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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 451 records · Page 25Linked to original sources

[Study of c-myc gene transfected T-24 human bladder cancer cells].

To investigate the roll of c-myc protooncogene in human bladder cancer, c-myc gene was transfected into T-24 human bladder cancer cells and the changes of cell characteristics were studied. C-myc gene transfection was performed, using the electroporation method described previously (J.J. Urology, 80, 1989). After electroporation, c-myc gene was transfected and neo cells were cloned in a neomycin containing medium. One typical cloned cell (myc-cl3) was obtained. And this cell clone was shown to contain more than 3 extra-copies of c-myc gene by Southern blotting analysis. Morphology and growth speed of the myc-cl3 cells were not significantly different from those of original T-24 cells. However, they easily made overlapped cell-layers in the confluent growth phase. In the soft-agarose semi-solid medium, myc-cl3 cells formed about 35 times more numerous colonies than T-24 cells. Myc-cl3 cells also formed tumors on nude-mice at a significantly higher rate than T-24 cells did. These results suggest that c-myc gene plays a key roll in clonal growth and tumor formation in human bladder cancer.

Animals↗

Pentavalent technetium-99m-DMSA uptake in a patient having multiple myeloma without amyloidosis.

A pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scan was performed on a patient with multiple myeloma without amyloidosis. A high accumulation of the tracer was found in numerous tumors. We believe that the accumulation of DMSA is unrelated to amyloidosis and that the DMSA scan may have potential for the staging of tumors in patients presenting with multiple myeloma.

Bone Neoplasms↗

[Pyeloureteritis cystica diagnosed by using a ureteroscope: a case report].

We report a case diagnosed as pyeloureteritis cystica by ureteroscopic examination. A 70-year-old female was admitted to our hospital with microhematuria. Intravenous pyelography and retrograde pyelography demonstrated multiple filling defects in bilateral renal pelvis and ureters. Urinary cytology findings indicated class III on both side. Ureteroscope and cold cup biopsy were performed, and histological examination revealed chronic ureteritis. Forty-four Japanese cases including our case are herein reviewed.

Aged↗

[Carcinoma of the urinary bladder in a patient receiving cyclophosphamide for Wegener's granuloma: a case report].

We present a case report of cyclophosphamide-induced bladder tumor. The patient is a 31-year old male who had received 240 g of cyclophosphamide for 8 years because of the therapy for Wegener's granuloma. Transurethral resection of bladder tumor was performed and transitional cell carcinoma pT1G2 ascertained by histological examination. Forty-three foreign cases and nine Japanese cases including our case are herein reviewed.

Adult↗

Changes in parameters of the coagulation-fibrinolysis system and platelet function after OKY-046 administration to patients with ruptured aneurysm of the cerebral artery.

The influence of the TXA2-synthetase inhibitor OKY-046 (Xanbon) on haematological findings for the coagulation-fibrinolysis system and platelet aggregation was investigated in patients with subarachnoid bleeding during or after the administration. Changes in alpha 2-PI activity and the levels of fibrinogen, t-PA and PAI antigen were observed. Especially, PAI activity and PAI antigen were found to be significantly increased as compared with levels before the administration. On the other hand, the platelet aggregation induced by various agents and the activity of AT-III were not greatly altered after the administration of OKY-046.

Adenosine Diphosphate↗

[Renal cell carcinoma-interferon therapy, its clinical adaptation and limitations].

Metastatic renal cell carcinoma has been treated by several types of combination therapy including interferon alfa (IFN-alpha). The line of experimental evidence suggested that IFN-alpha and chemotherapeutic agents or other cytokines have synergistic effects on cancer cells from in vitro and in vivo study. However, in clinical trials the response rate by these combination therapies for patients with metastatic renal cell carcinoma is not satisfactory. In future, some of these combination therapies must be evaluated by large-scale randomized trials. And to improve the poor prognosis and response rate, a new drug delivery system is needed such as chemoembolization.

Carcinoma, Renal Cell↗

The zinc fingers of human poly(ADP-ribose) polymerase are differentially required for the recognition of DNA breaks and nicks and the consequent enzyme activation. Other structures recognize intact DNA.

The recognition of double-stranded DNA breaks and single-stranded nicks by human poly(ADP-ribose) polymerase and the consequent enzymic activation were examined using derivatives of the enzyme expressed in Escherichia coli. The N-terminal 162 residues encompass two zinc fingers. Deletion or mutation of the first finger results in a loss of activation by DNA with either single-stranded or double-stranded damage. Destruction of the second finger reduces activation by double-stranded DNA breaks only slightly, but eliminates activation by single-stranded DNA nicks. These data suggest that activation by single-stranded DNA nicks requires two zinc fingers, but activation by double-stranded DNA breaks requires only the finger closer to the N terminus. Variant proteins that lack both zinc fingers are enzymically inactive but still exhibit weak DNA binding, which is independent of DNA damage. Thus, other regions are also capable of binding intact DNA, but the recognition of a strand nick or break which occasions the synthesis of poly(ADP-ribose) specifically requires the zinc fingers.

Amino Acid Sequence↗

A possible role of the beta-subunit of (Na,K)-ATPase in facilitating correct assembly of the alpha-subunit into the membrane.

mRNAs from the alpha- and beta-subunits (mRNA alpha and mRNA beta, respectively) of Torpedo californica (Na,K)-ATPase were injected into Xenopus laevis oocytes either separately or in combination, and the properties of the two subunits synthesized were studied. The alpha-subunit synthesized in oocytes injected with mRNA alpha alone was recovered in both the membrane and cytosol fractions and was susceptible to tryptic attack. When mRNA beta was coinjected with mRNA alpha, almost all the alpha-subunit was found in the membrane fraction and was resistant to trypsin. In all cases, essentially all of the beta-subunit was recovered in the membrane fraction and was resistant to trypsin. As the amount of mRNA beta coinjected increased, the amounts of both the alpha- and beta-subunits as well as (Na,K)-ATPase activity of the membrane fraction increased. These results suggest that the beta-subunit facilitates the correct assembly of the alpha-subunit into the membrane probably by forming a stable complex with the nascent alpha-subunit.

Animals↗

Assembly of the alpha-subunit of Torpedo californica Na+/K(+)-ATPase with its pre-existing beta-subunit in Xenopus oocytes.

The alpha- and beta-subunits of Torpedo californica Na+/K(+)-ATPase were expressed in turn in single oocytes by alternately microinjecting the specific mRNAs for the alpha- and beta-subunits. The mRNA first injected was degraded prior to the injection of the second mRNA by injecting the antisense oligonucleotide specific for the first mRNA. The pre-existing beta-subunit, which had been synthesized by injecting mRNA for the beta-subunit, could assemble with the alpha-subunit expressed later in the single oocytes and the resulting alpha beta complex acquired both ouabain-binding and Na+/K(+)-ATPase activities. On the other hand, formation of the alpha beta complex was not detected when the alpha-subunit was expressed first, followed by the beta-subunit. These data suggest that the beta-subunit acts as a receptor or a stabilizer for the alpha-subunit upon the biogenesis of Na+/K(+)-ATPase.

Animals↗

[Combination therapy with 5'DFUR and MPA as a second line treatment for advanced/recurrent breast cancer].

As a second line therapy after failure to previous therapies, a combination therapy with MPA 1,200 mg po and 5'DFUR 1,200 mg po daily was given to 31 patients with recurrent breast cancer. At a median follow up period of 18 months, the overall response rate was 42%. The response rates for bone and visceral lesions were still good for the second line therapy. Patients previously exposed to tamoxifen (24 patients), 5-FU or its derivatives (21) and/or adriamycin (18) had response rates of 42%, 33%, 33%, respectively. The median duration of response in responders was 10 months. The overall median survival for the entire series was 9 months after start of the treatment. Thirteen (81%) of 16 patients with bone lesions were relieved from their bone pain. It is of special interest that the pain relief was also obtained in 7 out of 10 NC/PD patients with bone lesions, resulting in much improvement of their performance status. Side effects included obesity 52%, edema of the leg 35%, diarrhea 16% and so on. One patient developed venous thrombosis of her lower extremities and 4 were suspected to have the same condition. Fifty-five % of the patients underwent dose reduction of MPA at the 5th month of treatment in a median. This combination therapy is useful for recurrent disease even in late stages, so long as close observation is made for the occurrence of thrombosis.

Adult↗

Inability of medroxyprogesterone acetate to down regulate estrogen receptor level in human breast cancer.

The influence of medroxyprogesterone acetate (MPA) on estrogen receptor (ER) and progesterone receptor (PR) levels was studied in 20 postmenopausal patients with ER-positive and PR-positive primary breast cancers. Each patient underwent drill biopsy and subsequently mastectomy. The drill biopsy and surgical specimens were assayed for the total ER and PR levels (cytosolic plus nuclear fraction) by enzyme immunoassay. Between the drill biopsy and mastectomy, ten patients received no treatment (control group) and the other ten patients were given MPA (1200 mg/day) for 7 days. In the control group, the total ER and PR levels of the surgical specimens decreased by 68.2 +/- 7.3% and 60.7 +/- 8.4%, respectively, taking the receptor values of the drill biopsy specimens as 100%, although no treatment was given preoperatively. This decrease seems to be attributable to the receptor degradation due to damages occurring during mastectomy. In the MPA group, the total ER and PR levels of the surgical specimens decreased by 64.2 +/- 8.0% and 23.3 +/- 7.6%, respectively. The decrease in PR, but not ER, was statistically significant between the control and MPA groups (P less than 0.01). These results demonstrate that MPA down regulates PR but not ER in human breast cancer and challenge the conventional idea, extrapolated from the results on the endometrium and endometrial cancer, that MPA antagonizes endogenous estrogens by down regulating ER.

Antineoplastic Agents↗

[A possible role of the beta subunit of (Na, K)ATPase on the biogenesis of the enzyme].

(Na, K)ATPase is composed of two heterologus subunits; a catalytic alpha subunit and a glycosylated beta subunit whose role remains unclear. To elucidate a possible role of the beta subunit, the alpha and beta subunits of Torpedo californica (Na, K)ATPase were expressed in the Xenopus oocytes system which allows the specific programmed synthesis of different subunits in a cell by alternately injecting individual mRNA. When oocytes were injected with mRNA alpha alone, no significant increase in (Na, K)ATPase activity was observed, whereas a slight increase was detected in oocytes injected with mRNA beta alone. The pre-existing beta subunit, which had been synthesized by injecting mRNA beta, could assemble with the alpha subunit, expressed later in the single oocytes and the resulting alpha beta acquired both ouabain-binding and (Na, K)ATPase activities. The results reported in this paper strongly indicate that the beta subunit plays an essential role, at least in the biogenesis of the enzyme.

Animals↗

Site-directed mutagenesis of Asp-376, the catalytic phosphorylation site, and Lys-507, the putative ATP-binding site, of the alpha-subunit of Torpedo californica Na+/K(+)-ATPase.

Point mutations of Asp-376 of the alpha-subunit of Torpedo californica Na+/K(+)-ATPase (the site of phosphorylation during the catalytic cycle) to Asn, Glu or Thr led to virtual abolishment of Na+/K(+)-ATPase activity and ouabain-binding capacity. Replacement of Lys-507 of the same subunit (the putative ATP-binding site) by Met resulted in decreases in Na+/K(+)-ATPase activity and ouabain-binding capacity. These results are in agreement with those reported for rabbit sarcoplasmic reticulum Ca2(+)-ATPase (Maruyama, K. and MacLennan, D.H. (1988) Proc. Natl. Acad. Sci. USA 85, 3314-3318).

Adenosine Triphosphate↗

Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring.

This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.

Adult↗

Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid Graves' disease.

Lipid metabolism was examined in patients with hyper- or hypothyroidism. Compared with corresponding age and sex matched controls, serum total cholesterol (T-chol), low density lipoprotein cholesterol (LDL-chol), phospholipid (PL) and LDL levels were significantly low and free fatty acid (FFA) levels were high with apparently normal triglyceride (TG), very low density lipoprotein (VLDL) and high density lipoprotein cholesterol (HDL-chol) levels in 61 hyperthyroid patients, while T-chol, LDL-chol, TG, PL, VLDL and LDL levels were high with normal FFA and HDL-chol levels in 31 hypothyroid patients. Serum lipid levels were then repeatedly measured in 7 men and 7 women with hyperthyroid Graves' disease before treatment (stage I), just after the patients became euthyroid with anti-thyroid drug (stage II) and more than 2 months after the patients remained euthyroid (stage III). Serum T-chol, LDL-chol, PL and LDL levels were low at stage I, significantly elevated at stage II and then normalized at stage III. Transient but significant elevation of serum TG, VLDL and HDL-chol levels at stage II were also observed in men. Accelerated catabolism and anabolism of lipid has been reported in hyperthyroidism. Transient elevation of serum lipid levels suggests a more rapid improvement in catabolism than in anabolism of lipid in an early stage of the medical treatment for hyperthyroidism.

Adult↗