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Biomedical subjects

T Okabe

Publications and source records attributed to T Okabe.

At least 253 records · Page 14Linked to original sources

Visualization of exocytotic secretory processes of mast cells by fluorescence techniques.

Secretory processes via exocytosis in rat peritoneal mast cells were visualized by two complementary fluorescence techniques; one staining pre-exocytotic granules with a basic probe and the other staining post-exocytotic granules with acidic probes. Granules within mast cells were selectively stained with acridine orange and emitted orange yellow fluorescence. Upon stimulation with compound 48/80, release of acridine orange from granules was observed both in population and single cell measurements. This release was seen in some localized area of mast cells. Opening of pores between plasma membranes and granule membranes was monitored using acidic fluorescence probes such as 6-carboxyfluorescein or lucifer yellow CH. Not only granules located at peripheral region, but also granules near the core region participated in exocytosis. The existence of junctions between these granules was suggested. TMA-DPH, a lipophilic membrane probe, which was localized at plasma membrane before stimulation, diffused into granule membranes after stimulation. This shows that after stimulation, some constituents of plasma and granule membranes were mixed. Even after extensive degranulation, mast cells extruded acidic probes, indicating the plasma membranes still play a role of barrier. Activation of lateral motion of granules preceding to exocytosis was not observed. It was concluded that the visualization of secretory processes by fluorescence and image processing techniques will be useful for the study of molecular mechanisms underlying exocytosis.

Acridine Orange↗

Cytotoxicity of amalgams, alloys, and their elements and phases.

The purpose of this study was to compare the relative cytotoxicity of amalgams, alloys, and their constituent elements and phases, by means of a rapid and sensitive in vitro cell culture test. Pure copper and zinc showed intensive cytotoxicity, significantly greater than that of pure silver and mercury. Pure tin was non-cytotoxic. The gamma-one phase (Ag2Hg3) revealed moderate cytotoxicity, which was significantly decreased by the addition of 1.5% and 5% Sn. However, the addition of 1.5% Zn to gamma 1 containing 1.5% Sn dramatically increased the cytotoxicity of gamma 1 to the same level as that of pure zinc. Whenever zinc was present in amalgams, higher cytotoxicity was revealed. High-copper amalgams showed the same cytotoxicity as a zinc-free low-copper amalgam. The addition of selenium did not reduce the cytotoxicity of amalgam. The cytotoxicity of amalgams was reduced after 24 h. The results of this study suggest that the major contributor to the cytotoxicity of alloy for amalgam is probably copper, while that for amalgam is zinc.

Copper↗

Characterization of haemagglutinin from Bordetella bronchiseptica.

In comparison with haemagglutinin (HA)-active strains of Bordetella bronchiseptica, the HA-deficient strains lacked a 150 kDa protein band on SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Adsorption of partially purified HA with bovine erythrocytes showed the loss of the 150 kDa band in the supernatant. This 150 kDa protein was purified by high-performance liquid chromatography using gel filtration columns. Electron microscopic examination revealed that the purified HA possessed a fine filamentous structure with dimensions of approximately 2 x 150 nm, which was considered to represent the filamentous haemagglutinin of B. bronchiseptica. Both the cell-free antigen obtained from the culture supernatant of phase-I strain of the bacteria and the bovine erythrocytes, which combined with crude HA showed an excellent protective activity of the challenge by virulent strain of B. bronchiseptica in mice.

Animals↗

Growth-promoting effect of human growth hormone on patients with achondroplasia.

To evaluate the effect of human growth hormone (hGH) on the growth of children with achondroplasia, three patients with achondroplasia and one patient with hypochondroplasia were treated with 0.5 IU/kg/W of pituitary-extracted hGH for 6-12 months. Mean height velocity was significantly increased from 4.0 +/- 0.4 to 7.5 +/- 0.7 cm/year (P less than 0.05) by hGH. The tibial index, defined as the length/width ratio of left tibia, did not change during the treatment, indicating that hGH promotes growth without exaggeration of tubular bone deformity. Case 2, who had atlantoaxial dislocation, developed sleep apnea and neurological deficits during the second hGH treatment, but these were cured by operation. Thus, hGH therapy is effective in promoting growth in patients with achondroplasia, but the complication of atlantoaxial dislocation should be explored and corrected before the treatment.

Achondroplasia↗

Evaluation of severity indexes of patients with paraquat poisoning.

1. Three indexes for evaluating the severity of paraquat poisoning based on plasma-paraquat concentration are presently in use; the curves of Proudfood et al. and Scherrmann et al. and the SIPP. Their effectiveness in determining the prognosis of patients with paraquat poisoning was evaluated. 2. To determine which index was more accurate, contigency tables of the three indexes were obtained and compared; Proudfoot's curve vs the SIPP Scherrmann's curve vs the SIPP. Proudfoot's curve and the SIPP were applied to patients admitted within 24 h after intoxication. Scherrmann's curve and the SIPP were applied to patients admitted more than 24 h after intoxication. The proportions of patients with true positive and true negative results to total patients were compared by a ratio test. 3. Proudfoot's curve was found to be more accurate than the SIPP for predicting the prognosis of patients admitted within 24 h (P less than 0.05). No significant difference, however, was noted between Scherrmann's curve and the SIPP in determining the prognosis of patients admitted after more than 24 h. 4. In conclusion, Proudfoot's curve proved a better index for predicting the outcome of patients who were admitted within 24 h. However, for the prognosis of patients admitted more than 24 h after the ingestion of paraquat, further study is required.

Evaluation Studies as Topic↗

Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody.

We produced a monoclonal antibody to endothelin (ET)-1, tested cross-reactivities with the related peptides by enzyme immunoassay, and investigated the effects of the antibody on ET-1- or ET-2-induced vasoconstriction of rat isolated thoracic aorta. The antibody recognized ET-1, ET-2 and ET-3, and the immunoreactive site proved to be the N-terminal region but not the C-terminal region of ET-1. Moreover, at an approximate molar-equivalent concentration, the antibody absorbed ET-1 and ET-2, and significantly inhibited ET-1- and ET-2-induced vasoconstriction notwithstanding the presence of the endothelin receptor.

Animals↗

Syntheses and biological activities of endothelin-1 analogs.

Endothelin-1 analogs replaced by various amino acids at position 21, namely [X21]-ET-1, were synthesized, and their agonistic vasoconstrictor activity on rat thoracic aortic strips and receptor binding activity on rat brain membrane fraction were examined to elucidate their structure-activity relationship. The vasoconstrictor activities of [Tyr21]- and [Phe21]-ET-1 were one order of magnitude smaller than that of ET-1, and those of [His21]-, [Gly21]-, [Ser21]-, [Ala21]- and [Lys21]-ET-1 were more than two orders of magnitude smaller than that of ET-1. On the other hand, the replacements by Ile, Glu, Gln and Pro resulted in distinguished losses of the vasoconstrictor activities. In addition, preincubation with these analogs did not blunt ET-1-induced vasoconstriction and showed no antagonistic activity. The binding inhibitory activities of these analogs against 125I-ET-1 were approximately conformable to the vasoconstrictor activities with only a slight exception. These findings demonstrate that the phenyl group at position 21 is important for both the vasoconstrictor activity and the receptor binding activity.

Animals↗

Induction of anti-Theileria sergenti antibodies in calves with murine monoclonal anti-idiotype antibody.

Anti-idiotype (anti-Id) antibody that contains an internal image of Theileria sergenti (T. sergenti) merozoite surface antigen was intramuscularly inoculated to calves to induce anti-T. sergenti antibody. In immunized calves, anti-anti-Id antibodies were induced and these antibodies bound to merozoites of T. sergenti were confirmed by immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). In this experiment, one calf with the highest antibody titer against anti-Id antibody was intravenously challenged with T. sergenti-infected erythrocytes to show insufficient protective effects of the anti-anti-Id antibodies against the challenge.

Animals↗

Structure-activity relationships of cadeguomycin analogs.

The relationship between the activity and the chemical structure of cadeguomycin (CDM, 7-carboxy-7-deazaguanosine) was studied with six analogs of CDM. Both activities of CDM, enhancing the incorporation of [3H]thymidine in K562 cells and potentiating the cytotoxicity of cytosine arabinoside for K562 cells, were significantly augmented by the replacement of the 7-carboxyl group with cyano (CDM-CN) or formyl (CDM-CHO), but they were not changed by the replacement with methyl. The activities were almost completely diminished by the replacement of ribose with arabinose, but the simultaneous replacement of carboxyl and ribose with formyl and arabinose showed higher activities than those of CDM. The replacement of 7-carboxy-7-deazaguanine with 7-carboxy-7-deazainosine markedly weakened the activity. CDM-CN and CDM-CHO at 0.2 micrograms/ml significantly potentiated the activity of cytosine arabinoside against MOLT-3 cells but CDM at 1 micrograms/ml did not. These results indicate that the ribose and guanine moieties in the CDM molecule are very important for its activity. Also replacing the carboxyl group at the C-7 position with cyano or formyl group is a useful way to strengthen the CDM activity. These compounds would effectively potentiate cytosine arabinoside against various kinds of tumor cells which CDM could not do.

Anti-Bacterial Agents↗

[Clinical efficacy and safety of long-term administration of YM617 for urinary obstruction of the lower urinary tract].

The efficacy and safety of YM617, a new alpha 1-blocker, were evaluated in 121 patients with urinary obstruction of the lower urinary tract in the long-term administration study for 1 year. A total of 121 patients, i.e., 111 with benign prostatic hypertrophy (BPH), 6 with bladder neck sclerosis (BNS), 3 with BPH with BNS and 1 with female urinary obstruction, were orally administered 0.1 to 0.4 mg of YM617 once daily. Patients showing improvement of patient's impression and of subjective symptoms judged by the physician were increased until the 16th to 20th week, and it had been maintained there after. Objective findings were improved to a constant level after the 4th week. Patient's impression and subjective symptoms were improved in a certain dose-response relationship Side effects were observed in 3 patients but none were serious. YM617 proved to be useful in the treatment of patients with urinary obstruction of the lower urinary tract like BPH because it maintained the efficacy and safety in the long-term administration.

Administration, Oral↗

Identity of brain-associated small cell lung cancer antigen and the CD56 (NKH-1/Leu-19) leukocyte differentiation antigen and the neural cell adhesion molecule.

Previous studies have demonstrated the monoclonal antibody, TFS-4, to recognize a cell surface antigen, 124,000 Daltons, of molecular weight expressed selectively on small cell lung cancer but not on non-small cell lung cancer, and to cross-react with the human brain, cardiac muscle and some smooth muscle cells. The cross-reactivity of TFS-4 with peripheral blood lymphocytes was examined by two color immunofluorescence analysis, using monoclonal antibodies to leukocyte differentiation antigens. Flow cytometric analysis revealed an identical subset of cells to express both BASCA and CD56(NKH-1 antigen). The immunofluorescence profiles for both TFS-4 and NKH-1 were, furthermore, identical to those of the background controls, identicating identical quantities of the antigens to be present on each cell within the population. Since CD56 has been show to be identical to the neural cell adhesion molecule (N-CAM), we determined the amino-terminal amino acid sequence of BASCA purified from the human brain. The amino-terminal amino acid sequence of BASCA was identical to that of N-CAM.

Amino Acid Sequence↗

Prevention of posttransfusional non-A, non-B hepatitis by a screening test for hepatitis C virus antibody of donor bloods.

The preventive effect on posttransfusional non-A, non-B hepatitis (PTH) of screening out HCV-Ab positive blood and the prevalence of HCV-Ab-positive donor blood were examined. The incidence of HCV-Ab-positivity in donor blood A was 0.9% and that in donor blood B was 1.35%. The mean ALT and guanase levels were 11.5 +/- 5.8 and 0.58 +/- 0.24 IU/l in HCV-Ab negative blood and 17.3 +/- 7.9 and 0.84 +/- 0.23 IU/l in HCV-Ab-positive blood. Both levels were significantly higher in HCV-Ab-positive blood. These differences were considered to be nonspecific, but there may be some relationship between the levels of ALT and guanase in donor blood and the HCV carrier status. After adoption the screening test for HCV-Ab positive blood, there was no case of a definite diagnosis of PTH, although 4 patients (6.6%) suspected of developing PTH. So, the incidence of PTH was clearly lower than the lowest incidence before adoption of this test. Therefore, we conclude that screening for HCV-Ab in donor blood should be routinely used for prevention of PTH.

Blood Donors↗

[Current status of continent urinary reservoirs for invasive bladder cancer patients undergoing total cystectomy].

Continent urinary reservoirs (CUR) have become one of the major options of urinary diversion for invasive bladder cancer patients who require cystectomy and cutaneous urinary diversion. We have experienced 100 cases of Kock pouch and 30 cases of indiana pouch during the past 5 years which comprise 45% of all cases. Standard ileal conduit and ureterocutaneostomy were performed in 34% and 20%, respectively, and orthotopic urinary reservoir by hemi-Kock pouch was done in only one case during the same years. There were 3 perioperative deaths, 2 had Kock pouch and one Indiana pouch. Early postoperative complications were not substantial. However, significantly high rates of late postoperative complications were seen in Kock pouch, i.e., both efferent (18%) and afferent (13%) nipple valves and stone formation (18%). Uretero-ileal anastomosis by hammock method done in 10 cases resulted in success in 8 cases, abolishing the afferent nipple. Indiana pouch, in which no nipple valves or foreign materials like staples or collars are necessary, has been adopted as a first choice for the past 3 years. Of 29 evaluable cases, Heineke-Mikulicz method was used in 7 cases, and ileal patch method in 22 cases. An hourglass-like deformity was seen in 2 cases in the former method. Severely difficult catheterization, parastomal abscess, and acidosis occurred in one. Overall, 24 cases (83%) have come up with satisfactory results with minimal overflow incontinence in the early postoperative course. Although much longer followup is necessary, CUR's by Kock or Indiana pouch are more acceptable by bladder cancer patients requiring cystectomy.

Adult↗