Search PubMed⌕ Search

Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 433 records · Page 24Linked to original sources

[A case report of complete remission of liver metastasis from rectal carcinoma treated with intra-arterial infusion chemotherapy].

We reported a case of metastatic liver cancer from rectal carcinoma, which was successfully treated by systemic continuous 5-Fluorouracil and intermittent Mitomycin C chemotherapy. A 70-year-old male with rectosigmoid carcinoma was admitted to our hospital. Abdominal CT and echography revealed solid mass in the liver. He underwent low anterior resection and infuse-a-port was inserted because of arterial infusion chemotherapy for metastatic liver cancer. 5-FU (250 mg per day) was infused continuously and MMC at the dose of 8 mg for one time in a week was administered. Two months later, hepatic tumor disappeared and the serum CEA level also normalized. At this writing, the patient is alive and well and complete remission has been obtained for more than 10 months.

Adenocarcinoma↗

[Adjuvant chemotherapy therapy of breast cancer].

Six to 12 cycles of CMF is regarded as the standard regimen for adjuvant chemotherapy for breast cancer, producing 10-20% increase in survival for premenopausal and node-positive patients. Tamoxifen combined with CMF has induced an additional reduction in recurrence rate only in postmenopausal patients. Oral administration of 5-FU or its derivatives combined with tamoxifen for as long as 1-2 years is the regimen most widely used in Japan for considerable improvement in survival. But it needs further evaluation in comparison with CMF, and in ultimate duration of treatment and better combination with other drugs. Adjuvant chemotherapy for node-negative patients is advocated in the U.S., where the recurrence rate is as high as 30%. Only 10% of Japanese n0 patients undergo recurrence. Therefore, adjuvant therapy should be given only to high-risk patients.

Aged↗

[New factors of possible prognostic value in breast cancer].

Over the past 10 years, we have witnessed a variety of potential prognostic factors of breast cancer including proliferative rate, ploidy, growth factor receptors, oncogenes and cathepsin D production. Some of these variables seem to predict the prognosis of the patients but the available data are conflicting and call for carefully conducted quality-control studies to analyze intra- and interlaboratory variations. In this review, we provided a framework from which prognostic factor information can be used directly to make treatment decisions.

Breast Neoplasms↗

Stimulation of the Na+/K+ pump by external [K+] is regulated by voltage-dependent gating.

Wild-type and mutants with alpha-subunits truncated at the N terminus of Na+/K+ pumps of Torpedo electroplax were expressed in Xenopus oocytes by injection of cRNAs encoding for one of the alpha-subunits and for the beta-subunit. Currents generated by the pump were investigated under voltage clamp in Na(+)-free solution, a condition where stimulation by external [K+] is the only voltage-dependent and rate-determining step in the pump cycle (Rakowski, R. F., Vasilets, L. A., LaTona, J., and Schwarz, W. (1991) J. Membr. Biol. 121, 177-187). Voltage dependence of the apparent Km value for pump stimulation and of maximum transport activity was investigated. Truncation of the intracellular N-terminal end of the alpha-subunit at the trypsin-accessible site (alpha delta K37, leaving Lys37) leads to nearly complete inhibition of pump current at physiological potentials, whereas ouabain binding capacity is retained indicating an essential involvement of the N-terminal end in the process of ion translocation. Truncation at the N-terminal end leaving Lys28 (alpha delta K28) or Thr29 (alpha delta T29) leads to removal of 6 or 7 lysine residues, respectively, and has no effect on maximum transport activity. On the other hand, the mutated pumps with alpha delta K28 or alpha delta T29 exhibit more pronounced voltage dependences for stimulation of pump current by external [K+] compared with the wild-type Torpedo pump. In particular, a pronounced increase in voltage dependence of the apparent affinity of pump stimulation is obtained by the removal of the Lys28. The results support the view that the lysine-rich region in the N-terminal end affects the cation binding to the pump molecule and that Lys28 is important.

Animals↗

The 'lysine cluster' in the N-terminal region of Na+/K(+)-ATPase alpha-subunit is not involved in ATPase activity.

The alpha-subunit of the Na+/K(+)-ATPases from several animal species have markedly similar amino acid sequences. However, the N-terminal sequences of the alpha-subunit are rather divergent except for lysine-rich sequences, the 'lysine cluster'. Here we report that the alpha-subunit from frog (Rana catesbeiana) has an N-terminal sequence with the 29 amino acid residues shorter than that of the Xenopus alpha-subunit deduced from its cDNA and hence lacks the 'lysine cluster'. Nevertheless, the Rana enzyme still exhibits ATPase activity. The ATP-dependent Na+ transport activity of the Rana enzyme was similar to that of the dog enzyme, which contains the 'lysine cluster'. Moreover, the Torpedo alpha-subunits deprived of the 'lysine cluster' by means of two gene deletions showed the same Na+/K(+)-ATPase activities as that of the wild type when expressed in Xenopus oocytes from their mRNAs. These results strongly suggest that the 'lysine cluster' in the N-terminal region of the alpha-subunit is not involved in the ATPase and ion transport activities. Since an active alpha-subunit was translated in Xenopus oocytes from mRNA lacking the N-terminal region including the 'lysine cluster', these regions were proved not to function as a membrane insertion signal sequence.

Adenosine Triphosphatases↗

Immunohistochemical, ultrastructural and biochemical studies of an amylase-producing breast carcinoma.

We describe a breast cancer with ectopic production of amylase, found in the patient's serum, urine and in the tumour. Clinically, serum amylase levels reflected both the progression of the disease and regression induced by various therapies. Using agarose gel electrophoresis and a wheat protein inhibitor assay, the predominant serum amylase appeared to be identical to pancreatic-type isoenzyme. However, the action mode analysis using a new fluorogenic substrate revealed that the serum contained non-salivary, non-pancreatic amylase. The tumour had microscopic features of invasive ductal carcinoma with some argyrophilic differentiation. The component cells stained positively for amylase, and ultrastructurally numerous secretory granules were seen.

Adult↗

Desmoplakin expression and distribution in cultured rat bladder epithelial cells of varying tumorigenic potential.

The expression and distribution of the desmosomal plaque proteins, desmoplakins (DPs) I and II, were studied in nontumorigenic (RBE-8) and a series of tumorigenic (AY34, R-4909, SS-24B, RBTCC-8, and 804G) rat bladder epithelial cell lines. These cell lines ranged from slow-growing papillary transitional cells (AY34) to rapidly metastatic carcinoma cells (RBTCC-8). DPs I and II were shown by immunoblotting and Northern analysis to be present in nontumorigenic RBE-8 cells as well as in all of the tumorigenic cell lines, albeit in differing amounts. Immunofluorescence microscopy revealed striking differences in DP distribution, corresponding in general with increases in tumorigenic potential. Whereas DPs of normal RBE-8 cells and less tumorigenic AY34 cells were localized predominantly at cell interfaces, the more tumorigenic lines exhibited a high proportion of DP in the form of cytoplasmic dots, a distribution reminiscent of that seen in epithelial cells maintained in low levels of extracellular calcium. In 804G cells, which represented the most extreme example of this phenomenon, the majority of DPs were organized as cytoplasmic dots. Electron microscopy revealed intermediate filament (IF)-associated spots in the cytoplasm as well as an elaborate array of IF-associated plaques at the cell-substratum interface. The IF-associated spots in the cytoplasm reacted with anti-DP antibody in immunogold labeling experiments while those at the cell-substratum did not react. In more dense cultures of 804G cells, certain cells stratified and expressed increased amounts of DP followed by the induction of new keratins including those of the skin type. Decreasing extracellular calcium resulted in a rearrangement of DP in each cell line; staining at cell-cell interfaces disappeared and was replaced with a pattern of cytoplasmic dots. These results demonstrate a possible relationship between desmosome assembly and/or maintenance and tumorigenic potential.

Animals↗

Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor).

Unlike trypsin-like serine proteases having only one conspicuous binding pocket in the active site, subtilisin BPN' has two such pockets, the S1 and S4 pockets, which accommodate the P1 and P4 residues of ligands (after Schechter and Berger notation) respectively. Using computer graphics, the geometrical nature of the two pockets was carefully examined and strategies for site-directed mutagenesis studies were set up against a protein SSI (Streptomyces subtilisin inhibitor), which is a strong proteinaceous inhibitor (or a substrate analogue) of subtilisin BPN'. It was decided to convert the P1 residue, methionine 73, into lysine (M73K) with or without additional conversion of the P4 residue, methionine 70, into glycine (M70G). The crystal structures of the two complexes of subtilisin BPN', one with the single mutant SSI (M73K) and the other with the double mutant SSI (M73K, M70G) were solved showing that (i) small 'electrostatic induced-fit movement' occurs in the S1 pocket upon introducing the terminal plus charge of the lysine side chain, and (ii) large 'mechanical induced-fit movement' occurs in the S4 pocket upon reducing the size of the P4 side chain from methionine to glycine. In both (i) and (ii), the induced-fit movement occurred in a concerted fashion involving both the enzyme and 'substrate' amino acid residues. The term 'substrate-assisted stabilization' was coined to stress the cooperative nature of the induced-fit movements.

Bacterial Proteins↗

Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer.

To elucidate the etiology of the thrombogenic effects of high-dose medroxyprogesterone acetate (MPA) in the treatment of breast cancer, hematologic parameters were sequentially assessed in 12 patients receiving MPA 800 mg p.o. daily for 6 months as adjuvant hormone therapy after mastectomy. The results were as follows. (1) Coagulation system: levels of factor VII and fibrinogen decreased significantly, whereas factors II and IX increased significantly, with a shortened activated partial thromboplastin time. (2) Fibrinolytic system: plasminogen and alpha 2-plasmin inhibitor-plasmin complex increased, whereas fibrinogen degradation products remained low. (3) Anticoagulation system: antithrombin III increased significantly. (4) These changes were most marked after 2 or 4 weeks of MPA treatment, and returned to the pretreatment level one month after discontinuation of treatment. (5) No patients in this study developed thromboembolic disease during or after MPA administration. These results indicate that MPA may induce a hypercoagulable state, but this state does not directly lead to the development of thrombosis.

Adult↗

[A study on hepatic dysfunction associated with rubella infection].

We had 11 patients with rubella infection accompanied by hepatic dysfunction from 1979 through 1989. The elevations of sGOT were moderate, but sLDH levels were high. Extra hepatic manifestations were suspected by analysis of LDH isozymes. In 9 out of 11 patients, the sGPT levels returned to normal within 8 weeks. But prolonged courses of abnormal transaminase levels were observed in 2 patients. One was accompanied by underlying chronic hepatitis type non-A, non-B, and the other was supposed to have a prolonged rubella infection. Liver biopsy specimen taken from one patient in the acute phase demonstrated a non-specific reactive hepatitis. These observations suggest that rubella infection should be taken into consideration in making the diagnosis of sporadic hepatitis type non-A, non-B.

Adult↗

Effect of salivary epidermal growth factor on wound healing of tongue in mice.

The role of salivary epidermal growth factor (EGF) in wound healing of the tongue was studied in mice. Sialoadenectomy (removal of the submandibular glands, which are the major source of salivary EGF) or sham operation was performed 2 wk before infliction of wound on the tongue. Salivary EGF levels were 1.98 +/- 0.47 and 0.20 +/- 0.04 (SE) microgram/ml in sham-operated male and female mice, respectively, whereas sialoadenectomy reduced salivary EGF to undetectable levels in both male and female mice. A circular superficial wound measuring approximately 2 mm in diameter was made in the middle of the tongue by mechanically ablating only the epithelial layer. The rate of wound healing was monitored by a stereomicroscopy. Sialoadenectomized male mice showed a significant delay in wound healing compared with sham-operated controls. Treatment of sialoadenectomized male mice with EGF (1 microgram/ml in drinking water) restored the rate of wound healing to normal levels. Transforming growth factor (1 microgram/ml) was as effective as EGF in the promotion of wound healing, whereas nerve growth factor (1 microgram/ml) was ineffective. Essentially the same results were obtained in female mice. In addition, two classes of EGF binding sites with high and low affinity were demonstrated in the epithelium of the tongue obtained from male and female mice. The maximum binding sites and dissociation constants of the EGF receptors were the same between males and females and were not affected by sialoadenectomy. These results suggest that salivary EGF is involved in the promotion of wound healing of the tongue in both male and female mice.

Animals↗

Pretranslational enhancement of epidermal growth factor receptor by direct effect of testosterone in mouse liver.

The effects of testosterone on the levels of epidermal growth factor receptor (EGFR) in mouse liver were studied. Orchiectomy resulted in 39% and 41% reductions in the levels of EGFR mRNA and EGF binding, respectively, within 2 weeks. Treatment of orchiectomized mice with a sc injection of testosterone propionate (TP; 100 micrograms/mouse.day) for 1 week restored these values to normal male levels. The hepatic levels of EGFR mRNA and EGF binding in females were 37% and 36% of those in males, respectively, and were not affected by ovariectomy, whereas treatment of females with TP (100 micrograms/mouse.day) increased EGFR to normal male levels within 1 week. On the other hand, neither orchiectomy nor androgen treatment affected levels of mRNAs for EGFR in the kidney or mRNAs for the structural protein beta-actin in the liver. To examine whether testosterone directly increased EGFR levels in the liver, TP (1.0 mg) pellets were implanted into the spleen of orchiectomized mice, so that testosterone released from the pellets reached the liver through the portal vein but did not enter the systemic circulation due to rapid clearance by the liver. The heptic levels of EGFR mRNA and EGF binding in orchiectomized mice were restored to normal male levels by intrasplenic implantation of TP (1.0 mg) pellets. This treatment also increased the hepatic levels of EGFR mRNA and EGF binding in female mice by 61% and 68%, respectively. In addition, sialoadenectomy, which reduced plasma EGF, as well as EGF antiserum treatment did not affect the androgen-dependent increase in EGFR levels in the liver, suggesting that endogenous EGF is not involved in the androgenic regulation of hepatic EGFR levels. These results suggest that hepatic EGFR levels are at least in part regulated at a pretranslational level by direct effects of androgens on the liver.

Animals↗

Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 13C nuclear magnetic resonance.

The 13C-NMR spectrum (Fig. 2,1) of cyclooctapeptide cyclo(L-phe-L-Pro-Gly-L-Pro)2 (A) in CDC13 suggested that its conformation involved the coexistence of two kinds of C2-symmetric conformation with trans-trans-trans-trans and cis-trans-trans-trans forms. Adding 0.5 equivalent of CsSCN or one equivalent of DL-Phe-OMe.HCl to the solution of cyclopeptide (A) in CDC13 yielded 13C-NMR spectra (Fig. 2,2 and Table I) which suggested a single C2-symmetric conformation with trans-trans-trans-trans form, resulting from the formation of complexes with CsSCN or DL-Phe-OMe.HCl. The 13C-NMR spectrum of complexes of A with DL-Phe-OMe.HCl displayed separate resonances for C(gamma), C(o), C(m), C(alpha), and C(beta) of D-Phe-OMe.HCl and L-Phe-OMe.HCl (Table I).

Amino Acid Sequence↗

Antithyroid drug therapy for Graves' hyperthyroidism: is long-term administration of a small maintenance dose necessary?

This retrospective study serves as an inquiry into the common practice of long-term administration of small maintenance doses of either methyl-mercaptoimidazole (MMI) or propylthiouracil (PTU) to Graves' hyperthyroid patients who became euthyroid with primary large doses of the same drugs. One hundred and two patients with Graves' hyperthyroidism treated with antithyroid drug (ATD) were studied. Sixty-one were treated with conventional long term therapy and 41 were treated with short-term therapy. Small maintenance doses of ATDs were not administered to the short-term therapy patients. The duration of long-term therapy was 28.6 +/- 20.2 months (from 12 to 48 months) and that of short-term therapy was 8.4 +/- 1.8 months (from 5 to 11). Post therapy and follow-up observation continued for 19.0 +/- 2.7 months (16-25 months) in both long-term and short-term patients. Of the 61 long-term therapy patients, 20 were relapsed and 41 (67.2%) continue to remain in remission. So too, of the 41 short-term therapy patients, 14 relapsed and 27 (65.9%) still remain in remission. There was no statistical difference between the long-term and short-term therapy group in age, sex, duration of symptoms before diagnosis, antithyroid antibodies, radioactive iodine uptake, free thyroid hormone levels or goiter size before treatment or in TBII levels at cessation of ATD. It is concluded that 'short-term ATD therapy' without a maintenance dose is sufficient and saves several months of the patient's and clinician's time.

Adult↗

Serum levels and thyroid tissue expression of CA50 and CA 19-9 in patients with thyroid tumor.

A 77-year-old man was admitted to the hospital with a thyroid nodule. The levels of serum tumor-associated carbohydrate antigens (CA 50, CA 19-9) and thyroglobulin (HTG) were markedly increased. We performed total thyroidectomy and right neck lymph node dissection. After treatment, the serum CA 50, CA 19-9 and HTG levels were markedly decreased. Histological examination of the thyroid tumor showed papillary adenocarcinoma and the dissected neck lymph nodes contained metastatic adenocarcinoma. The expression of CA 50 and CA 19-9 (defined by the monoclonal antibodies) was studied by immunoperoxidase staining from the normal and carcinomatous thyroid tissues and the dissected neck lymph node. CA 50 was expressed more strongly by the carcinoma cells than CA 19-9. The positive rates for serum CA 50 and CA 19-9 levels in other patients with papillary adenocarcinoma were not significantly higher compared with patients with benign nodules and normal subjects. But a significant positive correlation was found between the diameter of the carcinoma and the serum levels of CA 50 and CA 19-9. These results suggest that the serum levels of CA 50 and CA 19-9 might not become useful markers for diagnosing carcinoma of the thyroid, but might be useful markers for monitoring the growth or recurrence of papillary adenocarcinoma of the thyroid in patients with high serum levels of CA 50 and CA 19-9.

Adenocarcinoma, Papillary↗

Serum free triiodothyronine to free thyroxine ratio enables early prediction of the outcome of antithyroid drug therapy in patients with Graves' hyperthyroidism.

This study scrutinizes the correlation between serum free triiodothyronine (FT3) to free thyroxine (FT4) ratios and the eventual outcome of antithyroid drug (ATD) therapy in patients with Graves' disease. Forty-four patients with Graves' thyrotoxicosis were treated with methylmercaptoimidazole (methimazole). During the follow-up, 16 patients relapsed in the short period of one to five months after cessation of the drug (relapse group), and 28 patients remained in remission when checked at 12 to 20 months after treatment (remission group). Serum FT3 to FT4 ratios [(pg/ml/ng/dl) x 10] were less than 55 throughout ATD therapy in 27 of the 28 remission patients whereas the ratios of the relapse group exceeded 55 from the early phase of methimazole treatment in 10 of 16 patients. In eight of these 10 patients the increased ratios were detected within three months of therapy (1 month, 3 patients; 2 months, 4 patients; 3 months, 1 patient). The ratios for the remaining two patients rose above 55 at the fifth and sixth months. There was no statistical difference between the remission and relapse groups in the FT3 to FT4 ratios either before nor at the completion of the treatment. However, a clear difference could be measured at a point during the therapy. Those in whom this difference was pronounced later underwent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in mice.

The role of epidermal growth factor (EGF) in liver regeneration was studied in mice after partial hepatectomy. Two weeks before partial hepatectomy, mice were sham-operated (control) or sialoadenectomized (removal of submandibular glands) to reduce plasma EGF levels. Sialoadenectomized mice showed low plasma EGF levels (29.7 +/- 6.6 pmol/l; mean +/- S.E.M.) compared with controls (66.0 +/- 8.3 pmol/l). After partial hepatectomy, sialoadenectomized mice were treated with or without a daily s.c. injection of 5 micrograms EGF and the rate of DNA synthesis in the regenerating liver was monitored by [125I]iododeoxyuridine uptake. Control mice showed a sharp peak of DNA synthesis at 48 h after partial hepatectomy while sialoadenectomized mice showed a delayed and broad peak at 84 h. Treatment of sialoadenectomized mice with EGF (5 micrograms/mouse per day) completely restored the pattern of DNA synthesis so that a sharp peak appeared at 48 h. The total liver DNA content of the control mice (79.1 +/- 2.5% of the preoperative level; mean +/- S.E.M.) was significantly (P less than 0.01) higher than that of the sialoadenectomized mice (65.2 +/- 3.0%) 3 days after partial hepatectomy, but this difference disappeared on day 7 when liver regeneration was almost completed in both groups. Treatment of sialoadenectomized mice with EGF increased total liver DNA content (78.2 +/- 2.9%) to that of control mice on day 3 after partial hepatectomy. In addition, normal mice showed a rapid increase in plasma EGF levels at 1-8 h after partial hepatectomy, whereas sialoadenectomized mice showed low plasma EGF levels throughout the course of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗