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Hideto Sakai

Publications and source records attributed to Hideto Sakai.

36 records · Page 2Linked to original sources
PubMed2003

Detection of nuclear factor-kappaB in IgA nephropathy using Southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) is involved in inflammatory and immune responses through induction of various cytokines and growth factors. The aim of this study is to examine the correlation between NF-kappaB expression and severity of tissue injury in immunoglobulin A (IgA) nephropathy and the mechanism of such correlation. METHODS: The study included 43 renal tissue samples from 28 patients, including 28 samples of IgA nephropathy, 5 samples of non-IgA mesangial proliferative glomerulonephritis (non-IgA nephropathy), and 10 samples with nonproliferative glomerulonephritis (membranous nephropathy [MN] n = 5; minimal change nephrotic syndrome [MCNS]; n = 5). Tissue sections were examined by Southwestern histochemistry and immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and intercellular cell adhesion molecule-1 (ICAM-1), which are regulated by NF-kappaB. Normal portions of surgically resected kidney with adenocarcinoma served as controls. RESULTS: In normal kidney, MCNS, and MN sections, NF-kappaB expression was detected in a few mesangial cells and tubular epithelial cells. In IgA nephropathy and non-IgA nephropathy samples, NF-kappaB was expressed in mesangial, glomerular endothelial and epithelial cells, tubular epithelial cells, and infiltrating cells. Expression in both glomeruli and interstitium correlated with progression of tissue injury. In IgA nephropathy samples, MCP-1 and GM-CSF expression was increased in both glomeruli and interstitium and correlated with progression of tissue injury. Glomerular ICAM-1 expression was weaker in severe lesions, whereas interstitial expression correlated with progression of tissue injury. CONCLUSION: Our results indicate that NF-kappaB is involved in the progression of tissue injury in IgA nephropathy through the induction of transcriptionally regulated genes.

Adenocarcinoma↗
PubMed2003

Glomerular expression of connective tissue growth factor mRNA in various renal diseases.

Connective tissue growth factor (CTGF) is a cysteine-rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA-N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA-N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high-resolution in situ hybridization with digoxigenin-labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF-positive cytoplasm, in at least 10 randomly selected cross-sections of non-sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowman's capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA-N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA-positive cells between DN and IgA-N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA-N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end-stage renal failure.

Adult↗
PubMed2003

Expression of RET in follicular cell-derived tumors of the thyroid gland: prevalence and implication of morphological type.

Expression of the wild-type RET proto-oncogene has been observed in non-medullary, follicular cell-derived tumors (FCDT), but the relation with the histopathological features has not been fully demonstrated. To assess the expression of RET and protein products in relation to morphological types of FCDT, including follicular adenoma (FA), papillary carcinoma (PTC), follicular carcinoma (FTC) and anaplastic carcinoma (AnC), 58 non-neoplastic and neoplastic samples using pathological paraffin sections by immunohistochemistry (IHC), reverse transcriptase-polymerase chain reaction (RT-PCR) and laser capture microdissection (LCM) methods were analyzed. Expression of RET proto-oncogene was detected in 27.3% of FCDT by IHC and 25.5% by RT-PCR using a primer set at a regular break point. The present study also found higher expression ratios of RET in FA (50.0%) and the follicular variant of PTC (50.0%), in contrast to FTC (20.0%), ordinary PTC (20.0%) and poorly differentiated or AnC (14.3%) by RT-PCR. One patient with PTC showed a discrepancy in the results by RT-PCR using a different primer set at the C-terminus of RET. The study found that the RET proto-oncogene is often stimulated in FCDT, not only in PTC but also in follicular tumors (FA and FTC), and may contribute to tumorigenesis of these tumors.

Adenocarcinoma, Follicular↗
PubMed2003

Co-expression of parathyroid hormone and chromogranin A in secondary hyperparathyroidism: a functional marker for secretory activity of hyperplastic nodules.

The relationship between secretion of parathyroid hormone (PTH) and biologic characteristics, including cell proliferation or monoclonality, is not yet fully understood. To evaluate secretory activity of glands or nodules histopathologically, we focused on the co-expression of chromogranin A (CgA) and parathyroid hormone (PTH) in each gland or nodule. A total of 55 glands from 38 patients with normal parathyroid glands, hyperplastic glands (diffuse and nodular) and primary adenomas were compared. Co-expression of PTH and CgA was decreased to 44.4% in diffuse hyperplastic glands, and to 39.6% in 91 hyperplastic nodules, in contrast to normal glands and primary adenomas that showed constant co-expression of PTH and CgA. Immunohistochemical study of PTH showed a coarse granular pattern predominantly in PTH-positive/CgA-positive nodules, and a dot-like pattern mainly in PTH-positive/CgA-negative nodules. Laser scanning microscopy and immunoelectron microscopy confirmed that a dot-like pattern is based on a positive reaction of PTH at the Golgi apparatus. MIB-1 LI was 12.6 +/- 11.6 in PTH-positive/CgA-positive, and 19.3 +/- 27.3 in PTH-positive/CgA-negative nodules. In conclusion, a combination of PTH and CgA could provide more information about the physiologic state of secretory activity of each nodule than does the simple observation of PTH immunoreactivity.

Adenoma↗
PubMed2003

Long-term (3 years) prognosis of parathyroid function in chronic dialysis patients after percutaneous ethanol injection therapy guided by colour Doppler ultrasonography.

BACKGROUND: Secondary hyperparathyroidism (2HPT) is one of the most important complications in chronic dialysis (CD) patients. Percutaneous ethanol injection therapy (PEIT) of the parathyroid glands was introduced initially as an alternative treatment to parathyroidectomy and, with the technical progress of parathyroid imaging, it has now become a useful adjunct to medical therapy. The present study examined the possibility of maintaining parathyroid function in the long term (3 years) after PEIT. METHOD: PEIT, guided by power-Doppler flow mapping, was performed in 33 CD patients with severe 2HPT, and all glands >5.0 mm in diameter were destroyed. RESULTS: All patients showed a decline in the serum intact parathyroid hormone (i-PTH) concentration, on average from 695.5 to 248.0 pg/ml, after 1 year. After 3 years, the i-PTH concentration was controlled at <300 pg/ml in 85% of patients. The mean serum alkaline phosphatase (ALP) concentration also decreased from 322.7 to 154.4 IU/l after 1 year. In 76% of patients, ALP was maintained within the normal range (between 76 and 260 IU/l) at 3 years. Patients were classified into four groups according to the number of parathyroid glands detected by ultrasonography: one gland in group 1, two in group 2, three in group 3, and four in group 4. At 3 years after PEIT, i-PTH was controlled at <300 pg/ml in 100, 79, 83 and 82% of the patients in groups 1-4, respectively. CONCLUSIONS: It was possible to maintain long-term parathyroid function after PEIT in patients with 2HPT by using medical therapy, such as oral calcitriol pulse therapy and additional PEIT.

Adult↗
PubMed2003

Long-term prognosis of parathyroid function for chronic dialysis patients after minimally invasive radioguided parathyroidectomy (MIRP).

BACKGROUND: Minimally invasive radioguided parathyroidectomy (MIRP) for primary hyperparathyroidism for one gland, located by scanning with technetium 99m-labelled sestamibi (MIBI), has been performed. Total parathyroidectomy with autotransplantation or percutaneous ethanol injection therapy (PEIT) for severe secondary hyperparathyroidism (2HPT) has also been performed. METHODS: The present study examined the possibility of maintaining parathyroid function within a target range [intact parathyroid hormone (i-PTH) <or=300 pg/ml] in the long term after MIRP for 2HPT. Three patients resistant to calcitriol therapy gave their informed consent for MIRP. The principle of MIRP for chronic dialysis patients is to extract a hyper-functioning parathyroid gland resistant to medical therapy, including calcitriol pulse therapy, and then control the remaining glands with medical therapy. The follow-up period for this study was 2 years. RESULT: Two of the cases were controlled by MIRP followed by calcitriol pulse therapy. In all three cases, MIBI scintigraphy showed a solitary radioactive nodule; however, ultrasonography showed that in the two cases that were controlled by MIRP and calcitriol pulse therapy, there was one radioactive gland, but in the other case there were three, and this case required additional PEIT for control of hyperparathyroidism.

Adult↗
PubMed2003

Dysadherin: expression and clinical significance in thyroid carcinoma.

Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.

Adult↗
PubMed2003

[Usefulness of urine analysis in clinical nephrology].

In chronic glomerular nephritis (CGN), it is important to estimate the renal function and 24 hr urinary protein excretion to estimate the effectiveness of the treatment. In this study, we evaluated the usefulness of a microscopic urine test in making pathological diagnosis. As a result, we found that IgA nephritis has a significantly higher urinary RBC count among the CGN group, and found focal glomerular sclerosis and membranoproliferatine GN patients have significantly higher urinary RBC count among nephrotic patients. Among patients who have moderate renal insufficiency, acute tubular necrosis and acute interstitial nephritis have higher levels in urinary RBC counting. In summary, we can estimate the pathology of renal diseases by microscopic urinary tests to a certain extent. In western countries, physician have used the Cockcroft and Gault formula to estimate creatinine clearance, and they also have used urine protein-to-creatinine ratio to estimate 24 hr urinary protein excretion. We evaluated these formulae with Japanese, and as a result, found lower estimation of creatinine clearance and urinary protein excretion, which may be due to lower their muscle mass. We need further evaluation to make suitable changes to these formulae for Japanese.

Humans↗
PubMed2003

The sharing of target-epitopes between human anti-ABO hemagglutinating and anti-Pig (xeno) endothelium or anti-Pig thyroglobulin antibodies.

To select congenial pairs between donor-pig and recipient-human for the future xenotransplantation, the levels of xeno-IgM natural antibodies (NAb) were analyzed in healthy subjects and hemodialysis patients by ELISA tests, which target swine-derived crude endothelial cells (P16N) or proteins (thyroglobulin; TG). The total IgM concentration was lower in hemodialysis patients than in healthy subjects, but there was no difference in IgM NAb titer between the two groups. Individuals with non-B blood types (A, O) exibited significantly higher IgM NAb titer compared with those with B blood types (B, AB). A blood type individuals showed higher killing activity against P16N than those with B, AB or O types with a statistical significance. Sera from A blood type, after being absorbed with red blood cells (RBC) from B blood type, decreased their IgM titer against TG to the level of sera from B blood type. Meanwhile, sera from A blood type significantly decreased hemagglutinin titer against B-RBC after passage through a TG-coated affinity column. We conclude that human anti-B-RBC and anti-Pig xeno NAb have certain common binding epitopes, which might be a branched B carbohydrate structure.

ABO Blood-Group System↗
PubMed2002

Prognosis of parathyroid function after minimally invasive radioguided parathyroidectomy (MIRP) and percutaneous ethanol injection therapy (PEIT) for primary hyperparathyroidism.

During parathyroidectomy (PTx) for primary hyperparathyroidism (PHP), we surgically explored the contralateral parathyroid glands as well as those whose localization was clarified by ultrasonography and parathyroid scintigraphy. Although it is important to explore the contralateral side and other glands, we frequently treat only the gland whose localization is confirmed. Recently, we have performed minimally invasive radioguided parathyroidectomy (MIRP) that resects only one gland observed on the imaging under technetium 99m-labeled sestamibi (MIBI) scanning guidance after obtaining prior informed consent. In this surgery, even if recurrence is observed contralaterally, it is possible to apply a similar procedure to the contralateral side again. We examined six PHP patients who underwent MIRP and two PHP patients treated with percutaneous ethanol injection therapy (PEIT). The follow-up period was 2 years. PEIT was selected as a treatment method for two patients based on the patients' characteristics. When only one gland is treated, the efficacy of PEIT was considered to be similar to that of MIRP.

Administration, Cutaneous↗
PubMed2002

Renal proximal tubular metabolism of protein-linked pentosidine, an advanced glycation end product.

BACKGROUND: Pentosidine, an advanced glycation end product, accumulates in plasma proteins of uremic patients. Its fate is, however, yet to be fully understood. METHODS: Three cell lines, JTC-12 (proximal tubular cells), MDCK (distal tubular cells), and BALB3T3 (nonrenal cells), were cultured in a double chamber system and were exposed to uremic serum, and the contents of protein-linked pentosidine derived from uremic sera were determined in each medium by HPLC assay. The presence of pentosidine in the cytoplasm of these cells was assessed by immunoperoxidase staining. RESULTS: When the apical cell membrane was exposed to uremic serum (fortified in the upper chamber), the contents of protein-linked pentosidine in the upper medium decreased by up to 30% after 24- and 48-hour incubations of JTC-12 cells but not of other cells. On the other hand, the contents of protein-linked pentosidine in the lower medium did not change. By contrast, exposure of the basolateral cell membrane of the three cell lines to uremic serum (fortified in the lower chamber) did not change the contents of protein-linked pentosidine both in the upper and lower medium after a 24-hour incubation. Pentosidine was detected immunohistochemically in the cytoplasm of JTC-12 cells, but not of BALB3T3 and MDCK cells, the apical membranes of which were exposed to uremic sera for 8 h. The immunoreaction disappeared 48 h after exposure. Pentosidine was not detected in the cytoplasm of JTC-12 cells, the basolateral membranes of which were exposed to uremic sera. The relevance of the in vitro results to humans was demonstrated by immunohistochemical studies in normal human kidney tissues showing that pentosidine was identified in the proximal renal tubules. CONCLUSION: These results suggest that the proximal tubular cells play a role in the disposal of plasma pentosidine.

3T3 Cells↗
PubMed2002

Papillary thyroid carcinoma with fibromatosis-like stroma: a report of two cases.

Two cases of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. Tumor cells had nuclear features of a typical papillary carcinoma, i.e., overlapping, pale to ground glass and/or grooved nuclei. Tumors were characterized by an extensive stromal component accounting for 40-60% of the tumor. It has been reported that PTC is associated with a variable degree of fibrosis, but the exuberant proliferation of fibroblasts resembling fibromatosis is rare. The histogenesis and clinicopathologic significance of PTC have not been fully clarified because of its rarity. It is possible that the malignant nature of these PTC lesions may be overlooked because attention is focused on the stromal component of the tumor. A diligent search for this variant of papillary carcinoma is important.

Adult↗
PubMed2002

Acute interstitial nephritis with polyclonal B cell infiltration and development of mantle cell lymphoma.

A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic function developed acute renal failure. His clinical and laboratory examinations showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with high IgG levels. Renal biopsy showed interstitial nephritis with predominant B cell and plasma cell infiltration without monoclonality. After corticosteroid treatment, the patient showed remission in clinical symptoms and laboratory findings. However, one year later, he developed mantle cell lymphoma (MCL) with typical lymphocyte markers of cyclin D1 and CD5. When evaluated retrospectively, this patient appeared to have multicentric Castleman's disease initially and developed MCL later.

Acute Disease↗
PubMed2002

Expression and significance of c-met protein in papillary thyroid carcinoma.

The c-met protein, encoded by the c-met oncogene and its ligand, the hepatocellular growth factor/scatter factor, are known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. Recent studies have reported the prognostic significance of the c-met protein in malignant tumors. Papillary thyroid carcinoma, the most common histological type of thyroid carcinoma, can easily metastasize to regional lymph nodes, reflecting the activated motility and invasiveness of the carcinoma cells. We examined the expression of c-met protein in papillary thyroid carcinomas to assess its significance. Immunohistochemical staining of the c-met protein was performed on archival materials. The c-met protein was expressed in 10 cases of papillary thyroid carcinoma with recurrence, and in 5 of 10 cases without recurrence. Normal thyroids were negative for c-met protein. Expression of the c-met protein was statistically associated with recurrence of the thyroid carcinoma (p = 0.016). It is suggested that expression of the c-met protein plays a role in the recurrence of papillary thyroid carcinoma.

Adult↗