma with higher LPS doses at more than 100 ng/ml. In addition, the delay of NOS(II) mRNA induction in LPS1916 cells, compared to that in JA-4 cells, treated with LPS+IFN-gamma seems to suggest some additional inducer(s) of NOS(II) transcription, followed by LPS signaling.

Animals↗
PubMed1998

[Workers' stress after Hanshin-Awaji earthquake in 1995--symptoms related to stress after 18 months].

Stress-related symptoms were investigated in workers living in the area hit by the Hanshin-Awaji earthquake. Questionnaires were distributed among taxi and truck drivers, longshoremen, workers in factories, hospitals and local government offices 18 months after the event. Nearly 40% of them, 3,015 answered. The multiple regressive analysis showed that the degree of housing damage was the factor most relevant to the symptoms. Although the symptoms decreased as time passed, the group with seriously damaged housing still complained of severe stress-related symptoms even 18 months after the event. Symptoms related to post traumatic stress disorder (PTSD) were observed in 48.0% in the male group with seriously damaged housing immediately after the quake. The figure was 34.2% of after 3 months and 12.6% after 18 months. 21.8%, 12.9% and 3.7%, respectively, were the figures in the male group with nil or slightly damaged housing. The number of workers who complained of the recurrence and worsening of chronic diseases peaked 3 months after the event and had not changed much even after 18 months. Workers also complained of anxiety over the loss of work, job pressure, overwork, difficulty of commuting to and from the area, danger at work, decline in income and changes of job location.

Anxiety↗
PubMed1998

Class II MHC antigen-expressing cells in the pulp tissue of human deciduous teeth prior to shedding.

The distribution and ultrastructure of the class II major histocompatibility complex (MHC) antigen-expressing cells in the pulp tissue of human deciduous teeth during the process of physiological root resorption was surveyed by histochemical and immunocytochemical methods using an anti-human leukocyte antigen (HLA)-DR-monoclonal antibody. Dental pulp was found to contain numerous HLA-DR-positive cells of various shapes; those showing a dendritic appearance were located mainly in the periphery of the pulp tissue, associated closely with the odontoblasts. The immunopositive cells sometimes extended their cytoplasmic processes into the dentinal tubules and increased in number in the areas affected by dental caries, attrition or restorative procedures, implicating their role in immunosurveillance. The immunopositive cells were located consistently at the pulp-dentin border during the stage of active resorption, adjacent to the preodontoclasts or odontoclasts, and covered the exposed dentin surface after the detachment of the odontoclasts until the onset of cementum formation. These data suggest that the HLA-DR-immunopositive cells in the coronal pulp of human deciduous teeth play an inductive role in the differentiation, migration and/or activation of the odontoclasts and cementoblast-like cells during the stages of tooth resorption.

Dental Pulp↗
PubMed1998

Primary cardiac leiomyosarcoma growing rapidly and causing right ventricular outflow obstruction.

Leiomyosarcomas are extremely rare primary cardiac tumors. We report a rapidly growing primary leiomyosarcoma of the right ventricle, which obstructed the right ventricular outflow tract within one month after symptom onset in a 68-year-old man. Two-dimensional echocardiography was useful in diagnosing the extent and progression of the tumor. The tumor was surgically resected on an emergency basis, and the right ventricle and pulmonary artery were successfully reconstructed. Recurrence of the tumor on the right ventricle was observed, and the patient was overcome by sudden dyspnea and died three months after surgery.

Aged↗
PubMed1998

[Severe mycosis-factors with fungus and host].

The deep-seated mycosis occurred in immunocompromized patients. Normally, the deep-seated mycosis became sever infection because of the defects of host defense or the adverse effects of antifungal agents. The major factors of the reason on the severity of the deep-seated mycosis depends on the pathogenesity and the drug resistance for antifungal agents in infected fungi. The clinical factors related with hosts defenses are important to the other reason on the severity. We investigated that the multiple drug resistant (MDR) mechanism may be one of the major roles plays in the azole resistant Candida albicans strains isolated form the patients with oropharyngeal candidiasis infected HIV. We analyzed which clinical factors are related with the prognosis of the patients with pulmonary cryptococcosis and aspergilloma. The titer of cryptococcal capsular antigen was earlier improve in the patient without underline disease than in the patients with underline diseases diagnosed pulmonary cryptococcosis. CRP was higher in the death cases in the patients with pulmonary aspergilloma, compared with alive cases.

AIDS-Related Opportunistic Infections↗
PubMed1998

[A case of cutaneous pseudallescheriosis resembling sporotrichosis].

An 83-year-old man with aplastic anemia and steroid induced diabetes mellitus developed multiple nodules with pus on the back of his right hand and forearm. He had been treated with a daily dose of 30mg prednisolone for 2 months. These lesions had appeared a month before his visit. The histopathological findings revealed dermal abscesses containing hyphal structures, lymphocytes, histiocytes and giant cells. Grocott-Methenamine stain demonstrated abundant fungal elements. In culture, colonies grow rapidly and produce a white, cottony mycelium which later becomes gray in color. Microscopically, ovoid and pyriform conidia are produced at the ends of long slender conidiophores. On PCA agar, synnemata with small conidal heads developed at 37 degrees C but cleistothecia did not appear. The patient did not respond to itraconazole therapy, however, with hyperthermic treatment, the eruptions gradually healed. Based on these findings, this fungal infection was diagnosed as pseudallescheriosis.

Aged↗
PubMed1997

Mouse LIM-kinase 2 gene: cDNA cloning, genomic organization, and tissue-specific expression of two alternatively initiated transcripts.

LIM-kinase 1 and LIM-kinase 2 (LIMK1 and LIMK2) are members of a novel protein kinase subfamily containing LIM motifs at the N-terminus. There are two isoforms of Limk2 transcripts coding proteins with distinct N-terminal structures: LIMK2a, containing two LIM motifs, and LIMK2b, with one and one-half LIM motifs. Here we report the cDNA and genomic structures of mouse LIMK2. The deduced 638-aminoacid sequence of mouse LIMK2a shows 98% identity with that of rat LIMK2a. The mouse Limk2a gene consists of at least 16 exons and spans more than 50 kb. Exon/intron boundaries of the mouse Limk2a gene are exactly conserved with those of the mouse Limk1 gene. An additional exon encoding the Limk2b-specific 5'-terminal sequence was found to be located between exons 2 and 3, suggesting that Limk2a and 2b mRNAs are transcribed from a single Limk2 gene by an alternative usage of exons near the 5' end of the gene. Limk2a and Limk2b transcripts were expressed at different ratios in a variety of mouse tissues.

Alternative Splicing↗
PubMed1997

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Adenomatous Polyposis Coli↗
PubMed1997

Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant.

The nucleotide 73 (N73) "discriminator" base in the acceptor stem is a key element for efficient and specific aminoacylation of tRNAs and of microhelix substrates derived from tRNA acceptor stems. This nucleotide was possibly one of the first to be used for differentiating among groups of early RNA substrates by tRNA synthetases. In contrast to many other synthetases, we report here that the class II human lysyl-tRNA synthetase is relatively insensitive to the nature of N73. We cloned, sequenced, and expressed the enzyme, which is a close homologue of the class II yeast aspartyl-tRNA synthetase whose co-crystal structure (with tRNAAsp) is known. The latter enzyme has a strong requirement for G73, which interacts with 4 of the 14 residues within the "motif 2" loop of the enzyme. Even though eukaryotic lysine tRNAs also encode G73, the motif 2 loop sequence of lysyl-tRNA synthetase differs at multiple positions from that of the aspartate enzyme. Indeed, the recombinant human lysine enzyme shows little preference for G, and even charges human tRNA transcripts encoding the A73 found in E. coli lysine tRNAs. Moreover, while the lysine enzyme is the only one in E. coli to be encoded by two separate genes, a double mutant that disables both genes is complemented by a cDNA expressing the human protein. Thus, the sequence of the loop of motif 2 of human lysyl-tRNA synthetase specifies a structural variation that accommodates nucleotide degeneracy at position 73. This sequence might be used as a starting point for obtaining highly specific interactions with any given N73 by simple amino acid replacements.

Amino Acid Sequence↗
PubMed1997

Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B (MAP1B) gene.

Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated proteins (MAPs), is a major component of the neuronal cytoskeleton. It is expressed at high levels in immature neurons during growth of their axons, which indicates that it plays a crucial role in neuronal morphogenesis and neurite extension. To better define the role of MAP1B in vivo, we have used gene targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a slightly decreased brain weight and delayed nervous system development. Our data indicate that while MAP1B is not essential for survival, it is essential for normal time course development of the murine nervous system. These conclusions are very different from those of a previous MAP1B gene-targeting study (Edelmann, W., M. Zervas, P. Costello, L. Roback, I. Fischer, A. Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl. Acad. Sci. USA. 93: 1270-1275). In this previous effort, homozygotes died before reaching 8-d embryos, while heterozygotes showed severely abnormal phenotypes in their nervous systems. Because the gene targeting event in these mice produced a gene encoding a 571-amino acid truncated product of MAP1B, it seems likely that the phenotypes seen arise from the truncated MAP1B product acting in a dominant-negative fashion, rather than a loss of MAP1B function.

Animals↗
PubMed1997

Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae.

We have isolated 14 apg mutants defective in autophagy in yeast Saccharomyces cerevisiae (Tsukada and Ohsumi, 1993). Among them, APG1 encodes a novel Ser/Thr protein kinase whose kinase activity is essential for autophagy. In the course of searching for genes that genetically interact with APG1, we found that overexpression of APG1 under control of the GAL1 promoter suppressed the autophagy-defective phenotype of apg13-1 mutant. Cloning and sequencing analysis showed that the APG13 gene encodes a novel hydrophilic protein of 738 amino acid residues. APG13 gene is constitutively expressed bot not starvation-inducible. Though dispensable for cell proliferation, APG13 is important for maintenance of cell viability under starvation conditions. apg13 disruptants were defective in autophagy like apg13-1 mutants. Morphological and biochemical investigation showed that a defect in autophagy of delta apg13 was also suppressed by APG1 overexpression. These results imply genetic interaction between APG1 and APG13.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells.

It has been reported that PTH exerts bone-forming effects in vivo when administered intermittently. In the present study, the anabolic effects of PTH(1-34) on osteoblast differentiation were examined in vitro. Osteoblastic cells isolated from newborn rat calvaria were cyclically treated with PTH(1-34) for the first few hours of each 48-h incubation cycle. When osteoblastic cells were intermittently exposed to PTH only for the first hour of each 48-h incubation cycle and cultured for the remainder of the cycle without the hormone, osteoblast differentiation was inhibited by suppressing alkaline phosphatase activity, bone nodule formation, and mRNA expression of alkaline phosphatase, osteocalcin, and PTH/PTHrP receptor. Experiments using inhibitors and stimulators of cAMP/protein kinase A (PKA) and Ca2+/PKC demonstrated that cAMP/PKA was the major signal transduction system in the inhibitory action of PTH. In contrast, the intermittent exposure to PTH for the first 6 h of each 48-h cycle stimulated osteoblast differentiation. Both cAMP/ PKA and Ca2+/PKC systems appeared to be involved cooperatively in this anabolic effect. Continuous exposure to PTH during the 48-h incubation cycle strongly inhibited osteoblast differentiation. Although both cAMP/PKA and Ca2+/PKC were involved in the effect of continuous exposure to PTH, they appeared to act independently. A neutralizing antibody against IGF-I blocked the stimulatory effect on alkaline phosphatase activity and the expression of osteocalcin mRNA induced by the 6-h intermittent exposure. The inhibitory effect induced by the 1-h intermittent exposure was not affected by anti-IGF-I antibody. These results suggest that PTH has diverse effects on osteoblast differentiation depending on the exposure time in vitro mediated through different signal transduction systems. These in vitro findings explain at least in part the in vivo action of PTH that varies with the mode of administration.

Alkaline Phosphatase↗
PubMed1997

Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors.

1. We generated mice with targeted disruptions in the genes for both ryanodine receptor type 1 (RyR-1) and type 3 (RyR-3) to study the functional roles of RyR subtypes in skeletal muscle. 2. In permeabilized myocytes lacking both the RyRs, the Ca(2+)-induced Ca2+ release (CICR) mechanism was completely lost, and caffeine failed to induce Ca2+ release. 3. Replacement of potassium methanesulphonate in an experimental intracellular solution with choline chloride resulted in Ca2+ release in the wild-type muscle but not in the mutant muscle lacking RyR-1. 4. The double-mutant mice exhibited more severe muscular degeneration than RyR-1-deficient mice with formation of large vacuoles and swollen mitochondria while structural coupling between T-tubules and the sarcoplasmic reticulum was retained. 5. These results demonstrate that CICR is mediated solely by RyR-1 and RyR-3 in skeletal muscle cells, and suggest that RyR-1 is involved in Cl(-)-induced Ca2+ release. The results also suggest the presence of molecular components other than RyRs responsible for the triad formation. RyR-3 may have a role in the normal morphogenesis of skeletal muscle cells, although functionally it can be replaced by RyR-1.

Animals↗
PubMed1997

Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor.

The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia. To investigate its physiological function, Pebpb2 was mutated by a targeting strategy to generate a null mutant. The homozygous mutation in mice proved lethal in embryos around embryonic day 12.5, apparently due to massive hemorrhaging in the central nervous system. In addition, definitive hematopoiesis in the liver was severely impaired. The observed phenotype was indistinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF. Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis.

Animals↗