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Biomedical subjects

A Kuwabara

Publications and source records attributed to A Kuwabara.

34 records · Page 2Linked to original sources

Alteration of p53 clonality accompanying colorectal cancer progression.

The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.

Adenoma↗

Inhibition of TSH-induced hydrogen peroxide production by TNF-alpha through a sphingomyelinase signaling pathway.

Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be related to the pathogenesis of autoimmune thyroid diseases, nonthyroid illness, and other thyroid dysfunctions induced by infectious diseases. In relation to these, in vitro studies demonstrated that TNF-alpha influences growth and/or differentiated functions mediated by thyroid-stimulating hormone (TSH), including 125I organification. In the present study, we found that TNF-alpha inhibits TSH-induced H2O2 production, which is an inevitable process for iodide organification, and hence thyroid hormone synthesis, in FRTL-5 thyroid cells. In the cells, TNF-alpha induced ceramide production and the addition of exogenous ceramide or sphingomyelinase treatment of the cells simulated TNF-alpha actions. Although TSH stimulation of H2O2 production is mediated by the phospholipase C (PLC)-Ca2+ pathway, TNF-alpha and exogenous and endogenous ceramide affected neither TSH-dependent PLC activation and Ca2+ mobilization nor TSH-induced cAMP accumulation but attenuated Ca(2+)-induced H2O2 production. We conclude that TNF-alpha, through a sphingomyelinase-ceramide pathway, regulates TSH-induced H2O2 production at steps beyond the Ca2+ mobilization step in the PLC-Ca2+ signaling pathway coupled to TSH. This suggests participation of TNF-alpha in thyroid disorder in hormone synthesis induced by thyroid disease associated with the activation of immune systems.

Animals↗

Participation of the pituitary-thyroid axis in the cardiovascular system in elderly patients with congestive heart failure.

The relationship between the pituitary-thyroid axis and the cardiovascular system in patients with congestive heart failure (CHF) remains unknown. Therefore, we attempted to determine serum levels of thyroid hormones in relation to plasma atrial natriuretic peptide (ANP) levels and left ventricular (LV) function in patients with CHF. The echocardiographic ejection fraction significantly correlated with the thyroid stimulating hormone (TSH) (p < 0.005) and free triiodothyronine (FT3)/free thyroxine (FT4) ratio (p < 0.005), respectively, in patients with CHF but not in control subjects. TSH was positively correlated with the FT3/FT4 ratio (p < 0.01) in CHF. In patients with CHF, TSH and thyroid hormones may participate in regulatory mechanisms of the cardiovascular system and altered thyroid hormone metabolism, which was characterized by a euthyroid sick syndrome.

Aged↗

Ulcerative colitis with overexpression of p53 preceding overt histological abnormalities of the epithelium.

A 53-year-old man with a 22-year history of ulcerative colitis(UC) (pancolitis), had an ulcerating rectal tumor. Resection of the rectum and sigmoid colon was performed. Pathology showed an expansive ulcerating adenocarcinoma tumor (type 2) invading the adventitia against a background of UC in a resolving phase. Dysplasia was also found in granular and flat mucosa adjacent to the invading carcinoma. Immunostaining for p53 showed diffuse positivity in both the carcinoma and dysplasia, and also in the mucosa with indefinite dysplasia or no dysplasia neighboring the dysplasia and carcinoma. Mapping of neoplasms and the area with p53 protein overexpression showed that the grade of dysplasia increased as the lesion approached the invasive carcinoma and that the mucosa with dysplasia was surrounded by mucosa without dysplasia or indefinite for dysplasia, but with p53 protein overexpression. In some areas without dysplasia showing p53 overexpression, there was significant morphometric enlargement of the area and diameter of the nucleus p53 Immunostaining is a good marker for assessing the genetic alterations that precede histological abnormalities and for diagnosing carcinoma in UC. Objective findings such as p53-protein overexpression and morphometric values should be used to evaluate cytological abnormalities in UC, as well as in common colorectal cancer.

Adenocarcinoma↗

Untreated Graves' but not remission Graves' immunoglobulin G preparations increase intracellular Ca2+ in FRTL-5 thyroid cells.

We compared immunoglobulin G (IgG) preparations obtained from untreated Graves' patients with those from Graves' patients in remission and normal subjects in terms of their activity to stimulate the phospholipase C-Ca2+ signaling. Ca2+ mobilizing activity of the untreated Graves' IgG preparations in FRTL-5 thyroid cells was statistically (P < 0.01) and significantly higher than the activity of normal IgG preparations, whereas there was no significant difference in the activity between the remission Graves' and normal IgG preparations. Digital video imaging of fura2-loaded FRTL-5 cells confirmed that the Ca2+ mobilizing action of the untreated Graves' IgG preparations is an intracellular event. Phospholipase C activation by the untreated but not remission Graves' IgG preparations was statistically higher than that by normal IgG preparations. Involvement of the phospholipase C activation in the Ca2+ response mechanism was confirmed by the enhancement of the Ca2+ response by an adenosine derivative, N6(L-2-phenylisopropyl)adenosine (PIA) which can potentiate agonist-induced phospholipase C activation but not the Ca2+ mobilization itself. The Ca2+ response to the IgG preparations did not show a significant correlation with their cAMP response (TSAb). Therefore, the Ca2+ response to Graves' IgG preparations may be utilized as a functional marker for Graves' disease in addition to TSAb.

Animals↗

[Assay of circulating thyroid stimulator determined by I- efflux].

The thyroid stimulating antibodies (TSAb) have been widely used as a clinical marker for diagnosis of hyperthyroidism due to Graves' disease. Immunoglobulins (IgG) of Graves' patients as well as TSH is known to stimulate cAMP production in FRTL-5 cells, a cell-line derived from normal rat thyroid. On the other hand, it has been shown that TSH-induced I- efflux in these cells is associated with production of inositolphosphate as well as intracellular Ca2+ increase. An attempt was made to determine whether Graves' IgG also can mimic such TSH action as a cause of Graves' disease. Polyethyleneglycol precipitated serum fraction of Graves' patients were prepared. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% calf serum, insulin and hydrocortisone for TSH depletion. After preincubation with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions stimulated I- efflux dose-dependently. The mean potency of 12 patient's sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%, which was significantly higher (p < 0.001) than that for 8 normal subjects (110 +/- 16.1%). The results obtained herein indicate that IgG of Graves' patients activate both adenylate aclase-cAMP system and a phospholipid-Ca2 system. I- efflux stimulating immunoglobulins (IESI) activity is a useful marker in making a diagnosis or determining a remission of hyperthyroidism due to Graves' disease.

Adenylyl Cyclases↗

[Pituitary system with special reference to pituitary antibodies].

Amino et al. postulated a postpartum autoimmune thyroid syndrome and Sugiura et al. established an assay for detecting antibodies to anterior pituitary cell surface membrane (PCSA) by immunofluorescent methods. Using this technique, we attempted to determine the prevalence of PCSA before and after delivery. Studies were conducted with 16 pregnant women without any apparent diseases. Serial measurements of PCSA from the sera of each woman before and after delivery were performed by immunofluorescent methods using AtT-20 cells (mouse ACTH secreting cells) and GH3 cells (rat prolactin and GH secreting cells). Antibodies to AtT-20 cells were detected in 5 of 16 pregnant women at 36 weeks (31.3%), while those to GH3 cells were detected in 3 cases (18.8%). Following delivery, positive antibodies were observed in 12 women (75.0%) at 1 month, 15(93.7%) at 3 months and 13 (81.3%) at 6 months. A similar result also was obtained with GH3 cells. It is possible that some of the patients with positive antibodies have functional abnormalities of the anterior pituitary. The results obtained suggest the presence of postpartum autoimmune endocrine syndrome at the anterior pituitary level.

Animals↗

Enhanced sensitivity to anorexia and consumption of drinking water induced by interleukin-1 beta in obese yellow mice.

Exogenously administered interleukin-1 beta (IL-1) was reported to suppress food intake and endogenous CRF in the brain was reported to be involved in mediating the IL-1-induced anorexia. The present study was undertaken to investigate the effect of IL-1 (i.p.) on food and water intake in obese yellow mice and in lean mice. Enhanced sensitivity to IL-1-induced suppression of food and water intake were observed in obese yellow mice compared to lean mice (food intake suppression: lean 29.92%, obese 88.48%; water intake suppression: lean 25.18%, obese 71.56% of respective controls). After treatment of the mice with ibuprofen (10 mg/kg i.p.), the suppression of food and water intake was prevented in lean mice but unaffected in obese mice. The results suggest that there may be differential sensitivity to activation of CRF neurons induced by the peripheral injection of IL-1 in obese yellow and in lean mice.

Animals↗

Double cancer of the liver and stomach with situs inversus totalis--a case report.

A case of a 66-year-old woman with situs inversus totalis who developed hepatocellular carcinoma (HCC) as well as stomach cancer, is reported herein. The patient was successfully treated with a left hepatic lobectomy for the HCC and a B-I gastrectomy for the stomach cancer. Careful anatomical mapping made it possible to perform a combined resection of the liver and stomach in the presence of this congenital anomaly.

Aged↗

[Radiation treatment of metastatic breast cancer].

Breast cancer is rather radiosensitive. A total dose of 40-50 Gy (TDF about 80) is usually sufficient to control most metastatic breast cancer tumors. Radiation treatment should be applied to control tumors which are less responsive to chemo-endocrine therapy, i.e., large tumors or brain metastasis. Five-year survival rates after the start of radiation therapy to the first development of recurrence were 2/16 for local recurrence, 2/5 for supraclavicular node recurrence, 5/16 for bone recurrence and 1/4 for pulmonary recurrence, respectively. The quality of the remaining life of the patient should be the most important factor in deciding radiation treatment.

Bone Neoplasms↗

Type IV collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus.

We measured urinary albumin (U-Alb) and type IV collagen (uIV.C) in spot urine collected from 82 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 205 controls. Eighty-two NIDDM patients that had no increased excretion of either U-Alb or uIV.C were observed for 6 months. Prevalence of increased excretion of U-Alb and uIV.C at 6 months in these patients were 32.9%, and 62.2%, respectively. Increased excretion of uIV.C was detected in 27 patients without microalbuminuria. chi(2) analysis suggested that uIV.C was more sensitive than U-Alb, and that hypertension enhanced increased excretion of both U-Alb and uIV.C. uIV.C was significantly correlated (P<0.01) with U-Alb but not glycosylated hemoglobin A1C (HbA1C) in NIDDM patients. Taken together, uIV.C may be a useful marker for early diabetic nephropathy.

Adult↗

Success rates of formocresol pulpotomy and indirect pulp therapy in the treatment of deep dentinal caries in primary teeth.

PURPOSE: This study was performed to retrospectively evaluate treatment of deep caries in primary molars with formocresol pulpotomy (FP) and indirect pulp therapy (IPT). METHODS: 133 primary molars with deep caries approaching the pulp were treated with FP (N = 78) or IPT (N = 55) and followed 2-7 years. All IPTs received immediate stainless steel crowns (SSCs); 61 FPs got an immediate SSC, 13 an intermediate restorative material (IRM), and 4 amalgam. Thirteen IPTs and 25 FPs had pre-operative pain compatible with a diagnosis of reversible pulpitis. Treatment notes and radiographs were independently assessed. RESULTS: Overall IPT success was 93% (51/55) versus 74% (58/78) for FP. Molars with pain compatible with a diagnosis of reversible pulpitis were successfully treated by IPT 85% (11/13) versus 76% (19/25) for FP. FP-treated molars exhibited earlier exfoliation 38% (30/78), while all IPT molars exhibited normal exfoliation. FPs receiving immediate SSCs had 50/61 (82%) succeed; FPs restored with an IRM temporary succeeded 5/13 (39%), amalgam 3/4 (75%). CONCLUSIONS: IPT success was significantly higher than FP (P = 0.01) in the treatment of deep caries. Both IPT and FP were successful in treating teeth with pain compatible with the diagnosis of reversible pulpitis. FP significantly hastened the exfoliation of pulpotomized primary molars (P = 0.001). IPT in primary teeth can be successfully used in a one step procedure. SSCs placed immediately after FP significantly increased FP success vs. FP followed by IRM temporary (P = 0.01).

Chi-Square Distribution↗

Correlation of circulating interleukin-10 with thyroid hormone in acute myocardial infarction.

In patients with acute myocardial infarction (AMI), euthyroid sick syndrome (ESS) has been reported to be linked to increase in interleukin (IL)-6 and activation of its receptors. Recent reports have shown that IL-10, an anti-inflammatory cytokine, also plays a key role in the pathogenesis of AMI. Therefore we investigated the relationship between thyroid state and IL-10 in patients with AMI. We measured thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), IL-10, and IL-6 in plasma from 20 patients with AMI and 20 healthy controls. All 20 AMI patients showed significantly lower concentrations of FT3 than in controls accompanied by normal or subnormal levels of TSH, characterized ESS. Concentrations of IL- 10 and IL-6 were higher in patients than in controls. Both IL-10 and IL-6 significantly (p<0.05, respectively) correlated with thyroid hormone in patients with AMI. Time course of IL-10, IL-6, and FT3 seemed to be tightly linking. In conclusion, IL-10 and IL-6 appears to affect thyroid hormone homeostasis in patients with AMI.

Aged↗