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Biomedical subjects

K Hatano

Publications and source records attributed to K Hatano.

At least 55 records · Page 3Linked to original sources

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522.

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer.

Animals↗

The human amygdala plays an important role in gaze monitoring. A PET study.

Social contact often initially depends on ascertaining the direction of the other person's gaze. We determined the brain areas involved in gaze monitoring by a functional neuroimaging study. Discrimination between the direction of gaze significantly activated a region in the left amygdala during eye-contact and no eye-contact tasks to the same extent. However, a region in the right amygdala was specifically activated only during the eye-contact task. Results confirm that the left amygdala plays a general role in the interpretation of eye gaze direction, and that the activity of the right amygdala of the subject increases when another individual's gaze is directed towards him. This suggests that the human amygdala plays a role in reading social signals from the face.

Adult↗

Sporichthya brevicatena sp. nov.

A strain was isolated from soil that formed short chains of aerial mycelium dividing into motile spores on an agar medium, but not substrate mycelium. The organism had menaquinone 9(H8), LL-diaminopimelic acid in the cell wall amino acids and a DNA G + C content of 71 mol%. On the basis of the morphological and chemotaxonomic characteristics and phylogenetic analysis, this strain was classified into the genus Sporichthya. DNA-DNA hybridization revealed that the strain differed from the known species, Sporichthya polymorpha. Therefore, a new species, Sporichthya brevicatena sp. nov., is proposed. The type strain is S. brevicatena YU720-21T (= IFO 16195T).

Actinomycetales↗

Characterization of the serogroup O11 O-antigen locus of Pseudomonas aeruginosa PA103.

We previously cloned a genomic DNA fragment from the serogroup O11 Pseudomonas aeruginosa strain PA103 that contained all genes necessary for O-antigen synthesis and directed the expression of serogroup O11 antigen on recombinant Escherichia coli and Salmonella. To elucidate the pathway of serogroup O11 antigen synthesis, the nucleotide sequence of the biosynthetic genes was determined. Eleven open reading frames likely to be involved in serogroup O11 O-antigen biosynthesis were identified and are designated in order as wzzPaO111 (wzz from P. aeruginosa serogroup O11), wzxPaO11, wbjA, wzyPaO11, wbjB to wbjF, wbpLO11 and wbpMO11 (wbpL and wbpM from serogroup O11). Consistent with previous descriptions of O-antigen biosynthetic gene loci, the entire region with the exception of wbpMO11 has a markedly reduced G+C content relative to the chromosomal average. WzyPaO11 shows no significant similarity at the protein or DNA sequence level to any database sequence and is very hydrophobic, with 10 to 12 putative transmembrane domains, both typical characteristics of O-antigen polymerases. A nonpolar chromosomal insertion mutation in wzyPaO11 in P. aeruginosa PA103 confirmed the identity of this gene. There is striking similarity between WbjBCDE and Cap(5/8)EFGL, involved in type 5 and type 8 capsule biosynthesis in Staphylococcus aureus. There is nearly total identity between wbpMO11 and wbpMO5, previously shown by others to be present in all 20 P. aeruginosa serogroups. Using similarity searches, we have assigned functions to the proteins encoded by the PA103 O-antigen locus and present the potential steps in the pathway for the biosynthesis of P. aeruginosa serogroup O11 O antigen.

Bacterial Proteins↗

Activation of the right inferior frontal cortex during assessment of facial emotion.

We measured regional cerebral blood flow (rCBF) using positron emission tomography (PET) to determine which brain regions are involved in the assessment of facial emotion. We asked right-handed normal subjects to assess the signalers' emotional state based on facial gestures and to assess the facial attractiveness, as well as to discriminate the background color of the facial stimuli, and compared the activity produced by each condition. The right inferior frontal cortex showed significant activation during the assessment of facial emotion in comparison with the other two tests. The activated area was located within a triangular area of the inferior frontal cortex in the right cerebral hemisphere. These results, together with those of previous imaging and clinical studies, suggest that the right inferior frontal cortex processes emotional communicative signals that could be visual or auditory and that there is a hemispheric asymmetry in the inferior frontal cortex in relation to the processing of emotional communicative signals.

Adult↗

In vitro antibacterial activity of FK041, a new orally active cephalosporin.

The in vitro activity of FK041, a new orally active cephem antibiotic, against a wide variety of clinical isolates of bacteria was investigated and compared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gram-negative aerobes and anaerobes. FK041 was active against clinical isolates of Gram-positive organisms except Enterococcus faecalis with MIC90s less than 1.56 microg/ml. FK041 was more active than CFDN and CDTR against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Streptococcus pneumoniae. FK041 had no activity against methicillin-resistant staphylococci, like CFDN and CDTR. FK041 showed moderate activity against penicillin-resistant S. pneumoniae with an MIC range of 0.05 approximately 3.13 microg/ml, and was superior to CFDN but inferior to CDTR. Against clinical isolates of many Gram-negative organisms such as Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good activity comparable or superior to those of CFDN and CDTR. However, it was inferior to CDTR in activity against Moraxella catarrhalis, Haemophilus influenzae, Morganella morganii, and Serratia marcescens, and was inactive against Pseudomonas aeruginosa. With FK041 a small difference between MIC and MBC against S. aureus, E. coli, K. pneumoniae, and H. influenzae was found, indicating that its action is bactericidal against these species. FK041 was stable to group 2beta-lactamase hydrolysis but was unstable to group 1beta-lactamase hydrolysis. The stability of FK041 to these enzymes was similar to those of CFDN and CDTR. FK041 showed high affinity for the main penicillin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PBP 3, 4, lbs, 2, and 1a).

Bacteria↗

In vivo antibacterial activity of FK041, a new orally active cephalosporin.

The therapeutic activities of orally administered FK041 were evaluated in mouse models of systemic and local infections with a variety of bacteria and were compared with those of cefdinir (CFDN) and cefditoren pivoxil (CDTR-PI). FK041 exhibited potent therapeutic activity against lethal systemic infections induced by intraperitoneally inoculated Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae with 50% effective doses (ED50) in the range of 0.20 to 0.36 mg/kg and was more active than CFDN and CDTR-PI. This result correlated well with its in vitro activity. The therapeutic effects of FK041 and reference drugs on murine local infections were evaluated in an in vivo pharmacokinetic model simulating human plasma concentrations for oral administration of 50 mg, 100 mg, and 200 mg. Against murine subcutaneous abscess induced by S. aureus, FK041 was as effective as CFDN and significantly more effective than CDTR-PI in reducing the number of recoverable viable bacteria in the skin at the infection sites. The efficacy of FK041 against murine pneumonia with H. influenzae was comparable to that of CDTR-PI and was superior to that of CFDN in reducing viable bacteria activity in the lungs. These results strongly suggest that FK041 has potential for clinical use against various bacterial infections.

Animals↗

Neuroanatomical correlates of the assessment of facial attractiveness.

Frontal cortical damage can lead to changes in affective aspects of personality. However, the difficulty of dissociating such abnormalities from cognitive disorders has overshadowed most previous findings. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) while normal subjects were assessing facial attractiveness. Two left frontal regions showed a significant increase in rCBF while assessing facial attractiveness. The increased rCBF in the left anterior frontal cortex correlated with the overall percentage of assessments of a face as unattractive, while that in the left fronto-temporal junction correlated with the percentage of assessments of a face as attractive. These findings provide direct evidence that the left frontal regions are engaged in the assessment of facial attractiveness.

Adult↗

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes.

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.

Aged↗

Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET sigma receptor ligand.

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was labeled with 11C in two different positions by the alkylation of an N-despropyl precursor with [11C]propyl iodide and of an O-desmethyl precursor with [11C]methyl iodide and was evaluated for the potential as a tracer for mapping sigma 1 receptors in the CNS and peripheral organs by PET. Following i.v. injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two tracers showed similar tissue distribution patterns except for the liver and brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl-11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15 min after injection, whereas the effect was not significant for [O-methyl-11C]NE-100. The coinjection of NE-100 enhanced the brain uptake of the two tracers. Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl-3H]NE-100 was consistent with the distribution pattern of the sigma receptors. Four sigma drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70%-90% of the control. In an ex vivo autoradiographic study of the rat brain, the uptake of [O-methyl-11C]NE-100 was blocked by carrier NE-100 or haloperidol (53%-59% of the control in the cortex), which suggests a receptor-specific distribution. These results show that [O-methyl-11C]NE-100 has limited potential as a PET ligand for mapping sigma 1 receptors in the peripheral organs and the CNS because of high nonspecific binding.

Animals↗

Union of the genera Microbacterium Orla-Jensen and Aureobacterium Collins et al. in a redefined genus Microbacterium.

The 16S rRNA gene sequences of 19 strains, 11 strains representing validated Aureobacterium or Microbacterium species and eight strains of non-valid species or isolates, were determined. These sequences were aligned with the sequences of other validated Aureobacterium and Microbacterium species and related actinobacteria. A comparative sequence analysis of 43 strains revealed that the species of the genera Aureobacterium and Microbacterium form a monophyletic association in which species of both genera are intermixed. The high similarity in phylogenetic properties found in the species within both genera and the close relationship in physiological and chemotaxonomic features other than the diamino acid in the cell wall, provided strong evidence that the genera Aureobacterium and Microbacterium should be unified. An emended genus Microbacterium is proposed for the two combined genera. The following validated Aureobacterium species were combined to the genus Microbacterium: Aureobacterium arabinogalactanolyticum to Microbacterium arabinogalactanolyticum, Aureobacterium barkeri to Microbacterium barkeri, Aureobacterium esteraromaticum to Microbacterium esteraromaticum, Aureobacterium flavescens to Microbacterium flavescens, Aureobacterium keratanolyticum to Microbacterium liquefaciens, Aureobacterium luteolum to Microbacterium luteolum, Aureobacterium saperdae to Microbacterium saperdae, Aureobacterium schleiferi to Microbacterium schleiferi, Aureobacterium terrae to Microbacterium terrae, Aureobacterium terregens to Microbacterium terregens, Aureobacterium testaceum to Microbacterium testaceum, and Aureobacterium trichothecenolyticum to Microbacterium trichothecenolyticum.

Actinomycetales↗

Gordonia rhizosphera sp. nov. isolated from the mangrove rhizosphere.

The taxonomic position of bacterial strain 141T, isolated from the mangrove rhizosphere, has been clarified by phenotypic, chemotaxonomic and phylogenetic studies. The strain possesses wall chemotype IV, MK-9(H2) as the predominant menaquinone, relatively long-chain mycolic acids (56-64) carbon atoms) and straight-chain saturated and monounsaturated fatty acids with a small amount of tuberculostearic acid. The G+C content of the DNA is 66.8 mol%. Similarity values for genes encoding 16S rRNA indicated that strain 141T represents a new species within the genus Gordonia for which the name Gordonia rhizosphera sp. nov. is proposed. The type strain of G. rhizosphere is 141T (IFO 16068T).

Actinomycetales↗

Proposal of six new species in the genus Microbacterium and transfer of Flavobacterium marinotypicum ZoBell and Upham to the genus Microbacterium as Microbacterium maritypicum comb. nov.

Reference strains, including two mis-named organisms, 'Chromobacterium chocolatum' and Flavobacterium marinotypicum, isolates from soil and clinical specimens, all previously recognized as Aureobacterium or Microbacterium, were characterized taxonomically. On the basis of morphological, physiological and chemotaxonomic characteristics, as well as DNA-DNA hybridization data, six new species and one new combination are proposed in the genus Microbacterium: Microbacterium ketosireducens sp. nov. (type strain IFO 14548T), Microbacterium chocolatum sp. nov. (type strain IFO 3758T), Microbacterium aurantiacum sp. nov. (type strain IFO 15234T), Microbacterium hominis sp. nov. (type strain IFO 15708T), Microbacterium thalassium sp. nov. (type strain IFO 16060T), Microbacterium halophilum sp. nov. (type strain IFO 16062T) and Microbacterium maritypicum comb. nov. (type strain IFO 15779T).

Actinomycetales↗

A new genus of the order Actinomycetales, Cryptosporangium gen. nov., with descriptions of Cryptosporangium arvum sp. nov. and Cryptosporangium japonicum sp. nov.

Four strains that form sporangia with motile sporangiospores and mycelia were isolated from soil samples. Their many sporangia were covered by mycelia. They had glutamic acid, glycine, alanine and meso-diaminopimelic acid as cell wall amino acids (wall chemotype II), acofriose (3-O-mythylrhamnose) as a characteristic whole-cell sugar, and menaquinone 9(H6). The taxonomic characteristics of these strains differ from those of the previously described motile actinomycetes. On the basis of the morphological, physiological, chemotaxonomic and phylogenetic analyses, a new genus is proposed, Cryptosporangium, and two new species, Cryptosporangium arvum sp. nov (type strain IFO 15965T) for strain YU 629-21T and Cryptosporangium japonicum sp. nov (type strain IFO 15966T) for strains YU 636-3T, YU 655-31 and YU 656-31.

Actinomycetales↗

Transport of storage proteins to protein storage vacuoles is mediated by large precursor-accumulating vesicles

Novel vesicles that accumulate large amounts of proprotein precursors of storage proteins were purified from maturing pumpkin seeds. These vesicles were designated precursor-accumulating (PAC) vesicles and had diameters of 200 to 400 nm. They contained an electron-dense core of storage proteins surrounded by an electron-translucent layer, and some vesicles also contained small vesicle-like structures. Immunocytochemical analysis revealed numerous electron-dense aggregates of storage proteins within the endoplasmic reticulum. It is likely that these aggregates develop into the electron-dense cores of the PAC vesicles and then leave the endoplasmic reticulum. Immunocytochemical analysis also showed that complex glycans are associated with the peripheral region of PAC vesicles but not the electron-dense cores, indicating that Golgi-derived glycoproteins are incorporated into the PAC vesicles. These results suggest that the unique PAC vesicles might mediate a transport pathway for insoluble aggregates of storage proteins directly to protein storage vacuoles.

Journal Article↗

Complex serology and immune response of mice to variant high-molecular-weight O polysaccharides isolated from Pseudomonas aeruginosa serogroup O2 strains.

The O antigen of the Pseudomonas aeruginosa lipopolysaccharide is the optimal target for protective antibodies, but the unusual and complex nature of their sugar substituents has made it difficult to define the range of these structures needed in an effective vaccine. Most clinical isolates of P. aeruginosa can be classified into 10 O-antigen serogroups, but slight chemical differences among O polysaccharides within a serogroup give rise to subtype epitopes. These epitopes could impact the reactivity of O-antigen-specific antibodies, as well as the susceptibility of a target strain to protective, opsonic antibodies. To define parameters of serogroup and subtype-epitope immunogenicity, antigenicity, and surface expression on P. aeruginosa cells, we prepared high-molecular-weight O-polysaccharide vaccines from strains of P. aeruginosa serogroup O2, for which eight structurally variant O antigens expressing six defined subtype epitopes (O2a to O2f) have been identified. A complex pattern of immune responses to these antigens was observed following vaccination of mice. The high-molecular-weight O polysaccharides were generally more immunogenic at low doses (1 and 10 microg) than at a high dose (50 microg) and usually elicited antibodies that opsonized the homologous strain for phagocytic killing. Some of the individual polysaccharides elicited cross-opsonic antibodies to a variable number of strains that express all of the defined serogroup O2 subtype epitopes. Combination into one vaccine of two antigens that individually elicited cross-reactive opsonic antibodies to most members of the O2 serogroup inhibited, instead of enhanced, the production of antibodies broadly reactive with most serogroup O2 subtype strains. Thus, immune responses to P. aeruginosa O antigens may be restricted to a limited range of epitopes on structurally complex O antigens, and combining multiple related antigens into a single vaccine formulation may inhibit the production of those antibodies best able to protect against most P. aeruginosa strains within a given O-antigen serogroup.

Animals↗

[The trend of leprosy treatment in which the prevention of peripheral nerve damage being as its main theme].

We have examined in leprosy in Bangladesh the change in the rate of peripheral nerve damage before and after the treatment. In the well-organized NGO program where the early diagnose is given, the damage rate improves slightly during the treatment. But among the MB cases, it has been found that the damage rate taken at the time of patient's first check-up still stays high. Furthermore, during the treatment of MB cases, 72% cases show the episode of neuritis, and even during two years of observation period after treatment, 15% cases show the same episode. Among the recurrent cases of last ten years in Oku-Komyo-en, we have looked into the ways of drugs prescribed for the treatment of previous recurrent term in the double recurrent cases. In these prescription, the amount of each dosage was relatively a little and the prescription period was rather long. In RFP, prescription frequency was relatively high, and in DDS and CLF, they were low. We think that the treatment of leprosy in Japan should be based on WHO's regimen. However before making Japanese regimen, it is necessary to discuss more when to finish the treatment.

Aged↗

[Radiotherapy for carcinoma of the buccal mucosa: analysis of prognostic factors].

The radiotherapeutic results of 55 patients with carcinoma of the buccal mucosa were analyzed to determine the prognostic factors and appropriate treatment modality. They were classified into 5 groups according to treatment modality: group A (preoperative radiotherapy followed by surgery), group B (interstitial implant), group C (electron therapy), group D (mainly external radiotherapy) and group E (external radiotherapy followed by mold therapy with remote afterloading system). The overall 5-year survival rates for groups A, B, C, D, E and the entire group were 50%, 61%, 67%, 29%, 25% and 48%, respectively. The cumulative 5-year local control rates for groups A through E were 81%, 94%, 75%, 33% and 25%, respectively. In univariate analysis, T stage (T1-2 vs. T3-4), N stage (N0 vs. N1-3), clinical stage (II vs. III-IV), histologic grade (well differentiated vs. moderately and poorly differentiated) and treatment modality (A-C vs. D-E) were significantly related to overall survival (p < 0.05). Multivariate analysis revealed that treatment modality (groups A-C) and N0 stage were significantly associated with favorable prognosis (p < 0.05). These results suggest that interstitial implants are comparable with surgery for T1 to early T3 lesions, with or without slight invasion to the bucco-alveolar sulci or retromolar areas, that can be treated with a single-plane implant.

Adult↗