Biomedical subjects
Publications and source records attributed to S Hara.
The cerebro-spinal fluid in the subarachnoid space is delineated clearly with gradient field echo technique (TR = 60 ms, TE = 20 ms, flip angle = 20 degrees). Average area, width, depth, and curvature of the subarachnoid space in the cervical region were obtained in ten young normal subjects.
We studied the actions of a potent thromboxane A2/prostaglandin in H2 (TP) receptor antagonist, (+/-)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo [2.2.1]hept-2-exo-yl]heptenoic acid (S-145) on vascular and platelet receptors in the pig. S-145 showed almost the same affinity for both receptors in ligand binding studies with [3H]U46619 or [3H]SQ29, 548. The binding affinity of S-145 was 5-8 times higher than that of SQ29,548, a well-characterized TP receptor antagonist. However, S-145 inhibited U46619-induced contractions of pig coronary arteries with an IC50 value 52.5 times lower than that of SQ29,548, and was approximately equipotent with SQ29,548 in inhibiting U46619-induced secondary aggregation of pig platelets. Detailed kinetic studies on [3H]S-145 binding revealed that the apparent discrepancy between the pharmacological potency of S-145 in platelet and vascular systems was not due to tissue selectivity, but its small association constants for both receptors.
Direct current therapy (DC therapy), consisting of the application of electric current directly to the lesion, with chemotherapy using BLM was performed in 4 advanced inoperable lung cancer patients in whom chemotherapy and radiotherapy were not effective or could not be performed. Fluoroscopically two electrodes were inserted percutaneously into the tumor under local anesthesia. The distance between the two electrodes was about 3-4 cm. About 10 volts of direct current for 1 hour (totally over 40 coulombs) was passed between them using a DC treatment processor model 85 (Inter Nova Co., Ltd.), and simultaneously 15-30 mg of BLM was administered intravenously according to the general condition of the patient. The histologic type was adenocarcinoma in 3 cases and there was 1 large cell carcinoma. This treatment was performed once in 3 cases and twice in another. A reduction of tumor size was recognized in 3 cases (2 adenocarcinomas and 1 large cell carcinoma). In another adenocarcinoma case it was not measurable in size because of infiltrative shadow but histologically tumor destruction was recognized within a short period after DC therapy. The complications were mainly slight fever and light pain during the procedure. There was one small amount of hemoptysis and one pneumothorax but it was not necessary to perform special treatment for these complications. DC therapy with chemotherapy is based on our basic experimental experience that some anticancer agents accumulate around the electrodes in lung tissue when direct current is passed. In addition, current itself has cytocidal effects in some cases. Our clinical experience suggested the usefulness of this therapy to treat lung cancer lesions locally.(ABSTRACT TRUNCATED AT 250 WORDS)
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The biological nature of human sarcomatous Wilms' tumor (SWT) was studied by analyzing newly established SWT lines, both heterotransplantable in nude mice and cultured in vitro. Five lines in nude mice include two from clear cell sarcoma of the kidney (CCSK), two from malignant rhabdoid tumor of the kidney (MRTK), and one from unclassified sarcoma. Five in vitro lines include three from CCSK, one from MRTK, and one from unclassified sarcoma. All of these in vitro cell lines produced tumors when innoculated in nude mice. Most of lines, especially of MRTK and unclassified sarcoma, well maintained their original morphological characteristics. However, CCSK lines, both heterotransplantable and in vitro, often showed unique morphological changes such as the increase of cells with eosinophilic cytoplasms and the production of mucin. Ultrastructurally, clusters of intermediate filaments, twisted sheaves of filaments resembling tonofilaments, intermediate junctions, and intracellular canaliculi were found in these cells. These findings suggested that CCSK had the latent epithelial nature which became obvious in the cell lines. This was confirmed by immunohistochemical and immunoblotting analyses with anticytokeratin antibodies. The result proved that CCSK expressed cytokeratin 8 (Mr 52,000) and 19 (Mr 40,000) as well as nephroblastic Wilms' tumor and strongly indicated that there was a close relationship between CCSK and nephroblastic Wilms' tumor.
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A simple, rapid, and highly sensitive fluorometric high-performance liquid chromatographic method for the determination of N-acetylneuraminic acid and its mono-O-acetyl derivatives in human and rat sera is described. The neuraminic acids, released by hydrolysis of serum in 2 M acetic acid, are converted with 1,2-diamino-4,5-methylenedioxybenzene, a fluorogenic reagent for alpha-keto acids, to highly fluorescent derivatives without the occurrence of O-acetyl migration and de-O-acetylation. The derivatives are separated isocratically within 25 min by reversed-phase chromatography using a TSK gel ODS-120T column. The limits of detection are 57-192 fmol in a 10-microliters injection volume at a signal-to-noise ratio of 3. This sensitivity permits precise determination of the neuraminic acids in 5 microliters of human and rat sera.
Forty four patients, presenting metastasis only to bone from a primary breast cancer previously undergone mastectomy from 1975 to 1985 at Kinki University Hospital, were investigated for the purpose of early detection of bone metastasis. Clinical follow up and bone scintigraphy at regular interval were the most important to detect the early phase of bone metastasis. The patients with early phase of bone metastasis, detected by regular scintigraphy in every 6 months, had the frequent metastatic lesions in rib and sternum as well as lumbar. These metastatic lesions could not be found by X-ray examination but were confirmed by aspiration cytology. Among the tumor markers, Al-p and LDH, rather than CEA and Ca, were more useful for the diagnosis of early phase of bone metastasis.
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We compared the properties of vascular and platelet thromboxane A2/prostaglandin H2 receptors in the pig. The binding profiles of U46619, several prostaglandins and thromboxane A2/prostaglandin H2 receptor antagonists to the aorta and platelet receptors were almost the same irrespective of whether the agonist ([3H]U46619) or the antagonist ([3H]SQ29,548) radioligand was used, except that the receptor density in the latter was 4 times higher than that in the aorta. The antagonists suppressed U46619-induced contraction of pig coronary artery and secondary aggregation of platelets at potencies comparable to their KI values in the binding experiments. On the other hand, the responses of the artery specimens to U46619 and the prostaglandins differed from those of the platelets. Thus, the binding sites in the vascular and platelet receptors seem to be the same or quite similar, but there seem to be different mechanism(s) leading the agonistic binding signal to final responses.
The rapid resolution of racemic N-4-nitrobenzoylamino acid isopropyl esters was accomplished without the loss of enantioselectivity by supercritical fluid chromatography (SFC) on novel chiral valine-diamide phases with carbon dioxide and a polar methanol modifier. In each stationary phase, a chiral moiety was anchored to the silica gel surface by a long decamethylene spacer. The enantioselectivity in SFC was comparable to that in liquid chromatography using 2-propanol-n-hexane. The time required for analysis was less than 5 min, and the range of enantiomer resolution (Rs) was 10.8-1.25. On using 2-propanol in place of methanol the separation was improved, but was accompanied by a decrease in column efficiency. The end-capping effect of the remaining surface silanols on enantiomer resolution is discussed.
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The purpose of this study is to analyze the results of anorectal manometry and to evaluate the merits and disadvantages of this technique for the diagnosis of Hirschsprung's disease. Studies were performed in 268 patients with constipation, including 95 cases of Hirschsprung's disease. It is concluded from the results that Hirschsprung's disease can be confidently diagnosed by manometric studies. If the studies are performed carefully with a suitable probe, reliability is over 95%. Manometry is the most useful method to differentiate Hirschsprung's disease from other conditions, such as extremely short segment aganglionosis, colonic stenosis, and idiopathic megacolon.
We have developed a mouse monoclonal antibody 5C11 (IgG2a) against cell surface antigen of Ewing's sarcoma (ES). 5C11 specifically reacted with ESs but not with other small round cell tumours in childhood, i.e. neuroblastomas, primitive neuroectodermal tumours (PNETs), rhabdomyosarcomas and malignant lymphomas. 5C11 did not react with any other tumours in children except for hepatoblastomas. No reactivity has been identified in normal tissues with the exception of fetal hepatocytes. Immunoelectron microscopically, 5C11 reactive antigen was located on cell membrane of ES cells. Biochemically, 5C11 immunoprecipitated a cell surface protein having molecular weight of 81,000 Da. 5C11 is the first antibody which can clearly distinguish ES from neurogenic tumours, especially from PNETs which were recently reported to have common features to ESs regarding chromosal abnormality and proto-oncogene expression but show evident differentiation into neurogenic direction. The results strongly indicate the usefulness of 5C11 not only for diagnostic purpose when no specific marker is available but also for studying the histogenesis of ES. In addition, no reactivity in normal tissue implies its potential application as a therapeutic reagent when the management of ES patients is still a great problem in clinical field.
The aim of the present study was to investigate the events following interaction of antibody with an antigen planted on the surface of glomerular endothelial cell (GEN). A lectin, Helix pomatia agglutinin (HPA), was planted at the surface of rat GEN by the perfusion of the isolated left kidney with neuraminidase (NRD) and HPA. A subsequent perfusion with IgG fraction, but not with Fab fragments, of rabbit anti-HPA serum induced formation of granular immune deposits (IDs) on the surface of GEN. When the left kidney was revascularized after initial formation of IDs, acute glomerulonephritis ensued. Fifteen minutes after revascularization, granular IDs were observed at the subendothelial space. Two days later, there was decrease of subendothelial IDs with concomitant appearance of subepithelial IDs. At the seventh day, IDs were mainly localized in the subepithelial space. The results suggest that this model of experimental glomerulonephritis is characterized by: (1) initial formation of HPA immune complexes (ICs) at the surface of GEN; and by (2) subsequent movement of ICs from luminal side to subepithelial area with local formation of IDs. The results are relevant to the understanding of the kinetics of ICs resulting from interaction of antibodies with exogenous antigens "planted" in the glomerular capillary walls, and of the local formation of IDs.
Three serine proteinase inhibitors, MCTI-I, MCTI-II, and MCEI-I, were isolated from bitter gourd (Momordica charantia LINN.) seeds. MCTI-I and MCTI-II were inhibitors for trypsin and MCEI-I was an elastase inhibitor. Their amino acid sequences and the positions of disulfide bridges of MCTI-II were determined to be as follows. (sequence; see text)
Extracellular phospholipase A2 was purified about 1.7 X 10(5) fold to near homogeneity from human synovial fluid of rheumatoid arthritis by sequential use of column chromatographies on heparin-Sepharose, butyl-Toyopearl, and reversed-phase HPLC. The final preparation showed a single band on SDS-polyacrylamide gel electrophoresis, and its molecular mass was estimated to be approximately 13,700 daltons. The purified enzyme had a pH optimum of 9.0 and required Ca2+ for maximum activity. It hydrolyzed phosphatidyl-ethanolamine more effectively than phosphatidylserine and phosphatidylcholine. These properties were similar to those of an extracellular phospholipase A2 detected in the peritoneal cavity of caseinate-treated rats.
A chitinase was purified from the culture filtrate of Streptomyces erythraeus (SE). The enzyme (SE chitinase) has a molecular weight of 30,000 and pI 3.7, and shows optimal activity at pH 5.0 with an optimal ionic strength of less than 0.2 M NaCl. SE chitinase could hydrolyze chitin and its derivatives, but could not hydrolyze cell walls of Micrococcus lysodeikticus. The substrate specificity of SE chitinase was compared with those of hen egg white (HEW) and SE lysozymes. The binding mode of the chitinase to substrates was investigated using chitooligosaccharides and their derivatives. The results showed that the binding mode of SE chitinase to the substrate is similar to that of HEW and SE lysozymes.