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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 109 records · Page 6Linked to original sources

Enhancing effect of dietary oil emulsions on immune responses to protein antigens fed to mice.

Repeated intragastric administration of beta-lactoglobulin (beta-Lg) with emulsified soybean oil elicited an antigen-specific, systemic humoral immune response in different strains of mice. The antibody response was enhanced as the dose of oil was increased and the particle size of emulsions was decreased. Feeding of aqueous beta-Lg could induce the antibody response only when emulsified oil was fed almost simultaneously. However, the emulsion-driven humoral immune response was not observed when mice were treated with anti-CD40 ligand antibody or in athymic mice. It is likely that the intestinal coexistence of emulsified oil with dietary antigens modulates the immune system to crucially support B cell response. A practical application of the present results to the prevention of cow's milk protein sensitization in infants is proposed.

Animals↗

Eosinophil-adhesion-inducing activity produced by antigen-stimulated mononuclear cells involves GM-CSF.

BACKGROUND: The initial step of eosinophil accumulation in allergic inflammation is adhesion of circulating eosinophils to vascular endothelial cells (EC). There is evidence that the adhesive property of circulating eosinophils is upregulated following antigen exposure. Although the exact mechanism remains to be established, cytokine(s) produced by antigen-stimulated mononuclear cells is (are) likely key factor(s). OBJECTIVE: The objective of this study was to examine the factor(s) responsible for eosinophil adhesion and migration induced by the antigen-stimulated mononuclear cells obtained from atopic asthmatics. METHODS: Peripheral blood mononuclear cells (PBMC) isolated from house-dust-mite-sensitive bronchial asthmatics were cultured for 96 h in the presence or absence of 1 microg/ml Dermatophagoides farinae (Df) antigen. Eosinophils were isolated from peripheral blood of healthy subjects. Eosinophil-adhesion-inducing activity in the culture supernatants of PBMC was examined by the ability to modify the adhesion of eosinophils to human pulmonary microvascular endothelial cells (HPMEC) in the presence or absence of anti-cytokine/chemokine antibodies. Eosinophil migration induced by the supernatants was also examined. RESULTS: Eosinophil adhesion to HPMEC was significantly augmented by the supernatants of Df-stimulated PBMC, which was significantly inhibited by anti-GM-CSF, but not by anti-IL-5, anti-RANTES, or isotype-matched controls. On the other hand, eosinophil migration induced by the supernatants was inhibited by anti-GM-CSF and partly by anti-RANTES. CONCLUSION: Both eosinophil adhesion and migration induced by the antigen-stimulated PBMC involve GM-CSF. In contrast, RANTES is involved only in the eosinophil migration. These molecules may participate in the development of eosinophil accumulation at the allergic inflammation sites.

Antigens↗

Molecular characteristics of cutaneous papillomavirus from the canine pigmented epidermal nevus.

To investigate the relation between the canine pigmented epidermal nevus (PEN) and cutaneous papillomavirus, we cloned and sequenced the L1 gene of papillomavirus from the canine pigmented epidermal nevus (PEN). Amplification of DNA sample with the L1 consensus primers yielded an expected fragment of approximately 450-bp. The nucleotide sequences of the fragment showed about 64% of sequence similarity to the L1 region of human papillomavirus isolate CP6108 and less than 57% sequence similarity to those of canine oral papillomavirus (COPV). In situ hybridization determined the presence of papillomavirus DNA mainly in the upper stratum granulosum of skin in this case. The results indicated that the canine cutaneous papillomavirus from the PEN lesion was genetically close to human papillomavirus rather than COPV.

Animals↗

Apoptotic cell death in arrhythmogenic right ventricular cardiomyopathy: a comparative study with idiopathic sustained ventricular tachycardia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a specific heart muscle disease of unknown etiology characterized by fatty and fibrofatty replacement of the right ventricular myocardium. It often manifests life-threatened ventricular arrhythmias. Previous studies have hypothesized that myocyte apoptosis contributes to the myocyte cell loss and fatty change in ARVC and may be induced by recurrent ventricular tachycardia (VT). We examined whether these progressive pathological changes result from apoptotic cell death in both autopsied and biopsied right ventricular myocardium from 35 patients with ARVC by using in situ terminal deoxynucleotidyl transferase assay (TUNEL) and agarose gel electrophoresis. We also studied the biopsied myocardium from 30 patients with idiopathic sustained VT whose origin was the outflow tract of the right ventricle. TUNEL-positive cells indicating DNA fragments were observed in some cardiomyocytes and fibroblasts in ARVC, but the numbers of TUNEL-positive myocytes were very low in idiopathic VT. DNA laddering was confirmed in two autopsied cases in ARVC, but not in a non-cardiac case who died. These results suggest that at least some cardiomyocytes and fibroblasts are subjected to apoptosis in ARVC, leading to the loss of myocardium with characteristic pathological changes and subsequently progressive cardiomyopathy. Furthermore, the apoptotic process may not result from myocardial ischemia due to repetitive VT.

Adolescent↗

Lipid peroxidation levels in rat cardiac muscle are affected by age and thyroid status.

Free radicals, hydroxyperoxides and H(2)O(2) are all known to damage cell components. This study was designed to compare the concentrations of hydroxyperoxide and free radical scavengers in the cardiac muscles of old rats in the hyper- or hypothyroid condition, to determine whether rates of peroxidation would differ with age, thyroid status, or both. Rats were rendered hyper- or hypothyroid by administration of l-thyroxine or methimazole for 4 weeks. Among the old rats, the lipid peroxide (LPO) concentrations, measured as thiobarbituric acid (TBA) reactants, were significantly greater in the hyperthyroid than in the euthyroid state and the LPO concentrations measured as TBA+Fe(3+) reactants, which may be precursors of LPO, were significantly greater in the hyperthyroid state, whereas in young rats, the LPO concentrations measured by TBA or TBA+Fe(3+) methods did not differ significantly in the hyperthyroid state. In the euthyroid state, the concentration of LPO measured as TBA+Fe(3+) reactants was significantly reduced with age. Xanthine oxidase (XOD) activity also was markedly increased with age, being more pronounced in the hyperthyroid than in the euthyroid state. The Mn and Cu/Zn superoxide dismutase activities were greater in the hyperthyroid than in the euthyroid state. Glutathione peroxidase activity decreased with age in the euthyroid and, particularly, in the hyperthyroid state. Catalase activity was not affected in the old rats. Concentrations of alpha-tocopherol in the old rats were high in the hyperthyroid state and low in the hypothyroid state, whereas the levels of beta- and gamma-tocopherols in these rats were unchanged in both conditions as compared with the euthyroid state findings. Data suggest that the site of free radical generation differs in older rats, with additional shifts in the location of intracellular lipid peroxidation being noted during hyperthyroidism. Thus, as rats age, the reduction of the free radical scavenger system and the increase in LPO and XOD activities might induce myocardial dysfunction.

Aging↗

Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice.

A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Thl cell differentiation. When C17.8 was administered from 5 to 30 weeks of age, NOD mice exhibited suppression of both insulitis and diabetes. However, when C17.8 administration ceased at 15 weeks of age, 8 of 13 recipients showed diabetes at 30 weeks of age. These results suggest that IL-12 plays an important role not only in the development of effector cells but also in their activation. In contrast, when C17.8 was injected into 2-week-old female NOD mice for 6 consecutive days, all 16 recipients showed diabetes at 30 weeks of age, whereas 12 of 20 control mice became diabetic. This result suggests that depletion of endogenous IL-12 at a young age results in the enhancement of diabetes. Flow cytometric analysis indicated that activated memory T-cells were present in higher numbers after C17.8 treatment. Transfer of spleen cells from 15-week-old C17.8-treated NOD mice to NOD-scid mice resulted in an earlier onset and a higher incidence of diabetes. Furthermore, administration of C17.8 to 2-week-old NOD mice also resulted in a much earlier onset of diabetes. These results suggest that short-term treatment with anti-IL-12 antibody prohibits IL-2 production at a young age, which may influence the expansion and apoptosis of pathogenic T-cells, resulting in the acceleration of autoimmune diabetes.

Animals↗

Maternity blues and attachment to children in mothers of full-term normal infants.

OBJECTIVE: This study was conducted for evaluating incidence of maternity blues in Japan, in addition to clarifying the relationship between maternity blues and maternal attachment, and the factors involved. METHOD: A questionnaire survey was conducted on 417 mothers having given birth at the Nagoya Daini Red Cross Hospital. The questionnaire consisted of Zung's self-rating depression scale, and a 'postpartum maternal attachment' scale, consisting of subscales on 'core maternal attachment' and 'anxiety regarding children'. The survey was conducted 5.2 days +/-1.46 postpartum. RESULTS: ZSDS scores over 40 amounted to 66.8% of the responses. Analysis of the two scales revealed significant correlation/inverse correlation between 'maternity blues' and 'anxiety regarding children'/ 'core maternal attachment'. Path analysis revealed 'maternity blues' to be influencing 'core maternal attachment' and 'anxiety regarding children'. CONCLUSION: It was found that the incidence of maternity blues may be higher in Japan than was believed previously, and that an intimate association exists between 'maternity blues' and 'postpartum maternal attachment'.

Adult↗

[A clinical study of patients undergoing curative surgery for renal pelvic and ureteral cancers].

We retrospectively studied 30 patients who underwent curative surgery for renal pelvic and/or ureteral cancer between August 1987 and August 1998. Their clinicopathological features were classified by the criteria of the Japanese Urological Association. The 1-, 3-, and 5-year cause-specific survival rates were, respectively, 100, 95.5, and 85.1%, while the disease-free rates were 100, 78.9, and 78.9% by the Kaplan-Meier method. Prognostic factors were evaluated by the log-rank test. The significant prognostic factors were pT3 and pV1 for cause-specific survival (p = 0.0277, p = 0.0025), while pT2 (or higher), grade 3, and pV1 were significant for disease-free survival (p = 0.0271, p = 0.0327, and p = 0.0002). Nine patients who received adjuvant chemotherapy are alive, but 3 patients have relapsed. Chemotherapy did not have a significant effect on the cause-specific survival or disease-free survival.

Adult↗

[Cystolithotripsy for bladder stones: comparison of holmium:YAG laser with Lithoclast as a lithotripsy device].

From March 1995 to March 1999, endoscopic lithotripsy of bladder stones was done for 33 patients. We used Holmium:YAG laser for the initial 23 patients, and the Swiss Lithoclast for the recent 10 patients. We compared the safety and efficacy of the two modalities. Both lithotriptors were safe and effective to fragment the bladder stones. All the patients became stone-free at one session. However, we needed to use the Holmium:YAG laser in one patient to disintegrate the larger fragments after Lithoclast. For a big stone, Holmium:YAG laser is preferable.

Adult↗

[A case of left renal cell carcinoma in a young male adult with left varicocele].

A 25-year-old man presented to our hospital with the chief complaint of left-sided painless scrotal swelling. Varicocele was diagnosed and high ligation was performed. Two months later, he noticed asymptomatic gross hematuria. Transabdominal ultrasonography and abdominal computed tomographic scanning showed a left renal tumor measuring more than 10 cm in diameter. Radical nephrectomy (thoraco-abdominal approach) was performed and pathological diagnosis was granular cell carcinoma (G2, pT2, INF alpha, pNX, pMX). He then received intramuscular injections of interferon-alpha 3 million units on three days per week. The frequency of renal cell carcinoma was reported to be about 1-3% for individuals in the 20s in the recent Japanese literature, and renal cell carcinoma in a young man with left varicocele is very rare.

Adenocarcinoma↗

[Lens epithelial cell damage and apoptosis in atopic cataract--histopathological and immunohistochemical studies].

PURPOSE: To elucidate the relationship between damage of lens epithelial cells and apoptotic cell death in patients with atopic cataract. METHODS: Histopathological and immunohistochemical studies were carried out using anterior lens capsules obtained at surgery from 13 patients with atopic cataract and from 25 patients with senile cataract. RESULTS: No specific histopathological findings were found in the lens epithelial cells in atopic cases. However, the frequency and severity of histopathological findings such as flattening, nuclear pyknosis, and loss of cells were more frequent and more severe in atopic cases than in senile cases. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) method revealed that the mean ratio of cells containing fragmented DNA to whole epithelial cells was almost the same in both atopic and senile cases. However, the mean ratio of Bax-positive cells was significantly higher in atopic cases (mean +/- standard deviation, 29.1 +/- 35.0%) than in senile cases (2.7 +/- 7.0%) (p < 0.05). The mean ratio of Bcl-2-positive cells was significantly lower in atopic cases (1.4 +/- 3.4%) than in senile cases (44.3 +/- 35.7%) (p < 0.05). CONCLUSION: These results suggest that apoptotic cell death may play an important role in the development of lens epithelial cell damage in atopic cataract.

Adult↗

Endoscopic management of impacted ureteral stones using a small caliber ureteroscope and a laser lithotriptor.

PURPOSE: We reviewed our experience with retrograde endoscopy using a small caliber ureteroscope and a laser lithotriptor in 104 consecutive patients with impacted ureteral stones and also analyzed the associated endoscopic findings. MATERIALS AND METHODS: From July 1993 to October 1999 we performed retrograde endoscopic treatment in 104 patients with impacted ureteral stones. Average maximum stone diameter was 15.2 mm. (range 2 to 110), and 9 patients had stones larger than 3 cm. Mean duration of impaction was more than 14 months and the longest was 10 years. We used 6.9Fr rigid or 6.9 to 7.5Fr flexible ureteroscopes and a pulsed dye laser or holmium:YAG laser lithotriptor. RESULTS: Of the 104 ureteral stones 100 (96.2%) were completely fragmented by a single endoscopic procedure. Although 1 uric acid stone could not be disintegrated by either the pulsed dye laser or electrohydraulic lithotripsy early in this series, it was discharged spontaneously 2 weeks after the procedure. Additional extracorporeal shock wave lithotripsy (ESWL*) was required in 3 patients who initially had stones larger than 3 cm. A month after treatment no patient had evidence of residual stones. Using adjuvant ESWL a 100% success rate was attained with minimal morbidity. Endoscopic observation revealed inflammatory polyps of the ureter in 22 patients (21.2%), and stricture adjacent to the stone in 16 (15. 4%). There were no significant complications. CONCLUSIONS: Using a small caliber ureteroscope and a laser lithotriptor we could treat the target stone in all 104 patients with adjuvant ESWL in 3 cases. Endoscopic lithotripsy seems to be effective first line therapy for chronically impacted stones which are frequently associated with chronic inflammation, polyps and strictures, and avoids the futile repetition of ESWL and problems related to the prolonged passage of stone fragments.

Adult↗

[Intracameral and lenticular penetration of locally applied deuterium-labeled vitamin E in rats].

PURPOSE: To confirm the intraocular dynamics of 1% deuterium (D)-labeled alpha-tocopherol acetate (VEA) solution. METHODS: The concentrations of D3-VEA and D3-alpha-tocopherol (VE) derived from D3-VEA in the aqueous humor and lens were measured after instilling 1% D3-VEA continuously into the cul-de-sac of rat eyes for one and three weeks. D3-VEA and D3-VE concentrations were determined by gas chromatograph/mass spectrometry. RESULTS: D3-VEA and D3-VE concentrations in the aqueous humor after one and three weeks of continuous administration were 93.1 and 498.9, and 9.4 and 21.5 ng/ml, respectively. The concentrations in the lens were 15.0 and 6.1, and 9.8 and 4.8 ng/g, respectively. CONCLUSION: The penetration of VEA into the aqueous humor and lens by eyedrop application was confirmed.

Animals↗

[A questionnaire survey on the self-assessment to the asthmatic treatment in Saitama Prefecture: results from 2825 cases].

The aim of this study was to survey the self-assessment to the treatment of adult bronchial asthmatics in Saitama prefecture. A questionnaire on daily symptoms and medications was distributed to 2825 adult asthmatic subjects who were treated at 125 hospitals/clinics in Saitama prefecture between September 15th and October 30th 1998. More than half (52.7%) of patients described that their general condition of asthma was poorly controlled. Even among the patients described that their condition was good or fair, 30.2% of them had some asthmatic symptoms such as shortness of breath or nocturnal awakening. Although inhaled corticosteroids were used in 66.2%, the ratio of patients who used spacer and kept drug compliance as prescribed were 59.6% and 45.8%, respectively. According to the physician's reports, cysteinyl leukotriene antagonist was used in 35.7%, which was comparable to the total of another anti-allergic drugs (37.3%). These results suggest that more than half of asthmatic patients in Saitama prefecture were not satisfied with their conditions of the disease control. Furthermore, more thorough education on the technique and compliance of inhaled corticosteroids would be required.

Adolescent↗

[Inhibitory effect of suplatast tosilate on eosinophil migration].

Suplatast tosilate has been shown to inhibit generation of Th2-type cytokines in vitro and used in the treatment of allergic diseases. Although the exact mechanism remains unknown, this compound attenuates the eosinophil infiltration in the asthmatic airway. In the present study, we examined whether suplatast tosilate directly modulates eosinophil migration in response to inflammatory mediators in vitro. Suplatast did not modify the spontaneous migration of eosinophils. On the other hand, eosinophil migration in response to PAF (1 microM) was significantly inhibited by 1 microM suplatast. Similarly, IL-5 (100 pM)-induced eosinophil migration was inhibited by 1 microM suplatast. These results suggest that suplatast tosilate inhibits eosinophil locomotion in response to PAF or IL-5 and thereby attenuates infiltration of the cells in allergic inflammation.

Anti-Allergic Agents↗

Vascular endothelial growth factor and osteopontin in tumor biology.

Tumor growth and metastasis are angiogenesis-dependent and tumor angiogenesis is a result of complex interplay of positive and negative regulators. Vascular endothelial growth factor (VEGF) occupies a particular place among the positive regulators of angiogenesis due to its potency and specificity for endothelial cells. VEGF upregulates several molecules such as growth factors, adhesion molecules, proteases, and protease receptors and it actually induces microvascular hyperpermeability, resulting in activation of thrombin from prothrombin. Osteopontin (OPN) is a secreted arginine-glycine-asparic acid (RGD)-containing phosphoprotein and it contains a predicted thrombin cleavage site. OPN binds to several integrins and CD44 variants. OPN has diverse functions such as cell adhesion, chemoattraction, and immunomodulation, and it induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. OPN expression is upregulated in human carcinomas. This review documents the functional roles of VEGF and OPN in angiogenesis and their clinical significance in tumor biology.

Animals↗