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Biomedical subjects

M Shirato

Publications and source records attributed to M Shirato.

At least 37 records · Page 2Linked to original sources

Similarity and co-expression of tumour-associated antigens recognised by different monoclonal antibodies.

The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the 125I-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. 125I-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti-CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule.

Antibodies, Monoclonal↗

Construction of immunoradiometric assay for circulating c-erbB-2 protooncogene product in advanced breast cancer patients.

The human c-erbB-2 protooncogene product (erbB-2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB-2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2-61 gamma and 6G10, recognize erbB-2 protein but bind to separate epitopes. SV2-61 gamma was used as an immunoadsorbent and 6G10 as an 125I-labeled probe. A serum was considered positive for erbB-2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB-2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut-off value. These results suggest that circulating erbB-2 protein can be measured using the newly constructed IRMA. Since c-erbB-2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.

Adenocarcinoma↗

[Evaluation of a cytokeratin 19 assay kit "BALL ELSA CYFRA21-1"].

We evaluated "BALL ELSA CYFRA21-1" kit, an immunoradiometric assay kit for cytokeratin 19. Monoclonal antibodies KS19-1 and BM19-21 are used for immunoadsorbent and indicator, respectively. There was no problems in reproducibility, dilution test and recovery test. Minimum detectable concentration was 0.42 ng/ml. The antigen measured by this kit was immunologically cross-reactive with tissue polypeptide antigen (TPA) and CYFRA21-1 concentration was closely correlated with TPA concentration in patient's serum. One of twenty-six healthy subjects showed serum concentration over a cut-off value of 2.0 ng/ml. Serum CYFRA21-1 concentration elevated in 5 of 10 esophageal cancer patients, 5 of 10 gastric cancer patients, 7 of 10 colorectal cancer patients and 6 of 10 pancreatic cancer patients. Positive rate in patients with benign disease including hepatopathy was low. BALL ELSA CYFRA21-1 kit is reliable and CYFRA21-1 could be a useful tumor marker in gastrointestinal cancer.

Adult↗

Scintigraphic evaluation of tenosynovial giant-cell tumor using technetium-99m(V)-dimercaptosuccinic acid.

Technetium-99m(V) dimercaptosuccinic acid (DMSA) and 67Ga-citrate scintigraphy were performed in three patients with primary and recurrent tenosynovial giant-cell tumor (one localized type and two diffuse type). In all cases, 99mTc(V)DMSA showed marked accumulation in all primary and recurrent tumors; however, 67Ga-citrate showed no accumulation in any of the tumors. Technetium-99m(V)-DMSA scintigraphy was useful in detecting tenosynovial giant-cell tumor and in diagnosing recurrence of this tumor.

Adult↗

[Imaging diagnosis of lupus enteritis--especially about sonographic findings].

We evaluated 4 cases of lupus enteritis by US, abdominal X-ray and CT. On US examinations, in particular, we observed ascites and edematous thickening of the small intestine where Kerckring folds with submucosal edema resembled an accordion. After steroid treatment and consequent improvement of the disease, we noticed disappearance of the intestinal thickening and ascites on US examination, compatible with the diagnosis of lupus enteritis. Based on these results, US was useful for the diagnosis and follow-up of lupus enteritis.

Adult↗

[67Ga scintigram and MRI in malignant bone tumors and malignant soft tissue tumors].

We have analyzed the characteristics of 67Ga scintigram and MRI in 11 malignant bone tumors and 11 malignant soft tissue tumors. Osteosarcoma showed a high accumulation in 67Ga scintigram and low signal intensity in T1 weighted image. T2 weighted image were not characteristic. Chondrosarcoma showed medium 67Ga accumulation and low signal in T1 weighted image and high signal in T2 weighted image. Ewing sarcoma showed low accumulation in 67Ga scan and medium intensity in MRI. Malignant soft tissue tumors showed rather low 67Ga accumulation compared with malignant bone tumors. Malignant fibrous histiocytoma showed medium accumulation of 67Ga, low signal in T1 weighted image and high signal in T2 weighted image. Liposarcoma showed low 67Ga accumulation and medium signal in T1 weighted image and high signal in T2 weighted image. To summarize these characteristics, three dimensional display is demonstrated.

Bone Neoplasms↗

Pharmacological effects of oral E6123, a novel PAF antagonist, on biological changes induced by PAF inhalation in guinea pigs.

The effects of a newly synthesized PAF antagonist E6123, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2, 3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine, on in vivo inhaled PAF-induced pulmonary changes were investigated. E6123 inhibited PAF inhalation-induced bronchoconstriction in guinea pigs with an ED50 value (p.o.) of 1.3 micrograms/kg which was lower than those of other PAF-antagonists such as WEB2347 (ED50 = 26 micrograms/kg) and Y-24180 (ED50 = 12 micrograms/kg). E6123 significantly inhibited PAF inhalation-induced eosinophil infiltration into the bronchiole and trachea, and bronchial hyperreactivity in guinea pigs after oral administration at 1 and 10 micrograms/kg, respectively. E6123 inhibited the PAF-induced increase in intracellular free calcium ion concentration ([Ca2+]i) in guinea pig eosinophils with an IC50 value of 14 nM. The present results suggest that E6123 may be beneficial for the treatment of asthma, in which PAF is assumed to be involved.

Administration, Oral↗

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis.

The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.

Animals↗

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

Aerosols↗

[Injuries of the sigmoid colon following radiation therapy of carcinoma of the uterine cervix--a method of estimating the radiation dose to the sigmoid colon].

Grade 2 or 3 injuries of the sigmoid colon were observed in 4 out of 42 patients with carcinoma of the uterine cervix who were treated by radiation therapy. The irradiation was planned as the combination of the external irradiation (whole pelvic 30 Gy and 20 Gy with central shielding by 25 fractions, 5 weeks) and the intracavitary irradiation (RALS, 19 Gy at point A by 3 fractions). To analyze the causes of the radiation sigmoiditis, we have investigated the following factors: age, dose at point A, dose at point C, grade of tandem dislocation, uterine angle, obesity score, evidence of previous surgery to the pelvic cavity and hypertension. The dose at point C and the grade of tandem dislocation were determined from the confirming X-Ps at RALS therapy and external irradiation. The superimposition of these films was performed with corrections for the angle between the projection direction of the X-Ps and the vertical magnification factor of the central shielding area. Point C was defined as a point 2 cm anterior to the intersection of the tandem axis and a curvilinear line 1 cm outside from the margin of central shield on the X-Ps. Grades of tandem disclocation were decided as the number of tandem tips which were outside of the central shielding area on X-Ps. As the results, the doses at point C showed very high statistical significance (p less than 0.001) with the evidence of radiation sigmoiditis. All the cases with radiation sigmoiditis were received over 1290cGy at point C. Age had also some significance (p less than 0.05) with radiation sigmoiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Effects of a novel PAF antagonist, E6123, on passive anaphylaxis.

E6123 inhibited antigen-induced bronchoconstriction, the development of bronchial hyperreactivity and eosinophil infiltration in the airway in passively sensitized guinea pigs and protected mice from anaphylactic death. The inhibitory effects of E6123 on anaphylactic response were very potent compared with those of WEB 2347 and Y-24180.

Anaphylaxis↗

[Efficacy of pancreatic scan--comparison among conventional scan, SPECT and X-CT].

We studied the efficacy of pancreas scintigraphy using 75Se-selenomethionine by conventional method and SPECT in 26 patients diagnosed as pancreatic tumor or pancreatitis. X-CT was also performed in all patients and compared its efficacy with that of scintigraphy. In order to evaluate the image quality, 4 doctors analysed the images independently without clinical information and score them according to the possible abnormality. The average score of each film was adopted as an index for sensitivity, and the standard deviation was evaluated as objectiveness of the images. As for the detection of pancreatic tumor, both the sensitivity and the objectiveness of X-CT were superior to those of scintigraphies. However, evaluation by scintigraphy combined with X-CT increased the diagnostic sensitivity of pancreatitis than that of X-CT alone in some cases. These results suggest that the scintigraphy has no indication to suspected pancreatic tumor, but it still has some value in limited cases of pancreatitis. Almost no advantage was noted in SPECT combined with conventional image. Main reason was the artifact of SPECT preventing the accurate interpretation. Only benefits of SPECT were to decrease the false positive rate and to increase the objectiveness of 75Se-selenomethionine scan. When the scan is discussed as the examination, careful considerations should be done on the point of limited advantage on diagnostic efficacy and marked disadvantage of radiation to patients and environment.

Adult↗

[Radiotherapy of uterine cervix carcinoma].

Seventy-eight patients with uterine cervix cancer were treated radically with standardized radiation therapy at Teikyo University Hospital in Tokyo from January 1979 to December 1985. The age of these patients ranged from 32 to 88 years old (average age 66.0). The pathology and the stage of them were 71 cases of squamous cell carcinoma (1 in stage I, 11 in stage II, 58 in stage III and 1 in stage IV) and 7 cases of adenocarcinoma (6 in stage III and 1 in stage IV). The cumulative survival rates for 5 years by Kaplan-Meier method were 71.5% for squamous cell carcinoma stage II, 47.4% for squamous cell carcinoma stage III and 0% for adenocarcinoma stage III. Radiation injury was studied by the grading system of Kottmeier-NIRS in Japan. The incidence of the injuries for grade 2 and 3 was 12.8% (10/78), and the items of those were rectal injury 5.1% (4/78) and sigmoidal colonic injury 7.7% (6/78). The results of survival rate were fair for the squamous cell carcinoma compared with the other reports but poor for adenocarcinoma stage III. Concerning the therapy for advanced adenocarcinoma of the uterine cervix, special consideration should be given for irradiation doses or infusion chemotherapy.

Adenocarcinoma↗

[The effects of angiographic contrast media on the aggregation and morphology of red cells in vitro].

The effects of four angiographic contrast media on the aggregation and morphology of human red cells in vitro, using microscopic observations were studied. The media included an ionic contrast medium, sodium meglumine amidotrizoate (amidotrizoate); non-ionic low-osmolal contrast media, iopamidol and iohexol; and an ionic low-osmolal contrast medium, sodium meglumine ioxaglate (ioxaglate). Strong, large aggregates formed in the control blood, without media, where aggregation of red cells was inhibited by contrast media mixed with the blood in a ratio of 2:1. Almost no aggregates were observed for amidotrizoate, an ionic contrast medium, while there were a few rouleaux formed in the presence of ioxaglate. Nearly all of the red cells aggregated in the presence of iopamidol and iohexol; iohexol produced the greater aggregation of the two. Besides rouleaux, irregular aggregates were formed with iohexol. When the contrast media were mixed with blood in a ratio of 1:2, their inhibitory effects on aggregation declined. These results clearly indicate that contrast media inhibit the in vitro aggregation of red cells, and ionic-contrast media produced more potent inhibitory effects than non-ionic media. With added NaCl and meglumine, iohexol did not induce red cell aggregation. This suggests that ionic-contrast media have greater inhibitory effects on aggregation than non-ionic media, a result of their ionic properties. Red cells were morphologically quite normal in the presence of ioxaglate, where most red cells were crenated in the presence of iopamidol and iohexol, and shrank in the presence of amidotrizoate. In the presence of iopamidol and iohexol with the osmolality adjusted to that of a saline solution, both normal red cells and crenation were observed. This suggests that non-ionic contrast media may directly effect morphological changes in red blood cells. These results revealed that ioxaglate, an ionic contrast medium, was the best in vitro medium, to prevent aggregation of red cells and crenation deformity of erythrocytes.

Contrast Media↗

[Improved contrast enhancement with a positive pressure drip infusion method and 350 mg I/ml high concentration contrast media in routine contrast enhanced CT].

Sixty cases of routine contrast enhanced CT were analyzed about the utilities of positive pressure drip infusion method using high concentration contrast media 350 mgI/ml, 100 ml. They were divided into three groups and each twenty cases were received positive pressure drip infusion method using Iohexol 350 mg/ml, 100 ml (350PP), positive pressure drip infusion method using Iohexol 300 mgI/ml, 100 ml (300PP) or conventional drip infusion method using Iohexol 300 mgI/ml, 100 ml (300DI). Enhancement effects of the liver parenchyma, the aorta and the spleen at upper, middle and lower levels of the liver were evaluated with increased attenuation on pre- and postcontrast CT. And intrahepatic contrast was evaluated with attenuation difference between liver parenchyma and intrahepatic vessels on postcontrast CT. In result, 300PP kept better enhancement effects and obtained better intrahepatic contrast than 300DI at the each level of the liver, and 350PP was still better than 300PP. The analysis of relationship between intrahepatic contrast and body weight suggested that 300PP was the optimal choice for the cases with 40-50 kg body weight and 350PP was for the ones with 50-60 kg as the infusion method of routine contrast enhanced CT. And the dose of contrast media seemed to be more needed for the cases over 60 kg body weight. 350PP and 300PP were concluded as useful, safe and simple methods for routine contrast enhanced CT of the liver.

Body Weight↗

[Comparison of rhinomanometric values expressed by rate--validity and normal range].

The nasal patency during respiration is today usually expressed by the nasal resistance. However, the nasal resistance is not the same throughout the total respiratory phase. Therefore, the reference point to express the resistance is therefore necessary to facilitate the mutual comparison of the data. The international committee for standardization of rhinomanometry has been paying a great effort to decide where this reference point should be set up, but has not yet reached the final consensus. The purpose of this study is to present a new method to estimate nasal respiratory conductivity, regardless of the reference point. Pressure flow curves during nasal respiration are quite similar in nature and rarely cross one another. The parabolic curves which do not cross each other can be superimposed by multiplying the standard equation, V = n.f(P). Accordingly, n is only one parameter in comparing these curves. A standard curve is decided as follows. Rohrer's equation was examined by polynomial regression analysis and concluded to be adequate to simulate a pressure flow curve. Rohrer's equation is converted to the function of P. Integration of this equation along P gives the value of the area under the curve (AUC). The total AUC can be obtained by simply adding the AUC of right and left sides. Definite integration from the origin to 1.0 and 2.0 on the abscissa gives the numerical value of AUC in each curve. The mean AUC is easily calculated by simple mathematical averaging of the data. K1 and K2 of the standard curve are calculated by solving simultaneous equations using mean AUC. K1 and K2 during expiration and inspiration are calculated, respectively. 718 subjects who had not been recently suffered from nasal diseases were examined by active anterior rhinomanometry. 47 functionally normal subjects in twenties were selected for calculation of the standard curve using the above mentioned method. In expiration, the values of K1 and K2 were 0.5476 and 1.3653, respectively. In inspiration, they were 0.4080 and 1.4750. Individual curve can be expressed by only one parameter. The normal range during nasal respiration is considered to be more than 0.7. The method presented in this study is convenient for the mutual comparison of the data both in clinical and basic research.

Adolescent↗