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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 541 records · Page 30Linked to original sources

The narX and narL genes encoding the nitrate-sensing regulators of Escherichia coli are homologous to a family of prokaryotic two-component regulatory genes.

The nucleotide sequence of a 4.4-kilobase SacII-SspI fragment encoding the narXL operon and a part of the narK gene of Escherichia coli has been determined. The narX and narL genes encode proteins of molecular weight 67,275 and 23,927, respectively, and are transcribed from a common promoter, narXp, locating within 429 bases upstream of narX. Transcription from narXp is not significantly induced by nitrate under anaerobiosis, whereas transcription from narK promoter, which overlaps narXp region and is transcribed divergently, is fully induced by nitrate. The N-terminal two-thirds of the NarL protein has extensive homology with those of a diverse set of prokaryotic regulatory proteins, including OmpR, PhoB, SfrA, UhpA, CheY, CheB, NtrC, DctD, FixJ, VirG, SpoOF, and SpoOA. A segment locating in the C-terminal half of the NarL protein seems to have potential most likely to form the helix-turn-helix structure characteristic of a class of DNA-binding protein. The protein is considered to play a role as a transcriptional activator of the nitrate reductase operon, narCHJI, and the narK gene. The C-terminal region of the NarX protein also has homology with other regulatory proteins known as counterparts of two-component regulatory systems, such as EnvZ, PhoR, PhoM, CpxA, NtrB, DctB, FixL, and VirA. Presence of two copies of hydrophobic segments in the N-terminal half of the NarX protein suggests the role as a transmembrane receptor sensing nitrate.

Amino Acid Sequence↗

"Two-route chemotherapy" using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with angiotensin II is effective against peritoneally disseminated cancer in rats.

"Two-route chemotherapy" (TRC) using cis-diamminedichloroplatinum(II) (DDP) and its antidote, sodium thiosulfate (STS), combined with the angiotensin II (AT-II)-induced hypertension method was evaluated for its efficacy against peritoneally disseminated tumors in rats. A bolus i.p. injection of DDP (15 mg/kg) was given 1 min after the initiation of an AT-II (16.5 micrograms/kg) i.v. infusion lasting 11 min. Immediately after the termination of the AT-II infusion, 1,580 mg/kg STS was injected i.v. over a further 5 min. This modified TRC significantly improved the antitumor effect, evaluated by survival (increase in life span, 273%), compared with that achieved with other treatments, as follows: 15 mg/kg DDP i.p. and the concomitant i.v. infusion of 1,580 mg/kg STS (conventional TRC), 153% increase in life span; 5 mg/kg DDP i.p. with or without AT-II i.v. (167% and 107% increases in life span, respectively). As an index of nephrotoxicity, blood urea nitrogen (BUN) levels seen after modified TRC (21.1 mg/dl) were as low as those observed after conventional TRC (19.1 mg/dl), despite the postadministration of STS, and were much lower than those seen after DDP alone or DDP plus AT-II (35.6 and 35.7 mg/dl, respectively). Further evaluation of the effectiveness of modified TRC using various doses of DDP gave similar results. The feasibility of the administration of STS 10 min after DDP treatment was explained by the significant inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. Thus, TRC combined with AT-II has a superior therapeutic effect against peritonitis carcinomatosa induced in rats.

Angiotensin II↗

Na/Ca exchangers in collecting cells of rat kidney. A single tubule fura-2 study.

Single pieces of fura-2-loaded cortical collecting tubule (CCT) isolated either from normal or adrenalectomized (ADX) rats were superfused in vitro, and the cytosolic calcium concentration [( Ca2+]i) was calculated from fluorescence recordings. The effects of altering the sodium gradient across cell membranes were investigated. Switching external sodium from 164 mM to 27 mM (low [Na+]o) had little effect on [Ca2+]i in normal tubules (106 +/- 9 versus 101 +/- 9 nM, n = 15) whereas it resulted in a large peak of [Ca2+]i in CCT from ADX-rats (270 +/- 32 versus 135 +/- 11 nM, n = 21). Since CCT from ADX rats are known to have a reduced Na-pump activity, the effect of ouabain treatment on CCT from normal rats was also tested. When CCT from normal rats were exposed to 1 mM of ouabain in the presence of 164 mM of [Na+]o, [Ca2+]i increased only moderately (123 +/- 15 versus 111 +/- 11 nM, n = 13); when the low [Na+]o solution was applied to these ouabain-treated tubules, a large and transient increase in [Ca2+]i was obtained (287 +/- 38 versus 123 +/- 15 nM, n = 13). This response was absent with [Ca2+]o = 0. The data suggest the presence of 3 Na+/1 Ca2+ exchangers in cell membranes of rat CCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Cytosolic free calcium in single microdissected rat cortical collecting tubules.

Cytosolic free Ca2+ ([Ca2+]i) was measured in single fragments of rat cortical collecting tubule (CCT) by using fura-2 and a tubule superfusion device. Under basal conditions, i.e. with 1 mM of external Ca2+ ([Ca2+]o), the average steady state [Ca2+]i was 179 +/- 16 nM (n = 44 tubules). Random alterations of [Ca2+]o between 0 mM and 4 mM led to corresponding variations in steady state [Ca2+]i levels, which were linearly correlated with [Ca2+]o (average slope 93 +/- 34 nM [Ca2+]i per 1 mM [Ca2+]o for six tubules). In contrast, [Ca2+]i was little affected by decreasing external Na+ concentration. Cell membrane depolarization with 100 mM of external K+ induced a sustained drop in [Ca2+]i (21% as an average). The data suggest that steady state [Ca2+]i in CCT cells resulted from a non-saturable passive entry of calcium ions across cell membranes balanced with an active extrusion by calcium ATPase (pump and leak mechanism). The passive component cannot be accounted for either by Na+/Ca2+ exchangers nor by voltage-dependent calcium channels; it is best explained by the presence of voltage-independent calcium channels in cell membranes.

Animals↗

Stimulation by transforming growth factor-beta of epidermal growth factor-dependent growth of aged human fibro-blasts: recovery of high affinity EGE receptors and growth stimulation by EGF.

The stimulatory effects of transforming growth factor beta (TGF-beta) on epidermal growth factor (EGF)-dependent growth of adult and newborn human fibroblasts were investigated. EGF-stimulated growth in low serum of dermal fibroblasts from a 41 year-old adult (HSF-41) was less than half that of newborn foreskin fibroblasts (HFF). The EGF-stimulated growth of HFF after 55 population doublings (HFF-55) was similarly reduced. The decreased growth response to EGF of fibroblasts aged in vivo and in vitro appeared to result principally from a decreased sensitivity to EGF due to a decreased number and affinity of high affinity EGF receptors (H-EGFR). Pre-incubation of HSF-41 and HFF-55 with 25 pM TGF-beta enhanced the growth responses of these cells to EGF and increased the levels of high affinity EGF-binding by these cells. Thus, the stimulation by TGF-beta of EGF-dependent growth of human fibroblasts aged in vivo or in vitro is mediated by increased levels of high affinity EGF binding.

Adult↗

Different responses of coronary artery and internal mammary artery bypass grafts to ergonovine and nitroglycerin in variant angina.

The dynamic responses of a coronary artery and an internal mammary artery (IMA) graft to pharmacological intervention were examined by arteriography in 5 patients with variant angina who had undergone coronary artery bypass grafting with an in situ IMA to the left anterior descending coronary artery. Preoperative electrocardiographic findings included elevated ST segments in chest leads during attacks of angina, and all patients had severe fixed lesions in addition to marked spasm of the left anterior descending coronary artery after the administration of ergonovine maleate. Postoperatively with ergonovine stimulation, complete occlusion or marked subtotal narrowing was again observed at the primary fixed lesion in the proximal portion of the left anterior descending coronary artery, but the IMA graft and the coronary artery distal to the anastomotic site maintained satisfactory patency with no further occurrence of anginal pain or ST segment elevation. By computer-assisted graphic analysis, which allows highly reproducible measurements of vascular internal diameters, the diameter of the IMA showed only small changes under ergonovine (p = not significant) or nitroglycerin (p less than 0.05) stimulation in contrast to the marked vascular reactivity of the coronary artery (p less than 0.05 and less than 0.01, respectively). These findings indicate that the IMA graft is unresponsive to ergonovine at least in the amount required to produce coronary artery spasm in patients with variant angina and fixed lesions. The IMA graft appears to function well from a clinical and pharmacological viewpoint in patients with variant angina.

Adult↗

Elevation in metallothionein messenger RNA in rat tissues after exposure to X-irradiation.

Metallothionein (MT) mRNA levels in tissues were measured in rats following whole-body X-irradiation (2 and 20 Gy). When compared with control rats, the elevation in MT mRNA levels of liver, kidney, and thymus was observed in irradiated rats at 9 or 72 hr after irradiation. However, the elevation in MT mRNA levels was not observed in brain, spleen, lung, heart, and testis. When compared with other tissues, testicular MT mRNA levels in control rats were extremely high, and treatment with X-irradiation produced a slight decrease of testicular MT mRNA levels. Time-course experiments indicated that hepatic and renal MT mRNA reached a maximum at 6 hr after irradiation. In low-dose (2 Gy) irradiated rat, these values were returned to control values by 4 days after irradiation. However, in high-dose (20 Gy) irradiated rat, the values were not decreased to control values. These data indicate that treatment with X-irradiation produces an elevation in MT mRNA in rat tissues.

Animals↗

Clinical results and in vivo valve function after implantation of a Bicer valve prosthesis in the aortic position.

Between December 1981 and June 1987, 71 patients underwent aortic valve replacement with a Bicer monostrut tilting disc prosthesis. Clinical results and in vivo function of the artificial valve were assessed. The average age of the 71 patients at the time of operation was 51.3 +/- 11.5 years. The hospital mortality rate was 2.8% (two patients) and there were no further deaths during a mean (+/- SD) follow-up period of 2.4 +/- 1.6 years (range 1 month to 5.5 years) after surgery. There was also no occurrence of thromboembolism or valve dysfunction. Function of the Bicer valve prosthesis was assessed in 17 patients: 5 with a 21 mm valve, 7 with a 23 mm valve and 5 with a 25 mm valve. Examination was performed on average 10.3 +/- 8.1 months after surgery. Valve function was examined at rest and during exercise performed with a bicycle ergometer. Pressure gradients at rest were low: 21 mm valve = 8 mm Hg, 23 mm valve = 3 mm Hg and 25 mm valve = 2 mm Hg; the gradients during exercise were 11, 8 and 8 mm Hg, respectively. The valves had the following effective orifice area at rest: 21 mm valve = 1.54 cm2, 23 mm valve = 4.20 cm2 and 25 mm valve = 3.76 cm2; during exercise, the respective areas were 1.57, 3.48 and 3.01 cm2. These valves are deemed to be sufficiently wide for effective valve function. Aortographic observation indicated mild regurgitation that was within reasonable limits and posed no problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells.

In vitro hematopoiesis was evaluated in 37 patients with chronic renal failure (CRF) who developed moderate to severe anemia in order to clarify the relationship between the growth of erythroid progenitor cells and CRF-associated anemia. Bone marrow cells from these patients were cultured in the presence of recombinant erythropoietin. Both early and late erythroid progenitor cells (BFU-E and CFU-E) were significantly suppressed in patients with CRF compared to those in normal controls, while myeloid progenitor cells (GM-CFC) remained normal. Suppression of CFU-E was shown to be mediated by prostaglandin(s) secreted from bone marrow adherent cells. Furthermore, the suppression of CFU-E was inversely correlated with concentrations of uremic serum or parathyroid hormone added to the assay system. These observations suggest a possibility that late erythroid progenitor cells may be preferentially suppressed by the network consisting of parathyroid hormone, bone marrow adherent cells and prostaglandin(s).

Anemia↗

The development of a motor performance method for the measurement of pain.

The pain caused by occupational cervicobrachial disorder (OCD) or related diseases is habitually felt in the wrist, elbow, arm or shoulder when gripping, lifting, wringing, pushing or pulling movements are made. Many patients claim to feel such pain even when diagnosis shows no organic damage, and their arm movement no irregularity. Verbal reports of such pain are considered simply a manifestation of 'feigned' illness. In order to measure such pain, a motor performance, non-verbal method was developed; the plate-pushing task. The results of the performance of this task by subjects using their 'painful' arms showed a greater and more frequent deterioration in performance than when the 'no pain' or 'weak pain' arms were used. The degree of deterioration was estimated quantitatively using Satow's model (Satow 1985 a). The deterioration measured showed that pain was actually perceived during performance. Subjects' verbal reports on the pain thus perceived described the sensory qualities of their pain, rather than the quantitative aspects. These results were supported by previous work (Taniguchi and Satow 1988).

Adult↗

Giant congenital nevus and malignant melanoma.

Frequency of malignant transformation arising in giant congenital nevi is considered to be 4%-5%. More than a half of the patients in which malignant melanoma developed in giant congenital nevi were under the age of 10. It may be hypothesized that dermabrasion of giant congenital nevus may provoke malignant transformation. Some of the cell groups in giant congenital nevus are potentially malignant. Some groups of nevus cells were larger in size than those of other portions of nevus. Electron microscopic observation revealed that nuclei of these larger nevus cells were significantly indented, and melanization of melanosomes was irregular. Coexistence of alpha-like actin with beta- and gamma-actins in giant congenital nevus cells and disappearance of alpha-like actin in malignant melanoma cells were noted.

Actins↗

Altered expression of a third actin accompanying malignant progression in mouse B16 melanoma cells.

The expression of actin was examined and compared in several mouse B16 melanoma cell lines with different metastatic ability, by the use of two-dimensional gel electrophoresis or horizontal isoelectric focusing. In the mouse B16 melanoma cell lines, the expression of newly found AX actin (Mr = 43,000, pI = 5.2) decreased with the increase in in vitro and in vivo selection cycles (F number) for high-metastatic cells. On the contrary, the metastatic ability of each mouse cell line, assessed by lung colony-forming ability following iv administration, increased with increase in the F number. The half life of AX actin was much the same as that of beta- and gamma-actin and the different expressions of AX actin between the low- (F = 1) and high-metastatic (F = 10) cell lines were attributed to differences in the rate of synthesis but not in the decay rate of AX actin. The AX actin was incorporated into the cytoskeletal fraction with the same efficiency as beta- and gamma-actin. The invasiveness of the cells, assessed in vitro using matrigel, was increased with the decrease in AX expression. The actin stress fibers, observed staining with rhodamine-conjugated phalloidin, were organized better in a low-metastatic cell line (F = 1) than in a high-metastatic one (F = 10). These results suggest to us that depression of AX actin is involved in disorganization of the cytoskeletal system, the cellular flexibility and motility are enhanced and there is a consequent increase in the invasiveness and metastatic potential.

Actins↗

Efficacy of two-route chemotherapy using intraperitoneal neocarzinostatin and its antidote, intravenous tiopronin, for peritoneally disseminated tumors in mice.

We assessed the efficacy of "two-route chemotherapy (TRC)" using neocarzinostatin (NCS) given ip and its antidote, N-(2-mercaptopropionyl)-glycine (tiopronin), given iv for peritoneally disseminated tumors in mice. Whether or not the single iv administration of tiopronin (800 mg/kg) at various times after NCS ip would decrease the lethal toxicity induced by NCS ip was given attention. When compared with the LD50 (4.4 mg/kg) of NCS ip alone, simultaneous or postadministration of tiopronin together with NCS ip increased the LD50 of NCS ip by 2.8 to 7.6 fold in a time-dependent manner. Chemotherapy experiments on ip disseminated tumors in mice were done to compare the antitumor effects of the following treatments, at two dose levels (75 and 100% of LD10) of NCS, with or without tiopronin: treatment with NCS ip alone and combined chemotherapy using NCS ip plus tiopronin iv, simultaneously or postadministered. Based on the survival time of the treated mice, the groups given NCS plus tiopronin (postadministration, 15 or 25 min later) showed a significantly superior survival time to that of the group given NCS ip alone. The side effects, evaluated in terms of the changes in body weight and number of WBC of the mice, were not significantly different among the groups treated with 100% of LD10 of NCS.

Animals↗

Dual mechanism for stimulation of glutamate transport by potassium ions in Streptococcus mutans.

An ATP-driven primary transport system operative for L-glutamate or L-aspartate in Streptococcus mutans is, through the entire pH range from 5.5 to 8.5, specifically stimulated by extracellular potassium ions. The stimulation by potassium ions observed in the low pH range between 5.5 and 7 has been interpreted to be due to potassium ion-dependent regulation of the intracellular pH (the first mechanism). In the high pH range from 7 to 8.5, on the other hand, the present study demonstrates that potassium stimulation is essentially not associated with such intracellular pH regulation. This conclusion is based on our observation that potassium stimulation in the high pH range is insensitive to a proton conductor, carbonyl cyanide-p-trifluoromethoxy-phenyl-hydrazone. Since none of the other monovalent cations, including sodium, rubidium, ammonium, and Tris ions, could replace potassium ions in significantly stimulating glutamate transport, it is most likely that the influx of potassium ions specifically cancels the membrane potential derived by movement of glutamate with the net negative charges across a membrane and thus facilitates transport (the second mechanism). The second mechanism appears to be operative even in a low pH range, in addition to the first mechanism.

Adenosine Triphosphate↗

Direct effect of methimazole on rat thyroidal cell growth induced by thyrotropin and insulin-like growth factor I.

The direct effect of methimazole (MMI) on FRTL-5 cell growth was examined. TSH, (Bu)2cAMP, calf serum, insulin-like growth factor I, and Graves' immunoglobulin (IgG) increased [3H]thymidine incorporation into DNA during 72-h incubation. MMI (10(-3) M), which does not damage cell viability, significantly enhanced the increase in [3H]thymidine incorporation induced by TSH and (Bu)2cAMP. In contrast, MMI suppressed the increase in [3H]thymidine incorporation induced by calf serum, insulin-like growth factor I, and Graves' IgG. MMI had no effect on the production of cAMP by TSH. Accordingly, we concluded that MMI has opposite effects on cAMP- and non-cAMP-dependent cell growth pathways. Moreover, Graves' IgG, which has a modest effect on cAMP production, is believed to induce cell growth via the non-cAMP dependent cell growth pathway.

Animals↗

[Localization of epidermal growth factor and nerve growth factor mRNAs in mouse submandibular gland by a simplified in situ hybridization with riboprobes].

We simplified procedures of in situ hybridization with riboprobes on serial sections of paraffin-embedded tissues. We found that when tissues were fixed with 4% paraformaldehyde, embedded in paraffin, and cut serial sections with 5 microns thick, excellent results were obtained without proteolytic, heat, or HCl treatment. With our simplified method, both EGF and NGF mRNAs were detected intensively and specifically in granular convoluted tubule (GCT) cells of a male mouse submandibular gland, but not detected in either the acini or ducts other than the GCT. Accumulation of the silver grains was localized in the basal side of the GCT cells. No significant hybridization was observed in those cells with the sense probe and in the parotid and sublingual gland even with the anti-sense probe. Since our results were not only very consistent with other data, but also much more excellent than other results obtained by in situ hybridization on the similar tissues, our simplified method should be very useful to study gene expression on tissue sections.

Animals↗