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Biomedical subjects

T Kawano

Publications and source records attributed to T Kawano.

At least 19 recordsLinked to original sources

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer.

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.

Administration, Oral↗

New "pre-diabetes" category and the metabolic syndrome in Japanese.

BACKGROUND: Recently, impaired fasting glucose (IFG) was redefined as fasting plasma glucose of 100-125 mg/dl, and individuals with IFG and/or impaired glucose tolerance (IGT) were referred to as having "pre-diabetes". However, there is a lack of data using the new definition of IFG and "pre-diabetes". OBJECTIVE: The aim of this study was to examine associations of the metabolic syndrome components with the new "pre-diabetes" category in relatively lean Japanese. METHODS: Six hundred and sixty-one Japanese study participants underwent a 75 g oral glucose tolerance test. They were classified into three groups-normal (n=225), pre-diabetes (n=308), and diabetes (n=128). The metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III, as modified for waist circumference criteria by the Regional Office for the Western Pacific Region of WHO. RESULTS: Prevalence of the metabolic syndrome in each group was 10.7%, 27.9%, and 53.9%, respectively. Of the metabolic syndrome components, the OR for prevalent pre-diabetes was 2.00 (95% CI, 1.73-2.31, p<0.001) for fasting glucose, 1.93 (95% CI, 1.54-2.42, p<0.001) for waist circumference, and 1.36 (95% CI, 1.10-1.68, p=0.005) for triglycerides. Similar associations were found in prevalent diabetes. Insulin resistance assessed using Stumvoll's index was significantly associated with both pre-diabetes and diabetes. CONCLUSION: Pre-diabetes and the metabolic syndrome frequently coexist in relatively lean Japanese. This association seems to link with abdominal adiposity and insulin resistance.

Adult↗

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Adult↗

Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cells.

BACKGROUND: Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. beta2-agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. OBJECTIVES: To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. METHODS: Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. RESULTS: Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in beta2-agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. CONCLUSIONS: Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting beta2-agonists do not modify DCs-induced allergic airway inflammation.

Albuterol↗

Validity of an oblique posterior condylar radiographic view for revision total knee arthroplasty.

We have previously developed a radiographic technique, the oblique posterior condylar view, for assessment of the posterior aspect of the femoral condyles after total knee arthroplasty. The purpose of this study was to confirm the validity of this radiographic view based upon intra-operative findings at revision total knee arthroplasty. Lateral and oblique posterior condylar views were performed for 11 knees prior to revision total knee arthroplasty, and radiolucent lines or osteolysis of the posterior aspect of the femoral condyles were identified. These findings were compared with the intra-operative appearance of the posterior aspects of the femoral condyles. Statistical analysis showed that sensitivity and efficacy were significantly better for the oblique posterior condylar than the lateral view. This method can, therefore, be considered as suitable for routine follow-up radiographs of the femoral component and in the pre-operative planning of revision surgery.

Aged↗

Flow cytometric studies of the host-regulated cell cycle in algae symbiotic with green paramecium.

Paramecium bursaria (green paramecium) possesses endosymbiotically growing chlorella-like green algae. An aposymbiotic cell line of P. bursaria (MBw-1) was prepared from the green MB-1 strain with the herbicide paraquat. The SA-2 clone of symbiotic algae was employed to reinfect MBw-1 cells and thus a regreened cell line (MBr-1) was obtained. The regreened paramecia were used to study the impact of the host's growth status on the life cycle of the symbiotic algae. Firstly, the relationship between the timing of algal propagation and the host cell division was investigated by counting the algal cells in single host cells during and after the host cell division and also in the stationary phase. Secondly, the changes in the endogenous chlorophyll level, DNA content, and cell size in the symbiotic algae were monitored by flow cytometry and fluorescence microscopy. The number of algae was shown to be doubled prior to or during the host cell division and the algal population in the two daughter cells is maintained at constant level until the host cell cycle reenters the cytokinesis, suggesting that algal propagation and cell cycle are dependent on the host's cell cycle. During the host's stationary growth, unicellular algal vegetatives with low chlorophyll content were dominant. In contrast, complexes of algal cells called sporangia (containing 1-4 autospores) were present in the logarithmically growing hosts, indicating that algal cell division leading to the formation of sporangia with multiple autospores is active in the dividing paramecia.

Animals↗

Effect of prostaglandin E1 on inflammatory responses and gas exchange in patients undergoing surgery for oesophageal cancer.

BACKGROUND: Oesophageal surgery causes morbidity and mortality from respiratory complications. We tested the possibility that prostaglandin E1 (PGE1) could reduce inflammatory cytokine responses and improve gas exchange after oesophagectomy. METHODS: We randomized 14 patients into two groups. One group received PGE1 20 ng kg(-1) min(-1) i.v. during anaesthesia (PGE1 group) and the other group did not (control group). Anaesthesia was maintained with sevoflurane and epidural anaesthesia. During oesophagectomy, ventilation of one lung was carried out with a double-lumen bronchial tube. The patients were extubated on or after the first postoperative day. Blood samples were taken at induction of anaesthesia, at the end of thoracotomy, at the end of the operation, 2 h after surgery and on the first day after surgery. RESULTS: The groups were similar for ASA physical status, age, FEV1%, operation time, duration of thoracotomy, intraoperative fluid volume and blood loss. The arterial blood gas and arterial pressure during surgery were also similar in the PGE1 and control groups. However, the PaO2/FiO2 ratio on the first day after surgery was significantly greater in the PGE1 group compared with the control group. Serum concentrations of IL-6 and IL-8 increased after surgery in both groups. IL-6 was significantly less in the PGE1 group at the end of the operation and 2 h after the operation. CONCLUSIONS: Intraoperative PGE1 reduced IL-6 production in patients undergoing oesophagectomy and oxygenation was better in the postoperative period.

Aged↗

Impairment of gastrointestinal motility by nitrate administration: evaluation based on electrogastrographic changes and autonomic nerve activity.

BACKGROUND: Nitrates decrease the tone of the lower oesophageal sphincter, and may thus induce gastro-oesophageal reflux. AIM: In the present study, we evaluated electrogastrographic changes and heart-rate variability before and after the administration of nitrates. METHODS: In 15 patients with chest pain treated with nitrates, electrocardiography and percutaneous electrogastrography were performed before and after administration of nitrates. Autonomic nervous system function was evaluated by spectral analysis of heart-rate variability and serial changes in low frequency and high frequency power, and the low frequency/high frequency ratio were compared. Electrogastrograms were analysed by obtaining peak power amplitudes and their dominant frequencies. RESULTS: After the administration of nitrates (isosorbide dinitrate), high frequency power, an index of parasympathetic nervous activity, was significantly decreased, whereas the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased. The mean peak amplitude of the electrogastrogram significantly increased postprandially both before and after treatment. After isosorbide dinitrate treatment, however, mean peak amplitudes after a meal were significantly lower than those obtained before treatment. The mean dominant frequency of the electrogastrogram did not vary before and after treatment. CONCLUSIONS: The present study suggests that nitrates inhibit gastrointestinal motility by decreasing autonomic nervous activity.

Aged↗

Effects of primary and secondary low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low-grade RSV infections on allergic airway inflammation in a murine model of allergic asthma. METHODS: A low-grade RSV (2 x 10(3) plaque-forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN-gamma production in thoracic lymph nodes. To investigate interaction between low-grade virus and Dermatophagoides farinae (Df), airway hyper-responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low-grade RSV infections in four groups of mice; control, Df allergen-sensitized, RSV-infected and Df-sensitized RSV-infected mice. A direct comparison between low- and high-grade RSV infections was also performed in primary infection. To investigate the role of IL-5 during secondary RSV infection, anti-IL-5 monoclonal antibody (anti-IL-5 mAb) was injected in mice and similar parameters were compared in four groups of mice. RESULTS: Primary high-grade RSV infection increased allergen-induced airway inflammation, while primary low-grade RSV infection attenuated allergen-induced airway inflammation concomitant with significant IFN-gamma production in lung-draining lymph nodes. In marked contrast, secondary low-grade RSV infection increased both IFN-gamma and IL-5 production, resulting in exacerbation of allergen-induced airway inflammation. Anti-IL-5 mAb treatment in secondary low-grade RSV infection and Df allergen-sensitized mice attenuated virus and allergen-induced airway inflammation. CONCLUSIONS: Low-grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen-sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL-5 is critically involved.

Animals↗

Treatment strategy for Boerhaave's syndrome.

Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition.

Adult↗

Elasto-plastic contact analysis of an ultra-high molecular weight polyethylene tibial component based on geometrical measurement from a retrieved knee prosthesis.

The wear phenomenon of ultra-high molecular weight polyethylene (UHMWPE) in knee and hip prostheses is one of the major restriction factors on the longevity of these implants. Especially in retrieved knee prostheses with anatomical design, the predominant types of wear on UHMWPE tibial components are delamination and pitting. These fatigue wear patterns of UHMWPE are believed to result from repeated plastic deformation owing to high contact stresses. In this study, the elasto-plastic contact analysis of the UHWMPE tibial insert, based on geometrical measurement for retrieved knee prosthesis, was performed using the finite element method (FEM) to investigate the plastic deformation behaviour in the UHMWPE tibial component. The results suggest that the maximum plastic strain below the surface is closely related to subsurface crack initiation and delamination of the retrieved UHMWPE tibial component. The worn surface whose macroscopic geometrical congruity had been improved due to wear after joint replacement showed lower contact stress at macroscopic level.

Aged↗

The accuracy of image-guided knee replacement based on computed tomography.

Our study evaluated the accuracy of an image-guided total knee replacement system based on CT with regard to preparation of the femoral and tibial bone using nine limbs from five cadavers. The accuracy was assessed by direct measurement using an extramedullary alignment rod without radiographs. The mean angular errors of the femur and tibia, which represent angular gaps from the real mechanical axis in the coronal plane, were 0.3 degrees and 1.1 degrees, respectively. The CT-based system, provided almost perfect alignment of the femoral component with less than 1 degrees of error and excellent alignment with less than 3 degrees of error for the tibial component. Our results suggest that standardisation of knee replacement by the use of this system will lead to improved long-term survival of total knee arthroplasty.

Arthroplasty, Replacement, Knee↗

Development and clinical application of semi-loop-shaped retractor for gasless laparoscopic surgery.

BACKGROUND: Gasless laparoscopy has the advantage of avoiding the risk inherent in pneumoperitoneum, but has not gained widespread popularity because of limited exposure of the operative field. Improved retraction devices are therefore needed. METHODS: A loop-shaped metallic retractor was designed for planar lifting of the anterior abdominal wall. Four types of retractor (5/6-, 3/4-, and 1/2-circle with rod at 90 degrees, and 1/2-circle with rod at 97 degrees ) were studied in 15 pigs. The device was then used for 47 patients. RESULTS: The 1/2-circle was the most smoothly inserted retractor and was significantly safer than the 5/6-circle (p < 0.05, Fisher's exact probability test). The 1/2-circle with rod at 97 degrees was utilized for clinical cases. This retractor can be readied within 1 min and was used successfully for all operations. CONCLUSIONS: This new retractor for gasless laparoscopic surgery provides good exposure and has the potential to enhance the performance of advanced laparoscopic surgery.

Abdominal Wall↗

Roles of the reactive oxygen species-generating peroxidase reactions in plant defense and growth induction.

Extracellularly secreted plant peroxidases (POXs) are considered to catalyze the generation of reactive oxygen species (ROS) coupled to oxidation of plant hormone indole-3-acetic acid (IAA) and defense-related compounds salicylic acid (SA), aromatic monoamines (AMAs) and chitooligosaccharides (COSs). This review article consists of two parts, which describe H(2)O(2)-dependent and H(2)O(2)-independent mechanisms for ROS generation, respectively. Recent studies have shown that plant POXs oxidize SA, AMAs and COSs in the presence of H(2)O(2) via a conventional POX cycle, yielding the corresponding radical species, such as SA free radicals. These radical species may react with oxygen, and superoxide (O(2)(.-)) is produced. Through the series of reactions 2 moles of O(2)(.-) can be formed from 1 moles of H(2)O(2), thus leading to oxidative burst. It has been revealed that the ROS induced by SA, AMAs and COSs triggers the increase in cytosolic Ca(2+) concentration. Actually POXs transduce the extracellular signals into the redox signals that eventually stimulate the intracellular Ca(2+) signaling required for induction of defense responses. On the other hand, IAA can react with oxygen and plant POXs in the absence of H(2)O(2), by forming the ternary complex enzyme-IAA-O(2), which readily dissociates into enzyme, IAA radicals and O(2)(.-). This article covers the recent reports showing that extracellularly produced hydroxy radicals derived from O(2)(.-) mediate the IAA-induced cell elongation. Here a novel model for IAA signaling pathway mediated by extracellular ROS produced by cell-wall POXs is proposed. In addition, possible controls of the IAA-POX reactions by a fungal alkaloid are discussed.

Peroxidases↗

The neuroprotective effect of a novel calmodulin antagonist, 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, in transient forebrain ischemia.

A novel calmodulin (CaM) antagonist DY-9760e, (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), with an apparent neuroprotective effect in vivo, potently inhibits CaM-dependent nitric oxide synthase in situ. In the present study, we determined whether DY-9760e inhibits nitric oxide (NO) production and protein nitration by peroxynitrite (ONOO(-)) formation in the hippocampal CA1 region of gerbils after transient forebrain ischemia. In freely moving gerbils, NO production after 10-minute forebrain ischemia was monitored consecutively with in vivo brain microdialysis. Pretreatment with DY-9760e (50 mg/kg i.p.) significantly decreased the increased levels of NO(x)(-) (NO metabolites, NO(2)(-) plus NO(3)(-)) immediately after, 24 h after cerebral ischemia-reperfusion to the control levels of sham-operated animals. Western blot and immunohistochemical analyses using an anti-nitrotyrosine antibody as a marker of ONOO(-) formation indicated a marked increase in nitrotyrosine immunoreactivity in the pyramidal neurons of the CA1 region 2 h after reperfusion, and DY-9760e significantly inhibited increased nitrotyrosine immunoreactivity. Coincident with the inhibition of the NO production and protein tyrosine nitration, pretreatment with DY-9760e rescued the delayed neuronal death in the hippocampal CA1 region. These results suggest that the inhibitory effects of DY-9760e on the NO-ONOO(-) pathway partly account for its neuroprotective effects in cerebral ischemia.

Animals↗

Possible use of indole-3-acetic acid and its antagonist tryptophan betaine in controlled killing of horseradish peroxidase-labeled human cells.

It has been proposed that combination of indole-3-acetic acid (IAA) and horseradish peroxidase (HRP) could be useful as the basis for targeted cancer therapy involving antibody-, polymer-, or gene-directed approaches. By circulating IAA in human body, the cells labeled with HRP could be selectively killed since cytotoxic radical species are produced by IAA-HRP reaction. To enable the finely geared controls in selective killing of the cells, the author propose the use of a fungal alkaloid, hypaphorine known to act against IAA in growing plants, in combination with IAA. Previously, the author and colleagues have shown that hypaphorine competitively inhibits the IAA-dependent superoxide generation by HRP. Since hypaphorine is structurally similar to IAA, the effects of hypaphorine against IAA may be due to competitive binding to the IAA-binding domain on HRP. Our in vitro studies on hypaphorine-based control of the IAA-HRP reaction yielding superoxide, must be re-examined in in vivo systems prior to clinical examination.

Cell Death↗

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma.

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.

Adolescent↗