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Biomedical subjects

K Uno

Publications and source records attributed to K Uno.

At least 37 records · Page 2Linked to original sources

Anthracycline-induced cardiomyopathies evaluated by tissue Doppler tracking system and strain rate imaging.

OBJECTIVES: Anthracycline cardiotoxicity is known to occur from the subendocardial side of the left ventricular wall. Recent advances of tissue Doppler echocardiography may allow the evaluation of anthracycline cardiotoxicity by dividing the left ventricular wall into the subendocardial half and subepicardial half. The present study assessed the feasibility using the tissue Doppler echo tracking system (M-mode) and myocardial strain rate imaging (B-mode) to noninvasively detect anthracycline cardiotoxicity. METHODS: The tissue Doppler echo tracking system (M-mode) was used to measure systolic thickening of the subendocardial layer (delta Endo), subepicardial layer (delta Epi), and whole wall (delta Total) of the left ventricular posterior wall in 41 normal subjects and three groups of patients receiving anthracycline: 34 patients in the low dose group, 19 in the middle dose group, and 12 in the high dose group. Strain rate is the spatial gradient of local velocities, reflecting local compression and expansion rates not affected by overall heart motion. Myocardial strain rate imaging (B-mode) was used in 25 normal subjects, 9 patients in the low dose group, and 10 patients in the high dose group. The ratio of peak systolic strain rate of subendocardium to that of subepicardium (peak strain rate endo/epi), and the ratio of integrated strain rate during ejection time of subendocardium to that of subepicardium (integrated strain rate endo/epi) were measured. RESULTS: Tissue Doppler echo tracking system (M-mode) measurement of delta Endo/delta Epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, whereas delta Total failed to show significant differences. Myocardial strain rate imaging (B-mode) measurement of integrated strain rate endo/epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, but ejection fraction failed to show statistically significant differences. CONCLUSIONS: These methods are highly sensitive tools for monitoring anthracycline cardiotoxicity.

Anthracyclines↗

[Cord blood transplantation with two mismatched HLA loci in a child with acute lymphoblastic leukemia in second remission: follow-up of minimal residual disease using a clone-specific probe].

A 9-year-old girl with acute lymphoblastic leukemia in second remission underwent cord blood transplantation (CBT) from an HLA-mismatched (2 loci by serotype, 3 loci by genotype) unrelated donor. The infused nucleated cell count was 1.95 x 10(7)/kg. FK506 and mini-MTX were used to prevent graft-versus-host disease (GVHD), but grade II acute GVHD developed on the skin (stage III). The GVHD subsided after administration of corticosteroid, but marked hyperglycemia developed, which required transient insulin therapy for its control. Minimal residual disease (MRD) was assessed using a clone-specific probe for the JH region. MRD was positive before CBT, but became negative one month after CBT. Now, at 14 months after CBT, the patient is in a disease-free state without detectable MRD. These observations suggest that CBT with two mismatched HLA loci can be performed safely, and that sequential analysis of MRD is useful for evaluation of the disease status after CBT.

Blood Donors↗

[Transient myelodysplasia associated with human parvovirus B19 infection in a child without underlying disease].

Human parvovirus B19 (HPV-B19) infection is known to frequently induce aplastic crisis in patients with hemolytic anemia, but rarely causes hematological disorders in healthy subjects. We report a 5-year-old boy who showed transient myelodysplasia associated with HPV-B19 infection. He was admitted with severe nasal bleeding, and laboratory data showed marked thrombocytopenia (1,000/microliter), anemia (Hb: 8.4 g/dl), and mild leukopenia (3,000/microliter). A bone marrow smear revealed myelodysplastic changes in three cell lineages, but no giant proerythroblasts or megakaryocytes. The pancytopenia and myelodysplastic changes were resolved spontaneously within a week without any medication other than transfusion of red blood cells and platelets. Serological examination revealed an elevation of IgG antibody against HPV-B19 on days 15 and 120 and its subsequent decrease thereafter, although HPV-B19-specific DNA was not detected in the serum at onset. The clinical course and laboratory data suggest an etiologic role of HPV-B19 infection in the occurrence of transient myelodysplasia.

Child, Preschool↗

Electrocardiographic and echocardiographic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy and in their pedigrees.

Electrocardiographic and echocardiographic evaluations in 18 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and 29 family members (25 males and 25 females from 7 pedigrees) aged 5 to 64 years (mean +/- 1 SD 30 +/- 16) revealed that 5 of 28 ARVC family members (17%) fulfilled ARVC Task Force criteria. Indexes on late potentials of the signal-averaged electrocardiogram had a significant linear correlation with the age of patients with ARVC and of family members with echocardiographic wall motion abnormality.

Adolescent↗

Tbx5 and the retinotectum projection.

Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the Tbx5 gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.

Animals↗

Single site radiofrequency catheter ablation of atrial fibrillation: studies guided by simultaneous multisite mapping in the canine sterile pericarditis model.

OBJECTIVES: To test the hypothesis that when activation of Bachmann's bundle (BB) is critical to the unstable reentrant circuits that maintain atrial fibrillation (AF) in the sterile pericarditis canine model, a lesion in BB would prevent induction of stable AF. BACKGROUND: One mechanism of induced AF in this model is multiple unstable reentrant circuits, which frequently include BB as part of the reentrant pathway. METHODS: Simultaneous multisite mapping studies during AF and after ablation of BB were performed by recording (384 to 396 electrodes) from both atria and the atrial septum during six induced AF episodes in six dogs with sterile pericarditis. Activation maps of AF (mean duration, 24 +/- 28 min) during 12 consecutive 100-ms windows were analyzed. RESULTS: During AF, multiple unstable reentrant circuits (mean, 1.2 +/- 0.2 per window; range, 1 to 4) were observed, 68% involving BB. Nonactivation zones (mean duration, 57 +/- 16 ms in the right atrium and 53 +/- 23 ms in the left atrium) observed during AF were reactivated by a wave front most often coming from the atrial septum via BB (right atrium, 62%; left atrium, 67%). After successful radiofrequency catheter ablation of the midportion of BB, AF >5 s was not induced in all dogs. Mapping studies of transient AF (< or =5 s) induced after ablation showed neither reentrant circuits nor wave fronts activating the right atrium via BB. CONCLUSIONS: In this AF model, catheter ablation of BB terminates and prevents the induction of AF by preventing 1) formation of unstable reentrant circuits that involve BB, and 2) activation of the atrial-free walls after a nonactivation period.

Animals↗

Expression of thrombopoietin receptor and its functional role in human B-precursor leukemia cells with 11q23 translocation or Philadelphia chromosome.

Thrombopoietin (TPO) is a hematopoietic growth factor which plays a central role in normal megakaryocytopoiesis and thrombopoiesis. Although the interaction between TPO and its receptor c-Mpl encoded by the c-mpl gene is now known to be implicated in the proliferation and/or differentiation of abnormal myeloid cells and normal hematopoietic stem cells, little is known about a role of the TPO/c-Mpl system in lymphoid leukemia cells. In the present study, we first examined the expression of c-mpl/c-Mpl in 23 human lymphoid leukemic cell lines (T-lineage 4, B-lineage 19) using three distinct methods. The c-mpl mRNA was detectable in as many as 20 cell lines (T-lineage 3, B-lineage 17) by reverse transcriptase-polymerase chain reaction, but its translated product, c-Mpl, was demonstrable by Western blot only in B-lineage cell lines. Flow cytometric analysis revealed the surface c-Mpl expression in 13 of 17 B-lineage cell lines, but its higher expression (>40%) was restricted in nine B-precursor cell lines, eight of which had 11q23 translocation or Philadelphia chromosome (Ph1). We also demonstrated that two of eight cell lines with 11q23 translocation or Ph1 exhibited a significant proliferative response to TPO in the 3H-thymidine uptake and colony-forming assays. Triggering of these cell lines by TPO transiently up-regulated tyrosine phosphorylation of JAK-2 and Shc, indicating that their receptor is functional. Primary leukemia cells separated from patients with B-precursor acute lymphoblastic leukemia with Ph1 or 11q23 translocation also showed the surface c-Mpl expression and a significant responsiveness to TPO. These results suggest that the TPO/c-Mpl interaction may play a physiological role in the growth regulation of B-precursor leukemia cells particularly with specific chromosomal abnormalities.

Antigens, Surface↗

Studies on hemodynamic instability in paroxysmal supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power spectrum analysis on electrocardiographic RR variation.

Hemodynamic instability is a crucial determinant of the best therapeutic option in paroxysmal supraventricular tachycardia (PSVT). However, it is still unclear if hemodynamic instability is tachycardia dependent or independent. We performed frequency-domain analysis of electrocardiographic RR variations during induced PSVT and head-up tilt tests after successful ablation to investigate the role of autonomic vasomotor function in hemodynamic instability during PSVT. Thirty-six patients with (syncope group, n = 18) and without (nonsyncope group, n = 18) syncope and/or presyncope during PSVT were enrolled in this study. Serial blood pressure, heart rate, and variations in heart rate during induced PSVT and head-up tilt tests were examined. Initial blood pressure fall and heart rate changes during induced PSVT were greater in the syncope group than in the nonsyncope group. A significant positive linear relationship was found between these two. Delayed blood pressure fall was observed in the syncope group, independent of heart rate changes. Syncope in PSVT could be predicted from the results of head-up tilt tests with 82% accuracy. Heart rate responses after isoproterenol infusion were significantly greater in the syncope group than in the nonsyncope group. The changes in low frequency to high frequency (LF:HF) values during induced PSVT and head-up tilt tests were significantly greater in the syncope group than in the nonsyncope group, and an exponential correlation was found between LF:HF changes in both tests. We conclude that PSVT rate and vasomotor reaction are related with hemodynamic instability during PSVT and head-up tilt testing is a useful method for determining if patients will have syncope during PSVT.

Adolescent↗

1,21-Henicosanediol.

In the molecular structure of the title compound, C(21)H(44)O(2), the hydrocarbon skeleton has an all-trans conformation. One of the terminal hydroxyl groups is also trans with respect to the skeleton, while the other is gauche. In the crystal structure, the molecules lie parallel to the b axis, forming layers with a thickness of b/2. The packing is similar to that in the smectic A phase of liquid crystals. These features are similar to those of the homologues with an odd number of C atoms, but different from those with an even number.

Journal Article↗

[The significance of cancer screening by immunological parameters].

Provided by the evidences that, in cancer patients, the production of Th 1 cytokines including IL-12, IFN-gamma, and TNF-alpha, is impaired, we asked whether these cytokines can be useful parameters for cancer detection. To the aim 174 patients diagnosed cancer of various organs, and 100 control individuals without cancer were enrolled to the study. We evaluated mitogen-stimulated production of cytokines and induction of Th 1 subset using peripheral blood mononuclear cells in vitro. Th 2 population was measured as the counterpart of Th 1 subset. NK cell activity was also measured. As acquired values did not show the normal distribution we employed a non-parametric test to compare the values between cancer and control. PHA-induced production of IL-12, IFN-gamma and TNF-alpha, in cancer was lower than that in control. Th 1 subset induced in cancer was lower than that in control. We found no difference in Th 2 subset induction between cancer and control. On the other hand, NK cell activity was augmented in cancer patients. When patients were grouped to early stage and advanced stage, both groups showed suppressed production of all three cytokines and suppressed induction of Th 1 cells. Interestingly, none of cytokines nor Th 1 subset differed between the two stages, suggesting that the impaired cytokine production may be a common feature of cancer condition and participate in the etiology of cancer. In contrast, enhanced induction of Th 2 subset was seen in advanced stage compared to early stage, indicating that Th cells might be biased to differentiate to Th 2 cells in advanced stage. From the results IL-12, IFN-gamma, TNF-alpha and Th 1 subset as well as NK activity appear to be promising parameters for cancer detection. Above all, IL-12 and IFN-gamma seem to be the best parameters due to high sensitivity and specificity, and independence from the stage of cancer.

Adult↗

[A boy with summer onset paroxysmal cold hemoglobinuria induced by Donath-Landsteiner antibody with anti-I specificity].

We encountered 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH) in the middle of August. He was admitted due to progressive jaundice and pallor following fever and nausea. Laboratory data revealed severe anemia, increased serum indirect bilirubin and LDH, and decreased serum haptoglobin. Direct/indirect Coombs tests were positive. These findings yielded a diagnosis of autoimmune hemolytic anemia. Serological test for syphilis was negative. The patient's symptoms and signs promptly subsided after treatment with prednisolone, which was started on the 2nd hospital day. The patient has been in a disease-free state for 16 months without any medication. After discharge, he was finally given a diagnosis of PCH because a Donath-Landsteiner test was positive. The antibody belonged to an IgM subclass and showed anti-I specificity. Considering that development of PCH is common in winter, this case was unique because it developed in August. We speculated that exposure to a cool air-conditioned atmosphere prior to hospitalization and the cooling mechanism of the body after admission were involved in the summer onset of PCH and its prolonged clinical course.

Air Conditioning↗

[Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].

The mortality and morbidity associated with residual intracardiac floating thrombi in patients with acute pulmonary thromboembolism remain uncertain. Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary thromboembolism underwent echocardiography within 24 hours from onset of symptoms. Four patients (31%) had floating intracardiac thrombi in the right heart: 3 in the right atrium and one in the inferior vena cava. The time to evaluation by echocardiography was shorter than in the patients without thrombi. The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without adverse effects in these patients. After thrombolysis, clinical symptoms improved and pressure gradient between the right ventricle and right atrium decreased significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding complications occurred in 3 (43%) of the patients who underwent thrombolysis. Right-side intracardiac floating thrombus was easily detectable by early echocardiography. Thrombolytic agents are likely to be effective in patients with intracardiac floating thrombi.

Acute Disease↗

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

Adult↗

New insights regarding the atrial flutter reentrant circuit : studies in the canine sterile pericarditis model.

Background-We studied atrial activation during induced atrial flutter in the canine sterile pericarditis model to test the hypothesis that the atrial flutter reentrant circuit includes a septal component. Methods and Results-We studied 10 episodes of induced, sustained (>5 minutes) atrial flutter in 9 dogs. In all episodes, the reentrant circuit included a septal component. In 6 episodes, there were 2 reentrant circuits, one in the right atrial free wall and the second involving the atrial septum, Bachmann's bundle, and the right atrial free wall; both circuits shared a pathway in the right atrial free wall (figure-of-eight). The direction (superior or inferior) of the septal wave front of the second circuit correlated with the direction (clockwise or counterclockwise, respectively) of the right atrial free-wall circuit. A line of functional block in the right atrial free wall was part of both reentrant circuits. In the other 4 atrial flutter episodes, only 1 reentrant circuit was present, with activation in an inferior-to-superior direction in the septum and a superior-to-inferior direction in the right atrial free wall in 2 episodes and in the opposite direction in the other 2 episodes. In all atrial flutter episodes, the flutter wave polarity in ECG lead II was determined by the direction of activation in the left atrium; polarity was positive when the direction was superior to inferior and negative when the direction was inferior to superior. Conclusions-In this model of atrial flutter, the reentrant circuit (1) always included a septal component, (2) did not always require a right atrial free-wall reentrant circuit, (3) demonstrated figure-of-eight reentry when a reentrant circuit was present in the right atrial free wall, and (4) was associated with a line of functional block in the right atrial free wall.

Animals↗

Involvement of thioredoxin in rheumatoid arthritis: its costimulatory roles in the TNF-alpha-induced production of IL-6 and IL-8 from cultured synovial fibroblasts.

Thioredoxin (TRX) is a cellular reducing catalyst induced by oxidative stress and is involved in the redox regulation of transcription factors such as NF-kappaB. We found that the serum TRX concentration was elevated in patients with rheumatoid arthritis (RA) as compared with values from healthy individuals and patients with osteoarthritis (33.6 +/- 35.1 vs 11.8 +/- 6.6 ng/ml, p < 0.01). Moreover, the TRX concentration in the synovial fluid (SF) was much more elevated in RA patients than in osteoarthritis patients (103.4 +/- 53.3 vs 24.6 +/- 17.4 ng/ml, p < 0.001). Multiple regression analysis revealed that the serum C-reactive protein value was better correlated with the linear combination of SF TNF-alpha and SF TRX values than with SF TNF-alpha alone, suggesting that TRX might play a subsidiary role in the rheumatoid inflammation. We thus examined the effect of TRX on the TNF-alpha-induced IL-6 and IL-8 production using rheumatoid synovial fibroblast cultures. The extents of IL-6 and IL-8 production in response to TNF-alpha were greatly augmented by TRX as compared with TNF-alpha alone. TRX alone did not have such effects. We also found that TRX appeared to accelerate the nuclear translocation of NF-kappaB, a major transcriptional regulator for production of IL-6 and IL-8 on stimulation with TNF-alpha. Consistent with these findings, the IkappaBalpha phosphorylation at Ser32 and its subsequent degradation in response to TNF-alpha was facilitated by TRX. These findings indicate that the elevated TRX concentration in SF of RA patients might be involved in the aggravation of rheumatoid inflammation by augmenting the NF-kappaB activation pathway.

Adjuvants, Immunologic↗