American Gastroenterological Association. Our new president--Jon I. Isenberg, M.D.
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Gastroenterology↗
Biomedical subjects
T Yamada
Publications and source records attributed to T Yamada.
Apoptosis and p53 status predict the efficacy of postoperative administration of UFT in non-small cell lung cancer.
To examine whether efficacy of postoperative oral administration of UFT, a 5-fluorouracil derivative chemotherapeutic agent, may be influenced by incidence of apoptosis (apoptosis index) or apoptosis-related gene status (p53 and bcl-2) of the tumour, a total of 162 patients with pathologic stage I non-small cell lung cancer were retrospectively reviewed. UFT was administrated postoperatively to 44 patients (UFT group), and not to the other 118 patients (Control group). For all patients, 5-year survival rate of the UFT group (79.9%) seemed higher than that of the Control group (69.8%), although without significant difference (P = 0.054). For patients with higher apoptotic index, 5-year survival rate of the UFT group (83.3%) was significantly higher than that of the Control group (67.6%, P = 0.039); for patients with lower apoptotic index, however, there was no difference in the prognosis between these two groups. Similarly, UFT was effective for patients without p53 aberrant expression (5-year survival rates: 95.2% for the UFT group and 74.3% for the Control group, P = 0.022), whereas not effective for patients with p53 aberrant expression. Bcl-2 status did not influence the efficacy of UFT. In conclusion, apoptotic index and p53 status are useful factors to predict the efficacy of postoperative adjuvant therapy using UFT.
Antineoplastic Combined Chemotherapy Protocols↗
In vitro melanin binding of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist.
Characteristics of the in vitro binding of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, CAS 137431-04-0) to synthetic melanin were determined and compared with those of other drugs. At all the drug concentrations tested (12.5-200 mumol/l), chloroquine (CAS 54-05-7) had the highest melanin binding (%), followed by ofloxacin (CAS 82419-36-1), NS-49, norephedrine (CAS 154-41-6) and diazepam (CAS 439-14-5). Binding constants (Kb), calculated with the Langmuir adsorption isotherm were, in the order (largest to smallest) chloroquine, ofloxacin, NS-49, norephedrine, the Kb value for NS-49 being one-thirteenth that for chloroquine, one-seventh that for ofloxacin and ten times higher than that for norephedrine. 53% of NS-49 that was bound to synthetic melanin dissociated during 24 h of incubation after the binding experiment. The percent of dissociation for NS-49 was higher than the values for chloroquine (5%) and ofloxacin (39%). After 1 day incubation in the dissociation experiment, the amount of NS-49 bound per mg of melanin was 23 nmol, being less than the amounts of chloroquine (210 nmol) and ofloxacin (78 nmol). These findings indicate that NS-49 has a lower affinity for synthetic melanin than chloroquine and ofloxacin, which have high affinities and therefore accumulate in melanin containing ocular tissues.
Adrenergic alpha-Agonists↗
Effect of YM-40461, a novel surfactant secretagogue, on chronic obstructive pulmonary diseases and similar symptoms in guinea pigs.
YM-40461 (1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea, CAS 142912-85-4), is a novel surfactant secretagogue. The effect of YM-40461 on symptoms, e.g. change of airway functions and hypoxemia, were examined using guinea pigs with induced subacute bronchitis. Bronchitic guinea pigs exhibited basal lung resistance (RL) was 0.152 +/- 0.005 cm H2O/ml/s (normal: 0.130 +/- 0.002 cm H2O/ml/s) and basal lung compliance (CL) of 0.455 +/- 0.011 ml/cm H2O (normal: 0.509 +/- 0.009 ml/cm H2O). Although YM-40461 slightly improved the lung resistance in these animals, it improved significantly and dose-dependently the lung compliance (0.468 +/- 0.008 ml/cm H2O for 1 mg/kg, 0.477 +/- 0.008 for 3 mg/kg, 0.490 +/- 0.011 for 10 mg/kg, p < 0.05 at 10 mg/kg) compared to nontreated bronchitic guinea pigs. YM-40461 improved airway functions in bronchitic guinea pigs just as wall as the beta 2-adrenoceptor agonist salbutamol. Additionally, YM-40461 significantly reduced airway hyperreactivity in response to intravenously infused acetylcholine (ACh). Basal PaO2 was 83.1 +/- 0.7 cm H2O in healthy guinea pigs and 71.2 +/- 1.7 cm H2O in bronchitic guinea pigs, indicating hypoxemia. A dose of 10 mg/kg of YM-40461 relieved hypoxemia in these animals with the values returning to 81.8 +/- 1.9 cm H2O (p < 0.05). These results suggest that YM-40461 ameliorates chronic obstructive pulmonary disease (COPD)-like symptoms in bronchitis models due to increased surfactant in the airway.
Acetylcholine↗
Recurrent pregnancy loss: etiology of thrombophilia.
Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.
Abortion, Habitual↗
Polysomnographic assessment of spells in sleep: nocturnal seizures versus parasomnias.
A dilemma can arise when attempting to distinguish a nocturnal seizure from a parasomnia because both phenomena can be characterized by a general increase in motor and autonomic activity with a transient reduction in the level of consciousness. An additional problem is that an accurate clinical diagnosis generally relies heavily on a detailed history. As sleep related disorders occur at a time when the patient is not fully cognizant, polysomnographic analysis can on occasion supplement for the intrinsic paucity of detailed history. Simultaneously, correlating the clinical and polysomnographic analysis immediately prior to, during, and following an event of interest, can be helpful in differentiating nocturnal seizures from parasomnias.
Adult↗
Retortamonas intestinalis in the pancreatic juice of a patient with small nodular lesions of the main pancreatic duct.
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Animals↗
Identification of sinus node dysfunction by use of P-wave signal-averaged electrocardiograms in paroxysmal atrial fibrillation: a prospective study.
BACKGROUND: In patients with paroxysmal atrial fibrillation (Paf), the identification of the coexistence of sinus node dysfunction (SND) has therapeutic implications. This study sought to prospectively determine whether SND in patients with Paf would be identified by use of atrial early potential (EP), low-amplitude potentials early in signal-averaged P wave. METHODS: The study population consisted of 149 patients with Paf. Signal-averaged electrocardiography was recorded with the P-wave-triggering technique. The root mean square voltage for the initial 30 MS and the duration of initial low-amplitude signals < 4 microV of signal-averaged P wave were measured in the vector magnitude. The criteria of EP were defined as "the root mean square voltage for the initial 30 MS < 3.0 microV and the duration of initial low-amplitude signals < 4 microV >22 MS." SND was diagnosed by use of the conventional 12-lead electrocardiography, 24-hour Holter monitoring, and bedside electrocardiographic monitoring. RESULTS: Thirty-eight of 149 patients with Paf had EP. Eighteen (47%) of 38 patients with Paf and EP had SND, whereas SND was found in only 5 (5%) of the other 111 patients with Paf without EP (P <.0001). EP gave a sensitivity of 78% and a specificity of 84% for the detection of SND in patients with Paf. CONCLUSION: EP would be useful for the identification of SND in patients with Paf.
Aged↗
MR imaging and thermography of facial angioedema: a case report.
Magnetic resonance imaging and thermography were performed in a 67-year-old man with idiopathic facial angioedema. Thermography suggested decreased heat emission in the region of the angioedema. Magnetic resonance imaging revealed diffuse high intensity in the subcutaneous interstitial tissue and dilated veins on T2-weighted images. Marked contrast enhancement was noted in the subcutaneous tissue on postcontrast T1-weighted images.
Aged↗
Does pleural lavage cytology before thoracic closure predict both patient's prognosis and site of cancer recurrence after resection of esophageal cancer?
BACKGROUND: Operative manipulation occasionally exfoliates and spreads cancer cells in the surgical field, and it is a matter of concern whether the exfoliated cancer cells actually affect the patient's prognosis and sites of cancer recurrence. METHODS: In 240 patients with esophageal cancers, lavage cytology (LC) of the right pleural cavity was performed before and after esophageal resection combined with regional lymphadenectomy. The cytologic results were compared with the pathologic factors associated with cancer extension, postoperative survival, and cause of surgical failure. RESULTS: Only 3 patients (1.3%) were LC positive before resection. Of the 237 LC-negative patients, LC was also negative after resection in 215 patients (90.7%) (LC-/-), but LC became positive after resection in 22 patients (9.3%) (LC-/+). The 3-year survival rate was 0% in the LC-/+ group versus 65% in the LC-/- group, and the median survival rates were 10.9 months and 25.0 months, respectively (P <.0001). Multivariate analysis revealed that LC-/+ was an independent prognostic factor (P =.0331), along with nodal involvement and depth of cancer invasion. However, there were no significant differences in the sites of cancer recurrence between the 2 groups. Only 1 patient was found to develop the first recurrence in the pleural cavity. The LC-/+ group had a higher incidence of bulky lymph-node metastasis (P =.0009). CONCLUSIONS: Pleural LC after resection of esophageal cancer seems to be a prognostic indicator of overall recurrence, but not necessarily in the pleural cavity. Patients with a positive LC after resection may benefit most by effective systemic adjuvant chemotherapy.
Adult↗
Expression and clinical significance of the erbB family in intrahepatic cholangiocellular carcinoma.
The type I family of growth factor receptors is known to play a role in the development of several carcinomas, but its role in hepatic malignancies is not clearly understood. In this study we investigated the expression of this family of EGF-R, c-erbB-2, c-erbB-3 and c-erbB-4 in 38 intrahepatic cholangiocellular carcinomas (CCC) by means of immunohistochemistry. EGF-R expression was related to lymph node metastasis, aberrant p53 expression, proliferating activity, and carcinoma differentiation. c-erbB-2 expression was observed in more than 50% of the cases, but was not related to any clinicopathological features, c-erbB-3 expression was linked to lymph node metastasis, and c-erbB-4 expression was directly related to proliferating activity and lymph node metastasis. These results indicate that: 1) EGF-R contributes greatly to CCC progression, and c-erbB-3 and c-erbB-4 have roles similar to but less than that of EGFR, and 2) c-erbB-2 is expressed in CCC in high incidence, but its clinical role in CCC remains unclear.
Bile Duct Neoplasms↗
Chromosomal mapping of calmodulin 1 (CALM1) and alpha-globin 1 genes (HBA1) in the bovine.
Chromosomal mapping of the bovine calmodulin 1 and alpha-globin 1 genes was performed by analyzing bovine/murine somatic cell hybrid DNAs with PCR using primers specific for 3'-untranslated regions of those bovine genes. The calmodulin 1 and alpha-globin 1 genes were assigned to bovine chromosomes 25 and 29, respectively. Results from the present study should contribute to improvement in map resolution of bovine chromosomes and increase comparative information available on bovine chromosomes.
Alpha-Globulins↗
Counteracting regulation of chromatin remodeling at a fission yeast cAMP response element-related recombination hotspot by stress-activated protein kinase, cAMP-dependent kinase and meiosis regulators.
In fission yeast, an ATF/CREB-family transcription factor Atf1-Pcr1 plays important roles in the activation of early meiotic processes via the stress-activated protein kinase (SAPK) and the cAMP-dependent protein kinase (PKA) pathways. In addition, Atf1-Pcr1 binds to a cAMP responsive element (CRE)-like sequence at the site of the ade6-M26 mutation, which results in local enhancement of meiotic recombination and chromatin remodeling. Here we studied the roles of meiosis-inducing signal transduction pathways in M26 chromatin remodeling. Chromatin analysis revealed that persistent activation of PKA in meiosis inhibited M26 chromatin remodeling, suggesting that the PKA pathway represses M26 chromatin remodeling. The SAPK pathway activated M26 chromatin remodeling, since mutants lacking a component of this pathway, the Wis1 or Spc1/Sty1 kinases, had no M26 chromatin remodeling. M26 chromatin remodeling also required the meiosis regulators Mei2 and Mei3 but not the subsequently acting regulators Sme2 and Mei4, suggesting that induction of M26 chromatin remodeling needs meiosis-inducing signals before premeiotic DNA replication. Similar meiotic chromatin remodeling occurred meiotically around natural M26 heptamer sequences. These results demonstrate the coordinated action of genetic and physiological factors required to remodel chromatin in preparation for high levels of meiotic recombination and eukaryotic cellular differentiation.
Cell Differentiation↗
Primary synovial sarcoma of the lung: a case report confirmed by molecular detection of SYT-SSX fusion gene transcripts.
We report a rare case of primary synovial sarcoma of the lung. The patient was a 49-year-old woman who presented with a well-defined oval-shaped mass in the left upper lobe on a chest radiograph. A malignant pulmonary tumor was suspected and consequently a left upper lobectomy was performed. Grossly, the tumor measured 5 x 4 cm, was whitish-yellow in color and soft in consistency. Histologically, the tumor showed a dense proliferation of short spindle cells, partly arranged in interlacing fascicles. In some areas a hemangiopericytoma-like pattern, stromal myxoid change and necrosis of various sizes were noted. Numerous mitotic figures were also seen. Immunohistochemically, the tumor cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. As these features suggested a monophasic fibrous type of synovial sarcoma, we examined for the presence of SYT-SSXfusion gene transcripts using RNA samples from the frozen tumor tissue. A reverse transcription polymerase chain reaction amplified a single 583-base pair fragment characteristic of synovial sarcoma. As no other tumorous lesions were found during a follow-up period of 1 year, primary synovial sarcoma of the lung was our final diagnosis. This tumor should be considered in the differential diagnosis of round to short spindle cell tumors arising in the lung.
Female↗
A variable region on the chlorovirus CVK2 genome contains genes possibly involved in the host range determination.
A 22.6-kbp variable region near the left end of the chlorovirus CVK2 genome which was characterized. This region contained a tandem array of 5 gene copies for Vp260-like protein, a viral surface glycoprotein. The authentic 104-kDa Vp260 was encoded at another site on the genome and contained 13 internally located, tandem repeats of 61-65 amino acids like the prominent Rickettsia surface antigen. By Northern and Western blot analyses, these genes were demonstrated to be expressed late in infection and the proteins were incorporated into virions. These results implied that the extra copies of Vp260-like proteins may be involved in host range in the natural environment.
Gene Dosage↗
Regulatory mechanism of the gene expression during chlorovirus infection cycle.
In chlorovirus infection, immediate-early gene expression occurs within 5-20 min post infection (p.i.). We identified 16 major immediate-early transcripts. On Northern blot analysis, these transcripts showed unusual behaviors: (I) after 40 min p.i., their sizes reduced by approximately 100 nt, most likely caused by loss of a poly(A) tail and (II) after 40 min p.i., often appeared a few larger additional transcripts that may be formed by read-through from an upstream gene or into a downstream gene. These results indicate that the transcription of the viral genes changes drastically between before and after 40 min p.i.
Chlorella↗
Facile induction of apoptosis into plant cells associated with temperature-sensitive lethality shown on interspecific hybrid from the cross Nicotiana suaveolens x N. tabacum.
Two lines of suspension culture cells were obtained from a hybrid seedling of Nicotiana suaveolens Lehm. x N. tabacum L. cv. Hicks-2 expressing temperature-sensitive lethality. One of them (LH line) was inducible cell death in accordance with the lethality at 28 degrees C but not under high-temperature conditions (36 degrees C). Another one (SH line) lost the lethality and survived at 28 degrees C. The cells of LH line showed apoptotic changes when they were cultured at 28 degrees C. Fragmentation of nuclei was correlated with the lethality in the cells, as confirmed by fluorimetry of the nuclear DNA using laser scanning cytometry. Agarose gel analysis of DNA extracted from the cells expressing the lethality revealed a specific ladder pattern suggesting nucleosomal fragmentation that is one of the biochemical characteristics of apoptosis. From these facts, we confirmed that the process of cell death leading to hybrid lethality in the cells is certainly apoptosis. Hybrid cells were used in the experiments to estimate the point of no return in temperature-sensitive lethality and to examine the influence of cation in DNA fragmentation during apoptosis. The utility of hybrid cells as an experimental system for studies of hybrid lethality and apoptosis in plants was confirmed.
Apoptosis↗
Isolation of the protease component of maize cysteine protease-cystatin complex: release of cystatin is not crucial for the activation of the cysteine protease.
The maize cysteine protease complex, which required SDS for its activation in vitro, is a 179 kDa trimeric complex (P-I)3 of a cysteine protease (P) [EC 3.4.22] and a cysteine protease inhibitor (I), cystatin [Yamada et al. (1998) Plant Cell Physiol. 39: 106, Yamada et al. (2000) Plant Cell Physiol. 41: 185]. Here, we show the mechanism of the SDS-dependent activation of the trimeric (P-I) complex and stabilization of the activated protease by its specific substrates. The cystatin-free cysteine protease isolated by preparative SDS-PAGE was still specifically activated by SDS, and its profile of SDS-dependency was exactly the same as that of the trimeric (P-I) complex. It is, therefore, evident that an SDS-dependent conformational change of the protease itself, rather than the release of cystatin from the complex, is crucial for the activation. Pre-treatment analysis with SDS revealed that SDS was required for the initiation of the activation of the trimeric (P-I) complex. Furthermore, we found that once the protease was activated, if there was no substrate, it was rapidly inactivated under optimum conditions of proteolysis, and showed that such inactivation was not due to autolysis of the protease. In contrast, addition of specific substrates prevented the inactivation, and thus we presumed that the activity of the cysteine protease is regulated by both activation by conformational change and rapid inactivation after consumption of substrates.
Cystatins↗