Search for neutrino-induced low-energy-electron-event clusters in Kamiokande-II.
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Biomedical subjects
Publications and source records attributed to T Ishida.
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Adenocarcinoma of the lung obtained at surgical resection was examined for mutation at codons 12, 13, and 61 of the oncogenes K-ras, H-ras, and N-ras, using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in 18 of the 115 cases (15.7%), and 15 of 18 were at codon 12, 2 were at codon 13 of K-ras, and 1 was at codon 61 of N-ras. G to T transversions were most common. The ras gene mutations were more frequent in the male patients (P = 0.0048). No significant differences were found to be related to stage of the disease or tumor-nodes-metastases classification between positive and negative groups of the ras gene mutations. A history of tobacco use was not always a factor contributing to mutation. Of the completely resected group without lymph node metastasis, the 5-year survival rate in the ras-positive group was 53.3%, which was significantly poorer than the 83.6% survival rate in the ras-negative group (P less than 0.05). Our findings suggest that ras gene mutations may be prognostic, especially in the early stage adenocarcinoma of the lung.
The crystal structure of acidic phospholipase A2 from the venom of Agkistrodon halys blomhoffii has been determined by molecular replacement methods based on the known structure of Crotalus atrox PLA2, a same group II enzyme. The overall structures, except the calcium-binding regions, are very similar to each other. A calcium ion is pentagonally ligated to two carboxylate oxygen atoms of Asp-49 and each carbonyl oxygen atoms of Tyr-28, Gly-30 and Ala-31. A reason why the former enzyme functions as monomeric form, while the latter one does as dimer, could be presumed by the structural comparison of these calcium-binding regions. Although Gly-32 is usually participated as a ligand in the coordination with calcium ion in group I PLA2, it is characteristically replaced to Ala-31 in the present structure, and thus the coordination geometry of calcium ion is rather different from the usually observed one.
ECG-gated spin-echo imaging (ECG-SE) can reduce physiological motion artifacts. However, ECG-SE does not provide strong T1-weighted images because repetition time (TR) depends on heart rate (HR). We investigated the usefulness of low flip angle spin-echo imaging (LFSE) in obtaining more T1-dependent contrast with ECG gating. in computer simulation, the predicted image contrast and signal-to-noise ratio (SNR) obtained for each flip angle (0-180 degrees) and each TR (300 msec-1200 msec) were compared with those obtained by conventional T1-weighted spin-echo imaging (CSE: TR = 500 msec, TE = 20 msec). In clinical evaluation, tissue contrast [contrast index (CI): (SI of lesion-SI of muscle)2*100/SI of muscle] obtained by CSE and LFSE were compared in 17 patients. At a TR of 1,000 msec, T1-dependent contrast increased with decreasing flip angle and that at 38 degrees was identical to that with T1-weighted spin-echo. SNR increased with the flip angle until 100 degrees, and that at 53 degrees was identical to that with T1-weighted spin-echo. CI on LFSE (74.0 +/- 52.0) was significantly higher than CI on CSE (40.9 +/- 35.9). ECG-gated LFSE imaging provides better T1-dependent contrast than conventional ECG-SE. This method was especially useful for Gd-DTPA enhanced MR imaging.
Fluorescence and 1H-NMR spectroscopic experiments on the interaction of guanine base with cytosine base and Trp indole ring using the model compounds have shown the first clear-cut evidence that both of the hydrogen-bond pairing and aromatic stacking interactions, which are recognized as important forces for the strict molecular recognition, do not function independently, but highly help each other for the recognition of guest molecule.
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The purpose of this study was to elucidate a possible immune response to tumor cells mediated by tumor-infiltrating lymphocytes (TIL) in lung cancer. In flow cytometry, the majority of T-cells of TIL were CD45RA-, CD45RO+, and CDw29high, and expressed HLA-DR. The expression of interleukin 2 receptor beta chain increased in both CD4+ and CD8+ TIL compared with both types of T-cells in peripheral blood. These results indicate that the major population of TIL is activated memory T-cells. The TIL preparation, which was usually contaminated with 5 to 10% tumor cells, did not exhibit any response in autologous mixed lymphocyte-tumor culture even in the presence of interleukin 2 (IL-2) in all five cases tested. Although purified T-cells from TIL showed the positive response in only 1 of 10 cases tested without addition of IL-2, it occurred in 7 of 10 cases in the addition of a low concentration of IL-2. The IL-2-dependent response to irradiated autologous tumor cells was suppressed when nonirradiated autologous tumor cells were added to the culture. Culture supernatants of four lung cancer cell lines and freshly prepared lung cancer cells obtained from 6 cases exhibited suppressive activity against anti-CD3 antibody-induced mitogenesis of peripheral blood mononuclear cells from healthy donors. We suggest that, taken together, (a) the major population of TIL in lung cancer are activated memory T-cells, and they include tumor-reactive ones, and that (b) the function of the TIL is impaired by unavailability of IL-2 and/or by suppression due to lung cancer cell-derived factor(s).
In order to investigate the conformational variation of ascidiacyclamide, a cytotoxic cyclic peptide from marine tunicate Ascidian, single crystals were prepared from ethanol and aqueous ethanol solutions as its free form (crystal I) and H2O/0.5 C2H5OH solvate (crystal II), respectively, and were determined by the x-ray diffraction method. Crystal I showed a pseudo C2-symmetric saddle-shaped rectangular conformation. Similar conformations were also observed in crystal II, where there were two crystallographically independent C2-symmetric molecules (named Mol-A and -B) per asymmetric unit. Mol-A and -B included H2O and H2O/C2H5OH solvents within their ring structures, respectively. These water and ethanol molecules were located on the crystallographic dyad axes, and were stabilized by the van der Waals contacts (including hydrogen bonds) with the polar-ring N atoms and nonpolar D-Val side-chain atoms. The conformational characteristics of ascidiacyclamide and its fluctuation/variation were discussed based on the present and previously reported x-ray results.
Effects of hyperthermia on the intracellular calcium concentration (Cai) of an established mouse breast cancer cell line, MMT060562, were studied using fura-2 fluorescence microscopy and the whole-cell clamp technique. A sudden change of temperature from 37 to 45 degrees C induced a transient increase in the fluorescence ratio permeability of the cell membrane and inward current. Deletion of extracellular calcium abolished the fluorescence ratio response to the rise in temperature. Cai of some cells increased after hyperthermia treatment at 44-48 degrees C for 20 min, but the average increase of Cai was negligible. After hyperthermia treatment, spontaneous oscillation of Cai, chemical responses to ATP and bradykinin and the mechanically-induced spreading response diminished. However, the mechanically induced increase of Cai within the stimulated cell remained even after hyperthermia treatment. Suppression of the ATP-induced Cai response recovered to about half the original level within 12 h. Blockage of protein synthesis with cycloheximide (100 microM) had no effect on the recovery. The D-myo-inositol 1,4,5-triphosphate (IP3)-dependent increase of Cai remained intact even after hyperthermia treatment. It is concluded that hyperthermia treatment increases both the permeability of the cell membrane and Cai, but decreases the sensitivity of cells to ATP and bradykinin, presumably due to modification of the signal transduction mechanism.
Human Zn-alpha 2-glycoprotein (ZAG) in plasma samples from twelve populations was tested by immunoblotting after polyacrylamide gel isoelectric focusing. Eleven ZAG phenotypes produced by one common and nine rare alleles, including five new ones (ZAG*6-ZAG*10), were detected. Additionally, an application of separator IEF with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) was found to be useful for discriminating the rare ZAG 7 band.
Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 bp long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 +/- 0.7 million years (Myr) ago and human 4.7 +/- 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr.
Preoperative chemotherapy before limb-sparing surgery for osteosarcoma is used to reduce the size of the tumour, facilitate removal and prevent distant metastases. Fifteen patients with osteosarcoma were treated with six different protocols. Assessment of the clinical and radiological size of the lesion, of the histology of the resected specimen and of serum alkaline phosphatase levels were done. Greatest control of the tumour was obtained with the intravenous use of cisplatin, three times at intervals of three weeks before surgery, compared to the use of adriamycin or methotrexate in other protocols. Prompt surgery after preoperative chemotherapy and postoperative chemotherapy are advised.
A clinicopathological and immunohistochemical study of 12 cases of osteofibrous dysplasia (OFD), two cases of differentiated adamantinoma, and five cases of adamantinoma of long bones is presented. Although OFD and differentiated adamantinoma showed similar radiologic findings, differentiated adamantinoma was more likely to be a recurrent lesion than osteofibrous dysplasia and seemed to require a more extensive surgical procedure. Immunohistochemically, cytokeratin- and vimentin-positive cells were seen in both OFD and differentiated adamantinoma. The positive cells were scattered in the former, and were both scattered and nest-like in the latter. Both these lesions, however, were negative for epithelial membrane antigen. Excluding two cases of Ewing-like adamantinoma, the other three cases of adamantinoma were also positive for cytokeratin and vimentin. These results suggest that these three lesions share the same histogenetic origin. The two cases of Ewing-like adamantinoma differ from tibial adamantinoma in their radiological, histological and immunohistochemical aspects, and seem to constitute a distinct variant of adamantinoma with a different histogenesis.
A case of adamantinoma of the humerus with Ewing-like pathological features has been reported. In addition to the unusual pathological features, the apparently juxtacortical location of the lesion is of great interest--also a highly unusual feature for an adamantinoma.
Eight epithelioid sarcomas (ES) were studied by electron microscopy, immunohistochemistry, and DNA flow cytometry. Ultrastructurally, the tumour cells showed desmosome-like intercellular junctions and numerous microvilli, in addition to whorled arrangements of intermediate filaments. Tumour cells were positive for epithelial membrane antigen, cytokeratin, and vimentin, and negative for carcinoembryonic antigen and desmin. All seven cases examined by flow cytometry showed diploid or hyperploid (near diploid) DNA content. This seems to correspond to the relatively long clinical course and low-grade malignant nature of ES. Although the histogenesis of ES is still uncertain, the results of this study suggest that it is a tumour of primitive mesenchymal cells with the capacity to show epithelial differentiation.
Twenty-two patients, 40 years old or younger, were surgically treated for lung cancer between 1974 and 1989. The male to female ratio was 1.2:1. Ten patients were symptomatic, with the average duration of symptoms being 3.6 months. There were 13 patients with adenocarcinoma and 9 patients with large cell carcinoma. In terms, of postoperative stages, 5 patients were classified in stage I, 10 in stage IIIa, 5 in stage IIIb, and 2 in stage IV. Complete resection was performed in 14 patients, incomplete resection in 6, and exploratory thoracotomy in 2. The 3-year survival rate after complete resection was 66.2% in young patients, which was not significantly different from the 65.2% 3-year survival rate in older patients. There was no significant difference between the young and older groups according to histological cell type and TNM staging. In cases of incomplete resection or exploratory thoracotomy, 4 of 8 patients had been alive more than 2 years after operation. These results suggest that a long-term survival in the young patients is expected to be almost the same as that in the older patients after either complete resection or incomplete resection.
The clinical, radiographic, and pathological features of 10 patients with sclerosing hemangioma of the lung seen between 1974 and 1990 were reviewed. The incidence of sclerosing hemangioma was 22.2% of benign tumors surgically resected during that time. There were 2 male and 8 female patients aged 15 to 77 years at operation, and 9 patients were asymptomatic. All 10 patients had a solitary tumor with a well-defined homogeneous round or oval shadow on chest roentgenograms. Chest computed tomography revealed a homogeneous soft-density mass in 4 patients and a low-density portion within the tumor because of a cystic change in 1 patient. Microscopically, 5 patients had a preponderantly solid pattern, 3 had a preponderantly papillary pattern, and 1 patient had a preponderantly sclerotic pattern. One patient had an equal mixture of solid and papillary patterns. Nine of the 10 tumors consisted of a mixture of at least three of the four major patterns. Regarding treatment, thoracotomy is indicated for a definite diagnosis. If a benign tumor is suspected at operation, an intraoperative frozen section is recommended. Once the diagnosis has been established as sclerosing hemangioma, a limited resection is indicated.
We have tried to answer the question of whether the endothelium of Schlemm's canal is derived from and retains properties of blood vessels by studying: (1) the development of Schlemm's canal in human fetal eyes; (2) the existence of Weibel-Palade bodies in human neonatal, adult human and adult monkey eyes; and (3) the presence of blood coagulation Factor VIII-related antigen in adult human and monkey eyes. (1) We observed that the intrascleral plexus of the limbal region extended deep into the sclera forming a deep scleral plexus by the 17th week of gestation. After 17 weeks gestation, extensions from the deep scleral plexus had reached the region of the future corneoscleral meshwork where the trabecular cells appeared oriented circumferentially. The blind endings of these extensions appeared to grow circumferentially in the supposed region of Schlemm's canal and at 27 weeks gestation they formed an incomplete Schlemm's canal. A complete Schlemm's canal was observed in some sections of the limbal region at 28 weeks gestation and at approximately 40 weeks gestation the canal was complete in most sections. (2) Weibel-Palade bodies were found in the endothelium of aqueous veins and in the inner and outer wall endothelium of Schlemm's canal. (3) Blood coagulation Factor VIII-related antigen was detected in the endothelium of the collector channels and Schlemm's canal, as well as in the blood vessels of the other parts of the eye. Our results indicate that the endothelium of Schlemm's canal is derived from a vascular origin and that even in the adult eye it retains some of the properties of a blood vessel.