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Biomedical subjects

S Oka

Publications and source records attributed to S Oka.

At least 37 records · Page 2Linked to original sources

Sustained cytomegalovirus-specific CD4+ T cell response associated with prevention of recurrence of cytomegalovirus retinitis without secondary prophylaxis after highly active antiretroviral therapy in patients with AIDS.

It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Cycloprodigiosin hydrocloride suppresses tumor necrosis factor (TNF) alpha-induced transcriptional activation by NF-kappaB.

Cycloprodigiosin hydrochloride (cPrG.HCl) obtained from a marine bacterium Pseudoalteromonas denitrificans induces apoptotic cell death in various cancerous cell lines. cPrG.HCl alone caused a little cytotoxicity in HeLa cells, but it enhanced the apoptotic process progressively when co-administered with tumor necrosis factor (TNF)alpha. Here we studied the effect of cPrG.HCl on TNFalpha-induced activation of the transcription factor nuclear factor kappaB (NF-kappaB). Luciferase gene reporter assays revealed that cPrG.HCl potently suppressed the TNFalpha- and the phorbol myristate acetate-induced activation of NF-kappaB. The suppression occurred in the presence of imidazole, indicating that it was not related to the intracellular acidification resulting from the intrinsic H(+)/Cl(-) symporter activity of cPrG.HCl. cPrG.HCl inhibited neither the TNFalpha-induced phosphorylation and degradation of inhibitor of nuclear factor-kappaB, nor the subsequent nuclear translocation and DNA binding of NF-kappaB. cPrG.HCl also suppressed NF-kappaB-enhanced gene expression induced by Rac1, Cdc42, MEKK1, inhibitor of nuclear factor-kappaalpha (IKKalpha), IKKbeta, and a subunit of NF-kappaB, p65. These results indicate that cPrG.HCl suppresses NF-kappaB-dependent gene expression through the inhibition of transcriptional activation.

Apoptosis↗

Diagnosis and monitoring of human cytomegalovirus diseases in patients with human immunodeficiency virus infection by use of a real-time PCR assay.

We used a real-time PCR assay to measure human cytomegalovirus (HCMV) DNA load in whole blood and plasma of 70 patients who were infected with human immunodeficiency virus type 1. Break points of 3.0 x 10(3) copies/mL in whole blood and 1.0 x 10(3) copies/mL in plasma were well-correlated with the existence of definite HCMV disease (sensitivity, 93% and 86%; specificity, 89% and 85%; positive predictive value, 70% and 63%; and negative predictive value, 98% and 95%, respectively). In patients with < 50 cells/microL of CD4(+) T lymphocytes, positive predictive values increased to 78% and 71%, respectively. The viral loads of all patients who received anti-HCMV therapy declined to < or =2.0 x 10(2) copies/mL in parallel with the improvement of clinical symptoms. These findings show that the HCMV DNA load quantified with our method is a useful tool for diagnosis of HCMV diseases and for monitoring the disease activity in patients infected with HIV-1.

AIDS-Related Opportunistic Infections↗

Expression of macrophage asialoglycoprotein-binding protein is induced through MAPK classical pathway.

Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found that the expression of M-ASGP-BP mRNA in bone marrow cells was induced during the differentiation into macrophages. To investigate the mechanism by which M-ASGP-BP mRNA expression is induced, we used U937 cells as a model. Treatment of U937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in M-ASGP-BP mRNA expression within 6 h. This induction was completely inhibited by PKC inhibitors, calphostin C, and staurosporine. Furthermore, MAP kinase inhibitors PD98059, but not SB202190, blocked M-ASGP-BP mRNA expression. These data indicate that M-ASGP-BP mRNA expression occurs through the activation of PKC and the MAPK classical pathway in the course of cell differentiation into macrophages.

Animals↗

Identification and characterization of functional domains in a mixed lineage kinase LZK.

The mixed lineage kinase (MLK) family is a recently described protein kinase family. The MLKs contain a kinase domain followed by a dual leucine zipper-like motif. We previously reported the molecular cloning of LZK (leucine zipper-bearing kinase), a novel MLK, and that LZK activated the c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway through MKK7 in cells. Here, we reveal that LZK forms dimers/oligomers through its dual leucine zipper-like motif, and that this is necessary for activation of the JNK/SAPK pathway. We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7.

Amino Acid Sequence↗

Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer.

BACKGROUND AND OBJECTIVES: Limited operations for early gastric cancer (EGC) have been recommended based on data from lymph node (LN) metastasis detected by hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro-LN metastasis detected by cytokeratin (CK) immunostaining. Also, the correlation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated. METHODS: A total of 5,949 LNs from 160 patients with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were stained by CD. RESULTS: The incidence of LN metastasis increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro-LN metastasis increased according to the depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%). The CK-staining patterns were classified into the three subgroups (CK-negative, n = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage of CD-positive cancer cells of primary tumors in clustered type (17.2%) was significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P = 0.0036). CONCLUSIONS: The acidic protease CD may play an important role of cancer metastasis in EGC. The limited operation without lymphadenectomy should be indicated for EGC with CD-negative.

Cathepsin D↗

Pulmonary root translocation for biventricular repair of double-outlet left ventricle.

Double-outlet left ventricle is conventionally repaired with an extracardiac conduit when pulmonary stenosis is present. We report the use of pulmonary root translocation to the right ventricle to construct the posterior wall with autologous tissue and a porcine pericardial monocusp ventricular outflow patch anteriorly for 2 patients with double-outlet left ventricle. This technique allows minimization of pulmonary insufficiency, avoids coronary artery ligation with infundibulotomy, and has a major theoretical advantage for growth potential.

Cardiac Catheterization↗

Repair of total anomalous pulmonary venous connection without cardiopulmonary bypass.

Two infants with asplenia syndrome and pulmonary venous obstruction underwent repair of total anomalous pulmonary venous connection without cardiopulmonary bypass in 1988. Using a side-biting clamp, an anastomosis between the left upper pulmonary vein and left superior vena cava-atrial junction was satisfactorily created without undue instability. Furthermore, both cases had the advantage of efficient growth in the anastomotic site postoperatively.

Anastomosis, Surgical↗

Reoperation for interrupted aortic arch with the use of retrograde cerebral perfusion.

We treated 2 patients with recurrent coarctation after repair of interrupted aortic arch. Because they had been operated on with the use of vascular prostheses, severe scarring was considered prohibitive for safe dissection. We successfully carried out anatomic repair with the use of retrograde cerebral perfusion through a left thoracotomy in both cases.

Adolescent↗

Pulmonary agenesis with interrupted aortic arch.

This report describes a unique case of an infant with right pulmonary agenesis associated with interrupted aortic arch, ventricular septal defect, and aortic valvular stenosis. Blalock-Park arterial anastomosis and pulmonary arterial banding were performed without incidence. These techniques were useful for this complicated heart defect with pulmonary agenesis. The postoperative course of the patient was uneventful.

Abnormalities, Multiple↗

Anatomically corrective repair of complete atrioventricular septal defects and major cardiac anomalies.

BACKGROUND: Although satisfactory results of corrective surgery for atrioventricular septal defects (AVSDs) with complex lesions such as double-outlet right ventricle (DORV) or atrial isomerism have been reported in recent years, the optimal surgical options for isomerism hearts is still a controversial issue. METHODS: We performed anatomically corrective repair on 13 children with balanced forms of complete AVSDs and associated major cardiac anomalies. Eight of the 13 patients had atrial isomerism (right in 1, left in 7), 5 of whom had DORV. Four others had DORV with trisomy 21, and 1 had tetralogy of Fallot. Atrial septation for isomerism with the placement of an additional prosthesis was performed on 4 patients. RESULTS: Two hospital deaths and one late death occurred only in the isomerism group. Three reoperations were required solely in the left isomerism group: one replacement of the valved external conduit concomitantly with reconstruction of the left ventricular outflow obstruction, one mitral valve replacement for severe regurgitation of left atrioventricular valve, and one relief of progressing left ventricular outflow obstruction. CONCLUSIONS: The results of anatomically corrective surgery for AVSDs with major associated cardiac anomalies in the nonisomerism group were excellent. The optimal surgical options for isomerism heart, however, remain a controversial issue.

Double Outlet Right Ventricle↗

Repair of atrial septal defect through a right posterolateral thoracotomy: a cosmetic approach for female patients.

BACKGROUND: Because the operation for atrial septal defect is considered a low-risk procedure, the cosmetic result has become an important issue. Principally for cosmetic reasons, anterolateral thoracotomy is frequently used for closure of atrial septal defect in young female patients. However, in anterolateral thoracotomy, the skin incision frequently crosses the future breast line, which may cause breast and pectoral muscle maldevelopment. METHODS: We review the long-term results of a consecutive series of 126 patients in whom the atrial septal defect was closed through a right posterolateral thoracotomy. The mean age at operation was 7.1 years (range, 1 to 15 years), and the mean body weight was 23.9 kg (range, 6.9 to 56 kg). Defects repaired included 121 ostium secundum (central type), 3 sinus venosus, and 2 ostium secundum without inferior margin. RESULTS: The average cardiopulmonary bypass time was 65 minutes (range, 37 to 130 minutes), with an average fibrillation time of 41 minutes (range, 23 to 70 minutes). There was no operative or late mortality. A majority of patients were pleased with their cosmetic results. There were no other late complications. CONCLUSIONS: Atrial septal defect can be safely repaired through a right posterolateral thoracotomy approach. This approach offers the benefit of a total absence of scarring and cosmetic disfigurement of the anterior chest wall.

Adolescent↗