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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 469 records · Page 26Linked to original sources

Further fractionation of the glycoprotein families of porcine zona pellucida by anion-exchange HPLC and some characterization of the separated fractions.

The glycoproteins of porcine zonae pellucidae have been fractionated into three families (PZP1-3) by gel filtration HPLC [Nakano et al. (1987) Biochem. Int. 14, 417-423]. However, they still comprise heterogeneous molecular species differing in electric charge. We found that sulfate, but not phosphate, is contained in PZP1-3 by a simple and rapid method for microanalysis of the anionic groups. These families were efficiently separated into many fractions by anion-exchange HPLC. When elution was performed by stepwise increase in NaCl concentration in 8 M urea/20 mM Tris-HCl, pH 8.0, a single distinctive peak emerged for each step. The analyses of amino acids, monosaccharides, and anions of the eight separated fractions of the major family, PZP3, showed that larger amounts of sulfated lactosamine linked to the constituent proteins are present in the fractions that are eluted later: the chain length and/or the chain number of these polylactosamines and the sulfate content increased with stepwise increase in NaCl concentration. Composition analyses also revealed that twice as much N-glycolylneuraminic acid is present as N-acetylneuraminic acid in all fractions. The contents of these sialic acids in the fractions slightly increased in the order of elution. These results together with those of the analyses of endo-beta-galactosidase digests showed that the charge heterogeneity of the porcine zona proteins is due mainly to differences in the amount of sulfated lactosamine, which is predominantly distributed in the non-reducing regions of the sugar chains.

Amino Acids↗

Effects of dietary iodine on chemical induction of thyroid carcinoma.

Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2-hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/or promoting effects of TSH.

Administration, Oral↗

Effects of monensin on subcellular structure, thyroglobulin secretion and peroxidase activity of cultured thyroid cells obtained from patients with hyperthyroidism.

The effects of monensin on subcellular structure, release of thyroglobulin (TG) and peroxidase (PO) activity were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). TG concentration in the culture medium was measured by a sandwich enzyme immunoassay and the amount of TG in cultured cells was measured with an identical sandwich enzyme immunoassay after lysis of the cells with Triton X-100. PO activity of cultured cells was measured by a biochemical method. Addition of TSH (10 mU/ml/day) to the culture medium increased the synthesis and release of TG. When monensin (1 micron/l) was added to the medium on the last day of a 3-day incubation with TSH, the Golgi complex showed vacuolative change ultrastructurally, and the amount of intracellular TG was increased, whereas the amount of TG in the culture medium and PO activity became lower than those in the control group. These results suggest that in cultured Basedow's cells, TG is secreted through the Golgi complex, and that the activity of PO is elevated after processing in the Golgi complex.

Cells, Cultured↗

An immunohistochemical study of calcitonin-containing cells in benign and malignant thyroid lesions.

Parafollicular cells (C-cells) in benign and malignant thyroid lesions were studied immunohistochemically with a polyclonal anti-calcitonin (CT) antibody. The C-cells were seen most frequently in the middle third of the lateral lobes in the thyroid gland of normal individuals and patients with Graves' disease and chronic thyroiditis, although in the latter the number of such cells was significantly decreased (p less than 0.05). In adenomatous goiter, C-cells were present in nodular lesions from an early stage of nodule development (frequency about 19%), whereas in the later stage these cells were rarely observed inside type 1 nodules, which were generally characterized by an admixture of follicles with considerably different sizes. However, C-cells were not observed inside type 2 nodules, which were composed of similar-sized follicles, or in the parenchyma of 56 cases of benign and malignant thyroid tumors. These findings suggest that since C-cells are present in nodular lesions, the histogenesis of adenomatous goiter is quite different from that of follicular adenoma; thyroid neoplasms generally contain no C-cells in the parenchyma.

Adenoma↗

Involvement of epidermal growth factor deficiency in pathogenesis of oligozoospermia in streptozotocin-induced diabetic mice.

Based on previous findings that epidermal growth factor (EGF), which plays an important role in maintenance of spermatogenesis, is deficient in diabetic mice, the significance of EGF deficiency in the pathogenesis of oligozoospermia in streptozotocin-induced diabetic mice was studied. EGF levels in the submandibular glands and plasma of diabetic mice were 0.61 +/- 0.07 micrograms/mg tissue and 0.25 +/- 0.02 ng/ml (mean +/- SE), respectively, whereas those of normal mice were 1.63 +/- 0.08 micrograms/mg tissue and 0.54 +/- 0.04 ng/ml, respectively. The epididymal sperm counts of diabetic mice, 4.7 +/- 0.14 x 10(5)/mg tissue, were significantly lower (P less than 0.01) than those of normal mice, 6.0 +/- 0.10 x 10(5)/mg tissue. Administration of EGF (5 micrograms/mouse/day) to diabetic mice significantly (P less than 0.01) increased their sperm counts to 5.5 +/- 0.16 x 10(5)/mg tissue without affecting plasma levels of testosterone and glucose. Furthermore, insulin treatment (1 U/mouse/day) of diabetic mice restored the submandibular gland, plasma EGF concentrations, and sperm counts to normal levels. The restorative effects of insulin on sperm production appeared to be mediated, at least in part, by EGF, because its effect was significantly (P less than 0.01) reduced by the concomitant administration of EGF antiserum. In addition, the plasma testosterone levels of diabetic mice, 67 +/- 14.3 ng/ml, were lower that those of normal mice, 122 +/- 19.1 ng/ml. Administration of testosterone (1 mg/mouse/day) normalized the submandibular gland and plasma EGF levels and significantly increased sperm counts in the epididymis. These results suggest that EGF deficiency is a possible cause for the pathogenesis of oligozoospermia in diabetic mice.

Animals↗

Plasma atrial natriuretic peptide in patients with Graves' disease.

In order to clarify the effect of thyroid hormone on the plasma atrial natriuretic peptide (ANP) concentration, 14 patients with Graves' disease and 6 normal control subjects were studied. They were all under constant sodium intake because dietary sodium is known to affect the amount of plasma ANP. Sodium intake remained constant at 171 mEq daily for five consecutive days at which time the ANP concentration was measured. Graves' disease patients were tested both before and after surgery. The preoperative, hyperthyroid ANP level concentration in Graves' disease patients was 6.7 +/- 2.3 fmol/ml compared to a significantly lower level of 4.2 +/- 1.4 fmol/in normal control subjects. Seven days after surgery when Graves' disease patients became euthyroid their ANP markedly decreased to 4.2 +/- 2.9 fmol/ml. In the present study we were able to confirm that under a constant sodium diet, high plasma ANP in patients with Graves' disease was reduced after surgery when they became euthyroid. Results also suggest that high circulating ANP might play an important role in sodium and water metabolism and hemodynamic changes in hyperthyroidism.

Age Factors↗

[A case of pulmonary metastasis from adenoid cystic carcinoma of the trachea].

A 33-year-old woman with adenoid cystic carcinoma of the trachea was treated by resection of the upper and mid-trachea, plus total laryngectomy, subtotal thyroidectomy, partial resection of the cervical esophageal muscle layer and mediastinal tracheostomy. This tumor invaded directly into the thyroid gland, the larynx, the recurrent laryngeal nerve and the cervical esophagus. Three years after the operation, metastases developed in the right lung (S10, S2) and partial resection of the lung was performed. This patient is now free from disease. Aggressive surgical resection is important for the improvement of survival in this condition, although this tumor shows low grade malignancy and is slowly growing.

Adult↗

Stimulation of stromal cell growth by normal rat urothelial cell-derived epidermal growth factor.

Primary cultured adult rat urothelial (RU) cells caused increased thymidine incorporation in rat bladder stromal (RS) cells in a coculture system. The concentrated conditioned medium derived from RU cell culture (CM-RU) also stimulated the growth of RS cells, and induced anchorage independent growth of NRK-49F cells. Since these activities were heat and acid resistant, we investigated whether epidermal growth factor (EGF) and/or transforming growth factors were the humoral factor(s) responsible. The immunodiffusion analysis of CM-RU gave a positive precipitin line with rabbit anti-rat EGF IgG but not with rabbit anti-rat transforming growth factor-alpha antibodies. The anti-rat EGF IgG inhibited CM-RU-stimulated thymidine incorporation into RS cells, whereas normal rabbit IgG did not. By immunofluorescent technique using rabbit anti-rat EGF antibodies, immunoreactive EGF was demonstrated in RU cells and the urothelial of cryoinjury-induced reparative hyperplasia. Immunofluorescent technique also demonstrated the presence of EGF receptors on the cell membrane of RU and RS cells, basal cells of normal rat urothelium, and cells of whole epithelial layers of reparative hyperplasia. These data strongly suggest that EGF or an EGF-like substance produced by RU cells and released into medium stimulates the growth of RS cells possibly mediated by EGF receptors.

Animals↗

[Neurilemmoma of the neck; a report of 35 cases].

We reported 35 cases of neurilemmoma of the neck. All cases had a tumor and 12 cases had neurogenic symptoms or signs such as tenderness, radiating pain, coughing at pressure of the tumor and Horner's syndrome. Tumors originated from the vagus nerve in 10, brachial plexus in 5 and cervical sympathetic chain in 3 cases. The nerve of the origin could not be identified in 17 cases. We classified tumors into 4 types based upon macroscopic nature. Type 1 is that the nerve of the origin could not be identified. Type 2 is that normal nerve passes on the surface of the tumor. Type 3 is that nerve fibers slightly dilated on the tumor surface. Type 4 is that tumor originated from major nerve and tumor surface is covered by the nerve fibers. Postoperative functional deficit of the nerve is rare in type 1 and occurred in the most of type 4 although intracapsular excision was performed. Although neurilemmoma of the neck is rare, postoperative functional deficit can often occur in some types. At the diagnosis of the tumors of the neck we must take the neurilemmoma into consideration. We recommend careful intracapsular excision at the surgery of the neurilemmoma originated from major nerves.

Adult↗

Conformation of guanosine 5'-diphosphate as bound to a human c-Ha-ras mutant protein: a nuclear Overhauser effect study.

1H NMR spectra of a GDP/GTP-binding domain of human c-Ha-ras gene product (residues 1-171) in which glutamine-61 was replaced by leucine [ras(L61/1-171) protein] were analyzed. By one-dimensional and two-dimensional homonuclear Hartmann-Hahn spectroscopy and nuclear Overhauser effect (NOE) spectroscopy of the complex of the ras(L61/1-171) protein and GDP, the ribose H1', H2', H3', and H4' proton resonances of the bound GDP were identified. The guanine H8 proton resonance of the bound GDP was identified by substituting [8-2H]GDP for GDP. The dependences of the H1' and H8 proton resonance intensities on the duration of irradiation of the H1', H2', H3', and H8 protons were measured. By numerical simulation of these time-dependent NOE profiles, the conformation of the protein-bound GDP was elucidated; the guanosine moiety takes the anti form about the N-glycosidic bond with a dihedral angle of chi = -124 +/- 2 degrees and the ribose ring takes the C2'-endo form. Such an analysis of the conformation of a guanine nucleotide as bound to a GTP-binding protein will be useful for further studies on the molecular mechanism of the conformational activation of ras proteins on ligand substitution of GDP with GTP.

Base Sequence↗

Expression of human poly(ADP-ribose) polymerase with DNA-dependent enzymatic activity in Escherichia coli.

A cDNA for human poly(ADP-ribose) polymerase was inserted into a plasmid, transfected and expressed in E. coli. A lysate of the E. coli cells containing the expression plasmid reacted with antibody against human poly(ADP-ribose) polymerase and synthesized poly(ADP-ribose). The partially purified poly(ADP-ribose) polymerase expressed in E. coli had the same molecular weight and enzymological properties as human placental poly(ADP-ribose) polymerase, including affinity for NAD, turnover number and DNA-dependency for activity. This expression system should be useful for structure-function analysis of poly(ADP-ribose) polymerase.

Blotting, Western↗

Expression of active alpha-3 subunit of rat brain Na+,K+-ATPase from the messenger RNA injected into Xenopus oocytes.

Cloned cDNA encoding the so-far uncharacterized alpha-3 subunit of rat brain Na+,K+-ATPase (Hara et al. (1987) J. Biochem. 102, 43-58, Shull et al. (1986) Biochemistry 25, 8125-8132) was incorporated into a vector carrying the SP6 promoter. The mRNA produced in vitro was injected into Xenopus oocytes with the mRNA encoding the Na+,K+-ATPase beta subunit of Torpedo electroplax. Increased Na+,K+-ATPase activity in the oocyte membrane was observed. This newly expressed activity was inhibited by ouabain (Ki = 1.5 x 10(-7) M), suggesting that the alpha-3 subunit of rat brain Na+,K+-ATPase is a highly ouabain-sensitive catalytic subunit.

Animals↗

[The mechanism of postoperative tetany in Graves' disease].

The levels of serum calcium (Ca), inorganic phosphate (P) and mid-molecular parathyroid hormone (PTH) were measured in 37 patients with Graves' disease (12 in hyperthyroid state, 25 in euthyroid state followed by subtotal thyroidectomy), 6 with papillary carcinoma of the thyroid, 8 with benign nodular goiter and 19 healthy control subjects in order to investigate the change in these levels before and after thyroidectomy. The levels of serum Ca and P of the hyperthyroid patients with Graves' disease were 9.73 +/- 0.30 mg/dl and 4.47 +/- 0.44 mg/dl, respectively, which were significantly higher than those of healthy control subjects. No significant difference in the levels of serum PTH was observed between hyperthyroid patients with Graves' disease and healthy control subjects. The levels of serum Ca, P and PTH of euthyroid patients with Graves' disease were not significantly different from those of healthy control subjects. In the patients with Graves' disease who had undergone subtotal thyroidectomy followed by postoperative tetany, serum Ca and serum PTH decreased significantly from 9.39 +/- 0.45 mg/dl to 7.90 +/- 0.33 mg/dl and from 406.6 +/- 164.4 pg/ml to 229.9 +/- 136.0 pg/ml, respectively, after surgery, but there was no change in serum P. In the patients without postoperative tetany, serum Ca and serum P decreased significantly after surgery from 9.65 +/- 0.36 mg/dl to 9.15 +/- 0.33 mg/dl and from 4.03 +/- 0.46 mg/dl to 3.47 +/- 0.54 mg/dl, respectively, without any change in the levels of serum PTH. In the patients with papillary carcinoma or benign nodular goiter without postoperative tetany, the levels of serum Ca, P and PTH did not change after surgery. In the patients with papillary carcinoma followed by postoperative tetany, serum Ca decreased significantly after surgery with concomitant decrease of serum PTH. It was concluded that excessive thyroid hormones influenced Ca metabolism, and the transient tetany following subtotal thyroidectomy for Graves' disease seemed to be due to both the absorption of Ca by hungry bone and parathyroid hypofunction.

Adolescent↗

[Immunohistochemical study on oncogene product ras p 21 in thyroid carcinoma].

The oncogene product ras p 21 was detected by an immunohistochemical procedure in 132 cases of thyroid carcinoma and 14 cases of normal thyroid. In addition, semiquantitative analysis using percentage of positive cells and a serially diluting test of the primary antibody were performed in papillary and follicular carcinoma, and its non-neoplastic counterparts. Papillary carcinoma showed identical results in the immunostaining and semiquantitative analysis between minute and advanced carcinoma. Papillary and follicular carcinoma exhibited significantly increased expression of ras p 21 in the cytoplasm, although the former showed much more enhanced expression of ras p 21 than that in the latter. The immunostaining for ras p 21 in papillary carcinoma differed clearly from non-neoplastic counterparts in which ras p 21 expression was moderately enhanced, although this difference was statistically disappeared between follicular carcinoma and its non-neoplastic counterparts. However, non-neoplastic tissue located close to these neoplasms showed more increased immunostaining for ras p 21 than that observed in the thyroid tissues remote from the neoplasm, and in normal thyroid. Squamous cell, anaplastic and medullary carcinoma demonstrated non or poor expression of ras p 21. These results suggested that ras p 21 had some effects on papillary and follicular carcinoma, and the effects of oncogene product on the neoplasm and non-neoplastic counterparts differed considerably depending upon a histological type of thyroid carcinoma.

Adult↗

[Carcinoma of male breast--with special reference to noninvasive carcinoma].

Seven cases of carcinoma of male breast were reported. The mean age of them was about 65 years, 17 years older than that of female breast cancer. Six tumors out of 7 were located under the areola. By histological examination, 4 of 7 cases were proved to be noninvasive ductal carcinoma, and the others are invasive ductal carcinoma (2 : scirrhous, 1 : solid-tubular). We focused on clinicopathological features of noninvasive carcinoma. There were two points to be mentioned. One is the nipple discharge as a chief complaint, and the other is cyst formation as a macroscopic observation. These features are characteristic to noninvasive carcinoma and contribute to diagnosis. Therefore, for screening the mass of male breast, ultrasonography (U.S.) is most useful. For preoperative final diagnosis, aspiration or smear cytology is essential. In regard to postoperative survival, all of the 3 invasive cases were dead but all of the 4 noninvasive cases are alive. So the prognosis of noninvasive carcinoma of male breast does not appear to be worse than the female one. These observations indicate that the prognosis of carcinoma of male breast can be improved by early diagnosis and appropriate surgical therapy.

Aged↗

Structural differences between a ras oncogene protein and the normal protein.

One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.

Crystallography↗

Growth control of androgen-dependent Shionogi carcinoma cells by growth factor(s) produced from androgen-independent Shionogi carcinoma cells in a paracrine mechanism.

Androgen-dependent (SC3) and -independent (CADO21) cloned cell lines were established from androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). The effects of conditioned medium (CM) collected from SC3 and CADO21 cells on the anchorage-independent growth of SC3 cells in soft agar were studied. CM prepared from SC3 cells in the absence of testosterone was unable to stimulate the growth of SC3 cells, whereas CM prepared from SC3 cells in the presence of 10(-8) M testosterone stimulated the growth of SC3 cells in a concentration-dependent manner (21 colonies at 10% and 48 colonies at 20%) and this growth-stimulatory effect was not inhibited by 10(-6) M cyproterone acetate. CM prepared from CADO21 cells in the absence of testosterone was also able to stimulate the SC3 cell growth in a concentration-dependent manner (9 colonies at 10% and 19 colonies at 20%). These results suggest that the growth of androgen-dependent SC3 cells is stimulated by androgen-induced growth factor(s) produced from the same cells (autocrine mechanism) and is also regulated by autonomous growth factor(s) produced from androgen-independent cancer cells formed from the dependent cancer cells (paracrine mechanism). A suggested possible mechanism of the progression from androgen-dependent to -independent growth of cancer cells is also discussed.

Androgens↗