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Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 235 records · Page 13Linked to original sources

Peptide hormone production in small cell lung carcinomas with particular reference to gastrin-releasing peptide.

Tissues of 50 small cell lung carcinomas were examined for production of 17 peptide hormones. Only when the concentration of a peptide detected in the tumor was 10 pmol or more per g wet weight, was the peptide considered to be produced by the tumor. The frequency of production of at least one of these peptide hormones was 84%, and that of two or more hormones was 50%. These results indicate that peptide hormone production is a very common phenomenon in small cell lung carcinoma. Of the peptide hormones examined, gastrin-releasing peptide is produced with the highest frequency, suggesting that this peptide could play an important role in small cell lung carcinoma.

Adult↗

[Synthetic salmon calcitonin as an antihypercalcemic agent for hypercalcemia in malignancy].

Hypercalcemia is one of the most critical complications in patients with malignancy. We have used salmon calcitonin for treatment of hypercalcemia in these patients. The subjects were 49 hypercalcemic patients with various malignancies. Synthetic salmon calcitonin (SCT) was provided by Teikoku Hormone Mfg. Co. Ltd., Japan and 40 MRC units was administered twice daily i.m. or i.v. In 21 of 33 cases treated i.m. and in 8 of 16 cases treated i.v., a serum Ca decrease of more than 2 mg/dl was observed. The hypercalcemia was managed in 59% of patients within 6 days after initiation of the treatment and effective duration was 14 days. On the other hand, ineffective cases treated with a combination of SCT and glucocorticoid or SCT and mithramycin were managed in 57% and 86%. The 50% survival time was 69 days in the effective cases and 23 days in the uncontrolled cases (P less than 0.01). The main causes of death in the ineffective cases were renal insufficiency. On the other hand, in the effective cases, improvements of renal function were observed. The side effects were slight, and nausea and flushing were observed in 24% of cases. These data indicate that SCT is effective for lowering the serum Ca level in hypercalcemic patients with malignancies.

Adult↗

Immunocytochemical staining of estrogen receptor in paraffin sections of human breast cancer by use of monoclonal antibody: comparison with that in frozen sections.

Estrogen receptor (ER) in human breast cancer tissues was demonstrated in paraffin sections as well as in frozen sections by immunoperoxidase methods using monoclonal antibody (H222) against ER. The avidin-biotin-peroxidase complex method was used for the paraffin sections fixed in cold buffered formalin, and the peroxidase-antiperoxidase method was used for the fixed frozen sections. The results were compared with the ER content in the respective tumor tissue determined by dextran-coated charcoal assay. The specific staining for ER was located exclusively in the nuclei of cancer cells in both paraffin and frozen sections. Differences in the intensity and distribution of nuclear staining within a section were often observed, suggesting heterogeneity of the ER content of individual breast cancer cells. In 24 breast cancer tissues studied simultaneously by both paraffin and frozen section methods, 21 (88%) showed similar evaluation of the presence of ER. The results of immunocytochemical staining agreed with those of the dextran-coated charcoal assay in 89 (82%) of the 109 paraffin-sectioned tumor tissues and in 24 (86%) of the 28 frozen-sectioned tissues, indicating that ER can be demonstrated immunocytochemically by use of paraffin as well as frozen sections.

Antibodies, Monoclonal↗

[CA 15-3 is present as a novel tumor marker in the sera of patients with breast cancer and other malignancies].

As a novel tumor marker, we employed a quantitative sandwich RIA system utilizing two monoclonal antibodies (115D8, DF3) which react with a circulating antigen expressed by human breast cancer cells. The optimum condition for this assay was found be a 60 minute incubation at 37 degrees C for the first reaction and a 60 minute one at 25 degrees C for the second reaction. Under these optimum conditions, intra-assay variation of control sera was CV 3.6% and inter-assay variation was CV 6.6%. The observed range of CA 15-3 concentration in 75 healthy persons was 7.5 +/- 3.4 units/ml (mean +/- SD) and mean +2 SD was 14.2 U/ml. Less than 15 U/ml was decided as the cut off level. The positive rate in 113 patients with benign diseases was 18%, the serum levels being less than 25 U/ml. Increased CA 15-3 levels in sera of 178 patients were found respectively, in 0%, 41%, 45%, 50% and 75% of stage I, II, III, IV in primary breast cancer and advanced breast cancer. The sera of 10 patients with advanced breast cancer were collected regularly during a 2 to 4 month period. All patients with PD showed increased CA 15-3 levels and four patients in PR showed a clear decrease of serum levels. In 167 other malignancies, increased levels were found in 76%, 63%, 58%, 33%, 32% and 22% of the sera from uterine, pancreatic, ovarian, prostatic, lung and gastric carcinomas. The data revealed that serum CA 15-3 was clinically useful as a tumor marker especially a monitoring marker of advanced breast cancer, but presently the assay is not suitable for the early detection of breast tumors. Also its measurement seemed to be useful in ovarian cancer, uterine cancer, pancreatic cancer and adenocarcinoma of the lung.

Antigens, Neoplasm↗

Stimulation of hepatic glycogenolysis by 12-O-tetradecanoylphorbol-13-acetate (TPA) via a calcium requiring process.

12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulated glycogenolysis in perfused rat liver which was perfused with Krebs-Ringer-bicarbonate buffer containing 1 mM CaCl2 but no substrate. Verapamil (100 microM), diltiazem (100 microM) and trifluoperazin (100 microM), all inhibited the effect of TPA in the presence of CaCl2. Omission of CaCl2 from the perfusate or the addition of EGTA markedly attenuated the effect of TPA. TPA decreased net release of 45Ca from 45Ca-preloaded liver. The effect of maximal concentration of TPA (20 ng/ml) was not additive to that of 0.6 microM A23187. These data suggest that TPA increases calcium influx into hepatocytes and stimulates glycogenolysis through a calcium-calmodulin dependent mechanism.

Animals↗

Concomitant production of immunoreactive gastrin-releasing peptide and calcitonin in medullary carcinoma of the thyroid.

Immunoreactive gastrin-releasing peptide (IR-GRP) was found to be present in medullary carcinoma of the thyroid (MCT) by use of a radioimmunoassay (RIA) specific for the carboxyl-terminal portion of GRP. Immunohistochemical studies revealed IR-GRP in the MCT tumor cells, indicating that the tumor cells produce IR-GRP. Immunoreactive GRP was also detected in macroscopically normal thyroid tissue of patients with multiple endocrine neoplasia type II (MEN II, or Sipple's syndrome) and in areas of C cell hyperplasia and micronodules in the thyroids of patients with MCT. When these tissue extracts were examined with a bombesin RIA that recognizes bombesin but not GRP, no IR-bombesin was detected, suggesting that the IR-GRP detected in these tissues is more similar to GRP than to bombesin. IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was elevated to 130 to 780 pg/mL (normal: undetectable, less than 62.5 pg/mL) in three patients with metastatic MCT, and both calcium and tetragastrin increased the plasma levels of IR-GRP. Sephadex G-50 gel filtration of the MCT extracts revealed two peaks, one coeluted with porcine GRP (1-27) and the other eluted just after its carboxyl-terminal (14-27) fragment. There was a significant correlation (P less than 0.01) between the concentration of IR-GRP and that of IR-calcitonin in MCT tumor tissue and in macroscopically normal portions of thyroid tissue from two patients with MEN II, although the concentration of IR-GRP was only about 0.1% of that of IR-calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Bombesin↗

Rapid and specific radioimmunoassays for beta-endorphin and beta-lipotropin in affinity-purified human plasma.

Using rapid and reusable affinity columns, we established a method to measure beta-endorphin (beta END) and beta-lipotropin (beta LPH) separately in human plasma. One column contained antibodies against the N-terminal portion of beta LPH, and the other contained antibodies against beta END. The first column separated beta LPH from beta END and concentrated beta LPH as well, and the second separated beta LPH from concentrated beta END. Mean plasma levels (at 0830-0930 h) of beta END and beta LPH in 10 normal subjects were 1.1 +/- 0.1 (+/- SE) and 4.1 +/- 0.4 fmol/ml, respectively; both were markedly elevated in patients with ACTH/LPH hypersecretory states. The molar ratios of plasma levels of beta END and beta LPH were fairly constant in normal subjects (0.28 +/- 0.01), unchanged in patients with Cushing's disease and Cushing's disease after adrenalectomy, lower in patients with Addison's disease (P less than 0.001), higher in patients with chronic bone pain (P less than 0.001), and variable in patients with the ectopic ACTH syndrome. These data indicate that beta END and beta LPH can be measured separately in plasma by simple and reproducible procedures.

ACTH Syndrome, Ectopic↗

Phospholipase A2 of chicken erythrocyte membranes.

Chicken erythrocytes have been found to have at least two kinds of phospholipase A2. The first is a soluble enzyme from the cytosole fraction and has no calcium sensitivity. The second can be extracted from the plasma membrane fraction with the nonionic detergent Triton X-100. In this study the membrane-bound enzyme was partially purified by affinity chromatography on phosphatidylcholine-Sepharose, and its specific activity was increased 1100-fold compared with that of the cell homogenate without nuclei. It has an optimum pH of 8.5 and required calcium for maximum activity. It showed the specificity for both phosphatidylcholine and phosphatidylethanolamine, but reacted preferentially on the former substrate. Analysis by concanavalin A-Sepharose affinity chromatography revealed that the membrane-bound phospholipase A2 was retained on the resin and could be eluted specifically with a haptenic sugar, methyl alpha-D-mannopyranoside. The enzyme seems to be either a concanavalin A-binding glycoprotein or a part of a complex with certain concanavalin A-binding glycoproteins.

Animals↗

[Antitumor activity of human interferons: their direct cytotoxic activity and clinical effects].

It was found that both interferon-beta and interferon-alpha had a direct cytotoxic action against a few sensitive cultured cell lines. The action was not concentration dependent, but time dependent. Interferons expressed their maximum effect when they were given daily for long time to nude mice bearing transplantable ascitic human cancer cell lines, indicating that interferons had schedule dependency. In preliminary phase II study of interferons (3-9 X 10(6) U daily im, iv or local use) to 40 patients with various malignancies, only one patient with B-cell lymphoma responded to systemic use of both interferons and two out of five patients with pleural malignant effusion of breast cancer also responded to intrapleural use of interferons. Side effects were usually mild, but included fever, weakness, gastrointestinal, hematopoietic, liver and kidney function disturbances.

Animals↗