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M Toda

Publications and source records attributed to M Toda.

At least 55 records · Page 3Linked to original sources
PubMed2000

Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma.

BACKGROUND: We have recently demonstrated an increased number of glucocorticoid receptor-beta (GRbeta)-positive cells in steroid-insensitive subjects with severe asthma. Insensitivity to steroids may be a major contributing factor in fatal asthma; however, no such direct evidence has been report previously. OBJECTIVE: Our aims were to investigate the expression of GRbeta immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, within the airways of patients who died of slow-onset fatal asthma and to compare its expression in patients with emphysema and in nonasthmatic subjects who died of unrelated causes. Sections from airways, both large and small, were obtained from 7 patients who died of asthma, 6 who died from emphysema, and 8 who died from nonpulmonary diseases. Sections from lungs of 6 patients with mild asthma whose lungs were resected for carcinoma were also included as controls. METHODS: Tissue samples were processed for immunocytochemistry with a polyclonal antibody to GRbeta with use of the avidin-biotin technique and with monoclonal CD3, major basic protein, CD68, and elastase antibodies with the alkaline phosphatase-anti-alkaline phosphatase technique. Sequential immunocytochemistry was performed to phenotype the GRbeta immunoreactive cells. Tissue sections from both large (>2 mm) and small (<2 mm) airways were examined. RESULTS: There was a significantly greater number of GRbeta immunoreactive cells in fatal asthma compared with emphysema and controls (P <.001 and P <.05, respectively). There was no difference in the expression of GRbeta in emphysema compared with controls. GRbeta immunoreactivity was also significantly higher in fatal asthma compared with mild asthma. The expression of GRbeta in the small airways of patients with severe asthma did not differ significantly from that in the large airways. The majority of GRbeta-positive cells were T cells and to a lesser extent eosinophils, macrophages, and neutrophils. CONCLUSION: The results of this study support the association of GRbeta expression with fatal asthma and suggest that alternative anti-inflammatory agents need to be considered in the acute setting for patients who are not responding to steroid therapy.

Asthma↗
PubMed2000

Seasonal changes in calcium homeostasis affect the incidence of postoperative tetany in patients with Graves' disease.

BACKGROUND: We have found that postoperative tetany occurs in patients with Graves' disease who have secondary hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant with transient hypoparathyroidism after surgery. There are seasonal variations in serum 25-hydroxyvitamin D (25[OH]D) concentrations. The purpose of this study was to investigate the effects of seasonal changes in calcium homeostasis on the incidence of postoperative tetany in patients with Graves' disease who undergo subtotal thyroidectomy. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25(OH)D, and 1,25-dihydroxyvitamin D (1,25[OH]2D) in female patients with Graves' disease who underwent subtotal thyroidectomy during the summer (n = 89) and during the winter (n = 89). RESULTS: The serum levels of calcium, magnesium, and 25(OH)D were significantly higher, but iPTH levels and 1,25(OH)2D levels were lower in summer than in winter. The percentage of vitamin D deficiency (25(OH)D < 25 nmol/L) was 23% in summer and 62% in winter (P < .001). iPTH was below the detection limit on the first postoperative day in 15 patients (13.8%) in summer and in 13 patients (11.4%) in winter. In summery, tetany developed in only 4 of 15 patients and in one patient whose iPTH level was below normal (incidence of tetany, 5.6%). In winter, however, tetany developed in 6 of 13 patients and in 4 patients whose iPTH level was below normal (incidence of tetany, 11.2%). CONCLUSIONS: Patients with Graves' disease are more susceptible to calcium and vitamin D deficiency during the winter than during the summer, resulting in the tendency toward a higher incidence of postoperative tetany in winter.

Adult↗
PubMed2000

Calcium and its regulating hormones in patients with graves disease: sex differences and relation to postoperative tetany.

OBJECTIVE: To find out why female sex is the most important risk factor for tetany, as calcium and bone metabolism may differ between the sexes. DESIGN: Prospective study. SETTING: Thyroid centre, Japan. PATIENTS AND METHODS: 45 men (mean age 35 years, SD 13) and 178 women (mean age 33 years, SD 12) with Graves disease treated by subtotal thyroidectomy. INTERVENTIONS: Measurement of serum concentrations of intact parathyroid hormone (iPTH), calcium, electrolytes, 25-hydroxyvitamin D (25 (OH) D), and 1,25-dihydroxyvitamin D (1,25 (OH) 2D). MAIN OUTCOME MEASURES: Mean values of these substances, together with reductions in serum calcium concentration, relative youth, increased alkaline phosphatase activity, large goitre, and increased serum TSH binding inhibitory globulin concentration. RESULTS: Women had significantly lower calcium concentrations than men (mean (SD) 2.37 (0.13) compared with 2.43 (0.07), p = 0.003). Serum calcium concentrations correlated significantly with concentrations of 25 (OH) D (p < 0.001). 121 of the women (68%) compared with 13 (29%) of men had vitamin D deficiency as defined as 25 (OH) D < 25 nmol/l (p < 0.05). 15 patients (8%) developed tetany postoperatively compared with I man (2%, p = 0.2). CONCLUSION: Women with Graves disease are more susceptible to calcium and vitamin D deficiency than men, which may account for the higher incidence of postoperative tetany among women with the disease.

25-Hydroxyvitamin D 2↗
PubMed2000

Comparison of Fas- versus perforin-mediated pathways of cytotoxicity in TCR- and Thy-1-activated murine T cells.

T cell-mediated cytotoxicity can be triggered by cross-linking of TCR or Thy-1 surface proteins. While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it was not clear which mechanism was utilized by Thy-1-triggered signals and which pathway of cytotoxicity was triggered at low levels of antigen expression. It is shown that glycophosphatidylinositol-linked surface glycoprotein Thy-1 preferentially activates FasL-Fas- but not perforin-mediated cytotoxicity. This is explained by the lesser intensity of Thy-1-mediated signaling in T cells. The data suggest that Thy-1-triggered Fas-mediated cytotoxicity is completely dependent on cross-talk between Thy-1 and TCR signals since mutations in TCR-CD3 complex molecules or inhibition of tyrosine kinases or calcineurin abolished or strongly inhibited Thy-1-triggered FasL-Fas-mediated cytotoxicity. Lower concentrations of antigenic peptide or levels of cross-linking with anti-TCR-CD3 mAb are required to trigger Fas-mediated than perforin-mediated cytotoxicity by different cytotoxic T lymphocyte (CTL) lines and clones, and it is shown that cross-linking of Thy-1 is much less efficient in triggering accumulation of second messengers (intracellular Ca(2+)) than cross-linking of TCR on CTL. Taken together, these data reflect the possibility of differential activation of FasL and/or perforin pathways of cytotoxicity depending on the nature of activating stimuli and surface receptor.

Animals↗
PubMed2000

Identification of a sequential B-cell epitope on major allergen (Cry j 1) of Japanese cedar (Cryptomeria japonica) pollen in mice.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis is one of the most common allergic diseases in Japan. B cell epitopes on Cry j 1, a major allergen of CJ pollen, have been analyzed by the specific monoclonal antibodies to Cry j 1, and most of these epitopes may be conformational, but no previous report has addressed the analysis of sequential epitope mapping with synthetic peptides. The main purpose of the present study is to identify IgE and IgG B cell epitopes on Cry j 1 by using a synthetic peptide approach in mice. METHODS: We synthesized 35 overlapping peptides that cover the entire length of Cry j 1 and examined whether mouse IgE and IgG antibodies produced by immunization with Cry j 1 reacted to the Cry j 1 peptides. RESULTS AND CONCLUSION: We found that mouse IgE and IgG antibodies reacted strongly to Cry j 1 peptide No. 15 ((141)GVEPVHPQDGDALTLRTATN(160)), though those antibodies did not react with other peptides. IgE and IgG antibody binding to peptide No. 15 was completely inhibited by Cry j 1 and the peptide. To determine the minimum epitope in peptide No. 15, we conducted an ELISA inhibition test. IgE and IgG antibody binding to peptide No. 15 was inhibited by smaller peptides of this peptide. We found the core of the epitope to be (145)VHPQDGDA(152).

Allergens↗
PubMed2000

Interleukin-9 upregulates mucus expression in the airways.

Interleukin (IL)-9 has recently been shown to play an important role in allergic disease because its expression is strongly associated with the degree of airway responsiveness and the asthmatic-like phenotype. IL-9 is a pleiotropic cytokine that is active on many cell types involved in the allergic immune response. Mucus hypersecretion is a clinical feature of chronic airway diseases; however, the mechanisms underlying the induction of mucin are poorly understood. In this report, we show that IL-9 regulates the expression of a subset of mucin genes in lung cells both in vivo and in vitro. In vivo, the constitutive expression of IL-9 in transgenic mice results in elevated MUC2 and MUC5AC gene expression in airway epithelial cells and periodic acid-Schiff-positive staining (reflecting mucous glycogenates). Similar results were observed in C57BL/6J mice after IL-9 intratracheal instillation. In contrast, instillation of the T helper 1-associated cytokine interferon gamma failed to induce mucin production. In vitro, our studies showed that IL-9 also induces expression of MUC2 and MUC5AC in human primary lung cultures and in the human muccoepidermoid NCI-H292 cell line, indicating a direct effect of IL-9 on inducing mucin expression in these cells. Altogether, these results suggest that upregulation of mucin by IL-9 might contribute to the pathogenesis of human inflammatory airway disorders, such as asthma. These data extend the role of the biologic processes that IL-9 has on regulating the many clinical features of asthma and further supports the IL-9 pathway as a key mediator of the asthmatic response.

Animals↗
PubMed2000

[Effects of Ramadan fasting on the health of Muslims].

The fasting month of Ramadan is the ninth lunar month of the Islamic calendar. It is the most important month for Muslims because in which the Qur'an was revealed, and they abstain from food and drink from dawn to sunset to express their gratitude to God. Eating and drinking is permitted only at night, and Muslims typically eat two meals each day, after sunset and just before dawn. People tend to stay up late watching TV with the family, praying or reading the Qur'an. Ramadan teaches Muslims self-restraint and reminds them of the feelings of the impoverished. On the other hand, the biological effects of changes in lifestyle during Ramadan may also be expected. Some studies have reported substantial weight loss, signs of dehydration, raised serum concentrations of uric acid and cholesterol, etc. during Ramadan. However, these changes are unlikely to have much effect on healthy individuals, because generations of Muslims have undertaken fasting year after year. In conclusion, the observance of the Ramadan fast may produce some ill-effects in patients with some disease, e.g. hypertension, hypercholesterolaemia, hyperuricaemia, hyperglycaemia, and heart, liver and kidney disease.

Cholesterol↗
PubMed2000

Alpha-glucosidase inhibitors from clove (Syzgium aromaticum).

The ellagitannins, casuarictin and eugeniin, were isolated as rat intestinal maltase inhibitors from methanol extracts of clove (Syzgium aromaticum). Eugeniin showed inhibitory activity with an IC50 value of 10(-3) M. A structure-activity relationship study among the isolates and their related compound, penta-O-galloyl-beta-D-glucose, indicates that an increasing number of galloyl units in the molecule might lead to an increase in the inhibitory activity. Eugeniin also inhibited maltase activity toward the human intestinal epithelial cell line, Caco-2.

Animals↗
PubMed2000

[A clinical study of the nonrecurrent inferior laryngeal nerve in seven patients].

Nonrecurrent inferior laryngeal nerves (NRILNs) are generally discovered during thyroid or parathyroid gland surgery. If the presence of the NRILN is unknown, nerve injury can easily occur during surgery. Here we report seven cases of NRILN, describe how to identify a NRILN, and discuss whether preoperative or postoperative examination is necessary. Between October 1998 and March 2000, we performed cervicotomy in 1889 patients for thyroid and parathyroid disease and identified a NRILN in 7 of them (0.37%). A NRILN was found in 7 of 903 patients (0.78%) on the right side but in none of 855 patients on the left. The NRILN branched off the vagus nerve at the level of the upper or middle third of the thyroid in 5 patients, and in the other 2 patients branched off the vagus nerve at the level of the lower third of the thyroid. We had not predicted the presence of NRILN before surgery in any of these 7 NRILN patients. Clinically, three patients with NRILN had mild dysphagia and the sensation of a foreign body in the throat. Three patients had abnormal chest X-ray findings showing a linear aortic arch shadow, a sign regarded as evidence of arteria lusoria. Three patients underwent MR angiography, and an aberrant right subclavicular artery was identified. Surgery was performed safely, and no postoperative vocal cord palsy occurred in any of the seven NRILN patients. It is to some extent possible to predict the presence or absence of NRILN by routine diagnostic examinations before surgery for thyroid and parathyroid disease. We emphasize that digital subtraction angiography, MR angiography, or barium esophagography is not necessary for all patients before surgery, since NRILN is a relatively rare anomaly, and such examinations are either invasive or not cost-effective. When a NRILN has been identified during surgery, there is no need to examine for the presence of a vascular anomaly: Its presence is a matter of course. Surgery must be performed however, with knowledge of the possibility of a NRILN.

Abnormalities, Multiple↗
PubMed2000

[Comparison between repeated antigen and acetylcholine-induced bronchoconstriction in development of airway wall thickness in a chronic guinea pig model of asthma].

Asthma is associated with a chronic remodeling of the airways, but it remains to be elucidated whether repeated bronchoconstriction (BC) influences any structural attributes of the lungs. To investigate the role of repeated BC on the morphology of the airways, we chronically exposed guinea pigs to an aerosol of acetylcholine (ACH) over a period of 6 months. The guinea pigs were challenged with either ACH or saline daily for 10 days and thereafter were challenged once a week. To compare repeated BC with a chronic model of allergic inflammation, an additional group of animals were sensitized to aerosolized ovalbumin (OA) and subsequently exposed with OA. The airway wall area and basement membrane (BM) thickness were measured by standard morphometric techniques. Both airway wall area and BM thickness were significantly increased in OA exposed guinea pigs compared with both saline control and AHC-exposed guinea pigs. Our results suggest that persistent bronchoconstriction and/or allergic airway inflammation in asthmatics may contribute to the thickness of the airway wall observed in this disorder. However, repeated acute bronchoconstriction events may not contribute to the increase in the airway wall or BM thickness.

Acetylcholine↗
PubMed1999

Extracapsular invasion of lymph node metastasis. A good indicator of disease recurrence and poor prognosis in patients with thyroid microcarcinoma.

BACKGROUND: The majority of patients with thyroid microcarcinoma have a favorable prognosis. However, some patients may die from this tumor. Although the incidence of microcarcinoma is high, to the authors' knowledge no histologic risk factors have been identified. The objective of this study was to establish risk factors for patients with thyroid microcarcinoma. METHODS: The histologic findings for 1743 surgically excised thyroid microcarcinomas (</=10 mm in greatest dimension) and simultaneously obtained lymph nodes from 324 microcancer patients were reexamined to determine risk factors. Follow-up for the patients was 11.2 +/- 6.3 years (mean +/- standard deviation). These thyroid carcinomas were classified according to the World Health Organization Histological Classification system, and lymph node involvement was classified into two groups: those patients with extracapsular invasion of the lymph node metastasis (ECI) (62 patients) and those patients without (1681 patients). A Fisher exact test, an F test, univariate and multivariate proportional hazards regression analyses, and a Kendall correlation measurement were performed. RESULTS: No undifferentiated tumors were found among the microcarcinomas. During the follow-up period, 1643 of 1743 patients were alive without recurrence, 25 were alive with recurrence, 71 had died of thyroid-unrelated diseases including 2 patients with recurrence, and 4 had died of recurrent thyroid carcinoma. In total, recurrence was noted in 31 patients. Multivariate proportional hazards regression analysis revealed that the absence of Graves disease (risk ratio = 5) and the presence of ECI (risk ratio = 7) were significant risk factors for disease recurrence. Univariate analysis revealed that patient age and the presence of ECI were significant risk factors for thyroid carcinoma-related deaths. CONCLUSIONS: The presence of ECI of lymph node metastasis in patients with thyroid microcarcinoma was found to be a significant indicator of disease recurrence and a poorer prognosis.

Adult↗
PubMed1999

Suppression of an actin-binding protein, drebrin, by antisense transfection attenuates neurite outgrowth in neuroblastoma B104 cells.

Drebrins, actin-binding proteins, are dominantly expressed during embryogenesis and accumulated in neurite processes of postmigratory neurons. While the cytoskeletal proteins are the important factors for regulating neurite outgrowth, the cellular mechanism in neurons is still unclear. To address the role of drebrins in the neurite outgrowth, we have studied the effect of suppression of drebrin on a rat neuroblastoma B104 cell line, which constitutively expresses drebrin. Deprivation of serum or addition of gangliosides in the culture medium induced remarkable neurite outgrowth of B104 cells. We transfected B104 cells with an antisense construct of human drebrin E cDNA and found that the drebrin expression was significantly reduced in the stable antisense cell lines. In response to serum deprivation and gangliosides treatment, their ability to extend neurite processes was significantly attenuated. In contrast, the cell proliferation of the antisense transfectants was arrested by serum deprivation similar to control B104 cells. These data suggest that the drebrins are required for neurite outgrowth in neuronal cells.

Animals↗
PubMed1999

Frequency of clonally expanded T cells evaluated by PCR from a single cell.

In analyses of antigen-specific immune responses, it is essential to estimate the frequency of individual T cell clonotypes. This frequency has been estimated, however, only indirectly by the frequency of T cell receptor (TCR) mRNA. We have developed a method to determine T cell frequency directly by cell count using reverse transcription polymerase chain reaction (RT-PCR) amplification of TCR beta genes from single cell-derived cDNA (single cell PCR). In a study of clinical samples, the frequency of clonally expanded T cells estimated by TCR frequency analysis was found to be higher than that by single cell PCR. Single cell PCR can estimate T cell frequency accurately, as it is not affected by skewed PCR amplification or different TCR mRNA expressions in individual T cells.

Arthritis, Rheumatoid↗
PubMed1999

Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity.

The success of cancer gene therapy is likely to require the targeting of multiple antitumor mechanisms. One strategy involves the use of attenuated, replication-competent virus vectors, such as herpes simplex virus type 1 (HSV-1) mutant G207, which is able to replicate in human tumor cells with resultant cell death and tumor growth inhibition, yet is nonpathogenic in normal tissue. In this study, we demonstrate that infection of established tumors with G207 also induces a highly specific systemic anti-tumor immune response. In a syngeneic, bilateral established subcutaneous tumor model, with mouse CT26 colorectal carcinoma cells in BALB/c mice or M3 melanoma cells in DBA/2 mice, unilateral intratumoral inoculation with G207 caused a significant reduction in the growth of both the inoculated and contralateral noninoculated tumors. This elicited anti-tumor response is dependent on viral infection of the tumor, as intradermal inoculation of G207 in BALB/c mice had no effect on CT26 tumor growth. Treatment of subcutaneous CT26 tumors by intratumoral inoculation of G207 induced a tumor-specific T cell response. CD8+ cytotoxic T lymphocyte (CTL) activity was generated that recognized a dominant "tumor-specific" major histocompatibility complex (MHC) class I-restricted epitope (AH1) from CT26 cells. In immune-competent animals, G207 is acting as an in situ tumor vaccine. Therefore, intratumoral G207 inoculation is able to inhibit tumor growth both by local cytotoxic viral replication in tumor cells and induction of a systemic anti-tumor immune response.

Animals↗
PubMed1999

Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter pupillae.

Mechanisms of relaxation induced by nerve stimulation were examined in isolated porcine iris sphincter muscle in reference to norepinephrine, nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) and the functional interaction of inhibitory and excitatory nerves. Changes in isometric tension were recorded in strips of the sphincter pupillae, which were stimulated by transmurally applied electrical pulses. The presence of neurons containing acetylcholinesterase and tyrosine hydroxylase (TH) was determined histochemically. Transmural electrical stimulation (0.5-20 Hz) produced a frequency-related contraction, which was reversed to a relaxation by atropine in prostaglandin F2alpha-contracted strips. The relaxant response was abolished by timolol and suppressed by metoprolol, a beta1-adrenoceptor antagonist, but was not influenced by butoxamine, a beta2-receptor antagonist. Norepinephrine-induced relaxations were also attenuated only by timolol and metoprolol. Treatment with NG-nitro-L-arginine, a NO synthase inhibitor, and [D-p-Cl-Phe6,Leu17]VIP, a VIP receptor antagonist, did not inhibit the neurogenic relaxation. Contractions induced by nerve stimulation were potentiated by timolol and physostigmine but not by the NO synthase inhibitor. In the sphincter muscle, cholinesterase- and TH-positive nerve fibers and bundles were histologically detected. It is concluded that porcine iris sphincter is innervated by cholinergic excitatory and adrenergic inhibitory nerves. The neurogenic relaxation is associated solely with activation of beta1 adrenoceptors by norepinephrine but is not mediated by NO or VIP.

Acetylcholinesterase↗
PubMed1999

Presymptomatic detection and treatment of Japanese carriers of the multiple endocrine neoplasia type 2A gene.

DNA extracted from the peripheral blood leukocytes of 36 members of five families with multiple endocrine neoplasia (MEN) type 2A was analyzed for mutations of exons 10, 11, 13, 14, and 16 of the RET proto-oncogene by nonisotopic polymerase chain reaction-single-strand conformation polymorphism analysis and automated DNA sequencing. Germline mutations were found in all 9 of the affected individuals and in 6 of the 27 individuals of unknown status. A 70-year-old man who had been completely asymptomatic before genetic diagnosis underwent left adrenalectomy and total thyroidectomy, and was found to have pheochromocytoma and multifocal micromedullary thyroid carcinoma (MTC). A 32-year-old man and a 15-year-old boy, with elevated calcitonin levels detected by the C-cell-stimulation test, but no evident thyroid tumor, underwent total thyroidectomy. Histopathological diagnosis revealed multiple micro MTCs. A 7-year-old girl without evidence of a thyroid tumor or an elevated calcitonin level is being followed up. The remaining two subjects with an evident thyroid tumor and elevated calcitonin levels refused surgery. These results suggest that genetic screening for MEN type 2 afflicted family members can facilitate the presymptomatic detection of gene carriers. Thus, we must carefully evaluate whether immediate prophylactic total thyroidectomy is indicated for gene carriers of MEN 2A without an evident thyroid tumor or elevated calcitonin levels.

Adolescent↗
PubMed1999

IgE reactivity to alpha1 and alpha2 chains of bovine type 1 collagen in children with bovine gelatin allergy.

BACKGROUND: Anaphylactic reactions to measles, mumps, and rubella vaccines, including gelatin as a stabilizer, have been reported. It had been found that most of these reactions to live vaccines are caused by the bovine gelatin included in these vaccines. Gelatin mainly includes denatured type I collagen, which consists of alpha1 and alpha2 chains. OBJECTIVE: The current study was designed to investigate the IgE reactivity to alpha1 and alpha2 chains of bovine type I collagen in gelatin-sensitive children. METHODS: Serum samples were taken from 10 children who had anaphylaxis to the vaccines and high levels of specific IgE to bovine gelatin. Bovine type I collagen was isolated from bovine skin and then separated to alpha1 and alpha2 chains by column chromatography. IgE reactivity to denatured type I collagen and its alpha1 and alpha2 chains was analyzed by immunoblotting, ELISA, and histamine release from the mast cells passive sensitized with IgE antibodies in pooled serum of the children. RESULTS: All children had specific IgE to bovine type I collagen. Furthermore, IgE antibodies in their sera reacted with the alpha;2 chain but not with the alpha1 chain. Similarly, the mast cells sensitized with pooled sera in the children showed alpha2 chain-specific histamine release but not alpha1 chain-specific histamine release. CONCLUSION: In gelatin allergy denatured bovine type I collagen is a major allergen and IgE-binding sites exist in the alpha2 chain of type I collagen.

Anaphylaxis↗