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Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 127 records · Page 7Linked to original sources
PubMed1999

The restoration of the antitumor T cell response from stress-induced suppression using a traditional Chinese herbal medicine Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi-Tang).

We previously reported that restraint stress impairs the antitumor immune responses through its suppressive effect on the Th1-type cytokine production from CD4+ T cells. In this study, we investigated a potential of Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi-Tang) to restore stress-induced immunosuppression. The oral administration of TJ-41 was able to improve a decreased cellularity in the lymph node and spleen and to improve an inhibition of tumor-specific Th1-type cytokine production, both of which were induced by repeated restraint stress in tumor-bearing mice. The oral administration of TJ-41 also induced a partial recovery of the antitumor cytolytic activity in the stress-burdened tumor-bearing mice. More importantly, the growth of tumors in stress-burdened preimmunized mice was obviously inhibited by TJ-41, and resulted in tumor-free state in 75% of the mice. Regarding the mechanisms by which TJ-41 restored the antitumor responses in stress-burdened mice, we found that the serum levels of corticosterone and interleukin-12 were normalized by TJ-41. In addition, the expression of CD80 and CD86, which both decreased in the stress-burdened mice, was restored to the normal level by TJ-41. Taken together, our results indicate that the oral administration of TJ-41 is able to restore the antitumor T cell responses in stress-burdened tumor-bearing mice by normalizing the serum corticosterone, interleukin-12 and the expression of costimulatory molecules.

Adjuvants, Immunologic↗
PubMed1999

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis.

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.

Animals↗
PubMed1999

Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases.

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.

Acute Disease↗
PubMed1999

Invasion of the lacrimal system by basal cell carcinoma.

BACKGROUND: The rate of recurrence of basal cell carcinoma (BCC) in the periorbital region is higher than that in other areas because of the spread of the tumor along barrier structures. OBJECTIVE: A better understanding of the biological behavior of BCC in this area, in particular as it relates to the lacrimal system, should improve the outcome of surgery. METHODS: A study was made of two cases of BCC that developed in the periorbital region and invaded the lacrimal system. RESULTS: The tumors were found to have invaded the lacrimal system along the mucosal epithelium. Magnetic resonance imaging (MRI) did not suggest any abnormalities in this area. In one patient, the tumor had infiltrated the nasal cavity without destruction of the periorbital bone and nasal cartilage. A preoperative fiberscopic examination clearly demonstrated the involvement of the nasal cavity in this case. CONCLUSION: The lacrimal system is often invaded by BCC that originates from the periorbital region. Physicians and surgeons need to be well aware of the possibility of such aggressive infiltration by BCC.

Aged↗
PubMed1999

Increased serum concentration of interleukin-12 in patients with silent thyroiditis and Graves' disease.

We previously reported that interleukin-5 (IL-5), secreted from Th2 cells, was increased in patients with Graves' disease, but not in patients with silent thyroiditis. In this study, we investigated serum levels of interleukin-12 (IL-12) in order to examine the role of Th1-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-12 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 68 patients with Hashimoto's thyroiditis (26 of whom had silent thyroiditis), 74 patients with Graves' disease, 8 patients with subacute thyroiditis, and 27 normal controls. Serum levels of IL-12 in thyrotoxic patients with silent thyroiditis (385.2 +/- 164.5 pg/mL, mean +/- SD), and in thyrotoxic patients with Graves' disease (343.6 +/- 163.8 pg/mL) were significantly increased compared with serum levels in normal subjects (163.9 +/- 66.8 pg/mL, p < 0.0001, p < 0.0001, respectively) or in thyrotoxic patients with subacute thyroiditis (241.9 +/- 46.5 pg/mL, p < 0.01, < 0.05, respectively). The ratio of IL-12 to IL-5 in thyrotoxic patients with silent thyroiditis (64.2 +/- 39.7) was significantly higher than that in normal controls (33.7 +/- 13.3, p < 0.01) or in thyrotoxic patients with Graves' disease (40.6 +/- 36.0, p < 0.05). These data suggest that Th1-type immune response is predominant in silent thyroiditis, and that not only Th2-type immune response but also Th1-type immune response is important in the pathogenesis of Graves' disease.

Adult↗
PubMed1999

CD30 expression and interleukin-4 and interferon-gamma production of intrathyroidal lymphocytes in Graves' disease.

We reported that serum levels of interleukin-5 (IL-5) and soluble CD30, mainly secreted from T helper 2 (Th2) cells, were increased in Graves' disease. To clarify the immune balance of Th1/Th2 within the Graves' thyroid gland, we have compared the expression of CD30, a preferential marker for T cells producing type 2 cytokines, and the production of interferon-gamma (IFN-gamma) and IL-4 between intrathyroidal lymphocytes (ITL) and peripheral blood lymphocytes (PBL). In PBL, none of these parameters were different between patients and normal subjects. The proportion of CD30+ cells in ITL was markedly higher (5.1%+/-2.8%, p < 0.0001) than that in patients' PBL (0.4%+/-0.3%). Likewise, both the proportions of IFN-gamma+ (14.8%+/-5.5%) and IL-4+ cells (2.4%+/-0.5%) in ITL were higher than those in PBL (9.6%+/-2.5%; p < 0.01, 1.5%+/-0.4%; p < 0.0001, respectively). The proportion of type 0 (both IFN-gamma and IL-4 positive, 1.0%+/-0.4% p < 0.001), type 1 (IFN-gamma positive, 14.0%+/-5.6%, p < 0.01) or type 2 cells (IL-4 positive, 1.4%+/-0.5%, p < 0.05) in ITL was significantly higher as compared with those in PBL (0.4%+/-0.1%, 9.0%+/-2.4%, 1.1%+/-0.3%, respectively). The ratios of ITL/PBL in CD30+ (23.3+/-30.6) and type 0 cells (2.5+/-1.2) were higher than the ratios in other subsets. The proportion of CD30+ cells correlated with the proportion of type 0 cells (r = 0.686, p < 0.01), but not with type 1 or type 2 cells. These findings suggest that there is no obvious deviation of Th2/Th1 profile in the Graves' thyroid gland, although intrathyroidal CD30+ T cells and Th0 cells may play some role in the development of autoimmune abnormalities in Graves' disease.

Adolescent↗
PubMed1999

Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease.

Postpartum thyroid dysfunction is rather a common problem during the postpartum period being found in approximately 5% of mothers in the general population. It occurs from subclinical autoimmune thyroiditis that is aggravated after parturition and causes various types of thyroid dysfunction. Immune activity is physiologically suppressed during pregnancy so that the fetus is not rejected, and rebounds above the normal level after parturition. Graves' disease and Hashimoto's thyroiditis also spontaneously ameliorate during pregnancy, and are often aggravated after parturition. The high-risk mothers for postpartum thyroid dysfunction are well screened by antithyroid microsomal antibody (MCAb) and 60% to 70% of MCAb-positive mothers develop postpartum thyroid dysfunction, which is transient in most cases. New onset of Graves' disease may be screened by thyroid-stimulating antibody (TSAb) and 70% of TSAb-positive mothers develop either transient or persistent postpartum Graves' disease that usually occurs 3 to 6 months postpartum. Immune rebound after parturition may cause not only autoimmune thyroid diseases but other autoimmune diseases, which may be investigated with similar strategies to those in postpartum autoimmune thyroid disease. Thus, we found that postpartum onset of rheumatoid arthritis was found in 0.08% of women in the general population and could be partially predicted by measuring rheumatoid factors in early pregnancy. There are several case reports of other autoimmune diseases that develop after delivery; postpartum renal failure or postdelivery hemolytic-uremic syndrome, postpartum idiopathic polymyositis, postpartum syndrome with antiphospholipid antibodies, postpartum autoimmune myocarditis. Many other possible postpartum autoimmune diseases are still unexplored. Puerperal diseases should be carefully examined in relation to autoimmune abnormalities in the affected organs.

Antibody Formation↗
PubMed1999

Recombinant human monoclonal Fab fragments against rotavirus from phage display combinatorial libraries.

We prepared and characterized human monoclonal Fab fragments to rotavirus from IgG1 kappa combinatorial libraries (designated as N and O) constructed from peripheral blood lymphocytes (PBLs) from two healthy individuals. Approximately 30-fold enrichment in eluted phage was obtained in these libraries after five rounds of panning against rabbit polyclonal antibody-captured human rotavirus (HRV) Wa strain. Forty-eight clones from each library were tested for reactivity to HRV Wa in an enzyme-linked immunosorbent assay (ELISA), and the identities of positive clones were determined by BstNI fingerprinting. As a result, eight individual clones (five from N library and three from O library) were isolated. In testing the cross-reactivity of Fabs against a panel of self- or non-self antigens, all Fab clones were found to be specific for HRV Wa. Fab clones from the two libraries showed distinct characteristics with respect to their reaction patterns with Wa and crossreactivities with rotavirus strains, and displayed variable heavy (VH) chain gene usage, although they recognized the VP6 protein as determined by immunoblotting. The distinct epitope recognition by Fabs from two libraries suggests different courses of humoral immune response to rotavirus during infection in the two individuals.

Amino Acid Sequence↗
PubMed1999

Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor.

Pancreatic-type RNases are considered to have cytotoxic potential due to their ability to degrade RNA molecules when they enter the cytosol. However, most of these RNases show little cytotoxicity because cells have no active uptake mechanism for these RNases and because the ubiquitous cytoplasmic RNase inhibitor is considered to play a protective role against the endocytotic leak of RNases from the outside of cells. To study the cytotoxic potential of RNase toward malignant cells targeting growth factor receptors, the C-terminus of human RNase 1 was fused to the N-terminus of human basic fibroblast growth factor (bFGF). This RNase-FGF fused protein effectively inhibited the growth of mouse melanoma cell line B16/BL6 with high levels of cell surface FGF receptor. This effect appeared to result from prolongation of the overall cell cycle rather than the killing of cells or specific arrest in a particular phase of the cell cycle. Thus, human RNase 1 fused to a ligand of cell surface molecules, such as the FGF receptor, is shown to be an effective candidate for a selective cell targeting agent with low toxic effects on normal cell types.

Amino Acid Sequence↗
PubMed1999

Reconstruction of full-thickness lower eyelid defects using a blepharoplasty technique with a hard palate mucosal graft.

The authors report a method of reconstruction of a full-thickness lower eyelid defect using a blepharoplasty technique utilizing excess skin of the lower eyelid with a hard palate mucosal graft. In all patients the hard palate mucosa took well, and good functional and aesthetic results were obtained. The most suitable indication of this technique might be for the defect occurring horizontally (for which direct closure is difficult to apply) and located in the lateral side of the lower eyelid (when a large amount of excess skin can be utilized). The authors conclude that although the shape and size of the defect to which this method can be applied is restricted, this is a useful option in the reconstructive methods of a full-thickness lower eyelid defect.

Aged↗
PubMed1999

Left posteroseptal Mahaim fiber associated with marked longitudinal dissociation.

We report a patient who underwent radiofrequency catheter ablation of a left posteroseptal atrioventricular (AV) Mahaim fiber with a marked longitudinal dissociation. During atrial pacing, Wenckebach-type atrioventricular block over the accessory pathway was observed with progressive preexcitation and no change in polarity of the delta waves. The AV conduction curve was discontinuous, with a distinct "jump-up" in local AV conduction time of 84 ms. The earliest ventricular activation was recorded from the posteroseptal portion of the mitral annulus, and the unipolar electrogram from a distal electrode had a high, steep deflection with uniphasic QS-like activity with 62 ms of local AV conduction time.

Adult↗
PubMed1999

Role of diltiazem on tacrolimus pharmacokinetics in tacrolimus-induced nephrotoxic rats.

The effects of diltiazem on tacrolimus pharmacokinetics during tacrolimus-induced nephrotoxicity were studied. In normal rats, co-administration of diltiazem significantly increased AUC(0-infinity) of tacrolimus and reduced total body clearance, Cltot, after intravenous and oral administration. In tacrolimus-induced nephrotoxicity, AUC(0-infinity) of tacrolimus increased 40.7%, while the apparent volume of initial distribution space, Vd1, the apparent volume of steady-state distribution space, Vdss, and Cltot decreased 27.4%, 19.5% and 27.4%, respectively, as compared with the control. Co-administration of diltiazem lowered the AUC(0-infinity) of tacrolimus 36.2% and increased Vd1i.v. 62.8% in Vdss 45.9% and Cltot(i.v) 59.0% in tacrolimus-induced nephrotoxicity, resulting in partial improvement in renal function. These pharmacokinetic alterations due to diltiazem contrasted with those seen in normal rats. As a result, the pharmacokinetic parameters in tacrolimus-induced nephrotoxicity with coadministration of diltiazem resembled those in control rats. Mean tacrolimus concentrations in kidney cortex and medulla in a tacrolimus nephrotoxic group given diltiazem were 33.1% and 44.7% lower than those in a nephrotoxic model due to tacrolimus alone. But the tissue/blood concentration ratio of tacrolimus did not change regardless of the presence of diltiazem. Our findings suggest that co-administration of diltiazem has an advantageous effects on tacrolimus pharmacokinetics to protect against tacrolimus-induced nephrotoxicity.

Animals↗
PubMed1999

Examination of local anti-inflammatory activities of new steroids, hemisuccinyl methyl glycolates.

To overcome the side effects of steroids, novel steroid-17-yl methyl glycolates with succinyl group at C-20, derived from prednisolone and dexamethasone were prepared based on a concept of the antedrug. Their topical anti-inflammatory activity and systemic effects were evaluated through croton oil-induced ear edema and paper disk granuloma bioassay. Among them, (20S)-succinyl dexamethasone derivatives (7 and 11) indicated more potent anti-inflammatory activity than the parent dexamethasone and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss. Both 7 and 11 were immediately metabolized into active compound 3 and this metabolite was eliminated with mean half-lives of 0.786 to 0.866 h in rat serum. Our findings suggest that these two compounds might be candidates as the novel steroids, and that that introduction of the succinyl group into the methyl glycolates at C-20 is useful to avoid suppression of organs due to the side effects of corticosteroids.

Adrenal Glands↗
PubMed1999

Quantitative analysis of surface P-wave morphology in isthmus ablation for type 1 atrial flutter: differentiation between complete isthmus block and slow isthmus conduction.

Changes in P-wave morphology in inferior leads during atrial pacing at the margins of the carvo-tricuspid isthmus have been reported to be useful for predicting the creation of isthmus block in radiofrequency (RF) ablation of type I atrial flutter (AFL). However, it is not known whether these changes in P-wave morphology allow the clinician to differentiate between complete isthmus block and slow isthmus conduction. P-wave morphology during low lateral right atrial (LLRA) pacing, as well as during coronary sinus ostium (PCS) pacing, was evaluated prior to ablation, during slow isthmus conduction, and after complete isthmus block in 30 patients with AFL. Changes in P-wave morphology during LLRA pacing were not sufficient to differentiate between complete isthmus block and slow isthmus conduction. While changes in P-wave morphology in lead II from inverted to biphasic during PCS pacing were observed in both slow isthmus conduction and complete isthmus block, the ratio of the positive component to the total P-wave amplitude (P-wave ratio) was significantly different between slow isthmus conduction (20+/-17%) and complete isthmus block (40+/-11%) (P<0.0001). When the P-wave ratio in lead II during PCS pacing was more than 75% of the F-wave ratio in lead II during AFL, bilateral complete isthmus block was predicted with a sensitivity of 88%, a specificity of 71%, a positive predictive value of 75%, and a negative predictive value of 85%. These results indicate that a P-wave ratio greater than 20% or a P-wave ratio during PCS pacing greater than 75% of the F-wave ratio during AFL may predict a bidirectional complete isthmus block.

Aged↗