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Yuji Tanaka

Publications and source records attributed to Yuji Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed2003

Association study between the fibronectin gene and schizophrenia.

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia.

Adult↗
PubMed2003

Switch moiety in agonist/antagonist dual effect of S19 ribosomal protein dimer on leukocyte chemotactic C5a receptor.

The cross-linked homodimer of S19 ribosomal protein (RP S19) induces monocyte predominant infiltration due to a dual effect on the C5a receptor in leukocyte chemotaxis, agonistic to monocytes and antagonistic to polymorphonuclear leukocytes (PMN) (H. Nishiura, Y. Shibuya, T. Yamamoto, Lab Invest 1998, 78:1615-1623). The agonistic ligand moiety was recently determined to be -Leu131-Asp132-Arg133- (Y. Shibuya et al, Am J Pathol 2001, 159:2293-2301). In this study we determined the moiety responsible for the antagonistic function. A C-terminal analogue peptide of RP S19, with 18 residues containing the agonistic ligand moiety as a part, reproduced the dual function in the leukocyte chemotaxis. A C5a analogue peptide attracted PMN as well as monocytes. When C-terminal 12 residues of RP S19 after the agonistic moiety, IAGQVAAANKKH, were connected to the C5a peptide, the chimeric peptide newly obtained the dual function, indicating that the C-terminal portion of RP S19 functions as a converter from the agonist to the antagonist. C-terminal truncation analyses indicated that the C-terminal His was not essential but the next Lys was necessary for the converter function. The homodimer of a mutant RP S19 that was truncated for the C-terminal 4 residues lost the monocyte selectivity in the leukocyte infiltration in vivo as in the case of the leukocyte chemotaxis in vitro. These results indicated that the conversion of the RP S19 dimer from agonist to antagonist of C5a receptor is attributed to the IAGQVAAANKK moiety between Ile134 and Lys144.

Amino Acid Sequence↗
PubMed2003

Dendritic cell vaccination for patients with chronic myelogenous leukemia.

In this pilot study, we investigated the ability of autologous dendritic cells (DCs) pulsed ex vivo with leukemia-specific peptide to stimulate host antitumor immunity when administrated as a vaccine. Three patients with chronic myelogenous leukemia (CML) received three series of four administration of bcr-abl peptide-pulsed (1) blood DCs injected intravenously, (2) immature monocyte-derived DCs injected intradermally or (3) mature monocyte-derived DCs injected intradermally. Vaccination was well tolerated. No major toxicity occurred in any of the patients. In method (1), one patient developed peptide-specific cellular immune response with no clinical response. In method (2), one patient developed peptide-specific cellular immune response with no clinical response. In method (3), all patients developed peptide-specific cellular immune response with no clinical response. The clinical benefits of bcr-abl peptide-specific vaccination in CML remain to be determined. Further vaccine development is necessary to increase the clinical effect.

Cancer Vaccines↗
PubMed2003

HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm.

It is generally known that even with permanent sections, the differential diagnosis between follicular adenoma and follicular carcinoma is often difficult to determine. It is not unusual to encounter patients diagnosed with benign follicular adenoma whose diagnoses have to be changed to malignancies because of recurrence or metastasis. As the monoclonal antibody HBME-1 produced by mesothelioma cells has been shown to have reactivity in thyroid carcinomas, we investigated the diagnostic usefulness of HBME-1 in follicular neoplasms. Immunohistochemical staining for HBME-1 was performed on 205 various thyroid tumors using the labeled streptavadin biotin peroxidase method. When hematoxylin-eosin (HE) staining was performed again for this study and all cases were examined in accordance with the WHO Histological Classifications 2nd Edition, 87.2% (54/62) of adenomatous goiter and 72.6% (45/62) of follicular adenoma were negative. On the other hand, 84.6% (33/39) of follicular carcinoma and 97.2% (35/36) of papillary carcinoma were positive. All anaplastic (2/2) and medullary (4/4) carcinoma were negative. Examination in follicular neoplasms had a sensitivity of 84.6%, specificity of 72.6%, positive predictive value of 66.0% and overall accuracy of 77.2%. Among the cases treated as follicular adenoma clinically, the diagnosis of 13 cases was changed to follicular carcinoma, and 6 cases to papillary carcinoma for this study. These cases showed strong HBME-1 positivity. Two of the follicular carcinoma cases experienced recurrence. We conclude that immunohistochemical staining with HBME-1 may be useful clinically to pick out cases with a high risk of recurrence in follicular carcinoma, and that benign adenoma cases need close follow-up.

Adenocarcinoma, Follicular↗
PubMed2003

Sodium bicarbonate infusion test: a new method for evaluating parathyroid function.

We have developed a new test for estimating the secretory capacity of parathyroid hormone (PTH) from the parathyroid gland. Sodium bicarbonate solution [8.4% (w/v); 35 ml/m(2) body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium, plasma PTH (intact, midregion, carboxy-terminus) and related parameters were serially obtained. In 8 healthy volunteers, the mean (+/-SE) plasma ionized calcium fell promptly and significantly (from 1.21 +/- 0.01 to 1.11 +/- 0.01 mmol/L) after the sodium bicarbonate infusion. The mean (+/-SE) plasma intact PTH increased promptly and significantly, by more than four fold (42.3 +/- 4.2 to 182.4 +/- 34.7 pg/ml), and then gradually returned to basal levels. In patients with partial hypoparathyroidism who have detectable basal plasma levels of PTH, the absolute increment in PTH levels was much less, and in the plasma obtained from patients with complete hypoparathyroidism, absolutely no response was observed. Plasma obtained from patients diagnosed with primary hyperparathyroidism (parathyroid adenoma or hyperplasia) has high basal PTH levels. The response to the sodium bicarbonate infusion in these patients was markedly blunted (less than a two-fold increase in all cases examined). No significant adverse effects were observed during the procedure. Therefore, the sodium bicarbonate infusion test is a simple and sensitive method to stimulate PTH release, and is clinically useful for evaluating parathyroid gland function.

Adult↗
PubMed2003

[Intrathecal glutamate receptor antibodies in a patient with elderly-onset refractory epilepsy].

Antibodies against a glutamate receptor in the central nervous system are reported to be an important autoimmune factor in infantile or childhood refractory epilepsy and in adult-onset paraneoplasstic cerebellar ataxia. We here reported a patient with glutamate receptor antibodies-positive elderly-onset intractable epilepsy and advanced-stage stomach cancer. A 77-year-old man with a history of resected bladder cancer suddenly developed an attack of epilepsia partialis continua in the right arm, followed by a generalized epileptic status. The ictal EEG showed spikes in the left parietal region with diffuse slow wave backgrounds. The brain MRI demonstrated a focal high signal intensity in the left postcentral gyrus on the T2-weighted and FLAIR images. The SPECT showed a high uptake in the focal area corresponding to the MRI lesion, suggesting a seizure focus. The routine analysis in the CSF was normal, but the glutamate receptor antibodies (IgG, IgM and C-terminal) were all positive. The status epilepticus was refractory to anticonvalsants, and the barbiturate anesthesia was introduced. Subsequently, the epilepsy has been fairly controlled by valproic acid and phenobarbital. The post ictal MRI demonstrated a focal atrophy in the left postcentral gyrus. The systemic evaluations revealed an advanced-stage stomach cancer. The glutamate receptor antibodies may play a role in late-onset refractory epilepsy, and may be an autoimmune factor in paraneoplstic neurologic syndrome presenting with epilepsy.

Aged↗
PubMed2003

[Sustained remission of MDS overt leukemia associated with abrupt discontinuation of immunosuppression following relapse after the second course of allogeneic hematopoietic stem cell transplantation].

The case of a 32-year-old female with relapsed myelodysplastic syndrome (MDS) after second course of allogeneic transplantation is described. The peripheral blood stem cell transplantation was performed as early as 3 months after the initial bone marrow transplantation because of rejection and relapse; however, the patient again relapsed 2 months later. Immediate discontinuation of cyclosporine resulted in the progression of pancytopenia and the development of high fever, liver dysfunction and skin eruption. The patient was then treated with dexamethasone, which successfully stabilized these symptoms. After these clinical events, a dramatic hematological response was obtained; the blast rate was reduced from 10.6 to 0% in bone marrow aspiration, and pancytopenia was restored to normal levels. Moreover, fluorescence in situ hybridization analyses with X and Y chromosome-specific probes revealed that hematopoietic precursor cells were predominantly of donor origin. The patient subsequently received donor lymphocyte infusion (DLI) from the original donor. Currently, 2 years after DLI, the patient continues to be in remission.

Adult↗
PubMed2002

Reoperation for renal hyperparathyroidism.

Reoperation for secondary hyperparathyroidism (HPT) due to uremia (2HPT) may be required among patients with persistent renal failure if not all parathyroid glands are removed at the initial operation. Between March 1981 and July 2001, altogether 1,110 patients underwent total parathyroidectomy with forearm autograft for advanced 2HPT in our department. In this study, we evaluated the clinical features of patients who required reoperation and classified them into persistent HPT [the lowest intact parathyroid (PTH) level after initial operation remained higher than 60 pg/ml] and recurrent HPT (the lowest intact PTH level was normalized after surgery but reelevated became high enough to require reoperation). Removal of residual glands was indicated in 30 (2.7%) cases for persistent or recurrent HPT. All remaining glands were detected by preoperative imaging diagnoses. In 44 (4.0%) patients persistent HPT was recognized and in 15 of them (1.4% of all cases) reoperation was required. In 11 cases, the responsible glands were supernumerary ones removed from the mediastinum. In 4 cases, the glands were resected from the neck. In 15 cases (1.4%), reoperation was performed for recurrent HPT when residual glands were left either in the neck or in the thymic tongue. In all but one case, the missed glands were supernumerary. This study reveals that it is often difficult to avoid persistent HPT induced by mediastinal supernumerary glands and recurrent HPT caused by small glands left in the neck. Our findings indicate that patients with uremia should be closely followed considering the possibility that persistent or recurrent HPT may occur after parathyroidectomy.

Adult↗
PubMed2002

Expression of somatostatin receptor and effects of somatostatin analog on pancreatic endocrine tumors.

PURPOSE: Somatostatin analogs have been administered to patients with pancreatic endocrine tumors in an attempt to inhibit hormone hypersecretion and prevent tumor growth. It is speculated that their efficacy is correlated with the expression of specific subtypes of somatostatin receptors. The aim of this study was to immunohistochemically evaluate the expression of somatostatin receptor subtypes in human pancreatic endocrine tumors, and to determine whether the expression of these subtypes is correlated with the effectiveness of the somatostatin analogs. METHODS: Somatostatin receptor subtypes 1, 2, and 3 (sst 1, 2, and 3) were immunohistochemically investigated in seven pancreatic endocrine tumors: four insulinomas, one VIPoma, and two nonfunctioning tumors associated with multiple endocrine neoplasia type I, using paraffin sections. Three of the four patients with insulinoma were given an octreotide injection. RESULTS: Cells were homogeneously stained in the tumor region. More than 85% of the specimens expressed sst 1, 2, and 3. There was no difference among the immunohistochemical stainings of somatostatin receptor subtypes according to most tumor characteristics; however, the expression of sst 2 was extremely positive, and the expression of sst 3 was moderately positive in the specimen from a patient in whom the octreotide injection had proven very effective. CONCLUSION: These findings indicate that the efficacy of octreotide may be correlated with the density of sst 2 and 3 in an immunohistological study using paraffin sections.

Adult↗
PubMed2002

Generation of Fas-independent CD4+ cytotoxic T-cell clone specific for p190 minor bcr-abl fusion peptide.

In the majority of Ph+ALL patients, p190 bcr-abl fusion protein is generated in the Philadelphia chromosome. The fusion protein may serve as a leukemia antigen because it is not expressed in normal cells and hardly in any other malignancy. From a healthy donor, we have established a p190 bcr-abl fusion peptide-specific CD4+ cytotoxic T-cell clone, activation of which depends on HLA-DRB1*1501. This T-cell clone has a strong cytotoxic activity against autologus MoDCs pulsed with e1a2 peptide and its cytotoxicity is not mediated by Fas/Fas ligand or perforin pathway. Success in establishment of the p190 bcr-abl fusion peptide-specific T-cell clone encourages us to develop a new approach to an effective immunotherapy for Ph+ALL.

Amino Acid Sequence↗
PubMed2002

Increased expression of multidrug resistance-associated protein 1 (mrp1) in hepatocyte basolateral membrane and renal tubular epithelia after bile duct ligation in rats.

Components of the multidrug resistance-associated protein (mrp) family mediate the adenosine triphosphate (ATP)-dependent transport of conjugated organic anions in the liver. Of these, mrp1 and mrp2 have been shown to have similar substrate specificity and nucleotide sequence. The intracellular localization and distribution of mrp1 under normal condition and cholestasis have not been as yet completely elucidated. To clarify this point, in the present study we evaluated the intracellular localization of mrp1 in rat liver and kidney after bile duct ligation (BDL). Bile duct was ligated in Wistar rats. Sequential staining of mrp1 by immunofluorescence was carried out in rat liver and kidneys 1, 3, and 5 days after bile duct ligation using confocal laser scanning microscopy. Weak granular staining of mrp1 was observed in cytoplasm of control rat hepatocytes. In addition to increased cytoplasm staining of mrp1, belt-and granule-like staining of mrp1 in basolateral membrane of hepatocytes was also shown after BDL. Furthermore, mrp1 immunofluorescence increased over time after BDL. No specific immunoflurescence of mrp1 was detected in control rat kidney. However, mrp1-positive staining was observed in epithelia of some renal tubules after BDL. This study showed that mrp1 immunofluorescence increased in hepatocyte basolateral membrane and cytoplasm and epithelia of some renal tubules after BDL. This increased mrp1 expression may be an adaptive response to impairment of hepato-biliary organic anion transport during obstructive cholestasis.

Journal Article↗
PubMed2002

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience.

BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. METHODS: Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. RESULTS: Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. CONCLUSION: Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy.

Adult↗
PubMed2002

Increased renal expression of bilirubin glucuronide transporters in a rat model of obstructive jaundice.

Regulation of bilirubin glucuronide transporters during hyperbilirubinemia in hepatic and extrahepatic tissues is not completely clear. In the present study, we evaluated the regulation of the bilirubin glucuronide transporters, multidrug resistance-associated proteins (MRP)2 and 3, in rats with obstructive jaundice. Bile duct ligation (BDL) or sham operation was performed in Wistar rats. Liver and kidneys were removed 1, 3, and 5 days after BDL (n = 4, in each group). Serum and urine were collected to measure bilirubin levels just before animal killing. MRP2 And MRP3 mRNA expressions were determined by real-time RT-PCR. Protein expression of MRP2 and MRP3 was determined by Western blotting. Renal MRP2 function was evaluated by para-aminohippurate (PAH) clearance. The effect of conjugated bilirubin, unconjugated bilirubin, human bile, and sulfate-conjugated bile acid on MRP2 gene expression was also evaluated in renal and hepatocyte cell lines. Serum bilirubin and urinary bilirubin excretion increased significantly after BDL. In the liver, the mRNA expression of MRP2 decreased 59, 86, and 82%, and its protein expression decreased 25, 74, and 93% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. In contrast, the liver expression of MRP3 mRNA increased 138, 2,137, and 3,295%, and its protein expression increased 560, 634, and 612% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. On the other hand, in the kidneys, the mRNA expression of MRP2 increased 162, 73, and 21%, and its protein expression increased 387, 558, and 472% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. PAH clearance was significantly increased after BDL. The mRNA expression of MRP2 increased in renal proximal tubular epithelial cells after treatment with conjugated bilirubin, sulfate-conjugated bile acid or human bile. Upregulation of MRP2 in the kidneys and MRP3 in the liver may be a compensatory mechanism to improve bilirubin clearance during obstructive jaundice.

Aged↗