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Biomedical subjects

A Shibata

Publications and source records attributed to A Shibata.

At least 127 records · Page 7Linked to original sources

Analysis of heart-infiltrating T-cell clonotypes in experimental autoimmune myocarditis in rats.

Experimental autoimmune myocarditis (EAM) resembles the lethal giant cell myocarditis seen in humans, and the recurrent forms lead to dilated cardiomyopathy (DCM). EAM in rats induced by a subcutaneous injection of cardiac myosin has been shown to be a T cell-mediated autoimmune disease. Alpha beta T cells have proved to be important by the observation that antibodies to alpha beta T-cell receptor (TCR) prevent disease progression. Alpha beta cells recognize antigenic peptides bound to major histocompatibility (MHC) molecules by alpha beta TCR, and complementarity determining region 3 (CDR3) is considered the most important region for antigen recognition. To elucidate the nature of this T cell-mediated myocarditis, we analyzed TCR V beta chains of heart-infiltrating T cells. In the early state of EAM, none of 22 TCR V beta chain transcripts seemed to be dominant by reverse transcription-polymerase chain reaction analysis of total RNA and flow cytometric analysis. On the other hand, single-strand conformation polymorphism analysis of TCR V beta 8.2, V beta 8.5, V beta 10, and V beta 16 cDNA amplified by polymerase chain reaction encompassing the CDR3 revealed oligoclonal expansion in heart-infiltrating T cells isolated from animals at various disease stages. cDNA encoding V beta CDR3 from heart-infiltrating and pericardial effusion T cells in rats with EAM revealed more restricted sequences than did cells from rats with normal spleens. Clones from distinct lesions of the same animal were identical, and clones from heart-infiltrating and pericardial effusion T cells from the same animal showed overlap. Thus, CDR3 of the TCR beta chain may be important in rat EAM, and heart infiltrating T cells are considered to recognize the specific antigen.

Amino Acid Sequence↗

Activity immediately before the onset of non-fatal myocardial infarction and sudden cardiac death.

To investigate triggers for the occurrence of acute myocardial infarction (AMI) and sudden cardiac death (SCD), we examined the activities immediately before the time of onset in 149 cases of non-fatal AMI and 110 cases of SCD. All of the cases in which death occurred within 24 h from the onset of the underlying cause were considered SCD as long as the cause of death was of cardiac origin or unknown. We calculated the average time which is spent on each activity in the life cycle of Japanese people and estimated the number of incidence of each activity assuming a uniform distribution. Estimated values and actual values were compared. The results were as follows: 1) The incidence of non-fatal AMI and SCD was low while sleeping or resting or doing light work, and was high while using the toilet or doing sport or heavy work. 2) the incidence of SCD was also high even during moderate exertion, such as taking a bath or, walking or cycling, and it was significantly higher than that in the group of non-fatal AMI. 3) The incidence of non-fatal AMI was high while eating or drinking. 4) Many of the patients with SCD had past histories of circulatory diseases, compared to those with non-fatal AMI. This difference in past histories may account for the high incidence of SCD during moderate exertion.

Activities of Daily Living↗

Long-term results of radiofrequency catheter ablation in non-ischemic sustained ventricular tachycardia with underlying heart disease. Nonuniform arrhythmogenic substrate and mode of ablation.

This study examined 12 VTs in 8 patients who underwent radiofrequency (RF) catheter ablation for ventricular tachycardia (VT) associated with non-ischemic underlying heart diseases, and who were followed-up for more than 24 months after ablation. The site of VT origin was determined to be within a narrow site (within 1.0 x 1.0 cm) in 5 VTs (4 patients), but VT originated from a wide origin (more than 1.0 x 1.0 cm) in the other 5 VTs (3 patients). The remaining patient had two macroreentrant VTs revolving around an anatomical obstacle in both the clockwise and counterclockwise directions. Two of 5 VTs originating from a narrow site were successfully ablated by 2-3 RF applications. In VT associated with a wide origin, two perpendicular linear RF lesions with 6.0 +/- 1.8 RF applications were required to ablate the VT. Eight of the 12 VTs (66.7%) were finally ablated by RF current (30-50 watts), and they did not recur during the follow-up period of 31.2 +/- 6.5 months. An excellent long-term outcome is expected, even in VT associated with non-ischemic underlying heart disease, if VT is successfully treated by RF ablation.

Adult↗

Suppression of fluid accumulation following pericardial inflammation in a patient with primary chylopericardium.

The patient was a 50-year-old woman with primary chylopericardium. Triglyceride rich chyloid fluid was continuously drained from the pericardial space through an indwelling catheter. A surgical procedure was scheduled since a medium chain triglyceride diet was insufficient to control the fluid accumulation. Before the operation, inflammatory signs were apparent around the indwelling catheter and the catheter was removed immediately. The inflammation was easily treated with antibiotics, and the pericardial effusion no longer accumulated during a follow-up period of 10 months. The inflammatory process may have caused fibrin production and tissue adhesion in the pericardial cavity, and these might have prevented an accumulation of chyloid fluid and occluded the connection between the thoracic duct and the pericardial cavity.

Catheters, Indwelling↗

Clinical characteristics and EPS-guided therapy in 142 cases of sustained ventricular tachycardia.

One hundred and forty-two consecutive patients with sustained monomorphic ventricular tachycardia (VT) were investigated. Only 26.1% of VTs were associated with ischemic heart disease (IHD). The induction rate of sustained VT upon electrophysiologic study (EPS) was 82.9% in patients with IHD and 65.3% in non-IHD. Of 76 inducible sustained VTs, pharmacologic therapy was finally selected in 35 cases, ablative therapy in 25 and surgical therapy in 12. Long-term prognosis was compared between groups divided according to type of ventricular arrhythmia induced at final EPS after antiarrhythmic therapy as follows: Group A: complete suppression of VT, Group B: clinical or non-clinical nonsustained VT, Group C: clinical sustained VT. The event rate in IHD was 6.3% in Group A, 44.4% in Group B and 100% in Group C. In non-IHD, the event rate was 24.0%, 25.0% and 75.0% (Groups A, B and C, respectively). Complete suppression of VT showed a good prognosis in IHD, however, a slightly higher recurrence rate was observed in non-IHD. In ablative therapy, some recurrences and sudden deaths were observed in spite of complete suppression of both VTs in both the IHD and non-IHD groups. Review of the efficacy of antiarrhythmic procedures is recommended during the follow-up period.

Aged↗

Abnormal function of platelet G proteins in long QT syndrome.

Several hypotheses have been proposed for the pathophysiology of the congenital long QT syndrome, however, the underlying mechanism has not yet been elucidated. This study evaluated G protein function in patients with congenital long QT syndrome (LQTS) and compared it with that of normal subjects. Platelet-rich plasma was collected and the cyclic AMP (cAMP) level of platelets was measured in three conditions utilizing radioimmunoassay: the basal state (Basal cAMP), after stimulation by PGE1 (PGE1-cAMP), and after stimulation by PGE1 followed by inhibition by adrenaline (Adr-cAMP), and the results were compared between 7 LQTS patients and 10 healthy volunteers (control). Gs function was defined as (PGE1-cAMP)/(Basal cAMP) and Gi function as ¿(PGE1-cAMP)-(Adr-cAMP)¿/(PGE1-cAMP). Basal cAMP was lower in patients than in the controls: 2.9 +/- 0.6 pmol/ 10(8) cells vs. 4.2 +/- 0.7 pmol/10(8) cells (p < 0.05). The increase in cAMP after PGE1 was similar in the two groups but the peak was lower in the patients: 16.8 +/- 6.2 pmol/10(8) cells vs. 24.8 +/- 7.4 pmol/10(8) cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2 +/- 5.8 pmol/10(8) cells vs. 16.2 +/- 7.6 pmol/10(8) cells and the change was significantly smaller in the patients than in the controls: 0.17 +/- 0.12 vs. 0.38 +/- 0.16 (p < 0.05). Basal cAMP was weakly correlated with sinus cycle length (r = -0.48, p > 0.3) and QTc was correlated with Gs function (r = 0.52, p > 0.3) but not with Gi function. Patients with associated Torsade de Pointes had a significantly lower Gi function compared to those without (p < 0.05). In LQTS patients, G protein function was abnormal and the abnormality was associated with clinical characteristics of long QT syndrome. The relationship between the abnormal G protein function and the regulation of the repolarization of the ventricular myocardium needs to be studied further.

Adolescent↗

Induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: a clinical study of 10 cases, including a fatal [correction of fetal] case with thromboembolism.

Ten patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Eight of 10 patients achieved complete remission (CR), and among the 8 newly diagnosed cases, 7 achieved CR. Five of 8 CR cases remained in CR after 8 to 30 months. Except for hypotension and a large gastric ulcer resulting from hyperhistaminemia, the adverse effects of ATRA were generally mild. Severe thrombotic tendency occurred in a patient treated with ATRA combined with tranexamic acid. Intensive chemotherapy consisting of daunorubicin (DNR) and other agents was scheduled for the patients who achieved CR with ATRA.

Adult↗

Severe cryoglobulinemia in a patient with asymptomatic hepatitis C virus infection.

A patient with severe type II cryoglobulinemia after ten years of asymptomatic hepatitis C virus (HCV) infection is reported. Laboratory data showed hypergammaglobulinemia with polyclonal IgG and monoclonal IgM, blood hyperviscosity, high level of cryocrit (60%), HCV viremia, and normal levels of serum transaminases. Due to cold exposure, acrocyanosis and cardiac ischemic attack occurred; he recovered after being artificially warmed. Administration of prednisolone and natural interferon-alpha for three months resulted in significant decreases in the levels of serum IgM and cryocrit.

Cryoglobulinemia↗

Flushing pattern and idiopathic avascular necrosis of the femoral head.

A cooperative hospital-based case-control study of idiopathic avascular necrosis of the femoral head (IANF) was carried out to clarify the involvement of smoking, drinking, flushing pattern, and other factors in the development of IANF comparing 90 cases (64 males and 26 females) without history of systemic corticosteroid use with 180 matched controls (128 males and 52 females). The results of analyses were represented only for male subjects because of small number of female cases. There was no significant difference in smoking habits, daily and cumulative number of cigarettes smoked between case and control groups. Current drinkers had obviously higher risk (OR = 11.47) of IANF compared to nondrinkers or exdrinkers. In addition, there was a consistent risk increase with increasing alcohol consumption and the highly significant dose-response relationship remained unchanged after adjustment for all other factors (chi 2 = 14.33, p < 0.001 and chi 2 = 13.24, p < 0.001 for daily and cumulative alcohol consumption, respectively). For flushing pattern, although nonflushers had a significantly elevated risk (OR = 2.08) in the univariate analysis, the association disappeared (OR = 0.73) after adjustment for alcohol and other factors. Since nonflushers tend to be heavy drinkers, perhaps, an apparent risk increase among nonflushers may be due to alcohol drinking. Body mass index (BMI) was inversely related to the development of IANF. The risk reduction was found among subjects with higher BMI and an adjusted linear trend of OR was significant (chi 2 = 6.65, p < 0.05). However, further studies were required regarding the association between flushing pattern or BMI and IANF because of a few reports. History of liver diseases and occupational history were not significantly associated with the development of IANF after adjustment for other factors.

Adult↗

Serum G-CSF levels in primary myelofibrosis and chronic neutrophilic leukemia as estimated by the highly sensitive chemiluminescence enzyme immunoassay (CLEIA).

We previously reported that serum granulocyte colony stimulating factor levels of chronic myelogenous leukemia patients in chronic phase (CP) are significantly lower than those of healthy persons or other hematological malignancies as assessed by chemiluminescence enzyme immunoassay (CLEIA). In this study, we clarify the difference in serum G-CSF levels between patients with primary myelofibrosis (PMF, myelofibrosis with myeloid metaplasia; MMM) and those with secondary myelofibrosis caused by several hematological disorders, using the same highly sensitive CLEIA method. It is clearly demonstrated that serum G-CSF levels of the patients with PMF and chronic neutrophilic leukemia (CNL) are extremely low, similar to those in patients with CML in CP in this study. From these data, it is speculated that the abnormal proliferation of granulocytes in PMF and CNL may not be due to the stimulation by G-CSF, and that a negative feedback mechanism might exist between peripheral granulocytes and serum G-CSF.

Biomarkers↗

Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY.

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.

Antigens, CD↗

[Evaluation of image quality of medical facsimile as a radiological image recording system].

We examined the usefulness of a new medical facsimile (MFAX) system in recording and transmitting various kinds of medical images, including X-ray images and colored histopathologic images. The system consists of an image scanner, a magnetic disk for image storage, a transmission circuit and a thermal image printer. Transmission time for a FCR (Fuji computed radiography) image by super-fine mode was 6 minutes. We used ROC (receiver operating characteristics) curves to evaluate the ability of eight radiologists to detect the small simulated nodules placed on an anthropomorphic chest phantom and shown on MFAX images. The radiologists observed both the FCR films and MFAX copies and determined the presence or absence of simulated nodules using five confidence levels. The results obtained for FCR films and MFAX images showed no statistically significant difference.

Humans↗

Pathogenetic analysis of five cases with a platelet disorder characterized by the absence of thromboxane A2 (TXA2)-induced platelet aggregation in spite of normal TXA2 binding activity.

Five patients with mild bleeding tendencies characterized by defective thromboxane A2 (TXA2)-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TXA2. Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA2 mimetic (STA2)-induced platelet responses, including IP3 formation, Ca2+ mobilization, phosphatidic acid formation and GTPase activities were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. However, in the remaining two patients, these responses were all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mechanisms other than the TXA2 receptor-phospholipase C pathway are also involved in TXA2-induced platelet aggregation.

Adult↗

Clonal analysis of bilateral breast cancer.

Forty-nine pairs of bilateral breast tumors (41 synchronous and 8 asynchronous cases) were examined for X-chromosome inactivation status and p53 mutations to address the issue of their clonality. Among 12 cases that were informative for the trinucleotide repeat polymorphism in exon 1 of the androgen receptor gene on the X chromosome, 3 cases were found to have different alleles of the locus inactivated in the right and left breast tumors, indicating that the two tumors arose from distinct transformed cells. Thirteen tumors (13%) from 11 women (22%) contained somatic mutations in exons 5-8 of the p53 gene. In two cases, both breast tumors harbored p53 mutations, but the specific mutations were not identical. Seven synchronous and two asynchronous cases had p53 mutations in one tumor only. A germ line p53 mutation at codon 248, one of the most common p53 mutations in Li-Fraumeni syndrome, was observed in one case. Immunohistochemical analysis of p53 protein with a monoclonal antihuman p53 antibody showed concordant positivity between the right and left tumors in three bilateral breast cancer cases. Our results suggest that at least some bilateral breast tumors originate from distinct cells, but that some bilateral breast tumors may be related through a common p53 abnormality.

Adult↗

Plasma tissue factor pathway inhibitor in disseminated intravascular coagulation: comparison of its behavior with plasma tissue factor.

In order to assess the clinical implication of tissue factor pathway inhibitor (TFPI) in disseminated intravascular coagulation (DIC), plasma concentrations of TFPI were measured together with plasma tissue factor (TF) in 30 healthy subjects and 49 patients with DIC associated with a variety of underlying diseases. The mean TFPI concentration was elevated in patients with DIC at presentation (205.8 +/- SD 79.1 ng/ml) as compared with healthy subjects (97.3 +/- 22.2 ng/ml, P < 0.001). The mean plasma TF concentration in patients with DIC (412.7 +/- 445.7 pg/ml) was also higher than that in healthy subjects (137.5 +/- 50.6 pg/ml, P < 0.001). Elevated TF levels were found predominantly in patients with DIC caused by cancer and leukemia, whereas TFPI was elevated in all underlying disease categories. Plasma TFPI concentration did not correlate with plasma TF. In addition, hemostatic markers of DIC such as thrombin-antithrombin complex, prothrombin fragment 1 + 2, plasmin-plasmin inhibitor complex, FDP or fibrinogen did not correlate with TFPI. Serial determinations of plasma TFPI in each patient demonstrated that the behavior of TFPI was independent of the changes in plasma TF and other hemostatic parameters. These findings indicate that plasma TFPI does not decrease in DIC and is not valuable for monitoring the progress of DIC.

Disseminated Intravascular Coagulation↗

High frequency of chromosome 9p allelic loss and CDKN2 tumor suppressor gene alterations in squamous cell carcinoma of the bladder.

BACKGROUND: In the Western Hemisphere, 90% of bladder cancers are transitional cell carcinomas, while only 7% are classified as squamous cell carcinomas. In contrast, in Egypt and regions of the Middle East and Africa, where infection by the trematode Schistosoma haematobium is endemic, squamous cell carcinoma is the most common bladder cancer as well as the most common cancer in men. PURPOSE: We planned experiments to understand the genetic defects underlying the development of squamous cell carcinoma and to determine if the morphologically and clinically distinct squamous cell carcinoma and transitional cell carcinoma of the bladder evolve following different genetic alterations. METHODS: Squamous cell carcinoma specimens from high-risk (Egypt, n = 19) and low-risk (Sweden, n = 12) populations were examined for genetic defects known to be involved in transitional cell carcinoma tumorigenesis. Homozygous deletions of the CDKN2 tumor suppressor gene were detected by comparative multiplex polymerase chain reaction. Mutations in the CDKN2 and p53 (also known as TP53) genes were analyzed by single-strand conformation polymorphism and DNA sequencing. Immunohistochemical staining of p53 protein was also performed. Allelic losses in chromosome arms 9p, 9q, and 17p were determined by microsatellite analysis. RESULTS: Homozygous deletions and sequence mutations in the CDKN2 gene were found in 67% (eight of 12) of squamous cell carcinoma specimens, a frequency three times higher than that reported for uncultured transitional cell carcinomas (P = .009). Hemizygous and homozygous deletions in 9p, where CDKN2 resides, were found in 92% (11 of 12) of uncultured squamous cell carcinomas, while only about 39% (35 of 90) of transitional cell carcinomas showed these losses (P = .001). Deletions in 9p with no change in 9q were found in 92% (10 of 11) of squamous cell carcinomas compared with only 10% (11 of 110) of transitional cell carcinomas (P < .001) reported in the literature. The frequency of p53 mutations in squamous cell carcinomas was similar to that reported for invasive transitional cell carcinomas (60%), but the type and position of mutations differed between the two tumor types. Allelic losses in chromosome arm 17p, where the p53 gene resides, were found to be less frequent in squamous cell carcinomas (38%) than in invasive transitional cell carcinomas (60%). CONCLUSIONS: Our results suggest that a putative tumor suppressor gene on 9p, possibly CDKN2, may contribute to squamous cell carcinoma tumorigenesis. Our data on squamous cell carcinoma and previously reported data on transitional cell carcinoma indicate that these two bladder carcinomas differ in their genetic alterations, suggesting that distinct underlying genetic defects may explain, at least in part, the pathological differences between the two tumors of the bladder epithelium. IMPLICATIONS: Development of diagnostic and therapeutic strategies for squamous cell carcinoma of the bladder based on its distinct genetic alterations is warranted.

Alleles↗

Catheter ablation of ventricular tachycardia with radiofrequency currents, with special reference to the termination and minor morphologic change of reinduced ventricular tachycardia.

During catheter ablation with radiofrequency (RF) currents, the incidence of the termination of reentrant ventricular tachycardia (VT) during application of RF energy and the morphologic change of the reinduced VT were analyzed. Twenty-five patients (20 men and 5 women, aged 44 +/- 17 years) were studied. After induction of monomorphic sustained VT, the ablation site was determined by endocardial activation mapping, identification of isolated mid-diastolic potential, and pacing during tachycardia. Thirty-six monomorphic VTs were induced in 25 patients and terminated with programmed stimulation. The cycle length was 323 +/- 55 ms and all VTs were entrained with rapid ventricular pacing. The target site was the earliest site of activation of VT in 26 VTs in 16 patients, and the area of slow conduction in 10 VTs in 9 patients. VT was terminated soon after the application of RF currents in 33 VTs in 22 patients at 6.0 +/- 3.1 seconds, and VT was induced immediately after the cessation of RF currents in 11 patients. Of these, 4 patients with idiopathic left ventricular VT had an alternation in the QRS configuration before catheter ablation and required repeat ablation of the other VT morphology. In the other 7 patients, such morphology was not observed before ablation, but was observed in VT induced when the original VT was terminated. Repeated attempts of catheter ablation 2 to 9 times at the remapped site was, however, successful in 7 of 8 VTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Spatial orientation of the reentrant circuit of idiopathic left ventricular tachycardia.

In 6 patients with idiopathic left ventricular VT, the spatial orientation of the reentrant circuit was estimated from the results of transient entrainment of VT with rapid pacing at different sites. The entrance to the area of slow conduction was located toward the outflow tract, whereas the exist was located at the apicoposterior area of the left interventricular septum.

Adult↗