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Biomedical subjects

Shigetsugu Ohgi

Publications and source records attributed to Shigetsugu Ohgi.

At least 19 recordsLinked to original sources
PubMed2006

Hypertension accelerated experimental abdominal aortic aneurysm through upregulation of nuclear factor kappaB and Ets.

In this study, we focused on the effect of hypertension on the transcription factors nuclear factor kappaB (NFkappaB) and ets in the mechanisms of abdominal aortic aneurysm (AAA), and we investigated how hypertension affects the progression of AAA. AAA was produced by elastase perfusion in hypertensive rats and normotensive rats. The size of AAA rapidly increased in hypertensive rats as compared with normotensive rats. Western blot analysis demonstrated that the expression of matrix metalloproteinase (MMP)-2, -3 , -9, and -12, as well as intercellular adhesion molecule, was increased in hypertensive AAA rats, accompanied by upregulation of NFkappaB and ets. Moreover, in situ zymography showed that the activity of MMPs was increased in the aorta of a hypertensive AAA model as compared with that in a normotensive AAA model. Interestingly, transfection of chimeric decoy oligodeoxynucleotide (ODN) resulted in significant inhibition of aortic dilatation both in normotensive and hypertensive rats at 4 weeks after transfection. Destruction of elastic fibers was also significantly inhibited by transfection of chimeric decoy ODN in both hypertensive rats and normotensive rats. The expression of MMP-2, -3, -9, and -12, as well as intercellular adhesion molecule, was significantly attenuated by the chimeric decoy ODN, accompanied by inhibition of the migration of macrophages. Also, the effect of chimeric decoy ODN was confirmed in an organ culture. The present study demonstrated that hypertension accelerated the progression of experimental AAA through upregulation of NFkappaB and ets. Inhibition of NFkappaB and ets could be a novel therapeutic strategy to treat AAA in hypertensive patients.

Animals↗
PubMed2006

Resection of a cardiac tumor extending into the inferior vena cava presenting as Budd-Chiari syndrome.

This report describes the successful treatment of a case of cardiac adenocarcinoma with the clinical presentation as Budd-Chiari syndrome. Complete surgical excision of the atriocaval mass was successfully achieved under deep hypothermic circulatory arrest. Histopathological diagnosis of this tumor was tubular adenocarcinoma with positive immunostaining by carcinoembrionic antigen. Subsequent systemic search could not detect any evidence of extra-cardiac primary site and distant metastatic lesion. A 2-year follow-up without any adjuvant therapy revealed no sign of recurrence.

Adenocarcinoma↗
PubMed2006

Laparoscopic bilateral partial adrenalectomy for adrenocortical adenomas causing Cushing's syndrome: report of a case.

Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushing's syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushing's syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.

Adrenalectomy↗
PubMed2006

Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA microarray.

Despite the discovery of multiple TAAs, only a limited number is available for clinical application, particularly against epithelial malignancies. In this study we searched for novel TAAs using expression profiles of gastric cancer examined with cDNA microarray, and identified the SCRN1 gene as a candidate. SCRN1 was confirmed to be expressed in five out of seven gastric cancers with semiquantitative RT-PCR. With Northern blot analysis, it was detected abundantly in the testis and ovary, but it was barely detectable in 14 other normal human adult organs. Colony formation assay revealed that its augmented expression is associated with promoted cell growth. As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201. We synthesized the candidate peptides derived from SCRN1, and tried to induce CTLs with each peptide. The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously. These results strongly suggest that SCRN1-196 is an epitope peptide restricted to HLA-A*0201. Furthermore, we synthesized an anchor-modified peptide SCRN1-9 V (KMDAEHPEV), in which leucine at position 9 was substituted for valine to increase the binding affinity to the HLA-A*0201 molecules. The CTL clones induced by SCRN1-9 V also recognized tumor cells expressing its natural SCRN1 protein endogenously. These results strongly suggest that SCRN1 is a novel TAA and these peptides, both native and modified, may be applicable for cancer vaccines to treat gastric cancer.

Animals↗
PubMed2006

Role of AKT in cyclic strain-induced endothelial cell proliferation and survival.

Endothelial cells (ECs) are exposed to repetitive cyclic strain (CS) in vivo by the beating heart. The aim of this study was to assess the influence of CS amplitude and/or frequency on EC proliferation and survival and to determine the role of AKT in CS-induced EC proliferation and survival. Cultured bovine aortic ECs were exposed to 10% strain at a frequency of 60 (60 cpm-10%) or 100 (100 cpm-10%) cycles/min or 15.6% strain at a frequency of 60 cycles/min (60 cpm-15.6%). AKT, glycogen synthase kinase (GSK)-3beta, BAD, and cleaved caspase-3 were activated by CS in ECs. Increasing the magnitude or frequency of strain resulted in an earlier phosphorylation of GSK-3beta, although the magnitude of phosphorylation was similar. After CS at 60 cpm-10% for 24 h, the number of nontransfected ECs was significantly increased by 8.5% (P < 0.05). We found that the number of apoptotic ECs was slightly decreased with exposure to CS. ECs transfected with kinase-dead AKT (KA179) as well as plasmids containing a point mutation in the pleckstrin homology domain of AKT (RC25) not only prevented AKT, GSK-3beta, and BAD phosphorylation but also inhibited the CS-induced increase in cell number as well as the CS-induced protection against apoptosis (both P < 0.05). The ratio of 5'-bromo-2'-deoxyuridine-positive cells was increased when ECs transfected with RC25 and KA179 as well as nontransfected ECs and ECs transfected with Lipofectamine 2000 were exposed to CS. We conclude that AKT is important in enhancing the survival of ECs exposed to CS but is not involved in EC proliferation.

Animals↗
PubMed2005

Trapidil enhances the slowly activating delayed rectifier potassium current and suppresses the transient inward current induced by catecholamine in Guinea pig ventricular myocytes.

We examined the electrophysiological effects of trapidil on the ionic currents influencing the repolarization and on the transient inward current (ITi) that can cause triggered arrhythmia using the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Trapidil shortened the action potential duration (APD) and increased the delayed rectifier potassium current (IK) in a concentration-dependent manner. The effect of trapidil on the rapidly and slowly activating components of IK (IKr and IKs, respectively) was studied by the envelope of tails test. Trapidil failed to affect IKr and selectively enhanced IKs. Trapidil increased the amplitude of the L-type Ca2+ current (ICa,L), with an acceleration of its inactivation, whereas isoproterenol, a beta-adrenoceptor agonist, increased the amplitude of the ICa,L in a different manner. Isoproterenol activated ITi; however, trapidil not only failed to facilitate ITi but also suppressed isoproterenol-induced ITi. The inhibitory effect of trapidil on isoproterenol-induced ITi is at least partly via a reduction of Ca2+ overload through an acceleration of ICa,L inactivation and/or a sarcoplasmic reticulum (SR) Ca channel modulation. These results suggest that trapidil does not prolong the QT interval and has an antiarrhythmic effect on arrhythmias elicited by triggered activity secondary to Ca2+ overload at much higher concentrations than clinical concentration.

Action Potentials↗
PubMed2005

Expression of RUNX3 protein in human lung adenocarcinoma: implications for tumor progression and prognosis.

Runt-related transcription factor 3 belongs to the runt domain family of transcription factors that play a pivotal role during normal tissue development and tumorigenesis in several organs. We directed our attention to the expression of RUNX3 protein in human lung AC and non-neoplastic lung tissues, comparing the results with clinicopathological profiles. We evaluated the expression of RUNX3 protein in 17 pairs of lung AC and non-neoplastic lung tissue. Furthermore, 98 lung AC were studied to examine the frequency of RUNX3-positive cells. Western blot analysis showed a single band at 45 kDa in all 17 AC and non-neoplastic tissues. Immunohistochemistry revealed immunoreactivity in alveolar type II pneumocytes or Clara cells. RUNX3 was expressed more frequently in the carcinomas with a BAC component than in those without (P < 0.01). Lower RUNX3 levels were associated with poorly differentiated types (P = 0.049). The five-year survival rate was significantly higher in the 50 patients with higher levels of RUNX3 expression than in the 48 patients with lower levels (P = 0.027). The expression of RUNX3 protein in lung AC might play a pivotal role in tumor progression and patients' survival.

Adenocarcinoma↗
PubMed2005

Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas.

We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers.

3T3 Cells↗
PubMed2005

Mitral valve repair for mitral insufficiency due to infective endocarditis in a patient with idiopathic thrombocytopenic purpura.

A 63-year-old woman with an 18-year history of idiopathic thrombocytopenic purpura (ITP) was admitted with a persistent fever of unknown cause. Blood culture was positive for alpha-Streptococcus and echocardiography revealed severe mitral regurgitation and vegetation on the mitral valve. After antimicrobial therapy for six weeks, she underwent mitral valve repair using a Cosgrove ring. The platelet count increased and remained stable by perioperative treatment with intravenous high-dose gamma-globulin and platelet transfusion without steroids therapy or splenectomy. The hospital course was uneventful. Perioperative high-dose gamma-globulin therapy and platelet transfusion for the cardiac operation were useful to increase and maintain the platelet count for an ITP patient complicated with infective endocarditis.

Endocarditis, Bacterial↗
PubMed2005

[Pathogenesis, diagnosis, and treatment of postoperative deep vein thrombosis].

Most postoperative deep vein thrombosis (DVT) arises from the venous systems of the pelvis and lower extremities, especially the soleal veins. Embolization of venous thrombi is related to the size and location of thrombi and movement of the lower limbs and commonly occurs within 1 week from the onset of formation. There are three steps in the final diagnosis of DVT: probable diagnosis by anamnesis and physical examination; screening diagnosis using quantitative tests; and definitive diagnosis using imaging tests. To determine embolic sources, venous echography, which is noninvasive and convenient, is the first choice. Therapeutic methods are selected based on thrombi extent and time after formation. Anticoagulant therapy is indicated in all cases except in patients with possible bleeding tendency and continues for 3 months or more. Among the endovascular therapies, catheter-directed thrombolysis is a more effective approach when combined with a temporary vena cava filter than operative thrombectomy. Although the prevention of DVT is mandatory for surgeons, it is difficult to avoid venous thromboembolism completely. Systemic early diagnosis and emergent therapeutic strategies for venous thromboembolism are clinically effective and promising.

Humans↗
PubMed2004

Sentinel node navigation surgery using indocyanine green in patients with lung cancer.

PURPOSE: To investigate the potential use of sentinel node navigation surgery (SNNS) using indocyanine green (ICG) in lung cancer. METHODS: The subjects were 38 patients with stage cN0 lung cancer. After thoracotomy, we injected 5 ml ICG and 400 U hyaluronidase around the tumor, and identified the stained lymph nodes (LNs) intraoperatively by inspection. Postoperatively, we measured ICG concentrations in the dissected LNs. Lymph nodes with an ICG concentration of more than 1.5 times the mean were defined as sentinel nodes (SNs). RESULTS: There were 30 pN0, 6 pN1, and 2 pN2 cancers. The tumor size ranged from 11 to 75 (mean 31 +/- 15) mm. Sentinel nodes were identified by inspection in 7 (18.4%) of the 38 patients. Lymphatic mapping with ICG concentration was successful in 38 (100%) of 38. One SN was found in 18 patients and two SNs were found in 20. The SN predicted the status of metastasis of all LNs in 37 (97%) of 38. Metastases were identified in the SN alone in 5 (62.5%) of 8. There was one false negative, caused by a metastatic LN being occupied by tumor cells. CONCLUSION: These findings support the efficiency of SNNS for clinically node-negative lung cancer.

Adenocarcinoma↗
PubMed2004

Congenital pericardial defect associated with ruptured type A aortic dissection.

Congenital pericardial defect is a rare and little-known anomaly. Here we describe the unique clinical presentation of a 64-year-old man with partial defect of the left pericardium associated with ruptured acute type A aortic dissection manifesting massive left hemothorax. In this patient, the pericardial defect played the role of a pericardial draining window, which incidentally prevented the heart from cardiac tamponade. Emergent surgery was successfully performed with a prosthetic graft replacement.

Aortic Dissection↗
PubMed2004

State-dependent blocking actions of azimilide dihydrochlo-ride (NE-10064) on human cardiac Na(+) channels.

BACKGROUND: Azimilide reportedly blocks Na(+) channels, although its mechanism remains unclear. METHODS AND RESULTS: The kinetic properties of the azimilide block of the wild-type human Na(+) channels (WT: hH1) and mutant DeltaKPQ Na(+) channels (DeltaKPQ) expressed in COS7 cells were investigated using the whole-cell patch clamp technique and a Markovian state model. Azimilide induced tonic block of WT currents by shifting the h infinity curve in the hyperpolarizing direction and caused phasic block of WT currents with intermediate recovery time constant. The peak and steady-state DeltaKPQ currents were blocked by azimilide, although with only a slight shift in the h infinity curve. The phasic block of peak and steady-state DeltaKPQ currents by azimilide was significantly larger than the blocking of the peak WT current. The affinity of azimilide predicted by a Markovian state model was higher for both the activated state (Kd(A) =1.4 micromol/L), and the inactivated state (Kd(I) =1.4 micromol/L), of WT Na(+) channels than that for the resting state (Kd(R) =102.6 micromol/L). CONCLUSIONS: These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states.

Dose-Response Relationship, Drug↗
PubMed2004

Developmental changes of Ni(2+) sensitivity and automaticity in Nkx2.5-positive cardiac precursor cells from murine embryonic stem cell.

BACKGROUND: It is controversial which subtypes of T type Ca(2+) channels are implicated in automaticity of cardiac cells during the embryonic period. METHOD AND RESULTS: The effect of Ni(2+) on the automaticity of Nkx2.5-positive cardiac precursor cells sorted from embryonic stem cells during their differentiation was examined using patch clamp techniques. Although 40 micromol/L Ni(2+), which is enough to block Ni(2+)sensitive T type-Ca(2+) channels, decreased the spontaneous beating rate in all cells in the early and intermediate stage, Ni(2+) did not show any effects on the automaticity of 50% of the cells in the late stage. CONCLUSION: These results indicate that Ni(2+)-sensitive T-type Ca(2+) channels expressed in the Nkx2.5-positive cardiac precursor cells are developmentally regulated.

Animals↗
PubMed2003

Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets transcription factors.

BACKGROUND: Two phenomena, inflammation and matrix degradation, contribute to the progression of abdominal aortic aneurysm (AAA). Importantly, the inflammation is regulated by the transcription factor nuclear factor (NF)-kappaB, whereas the destruction and degradation of elastin fibers by matrix metalloproteinases (MMP) are regulated by ets. Thus, we developed a novel strategy to treat AAA by simultaneous inhibition of both NF-kappaB and ets by using chimeric decoy oligodeoxynucleotides (ODN). METHODS AND RESULTS: AAA was induced in rats by transient aortic perfusion with elastase, whereas transfection of decoy ODN was performed by wrapping a delivery sheet containing decoy ODN around the aorta. Gel-mobility shift assay at 7 days after treatment demonstrated that both NF-kappaB and ets binding activity were simultaneously inhibited by chimeric decoy ODN. Transfection of chimeric decoy ODN resulted in significant inhibition of the progression of AAA such as aneurysmal dilation at 4 weeks after treatment as compared with control, accompanied by a reduction of MMP expression. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with chimeric decoy ODN. Importantly, transfection of chimeric decoy ODN demonstrated potent inhibition of aneurysmal dilatation compared with NF-kappaB decoy ODN alone, whereas scrambled decoy ODN had no effects. Interestingly, the migration of macrophages was significantly inhibited by chimeric decoy ODN. CONCLUSIONS: We demonstrated that inhibition of the progression of AAA was achieved by a novel strategy with chimeric decoy ODN used against NF-kappaB and ets in rat model. NF-kappaB and ets are considered to play an important role in the pathogenesis of AAA.

Animals↗