Biomedical subjects

Kentaro Inoue

Publications and source records attributed to Kentaro Inoue.

35 records · Page 2Linked to original sources

PubMed2004

Comparison of intraperitoneal continuous infusion of floxuridine and bolus administration in a peritoneal gastric cancer xenograft model.

PURPOSE: To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer. METHODS: The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR. RESULTS: In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth. CONCLUSIONS: Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.

Animals↗

PubMed2004

A functional MRI study of simple arithmetic--a comparison between children and adults.

The purpose of this study was to examine brain areas involved in simple arithmetic, and to compare these areas between adults and children. Eight children (four girls and four boys; age, 9-14 years) and eight adults (four women and four men; age, 40-49 years) were subjected to this study. Functional magnetic resonance imaging (fMRI) was performed during mental calculation of addition, subtraction, and multiplication of single digits. In each group, the left middle frontal, bilateral inferior temporal and bilateral lateral occipital cortices were activated during each task. The adult group showed activation of the right frontal cortex during addition and multiplication tasks, but the children group did not. Activation of the intraparietal cortex was observed in the adult group during each task. Although, activation patterns were slightly different among tasks, as well as between groups, only a small number of areas showed statistically significant differences. The results indicate that cortical networks involved in simple arithmetic are similar among arithmetic operations, and may not show significant changes in the structure during the second decade of life.

Adolescent↗

PubMed2004

Carotenoid hydroxylation--P450 finally!

Cytochrome P450 monooxygenases are involved in the biosynthesis of various compounds in plants such as phenylpropanoids, lipids and phytohormones. Hydroxylation of the carotenoid epsilon-ring is an essential reaction for the formation of lutein, the most abundant carotenoid in photosynthetic tissues. Recently, Li Tian and colleagues reported that a new P450 is responsible for this reaction. This discovery not only adds to the list of various functions of plant cytochrome P450s but also identifies one of the missing pieces of the puzzle of carotenoid biosynthesis.

Arabidopsis↗

PubMed2004

The chloroplastic protein translocation channel Toc75 and its paralog OEP80 represent two distinct protein families and are targeted to the chloroplastic outer envelope by different mechanisms.

Toc75 is postulated to form the protein translocation channel in the chloroplastic outer envelope membrane. Proteins homologous to Toc75 are present in a wide range of organisms, with the closest homologs occurring in cyanobacteria. Therefore, an endosymbiotic origin of Toc75 has been postulated. Recently, a gene encoding a paralog to Toc75 was identified in Arabidopsis and its product was named atToc75-V. In the present study, we characterized this new Toc75 paralog, and investigated extensively the relationships among Toc75 homologs from higher plants and bacteria in order to gain insights into the evolutionary origin of the chloroplastic protein translocation channel. First, we found that the native molecular weight of atToc75-V is 80 kDa and renamed it (AtOEP80) Arabidopsis thalianaouter envelope protein of 80 kDa. Second, we found that AtOEP80 and Toc75 utilize different mechanisms for their targeting to the chloroplastic envelope. Toc75 is directed with a cleavable bipartite transit peptide partly via the general import pathway, whereas AtOEP80 contains the targeting information within its mature sequence, and its targeting is independent of the general pathway. Third, we undertook phylogenetic analyses of Toc75 homologs from various organisms, and found that Toc75 and OEP80 represent two independent gene families that are most likely derived from cyanobacterial sequences. Our results suggest that Toc75 and OEP80 diverged early in the evolution of plastids from their common ancestor with modern cyanobacteria.

Amino Acid Sequence↗

PubMed2004

Trends in long-term survival following surgery for gastric cancer: a single institution experience.

We reviewed cases at our institution in an attempt to identify temporal trends in survival of patients with operable gastric cancer. We analyzed data on 1632 patients who received a diagnosis of gastric adenocarcinoma between 1975 and 1995 and who underwent surgery at our institution. The time trends were examined by comparing three time periods (1975-1984, 1985-1989 and 1990-1995). Over time there was an improvement in the R0 resection rate: the rate significantly increased from 65% to 83%. Short-term outcomes following surgery have improved, with 30-day mortality dropping from 3.5% to 1%. The overall survival curve continuously improved with time. The five-year survival rates improved from 43% to 61%. The increased use of extended lymph node dissection with careful examination for metastases allowed for more accurate TNM staging. The incidence of peritoneal failure remains high, with peritoneal recurrence observed in 49% of the patients who underwent R0 resection between 1985 and 1995 and who experienced recurrences. Our results demonstrated that current efforts to improve gastric cancer management are finally meeting with noticeable success. However, advanced-stage cancer remains a medical problem. Multimodal treatment of advanced disease will be an important theme in coming years.

Adenocarcinoma↗

PubMed2003

Regional differences between 99mTc-ECD and 99mTc-HMPAO SPET in perfusion changes with age and gender in healthy adults.

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether (99m)Tc-HMPAO or (99m)Tc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8+/-6.6 years) were assigned to (99m)Tc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6+/-6.7 years) to (99m)Tc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq (99m)Tc-HMPAO or (99m)Tc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether (99m)Tc-HMPAO and (99m)Tc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.

Age Factors↗

PubMed2003

Protein translocation across biological membranes: cost what it may.

Protein translocation across biological membranes can expend a large portion of the total cellular metabolic energy. Although energy sources for this process have been well characterized, its total energy cost was unclear. Recently, this problem was addressed in the thylakoidal pH-dependent cpTat pathway. It was estimated that approximately 3% of the total energy output of the chloroplast is used by this pathway.

Energy Metabolism↗

PubMed2003

Two chloroplastic protein translocation components, Tic110 and Toc75, are conserved in different plastid types from multiple plant species.

Most chloroplastic proteins are nuclear-encoded and must be transported into the organelle post-translationally. Proteinaceous components in the outer and inner envelope membranes of chloroplasts responsible for this import process were originally identified from pea seedlings. We sought to determine whether these proteins are conserved among different plant species other than pea and among different plastid types. We analyzed plant EST databases and found the presence of homologues to pea chloroplastic protein translocation components, Tic110 and Toc75, in both monocot and dicot species. Because these clones were obtained from various tissues, their presence in different types of plastids is proposed. Protein extracts were prepared from several plant species and from different plant tissues, and then probed with antisera raised against pea Tic110 and Toc75. The results support the idea that translocation components originally found in pea chloroplasts are conserved among different plant species and are present in various plastid types.

Biological Transport↗

PubMed2003

A polyglycine stretch is necessary for proper targeting of the protein translocation channel precursor to the outer envelope membrane of chloroplasts.

Toc75 is a protein translocation channel in the outer envelope membrane of chloroplasts and its presence is essential for the biogenesis of the organelles. Toc75 is the only protein identified so far in the outer membrane of chloroplasts or mitochondria that is synthesized as a larger precursor, preToc75, with a bipartite transit peptide. Its N-terminus targets the protein to the stroma and is removed by the stromal processing peptidase, whereas its C-terminus mediates envelope targeting and is removed by a yet unknown peptidase. Several conserved domains have been identified in the C-terminal portion of the preToc75 transit peptide from six plant species. We evaluated their importance in the biogenesis of Toc75 by means of deletion or site-directed mutagenesis, followed by import experiments using isolated chlroplasts. Among the conserved domains, a polyglycine stretch was found to be necessary for envelope targeting. Substitution of this domain with other stretches of a single amino acid such as alanine caused mistargeting of the protein into the stroma, indicating an important role for this domain. Furthermore, a glutamate at +2 and two alanine residues at -3 and -1 to the second cleavage site were found to be important for processing. A potential mechanism for the biogenesis of Toc75 is discussed.

Amino Acid Sequence↗

PubMed2002

Regional differences in distribution volume of I-123 IMP in the human brain: effect on CBF calculated by ARG method.

OBJECTIVE: Two methods of quantitating cerebral blood flow (CBF) with iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123 IMP) and a two-compartment model had been proposed; one is the table look-up (TLU) method and the other is the autoradiographic (ARG) method. The TLU method provides values of the cerebral blood flow (CBF) values and distribution volume of I-123 IMP (Vd) independently. In the ARG method, a fixed Vd is applied for the entire brain to calculate CBF. Our purpose was to evaluate regional differences in Vd in the human brain, or possible effects of regional differences in Vd on CBF calculated by the ARG method. METHODS: In the present study, two SPECT scans were acquired from each of eight normal subjects (aged 44.0 +/- 16.7) at 40 min and 180 min of mid-scan-time after intravenous 1 min infusion of 111 MBq IMP. A single arterial blood sampling was performed 10 min after the IMP infusion. All images were anatomically normalized and analyzed with SPM99 and Matlab. We generated CBF and Vd images for each subject by the TLU method and evaluated differences in Vd among brain structures. We subsequently generated another set of CBF images by the ARG method and examined differences between CBF calculated by the TLU method and that by the ARG method. RESULTS: Significant main effects of subject and brain structure in Vd were observed (two-way ANOVA). Vd values were higher in the deep gray matter than in the cerebral cortical regions. Among the cerebral cortical regions, no significant difference in Vd was observed. In spite of the significant differences in Vd among the brain structures, the voxel-by-voxel analyses as well as the ROI analyses revealed no statistically significant difference between CBF calculated by the TLU method and that by the ARG method. CONCLUSIONS: Although regional differences in Vd were observed, the present results support the assumption that a fixed Vd does not cause significant error in the calculation of CBF by the ARG method.

Adult↗

PubMed2002

Synergistic effects induced by cycloprodigiosin hydrochloride and epirubicin on human breast cancer cells.

The effects of cPrG x HCl and epirubicin on the suppression of cell growth were examined on human breast cancer cell line (MDA-MB-231). Either cPrG x HCl or epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent manner, however, the combinatory use of cPrG x HCl together with epirubicin resulted in prominent synergistic effects on the breast cancer cells. In the in vitro studies, the combinatory use of these two drugs accelerated apoptotic cell death as revealed by morphological changes as well as by the appearance of subG1 population by flow cytometry. In addition, confocal microscopy revealed that the accumulation of epirubicin in nucleus increased apparently when cPrG x HCl were present. In the in vivo assay, nude mice bearing xenografted tumor cells received 4 weeks of intraperitoneal administration of cPrG-HCl and epirubicin. After 12 days, the combinatory treatment significantly suppressed the tumor growth compared to the controls. The TUNEL staining revealed that tumor cells in cPrG x HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition, 31P-NMR studies on the xenografted tumor revealed that cPrG x HCl lowered tumor pHi (below pH 6.9). while it did not affected muscle pHi. No pathological changes were observed in any intrinsic organs and the serum alanine aminotransferase levels remained within normal limits among the groups. These results suggest that the combinatory use of cPrG x HCl and epirubicin may be useful for breast cancer therapy.

Animals↗

PubMed2002

[A case of postoperative liver metastasis from gastric cancer which responded well to weekly chemotherapy with paclitaxel].

We report a case of postoperative liver metastasis from gastric cancer showing a remarkable response to weekly administration of paclitaxel (TXL). The patient was a 50-year-old woman who underwent total gastrectomy. One month later, liver metastasis and a small amount of ascites were detected by CT scan. Therefore, the patient was administered weekly TXL. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. Liver metastasis and ascites disappeared 3 months after administration. The toxic events were leukopenia (grade 1) and alopecia (grade 1). No major adverse effects were observed.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Evolution of the general protein import pathway of plastids (review).

The evolutionary process that transformed a cyanobacterial endosymbiont into contemporary plastids involved not only inheritance but also invention. Because gram-negative bacteria lack a system for polypeptide import, the envelope translocon complex of the general protein import pathway was the most important invention of organelle evolution resulting in a pathway to import back into plastids those nuclear-encoded proteins supplemented with a transit peptide. Genome information of cyanobacteria, phylogenetically diverse plastids, and the nuclei of the first red alga, a diatom, and Arabidopsis thaliana allows us to trace back the evolutionary origin of the twelve currently known translocon components and to partly deduce their assembly sequence. Development of the envelope translocon was initiated by recruitment of a cyanobacterial homolog of the protein-import channel Toc75, which belongs to a ubiquitous and essential family of Omp85/D15 outer membrane proteins of gram-negative bacteria that mediate biogenesis of beta-barrel proteins. Likewise, three other translocon subunits (Tic20, Tic22, and Tic55) and several stromal chaperones have been inherited from the ancestral cyanobacterium and modified to take over the novel function of precursor import. Most of the remaining subunits seem to be of eukaryotic origin, recruited from pre-existing nuclear genes. The next subunits that joined the evolving protein import complex likely were Toc34 and Tic110, as indicated by the presence of homologous genes in the red alga Cyanidioschyzon merolae, followed by the stromal processing peptidase, members of the Toc159 receptor family, Toc64, Tic40, and finally some regulatory redox components (Tic62, Tic32), all of which were probably required to increase specificity and efficiency of precursor import.

Active Transport, Cell Nucleus↗

PubMedDate not supplied

The superiority of ratio-based lymph node staging in gastric carcinoma.

BACKGROUND: The need for a precise lymph node staging without stage migration is of paramount importance when comparing and evaluating international treatment results. METHODS: We reviewed 1019 patients who underwent R0 resection at Kansai Medical University between 1980 and 1997. The patients were classified according to the 1997 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) pN classification or the N staging depending on the ratio between the number of excised and the number of involved lymph nodes (pN1, < or = 25%; pN2, < or = 50%; pN3, >50%). RESULTS: Among the 1997 UICC/AJCC pN subgroups, prognosis worsened with an increase in lymph node ratio. In contrast, the ratio-based classification showed more homogenous survival according to the number of involved lymph nodes. Multiple stepwise regression analysis showed that the ratio-based classification was the most significant prognostic factor, whereas the 1997 UICC/AJCC classification was not found to be an independent predictor of survival. In addition, the ratio-based classification showed a superiority to the 1997 UICC/AJCC classification with respect to stage migration. CONCLUSIONS: Ratio-based lymph node staging is simple and gives more precise information for prognosis with fewer problems related to stage migration than the 1997 UICC/AJCC staging system.

Adult↗

PubMedDate not supplied

Jejunal interposition helps prevent reflux gastritis.

BACKGROUND/AIMS: Jejunal interposition after distal gastrectomy is reported to prevent both duodenogastric reflux and rapid gastric emptying. However, comparing primary reconstruction with this procedure and Billroth-I in terms of clinical evaluation by the same surgeon is rare. In this study, the benefit of this procedure was retrospectively evaluated as compared to the Billroth-I method. METHODOLOGY: Of 30 patients with early gastric cancer located at the middle third of the stomach, 15 underwent distal gastrectomy with jejunal interposition and the other 15 underwent Billroth-I gastrectomy by the same surgeon. Isoperistaltic jejunal interposition measuring 10-12 cm was used. All the anastomoses without jejunojejunostomy were performed using auto-suture staplers. Assessment of postoperative symptoms and functions was performed one year after surgery. RESULTS: The mean operation time was significantly longer after jejunal interposition (p < 0.01). No serious complications occurred in either group, and the hospital stay after operation was also similar. There were no significant differences in terms of postoperative symptoms, food intake, and recovery of body weight. The incidence of bile regurgitation and reflux gastritis was very low or zero in the jejunal interposition group, which indicated differences (p < 0.05, p < 0.01, respectively). Reflux esophagitis was not found in jejunal interposition, but two patients after Billroth I showed grade B esophagitis. As regards gastric emptying, the retention capacity was very poor and there was no significant difference between the two groups. CONCLUSIONS: Jejunal interposition after distal gastrectomy was superior to the Billroth-I procedure in terms of reflux gastritis prevention. However, dumping syndrome and rapid gastric emptying were not prevented.

Aged↗

PubMedDate not supplied

Combined S-1 and cisplatin preoperative chemotherapy for patients with advanced gastric cancer: report of five cases.

BACKGROUND/AIMS: A high response rate with acceptable toxicities is required in the setting of neoadjuvant chemotherapy. Five cases (3 stage IV, 2 stage IIIb) of advanced gastric cancer were successfully treated by neoadjuvant chemotherapy consisting of a combination of S-1 and cisplatin. METHODOLOGY: All 5 patients were men younger than age 60, with no severe complications. S-1 was administered orally (80 mg/m2/day) twice daily for 21 consecutive days, and cisplatin (60 mg/m2) was infused over 2 hours on day 8 with hydration. This schedule was repeated every 5 weeks. After each cycle, the clinical response evaluation was performed with endoscopy, barium meal, and spiral CT scan. Surgery was carried out about 3 weeks after chemotherapy. RESULTS: All patients were responders (100%) after one or two cycles. However, there was no patient with either complete response, or down-staging. Toxicities, according to the WHO criteria, were very mild and none required treatment. Postoperatively one patient died of aspiration pneumonia unrelated to the chemotherapy. The others were discharged within 3 weeks after operation without complications. CONCLUSIONS: S-1 plus cisplatin seems safe and effective as neoadjuvant chemotherapy in advanced gastric cancer patients.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Role of pyloroplasty after proximal gastrectomy for cancer.

BACKGROUND/AIMS: The necessity of pyloroplasty as a drainage procedure after proximal gastrectomy remains controversial in terms of the postoperative quality of life. The aim of this retrospective study was to evaluate whether pyloroplasty is necessary after proximal gastrectomy. METHODOLOGY: Thirty-five patients who underwent proximal gastrectomy with jejunal interposition between 1993 and 2000 were studied. They were divided into two groups: Group A, jejunal interposition without pyloroplasty (n=17); Group B, jejunal interposition with pyloroplasty (n=18). The subjects were interviewed and examined to assess their symptoms, food intake and body weight at 6, 12, and 24 months after the operation. Endoscopy and a radioisotope gastric emptying test were performed one year postoperatively. RESULTS: A low incidence of epigastric fullness, nausea, and vomiting and a high frequency of patients with greater than 80% of pre-illness food intake were found in Group B. A high recovery of bodyweight was also achieved in Group B. On the other hand, a high incidence of reflux gastritis or bile regurgitation was found in Group B. Gastric emptying was significantly delayed in Group A. CONCLUSIONS: Pyloroplasty as a drainage procedure after proximal gastrectomy is necessary in terms of the clinical symptoms, dietary intake, recovery of body weight, or gastric emptying.

Anastomosis, Surgical↗