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Biomedical subjects

K Tsunoda

Publications and source records attributed to K Tsunoda.

At least 37 records · Page 2Linked to original sources
PubMed2000

Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus.

The development of experimental models of active autoimmune diseases can be difficult due to tolerance of autoantigens, but knockout mice, which fail to acquire tolerance to the defective gene product, provide a useful tool for this purpose. Using knockout mice lacking desmoglein 3 (Dsg3), the target antigen of pemphigus vulgaris (PV), we have generated an active disease model for this autoantibody-mediated disease. Dsg3(-/-) mice, but not Dsg3(+/-) littermates, produced anti-Dsg3 IgG that binds native Dsg3, when immunized with recombinant mouse Dsg3. Splenocytes from the immunized Dsg3(-/-) mice were then adoptively transferred into Rag-2(-/-) immunodeficient mice expressing Dsg3. Anti-Dsg3 IgG was stably produced in the recipient mice for more than 6 months without further boosting. This IgG bound to Dsg3 in vivo and disrupted the cell-cell adhesion of keratinocytes. Consequently, the recipient mice developed erosions in their oral mucous membranes with typical histologic findings of PV. In addition, the recipient mice showed telogen hair loss, as found in Dsg3(-/-) mice. Collectively, the recipient mice developed the phenotype of PV due to the pathogenic anti-Dsg3 IgG. This model will be valuable for developing novel therapeutic strategies. Furthermore, our approach can be applied broadly for the development of various autoimmune disease models.

Animals↗
PubMed2000

Time course of left ventricular remodeling after myocardial infarction: a two-dimensional echocardiographic study.

In order to forecast the clinical course of acute myocardial infarction (MI), the time course of the functional changes of the left ventricular myocardium that result in remodeling was evaluated with two-dimensional echocardiography (2DE). The study group comprised 45 patients with anterior MI treated with successful percutaneous transluminal coronary angioplasty. 2DE studies were performed on days 1, 3, 7 and 14; months 1 and 3 and 1 year after MI, and the following parameters were recorded: (1) infarcted wall thickness, (2) traced length of the endocardium and of the epicardium on end-diastolic apical long axis images, and (3) wall motion score (total of asynergy scores of 16 segments of left ventricle (LV); normal: 0, hypokinesis: 1, akinesis: 2, dyskinesis: 3). According to the peak creatine kinase (CK) level, patients were classified into L group (CK > or =8000 U/L, n=16), M group (8000> CK > or =4000, n=13) and S group (CK <4000, n=16). The following results were obtained. (1) There was progressive thinning of the infarcted myocardium up to 1 month after (1 day: 9.3+/-1.7, 14 days: 6.3+/-1.7 vs 1 month: 5.9+/-1.8 mm, p<0.05; vs 1 year: 5.9+/-1.9 mm, NS). (2) Dilatation of the LV cavity occurred shortly after MI and continued up to 14 days (endocardium at 14 days: 176.8+/-13.6 vs 1 day: 164.1+/-11.4 mm, p<0.01; vs 1 year: 176.3+/-12.7 mm, NS). (3) The wall motion score improved rapidly by 14 days, and continued to improve gradually to 1 year (1 day: 12.2+/-3.4, 14 days: 6.8+/-4.0, 1 year: 4.6+/-3.1). (4) The expansion ratio (endocardial length at 14 days/1 day) was significantly greater in the L group than in the S group (p<0.05). Comparing the groups, the LV cavity of the L group remained dilated up to 14 days, whereas that of the S and M groups was dilated up to 7 days (L group 14 days: 179.3+/-11.9 vs 1 day: 156.9+/-9.2mm, p<0.01; vs 1 year: 180.0+/-14.1 mm, NS) (S group 7 days: 171.7+/-13.6 vs 1 day: 161.5+/-7.2 mm, p<0.01; vs 1 year: 172.7+/-14.4 mm, NS) (M group 7 days: 170.5+/-10.5 vs 1 day: 157.7+/-14.5 mm, p<0.05; vs 1 year: 177.08+/-9.6 mm, NS). Serial 2DE on days 1 and 14 after MI were useful for evaluating the course of LV remodeling and to forecast cardiac function in the chronic phase of MI. Determining the length of hospital stay on the basis of infarction size is justified.

Aged↗
PubMed2000

Hoarse voice resulting from premature ageing in Werner's syndrome.

Werner's syndrome is characterized by clinical signs of premature ageing. A 42-year-old man presented with three-year history of hoarseness. Also noted were skin atrophy of the face and hands, ulcerations around the ankles, and a history of cataracts. A clinical diagnosis of Werner's syndrome was made. Laryngoscopy revealed bowed vocal folds resulting in a spindle-shaped defect with glottal incompetence during phonation. Examination also revealed decreased maximum phonation time and vocal fatigue. At surgery, atrophy of the vocalis muscle was noted. Furthermore, degeneration of muscle fibres was noted in the temporalis muscle. The atrophic changes in the vocal folds that occur with ageing and result in an increased fundamental frequency were seen in this patient. The characteristic hoarseness of Werner's syndrome appears to be the result of premature ageing of the vocal-folds.

Adult↗
PubMed2000

Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history.

Islet-1 (Isl-1) is one of the transcription factors that play an important role for the formation of the islet cells. We scanned the Isl-1 gene in 77 Japanese type 2 diabetic patients with a family history and found a heterozygous nonsense mutation (Q310X) in 1 diabetic patient. The mutation was not found in 180 nondiabetic subjects. This mutation is located in the putative transactivation domain and deletes 40 amino acids of the COOH-terminal lesion. The Q310X mutant exhibited a 50% reduction in activity compared with the wild-type when tested for stimulation of transcription of a human amylin promoter-linked luciferase reporter gene in betaTC3 cells. The patient was a 49-year-old nonobese man who was diagnosed as having type 2 diabetes at 32 years of age and has been treated with sulfonylureas. The mutation was found in his mother, who has type 2 diabetes, and in his 14-year-old daughter, who has normal glucose tolerance but a relatively low insulin response. This is the first reported finding of Isl-1 gene mutation in type 2 diabetes. Although Isl-1 is not a common predisposing gene for Japanese type 2 diabetes, the mutation in this gene may be a rare cause of diabetes in isolated families.

Adolescent↗
PubMed1999

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma and the effect of angiotensin converting enzyme (ACE) inhibitor.

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma was developed to evaluate the dynamics of endogenous AT II in various types of hypertension. Detection limit of this method was less than 2.3 pg/ml, and normal value is less than 25 pg/ml. Cross reactivity of antibody with AT I and III was 0.037% and 21%, respectively. There were good correlation between the value measured by direct method, and that of extraction method (r = 0.96, P < 0.01) and plasma renin activity (r = 0.80, P < 0.01). By oral administration of ACE inhibitor (captopril 50 mg), AT II levels were suppressed to 10 pg/ml or less in most patients with essential hypertension, renal parenchymal hypertension and renovascular hypertension up to 2 h. However, AT II levels in patients treated with ACE inhibitors chronically were not different from the AT II levels in patients without ACE inhibitor. In primary aldosteronism AT II was extremely low levels. AT II markedly increased by the stimulation test using furosemide (1 mg/kg i.v.). These results suggest that this method may be useful to clarify the pathophysiology of hypertension and the escape of the inhibition by ACE inhibitor.

Angiotensin II↗
PubMed1999

The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile.

BACKGROUND: Some patients with pemphigus vulgaris (PV) have mucous membrane erosions with minimal skin involvement (mucosal dominant type), and others show extensive skin blisters and erosions in addition to mucous membrane involvement (mucocutaneous type). Patients with pemphigus foliaceus (PF) show only skin involvement. OBJECTIVE: The purpose of this study is to determine whether there is a difference in autoantibody profile among mucosal dominant PV, mucocutaneous PV, and PF. METHODS: Antibody titer against desmoglein 1 (Dsg 1) and desmoglein 3 (Dsg3) were measured with enzyme-linked immunosorbent assay using recombinant Dsg1 and Dsg3. Sera were obtained during clinically active disease from 24 patients with mucosal dominant PV, 20 with mucocutaneous PV, and 23 with PF. RESULTS: All sera samples from patients with mucosal dominant PV sera were negative against Dsgl but positive against Dsg3. All sera samples from those with mucocutaneous PV were positive against both Dsg1 and Dsg3. All sera samples from patients with PF were positive against Dsg1, but negative against Dsg3. CONCLUSION: Each subtype has its own anti-Dsg autoantibody profile, indicating that the clinical phenotype of pemphigus is defined by the autoantibody profile.

Autoantibodies↗
PubMed1999

Cardiovascular effects of dihydrotestosterone in rats.

We conducted a study to evaluate the cardiovascular effects of 5 alpha-dihydrotestosterone (DHT), including the supplementary respiratory effects, using normal and obese groups of Wistar castrated male rats, and the association of the hormonal effect with sudden unexplained nocturnal death syndrome (SUNDS). The hormone-treated normal rats had a significantly greater weight of the right ventricular wall and atria and body weight ratio when compared with the controls. Cardiac function estimated from the parametric value multiplied heart rate by carotid maximum systolic pressure was significantly lowered in the hormone-treated rats, However, no difference in the right ventricular action between the hormone-treated and control rats was found. In respiratory parameters, expired CO(2) gas decreased significantly in the hormone-treated rats. On the other hand, the hormone-treated obese rats showed a significantly greater weight of the heart and body weight ratio. This was due to the significant gain of the ventricular septum weight, in addition to the weight gains of the right ventricular wall and atria. Cardiac function of the hormone-treated obese rats was significantly lower than that of the controls and lower than that of normal rats. Significant increase in respiratory rate and decrease in expired CO(2) gas were seen in the hormone-treated rats. Therefore, these results demonstrate that the hormone had hypertrophic effects mainly on the right ventricle or atria and suppressive effects on cardiovascular function or promotive effects on respiratory ventilation, with both of the latter effects enhanced comparatively in obese rats. These cardiac hypertrophic and ventilatory characteristics according to DHT do not seem to apply to the victims of SUNDS.

Journal Article↗
PubMed1999

Molecular scanning for mutations in the melanocortin-4 receptor gene in obese/diabetic Japanese.

Decreased function of the melanocortin-4 receptor (MC4R) was reported to cause late-onset obesity and insulin resistance in rodents. Thus mutations in the MC4R gene drew strong attention as a possible cause of obesity and diabetes. We screened for mutations in the MC4R gene in extremely obese [body mass index (BMI) > or = 35 kg/m2] Japanese with diabetes by direct sequencing. A heterozygous mutation (V103I) was detected in one case (2.0 %), however the frequency was not significantly different from that in non-obese (BMI < or = 24 kg/m2) and non-diabetic subjects (2.7 %). No other mutations were detected. These results suggest that mutations including V103I in the MC4R gene are not a major cause of obesity or diabetes in Japanese.

Animals↗
PubMed1999

The influence of pregnancy on sensation of ear problems--ear problems associated with healthy pregnancy.

We wondered how many women had experienced a sensation of fullness in the ear during pregnancy. To address this question, data were obtained from a group of healthy women who attended the gynaecology clinic in our hospital as pregnancy cases between February 1995 and January 1998 and who volunteered to participate in our study. A control group was drawn from healthy female co-medical staff members of our hospital who had never been pregnant. The data used for comparing the two groups were taken from a questionnaire about ear problems that was presented to all subjects. The results suggest that ear problems may be increased in pregnancy, particularly for hypotensive pregnant women. However, even for pregnant women complaining of ear problems, pure-tone audiometry and impedance audiometry showed normal hearing in all cases. Furthermore, these women's complaints resolved completely on delivery of their babies.

Acoustic Impedance Tests↗
PubMed1999

Apolipoprotein E polymorphism and plasma lipid levels in Native Mongolian sheep.

Apolipoprotein E (apoE) phenotypes were determined in 199 unrelated native sheep (Khalkhas line) of Central Mongolia, using a polyacrylamide gel isoelectric focusing-immunoblotting technique, and the plasma lipid levels in different phenotypes were assayed enzymatically. Twenty-eight phenotypes were identified in this sheep. In addition to all the previously detected seven apoE variants composing the phenotypes, four new variants were discovered, which were called E8, E9, E10, and E11. From the population data, these were found to be genetically controlled by four codominant alleles, designated APOE8, APOE9, APOE10, and APOE11, based on the same mode of inheritance as in the seven variants. These alleles were detected at a low frequency, in the range of 0.005 to 0.0126. The Khalkhas sheep differed most significantly from the Baruwal and Lampuchhre sheep of Nepal and the Vietnamese sheep with respect to the allele frequencies found in some Asian local sheep previously examined. Type 1/1 and/or 2/7 sheep had significantly higher plasma levels of total cholesterol and low-density lipoprotein cholesterol than type 7/7 sheep (P < 0.05 and/or P < 0.02).

Animals↗
PubMed1999

Percutaneous absorption of biotin in healthy subjects and in atopic dermatitis patients.

The study was designed to test the ability of sequential applications of biotin-containing ointment to increase serum biotin levels. Twenty atopic dermatitis patients (mean age, 20.5 yr) and 11 healthy subjects (mean age, 25.5 yr) volunteered to participate in this study. The diagnosis of atopic dermatitis was established dermatologically. Seven grams per day of ointment containing 0.3% biotin and 1-4 g per day of steroid ointment were both applied sequentially. The healthy subjects applied only biotin ointment. The biotin concentration was determined microbiologically. Before biotin treatment, the average serum biotin level was significantly lower in atopic dermatitis patients than in healthy subjects. The percutaneous application of biotin-containing ointment caused a significant increase in the serum biotin concentration in both healthy subjects (from 41.5 +/- 10.0 to 50.2 +/- 9.2 nmol/L) and in atopic dermatitis patients (from 27.9 +/- 17.4 to 50.7 +/- 21.6 nmol/L), especially in patients whose initial level was low, and also could be effective in regulating the atopic allergic response involving eosinophils. In conclusion, biotin appears to be readily absorbed through both normal and dermatitis-affected human skin.

Absorption↗
PubMed1999

[Cardiovascular responses during laryngeal mask airway insertion in normotensive, hypertensive and chronic renal failure patients].

The hemodynamic response to the insertion of the laryngeal mask airway (LM) following induction with propofol 2 mg.kg-1 was assessed and compared in normotensive (Normal), hypertensive (HT) and chronic renal failure (CRF) patients (n = 23 in each group). Before induction, in HT and CRF groups blood pressure and rate pressure products (RPP) were higher than in Normal group (P < 0.05). Although blood pressure and RPP were decreased in every patient by induction with propofol, no patients needed vasopressor drugs. The decreases of blood pressure and RPP were larger in HT and CRF groups than in Normal group (P < 0.05). There were no differences between groups in heart rate and rate of successful LM insertion. We concluded that LM insertion with propofol 2 mg.kg-1 was an effective induction method preventing the adverse circulatory responses in normotensive, hypertensive and chronic renal failure patients.

Adult↗
PubMed1998

Proximal row carpectomy versus limited wrist arthrodesis for advanced Kienböck's disease.

The outcomes in 20 patients with advanced Kienböck's disease treated by proximal row carpectomy (seven patients) or limited wrist arthrodesis (13 patients) were reviewed retrospectively. Postoperatively, the results were more satisfactory in terms of wrist pain, the range of wrist flexion-extension, and grip strength following limited wrist arthrodesis than after proximal row carpectomy, although the differences were not statistically significant. We recommend scaphotrapeziotrapezoid arthrodesis in selected patients with advanced Kienböck's disease who have a fragmented lunate.

Adolescent↗