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Biomedical subjects

T Yanagawa

Publications and source records attributed to T Yanagawa.

At least 91 records · Page 5Linked to original sources
PubMed1995

QRST time integral values in 12-lead electrocardiograms before and after radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

OBJECTIVES: We investigated the usefulness of QRST values obtained from 12-lead electrocardiograms (ECGs) for identification of repolarization abnormalities before and after radiofrequency ablation in patients with Wolff-Parkinson-White syndrome. BACKGROUND: Marked T wave abnormalities often appear after ablation and have been attributed to a continuation of repolarization abnormalities present before ablation (cardiac memory). However, to our knowledge repolarization properties before and after ablation have not been assessed quantitatively. METHODS: We calculated the ECG QRST values from 53 patients with Wolff-Parkinson-White syndrome and compared these values before, immediately after and 1 day and 1 week after successful ablation in 25 patients. RESULTS: QRST values were abnormally high in lead V1 in 7 of 28 patients with a left-sided accessory pathway and abnormally low in leads III and aVF and high in lead aVL in 12, 9 and 10 of 20 patients, respectively, with a right-sided accessory pathway. Preexisting QRST abnormalities were still present immediately and 1 day after ablation but were usually absent by 1 week after ablation. QRST values before, immediately after and 1 day after ablation were not significantly different in any lead. In 14 patients with ablation of a left-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in lead V1 and immediately after ablation in leads I, aVR and V2 were significantly different from QRST values in those leads 1 week after ablation. In six patients with ablation of a right-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in leads III, aVL and aVF and immediately after ablation in lead II were significantly different from QRST values in those leads 1 week after ablation. CONCLUSIONS: Electrocardiographic QRST values may provide useful quantitative information with respect to repolarization properties before and after ablation in patients with Wolff-Parkinson-White syndrome that is otherwise difficult to obtain by conventional ECG analysis.

Adult↗
PubMed1995

Absence of association between human spumaretrovirus and Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease. The etiology of GD is still not clear. Both genetic and environmental factors, such as infectious agents, are believed to be involved in its pathogenesis. Recent findings suggest a role for human spumaretrovirus (HSRV) in the pathogenesis of GD. To test this hypothesis, we looked for the HSRV gag region sequence in DNA extracted from the peripheral blood leukocytes and thyroid tissue of patients with GD, and controls. Genomic DNA was subjected to a highly sensitive nested polymerase chain reaction, followed by dot-blot hybridization with an internal probe. HSRV gag region DNA fragments were detected in the peripheral blood leukocytes of patients with GD and controls to a similar extent; 5.3% (2/38) of Caucasian patients with GD, 4.7% (2/43) of Caucasian controls, 4.7% (2/43) of African-American patients with GD, and 6.5% of (3/46) African-American controls. Similar values were obtained for the samples of thyroid tissues; 5.5% (1/18) of Caucasian patients with GD and 5.0% (1/20) of controls. The differences in all these comparisons were not statistically significant. These results do not support a role for HSRV in the pathogenesis of GD.

Base Sequence↗
PubMed1995

Production of thyroid-stimulating antibodies in mice by immunization with T-cell epitopes of human thyrotropin receptor.

We examined whether mice, immunized with TSH receptor (TSH-R) peptides, which are known to be T-cell epitopes in patients with Graves' disease, would show thyroid-stimulating antibody (TSAb). We immunized DBA/1J mice with TSH-R peptide amino acids 132-150, 145-163, 158-176, and 172-186 and with a pool of these four peptides. The antibodies produced in these mice were evaluated by measurement of TSAb activity using Chinese hamster ovary cells expressing human TSH-R. Seven of 20 mice showed TSAb activity that could be partially blocked with TSH-R peptides. To assess the role of T-cell epitope-specific T-cells in the production of TSAb, we transferred a T-cell line developed from a TSAb-positive mouse to other syngeneic DBA/1J mice. Two of 4 recipient mice showed TSAb activities. These findings suggest that specific T-cell epitopes of TSH-R play a crucial role in the production of TSAb.

Amino Acid Sequence↗
PubMed1995

CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population.

Graves' disease (GD) is an autoimmune thyroid disease. Multiple genetic factors are believed to be involved in its pathogenesis, but the factors are largely unknown, except for sex (female disease preponderance) and the role of human leukocyte antigen (HLA) genes on chromosome 6. To understand the mechanisms underlying the development of GD, a search for non-HLA-linked genes is crucial, and we tested several candidate genes, including the CTLA-4 gene on chromosome 2q33. CTLA-4 molecules may either facilitate or down-regulate the second signal to T-cells, which is provided by the interaction between the two accessory molecules CD28 and B7. One hundred and thirty-three Caucasian patients (26 males) with GD and 85 local controls were included in this study. Polymerase chain reaction was used to amplify DNA containing the (AT)n repeat within the 3'-untranslated region of exon 3 of the CTLA-4 gene. The 5'-forward primer was radiolabeled, and amplified products were resolved on 5-7% sequencing gels. All subjects were previously typed for HLA class II alleles. Twenty-one alleles were observed with sizes ranging from 88-134 basepairs. In the association analysis, the genotype frequencies between GD patients and controls differed significantly (P = 0.012), and the difference was attributable to a higher frequency of the 106-basepair allele among patients (relative risk, 2.82). When the patients were subdivided with respect to sex and HLA, the phenotype frequencies of allele 106 was higher in the female patients with protective HLA specificities (DQA1*0201 positive/DQA1*0501 negative) than in those with susceptible HLA specificities (DQA1*0201 negative/DQA1*0501 positive; 81.8% vs. 45.5%; P = 0.026). The CTLA-4 gene or a closely associated gene (including CD28) confers susceptibility to GD. This association may be more important in female patients with protective HLA specificities, who otherwise would be at low risk of developing the disease.

Abatacept↗
PubMed1995

T-cells recognize multiple epitopes in the human thyrotropin receptor extracellular domain.

In Graves' disease (GD), the TSH receptor (TSHR) is believed to be the major target of an autoimmune response. T-Lymphocytes regulate the immune system. To assess the interaction of T-cells with TSHR in the pathogenesis of GD, we tested the T-cell response of peripheral blood mononuclear cells and T-cell lines to the recombinant human TSHR extracellular domain (rhTSHR-ECD) and 31 synthetic peptides corresponding to the entire TSHR-ECD in 20 patients with GD, 8 patients with Hashimoto's thyroiditis, 7 with colloid nodular goiter (CNG), and 20 normal controls. Comparing patients from different groups with normal subjects, there was a significant response to rhTSHR-ECD and thyroglobulin in GD patients (P < 0.001) and HT patients (P < 0.05), but not in CNG patients (P > 0.1). All 20 patients with GD responded to at least one peptide. The reactivity in GD patients was heterogeneous and spanned the entire TSHR-ECD. However, the reactivity was significantly different from that in controls for peptide regions 44-88, 119-176, 227-263, and 343-376, and the stimulation index (SI) values were significantly different for peptides 272-291 and 301-320. Significant differences were confined to peptides 158-176 and 343-362 and the region 227-263 for comparison of the number of positive responses in patients and controls to individual peptides. Forty-six percent of human leukocyte antigen-DQA1 0501 allele-positive Graves' patients responded to peptides 158-176 and 248-263 (SI = 3 or more) compared to 14% of allele-negative patients. In HT and CNG patients, the response was mainly to peptides in the carboxy-terminal half of the TSHR-ECD. Concordance of the reactivity in T-cell lines and peripheral blood mononuclear cells was observed in 36% of direct comparisons in GD. Eighty-five percent and 90% of GD patients were positive for microsomal antibody and TSHR antibody, respectively, and 59% of microsomal antibody-positive and 67% of TSHR antibody-positive patients responded to rhTSHR-ECD (SI = 2 or more). However, there was no significant correlation between antibody-positive patients and reactivity to specific peptides. Using multiple criteria to define immunodominance, peptides 158-176, 237-252, 248-263, and 343-362 seem to be important epitopes and may be critical for T-cell triggering in GD.

Adult↗
PubMed1995

Mucosal protective effect of leminoprazole on reflux esophagitis induced in rats.

We examined the effect of leminoprazole (an acid pump inhibitor) on reflux esophagitis induced in rats. Intragastrically administered leminoprazole significantly and dose-dependently protected the esophageal mucosa against the reflux of gastric contents, without affecting gastric acid secretion. However, it had no effect on the esophagitis when administered intraduodenally, despite its significant inhibition (about 40%) of gastric acid secretion. Omeprazole significantly prevented the development of esophagitis, most probably through potent inhibition of gastric acid secretion. Indomethacin significantly reduced the synthesis of prostaglandin E2 in the esophagus. Since indomethacin pretreatment had no effect on the esophageal protection by leminoprazole, omeprazole or sucralfate, the involvement of endogenous prostaglandins can be ruled out as a possible underlying mechanism. Intragastrically, but not intraduodenally, administered sucralfate significantly prevented the esophagitis even at a dose not affecting gastric acid secretion. These results strongly suggest that both leminoprazole and sucralfate protect the esophageal mucosa directly.

Animals↗
PubMed1995

Detection of coronary artery disease using 12-lead electrocardiogram and simultaneous dual myocardial imaging with iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 in patients with unstable angina.

We investigated the usefulness of 12-lead electrocardiogram and simultaneous single-photon emission computed tomography (SPECT) with 123I-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 (201Tl) for detecting coronary artery disease (CAD) in 54 consecutive patients with unstable angina. Discordant BMIPP uptake was defined as less 123I-BMIPP uptake than 201Tl uptake in 123I-BMIPP/201Tl dual SPECT. In the detection of CAD, ischemic electrocardiographic change during anginal attack had high sensitivity and low specificity, while discordant BMIPP finding had low sensitivity and high specificity. In patients showing ST depression during anginal attack, discordant BMIPP uptake showed high sensitivity and high specificity for detecting CAD. In conclusion, both 12-lead electrocardiogram during anginal attack and discordant BMIPP uptake are useful in detecting CAD in patients with unstable angina.

Adult↗
PubMed1995

Neurohumoral factor responses to mental (arithmetic) stress and dynamic exercise in normal subjects.

We examined the responses of plasma catecholamine and plasma renin activity (PRA) during mental (arithmetic) stress and dynamic exercise in 15 normal subjects. Compared to rest values, there was a significant increase in the plasma epinephrine concentration (E), but not in the plasma norepinephrine concentration (NE) or PRA during mental arithmetic. During dynamic exercise, there were significant increases in both NE and E and in PRA. The ratio of E to NE was significantly higher during mental arithmetic than during dynamic exercise. NE was significantly correlated with PRA at rest, during mental arithmetic and dynamic exercise. No significant correlations were observed between E and PRA. Dynamic exercise primarily induces a sympathetic nervous response, and mental (arithmetic) stress mainly induces an adrenal response. The renin-angiotensin-aldosterone system response may in part be regulated by sympathetic nervous activity during both mental (arithmetic) stress and dynamic exercise.

Adult↗
PubMed1995

[Coronary artery spasm as a cause of perioperative myocardial infarction and stunned myocardium].

We report a male patient who had recurrent coronary artery spasm on withdrawal from cardiopulmonary bypass, which led to myocardial infarction and stunned myocardium. The spasm responded to conventional medication. Transesophageal echocardiogram showed no remarkable asynergy during the operation. However, MB fraction of creatine kinase was 132 IU.l-1 and electrocardiogram showed new Q waves. After stopping intravenous catecholamines, hypokinesis of the anteroseptal segment appeared in the echocardiogram. Spotty myocardial necrosis and stunned myocardium might have resulted from recurrent coronary artery spasm.

Aged↗
PubMed1995

Spatial ventricular gradient in patients with Wolff-Parkinson-White syndrome in comparison with normal subjects: vectorcardiographic evidence for significant repolarization changes due to preexcitation.

We investigated the use of the spatial ventricular gradient (VG) from vectorcardiogram (VCG) to determine whether significant repolarization differences were present in patients with WPW syndrome compared with normal subjects and also examined which VG parameter (i.e., elevation, azimuth, and magnitude) reflected the differences in repolarization properties during preexcitation. VG was calculated in 49 patients of Wolff-Parkinson-White (WPW) syndrome (group A: left-sided accessory pathway, n = 29; group B: right-sided, n = 20). Group N consisted of 607 normal subjects. In group A, the azimuth of VG was significantly (p < 0.01) greater than in groups B and N. In group B, the elevation of VG was significantly (p < 0.01) greater than in groups A and N. There were no significant differences in the magnitude of VG among groups. QRS duration was significantly (p < 0.01) related with the elevation of VG in group B. These findings suggested that VG is useful for spatial evaluation of repolarization abnormalities during preexcitation, which are related to the site of the accessory pathway.

Adolescent↗
PubMed1995

[Pulmonary involvement of collagen vascular diseases: studies on prognostic factors from basic and clinical viewpoints].

In 715 patients with collagen vascular diseases, interstitial lung disease and pulmonary hypertension were found to be important causes of death (37.5% and 6%, respectively). The prognosis of interstitial lung disease associated with collagen vascular disease was better than that of idiopathic interstitial pneumonia; patients with the latter were more likely to experience exacerbations. A distinct subgroup of patients with dermatomyositis and interstitial lung disease with a rapidly progressive course was characterized by mild muscle symptoms, low levels of creatine phosphokinase and negative tests for anti-Jo-1 antibody. CT scores and analysis of bronchoalveolar lavage fluid proved to be of some value in predicting outcome. Measurement of IL-6 in bronchoalveolar lavage fluid and local immunostaining for this pro-inflammatory cytokine were helpful in evaluating responses to therapy.

Antibodies, Antinuclear↗
PubMed1994

Spontaneous regression of lung metastases from osteosarcoma.

BACKGROUND: Spontaneous regression of malignancy is infrequent, but in osteosarcoma, such occurrence is extremely rare. Through a survey of many university hospitals and cancer centers in Japan, two patients with such regression were found. METHODS: In both patients, radiograms of the primary sites and histologic specimens were studied carefully for accurate diagnosis. The clinical records, serum alkaline phosphatase values, and changes in the pulmonary metastasis on chest radiograms were followed for 26 years and 13 years, respectively. In the second patient, metastatic lesions were studied histologically. RESULTS: The patients, a 19-year-old man and an 11-year-old boy each with osteosarcoma in the distal femur. Each was treated by amputation. Pulmonary metastases were found on routine checkup 5 months and 12 months after the surgery, respectively, despite adjuvant chemotherapy. The metastatic nodules of both patients became denser and smaller 12 and 5 months, respectively, after detection, and the alkaline phosphatase concentration returned to normal, without special treatment. To date, the patients are alive and well. In the second patient, histologic examination of the metastatic nodules showed no remarkable infiltration of lymphocytes that would suggest an immunologic response; however there was florid bone formation indicating maturation of the tumor cells. CONCLUSION: Cases that have been reported as spontaneous regression of pulmonary metastases from osteosarcoma often show equivocal pathologic or clinical signs, and some have shown only temporary regression of the lesions. The two patients presented here are unique, however, because they had a definite diagnosis of osteosarcoma and showed extraordinarily long-lasting regression, which presumably occurred spontaneously, not as a direct effect of chemotherapy.

Adult↗
PubMed1994

Proliferative responses of peripheral blood mononuclear cells from patients with Graves' disease to synthetic peptides epitopes of human thyrotropin receptor.

In Graves' disease thyrotropin receptor (TSH-R) autoantibodies cause hyperthyroidism. Production of TSH-R autoantibodies must be controlled by specific T cells. In this study we investigated T cell responses to 33 peptides corresponding to the sequence of the extracellular domain of human TSH-R. Peripheral blood mononuclear cells (PBMC) from 12 patients with Graves' disease and 9 healthy subjects were cultured with peptides for 3 days. The proliferative responses of PBMC were analyzed by measurement of [3H]thymidine incorporation. A stimulation index (SI; mean cpm in the presence of peptide/mean cpm in culture medium alone) of more than 3 was considered a positive response. When PBMC were stimulated with a pool containing all synthesized peptides, the mean SI of patients was significantly higher than that of controls (4.50 +/- 3.95 vs. 1.44 +/- 0.60; p < 0.05). When PBMC were cultured with individual peptides, PBMC from patients responded predominantly to two peptides, corresponding to sequence segments 152-157 (5 patients) and 207-222 (4 patients). No PBMC from controls responded to these two peptides. There was no clear correlation between the HLA-DR or HLA-DQ genotype and the stimulatory sequence segments. These results suggest that (a) TSH-R-specific T cells are present in peripheral blood of patients with Graves' disease, and (b) sequence segments 152-157 and 207-222 may be T cell epitopes of the human TSH-R in Graves' disease.

Amino Acid Sequence↗
PubMed1994

Strong association between HLA-DQA1*0501 and Graves' disease in a male Caucasian population.

Graves' disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and -DQA1*0501 in caucasians. The incidence of GD is 5 times higher in females than in males, possibly due to their greater immune reactivity. Although many attempts have been made to correlate HLA phenotypes and clinical features of GD little attention has been paid to possible heterogeneous HLA distribution among patients of different sexes. To investigate this possibility, 133 (26 males) unrelated caucasian patients with GD and 104 (43 males) control subjects were typed for HLA-DRB1, -DQA1, and -DQB1, using sequence-specific oligonucleotide probes to analyze polymerase chain reaction-amplified DNA. There were no significant differences in HLA distribution between male and female controls. The frequencies of HLA-DQA1*0501 were increased in both [88.5%; relative risk (RR) = 9.13; P = 0.000015] and female patients (66.4%; RR = 2.66; P = 0.00046) compared to that in the entire control group (42.3%). The frequencies of DR11 (RR = 2.83; P = 0.019) and DQB1*0301 (RR = 2.50; P = 0.034) were increased only in male patients, whereas that of DR3 was higher in female (RR = 2.39; P = 0.0066) and male (RR = 2.54; not significant, P = 0.051) patients, suggesting the possible heterogeneous HLA distribution between the sexes. When the male and female patients were compared, a significant difference was found only for DQA1*0501. The prevalence of DQA1*0501 was significantly higher in males than in females (P = 0.019). As females have augmented immune responsiveness, we speculate that considerable numbers of females may develop GD without a strong HLA susceptibility allele, whereas only a few males develop GD without it.

DNA↗
PubMed1994

Statistical issues on the no-observed-adverse-effect level in categorical response.

The determination of the value of the no-observed-adverse-effect level (NOAEL) when observed responses can be categorized by severity (categorical data) and sample sizes are small is discussed. The common situation of only two categories, where only the presence or absence of an effect is observed, is addressed first (dichotomous data). Three tests for dichotomous data are critically examined, including the Brown-La Vange test, a modified version of that test, and Dunnett's multiple comparison test. Although the modified test is an improvement, all three procedures have shortcomings in determining the value of the NOAEL, particularly when the sample size is small. An alternative method is suggested, based on the Akaike information criterion (AIC), which performs well. This method is extended to severity data with an arbitrary number of categories. Use of a dose-response curve for the NOAEL is discussed.

Data Interpretation, Statistical↗
PubMed1994

Generalized Mantel-Haenszel procedures for 2 x J tables.

Generalization of Mantel-Haenszel procedure for 2 x J (J > 2) tables is reviewed. Included are generalized Mantel-Haenszel tests, estimators for a common odds ratio, and generalized Breslow-Day test for the homogeneity of odds ratios across the strata.-Environ Health Perspect 102(Suppl 8): 57-60 (1994)

Adult↗