Biomedical subjects

M Akagi

Publications and source records attributed to M Akagi.

At least 163 records · Page 9Linked to original sources

PubMed1987

Comparative effectiveness of the tumour diagnostics, CA 19-9, CA 125 and carcinoembryonic antigen in patients with diseases of the digestive system.

Serum concentrations of CA 19-9, CA 125 and carcinoembryonic antigen (CEA) in 145 patients with gastrointestinal carcinomas and 89 with non-neoplastic diseases were determined to compare the clinical usefulness of these tumour markers. Significantly fewer positive cases were obtained with serum CA 19-9 (9%) and CA 125 (8%) tests than the CEA test (22%) (both p less than 0.05) in patients with benign diseases, while comparable sensitivities were achieved with the CA 19-9 (44%) test, the CA 125 (41%) test and the CEA test (47%) in those with a carcinoma. High incidences of raised concentrations of serum CA 19-9 and CA 125 were observed in case of cancer of the pancreas (CA 19-9: 87%, CA 125: 67%) and biliary tract (CA 19-9: 63%, CA 125: 48%). Combined tests of CA 19-9 and CA 125 revealed increments in the sensitivity (61%) and provided a higher specificity (87%) than that of the single CEA test (78%). These combined tests were most useful for a differential diagnosis of pancreatic carcinoma (97% positive) and biliary tract carcinoma (74%) from chronic pancreatitis (4%) and cholelithiasis (0%), respectively. Studies on the relations of clinical staging and serum concentrations of CA 19-9 and CA 125 revealed significant rises in cases of disseminated carcinoma. These results clearly show that serum CA 19-9 and CA 125 tests are most pertinent for diagnosing advanced carcinomas of organs in the digestive system.

Antigens, Neoplasm↗

PubMed1987

Inhibitory effects of oxatomide on intracellular Ca mobilization, Ca uptake and histamine release, using rat peritoneal mast cells.

Oxatomide at concentrations of 0.01-10 microM inhibited not only an increase in 45Ca uptake but also the intracellular Ca2+ release induced by compound 48/80 in rat peritoneal mast cells. At higher concentrations, ketotifen or other calcium antagonists caused similar inhibitory effects. However, the inhibitory effect of oxatomide on the 45Ca uptake into rat neonatal heart cells was much weaker than that of verapamil. Through image processing of quin 2-stained mast cells, it was revealed that oxatomide inhibited Ca2+ release from the intracellular store. Although oxatomide alone did not affect cAMP and cGMP contents in sensitized guinea pig lung samples, the drug effectively prevented changes in the nucleotide contents evoked by antigen challenge. These results suggest that the inhibitory effect of oxatomide on histamine release may be caused by a combination of prevention of Ca uptake, which is highly selective toward mast cells; inhibition of Ca2+ release from the intracellular Ca store, and elevation of the cAMP content in mast cells.

Aminoquinolines↗

PubMed1987

Necrobiosis-lipoidica-like skin manifestation in lymphomatoid granulomatosis (Liebow).

A 58-year-old man developed 3 indurative erythematous lesions like necrobiosis lipoidica on the right lower leg. He had had similar cutaneous lesions 1.5 years previously. These had been surgically excised, and a histologic diagnosis of necrobiosis lipoidica was made at another hospital. He was diagnosed as having lymphomatoid granulomatosis by lung biopsy in our hospital. Nasal involvement was confirmed in later examinations and the skin lesions were also considered to be the cutaneous manifestation of lymphomatoid granulomatosis. This outlines that cutaneous manifestations may allow early diagnosis of lymphomatoid granulomatosis.

Biopsy↗

PubMed1987

Antiallergic effects of terfenadine on immediate type hypersensitivity reactions.

Terfenadine dose-dependently inhibited rat homologous PCA (2.5-10 mg/kg, p.o.) and experimentally-induced asthma in guinea pigs (0.5-5 mg/kg, p.o.). Similarly, metabolites I and II dose-dependently inhibited experimentally-induced asthma but their respective potencies were approximately 1/2 and 1/15th that of terfenadine. These results suggest that the metabolites contribute to the antiallergic effects of terfenadine. In ex vivo, terfenadine (5-20 mg/kg, p.o.) also inhibited the release of both antigen-induced histamine and SRS-A from sensitized guinea pig lung samples and that of histamine from rat peritoneal mast cells. Terfenadine dose-dependently increased the cAMP content in rat mast cells and in the lungs; in the latter, the augmented cAMP is associated with an increase in adenylate cyclase activity, but not with the inhibition of phosphodiesterase activity. The above evidence indicates that the inhibitory effects of terfenadine on mediator release from mast cells are in some way related to its antiallergic effects, and that an elevated cAMP content may be effective to enhance mediator release inhibition.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1987

Isolation of complementary DNA clones for genes exhibiting reduced expression after treatment of mouse teratocarcinoma stem cells with a tumor-promoting phorbol ester.

For the study of the effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on early mammalian cell differentiation, a complementary DNA (cDNA) library was constructed on the poly(A)+RNAs extracted from undifferentiated F9 cells derived from a 129/Sv mouse teratocarcinoma OTT6050, and screening was done for the cNDA sequences corresponding to the mRNAs, the levels of which decreased significantly in the F9 cells after the TPA treatment. From about 80,000 clones screened, 3 different cDNA clones, pFT27, pFT43, and pFT60, were isolated and characterized. Levels of the RNAs hybridizable to these clones were decreased by fourfold to more than fiftyfold within 1-10 hours in the presence of TPA. Northern blotting experiments identified transcripts corresponding to these clones: pFT27 hybridized to 3.0 kb RNA, pFT43 hybridized to 1.5 kb RNA, and pFT60 hybridized to 1.0 kb RNA. The levels of these 3 transcripts were also decreased after treatment of the undifferentiated F9 cells with retinoic acid (RA) and dibutyryl cyclic AMP (cAMP). The TPA-induced as well as the RA- and cAMP-induced decreases in the RNAs hybridizable to pFT27 were regulated at the transcriptional level, whereas similar decreases in the RNAs hybridizable to pFT43 and pFT60 were regulated at the post-transcriptional level. These findings show that TPA treatment shares common effects with RA and cAMP on the undifferentiated F9 cells.

Animals↗

PubMed1987

[Postoperative changes in serum levels of iron, transferrin and ferritin in surgical patients].

The association of serum levels of iron, transferrin and ferritin with surgical trauma has been analyzed in 21 surgical patients. The apparent decline of serum iron concentration was seen in the early stage of postoperative period, which was significantly manifest among the patients with major surgical process, such as pancreatectomy and hepatectomy etc. And there was no relationship between serum levels of iron and volumes of bleeding during operation and/or volumes of blood transfusion. Similarly, serum transferrin concentration decreased. On the other hand, serum ferritin concentration elevated after operation. These factors gradually returned to the preoperative levels with recovery from surgical injury. The transferrin decline in serum concentration was thought to be due to a change as rapid turnover protein. However, the decline of serum iron concentration and the elevation of serum ferritin concentration might be associated with cellular proliferative activity to repair operative injury. These results suggest that the condition of iron metabolism in management of surgical patients should be important.

Adult↗

PubMed1987

The histogenesis of DMH-induced colonic carcinoma in rats.

Twenty-one Donryu male rats of six weeks old were injected with 1,2-dimethyl-hydrazine hydrochloride (DMH), once a week, for 4 to 20 weeks, and sacrificed at intervals of two weeks since a lapse of four weeks after the commencement of the injections. The DMH induced 320 atypia lesions, from 0.03 through 20 mm in size, of grade II or higher. The rate of benign lesions was higher in the group receiving less than 20 injections than in the group of 20 injections of DMH, while in the latter group, the rates of the benign, borderline and malignant lesions were stable, suggesting that benign lesions mainly develop in the earlier period of the DMH treatment, and thereafter various grades of lesions develop at a constant rate. All the benign lesions were less than 1 mm in size, and all lesions greater than 1 mm were malignant. In addition, the size of the lesion was significantly greater when it was occupied by malignant crypts in a greater rate. These results indicate that the benign lesions become cancerous before they reach a certain size (adenoma-carcinoma sequence). Twenty-seven minute lesions (less than 1 mm) were mixed lesions of malignant and benign atypia, suggesting that the adenoma-carcinoma sequence is elicited in any size of lesion. On the other hand, there were 41 minute malignant-only lesions, which constituted 27.7% of the overall minute lesions and included three "single crypt" cancers. In addition, malignant-only lesions were smaller when compared to the malignant-dominant mixed lesions. These results indicate that about 30% of colon cancers develop de-novo.

Animals↗

PubMed1986

Immunohistochemical detection of glycogen phosphorylase isoenzymes in rat and human tissues.

Glycogen phosphorylase has at least three isoenzymes, i.e. muscle-, liver-, and brain-types. Antibodies have been raised against highly purified isoenzymes from rat muscle, liver and brain and found to react specifically to extracts from human muscle, liver and brain, respectively. Using these antibodies and the unlabelled antibody-enzyme method, each of the three isoenzymes has been localized in both rat and human tissues.

Animals↗

PubMed1986

Distribution of actin filaments in rat mast cells and its role in histamine release.

The distribution of actin filaments was confirmed by immunofluorescence microscopy and immuno-electron microscopy in nonsecreting and secreting rat peritoneal mast cells. In a resting cell, immunofluorescence of the actin showed up as a net-like formation surrounding each granule. After stimulation with compound 48/80 or A-23187, the distribution of the actin filaments became very irregular and disordered, disappearing completely in some areas within the cell and expanding in conjunction with the swelling of the granules. Similar changes are seen in a passively sensitized mast cell exposed to antigen. When cells were pretreated with cytochalasin B or colchicine, the distribution of actin filaments was not greatly affected by stimulation. The results clearly show that actin filaments exist in mast cells.

Actins↗

PubMed1986

Tamoxifen binding sites in human mammary cancers.

Tamoxifen binding sites (TBS) were measured using 3H-tamoxifen, the objective being to evaluate the relationships among TBS and hormone receptors and/or clinical and pathological characteristics in malignant tissues from 60 patients with mammary cancer. TBS were detected in most (96.7 per cent) cancers in the breast tissues, and the mean content and affinity were 569 fmol/mg X protein with Kd: 1.98 nM. There was no significant correlation between TBS and the estrogen receptor and/or progesterone receptor, with respect to positivity or content. However, there was a significant correlation between TBS and histological grading, thereby indicating the differentiation and the proliferative activity in this tissue. The content of TBS was significantly higher in the group with a high grade of malignancy. The TBS content significantly increased in parallel with the degree of malignancy, as related to tubule formation, nuclear pleomorphism and mitotic activity. On the other hand, there was no significant correlation between TBS and age, tumor size, lymph node status or clinical stage. These results suggest the possibility that TBS may be associated with differentiation and cell-proliferation in breast cancer tissues.

Adenocarcinoma↗

PubMed1986

Enhanced endotoxin clearance in reversed Eck fistula rats during a tolerant stage.

The effects of tolerance to Escherichia coli endotoxin on the clearance activity of the hepatic reticuloendothelial system was examined using the experimental animal model of the reversed Eck fistula (REF). Compared with clearance rate of 51Cr-labeled endotoxin in the normal REF-rat, in the tolerant reversed Eck fistula animals, there was three fold increase in the clearance of endotoxin in the liver. The enhanced endotoxin uptake of the hepatic reticuloendothelial system was observed when the medium containing serum from tolerant animals was infused into the non-tolerant liver with a Harvard pump before the clearance studies, using 51Cr-labeled endotoxin administered via the femoral vein. Heat treatment of tolerant serum at 56 degrees C for 45 min destroyed the enhancing effect. These results suggest that during endotoxin tolerance, humoral factors, particularly complement, play an important role in the uptake of endotoxin from portal vein blood. A direct stimulation of the hepatic reticuloendothelial system may also occur.

Animals↗

PubMed1986

Mechanisms of acute gastric mucosal lesion accompanying obstructive jaundice--role of bile acids in plasma.

The mechanism of acute gastric mucosal lesion (AGML) accompanying obstructive jaundice was studied in male Wistar rats, with special reference to the effect of bile acids in plasma on mucosubstances in the gastric mucosa. Following ligation of the common bile duct, total plasma level of bile acids increased 24 folds over the control level, and gastric mucosal mucus contents, measured biochemically or histochemically, significantly decreased. Effect of increased bile acids in the blood stream on the gastric mucosa was estimated by continuous intravenous administration of sodium taurocholate. After 24 hours infusion, both gastric acid output and gastric mucus contents significantly decreased. Further imposition of restraint and water immersion stress produced AGML significantly earlier than in control rats with continuous intravenous infusion of 0.9% NaCl. These data suggest that the increased plasma level of bile acids play an important role on the reduction of the gastric-mucosal defense mechanism in obstructive jaundice directly through their toxic effects, and that this easily results in the formation of AGML under additional stresses.

Acute Disease↗

PubMed1986

Evaluation of serum CA125 values in healthy individuals and pregnant women.

CA125 is an antigenic determinant associated with human epithelial ovarian carcinoma. This study was undertaken to evaluate the distribution of serum CA125 levels and the effect of smoking on these levels among healthy individuals and clarify the relation of maternal serum CA125 level and pregnancy. Among 552 healthy individuals, the distribution of serum CA125 values was demonstrated to resemble logarithmic normal distribution. Analysis of variance about age and sex revealed apparent elevation of values for women under 49 years of age in comparison with those for women over 50 years of age and men. Values for these two groups were 143 units/ml for the former and 32 units/ml for the latter, with a 99.7% confidence limit. These values exclude 99.3% of the former and 99.7% of the latter. Serum CA125 values were not affected by smoking. The measurement of serum CA125 levels in 71 pregnant women disclosed a significant elevation during the first trimester in comparison with nonpregnant women under 49 years of age. These results indicate that CA125 values must be deliberatively evaluated in young women, especially during first trimester of pregnancy.

Adult↗

PubMed1986

Clinical significance of serum CA125 values in patients with cancers of the digestive system.

A study of 347 patients with gastrointestinal diseases revealed elevation of CA125 in sera of 63% of patients with pancreatic carcinoma, 46% of patients with carcinoma of the biliary tract, 40% of patients with liver carcinoma and 11-37% of patients with other carcinomas. All of the patients with acute pancreatitis, chronic pancreatitis, cholelithiasis, and peptic ulcer had normal CA125 values, but 35% of patients with liver cirrhosis and 10% of patients with chronic active hepatitis had elevated values. Patients with disseminated carcinomas had significantly higher levels than patients with localized carcinomas. CA125 did not significantly correlate with CA19-9 or carcinoembryonic antigen in patients with pancreatic carcinoma. Ninety-seven percent of patients with pancreatic carcinoma were defined as being positive when both serum CA125 and CA19-9 were evaluated. These results indicate that CA125 is useful for differentiating pancreatic carcinoma from chronic pancreatitis, especially when supplemented with CA19-9.

Antigens, Neoplasm↗

PubMed1986

Endotoxin inactivating activity of rat serum.

The ability of rat serum to inactivate endotoxin (LPS) was assessed with the aid of the limulus amebocyte lysate assay. Following the addition of various amounts of endotoxin to normal serum the mixture was incubated for 1 hr at 37 degrees C and the residual endotoxin activity determined. One milliliter of rat serum inactivated between 5 and 10 micrograms Escherichia coli LPS per hour. Heating serum for 45 min at 56 degrees C resulted in loss of 80-90% of the LPS inhibitor (LPSI) activity. Serum from cobra venom factor (CVF)-treated rats inactivated between 0.5 and 2.5 micrograms LPS/ml serum. Serum from tolerant rats, even after heating for 45 min at 56 degrees C, inactivates between 10 and 15 micrograms LPS/ml serum/hr; decomplemented tolerant rat serum neutralizes between 5 and 10 micrograms LPS/ml serum/hr. Clearly, the tolerant rat has large quantities of LPSI activity, which does not appear to be complement. The inhibitor found in tolerant rat serum is not species specific since it inactivates Salmonella minnesota and Salmonella typhimurium endotoxins to the same degree and in the same amount as E. coli endotoxin, the agent used to induce tolerance. Both heating serum (56 degrees C) and lead acetate reduce LPSI activity.

Animals↗

PubMed1986

Establishment of a cell line of gallbladder carcinoma (GBK-1) producing human colony stimulating factor.

A cell line designated GBK-1 was established from a patient with anaplastic carcinoma of the gallbladder, marked neutrophilia and fever, and has been propagated for the past 18 months. The cells grew as a monolayer sheet with a doubling time of 43 hr. The GBK-1 cells were of a pleomorphic polygonal epitheloid shape and they were transplantable into nude mice. Mice bearing the tumor developed marked granulocytosis. In the culture supernatant of GBK-1 cells, high colony stimulating factor (CSF) activity was evident with both human bone marrow cells and C57BL mouse bone marrow cells, and granulocytic colonies, macrophage colonies or granulocyte-macrophage mixed colonies were produced. The CSF activity was distributed in the molecular weight range of 25,000 to 60,000 with two distinct peaks at molecular weights of approximately 50,000 and 30,000. CSF activity was inactivated by heat treatment at 70 degrees for 30 min. GBK-1 is a new human cell line that produces heat-labile human GM-CSF.

Animals↗

PubMed1986

Plasminogen activator as a functional marker for estrogen dependence in human breast cancer cells.

To examine whether plasminogen activator reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors, such as cytoplasmic estrogen receptor (ERC), progesterone receptor (PgR) and nuclear estrogen receptor (ERN). With any receptor, plasminogen activator activity was significantly higher in receptor-positive tumors than in receptor-negative tumors. When these breast tumors were categorized into 8 groups in terms of combinations of receptor status, breast cancers which were positive for all these receptors were found to contain the highest plasminogen activator activity. Furthermore, quantitative analyses demonstrated positive correlations of the enzyme activity with either ERC content (correlation coefficient +0.37, P less than 0.001) or PgR content (correlation coefficient +0.45, P less than 0.001). These results strongly suggest that plasminogen activator can be used as an effective functional marker for hormone dependence in human breast cancer.

Breast Neoplasms↗

PubMed1986

Clinical evaluation of an immunoradiometric assay for CA15-3 antigen associated with human mammary carcinomas: comparison with carcinoembryonic antigen.

Serum levels of CA15-3, a mammary tumor associated antigen recognized by two different murine monoclonal antibodies (115D8 and DF3), were investigated in patients with mammary carcinoma and other benign or malignant diseases. The reference value of the serum CA15-3 level was obtained as 24 units/ml at the 99% confidence limit among healthy individuals (n = 462). Elevation of serum CA15-3 levels was observed in 24.3% of overall patients with mammary carcinoma. Serum CA15-3 levels in breast cancer patients correlated with the clinical stage; higher percentages of positivity were observed in those with advanced breast cancer (stage IV, 64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore, elevated serum CA15-3 levels in breast cancer patients responded well to the effect of therapy. Although the serum CA15-3 test gave percentages of positivity of breast cancer similar to those found by the serum CEA test, the serum CA15-3 test revealed lower percentages of positivity than the serum CEA test among patients with benign breast lesions, liver cirrhosis or other carcinomas. These results suggest that the serum CA15-3 antigen level provides a very useful marker for diagnosis and clinical monitoring of patients with breast cancer.

Adolescent↗