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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 505 records · Page 28Linked to original sources
PubMed1988

Ouabain sensitivity of a chimeric alpha subunit (Torpedo/rat) of the (Na,K)ATPase expressed in Xenopus oocyte.

A cDNA for a chimeric alpha subunit of the (Na,K)ATPase was constructed and expressed in Xenopus oocytes in order to elucidate structural features involved in ouabain sensitivity. A chimeric alpha subunit, in which the N-terminal 165 amino acid sequence of ouabain-resistant rat alpha subunit, including the first two transmembrane segments (M1 and M2), was replaced by a sequence from the corresponding region of ouabain-sensitive Torpedo alpha subunit, was ouabain-sensitive, suggesting that the M1-M2 junction is a site responsible for ouabain sensitivity of the (Na,K)ATPase.

Amino Acid Sequence↗
PubMed1988

Functional activity of oligosaccharide-deficient (Na,K)ATPase expressed in Xenopus oocytes.

(Na,K)ATPase from Torpedo californica was expressed in Xenopus laevis oocytes in the presence of tunicamycin by injecting mRNAs for the alpha- and beta-subunits derived from the cloned cDNAs into the oocytes. The oligosaccharide-deficient ATPase thus synthesized was transported to the oocyte plasma membrane, where it exhibited virtually the same ATPase activity, ouabain-binding capacity and 86Rb+ transport activity as the fully glycosylated enzyme. We conclude that the oligosaccharide chains on the beta-subunit has no effect on the catalytic activities of (Na,K)ATPase.

Animals↗
PubMed1988

Growth-stimulatory effect of androgen-induced autocrine growth factor(s) secreted from Shionogi carcinoma 115 cells on androgen-unresponsive cancer cells in a paracrine mechanism.

Androgen-responsive (SC-3) and -unresponsive (SC-4) cloned cell lines in culture were established from an androgen-responsive mouse mammary tumor, Shionogi carcinoma 115. By using a serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], characteristics of androgen-induced and autonomous growth factors (GFs) were examined. Serum-free conditioned medium (CM) obtained from testosterone-stimulated (+T) SC-3 cells had remarkable growth-stimulatory effects on both SC-3 and SC-4 cells. To examine the molecular characteristics of GF, CM(+T) from SC-3 was fractioned by heparin-Sepharose affinity chromatography; two peaks, eluted at 0.5 M (GF-low) and 1.1 M NaCl (GF-high) were identified. GF-high had the ability to stimulate growth with a morphological change of both SC-3 and SC-4 cells; the GF-high was not found in CM from T-unstimulated (-T) SC-3 or CM from SC-4. GF-low stimulated the growth without the morphological change of only SC-4 cells; the GF-low was also present in CM(-T) from SC-3 and CM from SC-4. The present findings demonstrate that T-induced autocrine GF-high secreted from SC-3 cells can also stimulate the growth of progressed unresponsive SC-4 cells in a paracrine mechanism and that autonomous GF-low secreted from both SC-3 and SC-4 cells can stimulate the growth of only SC-4 cells.

Androgens↗
PubMed1988

Augmentation of anticancer effect with angiotensin II in intraarterial infusion chemotherapy for breast carcinoma.

We investigated the effect of angiotensin II (AT II) on blood flow in breast cancer patients using 81mKr and found that it increased tumor blood flow 2.3-fold while decreasing blood flow in adjacent normal tissue 0.7-fold. We, then, used AT II in conjunction with intraarterial infusion chemotherapy (IAC) for locally advanced breast cancer in order to increase drug delivery to the tumor and enhance its anticancer effect. Eleven patients (from 1976-1981) received IAC with doxorubicin through the internal thoracic and subclavian arteries, alternately, for 10 days (AT II- group). Twenty-four patients (from 1981-1985) received IAC with doxorubicin and concomitant infusion of AT II (1.3 micrograms/min through the internal thoracic artery and 2.6 micrograms/min through the subclavian artery) (AT II+ group). The response rate of the primary breast tumor was higher in the AT II+ group (92%) than in the AT II- group (73%) (P = 0.66). Complete tumor necrosis was 46% in the AT II+ group, but only 27% in the AT II- group (P = 0.51). These preliminary results suggest that the anticancer effect of IAC for breast cancer can be enhanced with concomitant infusion of AT II.

Adult↗
PubMed1988

[Studies on serum ketone bodies in patients with hyperthyroidism].

In order to investigate effects of thyroid hormone on ketone bodies metabolism, fasting levels of serum ketone bodies, serum free fatty acids (FFA), serum insulin (IRI), plasma glucagon (IRG) and plasma glucose were examined in 29 untreated patients with hyperthyroidism and 20 healthy subjects. In 21 patients the levels of serum ketone bodies were re-examined when euthyroidism was achieved after treatment. In all of healthy subjects and 17 patients changes in the levels of serum ketone bodies after oral glucose load were examined. The results were as follows: 1). Fasting levels of serum FFA and total ketone bodies (TK), acetoacetate (AcAc), 3-hydroxy-beta-butylate (3OHBA), ratio of 3OHBA to AcAc in the patients were significantly higher than those in healthy subjects. The levels of IRI, IRG or ratio of IRG to IRI in the patients were not different from those in healthy subjects. In the patients, the fasting level of TK was significantly correlated with the level of FFA. 2). After oral glucose load the levels of TK and FFA in the patients decreased gradually. 3). The fasting levels of TK and FFA in the patients decreased when euthyroidism was achieved after treatment. It was suggested that the fasting levels of serum ketone bodies in patients with hyperthyroidism elevated probably due to activated lipolysis.

Blood Glucose↗
PubMed1988

Degradation of epidermal growth factor receptors by cathepsin L-like protease: inhibition of the degradation by c-Ha-ras gene products.

Extract of NIH3T3 mouse fibroblasts contains a protease which can cleave epidermal growth factor receptor (EGF receptor). This protease was tentatively named cathepsin X and purified to near homogeneity. The characteristics of cathepsin X were similar to those of cathepsin L and the proteolytic activity of cathepsin X was inhibited by c-Ha-ras gene products.

Animals↗
PubMed1988

Crystallization and preliminary crystallographic data of a truncated derivative from the human c-Ha-ras protein.

A truncated derivative of the human c-Ha-ras protein has been crystallized from polyethylene glycol 6000 solution by a vapour diffusion technique. The rectangular prism diffracts X-rays to at least 2.5 A resolution (1 A = 0.1 nm). The unit cell is monoclinic, space group P21, with unit cell parameters of a = 50.2 A, b = 110.9 A, c = 36.4 A, beta = 97.2 degrees. The unit cell contains four molecules.

Crystallization↗
PubMed1988

Management of inflammatory carcinoma of the breast with combined modality therapy including intraarterial infusion chemotherapy as an induction therapy. Long-term follow-up results of 28 patients.

Twenty-eight patients with inflammatory breast cancer were treated with combined modality therapy consisting of (1) intraarterial infusion chemotherapy (IA chemotherapy) through the internal thoracic artery and subclavian artery, (2) surgical ablation, (3) extended radical mastectomy, and (4) adjuvant chemotherapy in that order. The IA chemotherapy included Adriamycin (n = 14) and mitomycin C plus 5-Fluorouracil (n = 14) were used. The response rate of the primary breast lesions to IA chemotherapy was as high as 83%, and complete necrosis of the tumor was histologically documented in 43% of the cases. The median interval from the initiation of IA chemotherapy to surgery was 7 weeks. Toxicity was acceptable and every patient completed the treatment. The 5- and 10-year disease-free survival rates were 59% and 53%, respectively. These results suggest that IA chemotherapy is a very useful induction therapy for inflammatory breast cancer in terms of excellent local effects and the short time required for therapy before surgery.

Adult↗
PubMed1988

Induction of progesterone receptor with tamoxifen in human breast cancer with special reference to its behavior over time.

The behavior of progesterone receptor (PR) values over time in human breast cancer during tamoxifen treatment was studied. Of 97 patients with operable breast cancer, 24 were preoperatively treated with tamoxifen (20 mg twice daily) for 3 days (TAM 3-day), 22 were treated for 7 days (TAM 7-day), 21 for 14 days (TAM 14-day), and 30 received no treatment (control group). Surgically removed breast tumors were assayed for the progesterone receptor by the dextran-coated charcoal method. The PR values (fmol/mg DNA) (mean +/- standard error [SE]) of PR-positive tumors in the control, TAM-3, TAM-7, and TAM-14 day groups were 571 +/- 176, 1699 +/- 408 (P less than 0.01), 1675 +/- 463 (P less than 0.05), and 686 +/- 191, respectively. There was a 4.6-fold increase in the mean PR value in postmenopausal patients and a two-fold increase in premenopausal patients after TAM treatment for 3 and 7 days. We concluded that PR induction provoked by TAM reached a peak on day 3, continuing at this level until day 7. A longer treatment (14 days) with TAM appears to abolish the PR inducing activity, probably because of, first, estrogenic and, later, the antiestrogenic effects of TAM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Crystallization of human c-H-ras oncogene products.

There is compelling evidence that cancer develops as a consequence of genetic changes (probably multiple) in some members of a selected set of cellular genes. DNA isolated from a variety of tumors, but not normal tissues, possesses the ability to malignantly transform non-tumorigenic cells. Many oncogenes responsible for such transformation have been isolated from transformed cell lines and animal and human tumors induced spontaneously, by virus, by chemical, or by radiation. The most commonly found transforming genes isolated from human tumor cells by DNA transfection assay are the ras gene family (c-H-ras, c-K-ras and N-ras). We report crystallization of several human c-H-ras oncogene proteins.

Crystallization↗
PubMed1988

Inhibition of cathepsin L-induced degradation of epidermal growth factor receptors by c-Ha-ras gene products.

The inhibitory activities of c-Ha-ras gene products (p21s) toward several cysteine proteinases have been investigated. The activity of cathepsin L was inhibited by p21s most effectively while those of cathepsin B and papain were slightly inhibited by p21s. p21s did not show any inhibitory activity toward cathepsin H. In order to connect the protease-inhibitor activity of p21s with cell growth, the degradation of epidermal growth factor receptors (EGF-receptors) was investigated. EGF-receptors were preferentially cleaved by cathepsin L but not by cathepsin B or H. The cleavage of EGF-receptors by cathepsin L was inhibited by p21s dose-dependently. These results raise the possibility that p21s can suppress the degradation of growth-related proteins such as EGF-receptors and thereby affect cell growth.

Carcinoma, Squamous Cell↗
PubMed1988

Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21.

The crystal structure at 2.7 A resolution of the normal human c-H-ras oncogene protein lacking a flexible carboxyl-terminal 18 residue reveals that the protein consists of a six-stranded beta sheet, four alpha helices, and nine connecting loops. Four loops are involved in interactions with bound guanosine diphosphate: one with the phosphates, another with the ribose, and two with the guanine base. Most of the transforming proteins (in vivo and in vitro) have single amino acid substitutions at one of a few key positions in three of these four loops plus one additional loop. The biological functions of the remaining five loops and other exposed regions are at present unknown. However, one loop corresponds to the binding site for a neutralizing monoclonal antibody and another to a putative "effector region"; mutations in the latter region do not alter guanine nucleotide binding or guanosine triphosphatase activity but they do reduce the transforming activity of activated proteins. The data provide a structural basis for understanding the known biochemical properties of normal as well as activated ras oncogene proteins and indicate additional regions in the molecule that may possibly participate in other cellular functions.

Amino Acid Sequence↗