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Biomedical subjects

K Kubota

Publications and source records attributed to K Kubota.

At least 19 recordsLinked to original sources

Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan.

BACKGROUND: To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design. PATIENTS AND METHODS: A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP). RESULTS: The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated. CONCLUSION: The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.

Adenocarcinoma↗

A case of symptomatic Morgagni's hernia and a review of Morgagni's hernia in Japan (263 reported cases).

An 81-year-old female patient was admitted to the emergency room of our hospital with complaints of respiratory distress, abdominal ache, nausea, and intermittent vomiting. A plain X-ray of the abdomen and chest revealed air-fluid levels on the abdomen and the right side of the chest. Laboratory tests showed severe acidemia with a blood base excess level of -24.9 mmol/L. Since the patient was considered to have acute intestinal obstruction due to transverse colon herniation into the thorax through a foramen of Morgagni, emergency surgery was performed. Operative findings revealed that the retrosternal diaphragm had a defect of 5 cm in diameter and 20 cm in length with the transverse colon herniated into the thorax. The diaphragm defect was sutured first, and partial resection of the transverse colon was performed. After the operation, the patient had no symptoms and no recurrence has been observed during the 1-year follow-up. There have been 263 reported cases of Morgagani hernia in Japan. The case of the Morgagni hernia is reported here with some bibliographical comments.

Aged, 80 and over↗

Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery.

BACKGROUND: Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. METHODS: Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. RESULTS: Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. CONCLUSION: Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery.

Animals↗

Development and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping of Vibrio cholerae.

PulseNet is a network that utilizes standardized pulsed-field gel electrophoresis (PFGE) protocols with the purpose of conducting laboratory-based surveillance of foodborne pathogens. PulseNet standardized PFGE protocols are subject to rigorous testing during the developmental phase and careful evaluation during a validation process assessing its robustness and reproducibility in different laboratories. Here we describe the development and validation of a rapid PFGE protocol for subtyping Vibrio cholerae for use in PulseNet International activities. While the protocol was derived from the existing PulseNet protocol for Escherichia coli O157, various aspects of this protocol were optimized for use with V. cholerae, most notably a change of the primary and secondary restriction enzyme to SfiI and NotI, respectively, and the use of a two-block electrophoresis program. External validation of this protocol was undertaken through a collaboration between three PulseNet Asia Pacific laboratories (Public Health Laboratory Centre, Hong Kong, National Institute of Infectious Diseases, Japan, and International Center for Diarrhoeal Diseases Research-Bangladesh) and PulseNet USA. Comparison of PFGE patterns generated by each of the participating laboratories demonstrated that the protocol is robust and reproducible.

Bangladesh↗

Retinoic acid-inducible gene-I is induced in gingival fibroblasts by lipopolysaccharide or poly IC: possible roles in interleukin-1beta, -6 and -8 expression.

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH family of proteins, and little is known of its biological function in the oral region. We previously reported that interleukin 1beta (IL-1beta) induced RIG-I expression in gingival fibroblasts. In this study, we studied the mechanism of RIG-I expression induced by lipopolysaccharide (LPS) or double-stranded RNA (dsRNA) in gingival fibroblasts. We also addressed the role of RIG-I in the expression of IL-1beta, IL-6 and IL-8 in gingival fibroblasts stimulated with LPS or dsRNA. We stimulated cultured human gingival fibroblasts with LPS or dsRNA, and examined the expression of RIG-I mRNA and protein. The effect of cycloheximide, a protein synthesis inhibitor, on RIG-I induction by these stimuli was examined. The expression of IL-1beta, IL-6 and IL-8 in gingival fibroblasts transfected with RIG-I cDNA stimulated with LPS or dsRNA was examined. LPS or dsRNA induced the expression of mRNA and protein for RIG-I in concentration- and time-dependent manners. We also examined the localization of RIG-I, and found that it was expressed in cytoplasm. Cycloheximide did not suppress the LPS or dsRNA-induced RIG-I expression. Introduction of RIG-I cDNA into gingival fibroblasts resulted in enhanced expression of IL-1beta, IL-6 and IL-8; moreover, overexpression of RIG-I stimulated with LPS or dsRNA synergistically increased expression of IL-1beta, IL-6 and IL-8. RIG-I may have important roles in the innate immune response in the regulation of IL-1beta, IL-6 and IL-8 expression in gingival fibroblasts in response to LPS and dsRNA.

Blotting, Western↗

[Embolism of the lower limb caused by native aortic valve thrombosis].

Native aortic valve thrombosis is an uncommon event with heart valve disease, during cardiac catheterization, bacterial endocarditis, or a hypercoagulative state as in antiphospholipid antibody syndrome. We report a case of thrombus formation on a native aortic valve, which was found by the transesophageal echocardiography during thrombectomy of the lower limb. We supposed that the atheromatous plaque of aortic valve was related to thrombus formation.

Aortic Valve↗

Loss of peritubular capillaries in the development of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. In this study, we examined the role of peritubular capillary (PTC) injury in the development of CAN. METHODS: We studied renal biopsies (n = 79) obtained from grafts with CAN. PTC injury was examined morphologically by immunohistochemistry for CD34. These findings were correlated with interstitial fibrosis and graft dysfunction. Humoral immunity involved in CAN was studied by C4d staining. RESULTS: The CAN cases in the present study included chronic rejection (CR) (n = 14, 17.8%) and C4d-positive chronic humoral rejection (CHR; n = 6, 42.9% in CR cases). Irrespective of CR, CHR, or other CAN, the development of CAN was characterized by injury to and loss of identifiable PTCs, accompanied with the development of interstitial fibrosis. In CR and CHR cases, the loss of PTCs was prominent and seemed to progress within a relatively short period after transplantation. A decrease in the number of PTCs significantly correlated with the development of interstitial fibrosis (r = -0.75, P < .001) and impairment of graft function (r = -0.69, P < .001). CONCLUSIONS: Irrespective of whether CR, CHR, or other factors contribute to CAN, the processes involved in its development appear similar and are characterized by progressive injury and loss of PTCs, with the development of renal scarring. Immunohistochemistry for CD34 in human renal biopsies is a useful method for the detection of microvascular injury.

Antibody Formation↗

Japanese collaborative study for fibrinogen assay: variability of the fibrinogen assay between different laboratories does not improve when a common calibrator is used.

Several national and local external quality assurance schemes have been developed to improve the plasma fibrinogen assay in Japan over the past 30 years. Now most commercial calibrant plasma may be calibrated against an International Standard preparation, in order to achieve agreement of results obtained by different laboratories. However, we have never achieved satisfactory results, according to an external quality control survey regarding the fibrinogen assay. Therefore, we distributed two kinds of fibrinogen standards to be used as common calibrators, along with three plasma samples, among 183 general laboratories in Japan. The results of this collaborative study showed that the assigned value for the commercially available calibrators remained problematic. Furthermore, it was concluded that the between-laboratory variability could not be improved beyond a certain degree of standardization, even if a common calibrator was used for the Clauss-derived assay carried out by an automatic coagulometer.

Calibration↗

Species status and phylogeography of two closely related Coptolabrus species (Coleoptera: Carabidae) in South Korea inferred from mitochondrial and nuclear gene sequences.

We investigated the species status and intraspecific phylogeography in South Korea of two ground beetle species, Coptolabrus jankowskii and Coptolabrus smaragdinus (Coleoptera: Carabidae), using statistical parsimony networks and nested clade analyses based on sequences from the mitochondrial cytochrome oxidase subunit I (COI) and nuclear phosphoenolpyruvate carboxykinase (PepCK) and wingless (Wg) genes. Although traditional parsimony tree construction generally failed to resolve interspecific relationships and construct biologically meaningful genealogies, analysis using statistical parsimony networks yielded statistically significant inter- and intraspecific genealogical structures. We found that although these two species represent a notable case of trans-species polymorphisms in both mitochondrial and nuclear gene sequences, their status as separate species was evidenced by the nonrandom association between species and nested clades at various nesting levels. The exceptional occurrence of shared identical or very similar COI sequences was considered to be the result of introgressive hybridization. In addition, range expansion and fragmentation events across the Korean Peninsula and adjacent islands were inferred from nested clade phylogeographical analyses. The COI gene revealed the geographical divergence of major eastern and western clades and historical biogeographical events within each major clade, whereas the nuclear PepCK gene, which did not reveal corresponding east-west clades, indicated past fragmentation and range expansion across wide areas that may have been the result of older biogeographical events. Thus, phylogeographical inferences drawn from analyses of mitochondrial and nuclear genes can reveal different and potentially complementary information about phylogeographical processes.

Animals↗

Retinoic acid-inducible gene-I is induced by interleukin-1beta in cultured human gingival fibroblasts.

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box family protein, and details of its biological function are not known. We have studied the mechanism of the interleukin-1beta (IL-1beta)-induced RIG-I expression in human gingival fibroblasts in culture. We also addressed the possibility of enhanced expression of COX-2, RANTES and galectin-9 in fibroblasts overexpressed RIG-I. We stimulated cultured human gingival fibroblasts with IL-1beta and examined the expression of RIG-I mRNA and protein by reverse transcriptase-mediated polymerase chain reaction and Western blot analysis. The effect of cycloheximide, a protein synthesis inhibitor, on the IL-1beta-induced expression of RIG-I was examined. The expression of COX-2, RANTES, galectin-9 and monocyte chemoattractant protein-1 in gingival fibroblasts transfected with RIG-I cDNA was also examined. IL-1beta stimulated the expressions of mRNA and protein for RIG-I, in cultured fibroblasts, in a time- and concentration-dependent manner. Cycloheximide did not suppress the IL-1beta-induced RIG-I expression. Introduction of RIG-I cDNA into fibroblasts resulted in enhanced expression of COX-2 mRNA, and slightly enhanced the expression of mRNA for RANTES and galectin-9. In contrast, RIG-I overexpression did not alter the level of mRNA for monocyte chemoattractant protein-1. We conclude that IL-1beta stimulates RIG-I expression in human gingival fibroblasts.

Blotting, Western↗

Analysis of Salmonella enterica serotype Typhi pulsed-field gel electrophoresis patterns associated with international travel.

Typhoid fever is a significant cause of morbidity and mortality worldwide, causing an estimated 16 million cases and 600,000 deaths annually. Although overall rates of the disease have dramatically decreased in the United States, the number of travel-related infections has increased in recent decades. Drug resistance among Salmonella enterica serotype Typhi strains has emerged worldwide, making antimicrobial susceptibility testing an important function in public health laboratories. Pulsed-field gel electrophoresis (PFGE) subtyping of food-borne and waterborne pathogens has proven to be a valuable tool for the detection of outbreaks and laboratory-based surveillance. This retrospective study examined the distribution of PFGE patterns of S. enterica serotype Typhi isolates from patients with a history of international travel. Isolates were collected as part of a passive laboratory-based antimicrobial susceptibility surveillance study. Isolates were PFGE subtyped by using the restriction enzyme XbaI to restrict the total genomic DNA. Isolates indistinguishable with XbaI were further characterized using the restriction enzyme BlnI. A total of 139 isolates were typed, representing travel to 31 countries. Restriction fragment patterns consisted of 14 to 18 fragments ranging in size from 580 to 40 kbp. Seventy-nine unique PFGE patterns were generated using XbaI. Isolates from the same geographic region did not necessarily have similar PFGE patterns. Of the 139 isolates, 46 (33%) were resistant to more than one antimicrobial agent (multidrug resistant [MDR]). Twenty-seven (59%) of 46 MDR isolates had indistinguishable PFGE patterns with both XbaI and BlnI. It appears that MDR S. enterica serotype Typhi has emerged as a predominant clone in Southeast Asia and the Indian subcontinent.

Drug Resistance, Multiple, Bacterial↗

Level of 5-fluorodeoxyuridine 5'-monophosphate in cancerous tissue in patients with gastric cancer under preoperative administration of TS-1. A preliminary study.

Metabolizing enzymes such as thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have long been known to be useful for predicting response and outcome in patients receiving 5-fluorouracil (5-FU). However, few studies have examined the cancerous tissue levels of 5-fluorodeoxyuridine 5'-monophosphate (FdUMP), a metabolite of 5-FU that has an important role in inhibiting DNA synthesis. In this study, for the first time to our knowledge, we measured concentrations of FdUMP in tumor specimens and surrounding non-cancerous tissue obtained at operation in 10 patients with gastric cancer who received TS-1 before surgery (80 mg/m2, 3 days). The FdUMP level in the cancerous tissue was significantly higher than that in the non-cancerous tissue (153.0 +/- 85.7 pmol/g tissue vs. 53.0 +/- 47.0 pmol/g tissue)(p = 0.0046). Furthermore, the TS level in tumor was significantly higher than that in non-cancerous tissue (6.362 +/- 5.106 pmol/g tissue vs. 2.092 +/- 2.050 pmol/g tissue) (p = 0.0310). The mean ratios of TS-bound FdUMP to TS and FdUMP concentrations in the cancerous tissues were 45.9% and 2.00%, respectively. Our results demonstrate that in cancerous tissue, TS-1 may produce high FdUMP concentration and suppress about half FdUMP concentration by forming ternary complexes.

Adult↗

A comparison of the inflammatory response and the recovery of bowel function between trans- and extraperitoneal approaches of abdominal aortic aneurysmectomy.

AIM: To determine whether surgical stress is less with transperitoneal or extraperitoneal abdominal aortic aneurysmectomy, blood concentrations of inflammatory cytokines and other inflammatory markers with recovery of bowel function were examined. METHODS: Patients who underwent abdominal aortic aneurysmectomy electively via the transperitoneal (T-group; n=15) or the extraperitoneal approach (E-group; n=17) were evaluated. Inflammatory cytokines (interleukin[IL]) IL-6, IL-8, C-reactive protein concentrations, and systemic inflammatory response syndrome score were determined before operation and after operation on days (POD) 1, 3, 7, and 14. Recovery of bowel function was estimated by the time taken for resumption of bowel movement and oral intake, and by the volume of fluid collection from the nasogastric tube. RESULTS: Cytokine (IL-8) concentrations were higher in the T-group than the E-group with significant difference on POD 7 (4.8+/-0.5 versus 3.4+/-0.2 pg/mL, respectively; P=0.02). Recovery of bowel function and oral intake were earlier, and the volume of fluid collection from the nasogastric tube was smaller in the E-group than the T-group significantly. CONCLUSIONS: Early recovery of bowel function and low concentration of inflammatory cytokines suggest that the extraperitoneal approach to the abdominal aorta is less stressful to the transperitoneal approach. Postoperative inflammatory response may mainly depend on damage of the bowel in the operation of the abdominal aortic aneurysm.

Adult↗

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗