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Biomedical subjects

Y Yamada

Publications and source records attributed to Y Yamada.

At least 199 records · Page 11Linked to original sources
PubMed2001

Automation of expiratory trigger sensitivity in pressure support ventilation.

Patients under pressure support ventilation sometimes encounter patient-ventilator asynchrony in the transition from inspiration to expiration, that is, expiratory asynchrony. This problem is caused by the incompatibility of the fixed level of expiratory trigger sensitivity termination criteria (i.e., flow termination criteria) in the ICU ventilators to various patient conditions. The user-adjustable expiratory trigger sensitivity implemented in some newly released ventilators has been experienced to be difficult to use and unable to adapt ever-changing patient conditions without user intervention, although it provides more flexibility. This article elucidates the rationale for automatic control of the expiratory trigger sensitivity and evaluates the automation system with a bench setup. The evaluation data suggest that good expiratory synchronies can be achieved through automatic adjustments of expiratory trigger sensitivity.

Humans↗
PubMed2001

Development of a three-dimensional jaw-tracking system implanted in the freely moving mouse.

A high-resolution mandibular tracking system was designed and tested in a freely moving mouse. A sensor unit, which consisted of four small magnetic sensors, was employed to trace small magnet movements in the three-dimensional space. After the sensor's output-to-displacement transformation equations were obtained from a multiple regression analysis of pre-experimental calibration data, the magnet and the sensors were transferred to the mouse, being kept at the same configuration as determined in the calibration system. In order to measure the three-dimensional jaw movements, the magnet was glued on the mandibular surface of the mouse and the sensor unit was implanted in the nasal bone. Jaw-movement trajectories were obtained as electrical signals from the sensors after being compensated by the output-to-displacement transformation equations of the sensors with a personal computer. This sensor system, applied to the freely moving mouse, could trace the jaw trajectories with an accuracy of better than 20 microm in three-dimensional space. Consequently, the typical pattern of the rhythmical jaw movements of the mouse during mastication was obtained. The mouse protruded the mandible to the most anterior position in the jaw-opening phase and retruded to it the most posterior position in the jaw-closing phase. This tracking system may also be applied to other small animals.

Animals↗
PubMed2001

Curative treatment of central hemangioma in the mandible by direct puncture and embolisation with n-butyl-cyanoacrylate (NBCA).

Management of central hemangioma in the mandible is difficult because of the abundant vascular network in this region. One of the most common signs of these patients, especially in the mixed dentition period, is hypermobility of the teeth with spontaneous hemorrhage from the surrounding gingival sulcus. Various therapeutic modalities have been considered, but surgery is the most frequently used. In cases of a large extensive lesion, however, intralesional injections of sclerosing agents have often been successful. A case of central hemangioma of the mandible with arteriovenous malformations in a 10-year-old girl is reported. She was treated with direct injection of an embolic material, n-butyl-cyanoacrylate, which brought satisfactory results. Preoperative embolisation of feeder vessels with Gelfoam and Avitene soaked in thrombin together with this direct injection is a safe treatment modality that is as effective as surgery.

Child↗
PubMed2001

Human T-cell leukemia virus type I tax protein induces the expression of anti-apoptotic gene Bcl-xL in human T-cells through nuclear factor-kappaB and c-AMP responsive element binding protein pathways.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), which is an aggressive form of human T-cell malignancy. The viral protein, Tax, immortalizes human T-cells and inhibits various types of apoptosis, and is thought to play crucial roles in the development of ATL. We have recently demonstrated that Tax induces the constitutive expression of the anti-apoptotic protein, Bcl-xL, in a mouse T-cell line. The mouse, however, is not a natural host of HTLV-I, and HTLV-I does not induce this malignancy in mice. We thus examined whether Tax also activates the expression of Bcl-xL in human T-cells. Expression of Tax in a human T-cell line, Jurkat, induced the expression of the Bcl-xL gene, but did not significantly affect the expression of the other apoptosis-related genes, Bcl-2 and Bax. Transient transfection assays showed that Tax stimulated human Bcl-xL promoter activity in Jurkat cells. Deletion of the two potential nuclear factor (NF)-kappaB binding sites in the human Bcl-xL promoter significantly decreased Tax-induced transactivation. In addition to NF-kappaB, Tax activates transcription through the c-AMP responsive element binding protein (CREB). Tax mutants segregating these two pathways showed that both the NF-kappaB and CREB pathways of Tax are required for maximum activation of a human Bcl-xL promoter, nevertheless, NF-kappaB alone was sufficient for that of a mouse Bcl-xL promoter. Northern blot analysis showed that all the human T-cell lines expressing Tax had higher levels of Bcl-xL mRNA than HTLV-I-uninfected ones. Furthermore, the sample from one patient with ATL expressed higher levels of Bcl-xL mRNA compared with levels from uninfected peripheral blood mononuclear cells. Our results suggest that Tax induces the expression of Bc-xL through the NF-kappaB and CREB pathways in HTLV-I-infected human T-cells, and then inhibits apoptosis, and such inhibition is necessary for the infected cells to advance to the leukemia in vivo.

Apoptosis↗
PubMed2001

Phase II trial of paclitaxel by three-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reactions.

PURPOSE: To determine the antitumor activity and toxicity of paclitaxel administered as a three-hour infusion and to estimate the incidence of hypersensitivity reactions using a short-course prophylaxis regimen in patients with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients with advanced measurable gastric cancer and performance status 0 to 2, who had received at most one prior chemotherapy regimen, were treated with paclitaxel 210 mg/m2 over three hours following a short-course premedication with dexamethasone, diphenhydramine and ranitidine administered 30 min prior to the delivery of paclitaxel. Cycles were repeated every three weeks. Twenty-six patients (43%) had received prior chemotherapy for metastatic disease and six patients had received adjuvant chemotherapy. The response rate to prior chemotherapy was 50% (13 of 26). RESULTS: Objective responses were observed in 14 of 60 patients (23%; 95% confidence interval (95% CI): 13%-36%). Six of twenty-eight (21%) patients with no prior chemotherapy and 7 of 26 (27%) previously treated patients for metastatic disease developed a PR. There were no complete responses. The median duration of response was 152 days. The study treatment was well tolerated. Twenty-two of sixty patients (37%) experienced grade 3 or 4 neutropenia, which was the most common and serious toxicity. Grade 3 peripheral neuropathy occurred in one patient. Hypersensitivity reactions were observed in only nine patients (15%) and were all grade 1. CONCLUSIONS: A three-hour infusion of paclitaxel is both an active and safe treatment for gastric cancer using the short-course premedication schedule. Paclitaxel appears to be non-cross resistant to other active agents for gastric cancer.

Adult↗
PubMed2001

Phase I-II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer.

BACKGROUND: Irinotecan (CPT-11) shows synergism with mitomycin-C (MMC) in a preclinical setting. The goals of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity, the recommended dose (RD), and preliminary anti-tumor activity in a combined CPT-11 and MMC treatment of advanced gastric cancer. PATIENTS AND METHODS: The study was designed to evaluate escalated doses of CPT-11 and MMC administered every two weeks. Five escalating dose levels were studied (CPT-11/ MMC: 100/5; 125/5; 150/5; 150/7; 150/10 mg/m2). RESULTS: Thirty-one patients were enrolled. Thirty patients were assessable for toxicity and tumor response for 89 treatment cycles. The median age was 60 years (32-73 years), and most patients (90%) had a performance status of 0 to 1. Fourteen patients were previously treated and 17 were chemotherapynaive. The MTD was CPT-11 150 mg/m2 plus MMC 10 mg/m2, in which all three patients experienced grade 4 neutropenia. including one episode of prolonged and one of febrile neutropenia, and one patient experienced grade 3 diarrhea during the first cycle. Fifteen partial responses were observed. CONCLUSIONS: The RD based on this phase I-II study was CPT-11 150 mg/m2 plus MMC 5 mg/m2 administered every two weeks. This combination demonstrates promising activity against advanced gastric cancer and warrants further investigation in another phase II study.

Adult↗
PubMed2001

gamma-Hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor.

UFT, a drug composed of uracil and tegafur at the molar ratio of 4:1, is an orally active agent for the treatment of a wide variety of malignant tumours. Using a murine dorsal air sac (DAS) assay, we have previously shown that UFT and its metabolites, gamma-hydroxybutyric acid (GHB) and 5-fluorouracil (5-FU), inhibited the angiogenesis induced by murine renal cell carcinoma. Here we report that UFT was more effective than other fluorinated pyrimidines such as 5-FU and doxifluridine (5'-DFUR) in blocking the angiogenic responses elicited by five human cancer cell lines which produced high levels of vascular endothelial growth factor (VEGF), but no detectable fibroblast growth factor-2 (FGF-2) in vitro. In contrast, UFT was unable to block the angiogenic response to one human gastric cancer cell line which produced both VEGF and FGF-2 in vitro. However, the production or secretion of VEGF by these cells was unaffected by GHB and 5-FU treatment. Interestingly, GHB suppressed the chemotactic migration and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by VEGF, without inhibiting their DNA synthesis. Since GHB did not affect the FGF-2-driven activities in HUVECs, its action appears to be VEGF-selective. On the other hand, 5-FU inhibited DNA synthesis and migration of HUVECs stimulated by both VEGF and FGF-2, and tube formation driven by VEGF, suggesting that 5-FU is cytotoxic to endothelial cells. The inhibitory effects of 5-FU, and especially those GHB, were reproduced under in vivo condition using the DAS assay. The VEGF-mediated angiogenesis was significantly inhibited by UFT, 5-FU, and especially by GHB. We propose that the selective inhibitory effects of GHB on VEGF-mediated responses of endothelial cells are involved in the anti-angiogenic activity of UFT.

Angiogenesis Inhibitors↗
PubMed2001

Quantitative relationship between myocardial concentration of tacrolimus and QT prolongation in guinea pigs: pharmacokinetic/pharmacodynamic model incorporating a site of adverse effect.

Clinical cases have been reported of tacrolimus (FK506)-induced QT prolongation. We have previously demonstrated sustained QT prolongation by FK506 in guinea pigs. Herein, we aimed to conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis of FK506, using a model involving the myocardial compartment. The pharmacokinetics of FK506 and its effects on QTc intervals were investigated in guinea pigs. In the pharmacokinetic study, whole blood and ventricular FK506 concentrations were analyzed, using a 4-compartment model during and after intravenous infusion of FK506 (0.01 or 0.1 mg/hr/kg). Subsequently, the concentration-response relationship between ventricular FK506 concentration and change in QTc interval was analyzed, using the maximal effect (Emax) model. Pharmacokinetic profiles of FK506 showed a delayed distribution of FK506 into the ventricle. Furthermore, the observed QT prolongation paralleled the ventricular FK506 concentrations, with no lag-time between the two. The Emax model successfully described the relationship between changes in QTc interval and ventricular FK506 concentrations. In conclusion, the PK/PD model where the myocardial drug concentration of FK506 was linked with its adverse effect could describe, for the first time, the anti-clockwise hysteresis observed in the relationship between blood FK506 concentration and QTprolongation. Such a hysteresis pattern for QTprolongation might be caused, therefore, mainly by the delayed disposition of FK506 to ventricular myocytes.

Animals↗
PubMed2001

Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.

Hirschsprung disease (HSCR) is sometimes associated with a set of characteristics including mental retardation, microcephaly, and distinct facial features, but the gene mutated in this condition has not yet been identified. Here we report that mutations in SIP1, encoding Smad interacting protein-1, cause disease in a series of cases. SIP1 is located in the deleted segment at 2q22 from a patient with a de novo t(2;13)(q22;q22) translocation. SIP1 seems to have crucial roles in normal embryonic neural and neural crest development.

Animals↗
PubMed2001

Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene.

Perlecan is a large heparan sulfate (HS) proteoglycan present in all basement membranes and in some other tissues such as cartilage, and is implicated in cell growth and differentiation. Mice lacking the perlecan gene (Hspg2) have a severe chondrodysplasia with dyssegmental ossification of the spine and show radiographic, clinical and chondro-osseous morphology similar to a lethal autosomal recessive disorder in humans termed dyssegmental dysplasia, Silverman-Handmaker type (DDSH; MIM 224410). Here we report a homozygous, 89-bp duplication in exon 34 of HSPG2 in a pair of siblings with DDSH born to consanguineous parents, and heterozygous point mutations in the 5' donor site of intron 52 and in the middle of exon 73 in a third, unrelated patient, causing skipping of the entire exons 52 and 73 of the HSPG2 transcript, respectively. These mutations are predicted to cause a frameshift, resulting in a truncated protein core. The cartilage matrix from these patients stained poorly with antibody specific for perlecan, but there was staining of intracellular inclusion bodies. Biochemically, truncated perlecan was not secreted by the patient fibroblasts, but was degraded to smaller fragments within the cells. Thus, DDSH is caused by a functional null mutation of HSPG2. Our findings demonstrate the critical role of perlecan in cartilage development.

Animals↗
PubMed2001

Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole.

1. The role played by the epithelium in H(2)O(2)-induced modulation of the mechanical responses induced by acetylcholine (ACh) in rabbit intrapulmonary bronchioles was investigated in epithelium-intact and -denuded strips. 2. When ACh (3 microM) was applied intermittently, H(2)O(2) (30 microM) enhanced the ACh-induced contractions in epithelium-intact strips. In contrast, in epithelium-denuded strips H(2)O(2) (30 microM) inhibited such contractions. At higher concentrations, H(2)O(2) concentration-dependently attenuated the ACh-induced contractions in both epithelium-intact and -denuded strips, its action being more potent in the latter strips than in the former. 3. Diclofenac (a cyclo-oxygenase inhibitor; 3 microM) reduced the H(2)O(2)-induced enhancement of ACh-contractions in epithelium-intact strips but had no effect on the H(2)O(2)-induced inhibition in epithelium-denuded strips. N(G)-nitro-L-arginine did not alter the effect of H(2)O(2) on ACh-induced contractions in epithelium-intact strips. 4. Catalase (500 u ml(-1)) completely blocked both H(2)O(2)-induced effects on ACh-contractions (enhancement and inhibition). Neither superoxide dismutase (200 u ml(-1)) nor deferoxamine (0.5 mM) had any effect on H(2)O(2)-induced inhibition in epithelium-denuded strips. 5. Aminotriazole (an inhibitor of catalase; 50 mM) significantly potentiated the H(2)O(2)-induced inhibition of ACh-contractions in epithelium-intact strips but not in epithelium-denuded strips. 6. The density ratio for catalase (epithelium-intact over -denuded strips) analysed by Western blot was about 2.1, suggesting that epithelium contains more catalase than smooth muscle. 7. It is concluded that in rabbit intrapulmonary bronchioles, H(2)O(2) has dual actions on ACh-contractions. It is suggested that the epithelium may act as a powerful biochemical barrier via both the action of catalase (scavenging H(2)O(2)) and the release of bronchoconstrictor prostaglandins, thus attenuating the H(2)O(2)-induced modulation of ACh-contractions.

Acetylcholine↗
PubMed2001

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Adult↗
PubMed2001

Efficient production of menaquinone (vitamin K2) by a menadione-resistant mutant of Bacillus subtilis.

Efficient production of menaquinone (MK) by Bacillus subtilis was achieved. An edible strain of B. subtilis, isolated from the traditional Japanese food natto, was mutated to improve MK productivity. A menadione-resistant mutant producing 30% more MK than its parent strain was obtained. Soybean extract and glycerol were the best nitrogen and carbon sources, respectively, among the sources tested. Addition of yeast extract also increased MK productivity. The maximum concentration of MK reached about 35.0 mg/l after 4 days of culture in a jar fermenter. The pH of the medium decreased to 5.5 after the start of cultivation, then spontaneously increased to 7.7-8.0. This pH change might be important in the production of MK because only small amounts of MK were obtained when pH was controlled at 5.7, 6.0, 7.0, 7.5 or 8.0.

Bacillus subtilis↗
PubMed2001

A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303.

This phase II trial was performed to evaluate the efficacy of a new granulocyte colony-stimulating factor (G-CSF)-supported multi-agent chemotherapy protocol, LSG15, for aggressive adult T-cell leukaemia-lymphoma (ATL). Ninety-six previously untreated patients with aggressive ATL were enrolled and grouped as: acute type (58), lymphoma type (28) and unfavourable chronic type (10). Therapy consisted of seven cycles of VCAP (vincristine, cyclophosphamide, doxorubicin and prednisone), AMP (doxorubicin, ranimustine and prednisone) and VECP (vindesine, etoposide, carboplatin and prednisone). G-CSF was administered during the intervals between chemotherapy until neutrophil reconstitution was achieved. Eighty-one per cent of the 93 eligible patients responded [95% confidence interval (CI), 71.1-88.1%], with 33 patients obtaining complete response (35.5%) and 42 obtaining partial response (45.2%). The median survival time (MST) after registration was 13 months and the median follow-up duration of the 20 surviving patients was 4.2 years (range 2.8-5.6). Overall survival at 2 years was estimated to be 31.3% (95% CI, 22.0-40.5%). Grade 4 haematological toxicity of neutropenia and thrombocytopenia were observed in 65.3% and 52.6% of the patients respectively, but grade 4 non-haematological toxicity was observed in only one patient. LSG15 is feasible with mild non-haematological toxicity and improved the clinical outcome of ATL patients. MST and overall survival at 2 years were superior to those obtained by our previous trials.

Adult↗
PubMed2001

Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis.

Derangement of either apoptosis or cell division is known to play an important role in tumorigenesis. Fas-mediated apoptosis on normal and leukaemic T cells is finely tuned by inhibitory proteins, such as FAP-1, FLIP and survivin, and defective caspase isoform which can attenuate the function of its intact caspase as a decoy molecule. However, complex involvement of such inhibitors in tumour biology relating to apoptotic pathology remains unclear in the neoplasms. We report the aberrant expression of FAP-1, FLIP and survivin mRNAs on leukaemic T cells from adult T-cell leukaemia (ATL) patients. Among these inhibitors, only survivin was aberrantly expressed in all ATL cases, but not in any normal peripheral blood mononuclear cells (PBMCs). Furthermore, survivin mRNA expression level was characteristic in each subtype of ATL and represented an important determinant for ATL prognosis. However, the apoptotic effector of casp-8, which is essential in Fas-mediated signal transduction, was dominant in defective casp-8 rather than intact casp-8 in ATL cells, suggesting a favourable biological situation for escape from apoptosis. Taken together, ATL cells probably possess many different regulatory mechanisms in order to attenuate Fas-mediated signalling and subsequently expand their populations under escape from apoptosis. Among these inhibitors, survivin is a useful bio-marker to assess tumour biology and may be a potential new target for apoptosis-based selective therapy in neoplasms as the expression is a general feature of neoplasia, but not normal tissues.

Apoptosis↗
PubMed2001

A complex role for the gamma-butyrolactone SCB1 in regulating antibiotic production in Streptomyces coelicolor A3(2).

Many streptomycetes produce extracellular gamma-butyrolactones. In several cases, these have been shown to act as signals for the onset of antibiotic production. Synthesis of these molecules appears to require a member of the AfsA family of proteins (AfsA is required for A-factor synthesis of the gamma-butyrolactone A-factor and consequently for streptomycin production in Streptomyces griseus). An afsA homologue, scbA, was identified in Streptomyces coelicolor A3(2) and was found to lie adjacent to a divergently transcribed gene, scbR, which encodes a gamma-butyrolactone binding protein. Gel retardation assays and DNase I footprinting studies revealed DNA binding sites for ScbR at - 4 to - 33 nt with respect to the scbA transcriptional start site, and at - 42 to - 68 nt with respect to the scbR transcriptional start site. Addition of the gamma-butyrolactone SCB1 of S. coelicolor resulted in loss of the DNA-binding ability of ScbR. A scbA mutant produced no gamma-butyrolactones, yet overproduced two antibiotics, actinorhodin (Act) and undecylprodigiosin (Red), whereas a deletion mutant of scbR also failed to make gamma-butyrolactones and showed delayed Red production. These phenotypes differ markedly from those expected by analogy with the S. griseus A-factor system. Furthermore, transcription of scbR increased, and that of scbA was abolished, in an scbR mutant, indicating that ScbR represses its own expression while activating that of scbA. In the scbA mutant, expression of both genes was greatly reduced. Addition of SCB1 to the scbA mutant induced transcription of scbR, but did not restore scbA expression, indicating that the deficiency in scbA transcription in the scbA mutant is not solely due to the inability to produce SCB1, and that ScbA is a positive autoregulator in addition to being required for gamma-butyrolactone production. Overall, these results indicate a complex mechanism for gamma-butyrolactone-mediated regulation of antibiotic biosynthesis in S. coelicolor.

4-Butyrolactone↗
PubMed2001

Lower abdominal phlegmon due to spontaneous rupture of an ileal neobladder.

A case is presented of spontaneous rupture of an ileal orthotopic neobladder due to a large residual urine volume. The present case is the 13th such case reported; however, this case is the first to show lower abdominal phlegmon and in which the perforation site was detected using computed tomography scanning. The indications for neobladder should be considered with great care. If spontaneous rupture is suspected, an early diagnosis of the perforation site and a measure of the extravasation volume using computed tomography are necessary. Appropriate treatment should include laparotomy.

Abdomen↗