Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 19 recordsLinked to original sources

PubMed1992

Stimulation of anchorage-independent cell growth by endothelin in NRK 49F cells.

Endothelin (ET) is a vasoconstrictor peptide originally isolated from vascular endothelial cells. Recent studies have revealed that ET has many biological functions including growth factor-like activity. The present study aims to clarify whether ET-1 possesses the ability to stimulate anchorage-independent cellular growth, an indicator of factors with transforming activity. We found that NRK 49F cells possess a large number of high-affinity ET-1 receptors; labeled 125I-ET-1 binding was displaced by unlabeled ET-2 in a similar dose response, but in the case of ET-3, 100-fold more was required. Specific 125I-ET-3 binding was undetectable in NRK 49F cells, indicating that ET receptors in NRK 49F cells are ET-1/ET-2 selective. NRK 49F is a cell line which is most commonly used to assay for anchorage-independent cellular growth. Therefore, we explored whether ETs promote anchorage-independent cellular growth in this cell line. ET-1 and ET-2 stimulated NRK colony formation dose dependently in the presence of 1 nM epidermal growth factor (EGF). In contrast, ET-3 did not have colony-stimulating ability. In the presence of EGF, the maximal effect of ET-1 was approximately 90% of that of transforming growth factor-beta. Moreover, in the presence of maximal stimulating concentrations of EGF and transforming growth factor-beta, ET-1 additionally induced colony formation. These results indicate that ET-1 and -2 possess transforming growth factor-like activity for NRK 49F cells. Since ET-1 and -2 increased intracellular calcium levels, this ion may participate in signal transduction pathways by which ET-1 and -2 promote colony formation.

Animals↗

PubMed1992

Differential expression of the "B" subunit of the vacuolar H(+)-ATPase in bovine tissues.

The B subunit is one of two nucleotide-binding polypeptides found in all members of the vacuolar class of H(+)-translocating ATPases. We have isolated aDNA clone encoding the bovine brain B (58 kDa) subunit and have deduced its amino acid sequence. The bovine brain amino acid sequence is 99% identical to a partial cDNA reported from human brain. Northern blot analysis of RNA isolated from bovine tissues and a bovine kidney cell line reveals that two messages of approximately 3.2 and 2.0 kilobases (kb) are expressed in all tissues examined except brain, where only the 3.2-kb message can be detected. Northern blotting of RNA isolated from human fibroblast and human lung tumor cell lines reveals that three messages of approximately 6.0, 3.2, and 2.0 kb are expressed, whereas only the 3.2-kb message is expressed in a human brain tumor cell line. This is the first demonstration of tissue-specific expression of multiple forms of a vacuolar H(+)-ATPase subunit. We have also isolated a partial cDNA clone from bovine brain which appears to encode an isoform of the B subunit. The deduced amino acid sequence is 82% identical to the major bovine brain B subunit sequence; it does not hybridize with either the 3.2- or 2.0-kb message on Northern blot. Southern blot analysis of bovine genomic DNA with probes derived from both isolated cDNAs indicates that the bovine B subunit is encoded by a multigene family.

Amino Acid Sequence↗

PubMed1992

Analysis of cytosol CA15-3, carcinoembryonic antigen, estrogen and progesterone receptors in breast cancer tissues.

Cytosol levels of carcinoembryonic antigen (CEA), CA15-3, estrogen receptor (ER) and progesterone receptor (PgR) of 194 primary breast cancer tissues were measured. ER and PgR determined by enzyme immunoassay methods correlated inversely with Page's grades of histological atypia and mitotic rate. Cytosol CA15-3 correlated inversely with the grades of tubular and nuclear atypia and positively with the mitotic rate. CA15-3 correlated positively with ER and PgR. Cytosol CEA showed no correlation with the pathological grade or hormone receptor status. These results indicate that hormone receptor-positive breast cancers tend to have more differentiated morphology and slower growth rate than those without those receptors and that the cytosol CA15-3 level may reflect some of the intrinsic malignant potency, particularly the growth rate, of breast cancer. Cytosol CA15-3 as well as the hormone receptor status may have prognostic value for patients with breast cancer.

Adult↗

PubMed1992

Bioavailability of morphine in rabbits after rectal administration of suppository containing controlled release morphine tablet.

Two kinds of sustained release morphine suppositories have been prepared; one is an oleaginous base suppository (MSC) containing a controlled release morphine tablet (MST: MS Contin), and the other is a hollow-type suppository (MSCH) containing MST and morphine powder packed in its hollow space. In vitro release tests and in vivo rectal absorption experiments in rabbits were performed. The profiles of morphine release from MST and MSC in vitro were similar, and revealed that suppository bases had no effect on the release profile of morphine from the preparation. Morphine release from MSCH was rapid in the early phase, and then enclosed morphine was slowly and continuously released from MST. Phamacokinetics of morphine from the suppository were compared with the orally administered MST, and it was found that there was no difference in the maximum plasma concentration (Cmax) and the peak time (Tmax) between MSC and MST, but the mean residence time (MRT) of MSC was approximately three times longer than that of MST, and the extent of bioavailability (BA) of MSC was significantly larger than that of MST (71.6 +/- 14.2% and 11.9 +/- 4.0%, respectively). Cmax can be altered arbitrarily by changing the morphine content in the hollow space of MSCH. As in the case of MSC, the plasma concentration of morphine from MSCH was maintained. It is concluded from the above results that MSC is a satisfactory sustained release morphine suppository for the treatment of cancer pain, administering it twice a day, and that MSCH is effective due to its fast analgesic effect and sustained release nature not only for cancer pain but also for surgical operations.

Administration, Rectal↗

PubMed1992

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve terminals in the whole mount preparations of the dog urethra.

To visualize the entire shape of the intraepithelial nerve fibers, whole mount preparations of the dog urethra were produced and immunostained with an antiserum against CGRP, one of the predominant substances contained in the nerves. The immunoreactive nerves in the lamina propria were smooth (non-beaded) in appearance and weak in immunoreaction. Within the epithelium, they displayed typical beaded profiles and were intense in immunoreaction. The intraepithelial fibers branched and wound into an extensive network with wide meshes ("reticular terminal"). The bead-like swellings included large ones resembling Herring bodies in hypophyseal neurosecretory fibers. Another type of nerve terminal, consisting of fine and weakly immunopositive fibers, was also found in the epithelium. These branched in dendritic or in dense bouquet-like fashion, occupying smaller areas ("bouquet-like terminals). Vesicular swellings often characterized these terminals, though they were smaller and more uniform in size and far less in their amount of immunoreactive substance than were the swellings in the reticular terminals. Both types of nerve terminals originated from the same nerve trunk. The connection between the reticular and bouquet-like terminals, which may presumably represent secretory and receptive parts, respectively, morphologically supports the possible occurrence of an axon reflex in the urethral CGRP neurons. Our whole mount preparations, when doubly stained with CGRP and serotonin antibodies, further revealed the CGRP-positive reticular terminals being closely associated with serotonin- or CGRP-immunoreactive paraneurons dispersed in the epithelium.

Animals↗

PubMed1992

Calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the tracheal epithelium of rats: an immunohistochemical study by means of whole mount preparations.

The airway mucosa is known to be densely supplied with several types of peptidergic nerve fibers. The distribution of the nerve fibers in a large extent of the mucosa, however, has been difficult to visualize by observation of conventional thin sections. In the present study, whole mount preparations of the rat tracheal mucosa were designed to demonstrate calcitonin gene-related peptide (CGRP)-containing nerves which are most predominant among peptidergic nerves in the trachea. The mucosal sheet of the trachea was separated from the cartilaginous base by means of dispase, a protease, to be processed to immunohistochemistry for CGRP. In the cartilaginous portion, thick nerve bundles immunoreactive for CGRP ran transversely between the cartilage rings, sending terminal branches toward the epithelium. In the membranous portion, immunoreactive nerve bundles were thinner than those in the cartilaginous portion and ran longitudinally. A very dense nerve plexus of CGRP-immunoreactive fibers was demonstrated to extend in the basal part of the epithelium; every epithelial cell appeared to contact more than one nerve fiber. Immunohistochemistry of the whole mount preparations also clearly demonstrated the distribution and entire shape of broncho-pulmonary paraneurons scattered in the epithelium. Ultrastructurally, the CGRP-immunoreactive intraepithelial nerves were found to lack myelin and Schwann sheaths, and to run through the bases of the epithelial cells; they were most frequently surrounded by the cytoplasmic processes of the epithelial cells. The present study demonstrates that immunohistochemistry of whole mount preparations is a useful tool to morphologically analyze neuronal and paraneuronal distribution throughout the tracheal epithelium.

Animals↗

PubMed1991

A single gene encodes the catalytic "A" subunit of the bovine vacuolar H(+)-ATPase.

We have previously demonstrated that the 73-kDa (A) subunit of the bovine coated vesicle (H+)-ATPase possesses a nucleotide binding site required for catalytic activity (Arai, H., Berne, M., Terres, G., Terres, H., Puopolo, K., and Forgac, M. (1987) Biochemistry 26, 6632-6638). Here we report the cDNA sequence of the coding region of the bovine brain A subunit. Comparison of the deduced amino acid sequence with those previously reported for the A subunits of vacuolar ATPases from lower eukaryotes, plants, and archaebacteria reveals significant homology, especially in sequences implicated in nucleotide binding. The message encoding the bovine brain A subunit is relatively large, approximately 4.6 kilobases; Northern blotting of RNA isolated from rat brain and human brain tumor cells reveals a message of similar size. Northern analysis of several bovine tissues indicates that only one message for this subunit is expressed. Southern blot analysis of bovine genomic DNA indicates that the bovine A subunit is encoded by a single gene.

Amino Acid Sequence↗

PubMed1991

Endothelin-1 inhibits adipogenic differentiation of 3T3-L1 preadipocytes.

The effect of endothelin (ET)-1 on the adipogenic differentiation of 3T3-L1 preadipocytes was examined. Cellular morphology and lipoprotein lipase activity were used as differentiation markers. ET-1 inhibited the hormone-induced adipogenic differentiation of 3T3-L1 preadipocytes morphologically and biochemically in a dose-dependent manner. These findings promote ET-1 as a potent inhibitor of adipogenic differentiation, playing an important role in cellular differentiation of preadipocytes and making it a significant regulator of lipid metabolism.

Adipose Tissue↗

PubMed1991

A case of cervical carcinoma of the uterus presenting with hyperosmolar non-ketotic coma as a manifestation of ectopic adrenocorticotropic hormone syndrome.

A case of advanced cervical carcinoma of the uterus with ectopic adrenocorticotrophic hormone (ACTH) syndrome is described. The patient was seen for general malaise 21 months after surgical treatment of the primary lesion whose histology was undifferentiated small cell carcinoma of the uterine cervix. She had extensive metastases in the liver and the abdominal wall. In addition to the typical clinical manifestations of Cushing's syndrome such as moon face, central obesity and acne vulgaris, hyperglycemia was so severe that she was in a hyperosmolar non-ketotic coma. Endocrinological examinations revealed elevated plasma ACTH and cortisol, and urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids, which were not suppressed by high-dose dexamethasone administration. Based on these clinical and laboratory findings, a diagnosis of ectopic ACTH syndrome was made. Among the results of other endocrinological examinations conducted to find the etiological cause of the hyperglycemic coma, which seemed to be unusual for ectopic ACTH syndrome, the plasma somatostatin level was abnormally high. Metastatic tumors in the liver obtained at the time of autopsy contained large amounts of both ACTH and somatostatin, and gel filtration studies revealed that the peptides produced by the tumor had the molecular sizes of the biologically active forms of the respective peptides. These observations suggest possible involvement of the somatostatin in deteriorating glucose intolerance to develop hyperglycemic hyperosmolar non-ketotic coma as a drastic disturbance of metabolism.

Adrenocorticotropic Hormone↗

PubMed1991

Study on the cupric phenanthroline-induced beta-glucuronidase release in saponin-permeabilized polymorphonuclear leukocytes.

Saponin-permeabilized polymorphonuclear leukocytes (PMNs) released beta-glucuronidase, a lysosomal enzyme, dose-dependently in response to cupric phenanthroline (CuPh), a mild oxidant, which catalyzes the formation of disulfide bridges. The beta-glucuronidase release induced by CuPh was inhibited by ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). Both dithiothreitol (DTT) and N-(6-aminohexyl)-5-chloro-naphthalene sulfonamide (W-7) also inhibited the beta-glucuronidase release induced by CuPh. CuPh elicited a decrease in protein-bound free sulfhydryls simultaneously, and this decrease was not restored by EGTA treatment. CuPh inhibited Ca2+ uptake into Ca2+ store sites, and promoted a Ca2+ efflux from Ca2+ store sites. It also inhibited Ca(2+)-adenosine triphosphatase (ATPase) activity in permeable PMNs. DTT, a sulfhydryl reducing agent, suppressed both the beta-glucuronidase release and the Ca2+ uptake in CuPh-treated permeable PMNs. On the other hand, chloromercuriphenylsulfonic acid (CMPS), a sulfhydryl modifier, decreased the amount of free sulfhydryls in protein and released beta-glucuronidase in permeable PMNs dose-dependently, but EGTA did not inhibit either reaction. Neither CuPh nor CMPS released beta-glucuronidase from intact PMNs. These results indicate that both CuPh and CMPS act on intra-PMN target molecules to exert their influence, but the involved mechanisms are different in nature. Alteration in calcium movement is responsible for the beta-glucuronidase release in the CuPh-treated permeable PMNs.

Animals↗

PubMed1991

[First-pass metabolism of acetaminophen in thyroxine treated rats].

The study on the first-pass metabolism of acetaminophen was carried out in normal and thyroxine-treated rats, administered 30 mg/kg by three routes of intravenous, intraperitoneal, and oral one. Unconjugated acetaminophen and two major metabolites, glucuronide and sulfate in the plasma and urine were then measured 5 and 24 h after the administration, respectively. It was found that there was no difference in total percentage of excreted amount, independent of the routes for administration, between normal and thyroxine-treated rats. This fact shows that acetaminophen is absorbed completely from the gastrointestinal tract. However, it was also found that the extraction ratio of gastrointestinal tract in thyroxine-treated rats became smaller, and that the volume of distribution and total body clearance became larger than those in normal rats. The first-pass metabolism of acetaminophen was found to be influenced by the continuous administration of thyroxine.

Acetaminophen↗

PubMed1991

[Promotion of intestinal drug absorption by milk fat globule membrane].

A soybean oil emulsion was prepared by using milk fat globule membrane (MFGM) materials as an emulsifier. Its stability and effect on the intestinal absorption of vitamin D3, amphotericin B and kanamycin were studied. The MFGM emulsion was as highly stable as a Tween 80 emulsion. When the MFGM emulsion was sonicated with ultrasonic disrupter, the emulsion became more stable. Quantification of vitamin D3 in the intestinal lymph indicated that the MFGM emulsion enhanced lymphatic absorption of vitamin D3. The recovered percentage of vitamin D3 emulsified with MFGM in the lymph was 1.4 times that by Tween 80, and 2.5 times that of oil-in-water suspension. Statistically significant difference was found among them (p less than 0.05). The volumes of an oil phase in the emulsion affected the absorption of vitamin D3. The recovered percentage of vitamin D3 from the lymph increased with reducing the volume of the oil phase. Sonication of the emulsion did not affect the intestinal drug absorption. Furthermore, the MFGM emulsion had no effect on the intestinal absorption of amphotericin B and kanamycin.

Amphotericin B↗

PubMed1991

GRP (gastrin-releasing peptide)-containing nerves in the rat stomach and stress-induced depletion of their synaptic vesicles. An electron microscope study.

Gastrin-releasing peptide (GRP)-containing nerves are extremely numerous in the mucosa of the gastric body. Our previous study demonstrated that depletion of GRP from the nerves occurred in close relation to ulceration in the stomach. The present study deals with the ultrastructure of the GRP-immunoreactive nerves under normal conditions and its changes induced by conditions of stress. The immunoreactivity for GRP was recognized selectively in large cored vesicles in the swollen axoplasm of the nerves. The same axoplasm further revealed immunonegative small clear vesicles which were believed to contain acetylcholine. In materials where the GRP-immunoreactive nerves markedly decreased in number, both large and small synaptic vesicles were depleted from the nerves. These findings suggest that GRP and acetylcholine coexist in single nerves in the oxyntic mucosa, and that by nerve stimulation, they are coreleased into the lamina propria.

Acetylcholine↗

PubMed1991

Small cell carcinoma of the uterine cervix showing Cushing's syndrome caused by ectopic adrenocorticotropin hormone production.

A uterine cervical cancer is reported in a woman who developed Cushing's syndrome. The tumor measured 1.3 x 0.7 cm, and was a pure small cell carcinoma, identical to that in the lung. The primary tumor cells showed argyrophilia with Grimelius staining and reacted positively to the anti-chromogranin antibody. Clinically, the neoplasm behaved in an aggressive manner in spite of adjuvant chemotherapy and radiotherapy, and the patient died of widespread metastasis. Cushing's syndrome was noted after the occurrence of liver metastasis with an elevation of the serum adrenocorticotropin hormone (ACTH) level. At autopsy, metastatic tumor cells from the liver reacted immunohistochemically positively not only to anti-ACTH but also to antichromogranin, anti-gastrin and anti-calcitonin antibodies. This is the first report of an immunohistochemical analysis of, and comparison of primary and metastatic sites in cervical carcinoma showing Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1991

Cytotoxic activity of FK973 against human oral and breast cancer cells.

FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1, 11-diazatetracyclo [7.4.1.0.0] tetradeca-2, 4, 6-trien-6, 9-diyl diacetate), an analogue of mitomycin C (MMC), was tested against human oral squamous cancer cell lines Ca 9-22, HSC-2, HSC-3, breast adenocarcinoma cell lines MCF-7, BT-20 and breast ductal carcinoma cell line T-47D using MTT assay. FK973 showed cytotoxic effects against six tested cell lines and much wider effective dose range than MMC, adriamycin (ADM), and cisplatin (CDDP). FK973 was the most potent of the four drugs tested against the growth of the three squamous cancer cell lines derived from oral cavity. However, in breast cancer cell lines, FK973 was less potent than MMC and ADM. FK973 was time and dose dependent. The combination effects of FK973 with 5-Fluorouracil (5FU) or CDDP were synthetical. It may be a promising candidate for the treatment of oral and breast cancer.

Adenocarcinoma↗

PubMed1991

Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines.

Triptolide (Tri) is a diterpenoid triepoxide isolated from Tripterygium wilfordii Hook F. The effects of Tri on the colony formation of breast cancer cell lines MCF-7 and BT-20, stomach cancer cell lines MKN-45, MKN-7, and KATO-III, and promyelocytic leukemia cell line HL-60 were reported. Using Hamburger-Salmon's double layer agar technique with certain modifications, cancer cells were cultured in 0.3% agar in a highly humidified atmosphere of 5% CO2 at 37 degrees C for 14-21 d. Colonies were counted on d 14 (occasionally d 21) with the colony analyzer system CA-7A. Of the 5 solid tumor cell lines tested, 4 showed diminished colony formation in soft agar by greater than 70% of control value in Tri 10(-8) mol.L-1 (continuous exposure). The magnitudes of the inhibitory effect of Tri on most breast and stomach cancer cell lines were similar to that on the leukemia cell line HL-60. IC50 were 0.504-1.22 micrograms.L-1. The clinically achievable peak plasma concentration (PPC) of Tri was estimated as 0.15 mg.L-1, being 72-126 times higher than the IC70 of the cancer cell lines except KATO-III. The results suggest that Tri might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers.

Antineoplastic Agents↗

PubMed1991

[Evaluation of myocardial uptake of thallium-201 in whole body scintigraphy].

Whole body scintigraphy (WBS) was performed to assess the myocardial uptake in the dipyridamole (DP), exercise loading (EX) and thallium-201 (Tl-201) myocardial scintigraphy. DP-WBS was studied in 15 patients (pts), EX-WBS was studied in 17 pts and resting (RE)-WBS was studied in 20 pts. All pts had some kinds of heart disease clinically, but their myocardial scintigraphy showed no abnormal findings. DP-WBS and EX-WBS were performed both immediately (early image DP-E, EX-E) and 3 hours later (delayed image EX-D, DP-D) after injection of Tl-201. RE-WBS were performed immediately (early image REST) after injection of Tl-201 only. The percent myocardial uptake, background ratio of the myocardium and washout ratio of some organs were calculated from the ROIs (region of interest) over the whole body, heart, lung, mediastinum, abdomen and thighs. The myocardial uptake of DP-E was 9.1 +/- 1.4%, myocardial uptake of EX-E was 6.3 +/- 0.8% and myocardial uptake of REST was 7.1 +/- 1.2%. The thighs uptake of DP-E was 10.4 +/- 1.1%, thighs uptake of EX-E was 25.3 +/- 2.6% and thighs uptake of EX-E was 25.3 +/- 2.6% and thighs uptake of REST was 10.1 +/- 1.5%. The percent myocardial uptake of DP-E was not only higher than that of EX-E (p less than 0.001) but also higher than that of REST (p less than 0.01). Thus, we conclude that DP scintigraphy showed clearer myocardial image than EX scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole↗

PubMed1991

Effects of continuous vindesine administration of advanced breast cancer resistant to chemotherapy including adriamycin.

Vindesine (VDS) at a dose of 1.2 mg/m2/day was administered by intravenous drip infusion for five days to advanced breast cancer patients with multiple organ metastases who had developed a clinical resistance to various chemotherapeutic agents. The blood concentration of VDS was determined serially by radioimmunoassay, and the anticancer effect and side effects were evaluated. Of the 31 patients selected for this study, 29 were eligible, and the treatment was effective (complete or partial remission) in 11 (38%). There was, however, no correlation between clinical effects and VDS blood concentration. Continuous VDS administration induced various side effects, but all were controllable. Blood concentration was correlated with side effects. Continuous intravenous administration of VDS is considered to have a therapeutic effect on advanced breast cancer which has developed resistance to multiple-drug therapy including adriamycin.

Adult↗