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Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 541 records · Page 30Linked to original sources

Determination of an antibody-antigen binding constant by enzyme immunoassay and a theory for analysis of competitive binding of two ligands to heterogeneous receptor.

A method for determining antigen-antibody binding constants by using enzyme-labeled antigens has been developed. In the measurement, enzyme-labeled and unlabeled antigens (Ag* and Ag) were allowed to compete in binding to the antibody (Ab) under conditions where Ag* much less than Ab much less than Ag. The data were analyzed according to a new theory developed for the analysis of competitive binding of two ligands to a heterogeneous receptor. The theory indicates that the binding degree of a labeled ligand measured at various concentrations of the receptor can be used to prepare a standard curve relating the binding degree of the labeled ligand and the average of the concentrations of the free receptor components which are in binding equilibrium with another unlabeled ligand. For homogeneous receptors, the method gives usual binding constants for the unlabeled ligand, but for heterogeneous receptors, it gives a new type of average binding constant for the unlabeled ligand in which the contribution of each receptor component is amplified in proportion to its affinity against the labeled ligand. This average binding constant was named the "affinity-average binding constant." A rabbit anti-blasticidin S (BLS) antiserum analyzed by the present method using beta-galactosidase-labeled BLS as the labeled ligand was found to be fairly homogeneous with respect to the affinity and to have a binding constant of 1.48 +/- 0.24 (S.D.) X 10(8) M-1 for unlabeled BLS.

Animals↗

Renal cell carcinoma originating from dysplastic kidney.

A case of renal cell carcinoma developing from a unilateral dysplastic kidney is presented. The patient was a 33-year-old woman who had lumbago one year and a half prior to death. Multiple abnormal uptakes of 67Ga were seen by scintigraphy. Bone marrow biopsy indicated adenocarcinoma but the primary site was unknown despite extensive examination. At autopsy the carcinoma was wide-spread but no obvious primary-appearing lesion was detected in all the organs except the left kidney. Incidentally the patient had unilateral (left) renal dysplasia. An elaborate study revealed the primary site of the carcinoma within the cystic structure of the dysplastic kidney. This tumor showed reactivity with Dolichos biflorus agglutinin associated antigen (DBA-Ag), soybean agglutinin (SBA), and peanut agglutinin (PNA) which have reactivity with renal tubules.

Adult↗

A pitfall in the interpretation of intestinal metaplasia of the stomach.

Four cases having vacuolated gastric (pyloric) cells resembling the goblet cells of intestinal metaplasia are presented. Contrary to goblet cells of intestinal metaplasia, the vacuolated pyloric cells in the four cases herein reported were negative for mucus stains. Although the nature of these mucus-free vacuolated gastric cells remains obscure, their occurrence should be considered in studies of intestinal metaplasia of the stomach.

Gastric Mucosa↗

Promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis.

The possible discrepancy between the dose level required for promoting action (when given after the initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen) of hepatic promoters were investigated in an attempt to obtain a "practical" threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichlorethane (DDT) were used as promoters and 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) was used as the carcinogen. Male weanling rats were treated with either 600 ppm 3'-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5-500 ppm), or the animals were treated with a low dose (100 ppm) of 3'-Me-DAB plus a promoter at various dose levels (20-500 ppm). The effects of promoters were measured by scoring size and number of enzyme-altered islands (EAIs) at 12 and 24 weeks of age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10-500 ppm and 20-500 ppm, respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced carcinogenesis at all the dose levels tested, in contrast with the inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens.

Animals↗

Effect of a prostaglandin E1 derivative (OP-1206) and acetylsalicylic acid on electrically induced thrombosis in guinea-pig mesenteric artery and its modification by an inhibitor of prostaglandin I2 synthetase, tranylcypromine.

The antithrombotic effect of a prostaglandin E1 derivative, OP-1206 (17S-20-dimethyl-trans-delta 2-PGE1) X alpha-cyclodextrin clathrate (OP-1206 X alpha-CD), was compared with that of acetylsalicylic acid (ASA) in a electrically induced thrombosis model of guinea-pig mesenteric arteries using intact animals and animals subjected to the superfusion of tranylcypromine (TC, 15 mM) over their mesentery. The drug-effect was assessed by the change of the threshold voltage for the thrombus formation. 1) TC (1.5-15 mM) lowered the threshold voltage, and the effect was comparable to its inhibitory effect on PGI2 formation in vitro, suggesting that PGI2 generated in mesenteric arteries acts to prevent thrombus formation. 2) In intact animals, OP-1206 X alpha-CD at doses of 0.01-0.3 mg/kg, p.o. (as OP-1206), significantly and dose-dependently elevated the threshold voltage. ASA (30-1000 mg/kg, p.o.) significantly elevated the threshold voltage, but the effect reached to its maximum at 100 mg/kg and lessened with further increase of ASA. 3) In TC-treated animals, OP-1206 X alpha-CD elevated the threshold voltage dose-dependently, but the elevation of threshold voltage by ASA reached to its plateau level which was significantly lower than that obtained with OP-1206 X alpha-CD at 0.3 mg/kg, indicating that the antithrombotic effect of ASA is incomplete in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

Stimulatory guanine nucleotide binding protein activity in the erythrocyte membrane of patients with pseudohypoparathyroidism type I and related disorders.

The activity of stimulatory guanine nucleotide regulatory protein (Ns) in the erythrocyte membrane was assayed by the reconstitution method using plasma membrane of cyc S49 mouse lymphoma cells in 18 patients with type I pseudohypoparathyroidism (PHP-I), 2 with pseudopseudohypoparathyroidism (PPHP) and 30 normal subjects, in parallel with other clinical parameters. The Ns activity as expressed by per cent of pooled standard (mean +/- SE) was 78.9 +/- 6.1 in PHP-I patients, which was significantly lower (P less than 0.01) than the value in normal subjects, 99.5 +/- 2.4. In PHP-I patients, the Ns activities (Y) were in significant correlation with three clinical parameters examined (X), i.e., with body height in standard deviation score from the mean of the normal population at the corresponding age, Y = 89.4 + 10.4X (r = 0.616, P less than 0.01); with urinary cAMP excretion in relation to creatinine [cAMP(nmol)/Cr(mg)], Y = 56.3 + 7.2X (r = 0.501, P less than 0.05); and with TSH levels in plasma (microU/ml), Y = 129 - 3X (r = 0.639, P less than 0.01). The Ns activities of PPHP were as low as 53.8 and 60.0. The decrease of Ns activity in the cell membrane may be implicated in the development of the clinical symptoms such as short stature, decrease in urinary excretion of cAMP and latent or manifest primary hypothyroidism in PHP-I and possibly in skeletal abnormality in PPHP.

Adenosine Diphosphate↗

Enzyme immunoassay for the quantification of mithramycin using beta-D-galactosidase as a label.

A sensitive enzyme immunoassay for mithramycin (MTM) has been developed by using antibody induced in rabbits, beta-D-galactosidase-labeled MTM, and a double-antibody separation technique, which allowed us to measure accurately as little as 100 pg of MTM per assay tube. MTM-antibody was produced against MTM-bovine serum albumin conjugate prepared by the use of diazotized p-aminobenzoic acid as a cross-linker. The beta-D-galactosidase-labeled MTM conjugate was similarly prepared by a geometric m-isomer of diazotized aminobenzoic acid. This enzyme immunoassay was specific to MTM and showed a very slight cross-reactivity with MTM analogues, chromomycin A3 (5.6%) and olivomycin (2.4%), but no cross-reactivity with drugs commonly used with MTM in combination chemotherapy for cancer treatment. The values of MTM concentrations detected by this assay were comparable to those detected by the high-pressure liquid chromatography method. However, the enzyme immunoassay method was 100 times more sensitive in detecting MTM in lower concentrations. Using this assay, drug levels were easily determined in the blood and urine of rats during 6 h after i.v. administration of MTM in a single dose of 2.0 mg/kg. Since MTM has long been used against a variety of human cancers, the enzyme immunoassay of the drug will be a valuable new tool in clinical pharmacological studies.

Animals↗

Ultrastructure of pancreatic exocrine cells of the rat during starvation.

Ultrastructural changes of the pancreatic exocrine cells after 3, 7, 14, 21, 28, 35 and 42 days of starvation were observed in male rats aged from 16 to 18 months weighing between 600 and 700 grams. The number of zymogen granules after starvation decreased to less than about 70 per cent of that of the control. Changes in the rough endoplasmic reticulum were hardly seen up to 14 days of starvation as compared with the control, but were observed in the apical and basal cytoplasm of the cell from 21 days after starvation. Particularly in 35- and 42-day starved rats, the rough endoplasmic reticulum was frequently shortened and dilated, and changed to disorganized membranous structures. The lysosomes in the apical cytoplasm of the cell gradually increased in number after starvation, and contact or fusion between the zymogen granules and lysosomes (viz, so-called crinophagy) was often seen at 35 and 42 days of starvation. Large autolysosomes especially those containing zymogen granules and rough endoplasmic reticulum were also marked in the basal cytoplasm of the cell after 35 and 42 days of starvation. Alterations in the basal cytoplasm of the cell appeared later than those in the apical cytoplasm. It was considered that, owing to its role in protein synthesis, the basal cytoplasm of the pancreatic exocrine cells in starved rats might be protected as far as possible during long-term starvation.

Animals↗

Ultrastructural changes in pancreatic acinar cells of rats after administration of 4-hydroxyaminoquinoline-1-oxide.

Ultrastructural changes in the exocrine pancreas 24, 48, 72 and 168 hours after a single intravenous injection of 4-hydroxyaminoquinoline-1-oxide (4-HAQO), at a dose of 14 mg.per kg., were observed in male rats. At 24 hours after administration, multiple focal degenerative lesion-like large vacuoles in the acini, and a decrease in zymogen granules with dilation of the rough endoplasmic reticulum cisternae in the acinar cells were marked. At 48 hours, acinar cell degeneration and necrosis progressively increased. The nucleus, especially, appeared to be disorganized and lysosome-like bodies with various sizes were frequently observed. At 72 hours, acinar cell degeneration persisted in the acini, and the interstitial space with infiltration of inflammatory cells appeared edematous. In addition, ductular-like cells, which resembled intercalated duct cells, possessing a light cytoplasm with occasional mitoses were observed around the duct lumen. At 168 hours, the exocrine pancreas was occupied with proliferated ductular-like cells. Furthermore, acinar cells and acini regenerated to the normal pattern were sometimes found. Thus, the exocrine pancreas degenerated progressively up to 48 hours after administration of 4-HAQO, gradually came to be repaired by degrees from 72 hours and then partly appeared to be regenerated at 168 hours. It is suggested that the ductular-like cell might be the precursor of the acinar cell in the regenerating process after injection of 4-HAQO.

4-Hydroxyaminoquinoline-1-oxide↗

[Proton beam therapy].

Proton beam therapy has been developed for about the last ten years as one of the most reasonable treatment techniques in cancer therapy, based upon the beneficial features of proton beams. Because of the favorable clinical results obtained further progress in this form of treatment is expected. The fundamental and clinical features of this technique and also the future plans being studied at the moment are discussed here, based on the clinical results obtained mainly at the Particle Radiation Medical Science Center of Tsukuba University. The fundamental features of a proton beam are the possibility of selective irradiation of the tumor lesion and minimal irradiation of the surrounding normal tissues due to its fine dose distribution and favorable biological response which is similar to that of 60Co gamma rays. Due to these beneficial features of proton beams, tumor lesions have been successfully irradiated with sufficiently large doses, avoiding irradiation of important organs close to the lesions. Treatment results revealed sufficient control of lesions resistant to conventional radiotherapy, such as locally advanced lesions, lesions with large volume or those with low sensitivity. These results suggested that proton beam therapy could be applied to radical treatment of lesions over a much wider indication range, especially in deep-seated organs, compared with conventional radiotherapy. Investigations of proton beam treatment are to be further continued with the development of techniques to delives precisely controlled irradiation to lesions in moving organs and of a treatment unit installable in cancer hospitals.

Carcinoma, Squamous Cell↗

[Clinical investigation of indications in proton therapy].

The indications for curative treatment with proton therapy were investigated by the clinical results of 31 cancer patients treated with proton beams between 1983 and 1985 at the Particle Radiation Medical Science Center of Tsukuba University. Many locally extended, radioresistant lesions, lesions with large volume and small radiocurable lesions in this series revealed sufficient improvement without definite late damage in the surrounding normal tissues. This clinical result suggests that proton beam treatment could be applied to lesions in a much wider range for curative purposes as compared with conventional radiotherapy. This study is to be continued further.

Adult↗

[Postoperative recurrence and death rates of poorly differentiated carcinoma of the thyroid].

Postoperative recurrence and death rates of 54 cases of poorly differentiated thyroid carcinoma were analyzed. The rates of recurrence of 18 widely resected cases during 1979 and 1981 and 36 patients undergoing conventional surgery during 1965 and 1978 were 22.2% and 50%, respectively. The difference between the figures was statistically significant (p less than 0.05). The death rates of the two groups were 5.6% and 41.7%, respectively. These results indicate that wide resection is appropriate in the surgical treatment of the thyroid.

Carcinoma↗

[Combination chemotherapy with vincristin, actinomycin D, cyclophosphamide and adriamycin in soft-part sarcoma].

Fifteen patients with soft-part sarcoma were treated with combination chemotherapy consisting of vincristin, actinomycin D, cyclophosphamide and adriamycin (VACA therapy). The cumulative five-year survival rate by the Kaplan-Meier method was about 73%. This VACA therapy was effective for malignant fibrous histiocytoma and synovial sarcoma as well as rhabdomyosarcoma. Side effects such as anemia, leucocytopenia, nausea and alopecia were observed, but could be managed. VACA therapy is considered to be useful as a combination chemotherapy for patients with soft-part sarcoma.

Adolescent↗

[Pulmonary malignant lymphoma--a case report].

A case of pulmonary malignant lymphoma is reported. A 65-year-old woman had no complaint. But chest roentgenography and CT revealed an infiltrating shadow with marked airbronchogram in the left S3. TBLB revealed marked subepithelial lymphocytic infiltration of the bronchial wall. Because the shadow had gradually enlarged, malignancy was suspected and lobectomy was performed. The resected specimen showed a 60 X 56 X 30 mm greyish-yellow, medullary tumor with intrapulmonary metastasis. Microscopically, well-differentiated small lymphocytic tumor cells severely infiltrated the pulmonary parenchyma, pleura and bronchial cartilage. There was no lymph node metastasis or extrapulmonary involvement. Immunohistochemical study proved the monoclonality of the K chain. She was treated with chemotherapy postoperatively.

Aged↗