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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 163 records · Page 9Linked to original sources

Prenylagaramides A and B, new cyclic peptides from two strains of oscillatoria agardhii

Prenylagaramides A (1) and B (2), two new cyclic peptides, were isolated from the cultured cyanobacteria Oscillatoria agardhii (NIES-205) and O. agardhii (NIES-596), respectively. The structures of 1 and 2, which both contain a rare O-prenyltyrosine (Ptyr) unit, were established as cyclo(-Ptyr1-Gly2-Thr3-Gly4-Glu5-Phe6-Phe7-Asn8-Pro9-) and cyclo(-Ptyr1-Leu2-Tyr3-Pro4-Ile5-Asn6-Pro7-), respectively, by spectroscopic analysis and chemical degradation.

Journal Article↗

Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma.

BACKGROUND: Portal venous tumour extension and intrahepatic metastasis result in a poor prognosis following hepatectomy for hepatocellular carcinoma (HCC). Anatomical resection is, in theory, preferable for eradicating these types of invasion. Des-gamma-carboxy prothrombin (DCP) has been reported to be associated with adverse pathological variables. This study investigated the significance of anatomical resection and DCP as predictive factors for postoperative recurrence of HCC. METHODS: A retrospective cohort study was carried out in 138 consecutive patients who underwent hepatectomy for HCC smaller than 5 cm using the Cox proportional hazards model. RESULTS: Eight factors were univariately related to poor prognosis (in decreasing order of hazard ratio): intrahepatic metastasis, multiple tumours, alpha-fetoprotein 32 ng/ml or more; DCP greater than 0.1 arbitrary units (AU), tumour-exposed surgical margin, vascular invasion, non-anatomical resection and tumour 2.5 cm or more. Three variables (DCP, vascular invasion and tumour-exposed surgical margin) were excluded by a stepwise procedure in multivariate analysis. Although DCP was not an independent prognostic factor, a model replacing intrahepatic metastasis with DCP showed similar predictive accuracy in a receiver-operating characteristic curve. CONCLUSION: Anatomical resection appeared to have a beneficial effect on recurrence-free survival after hepatectomy for HCC. DCP measurement was effective in predicting HCC recurrence and had the advantage that it can be assessed before operation.

Biomarkers↗

Interaction of a novel antitumor agent TAS-103 with DNA.

Interaction of a novel antitumor agent TAS-103 with DNA has been studied by a variety of methods including thermal melting study, UV-Visible spectroscopy, 1H- and 31P-NMR spectroscopy. Thermal melting study indicated that TAS-103 stabilizes the double stranded form of DNA and the relative binding strength of TAS-103 is equal to that of ethidium bromide (EtBr). UV-Visible spectroscopy demonstrated that titration curves are nearly identical with all DNA oligomers producing a hypochromic and hypsochromic effect. A hypsochromic effect of TAS-103 is differ from typical intercalators such as EtBr and Actinomycin D that exhibit a bathochromic effect. 1H- and 31P-NMR spectroscopy revealed that TAS-103 has mainly two binding modes. Major binding mode is outside binding and minor binding mode is intercalation.

Aminoquinolines↗

Pattern of epitopic reactivity of the anti-Hu antibody on HuD with and without paraneoplastic syndrome.

Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/IPSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90-101 or aa 171-206. Some anti-Hu samples reacted with the deletion fragments containing aa 223-234, aa 235-252, or aa 354-373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/ PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90-101 and aa 171-206 are the major epitopes with which all anti-Hu serum samples react, and aa 223-234, aa 235-252, and aa 354-373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.

Antibodies↗

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.

Adaptation, Physiological↗

[Cochlear implantation in children with inner ear malformation and postoperative performance].

Cochlear implantation in children with cochlear malformation is on the rise. However, only one case has been reported in Japan. The objective of this paper is to report the authors' experiences with cochlear implants in children with cochlear malformations and, to investigate the morphological classification of cochlear malformation, surgical procedure, complications, and speech perceptions after implantation. Five children (6 ears, including 1 Usher's syndrome and 1 CHARGE association) with congenital inner ear malformations were implanted with multichannel cochlear implants (Nucleus Mini 22 device) between 1994 and 1998. Malformations included common cavity deformity 2, and incomplete partition 4. On the other hand, 4 cases with incomplete partition deformity underwent cochlear implantation by the transmastoid facial recess approach, 2 patients with common cavity deformity received implantation by the transmastoid labyrinthotomy approach. Complications such as facial twitching, cerebrospinal fluid (CSF) gusger, and flap-related problems were encountered. Facial twitching occurred in 1 of 2 patients with common cavity where the electrode array extended into the internal auditory canal. CSF gusher was encountered in 1 of 4 patients with incomplete partition, and revision surgery was performed one week later. One patient had delayed cochlear implant infection and a split pericranial flap was used to cover the defect in the skin flap. Within 6 months, however, the revised pedestal site broke down because of recurrent flap infection. Finally, the cochlear implant was explanted, and the patient underwent a new cochlear implantation in the contralateral ear. All the patients had satisfactory speech reception and word acquisition, but still poor phonetic expression.

Cerebrospinal Fluid Otorrhea↗

Inhibitory effect of TNP-470 on experimental choroidal neovascularization in a rat model.

PURPOSE: To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model. METHODS: Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups. RESULTS: The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14. CONCLUSIONS: TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.

Animals↗

The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes.

PURPOSE: To investigate the distribution of inflammatory mediators such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha and angiogenic cytokines such as vascular endothelial growth factor (VEGF) and to identify their cellular source in surgically excised choroidal neovascular membranes (CNVMs) of various origins. METHODS: Immunoperoxidase staining was performed on paraffin-embedded sections of 11 surgically excised CNVMs to identify cellular distribution and localization of cytokines. Immunofluorescent double staining was performed to detect the cellular source of cytokines. RESULTS: Cytokeratin-positive cells were detected in the RPE layer, in stromal cells, and around neovascular vessels. Macrophages identified by their cellular marker CD68 showed almost the same distribution as cytokeratin-positive cells, although they were most prominent in the stroma. A substantial number of neovascular vessels were also immunoreactive to IL-1beta and TNF-alpha. Immunofluorescent double staining revealed that the RPE layers immunopositive for cytokeratin were also immunopositive for all cytokines, whereas stromal cells immunostained for CD68 were positive for IL-1beta and TNF-alpha, but not for VEGF. CONCLUSIONS: These results indicate that IL-1beta and TNF-alpha secreted by macrophages may promote, at least in part, angiogenesis in CNVMs by stimulating VEGF production in RPE cells.

Adult↗

Selective suppression of cerebellar GABAergic transmission by an autoantibody to glutamic acid decarboxylase.

Humoral immune response to glutamic acid decarboxylase (GAD) has been implicated in the pathogenesis of stiff-man syndrome and cerebellar ataxia, but the underlying pathomechanism is unclear. Using a whole-cell patch-clamp technique with rat cerebellar slices, we found that immunoglobulins present in the cerebrospinal fluid of an ataxic patient acted presynaptically to cause a selective suppression of GABAergic transmission. This synaptic depression was most likely elicited by an autoantibody to GAD.

Aged↗

Genomic organization and the 5' upstream sequences associated with the specific spatio-temporal expression of HrEpiC, an epidermis-specific gene of the ascidian Halocynthia roretzi.

An epidermis-specific gene HrEpiC of the ascidian Halocynthia roretzi is activated in all presumptive blastomeres by the 64-cell stage. To explore the molecular mechanisms underlying the regulation of the timing of activation of HrEpiC, we studied the genomic organization and the 5' upstream sequences of HrEpiC associated with specific spatio-temporal expression of the gene. The restriction site mapping and sequencing of genomic clones showed that the H. roretzi genome contained two copies of HrEpiC gene, HrEpiC1 and HrEpiC2, aligned tandemly in about 8 kb of the genome. Analysis of various deletion constructs with the 5' flanking sequences of HrEpiC1 revealed that 103 bp of the 5' flanking region was sufficient for the minimal epidermis-specific expression of HrEpiC1 and that the region between -281 bp and -198 bp of the 5' flanking region was associated with the amplification of the minimal expression of the reporter gene in the epidermis. This module between -281 bp and -198 bp was also shown to be associated with the timing of the activation of HrEpiC1 by the 64-cell stage. We discussed how the spatio-temporal expression pattern of HrEpiC1 is regulated by the two modules.

Amino Acid Sequence↗

[Effectiveness of portable toothbrush use on reducing cigarette consumption and improving oral health].

There have been many studies on the influence of smoking on health, and in recent years, there have also been studies examining the relationship between smoking and oral health, concluding that smoking has a considerable detrimental effect on oral health. We introduced in a number of companies the idea of "Non smoking through the use of a portable toothbrush" as a means of giving up smoking while at the same time promoting oral health. The results demonstrated that consumption of cigarettes was reduced in about 50 percent of cases, while some improvement in mouth freshness was seen in about 90 percent. The study also showed that the success rate in reducing cigarette consumption through the use of a portable toothbrush was higher in highly motivated subjects, leading us to conclude that motivation is a major factor in reducing cigarette consumption. The study impressed on us the importance of educating people on the effect of smoking on oral health and the possibility of using a portable toothbrush as a means of reducing smoking.

Adult↗

Effect of serum fatty acid composition on coronary atherosclerosis in Japan.

The serum lipid profiles of patient's with or without significant coronary stenosis diagnosed by coronary angiography and of control subjects were compared. The level of high-density-lipoprotein cholesterol and eicosapentaenoic acid were significantly lower in the patients with significant coronary stenosis than in the control subjects. It suggests that high-density-lipoprotein cholesterol and omega3 fatty acids may have a protective effect on the progress of coronary atherosclerosis. The frequency of eating dark-meat fish was positively associated with serum eicosapentaenoic acid and docosahexaenoic acid, omega3 fatty acids, and inversely associated with serum stearic acid and linoleic acid. The frequency of eating soybean products was positively associated with serum docosahexaenoic acid and inversely associated with serum linoleic acid. It is necessary to discuss a way to popularise a diet of dark-meat fish and soybean products as a means of preventing coronary heart disease.

Aged↗

Helicobacter pylori infection enhances N-methyl-N-nitrosourea-induced stomach carcinogenesis in the Mongolian gerbil.

No previous report has demonstrated the relationship between Helicobacter pylori (HP) infection and gastric carcinogenesis in an experimental animal model. A total of 170 male Mongolian gerbils (MGs) were divided into nine groups (18 < or = n < or = 20 for each group). MGs of four groups were inoculated with HP before or after continuous N-methyl-N-nitrosourea (MNU) administration via the drinking water. Both intestinal-type and diffuse-type adenocarcinomas, including signet ring-cell carcinomas, were found at 40 weeks after the study commenced, but only in the HP inoculation groups with MNU exposure and not in the MNU alone or HP inoculation alone control groups. The present findings demonstrate that HP infection increases the incidence of MNU-induced adenocarcinoma of the glandular stomach in MGs.

Adenocarcinoma↗

(110) HREM of interfacial structures in semiconductor hetero-structures.

We have established a (110) cross-sectional high-resolution transmission electron microscopy (HREM) method to observe atomic structures of semiconductor hetero-interfaces. We show theoretically that the semiconductors in a hetero-structure exhibit strong contrast for an EM specimen thickness near their extinction distances, allowing atomic-scale observations of the interfacial structures between them. Furthermore, to obtain a clear HREM image, an EM specimen preparation technique is developed in which chemical etching is used to remove ion milling artifacts. This HREM method allows edge-on imaging of interfaces formed along the (110) direction; observations of atomic steps at AlAs/GaAs interfaces and a chemically ordered structure at Si/Ge interfaces are demonstrated.

Image Enhancement↗

Infrequent frameshift mutations of polynucleotide repeats in multiple primary cancers affecting the esophagus and other organs.

Frequent frameshift mutations of simple nucleotide repeats in the protein-encoding regions, as well as replication errors (RERs) at microsatellite loci, have recently been demonstrated in gastrointestinal tumors. These genetic instabilities have been considered indicative of an increased risk of accumulating mutations in cancer-associated genes and of developing multiple cancers. We studied frameshift (or insertion/deletion) mutations of simple nucleotide repeats in five genes (TGFbeta type II receptor [TGFbetaRII], E2F4, MSH2, MSH3, and MSH6) in 23 tumors from 12 patients who had synchronous cancers of the esophagus and other organs. Genetic instability at four microsatellite loci, as well as mutations in the TP53, APC, and KRAS2 genes, were also studied. No frameshift mutations were observed in the TGFbetaRII, MSH3, and MSH6 genes. RER and a deletion mutation of BAT26 in MSH2 were present in one (1/23; 4%) gastric cancer. This tumor also carried a deletion mutation in the serine (AGC) repeat of the E2F4 gene. Mutation screening of the TP53, APC, and KRAS2 genes revealed that the synchronous cancers did not carry the same mutations. Our results suggested that genetic instability, such as insertion/deletion mutations in simple nucleotide repeats, is not significantly associated with the development of multiple primary cancers of the esophagus and other organs, and that these synchronous cancers developed independently according to their different environmental factors.

Colonic Neoplasms↗

Intramuscular injection of plasmid DNA expressing mRNA7 coding the nucleocapsid protein of JHMV partially protected mice against acute infection with JHMV.

We constructed a plasmid expressing mRNA7 coding the nucleocapsid (N) protein of JHM strain of mouse hepatitis virus (JHMV) under the control of Rous sarcoma virus LTR, referred to as pRSV-mRNA7. When C57BL/6 mice injected intramuscularly (i.m.) with control plasmid DNA which contained no viral sequence were infected with JHMV, necrotic figures of neural cells and diffuse immersion of lymphatic cells in the pedunculus cerebri were observed. In the hypothalamus, vascular cuffing consisting of lymphatic cells was observed. In contrast, no histological change was observed throughout these areas of the brains in the JHMV-infected mice after injection with pRSV-mRNA7. These results showed that the injection with plasmid DNA expressing mRNA7 of JHMV partially protected mice against acute infection with JHMV in the brain. The plasmid DNA was i.m. injected into mice and the cytolytic activity of spleen cells from the mice was assessed by 51Cr-release assay. The spleen cells from the mice administrated with pRSV-mRNA7 showed a significant level of cytolytic activities against the transfected cells expressing the viral N protein even though the spleen cells were not cocultivated with stimulator cells. When the spleen cells from administrated mice with pRSV-mRNA7 were cocultivated with stimulator cells, higher cytolytic activity was observed against the transfected cells, compared with the activity without stimulation.

Acute Disease↗