Biomedical subjects

Fumio Matsuzuka

Publications and source records attributed to Fumio Matsuzuka.

At least 73 records · Page 4Linked to original sources

PubMed2003

Relation of CD30 molecules on T-cell subsets to the severity of autoimmune thyroid disease.

The prognosis of patients with autoimmune thyroid disease (AITD) varies. To clarify the immunologic differences among patients with various severities of AITD, we examined two types of molecules on peripheral T lymphocytes: CD195 (CCR5), which express dominantly on CD4(+) type 1 helper T (T(H)1) cells, and CD30, which is known as a marker of CD4(+) type 2 helper T (T(H)2) cells and a regulatory molecule of CD8(+) autoreactive cytotoxic T cells. We found presence of patients with high proportion (> 9%) of CD30 expression in CD4(+) cells in a group of patients with Graves' disease (GD) in remission compared to the patients with intractable GD and a decrease in the intensity of CD30 expression on CD8(+) cells from patients with severe Hashimoto's disease (HD) treated for hypothyroidism compared to patients with untreated and euthyroid HD. There was no difference in CD195 expression between these patients with GD or HD with different severities, but there was a decreased intensity of CD195(+) cells in thyrotoxic patients with GD. These results indicate that CD30 molecules on CD4(+) and CD8(+) cells may be related to the severities of GD and HD, respectively.

Adult↗

PubMed2003

An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid.

The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has resulted in a marked increase in the number of patients with papillary microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this sophisticated tool. On the other hand, it is debatable whether patients with papillary microcarcinoma should always undergo surgery after diagnosis, because a high incidence of occult papillary carcinoma has been observed in autopsy studies. Thus, we proposed observation without surgical therapy as a treatment option in 732 patients diagnosed with papillary microcarcinoma by the above technique from 1993 to 2001. One hundred sixty-two patients chose observation and were classified as the observation group. During the follow-up period for patients in the observation group, more than 70% of tumors either did not change or decreased in size compared to their initial size at diagnosis. They enlarged by more than 10 mm in 10.2%, and lymph node metastasis in the lateral compartments appeared in only 1.2% of patients during follow-up. On the other hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the observation group who underwent surgery after a period of follow-up were classified as the surgical treatment group. Of these 626 patients, lymph node dissection was performed in 594 patients, and metastasis was confirmed histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients. In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years after surgery. Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence.

Adolescent↗

PubMed2003

Decreased expression of catalase mRNA in thyroid anaplastic carcinoma.

BACKGROUND: A decreased expression of glutathione peroxidase mRNA, an antioxidant enzyme, was previously observed in thyroid anaplastic carcinomas. METHODS: To clarify the expression of antioxidant-related enzymes in thyroid anaplastic carcinomas, the expression levels of catalase, copper and zinc superoxide dismutase and manganese superoxide dismutase mRNA in 85 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Decreased expression levels of catalase and copper and zinc superoxide dismutase mRNAs, but not manganese mRNA, were observed in five anaplastic carcinomas compared with normal thyroid tissues and differentiated tumors. CONCLUSION: These results suggest the possibility that anaplastic carcinoma cells are more likely to suffer damage by oxygen free radicals than normal thyroid cells or differentiated tumor cells.

Adenoma↗

PubMed2003

Overexpression of human tumor-associated antigen, RCAS1, is significantly linked to dedifferentiation of thyroid carcinoma.

OBJECTIVE: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. METHODS: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. RESULTS: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). CONCLUSION: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.

Adenocarcinoma, Follicular↗

PubMed2003

Changes in serum TSH receptor antibody (TRAb) values in patients with Graves' disease after total or subtotal thyroidectomy.

TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p<0.05) lower in the TT group than in the ST group (16.7 +/- 3.3% vs 28.0 +/- 2.6%, 12.6 +/- 3.4% vs 29.3 +/- 3.8%, 5.6 +/- 0.9% vs 25.4 +/- 4.1%, respectively). The normalization rates of TRAb were not significantly different between the groups until 1 year after surgery. However, the normalization rates 3, 5 and 7 years after surgery were significantly (p<0.05) higher in the TT group than in the ST group (65.7% vs 42.4%, 77.3% vs 46.7%, 100% vs 59.1%, respectively). The surgical complication rates of TT were similar to ST except for permanent hypoparathyroidism. TT is a treatment option for Graves' disease, especially in patients with a high TRAb value who wish to have children or who have Graves' opthalmopathy.

Adolescent↗

PubMed2003

Successful management of a patient with pseudomalabsorption of levothyroxine.

Pseudomalabsorption of levothyroxine is a factitious disorder. Despite the administration of large doses of levothyroxine, patients with this disorder show hypothyroidism due to noncompliance. These patients are different from the patients with simple noncompliance in that they have a psychiatric disorder. Because their psychological identities are rooted in their being a "patient," they go to great lengths to become and stay a patient. We report a case of pseudomalabsorption of levothyroxine. A 28-year-old woman was referred to us because she was believed to have unusual malabsorption of levothyroxine. We diagnosed the patient as having this factitious disorder, and as treatment, had her visit a hospital twice a week to take medicine under the observation of nurses so that she would not lose her status as a "patient." Her serum free T4 level normalized during three years with twice weekly dosing of thyroxine after hospital discharge. Our approach could be a therapeutic choice for this intractable disorder. To our knowledge, this is the first report of successful management of a patient with pseudomal-absorption of levothyroxine.

Adult↗

PubMed2002

Decreased expression of glutathione peroxidase mRNA in thyroid anaplastic carcinoma.

Our recent study using serial analysis of gene expression show the decreased expression of glutathione peroxidase (GPx), an antioxidant enzyme, in an anaplastic carcinoma. To clarify the expression of GPx in various kinds of thyroid tumors, the expression levels of GPx mRNA in 79 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. A decreased expression of GPx mRNA was observed in all of five anaplastic carcinomas and some of the papillary carcinomas. A molecular-based therapy which produces O(2) radical may be considered as an alternative choice for the treatment of anaplastic carcinomas.

Carcinoma↗

PubMed2002

Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.

Although sporadic medullary thyroid carcinoma (MTC) tends to be unicentric and confined to one lobe, total thyroidectomy is usually performed because of the risk of a hereditary or bilateral process. Germline RET mutation analysis can discriminate hereditary MTC and truly sporadic, nonhereditary MTC. We analyzed 72 of 94 patients with MTC to establish the genetic nature and the clinical features of nonhereditary MTC. Since 1996 we have prospectively treated 15 patients with nonhereditary MTC (prospective study group, or PSG) according to a unilateral surgery policy. A group of 22 previously operated patients in whom the nonhereditary nature was established served as controls (retrospective study group, or RSG). Systematic central and ipsilateral neck dissection was performed in both groups. Outcome was assessed using postoperative stimulated serum calcitonin levels; a normal value was considered a biochemical cure. All 24 hereditary MTC patients carried germline RET mutations: 8 of 48 patients with apparently sporadic MTC had the mutations, and 6 of the 8 had bilateral MTC. All 40 patients without mutations had a unilateral tumor. In the RSG group 15 of 22 (68%) patients underwent total thyroidectomy, and the biochemical cure rate was 68%. Although only 3 of 15 (20%) of the PSG patients underwent total thyroidectomy, 12 of the 15 (80%) achieved biochemical cure. Univariate analyses revealed that pathologic node involvement- high T and N stages-was adversely related to biochemical cure. The extent of thyroid resection was not related to biochemical cure. Of 20 patients with node involvement, 10 achieved biochemical cure, indicating the importance of systematic neck dissection. Hemithyroidectomy with systematic central and ipsilateral neck dissection is appropriate surgery for nonhereditary MTC.

Adult↗

PubMed2002

Excessive survivin expression in thyroid lymphomas.

Thyroid lymphoma occurs most commonly in the thyroid glands with a background of Hashimoto's thyroiditis. Therefore, it is occasionally difficult to distinguish lymphoma from Hashimoto's thyroiditis because of some cellular and histologic similarities. We have examined whether survivin or human telomerase reverse transcriptase (hTERT) expression can differentiate between the 2 disorders. Surgically removed tissue samples from 6 patients with thyroid lymphoma and 6 patients with Hashimoto's thyroiditis were analyzed for mRNA levels of survivin and hTERT by real-time quantitative reverse-transcription polymerase chain reaction. Expression of survivin protein was examined by immunohistochemical stain using a polyclonal antibody. Survivin mRNA levels were greater in thyroid lymphoma than in Hashimoto's thyroiditis: 49.1 +/-36.4 versus 6.6 +/-2.7 pg/ng rRNA (mean +/- SD) (P <0.005). Immunohistochemical stain confirmed an abundance of survivin protein in lymphoid cells of thyroid lymphoma. The amount of hTERT mRNA did not differ in the 2 disorders. Our study shows that measuring survivin mRNA levels or immunohistochemistry of the protein expression can be useful to aid the diagnosis of thyroid lymphoma when histologic diagnosis is difficult.

Biomarkers, Tumor↗

PubMed2002

Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation.

Previous studies have demonstrated that cell proliferating activity accurately reflects the biological aggressiveness of thyroid neoplasms. In this study, we focused on the G2-M boundary regulators of the cell cycle and investigated the expression of three proteins, cyclin A, cyclin B1 and cdc2. The incidence of cyclin A overexpression was significantly linked to carcinoma differentiation (p < 0.0001) and, in particular, all 21 cases of undifferentiated carcinoma overexpressed this protein. On the other hand, cyclin B1 was overexpressed in four undifferentiated carcinomas (19.0%), but not in carcinomas of other types. Cdc2 overexpression was also related to carcinoma differentiation (p < 0.0001), and was directly linked to cyclin A overexpression (p < 0.0001), but not to cyclin B1 overexpression. No significant relationship could be established between the overexpression of these proteins and the histological type of follicular tumor. These results suggest that cyclin A, rather than cyclin B1, contributes significantly to the aggressive character of thyroid carcinoma, together with cdc2.

Adenoma↗

PubMed2002

Independent involvement of CD8+ CD25+ cells and thyroid autoantibodies in disease severity of Hashimoto's disease.

Hashimoto's disease (HD) is well known as an autoimmune thyroid disease caused by the destruction of the thyroid follicles, and can be diagnosed in the subclinical stage with thyroid-specific autoantibodies. However, some patients with HD develop hypothyroidism and are treated with thyroxine (severe HD), but most do not throughout their lives (mild HD). To clarify the immunologic differences between these two groups of patients with HD, we examined serum thyroid autoantibodies (antithyroid peroxidase antibodies and antithyroglobulin antibodies), CD4+ CD25+ cells that contain regulatory T cells and activated helper T cells, and CD8+ CD25+ cells that are activated cytotoxic T cells. There was no significant difference in CD4+ CD25+ cells between these HD groups, although the proportion of CD25+ cells within CD4+ cells increased in both groups as compared to normal controls. The serum titers of the thyroid autoantibodies and the proportion of CD25+ cells within CD8+ cells were higher in patients with severe HD than in those with mild HD. There was no correlation between these two parameters, and a two-dimensional analysis with these parameters differentiated these two groups of patients with HD more clearly. These results indicate that both thyroid autoantibodies and CD8+ CD25+ cells are independently involved in the disease severity of HD and CD4+ CD25+ cells are not related to the severity of HD.

Adult↗

PubMed2002

Quantitative analysis of thymosin beta-10 messenger RNA in thyroid carcinomas.

BACKGROUND: Genes that are differentially expressed in benign and malignant tissues are important for the establishment of molecular-based diagnosis of carcinomas. Our recent study on the gene expression profile of thyroid carcinomas revealed an increased expression of thymosin beta-10 mRNA. METHODS: To confirm this, we measured the expression levels of thymosin beta-10 mRNA in 84 thyroid benign and malignant thyroid tissues, including five anaplastic carcinomas, by means of real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: We found an increased expression of thymosin beta-10 mRNA in thyroid carcinomas, especially in anaplastic carcinomas. Expression levels of thymosin beta-10 mRNA relative to thyroglobulin mRNA in anaplastic carcinomas were greatly increased compared with those in differentiated carcinomas. CONCLUSION: These results suggest the usefulness of the quantitative measurement of thymosin beta-10 mRNA in molecular-based diagnosis of thyroid anaplastic carcinomas, but not of differentiated carcinomas.

Biomarkers, Tumor↗

PubMed2002

Fas and Fas ligand gene mutations in Hashimoto's thyroiditis.

To clarify whether Fas and Fas ligand (FasL) mutations are involved in the pathogenesis of Hashimoto's thyroiditis (HT), we examined the open reading frame of Fas and FasL in 21 cases. Mutations of Fas and FasL genes were detected in 8 (38.1%) and 1 (4.8%) of 21 cases, respectively. All but one of the Fas mutations were frameshift mutations, which affect the cytoplasmic region (death domain) known to be involved in apoptotic signal transduction and thus could be loss-of-function mutations. FasL mutation in one case was a 46-bp deletion from nucleotide 349 to 394, which corresponded to exon 2. Lack of exon 2 results in a frameshift, which generates a stop codon at residue 128. This mutant encodes the protein that contains only a part of the intracellular domain, thus the abnormal protein might not be expressed on the cell surface. The cells with Fas mutations were confined to the mantle zone and the germinal center, as determined by microdissection methods. These findings suggest that the cells with Fas mutations might accumulate in those areas and might be involved in the pathogenesis of Hashimoto's thyroiditis.

Aged↗

PubMed2002

Quantitative analysis of osteonectin mRNA in thyroid carcinomas.

Our recent study of the gene expression profile in thyroid carcinoma showed an overexpression of osteonectin mRNA, an extracellular matrix protein, in an anaplastic carcinoma. To confirm this, we measured the expression levels of osteonectin mRNA in 84 thyroid normal and tumor tissues, including five anaplastic carcinomas by realtime quantitative reverse-transcription PCR. Increased expression of osteonectin mRNA was observed in anaplastic carcinoma tissue. However, in five anaplastic carcinoma cell lines, no increase was observed in the expression levels of osteonectin mRNA. These findings suggest the possibility that increased expression of osteonectin mRNA in anaplastic carcinoma tissue may be due to its overexpression in stromal cells, but not in anaplastic carcinoma cells.

Carcinoma↗

PubMed2002

Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues.

p57 (Kip2) belongs to the Cip/Kip family and is one of the universal negative regulators of the cell cycle. In this study, we investigated the p57 expression of various types of thyroid neoplasm. p57 overexpression was observed in only 4.2% of normal thyroid tissues. In follicular adenoma and minimally invasive follicular carcinoma, p57 was overexpressed in 100% and 91.7% of the cases, respectively. However, its incidence was significantly lower (p<0.0001) in widely invasive follicular carcinoma, of which only 36.4% overexpressed p57. This phenomenon was seen in 63.1% of papillary carcinoma and 13.3% of anaplastic (undifferentiated) carcinoma. Furthermore, poorly differentiated and undifferentiated carcinoma more frequently lacked p57 expression (p<0.0001). These results suggest that the down-regulation of p57 may play a role in the dedifferentiation of thyroid carcinoma and in follicular carcinoma mutating to be more invasive.

Cell Differentiation↗

PubMedDate not supplied

Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation.

BACKGROUND: Apoptosis, programmed cell death, is one of the promnent factors in the evaluation of carcinoma characteristics. It is well-known that bcl-2 and its related proteins significantly modulate apoptosis. Bag-1 is a recently identified bcl-2-related protein and is known to be linked to the biological aggressiveness of some carcinomas. MATERIALS AND METHODS: We immunohistochemically investigated bag-1 and bcl-2 expression in various thyroid neoplasms using monoclonal antibodies. RESULTS: High bag-1 expression was observed in 66.7% of follicular adenoma and 75.0% of follicular carcinoma, and no statistical difference was established between them. In papillary carcinoma, 60.7% were classified with high bag-1 expression, whereas only 4.5% of anaplastic (undifferentiated) carcinoma highly expressed bag-1, and the incidence was significantly lower (p < 0.0001) than in papillary and follicular carcinomas. Furthermore, in thyroid neoplasm, bag-1 expression was directly linked (p < 0.0001) to bcl-2 expression. CONCLUSION: These findings suggest that bag-1 may interact with bcl-2 to play an important role in thyroid neoplasm before anaplastic transformation, and the disruption of events mediated by bag-1 and bcl-2 may be a typical characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Survivin expression is significantly linked to the dedifferentiation of thyroid carcinoma.

Survivin is a novel member of the apoptosis protein inhibitors, but according to previous reports, it is also significantly linked to cell proliferating activity. In this study, we investigated the expression of survivin in thyroid neoplasms. Survivin was only occasionally expressed in normal follicular cells, whereas in follicular and papillary carcinomas, about 20% of cases were positive for survivin. The incidence was significantly higher in advanced stage papillary carcinoma (p=0.0080) and papillary and follicular carcinomas with poorly differentiated lesions (p=0.0150). In anaplastic carcinoma, survivin positivity was observed in 84% of the cases, which was in significantly higher incidence than in papillary or follicular carcinoma (p<0.0001). These results suggest that survivin is strongly related to the dedifferentiation of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Decreased expression of cyclin G2 is significantly linked to the malignant transformation of papillary carcinoma of the thyroid.

BACKGROUND: Cyclin G2 is a novel cyclin negatively regulating the cell cycle progression, contrary to the characteristics of conventional cyclins. However, little is known about the cyclin G2 expression in human carcinomas. We thus investigated cyclin G2 expression in human thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically examined cyclin G2 expression in 40 normal thyroids and 80 thyroid neoplasms. RESULTS: Normal thyroids expressed cyclin G2 in more than 5% of follicular cells. Of 30 papillary carcinomas including 6 microcarcinoma, cyclin G2 expression was not, or only occasionally, observed in carcinoma cells, indicating its expression decreased in all these cases. On the other hand, in 16 of the 24 follicular adenomas (66.7%) and 5 of the 23 follicular carcinomas (21.7%), cyclin G2 expression was retained (more than 5% of neoplastic cells were positive), and adenomas more frequently (p = 0.0032) retained cyclin G2 expression than carcinomas. CONCLUSION: Our results suggest that lack of cyclin G2 plays an important role in the malignant transformation of papillary carcinoma. Also, it may play an adjuvant role in the transformation of follicular adenoma to carcinoma. This is the first study of the expression of cyclin G2, a novel cyclin having a role opposite to that of conventional cyclins, in human carcinoma.

Carcinoma↗