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Biomedical subjects

K Tahara

Publications and source records attributed to K Tahara.

At least 37 records · Page 2Linked to original sources

Intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy for lung or liver cancers with a fusion of CT and linear accelerator (FOCAL) unit.

PURPOSE: To evaluate intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy (SRT) for lung or liver cancers, we checked repeated CT scanning, with a fusion of CT and linear accelerator (FOCAL) unit. METHODS AND MATERIALS: The FOCAL unit is a combination of a linear accelerator (Linac), CT scanner, X-ray simulator (X-S), and carbon table, and is designed to achieve CT-guided SRT with daily CT positioning followed by immediate irradiation while patients keep reduced shallow respirations. To evaluate intrafractional tumor position stability, 50 lung or liver lesions in 20 patients were checked by repeated CT scanning just before and after irradiation, and the obtained images were compared. RESULTS: There was no case with the intrafractional error judged to be greater than 10 mm. In 68% of cases, the intrafractional positioning errors were negligible (0-5 mm). CONCLUSIONS: Using the FOCAL unit, SRT for lung or liver cancers could be performed with intrafractional positioning errors not greater than 10 mm.

Equipment Design↗

Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis.

We compared lymphocyte-suppressive potencies of prednisolone and methylprednisolone in rheumatoid arthritis (RA). IC(50)s of the glucocorticoids (GCs) on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) from 44 RA patients and 30 healthy subjects were estimated in vitro, and differences in the IC(50)s of the two GCs were evaluated. The mean (+/-SD) IC(50)s for prednisolone and methylprednisolone on PBMC-blastogenesis of RA were 17.2+/-17.1 and 12.6+/-18.4 ng/ml, respectively, and no significant differences were observed between prednisolone-IC(50) and methylprednisolone-IC(50). In contrast, the mean IC(50)s of prednisolone and methylprednisolone on healthy PBMCs were 19.4+/-22. 4 and 3.7+/-3.9 ng/ml, respectively, and thus methylprednisolone potency was significantly higher than prednisolone potency (p<0.01). Methylprednisolone potency against PBMCs in RA patients exhibiting a high level of rheumatoid factor (RF) (>20 IU/ml) and the rheumatoid arthritis particle-agglutination value (RAPA) (>80) was significantly higher than that of patients exhibiting a lower level of RF or RAPA (p<0.05). In prednisolone-IC(50), however, such differences between the two patient-subgroups were not observed. Unlike reported cases of renal transplantation and healthy subjects, there was no difference in the lymphocyte-suppressive potencies for both prednisolone and methylprednisolone on RA-PBMCs. However, PBMCs from RA patients exhibiting high levels of RF or RAPA are more sensitive to methylprednisolone rather than prednisolone.

Aged↗

Cetraxate, a mucosal protective agent, combined with omeprazole, amoxycillin, and clarithromycin increases the eradication rate of helicobacter pylori in smokers.

BACKGROUND: Our previous study demonstrated that Helicobacter pylori eradication was less effective in smokers than in non-smokers. Cetraxate is an anti-ulcer drug that increases gastric mucosal blood flow. AIM: To evaluate the effect of cetraxate combined with new triple therapy for the eradication of H. pylori in smokers. METHODS: This study had a single-centre, double-blind, randomized non-placebo design. A total of 106 consecutive H. pylori-positive smoking patients were randomly allocated to one of two regimens: one group received omeprazole (20 mg), amoxycillin (1500 mg), and clarithromycin (600 mg) for 7 days (OAC, n=55). The other group recieved OAC plus cetraxate (600 mg) for 7 days (OAC + CET, n=51). The success of H. pylori eradication was evaluated by histology and the 13C-urea breath test at 4 weeks after completion of treatment. RESULTS: By intention-to-treat analysis, the H. pylori eradication rate was 55% in the OAC group and 92% in the OAC + CET group (P<0.01). By per protocol analysis, the H. pylori eradication rate was 58% in the OAC group and 94% in the OAC + CET group (P<0.01). CONCLUSION: Cetraxate combined with new triple therapy increases the eradication of H. pylori in smokers.

Adult↗

Choledochal cyst associated with duodenal obstruction.

The association between congenital duodenal obstruction and concomitant choledochal cyst has not been reported, although duodenal obstruction is known to be associated with many other anomalies. The authors describe 2 patients with choledochal cyst with duodenal obstruction. In 1 patient, a diverticulum type of choledochal cyst was found within an annular pancreas. Cyst excision, choledochojejunostomy, and side-to-side duodeno-duodenostomy were performed. The other patient showed separated duodenal atresia and other multiple anomalies including imperforate anus. A choledochal cyst was noted at the time of duodeno-duodenostomy and sigmoid colostomy. Cyst-enterostomy was performed at the age of 8 months, but the patient died of multiple anomalies. Intraoperative cholangiography indicated an anomalous pancreatobiliary ductal junction (APBDJ). In both patients the bile in the cyst contained high levels of amylase, suggesting the presence of an APBDJ. An APBDJ is considered to play an etiologic role in the development of the choledochal cysts associated with duodenal obstruction.

Choledochal Cyst↗

The prevalence and clinical significance of blocking thyrotropin receptor antibodies in untreated hyperthyroid Graves' disease.

The goal of this study was to evaluate the clinical significance of the blocking thyrotropin receptor antibodies (TSHRAb) in Graves' disease. The amount of blocking and stimulating TSHRAb were measured in 200 patients with untreated hyperthyroid Graves' disease using several cell lines carrying different TSHR chimera. Stimulating TSHRAb were measured in Chinese hamster ovary (CHO) cells with wild-type human TSHR (CHO-hTSHR) or a TSHR chimera with residues 90-165 (Mc2) or 8-165 (Mc1+2) substituted by equivalent residues of rat luteinizing hormone/chorionic gonadotrophin (LH/CG) receptor or in FRTL-5 cells. Blocking TSHRAb were measured in Mc2 cells. The activities of different TSHRAb were assessed and clinical features were compared to patients who were positive or negative for blocking TSHRAb antibodies. Blocking TSHRAbs were detected in 18.5% of patients (37/200) with hyperthyroid Graves' disease. Patients with blocking antibodies had significantly lower mean stimulating TSHRAb activities than those without blocking antibodies in wild-type CHO-hTSHR cells (301 +/- 179 vs. 446% +/- 537%, p = 0.005). Mean stimulating TSHRAb activities measured by FRTL-5, Mc1+2, or Mc2 cells and mean thyrotropin receptor inhibitor immunoglobulin (TBII) activities were not different between the two groups. The patients with blocking antibodies were not different from those without blocking antibodies in age, gender ratio, initial serum free thyroxine (T4) levels, or goiter size. However, the prevalence of exophthalmos was higher (35.1% vs. 17.5%, p = 0.024) in the patients with blocking antibodies than those without. In summary, the presence of blocking TSHRAb is not rare in patients with hyperthyroid Graves' disease when measured with chimeric receptor expressing cells. Blocking TSHRAb in Graves' sera do not strongly antagonize the action of stimulating TSHRAb in vivo, but could be a major factor responsible for underestimation of stimulating TSHRAb activities measured by CHO-hTSHR. The association of blocking TSHRAb with ophthalmopathy suggests that the TSHRAb repertoire of Graves' patients is different in those who do and who do not have ophthalmopathy.

Adult↗

Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies.

Blocking-type TSH-binding inhibitor Igs (TBIIs) are known to cause hypothyroidism and an atrophic thyroid gland in patients with primary myxedema. They can block the activity of thyroid-stimulating antibodies (TSAbs) in Graves' patients as well as the activity of TSH. The majority of the epitopes for these blocking-type TBIIs have been, and are shown herein, to be present on the C-terminal region of the extracellular domain of the human TSH receptor (TSHR), whereas those for Graves' TSAbs are on the N-terminus. We report on a patient with Hashimoto's thyroiditis who suffered from mild hypothyroidism and a moderately sized goiter. Her serum had a potent blocking-type TBII and a weak TSAb in human and porcine TSHR systems. Using human TSHR/lutropin-CG receptor chimeras, we determined that the functional epitope of her blocking-type TBII was uniquely present on the N-terminal, rather than the C-terminal, region of the extracellular domain of the TSHR, unlike the case for blocking-type TBIIs in primary myxedema patients. The epitope of her TSAb was also unusual. Although the functional epitopes of most TSAbs are known to involve the N-terminal region of the receptor, her TSAb epitope did not seem to be present solely on the N- or C-terminus of the extracellular domain of the receptor. Blocking-type TBIIs from patients with primary myxedema blocked her TSAb activity as well as stimulation by TSH; her blocking-type TBII was able to only partially block her TSAb. In contrast, her blocking-type TBII almost completely blocked TSAbs from Graves' patients. Thus, we suggest that the unique epitopes of this patient's heterogeneous population of TSH receptor antibodies, at least in part, contribute to regulation of her thyroid function.

Animals↗

A case of seborrhoeic blepharitis.

A fifty five-year old woman suffered from itching and scaling of the edge of her eyelid. She had long used topical corticosteroid for this condition. Direct examination of the scale by Parker KOH showed numerous fungal elements of spores and hyphae of Malassezia furfur. She was treated with oral itraconazole (100 mg daily or twice a week) for 8 weeks and was cured clinically and mycologically. The result suggests the possibility of treatment with an anti-fungal drug for seborrhoeic blepharitis or seborrhoeic dermatitis.

Antifungal Agents↗

MAGE-specific cytotoxic T lymphocytes require non-specific CD54 adherence receptors on carcinoma cells.

We investigated several factors that could regulate the susceptibility of carcinoma cells to MAGE-2-specific CTL mediated lysis. Cytofluorometric analysis showed that the cytolysis correlated with the expression of CD54. IFN-gamma treatment induced the TAP-1 and LMP-2 genes, continuously up-regulated the HLA class I expression and increased cytolysis. Although HLA class I were highly induced in MRKnu1 cells, CD54 was not induced and the cytolysis was minimal. Cytotolysis of IFN-gamma-treated MKN-1 cells was completely inhibited by a monoclonal anti-CD54 antibody. These results suggest that HLA-restricted CTL lysis requires non-specific CD54 adherence receptors in addition to specific TCR signals.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Two cases of rheumatoid arthritis associated with IgA -type multiple myeloma].

We report here two Japanese cases of rheumatoid arthritis (RA) associated with IgA [symbol: see text]-type multiple myeloma (MM). Case 1. The patient was a 68-year-old man with eight-years history of RA. The M-proteinemia (IgA 2838 mg/dl) in laboratory findings suggested a complication of MM which had been noticed since four years ago. On May 1997, he was referred and admitted to our hospital because of cough, right chest pain and dyspnea. Serum immunoelectrophoresis showed monoclonal IgA[symbol: see text]-type light chain. Bone marrow aspirate contained 6.5% atypical plasma cells. The X-ray findings revealed radiolucent myelomatous foci in the skull. From these findings, IgA[symbol: see text]-type MM was diagnosed. His condition was recovered by administration of antibiotics for bacterial pleuritis. Case 2. The patient was a 75-year-old woman with twelve-years history of RA. The laboratory findings of M-proteinemia (IgA 1215 mg/dl) with the decrease of other serum immunoglobulin level (IgG 611 mg/dl, IgM 60 mg/dl) and monoclonal IgA[symbol: see text]-type light chain in serum immunoelectrophoresis suggested MM four years ago. Bone marrow aspirate contained 5% plasma cells. From these findings, IgA[symbol: see text]-type MM was diagnosed. In the review of reported Japanese cases of RA associated with MM, it might be characteristic that IgA type MM was found more frequently in RA patients than other immunoglobulin types.

Aged↗

Laparoscopic resection of an adrenal neuroblastoma detected by mass screening that grew in size during the observation period.

Neuroblastomas (NB) identified by mass screening tests are characterized by benign features. Recently, laparoscopic resection has been applied to the treatment of patients with small adrenal NB (<2-3 cm). However, an increasing number of cases of small NB are followed without any treatment in Japan because many cases regress spontaneously. We describe a case of right adrenal NB detected by mass screening that increased in size during an observation period of 8 months. In this case, laparoscopic resection was performed successfully. The size of the tumor was 27 x 20 x 18 mm at diagnosis and 51 x 42 x 35 mm when it was excised. Small adrenal NB that do not regress during the observation period may require laparoscopic resection before they reach 5 cm in maximum diameter.

Adrenal Gland Neoplasms↗

Expression of the MAGE gene family in human hepatocellular carcinoma.

BACKGROUND: The 12 members of the MAGE gene family encode tumor specific antigens that are recognized by autologous cytotoxic T lymphocytes (CTL). The MAGE genes are expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on their expression in hepatocellular carcinoma (HCC). The authors thus studied the expression of the MAGE gene family in human HCC and discuss the possibility of specific immunotherapy using MAGE peptides. METHODS: Tumor tissue samples of HCC and paired nontumor tissues of the liver were obtained from 22 HCC patients. Total RNA was extracted and cDNA was synthesized. Polymerase chain reaction amplification using each MAGE gene specific primer was then performed to detect the expression of each MAGE gene. Immunoblotting and immunohistochemical analysis were performed to confirm the expression of MAGE-3 gene product in HCC. RESULTS: The expression rate of each MAGE gene was as follows: MAGE-1 and -3 were expressed in approximately 68% of the tumors; MAGE-8 was expressed in 46%; and MAGE-2, -6, -10, -11, and -12 were expressed in approximately 30%. Nineteen (86%) of 22 tumors expressed at least 1 MAGE gene. On the other hand, no expression was detected in the noncarcinomatous liver tissue specimens. Actual expression of the gene product of MAGE-3 was detected in 50% of tumors. Clinicopathologic data on the MAGE positive and negative cases were compared. Significant differences were observed between MAGE expression status and a few clinicopathologic factors; however, further investigation is required to elucidate these correlations completely. CONCLUSIONS: These findings demonstrated that MAGE gene expression is frequent in HCC, thus suggesting that HCC patients may be good candidates for specific immunotherapy using MAGE peptides.

Aged↗

A MAGE-1-encoded HLA-A24-binding synthetic peptide induces specific anti-tumor cytotoxic T lymphocytes.

Although several MAGE-1 peptides have already been identified, the MAGE-1-encoded peptide presented by HLA-A24, which is the most common allele in Japanese population and is also frequently present in Caucasians, might have a wide applicability for immunotherapy using these peptides. To identify this potential peptide, we examined the induction of specific cytotoxic T lymphocytes (CTL) from the peripheral-blood mononuclear cells (PBMC) in HLA-A24 healthy donors by in vitro stimulation with MAGE-1-encoded synthetic peptides with a binding affinity for HLA-A24, by a simplified method. Of the 5 peptides tested, the highest HLA binder (NYKHCFPEI) was able to elicit CTL from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PMBC as antigen-presenting cells (APC) and by also using interleukin 7 and keyhole-limpet hemocyanin for a primary culture. The induced CTL could thus lyse HLA-A24 tumor cells expressing MAGE-1, as well as the peptide-pulsed target cells, in an HLA-class-I-restricted manner. By using the MAGE-1/HLA-A24 peptide, NYKHCFPEI, we found it possible to immunize many more patients, especially Japanese patients, by means of such peptide-based immunotherapeutic approaches to MAGE-1-positive malignant tumors.

Alleles↗

Generation of specific antitumor reactivity by the stimulation of spleen cells from gastric cancer patients with MAGE-3 synthetic peptide.

The induction of cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using MAGE peptide has been investigated in order to use MAGE antigens immunotherapeutically. We therefore developed a simplified method for inducing peptide-specific CTL that kill tumor cells expressing MAGE from the PBMC of either healthy donors or even cancer patients. Since the spleen is a major lymphoid organ, we used a simple method to examine the capacity of spleen cells to generate MAGE-specific CTL by in vitro stimulation with MAGE peptide in gastric cancer patients. The CTL responses could thus be induced from unseparated spleen cells in HLA-A2 patients with gastric carcinoma expressing MAGE-3 by stimulating these cells with autologous spleen cells pulsed with HLA-A2-restricted MAGE-3 peptide as antigen-presenting cells and by using keyhole limpet hemocyanin and interleukin-7 for the primary culture. The induced CTL were thus able to lyse HLA-A2-positive carcinoma cells transfected with MAGE-3 and expressing MAGE-3, as well as the target cells pulsed with the peptide, in an HLA-class-I or -A2-restricted manner. Since MAGE-specific CTL could be induced from the spleen cells of gastric cancer patients, the spleen appears to play an important role in either clinical tumor vaccination or the treatment of cancer patients by adoptive immunotherapeutic approaches using the MAGE peptide.

Antibodies, Monoclonal↗

Daily positioning accuracy of frameless stereotactic radiation therapy with a fusion of computed tomography and linear accelerator (focal) unit: evaluation of z-axis with a z-marker.

To evaluate quantitative positioning errors of frameless stereotactic radiation therapy with a fusion of computed tomography (CT) and linear accelerator unit, Z-type CT markers were attached to patients, and CT images were obtained before and after daily treatment. In 40 verification tests, geometrical errors were never more than 1 mm.

Brain Neoplasms↗

Effect of smoking and histological gastritis severity on the rate of H. pylori eradication with omeprazole, amoxicillin, and clarithromycin.

BACKGROUND: The combination of omeprazole, amoxicillin, and clarithromycin is a common regimen against Helicobacter pylori. Several recent studies have shown that smoking, high intragastric acidity, and the degree of histological gastritis are associated with H. pylori eradication failure. MATERIALS AND METHODS: One hundred and thirty-seven H. pylori-positive patients were treated with a 1-week regimen composed of omeprazole, 20 mg once daily; amoxicillin, 500 mg; and clarithromycin, 200 mg thrice daily. Success of the treatment was evaluated by histology and the 13C-urea breath test at least 4 weeks after completion of therapy. Data about age, gender, alcohol intake, smoking habits, and previous proton pump inhibitor intake were collected in patient interviews. We evaluated fasting gastric pH and the degree of histological gastritis before eradication of H. pylori. RESULTS: The overall eradication of H. pylori at 4 weeks was successful in 98 of 137 patients (72%). On the multivariate analysis, a low grade of inflammation in the antrum (p </=.01; 95% confidence interval [CI], 2.34-16.75), low grade of activity in the fundus (p </=.05; 95% CI, 1.31-9.65), and smoking (p </=.05; 95% CI, 1.27-6.82) were the significant independent factors predicting treatment failure. CONCLUSIONS: These findings indicate that H. pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin is less effective in patients who smoke and more effective in patients with high scores of antral inflammation and fundal activity at baseline biopsy.

Adult↗

Two Graves' disease patients who spontaneously developed hypothyroidism after antithyroid drug treatment: characteristics of epitopes for thyrotropin receptor antibodies.

Few reports have identified blocking thyrotropin receptor antibodies (TSHRAbs) as a pathogenic mechanism explaining spontaneous hypothyroidism after antithyroid drug (ATD) treatment of Graves' disease. Here we report 2 Graves' patients who showed different courses of hypothyroidism after ATD treatment. The first patient had Graves' hyperthyroidism and was treated with ATD for 1 year. After a short period of euthyroidism, she developed permanent hypothyroidism with blocking TSHRAb. The second patient became euthyroid after 1 year of ATD treatment. After 3 years, however, she presented with hypothyroidism with blocking TSHRAb activity. Her hypothyroidism was transient, and restoration of euthyroidism was followed by disappearance of blocking TSHRAb. Blocking and stimulating TSHRAbs activities of these 2 patients were serially measured using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR (CHO-hTSHR) and 2 TSHR chimeras with residues 8-165 (Mc1+2) or 90-165 (Mc2) substituted by equivalent residues of the luteinizing hormone/chorionic gonadotropin receptor (LH/CGR). During their hypothyroid phases, blocking TSHRAbs activities were positive in all 3 kinds of assays and stimulating TSHRAbs activities were negative in CHO-hTSHR or in Mc 1+2 assay. Mc2 stimulating TSHRAb activity was detected in sera of hypothyroid phase of the second patient who had transient hypothyroidism but not in the first whose hypothyroidism was permanent. In these 2 cases, we demonstrate the causative role of blocking TSHRAb in the development of hypothyroidism after ATD treatment in Graves' patients. Interestingly, the difference in the course of blocking TSHRAb-induced hypothyroidism was associated with the difference in epitope reactivities of TRAb during hypothyroid phase that developed after ATD treatment of Graves' disease.

Adult↗

Epitope heterogeneity of thyrotropin receptor-blocking antibodies in Graves' patients as detected with wild-type versus chimeric thyrotropin receptors.

The stable transfectants of wild-type (W25) and mutant thyrotropin-receptor (TSH-R) allow detection of the bioactivities of TSH-R antibodies in Graves' patients. A mutant Chinese hamster ovary (CHO) cell line (Mc1+2) transfected with a chimeric construct, where residues 8 to 165 of the TSH-R are replaced with residues 10 to 166 of the lutropin/choriogonadotropin (LH/CGR) receptor, lacks the cyclic adenosine monophosphate (cAMP) response to most thyrotropin stimulating antibodies (TSAb), yet retains the response to TSH and acquires the response to LH/CG. We compared Mc1+2 cells with wild-type W25 cells for their ability to detect TSAb as well as thyrotropin-blocking antibodies (TBAb) in Graves' sera. Eighteen normal and 39 Graves' sera were tested for TSAb and TBAb levels by in vitro bioassays using W25 and Mc1+2 cells. In addition, these sera were also tested for thyrotropin-binding inhibitory activity (TBII) by a radioreceptor assay. Eighteen (47%) Graves' sera had TBAb activity measured with W25 cells but not with Mc1+2 cells. These TBAbs were, therefore, a population of antibodies with functional epitopes on the N-terminus of the extracellular domain. This TBAb activity by W25 cells exhibited a high degree of correlation with TBII levels by a radioreceptor assay (r = 0.70, p = 0.001). Ten (25.6%) Graves' sera had positive TBAb activity in both W25 and Mc1+2 cells; moreover, their activity in both assays was similar (r = 0.83, p < 0.001). The TBAb activity in these sera, however, did not correlate with TBII activity. Eleven (28%) Graves' sera had no TBAb activity. Overall, thyroid-stimulating antibodies were detected in 87% and 28% of the 39 Graves' sera by W25 and Mc1 +2 cells, respectively. Thus, using the 2 cell lines, at least 2 distinct populations of TBAbs were detected. One is detected in a similar fashion by both W25 and Mc1+2 cell lines and likely interacts with the epitopes residing in the unaltered C-terminus of the TSH-R. The other is reactive in W25 cells only, indicating the loss of TBAb epitope in the chimeric receptor located in the N-terminus of the TSH-R. Furthermore, our results indicate that the TBAb binding epitope in 8-165 residues of the native TSH-R is highly associated with TBII activity in Graves' disease. These results indicate that patients with Graves' disease harbor TBAbs with epitope heterogeneity and favor the notion that there are different sites and mechanisms by which TBAbs act in Graves' patients. It remains to be determined whether or not TBAb subtyping will have a useful predictive role in the management of patients with Graves' disease.

Adult↗