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Biomedical subjects

N Uchida

Publications and source records attributed to N Uchida.

At least 253 records · Page 14Linked to original sources
PubMed1980

Undersulfated proteoglycans are secreted by cultured chondrocytes in the presence of the ionophore monensin.

The monovalent ionophore, monensin, inhibits secretion of many different proteins from a wide variety of cells. The site of blockage is at the golgi complex. We have exposed chick embryo chondrocytes in suspension culture to monensin, at concentrations ranging from 10(-8) to 10(-6) M. At the higher concentrations, between 10(-7) and 10(-6) M, monensin inhibited secretion of type II procollagen, which accumulated in the chondrocytes. At these concentrations of the ionophore, proteoglycan synthesis was inhibited, as measured by radioactive serine incorporation into core proteins and by radioactive glucosamine or SO4 incorporation into glycosaminoglycans. However, at a monensin concentration of 3 x 10(-8) M, the incorporations of serine and glucosamine were close to normal while SO4 incorporation was at 30% of control values. The ratio of glucosamine to serine in pronase-released glycosaminoglycans from culture media was unaffected by 3 x 10(-8) M monensin but the sulfate to serine ratio decreased to 29% of control values. Examination of the glycosaminoglycans by gel filtration showed a progressive increase in Kav values as sulfation decreased. Undersulfation was demonstrated by radiochromatographic analysis of the digestion products following incubation with chondroitinase ABC. The composite results show that monensin interferes with sulfation of newly synthesized proteoglycans.

Animals↗
PubMed1980

Intra- and postoperative autotransfusion in open heart surgery under simple hypothermia in children.

A new autotransfusion unit was developed by the authors and the favorable results of 21 operations of open heart surgery under simple hypothermia were described. The patients were all children with simple congenital heart diseases. The amounts of autotransfused blood ranged from 2.8 to 15.5 ml/kg. Intraoperative autotransfusion proved to be an effective means of minimizing blood loss during surgery (range 3.2 to 12.8 ml/kg) and performing open heart surgery without donor blood transfusion. Postoperative autotransfusion (range 0 to 14.3 ml/kg) served as a supplementary means of avoiding homologous blood transfusion. Among the 21 autotransfused patients, there were no complications, while two patients developed hepatitis out of 19 patients who received homologous blood in the control group.

Adolescent↗
PubMed1980

Enhancement of cooling and rewarming by a jet water system in surface-induced deep hypothermia.

To shorten the time of cooling and rewarming in surface-induced deep hypothermia, we devised a jet water system for hypothermia which was constructed within the water bath of the operating-table. In the clinical applications for open heart surgery under surface-induced deep hypothermia, we found that the time required for cooling and rewarming, particularly the later, was significantly reduced without any adverse effects.

Adolescent↗
PubMed1980

Immunocytochemical localization of procollagen and fibronectin in human fibroblasts: effects of the monovalent ionophore, monensin.

The monovalent ionophore monensin inhibits the secretion of both procollagen and fibronectin from human fibroblasts in culture. The distribution of these proteins in control and inhibited (5 x 10(-7) M monensin) cells has been studied by immunofluorescence microscopy. In control cells, both antigens are present throughout the cytoplasm and in specific deposits in a region adjacent to the nucleus, which we identify as a Golgi zone by electron microscopy. Treatment of cells with monensin causes intracellular accumulation of procollagen and fibronectin, initially in the juxta-nuclear region and also subsequently in peripheral regions. Electron microscope studies reveal that in such cells the juxta-nuclear Golgi zone becomes filled with a new population of smooth-membraned vacuoles and that normal Golgi complexes are not found. Immunocytochemically detected procollagen and fibronectin are localized in the region of these vacuoles, whereas more peripheral deposits correspond to the dilated cisternae of rough endoplasmic reticulum, which are also caused by monensin. Procollagen and fibronectin are often codistributed in these peripheral deposits. Accumulation of exportable proteins in Golgi-related vacuoles is consistent with previous analyses of the monensin effect. The subsequent development of dilated rough endoplasmic reticulum also containing accumulated proteins may indicate that there is an additional blockade at the exit from the endoplasmic reticulum, or that the synthesized proteins exceed the capacity of the Golgi compartment and that their accumulation extends into the endoplasmic reticulum.

Cell Line↗
PubMed1980

Effect of androgen depletion on postoperative regrowth of androgen-dependent and -independent Shionogi carcinomas in mice.

About 350 castrated male DS mice given testosterone propionate (TP, 100 micrograms/mouse/day) were grafted with androgen-dependent SC115 tumor or androgen-independent tumors (NHD with positive receptor; NHF with negative receptor). After 20 or 15 days, most of the developed tumors were excised and the mice were divided into 3 groups. TP injection was continued in one group and TP was stopped immediately or 20 days after the excision in the other groups. The cumulative 120-day mortality after transplantation of SC115 tumor into mice was significantly lower in the immediate androgen removal group (10%, 6/59) than in the androgen-injected group (59%, 51/87) or the delayed androgen removal group (42%, 19/45). The cumulative mortalities in mice with androgen-independent NHD and NHF tumors in the immediate androgen removal groups (97 and 91%, respectively) were similar to those in the androgen-injected groups (90 and 95%, respectively). All non-operated and TP-injected mice grafted with SC115 and androgen-independent tumor died due to the tumors within 50 and within 30 days after the transplantation, respectively. These findings suggest the usefulness of adjuvant endocrine therapy for preventing the recurrence of hormone-dependent tumors.

Androgens↗
PubMed1980

Effect of serial passage in female nude athymic mice on androgen dependency of Shionogi carcinoma 115.

When Shionogi carcinoma 115 (SC115, an undifferentiated medullary carcinoma showing a compact cell pattern and containing androgen receptor) was transplanted into male and female DS mice, it grew only in males. In contrast with this strict androgen dependency in DS hosts, SC115 tumors grew in male and female nude athymic (BALB/c-nu/nu) mice. Although most of the tumors developing in female nude mice were composed of spindle-shaped cells and did not contain androgen receptor, about 5% of tumors in female nude mice retained morphological and biochemical characteristics of the original SC115 tumor. Such a tumor was serially transplanted in female nude mice. Although no significant changes were detectable in histological and chromosomal features and in androgen receptor values, the growth speed in female nude mice accelerated and became comparable to the growth speed of the original SC115 tumor in intact male DS mice. However, this subline of SC115 tumor showed a marked androgen dependency when reinoculated into male and female DS mice after 14 passages in female mice nude mice in spite of its relative androgen independency in nude hosts. Therefore, the present results seem to suggest that the immunological status of the hosts may affect the hormone dependency of tumors.

Androgens↗
PubMed1979

Monovalent ionophores inhibit secretion of procollagen and fibronectin from cultured human fibroblasts.

Procollagen and fibronectin are major products of confluent fibroblasts in culture and both are released from the cells. Procollagen is secreted by known pathways, while the mechanism of fibronectin release is controversial. We find that the secretion of both these proteins can be reduced to 20% by low concentrations (0.1-1 muM) of ionophores that have affinity for monovalent cations. In contrast, little effect upon secretion was found for similar concentrations of an ionophore that binds divalent cations. Electron microscopy showed that the inhibition of secretion is accompanied by accumulation of membranous vacuoles. We believe that the ionophores impede secretion by acting on the secretory structures rather than on the proteins themselves. Biochemical studies supported this interpretation because no changes were detected in hydroxylation or glycosylation of procollagen or glycosylation of fibronectin, nor were significant changes in cellular amino acid incorporation observed. Pulse-chase studies indicated that the rates of secretion were impaired by the ionophore without enhancing intracellular degradation. The decreased secretory rates accounted for the lower levels of procollagen and fibronectin in the culture medium; no evidence for increased catabolism of the secreted proteins was found. Secretion could be readily restored by removing the ionophore from the culture medium. The results indicate that procollagen and fibronectin may be simultaneously secreted, possibly utilizing a common pathway for secretion; the ionophores effectively interfere with cellular secretory pathways without impairing protein synthesis or protein glycosylation or altering protein catabolism.

Anti-Bacterial Agents↗
PubMed1979

Development of androgen-independent spindle cell tumors from androgen-dependent medullary Shionogi carcinoma 115 in androgen-depleted nude mice.

When Shionogi carcinoma 115 (SC115, undifferentiated medullary carcinoma showing compact cell pattern and containing androgen receptor) was transplanted into male and female DS mice, it grew only in males. In contrast to this strict androgen dependency in DS hosts, tumors composed of spindle-shaped cells appeared in more than 80% of cases when SC115 tumor was inoculated into female or castrated male nude athymic (BALB/c-nu/nu) recipients. These spindle cell tumors neither contained cytosol androgen receptor nor showed biologically defined androgen dependency. As spindle cell tumors could be serially transplanted in DS mice but not in BALB/c-+/+ mice and as the original SC115 (medullary carcinoma showing a compact cell pattern) tumor and the spindle cell tumor had many identical chromosome abnormalities, these two types of tumors seem to have a common origin in spite of their morphological, biochemical, and biological differences. Since spindle cells could not be detected histologically in SC115 tumors maintained in intact male DS mice, the present results seem to suggest that SC115 cells may change their morphological, biochemical, and biological characteristics within one passage in androgen-depleted nude athymic mice.

Androgens↗
PubMed1978

Synthesis and antitumor activity of preactivated isophosphamide analogues bearing modified alkylating functionalities.

In search of cancer chemotherapeutic agents with greater efficacy than cyclophosphamide, 4-hydroperoxyisophosphamide analogues bearing modified alkylating functionalities such as 2-bromoethyl, 2-iodoethyl, 2-methyl-sulfonyloxyethyl, and 2-ethylsulfonyloxyethyl groups were prepared by ozonolytic cyclization reaction of N,N'-substituted 3-butenyl phosphorodiamidates. Comparative cytotoxicity against L1210 cells and antileukemic life-span activity against L1210 implanted BDF1 mice of the newly synthesized compounds were tabulated. The 4-hydroperoxyisophosphamide analogues which have different alkylating groups in a molecule showed slightly greater cytoxicity in vitro than those with the same alkylating groups. Most of the compounds having different alkylating groups also showed high antileukemic activity in vivo. Among them, the highest efficacy was found for 2-[N-methyl-n-(2-chlorethyl)]amino-3-(2-methylsulfonyloxyethyl)-4-hydroperoxy-1,3,2-oxazaphosphorinane 2-xoide (NSC 280122D) whos life-span activity was also greater than that of 4-hydroperoxyisophosphamide, cyclophosphamide, and isoposphamide. The superiority of this compound was especially apparent by oral administration.

Alkylating Agents↗
PubMed1978

[Irritative activity of antiinflammatory agents, betamethasone 17-valerate, beclomethasone 17, 21-dipropionate, betamethasone 17, 21-dipropionate, or indomethacin on the gastrointestinal tract in rats and dogs (author's transl)].

Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by beta-methasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.

Animals↗