Biomedical subjects

M Watanabe

Publications and source records attributed to M Watanabe.

At least 163 records · Page 9Linked to original sources

PubMed2002

Fine reconstruction of the pancreatic ductular system at the onset of pancreatitis.

The three-dimensional structure of the pancreatic ductular system (from the intercalated duct to the intercellular secretory canaliculus) is controversial and unclear. The aim of this study is to reveal the three-dimensional structure of the pancreatic ductular sysytem at the onset of pancreatitis. One day following rat pancreatic duct ligation, dilated lumina from the pancreatic ductular system were reconstructed by light microscopic and scanning electron microscopic examination of pancreatic tissue serial sections. The existence of the intra-acinar duct, which is formed only by centroacinar cells and interconnects the adjacent central lumina in an acinus, was demonstrated. The intercellular secretory canaliculi, which are the terminal parts of the pancreatic ductular system, anastomose and end blindly in the intercellular space located between adjacent lateral surfaces of the acinar cells. The intercalated ducts, the intra-acinar ducts, the central lumina, and the intercellular secretory canaliculi are arranged together in a complex connecting and branching system. However, there were no anastomoses found among the central lumina or acini.

Animals↗

PubMed2002

[Clinical analysis of surgically resected multiple primary lung cancer].

Synchronous and metachronous lung cancer is occasionally encountered. Frequency of the occurrence is increasing because of recent progress of imaging technique such as high resolution CT and CT based annual lung survey. We analyzed clinical characteristics of both synchronous and metachronous lung cancer treated surgically in our facility. There were 20 cases of multiple lung cancer cases, which is consisted of 12 synchronous multiple lung cancer cases and 8 metachronous lung cancer cases. Mean age was 62 years old and there were 14 male and 6 female cases. Among synchronous group, 8 cases have multiple shadow in ipsilateral hemithorax and 4 cases in both side. Surgery was carried out according to the extent of the disease and lung reserve. Associated cancer was diagnosed stage IA or IB in all cases. Five-year survival was 58.9%. Meanwhile, as regards to metachronous group, mean interval between first cancer and second cancer was 73 months. Seven cases have contralateral second primary lung cancer and one case has ipsilateral second primary lung cancer. In 3 cases, histology of the first and the second disease were different and in 5 cases that were the same. The first procedures were complete resection with systemic mediastinal LN dissection. The second procedures were determined based on the lung reserve. Pathological stage of the second disease were either stage IA or IB. There were no operative mortality and 5 years survival was 75%. Since there is no operative mortality and the outcome seems satisfactory when the patient has enough lung reserve, aggressive surgical resection should be considered in the case of multiple primary lung cancer. There is an increasing chance of synchronous multiple primary lung cancer because of improvement of imaging system. We have to prepare new therapeutic strategy for those patients.

Aged↗

PubMed2002

[A case of mitral regurgitation with a giant thrombus thought to be caused by anti-phospholipid syndrome].

A 58-year-old woman suffered from mitral valve regurgitation with a giant thrombus in right atrium was thought to be complicated by anti-phospholipid syndrome (APS). Positive anti-loops anti-coagulant and histories of cerebral infarction and miscarriage strongly indicated the diagnosis of APS. She underwent mitral valve replacement using bileaflet mechanical prosthetic value and removal of thrombus. She recovered uneventfully and strict anti-coagulation therapy has been continuing.

Antiphospholipid Syndrome↗

PubMed2002

[First successful clinical application of tissue engineered blood vessel].

With this tissue engineering (TE) technique, the peripheral pulmonary artery was successfully reconstructed, using the patient's own venous cells in a 4-year-old girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of single right ventricle, double-outlet right ventricle and pulmonary atresia. She underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at 2 years and a month old. She underwent again pulmonary artery angioplasty and Fontan operation at 3 years and 3 months. An angiographical examination 7 months after the operation revealed total occlusion of the right intermediate pulmonary artery. TE technique using autologous cells was indicated. The application of this procedure was approved by the ethical committee in Tokyo Women's Medical University. The patient's parents were thoroughly informed and signed a consent form. Approximately 2 cm of the peripheral vein was explanted under sterile conditions. The tissue was minced, placed in tissue culture dishes and cultured at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The number of cells substantially increased to reach 12 millions for almost a month. The culture medium was changed every 3 days. The polymer tube that served as a scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The number of seeded cells was approximately a million/cm2. The graft transplantation was performed 10 days after seeding cells. The occlusive right intermediate pulmonary artery was reconstructed with the TE vessel graft under extracorporeal circulation with a pump-oxygenator. The patient followed a satisfactory postoperative course. The postoperative angiography demonstrated that the graft was not constricted and dilated but that it preserved good patency. Long-term follow-up are necessary. We plan to continue to use the TE technique using autologous cells in the low pressure system like venous or pulmonary circulation. Because our results even in early experimental phase were valuable and promising, we believe that the TE approach may play an important role in the near future as an another alternative, together with transplantation and artificial organ, especially in the field of cardiovascular surgery that mostly needs replants.

Blood Vessel Prosthesis Implantation↗

PubMed2002

[Eleven cases of surgery for Marfan syndrome].

The surgical outcomes in 11 patients with a Marfan syndrome (mean [+/- SD] age, 32 +/- 16: range 0.5 to 60) were evaluated. Echocardiography demonstrated annuloaortic ectasia (AAE) in nine patients, mitral regurgitation (5 months baby: valve replaced) and abdominal aortic aneurysm in one each. Among 9 AAE, root were replaced in 8 patients and aortic valve was preserved only one patient. Our early-time result is encouraging in our valve-sparing operation.

Adolescent↗

PubMed2002

Runoff characteristics of nutrients from citrus fruit grove and its effects on water area.

In this study, field observations are carried out in order to make clear the runoff characteristics of pollutants from citrus fruit grove, especially nutrients such as nitrogen, phosphorus and other inorganic materials. Long-term observation in the test fields continued for more than 7 months and detailed observations during one rainfall are also carried out. From these observations, the following results are obtained. 1) Nitrogen concentration in grove soil leachate is usually in a range of 25 to 45 mgN/L, and the main component is nitrate, whereas phosphorus concentration is in a range of 0.1 to 0.8 mgP/L and the main component is phosphate. Concentration of nutrients is higher than that in environment around it. 2) Runoff loading rate of any materials from grove soil can be unified and expressed as a power function of the flow rate. In this case, runoff style of each material is characterized by the power coefficient beta x. 3) It is understood that the runoff characteristics are affected by the pH and rate of rainfall, and the ways of affecting the runoff characteristics are different in each material. 4) It is also suggested that detailed investigations are required to estimate the effect of pollutant runoff because the runoff characteristics are widely changed by the rainfall characteristics.

Agriculture↗

PubMed2002

[Expression of telomerase activity in thymoma and thymiccarcinoma tissues; a clinicopathological study].

BACKGROUND: Telomerase is a nucleoprotein complex that caps the physical termini of all eukaryotic chromosomes. It is suggested that telomerase play important roles in unlimited cell division acquisition of the malignant phenotype. We studied the relation of telomerase activity in thymoma and thymic carcinoma to the clinicopathological features of these lesions. METHODS: Tissue specimens were surgically resected from patients with thymoma and thymic carcinoma. Telomerase activity was evaluated according to a modified telomeric repeat amplification protocol (TRAP) assay. RESULTS: Telomerase activity was detected in all thymic epithelial tumors. The activity (mean +/- SD: unit/microgram.protein) in thymoma (n = 17) was significantly higher than that in thymic carcinoma (n = 7) [431.8 +/- 400.1 vs. 68.8 +/- 39.8: p < 0.01]. Telomerase activities in thymoma and thymic carcinoma were significantly higher than that in primary lung adenocarcinoma (33.5 +/- 39.2: n = 47), studied as control (p < 0.01). In patients with thymoma, telomerase activity did not correlate with tumor stage according to Masaoka classification (p = 0.776). In patients with thymic carcinoma, however, telomerase activity positively correlated with tumor stage (p = 0.02). In thymoma, telomerase activity positively correlated with the ratio of induced lymphocytes according to Rosai's classification (p = 0.045). CONCLUSION: In thymoma, telomerase activity reflects the presence of immature T-cell lymphocytes in tumor tissue rather than tumor stage or malignant phenotype. In thymic carcinoma, telomerase activity derived directly from cancer cells may relate to tumor stage.

Adenoma↗

PubMed2002

[Angina pectoris with a left atrial myxoma; report of a case].

A 78-year-old woman who had been diagnosed as left atrial myxoma and angina pectoris underwent simultaneous coronary artery bypass grafting (CABG) and resection of the left atrial myxoma. CABG was preceded by resection of myxoma to avoid systemic embolism of fragment of myxoma. Myocardial protection was secured by combination of antegrade and retrograde infusion of cardioplegia. The patient recovered well and discharged uneventfully.

Aged↗

PubMed2002

2-Nicotinamidoethyl nitrale (2-NN) protects myocardium in ischemia and reperfusion via the protein kinase C pathway.

BACKGROUND: Several recent studies have suggested an ATP-sensitive potassium channel opener (2-nicotinamidoethyl nitrate: 2-NN) may exert a protective effect against the myocardial ischemic/reperfusion injury. This study examines the effects of 2-NN on intracellular signaling by measuring intracellular cyclic AMP, cyclic GMP accumulation and protein kinase C (PKC) activity after 2-NN perfusion. METHODS: Ischemia/reperfused hearts were made by LAD occlusion for 30 min followed by 30 min of reperfusion in isolated rat hearts. Hearts were pre-perfused with 0.1 mM 2-NN, 100 nM Calphostin C, or 2-NN plus Calphostin C for 10 min prior to ischemia. The left ventricular function, cyclic AMP, cyclic GMP and LDH were examined to determine the effects of 2-NN on ischemic/reperfusion injury. Four separate groups of hearts were stained with a bisindolylmaleimide PKC inhibitor conjugated to fluorescein (fim, Teflabs) and PKC activity was measured. RESULTS: 2-NN reduced ischemia/reperfusion injury as evidenced by the enhanced myocardial functional recovery, decreased LDH release after reperfusion, and decreased reperfusion arrhythmias. The PKC inhibitor attenuated myocardial functional recovery but not reperfusion arrhythmias. Cyclic AMP levels decreased after 10 min of 2-NN perfusion, compared to controls. We observed an increase in PKC activity after 2-NN treatment. CONCLUSIONS: These results suggest that PKC plays a significant role in the cardioprotective effect of 2-NN on ischemic and reperfused myocardium. The anti-arrhythmic effect of 2-NN in the reperfusion phase may be linked its action on the ATP-sensitive potassium channel itself rather than its effect on PKC activity.

Animals↗

PubMed2002

Monitoring of shallow sea environment by using snapping shrimps.

We examine the validity of pulse count of snapping shrimps for sea environmental monitoring. Snapping shrimps, which make a peculiar pulse sound, are found everywhere in the world. Pulse count can be achieved merely by recording their sounds for a few minutes by using a hydrophone without special biological knowledge. From field surveys and laboratory experiments, we found that the pulse count depends on water temperature when sea environment is normal, and it falls due to the occurrence of oxygen-deficient water. The results show that this method can be a useful index of the effect of water pollution on benthic animals in fixed-point observation.

Acoustics↗

PubMed2001

Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development.

Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor delta2 subunit (GluRdelta2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluRdelta2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluRdelta2 mutant PCs were associated with voltage-dependent Ca(2+) signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca(2+) signals involved both proximal and distal dendrites. Morphologically, CFs of GluRdelta2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wild-type and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluRdelta2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluRdelta2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.

Aging↗

PubMed2001

Apoptosis is required for the proper formation of the ventriculo-arterial connections.

The role of apoptosis in cardiac morphogenesis has not been directly tested. Cardiomyocyte apoptosis is prevalent during the remodeling of the embryonic chicken cardiac outflow tract (OFT) in the transition from a single to a dual circulation. We tested the hypothesis that OFT cardiomyocyte apoptosis drives the shortening and rotation of the embryonic cardiac OFT and is required to achieve the mature ventriculo-arterial configuration. Chick embryos were treated with the peptide Caspase inhibitors zVAD-fmk or DEVD-cho at HH stages 15-20 (looped heart). Morphology of control and experimental embryos was assessed at HH stage 35, at which time the control hearts have developed a dual circulation. Infection of the hearts with a recombinant adenovirus expressing green fluorescent protein was used to follow the fate of the OFT cardiomyocytes. Affected embryos displayed abnormal persistence of a long infundibulum (OFT myocardial remnant) beneath the great vessels, indicating failure of OFT shortening. In some instances, the infundibulum connected both great vessels to the right ventricle in a side-by-side arrangement with transposition of the aorta, indicating a failure of rotation of the OFT, and modeling human congenital double outlet right ventricle. Defects were also observed at other sites in the heart where apoptosis is prevalent, such as in the formation of the cardiac valves and trabeculae. To more specifically target the apoptosis of the OFT cardiomyocytes, recombinant adenovirus was used to express the X-linked inhibitor of apoptosis protein in these cells. This resulted in an effect on outflow tract shortening and rotation similar to that of the peptide inhibitors, while the effects on the other cardiac structures were not observed. These results demonstrate that elimination of OFT cardiomyocytes by apoptosis is necessary for the proper formation of the ventriculo-arterial connections, and suggest apoptosis as a potential target of teratogens and genetic defects that are associated with congenital human conal heart defects.

Animals↗

PubMed2001

Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity.

Recognition of altered self-antigens in tumor cells by lymphocytes forms the basis for antitumor immune responses. The effector cells in most experimental tumor systems are CD8(+) T cells that recognize MHC class I binding peptides derived from molecules with altered expression in tumor cells. Although the need for CD4(+) helper T cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumor responses remain unclear. We examined whether broadly expressed wild-type molecules in murine tumor cells eliciting humoral immunity contributed to the generation of CD8(+) T cells and protective antitumor immune responses to unrelated tumor-specific antigens [mutated ERK2 (mERK2) and c-erbB2/HER/neu (HER2)]. The immunogenic wild-type molecules, presumably dependent on recognition by CD4(+) helper T cells, were defined by serological analysis of recombinant cDNA expression libraries (SEREX) using tumor-derived lambda phage libraries screened with IgG antibodies of hosts bearing transplanted 3-methylchoranthrene-induced tumors. Coimmunization of mice with plasmids encoding SEREX-defined murine wild-type molecules and mERK2 or HER2 led to a profound increase in CD8(+) T cells specific for mERK2 or HER2 peptides. This heightened response depended on CD4(+) T cells and copresentation of SEREX-defined molecules and CD8(+) T cell epitopes. In tumor protection assays, immunization with SEREX-defined wild-type molecules and mERK2 resulted in an inhibition of pulmonary metastasis, which was not achieved by immunization with mERK2 alone.

Animals↗

PubMed2001

Preferential expression of an intact WRN gene in Werner syndrome cell lines in which a normal chromosome 8 has been introduced.

Werner syndrome (WS) is a premature aging syndrome caused by mutations in the WRN gene. All mutations of the WRN gene reported thus far are predicted to produce the truncated WRN proteins. The mRNAs that contain chain-termination mutations are supposed to be unstable due to degradation by nonsense-mediated mRNA decay (NMD). In the present study, we investigated the expressions of intact and nonsense-mutated WRN genes in Werner syndrome cell lines in which a normal chromosome 8 had been introduced by microcell fusion. We demonstrate here that the expression of the mutated WRN gene that produces nonsense mRNAs remains at low levels, resulting in the preferential expression of the intact WRN gene in the WS microcell hybrids. This result supports the idea that imperfect messages containing premature termination codons are eliminated by the RNA surveillance system, suggesting the significance of the NMD mechanism in the etiology of Werner syndrome.

Cell Line↗

PubMed2001

Opposing effects of anti-activation-inducible lymphocyte-immunomodulatory molecule/inducible costimulator antibody on the development of acute versus chronic graft-versus-host disease.

The functional role of inducible costimulator (ICOS)-mediated costimulation was examined in an in vivo model of alloantigen-driven Th1 or Th2 cytokine responses, the parent-into-F(1) model of acute or chronic graft-vs-host disease (GVHD), respectively. When the Ab specific for mouse ICOS was injected into chronic GVHD-induced mice, activation of B cells, production of autoantibody, and development of glomerulonephritis were strongly suppressed. In contrast, the same treatment enhanced donor T cell chimerism and host B cell depletion in acute GVHD induced host mice. Blocking of B7-CD28 interaction by injection of anti-B7-1 and anti-B7-2 Abs inhibited both acute and chronic GVHD. These observations clearly indicate that the costimulatory signal mediated by CD28 caused the initial allorecognition resulting in the clonal expansion of alloreactive T cells, whereas the costimulatory signal mediated by ICOS played a critical role in the functional differentiation and manifestation of alloreactive T cells. Furthermore, treatment with anti-ICOS Ab selectively suppresses Th2-dominant autoimmune disease.

Acute Disease↗

PubMed2001

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Adolescent↗

PubMed2001

Control of methanol oxidation by ionic behavior in supercritical water.

In supercritical water the rate of methanol oxidation was controlled by ionic behavior as follows: the oxidation rate of methanol decreased with increasing proton and hydroxide ion concentration, possibly due to stabilization of the reactant, while that of CO was suppressed by added protons and enhanced by added hydroxide ions.

Journal Article↗

PubMed2001

Characterization of expressed genes in the SLL2 region of self-compatible Arabidopsis thaliana.

Self-incompatibility in Brassica species is regulated by a set of S-locus genes: SLG, SRK, and SP11/SCR. In the vicinity of the S-locus genes, several expressed genes, SLL2 and SP2/ClpP, etc., were identified in B. campestris. Arabidopsis thaliana is a self-compatible Brassica relative, and its complete genome has been sequenced. From comparison of the genomic sequences between B. campestris and A. thaliana, microsynteny between gene clusters of Arabidopsis and Brassica SLL2 regions was observed, though the S-locus genes, SLG, SRK, and SP11/SCR were not found in the region of Arabidopsis. Almost all genes predicted in this region of Arabidopsis were expressed in both vegetative and reproductive organs, suggesting that the genes in the SLL2 region might not be related to self-incompatibility. Considering the recent speculation that the S-locus genes were translocated as a single unit between Arabidopsis and Brassica, the translocation might have occurred in the region between the SLL2 and SP7 genes.

Arabidopsis↗