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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 361 records · Page 20Linked to original sources

Effect of thyroid-stimulating hormone on cultured thyrocytes obtained from patients with Graves' disease and inhibitive effect by sodium iodide: a functional study.

Thyrocytes obtained from patients with Graves' disease were cultured for 3 days. This was followed by culture with 10 mU/mL thyroid stimulating hormone (TSH) (TSH group), TSH and sodium iodide (Nal group), or without (control group) for 3 additional days. On the 8th culture day, the amounts of intra- and extra-cellular cyclic adenosine monophosphate (cAMP), extracellular cAMP and thyroglobulin (TG), peroxidase (PO) activity, and cell numbers were measured. The amounts of intra- and extra-cellular cAMP correlated well. TSH increased the values of cAMP, TG and PO to levels higher than those of the control group. As the amount of Nal added to the medium increased, these values decreased. Addition of 10(-5) mol/L Nal lowered the value of cAMP only. When 10(-4) mol/L Nal was added, these three levels were lower than those of the TSH group and the value of cAMP was almost equal to that of the control group. On cell number, no difference was found between the cells cultured with TSH, TSH and Nal, and without TSH or Nal. When the thyrocytes were cultured with 1 mmol/L dibutyryl cAMP sodium salt or 8-bromoadenosine 3',5'-cyclic monophosphate instead of TSH, 10(-4) mol/L Nal did not lower the values of thyroglobulin and peroxidase activity. These results suggest that the Nal blocks the intracellular signal transduction provoked by TSH, only at the cAMP production level.

8-Bromo Cyclic Adenosine Monophosphate↗

Schedule-intensified M-VAC chemotherapy for advanced urothelial cancer with recombinant human granulocyte colony stimulating factor (rhG-CSF).

M-VAC (Methotrexate, vinblastine, adriamycin and cisplatin) combination systemic chemotherapy is useful for treating invasive or metastatic transitional cell carcinoma. Granulocytopenia is the major dose-limiting factor of this chemotherapy and it takes 4 weeks or more to complete a single course of M-VAC. We have tried to shorten the period of M-VAC chemotherapy from 4 to 3 weeks by using rhG-CSF. With this modified M-VAC regimen, the number of days on which the absolute neutrophil count was less than 1000/mm3 was significantly reduced and the period to reach the neutropenia nadir was shortened. No severe side-effects were observed. In all patients treated with 2 courses of this modified M-VAC short regimen, the period of hospitalization could be reduced by 2 weeks. We emphasize the possibility of shortening the M-VAC regimen.

Aged↗

Extraocular muscles in Graves ophthalmopathy: usefulness of T2 relaxation time measurements.

PURPOSE: To determine if T2 relaxation time measurements with magnetic resonance (MR) imaging in patients with Graves ophthalmopathy (GO) can predict response to therapy. MATERIALS AND METHODS: Studied were 84 patients with GO, 27 with Graves disease without ophthalmopathy (GD), and 12 control subjects without Graves disease. T2 times of extraocular muscles and retrobulbar fat tissue were measured. Twenty-five patients with GO were treated with systemic corticosteroids and retroorbital radiation therapy. RESULTS: T2 relaxation times of muscles in patients with GD were the same as those in controls but were longer in patients with GO (P < .05). T2 times of fat in all patients were the same as those of the controls. The predicted probability of response to treatment increased with increased mean T2 relaxation times of extraocular muscles prior to therapy. Of the 25 patients with combined therapy, only those with particularly prolonged T2 relaxation times showed impressive response. CONCLUSIONS: T2 relaxation time measurements with MR allow noninvasive detection of acute muscle inflammation and predict which patients with GO will likely benefit from antiinflammatory therapy.

Adipose Tissue↗

Increased serum immunoreactive parathyroid hormone-related protein levels in chronic hypocalcemia.

To elucidate possible negative feedback regulation of circulating PTH-related protein (PTHrP) by serum calcium levels, we measured serum immunoreactive PTHrP (iPTHrP) by a specific RIA for PTHrP-(1-34) in patients with hypocalcemia due to PTH deficiency or resistance. Serum iPTHrP levels were not detectable (< 4 pmol/L) in 9 of 11 patients with postoperative hypocalcemia who presented with transient tetany, in 1 patient with hypocalcemia due to hypomagnesemia induced by cisplatin treatment, in normal subjects (n = 60), or in 1 normocalcemic patient with pseudopseudohypoparathyroidism. In contrast, the other 2 patients with postoperative hypocalcemia who had had hypocalcemic symptoms for longer periods (6 months and 3 yr, respectively) showed increased iPTHrP levels (6.3 and 5.3 pmol/L). All 6 patients with idiopathic hypoparathyroidism showed undetectable or low PTH, but increased iPTHrP, ranging from 6.5-19.5 pmol/L (mean +/- SD, 10.8 +/- 4.8 pmol/L). Elevated serum iPTHrP levels (7.4 and 8.1 pmol/L) were also found in both patients with pseudohypoparathyroidism type I. When chronic and profound hypocalcemia in these patients was normalized by treatment with 1 alpha-hydroxyvitamin D3, the elevated serum iPTHrP levels were normalized (undetectable, < 4 pmol/L) in all 6 patients examined. These results suggest that chronic and profound hypocalcemia and/or vitamin D deficiency can stimulate endogenous PTHrP secretion via a negative feedback mechanism, although elevated iPTHrP does not normalize the decreased serum calcium levels.

Adolescent↗

Complex formation of cyclo(L-Phe-L-Pro)4 with noradrenaline hydrochloride.

The 13C-NMR spectrum of cyclo(L-Phe-L-Pro)4 (1) and DL-noradrenaline hydrochloride (DL-NA.HCl) in a mixture of CDCl3 and CD3OD suggested the formation of a complex, which was demonstrated to be 1:1 from examination of the titration curves. The complex retained the C2-symmetric conformation of 1 containing two cis-peptide bonds, and was linked through hydrogen bonds between the carbonyl groups of the Phe1 and Pro2 residues, and the ammonium moiety of NA.HCl.

Hydrogen Bonding↗

Thyroglobulin and lactic dehydrogenase isozymes in cystic fluid of thyroid nodules.

Although fine needle aspiration biopsy (FNAB) is most valuable in the diagnosis of thyroid cancer, it is hampered by the fact that no specimen suitable for cytological examination can be collected from all cystic lesions. Often inadequate aspirates, consisting only of fluid or a few foamy cells and lacking the necessary epithelial cells, are all that an aspirationist is able to collect. Therefore an alternative method of determining the benign or malignant characteristics of cyst fluid is of vital importance. In this study we examine thyroglobulin (Tg) concentrations and lactic dehydrogenase (LDH) isozyme patterns of cyst fluid and discuss how these variables help us estimate the probability of malignancy. Fifty-three differentiated cancers (39 papillary and 14 follicular carcinomas) and 72 surgically resected benign thyroid nodules (40 adenomas, 19 colloid goiters, and 13 cysts) were analyzed. Only 28 (53%) of 53 malignant lesions were correctly diagnosed by FNAB. The mean logarithmic value for the Tg concentration (log10 Tg) was significantly lower in malignant cyst fluid than it was in benign nodules (mean +/- SD: 5.8 +/- 1.0 vs. 6.8 +/- 1.0; P < 0.001). The LDH 1 and 2 isozyme percentage was greater in the malignant group than in the benign group (49.1 +/- 12.7% vs. 38.1 +/- 16.9%; P < 0.01). In multiple logistic regression analysis, log10 Tg and the total of LDH 1+2 percentage was significant in estimating the probability of malignant nodules. The results of our study suggest that determining the Tg concentration and the LDH isozyme patterns of cyst fluid could provide new information for the evaluation of cystic thyroid nodules.

Body Fluids↗

Immunohistochemical localization of acidic and basic fibroblast growth factors in human benign and malignant thyroid lesions.

The localization of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) was investigated immunohistochemically in human benign and malignant thyroid lesions. Immunostaining for aFGF and bFGF displayed diffuse or granular deposits of the reaction products in the cytoplasm of neoplastic cells, especially in the marginal region of follicular adenoma, follicular carcinoma and papillary carcinoma. All lesions except for diffuse hyperplasia, which was completely negative in immunostaining for all antibodies, showed an increased immunostaining for bFGF (Ab-1) over that of aFGF and bFGF (Ab-2). Basement membranes of follicular and papillary structure and the fibroblasts located in the stromal tissues were free from immunostaining for all antibodies. The ratio of positive immunostaining for all antibodies was highest in papillary carcinoma, with an incidence of more than 80.0%, followed, in descending order, by widely invasive follicular carcinoma, minimally invasive follicular carcinoma, follicular adenoma and normal thyroid, in which some follicular cells exhibited weak reaction products. aFGF with a molecular weight of 18 kDa was identified in papillary carcinoma of the thyroid. From these data, we concluded that aFGF is synthesized in the neoplastic follicular cells of the thyroid, and aFGF and bFGF may have important roles in the neoplastic proliferation of follicular cells.

Adenocarcinoma, Follicular↗

Differentiation of primary and secondary breast cancer with clonal analysis.

BACKGROUND: It is often difficult to draw a firm conclusion as to whether the second breast cancer is primary or secondary (metastasis from the initial breast cancer) in a patient with metachronous bilateral breast cancer. In this study we have applied clonal analysis of breast cancer to distinguish whether the second breast cancer is primary or secondary. METHODS: A 54-year-old woman underwent modified radical mastectomy of the right breast as a result of breast cancer. Five years later she had tumors in the right chest wall and left breast. Fine-needle aspiration cytologic examination revealed that both tumors were adenocarcinoma. To elucidate the origin of these tumors, clonal analysis was done on DNA samples prepared from cryostat sections of the initial right breast cancer and from fine-needle aspirates of the tumors in the right chest wall and left breast. The method for clonal analysis was based on restriction fragment length polymorphism of X chromosome-linked phosphoglycerokinase gene and on differential methylation of the gene caused by random inactivation of one of two X chromosomes. RESULTS: Clonal analysis revealed that clonal origin of the right breast cancer was different from that of the left breast cancer and identical to that of the chest wall tumor. Therefore it was concluded that the left breast cancer was primary and the chest wall tumor was concluded that the left breast cancer was primary and the chest wall tumor was a recurrence of the initial breast cancer. CONCLUSIONS: Clonal analysis appears to be a useful method in discriminating a primary from a secondary cancer.

Base Sequence↗

Clonal analysis of solitary intraductal papilloma of the breast by means of polymerase chain reaction.

Clonality of solitary intraductal papillomas of the breast was analyzed using a method based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase (PGK) gene and on random inactivation of the gene by methylation. The application of polymerase chain reaction to this method enabled clonal analysis of such a small intraductal lesion as papilloma. Clonal analysis of DNA samples obtained from the nine solitary intraductal papillomas and adjacent normal breast tissues showed that all of the papillomas were monoclonal and all the normal breast tissues were polyclonal in origin. When DNA samples were obtained from four widely separated sites in the papillomas, clonal analysis showed that all were monoclonal and, in addition, the same allele of PGK gene was inactivated in each case. These results demonstrate that solitary intraductal papilloma arises as a single monoclonal tumor and extends along the ducts rather than occurring as multicentric monoclonal tumors and merging together subsequently. Immunohistochemical staining of smooth muscle alpha-actin, a marker protein of myoepithelial cells, revealed that solitary intraductal papilloma was composed of approximately equal mixtures of luminal epithelial and myoepithelial cells. Since solitary intraductal papillomas were shown to be monoclonal in origin, it was suggested that this disease originates from a common precursor that could differentiate into both luminal epithelial and myoepithelial cells.

Base Sequence↗

[Clonal analysis of human breast tumors by means of polymerase chain reaction].

Clonal analysis has been done using the method based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Introduction of polymerase chain reaction (PCR) of this method has enabled clonal analysis of minute lesions. Utilizing this PCR-based method, clonality of a variety of human breast tumors (breast carcinoma, fibroadenoma, phyllodes tumor, intraductal papilloma, and atypical ductal hyperplasia) was studied in the present investigation in order to obtain valuable information on the histogenesis of these tumors.

Base Sequence↗

[M-VAC chemotherapy for advanced urothelial cancer--side effects and their management].

Since the M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen was reported by Sternberg in 1985, it has been widely accepted for the treatment of metastatic transitional cell carcinoma. This regimen has a significantly high response rate, but bone marrow suppression and gastrointestinal (GI) symptoms are inevitable. To complete this M-VAC regimen, preventive therapy for side effects is necessary. From November 1986 to March 1993, a total of 72 patients were admitted and received M-VAC therapy at our hospital. All of them had metastatic or invasive transitional cell carcinoma and they received a total of 163 complete courses of M-VAC therapy. We examined the side effects of this M-VAC regimen, and evaluated the effectiveness of colony-stimulating factor for prevention of granulocytopenia or granisetron for prevention of GI symptoms. Twenty-three patients (39 courses) were given recombinant colony-stimulating factor. This cytokine prevented the nadir of neutropenia and shortened the period to reach the nadir and period that the neutrophil count was below 1,000/mm3. Twelve patients (26 courses) were given granisetron, with significant reduction of the incidence of GI symptoms. These findings suggest that M-VAC therapy is effective and safe when used in combination with these drugs.

Adult↗

[Recent advance of hormonal treatment for breast cancer].

Since ER positivity in breast cancer is highest in the early stage of its natural history, hormonal treatment should be given as the initial treatment after both surgery and recurrence. Tamoxifen and medroxyprogesterone acetate have been commonly used as the standard hormonal treatment with a response rate of 20-30% and a median duration of response of 6-10 months. New agents for hormone therapy include tamoxifen analogues, LH-RH analogues and aromatase inhibitors. They are now on or have just cleared phase studies. LH-RH analogue is a unique drug that is active for premenopausal patients and should be used as the first-line therapy for them. Aromatase inhibitors lower serum estrogen levels by inhibiting conversion from andreogens to estrogens, thus inducing regression of ER-positive tumors. They are used as the second-line treatment after tamoxifen failure for postmenopausal patients. An increasing body of information has been accumulated as to how the hormonal treatments affect breast cancer at subcellular levels. New approaches controlling growth factors such as anti-angiogenesis are under way.

Antineoplastic Agents↗

[A study on reservoir function of Kock pouch during a 3-year postoperative period].

Kock continent ileal reservoir has been one of the major options of urinary diversion for the patients with bladder cancer. We performed Kock pouch operation in 16 patients (male 12, female 4; from 41 to 66 years old, mean age 57 years old). Since the reservoir function of Kock pouch after a long postoperative period is not well known, we examined the volume capacity, the compliance and the length of efferent valve of Kock pouch in 8 patients during a 3-year postoperative period. Although the compliance was stable, the volume capacity and the length of the efferent valve showed a decreasing tendency. The shorter efferent valve was not always associated with the case of urinary incontinence. Most of the complications in 15 patients was trouble of efferent valve (prolapse of efferent valve in 7 cases and eversion or fistula formation that required reconstruction surgery in 3 cases). Although some complications were observed, the reservoir function of the pouch was stable. Therefore this method is reliable for permanent urinary diversion.

Adult↗

[A case of convexity arachnoid cyst associated with chronic subdural hematoma and intracystic hemorrhage].

Arachnoid cysts account for about 1% of all intracranial tumors, in which about 50% arise from the middle cranial fossa, and rarely occur at the cerebral convexity. They sometimes are associated with chronic subdural hematoma (CSDH) but the exact mechanism of their development is still unclear. A 15-year-old boy was admitted to our hospital with an arachnoid cyst at the right frontal convexity. When he experienced recurrent generalized seizure, CT and MRI revealed CSDH localized at the surface of the arachnoid cyst. Radical operation for the cyst with CSDH was successfully performed. As far as we know, it is rare that CSDH and hematoma are colocalized over an arachnoid cyst at the cerebral convexity. In this report, the operative findings of this patient and possible mechanism of CSDH formation were reported.

Adolescent↗

Immunohistochemical survey of pS2 expression in intraductal lesions associated with invasive ductal carcinoma of the breast.

We examined the expression of pS2 protein in 48 invasive ductal breast carcinomas with an extensive intraductal component, using immunohistochemical staining of paraffin-embedded sections. The patients selected for this study would have met the criteria for breast-conserving surgery applied at our institute at present. The rate of pS2 expression in the intraductal lesion was significantly higher than that in the main invasive lesion. The incidence of pS2 protein expression in the latter lesions was very similar to that in invasive carcinoma without intraductal lesions. The pS2 positivity of the intraductal lesion was equal to or higher than that of the invasive lesion. Of intraductal lesions, those classified as non-comedo carcinomas frequently contained more pS2 protein than did comedo carcinomas.

Breast Neoplasms↗

Structural characterization of the N-linked carbohydrate chains from mouse zona pellucida glycoproteins ZP2 and ZP3.

N-linked oligosaccharides of mouse zona pellucida glycoproteins ZP2 and ZP3 were prepared as pyridylaminated derivatives. Anion-exchange HPLC revealed that 95% or more of them are acidic. About 80% of these acidic chains were neutralized by digestion with Arthrobacter ureafaciens sialidase and a small amount of sulfate was found in the residual acidic chains. The neutralized fractions (SN fractions) from ZP2 and ZP3 were similarly fractionated by size-fractionation HPLC into many peaks having different numbers of LacNAc in the non-reducing regions. The SN fractions from ZP2 were cleaved by endo-beta-galactosidase into the core and non-reducing regions. The tri- and tetra-antennary complex-type chains with a Fuc residue were predominant in the core region. On the other hand, four kinds of fragment containing the LacNAc sequence were obtained from the non-reducing region. Sialic acids were shown to be linked to the core fragments, as well as the non-reducing fragments. The N-linked oligosaccharides of ZP3 were suggested to have essentially the same structures as those of ZP2.

Animals↗

[Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis].

This retrospective study was aimed at establishing the importance of the leukocyte differentiated count and not only routine white blood cell count in patients treated with antithyroid drug. From 1975 to September 1992, 77 patients with antithyroid drug-induced agranulocytosis were examined. In 12 patients (15.6%), the total white blood cell (WBC) count was greater than 3000/mm3. Eight of them showed a downward trend in their leukocyte counts (3000-4000/mm3). Consequently, granulocyte counts were measured. Two of the 12 patients had "symptomatic" agranulocytosis detected after the occurrence of infection. Because antithyroid drug-induced agranulocytosis was strongly suspected, granulocyte counts were checked. In the remaining two patients, the total WBC count was 5700/mm3 and 5900/mm3, respectively. One was hospitalized to receive thyroid surgery. Although she was asymptomatic, agranulocytosis was unexpectedly detected on a routine preoperative examination. The other was diagnosed as agranulocytosis by routine WBC and granulocyte count monitoring since June 1989. Correct diagnosis was based on the leukocyte differentiated counts. We concluded that the leukocyte differentiated count and not only routine white blood count was critically important for the correct diagnosis of antithyroid drug-induced agranulocytosis in patients with Graves' disease.

Adolescent↗