Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 379 records · Page 21Linked to original sources

PubMed1993

Clonal analysis of fibroadenoma and phyllodes tumor of the breast.

Clonality of fibroadenoma and phyllodes tumor of the breast was analyzed by means of the polymerase chain reaction using small DNA samples prepared from cryostat sections. The method of clonal analysis was based on restriction fragment length polymorphism of X-chromosome-linked phosphoglycerokinase gene and on differential methylation of the gene. Specimens from 10 fibroadenomas and 5 phyllodes tumors heterozygous for the BstXI polymorphism of PGK gene were subjected to clonal analysis. It was found that fibroadenoma was polyclonal, but phyllodes tumor was made up of both monoclonal and polyclonal cell components. Since these tumors contained both epithelial and stromal components, clonality of each component was analyzed separately. Analysis of clonality of each cell component showed that both the epithelial and stromal cells were polyclonal in fibroadenoma and that the epithelial cells were polyclonal, but the stromal cells were monoclonal in phyllodes tumor. When DNA samples were prepared from widely separated sites of phyllodes tumors, every sample was found to contain a monoclonal stromal cell component. These results demonstrate that fibroadenoma is a hyperplastic lesion rather than a neoplasm, and that phyllodes tumor is a neoplasm of the stromal cells.

Adenofibroma↗

PubMed1993

Down-regulation of transforming growth factor-alpha by tamoxifen in human breast cancer.

BACKGROUND: The influence of tamoxifen treatment on transforming growth factor-alpha (TGF-alpha) levels in human breast cancer rarely has been studied in vivo. METHODS: Postmenopausal patients with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive primary breast cancer underwent two fine-needle aspiration biopsies (FNA) of the tumors. Between the two FNAs, 10 patients received no treatment (control group), and the other 10 patients received tamoxifen (20 mg/day) for 10 (8-12) days (TAM group). TGF-alpha levels in FNA samples were assayed by enzyme immunoassay. RESULTS: No significant difference was found in TGF-alpha levels between the first and second FNA samples in the control group. On the other hand, in the TAM group, TGF-alpha levels in the second FNA samples (2.5 +/- 0.5; mean +/- SEM ng/mg.DNA) were significantly (P < 0.01) lower than those in the first (4.5 +/- 0.8). Studies on the influence of tamoxifen treatment on TGF-alpha levels in ER-negative and PR-negative breast cancer showed that TGF-alpha levels were not affected by tamoxifen treatment. Positivity of epidermal growth factor receptor (EGFR) was 60% in ER-negative and PR-negative breast cancer and 30% in ER-positive and PR-positive breast cancer. CONCLUSIONS: Tamoxifen downregulates TGF-alpha levels in ER-positive and PR-positive breast cancers through ER. The significance of TGF-alpha as an autocrine growth factor appears to be more important in ER-negative and PR-negative breast cancer with high EGFR positivity than in ER-positive and PR-positive breast cancer with low EGFR positivity.

Biopsy, Needle↗

PubMed1993

[Studies on onset patterns in antithyroid drug-induced agranulocytosis].

We studied the patterns of the onset of antithyroid drug-induced agranulocytosis. From 1975 to 1990, 19,050 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. For all patients with Graves' disease treated with an antithyroid drug, a routine white blood cell count was done every 2 weeks until euthyroid state was gained, and a count was done once every moth thereafter. Of these, 70 were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 500/mm3 or less. In only 19 of the 70 was agranulocytosis detected after the occurrence of infection (symptomatic: classical agranulocytosis). The remaining 51 patients were asymptomatic when agranulocytosis was detected during routine white blood cell and granulocyte count monitoring. However, 17 of the 51 patients became symptomatic several days after the withdrawal of antithyroid drug treatment (shifted from asymptomatic to symptomatic agranulocytosis). Thirty-four patients had no symptoms of infection throughout the course of the disease (asymptomatic agranulocytosis). In conclusion, 1) We found three patterns in the onset of antithyroid drug-induced agranulocytosis: classical (symptomatic), a shift from asymptomatic to symptomatic, and asymptomatic agranulocytosis, 2) Unexpectedly, classical (symptomatic) agranulocytosis was seen in only 19 of the 70 patients, 3) We were again remained of the importance of routine white blood cell and granulocyte count monitoring.

Adolescent↗

PubMed1993

Granulocyte colony-stimulating factor treatment of antithyroid drug-induced granulocytopenia.

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Adult↗

PubMed1993

Up-regulation of estrogen receptor by tamoxifen in human breast cancer.

BACKGROUND: Influence of tamoxifen treatment on estrogen receptor (ER) and progesterone receptor (PR) levels in human breast cancer has not been fully elucidated in vivo. This problem was studied in 20 postmenopausal patients with ER-positive and PR-positive primary breast cancer. METHODS: Each patient underwent two fine-needle aspiration (FNA) biopsies. Between two FNA, 10 patients received no treatment (control group) and the other 10 patients were given tamoxifen (20 mg/day) for an average of 8 days (range, 6-10 days) (TAM group). Total ER and PR values (cytosolic plus nuclear fraction) in FNA samples were determined by enzyme immunoassay (EIA) for detecting ER and PR regardless of their occupancy with corresponding ligands. RESULTS: In the control group, no significant difference was found in ER and PR values between the first and second FNA samples. In the TAM group, ER and PR values (mean +/- standard error of the mean [SEM] fmol/mg DNA) in the second FNA samples were 605 +/- 186 and 1130 +/- 344, respectively, and were significantly higher (P < 0.05) than ER and PR values in the first FNA samples, which were 312 +/- 74 and 639 +/- 159, respectively. ER and PR values increased by 201 +/- 27% and 163 +/- 23%, respectively, on an individual basis after tamoxifen treatment. CONCLUSIONS: These results demonstrated that tamoxifen up-regulates ER and PR in human breast cancer.

Biopsy, Needle↗

PubMed1993

Voltage-dependent inhibition of the sodium pump by external sodium: species differences and possible role of the N-terminus of the alpha-subunit.

Currents generated by the Na+/K+ ATPase were measured under voltage clamp in oocytes of Xenopus laevis. The dependence of pump current on external [Na+] was investigated for the endogenous Xenopus pump as well as for wild-type and mutated pumps of electroplax of Torpedo californica expressed in the oocytes. The mutants had alpha-subunits truncated before position Lys28 (alpha delta K28) or Thr29 (alpha delta T29) of the N-terminus. The currents generated by all variants of pump molecules in the presence of 5 mM K+ show voltage-dependent inhibition by external [Na+]. The apparent KI values increase with membrane depolarisation, and the potential dependence can be described by the movement of effective charges in the electrical potential gradient across the membrane. Taking into account Na(+)-K+ competition for external binding to the E2P form, apparent KI values and effective charges for the interaction of the Na+ ions with the E2P form can be estimated. For the Xenopus pump the effective charge amounts to 1.1 of an elementary charge and the KI value at 0 mV to 44 mM. For the wild-type Torpedo pump, the analysis yields values of 0.73 of an elementary charge and 133 mM, respectively. Truncation at the N-terminus removing a lysine-rich cluster of the alpha-subunit of the Torpedo pump leads to an increase of the effective charge and decrease of the KI value. For alpha delta K28, values of 0.83 of an elementary charge and 117 mM are obtained, respectively. If Lys28 is included in the truncation (alpha delta T29), the effective charge increases to 1.5 of an elementary charge and the apparent KI value is reduced to 107 mM. The KI values for pump inhibition by external Na+, calculated by taking into account Na(+)-K+ competition, are smaller than the K1/2 values determined in the presence of 5 mM [K+]. The difference is more pronounced for those pump variants that have higher Km values. The variations of the parameters describing inhibition by external [Na+] are qualitatively similar to those described for the stimulation of the pumps by external [K+] in the absence of extracellular [Na+]. The observations may be explained by an access channel within the membrane dielectric that has to be passed by the external Na+ and K+ ions to reach or leave their binding sites. The potential-dependent access and/or the interaction with the binding sites shows species differences and is affected by cytoplasmic lysine residues in the N-terminus.

Animals↗

PubMed1993

The effect of N-myc amplification and expression on invasiveness of neuroblastoma cells.

Most neuroblastomas with N-myc amplification, a sign of extremely poor prognosis, are extensively invasive to surrounding tissues. Therefore, we investigated the relationship between N-myc amplification and invasiveness of neuroblastoma cells, using an in-vitro assay system. Five human neuroblastoma cell lines were used for this study. IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a highly invasive capacity. In contrast, SK-N-SH without N-myc amplification showed extremely low invasiveness. ST unexpectedly showed high invasiveness in spite of the lack of N-myc amplification. Treatment of GOTO with 10(-5) mol/L all-trans-retinoic acid (RA) for 72 hours markedly decreased both N-myc expression and invasiveness. Treatment of GOTO with 2 mmol/L dibutyryl cyclic AMP (dbcAMP) for 72 hours caused a slight decrease of N-myc expression and invasiveness. These results indicate that N-myc amplification and expression might be closely related to the invasiveness of human neuroblastoma cells.

Cell Movement↗

PubMed1993

Inhibitory effect of a somatostatin analogue (SMS 201-995) on the growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115).

The influence of a somatostatin analogue, SMS 201-995 (SMS), on the growth of an androgen-dependent mouse mammary tumor, Shionogi carcinoma 115 (SC115), was studied. Treatment of SC115 tumor-transplanted male mice with s.c. injections of SMS (0.04, 0.2, 1, and 5 micrograms twice a day) resulted in a dose-dependent inhibition of tumor growth. The growth-inhibitory effect of SMS reached its peak at a dose of 1 microgram twice a day. SMS was found not to elicit its growth-inhibitory effect through lowering plasma testosterone levels or down-regulating androgen receptor of SC115 tumors. Since specific binding sites for somatostatin were not observed in the membrane fractions of SC115 tumors and SMS did not inhibit the proliferation of primarily cultured SC115 tumor cells, a direct inhibitory mechanism of SMS on SC115 tumors was unlikely to be operative. Since SMS is a very potent inhibitor of growth hormone (GH) secretion, it was speculated that SMS might inhibit the growth of SC115 tumors indirectly through down-regulation of plasma GH levels. This possibility was evaluated by studying the influence of GH replacement on the growth of SC115 tumors grown in SMS-treated mice. GH replacement was done both in a male secretory pattern (intermittent injection, human GH 500 micrograms/kg twice a day) and in a female secretory pattern (continuous infusion, 1000 micrograms/kg/day). Intermittent injections of GH fully restored the growth of SC115 tumors in the SMS-treated mice to that in the normal controls but continuous infusion of GH was without effect. These results suggest that SMS inhibits the growth of SC115 tumors through suppression of GH secretion, and that the mode of GH administration is an important determinant of its action on SC115 tumor growth.

Animals↗

PubMed1993

Immunohistological differentiation of benign thyroid follicular cell tumors from malignant ones: usefulness of anti-peroxidase and JT-95 antibodies.

An immunohistological investigation using anti-thyroid peroxidase (PO) and JT-95 (JT) antibodies was conducted on surgical specimens of papillary carcinoma (n = 12), follicular carcinoma (n = 8), follicular adenoma with prominent papillary structure (n = 12), follicular adenoma (n = 8) and adenomatous goiter (n = 8). In benign lesions, follicle-forming and papillae-forming epithelia showed positive staining with anti-PO antibody. In 26 of 28 benign lesions, PO-positive areas covered 50% or more of the cut surface area of the lesions. However in carcinomas, PO-positive areas were non-existent (13/20) or only focal (7/20) and the papillae did not stain. The incidence of JT-positive cases was higher in papillary carcinomas (12/12) than in other lesions (13/36). JT-positive areas were much wider than PO-positive areas in papillary carcinomas, whereas in benign lesions, PO-positive areas were wider than or at least roughly equal to, JT-positive areas. Follicular carcinomas did not stain or stained only focally with these antibodies. In conclusion, these two antibodies seem useful in differentiating benign from malignant follicular cell tumors.

Adenocarcinoma, Follicular↗

PubMed1993

Identification of basic fibroblast growth factor in papillary carcinoma of the thyroid.

Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin-Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.

Carcinoma, Papillary↗

PubMed1993

Levator palpebrae superioris muscle: MR evaluation of enlargement as a cause of upper eyelid retraction in Graves disease.

Sympathetic stimulation of the Müller muscle may be responsible for most of the medically reversible cases of eyelid retraction in patients with Graves disease. The authors studied 21 patients with class I Graves ophthalmopathy (GO), 32 patients with Graves disease without ophthalmopathy (GD), and 12 control subjects. T1-weighted spin-echo magnetic resonance (MR) imaging was performed with a 0.5-T superconducting system. The thickness of the levator palpebrae superioris muscle was determined from sagittal MR images. The thickness of the levator muscles in patients with GD did not differ from the thickness in control subjects, but the levator muscles in patients with GO were significantly thickened (P < .01). The thickness of the levator muscles in patients with GO was significantly greater than in those of patients with GD (P < .01). In 64 orbits of patients with GD, 3% of levator muscles were thickened. In 33 of 40 (83%) orbits of patients with GO presenting with upper eyelid retraction, the levator muscles were thickened. Sagittal MR imaging demonstrated thickening of the levator muscles in patients with persistent upper eyelid retraction. The authors conclude that a thickened levator muscle probably causes upper eyelid retraction in patients with GO.

Adult↗

PubMed1993

ErbB-2 protein levels in nipple discharge: role in diagnosis of early breast cancer.

The levels of c-erbB-2 oncoprotein (ErbB-2 protein) in nipple discharge were evaluated together with those of carcinoembryonic antigen (CEA) in 9 patients with breast cancer, 2 patients with borderline lesions, 8 patients with intraductal papilloma, and 19 patients with fibrocystic change. When the tentative cutoff value was set at 40 ng/ml in the nipple discharge, elevated ErbB-2 protein levels were found in all 3 patients with palpable breast cancer and 3 of the 6 patients with nonpalpable cancer. Two of the 8 patients with intraductal papilloma had high ErbB-2 protein levels. A combination test with CEA resulted in positive detection in all cancer patients. Two patients with borderline lesions, 2 with intraductal papilloma and 2 with fibrocystic change were positive in a combination test. In addition, elevated ErbB-2 protein levels in nipple discharge correlated well with the overexpression of ErbB-2 protein in the tumor. All the patients with ErbB-2 protein levels over 100 ng/ml in their nipple discharge had comedo or solid intraductal carcinomas. Thus, measurement of ErbB-2 protein levels in nipple discharge can assist in the diagnosis of intraductal carcinoma and also in detecting tumors with a high proliferation rate and an overexpression of ErbB-2 protein: usually comedo or solid carcinomas.

Adult↗

PubMed1993

Neuro-otologic abnormalities in myelopathy associated with human T-cell lymphotropic virus type 1.

Auditory testing (pure tone audiometry, auditory brain stem response), and vestibular tests (eye tracking test, optokinetic pattern test, and caloric test) were performed to define neuro-otologic abnormalities in myelopathy associated with human T-cell lymphotropic virus type 1. Of the eight patients tested, seven showed sensorineural hearing loss and one showed mixed hearing loss on pure tone audiometry. The auditory brain stem responses of five patients showed increases of the I-III and I-V interpeak latencies. Two patients showed fast superimposed saccadic movements on the smooth pursuit test, and one other patient showed canal paresis on the caloric test. These findings suggest both the presence of neuro-otologic abnormality and involvement of the brain stem in myelopathy associated with human T-cell lymphotropic virus type 1.

Adult↗

PubMed1993

Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 1H- and 13C-nuclear magnetic resonance spectroscopy, and its enantioface-differentiating ability.

Analyses of the 1H- and 13C-nuclear magnetic resonance (1H- and 13C-NMR) spectra of the cyclooctapeptide cyclo (L-Phe-L-Pro-Gly-L-Pro)2 (3) in CDCl3 with the aid of the C-H correlated spectroscopy (C-H COSY) two-dimensional NMR spectrum (Fig. 2) suggested that two kinds of C2-symmetric conformation with all trans and cis-trans-trans-trans forms coexist. When 0.5 eq of CsSCN or 1 eq of D- and L-PheOMe.HCl (D/L ratio = 1/2) was added to a solution of the cyclooctapeptide (3) in CDCl3, the 1H- and 13C-NMR spectra (Fig. 3) suggested the presence of only one C2-symmetric conformation (all trans), resulting from the formation of complexes with CsSCN or D- and L-PheOMe.HCl. The 13C-NMR spectra of the complexes of the cyclooctapeptide (3 or 4) with D- and L-PheOMe.HCl displayed separate resonances for each carbon atom of D-PheOMe.HCl and L-PheOMe.HCl. Furthermore, the ability of 3 to distinguish the D from the L enantiomer, is superior to that of 4 (Table II).

Amino Acid Sequence↗

PubMed1993

Serum sialic acid levels in the diagnosis and follow-up of subacute granulomatous thyroiditis.

To evaluate the usefulness of monitoring serum sialic acid (SA) levels for diagnosis and follow-up of subacute granulomatous thyroiditis (SAT), 43 patients were studied at our clinic. In the acute phase of the disease their SA levels averaged 104.9 +/- 19.7 mg/dl (normal 44-69 mg/dl). In the recovery phase SA levels returned to a range of 60.5 +/- 6.9 mg/dl. However, an increase in SA (87.4 +/- 18.2 mg/dl) was detected at the time of recurrence in 14 patients. In 29 non-recurrent patients, serum SA gradually reduced during the course of therapy and normalized in all patients by the time glucocorticoid therapy was discontinued. Thyroglobulin (Tg) and the erythrocyte sedimentation rate (ESR), however, had normalized in only half the cases even at the time of cessation of therapy (Tg 5/11, ESR 4/8). C-reactive protein (CRP) returned to negative in most patients (19/24) only one week after initiation of the therapy. These results suggested that the monitoring of SA levels can be a useful tool in diagnosis and follow-up of SAT.

Adult↗

PubMed1993

Identification of metastatic carcinoma in the thyroid by determination of thyroglobulin level in aspirates and ultrasonic findings.

A 49-year-old female with a metastatic renal cell carcinoma to the thyroid is presented. The thyroglobulin (Tg) level in tumor aspirates of this patient was 37.3 micrograms/l, while that of 49 patients with primary thyroid nodules ranged from 2.0 x 10(3) to 7.5 x 10(8) micrograms/l. Ultrasonogram of the thyroid demonstrated a well-demarcated oval nodule with a cystic region, the solid part of which was hypoechoic and homogeneous. However, similar ultrasonic findings were observed in only 1.1% of 1,054 patients with primary thyroid nodules. Determination of Tg in tumor aspirates and ultrasonography of the thyroid may contribute to the differentiation of metastatic thyroid nodules from primary thyroid nodules.

Carcinoma, Renal Cell↗

PubMed1993

Evaluation of first- and second-generation assays for detection of antibody to hepatitis C virus in non-A, non-B chronic liver diseases--evaluation of 1st and 2nd-generation assays in NANBH.

The positive rates of the second-generation enzyme-linked immunoassay (2nd-generation assay), and two first-generation immunoassays (C100-3 and KCL-163 assay) to test for anti-HCV antibodies in the serum of patients with non-A, non-B chronic liver disease were determined. The clinical usefulness of these assays was also evaluated. The group positive for the 2nd-generation assay alone was compared with that positive for the 2nd-generation and C100-3 assays with respect to the serum GPT levels determined simultaneously with the antibodies. The latter group showed slightly higher GPT levels. These findings suggest that the 2nd-generation assay is useful for the diagnosis of hepatitis C, and that C100-3 and KCL-163 assays are useful indicators of the activity of hepatic disorders.

Adult↗

PubMed1993

Insulin-like growth factor-I ameliorates transient ischemia-induced acute renal failure in rats.

Acute renal failure in rats was induced by transient occlusion of bilateral renal arteries and veins to investigate whether insulin-like growth factor-I (IGF-I) has an effect on the damaged renal function or not. Administration of IGF-I at 0.01, 0.1 and 1 mg/kg by s.c. injection caused a 18.7, 33.0 and 66.5% increase of glomerular filtration rate and 54.8, 61.2 and 84.1% decrease of blood urea nitrogen, respectively, compared with the values in the saline-treated group 2 days after ischemia. Other renal parameters tested such as fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and tubular reabsorptance of phosphorus which are thought to represent renal function of proximal and distal tubules, respectively, were also improved by IGF-I treatment. A histochemical study also supported these observations. Severe epithelial necrosis of proximal tubules and decrease of brush borders were observed 2 days after transient ischemia in the saline-treated group, whereas marked histochemical alterations were not observed in the IGF-I-treated group. L-NG-nitroarginine, an inhibitor of nitric oxide synthetase, prevented the improvement of glomerular filtration rate and blood urea nitrogen by IGF-I at 1 mg/kg, suggesting that the ameliorative action on renal function by IGF-I is mediated via nitric oxide, possibly its vasodilating action. These findings provide the first evidence for the efficacy of IGF-I in the model of acute renal failure, suggesting that IGF-I may be useful for the treatment of acute renal failure.

Acute Kidney Injury↗