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Biomedical subjects

S Maeda

Publications and source records attributed to S Maeda.

At least 73 records · Page 4Linked to original sources

Separation of signal and noise from in vivo optical recording in Guinea pigs using independent component analysis.

Optical recording in vivo severely suffers from the interference of heartbeat noise. So far, heartbeat noise has been minimized by subtracting from each experimental trial an average of interlaced control recordings. This method, however, is time-consuming and increases tissue damage due to phototoxicity. Here we applied independent component analysis (ICA) to in vivo optical recordings, for separation of auditory signals and noises. Our results show that ICA can be successfully used to separate sound-evoked signals and heartbeat noises. Compared with the previous method, ICA has a comparable power of separation and does not require background recordings.

Acoustic Stimulation↗

Comparative expressed-sequence-tag analysis of differential gene expression profiles in BmNPV-infected BmN cells.

To compare the gene expression profiles of uninfected and Bombyx mori nucleopolyhedrovirus (BmNPV)-infected BmN cells, we constructed four cDNA libraries for mock-infected cells, and cells at 2, 6, and 12 h postinfection (h.p.i.). A total of 2645 partial sequences obtained for expressed-sequence-tags (ESTs) from the libraries were categorized using BLAST searches of the public database and the BmNPV genome sequence. The following proportions of BmNPV-derived ESTs were observed: 0.4, 4.5, and 57% at 2, 6, and 12 h.p.i, respectively. Moreover, 31 BmNPV open reading frames (ORFs) were newly identified for transcripts and the baculovirus-repeated ORFs (bro) showed the highest levels of expression in the 12 h.p.i. library. Most of the host genes decreased in number as the infection progressed. However, several, including cytochrome c oxidase 1, increased in the late stages of infection. Two apoptosis-related host genes were also identified.

Amino Acid Sequence↗

Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fibroblasts.

The effects of nifedipine on the death and proliferation of gingival fibroblasts were investigated to elucidate the mechanism of gingival overgrowth that is associated with chronic administration of Ca2+ channel blockers. The number of adhered viable and dead fibroblasts obtained from healthy human gingiva increased after confluence, whereas cell death was inhibited by nifedipine in a concentration-dependent manner. A similar inhibition was also observed in the presence of other calcium channel blockers, such as nicardipine, diltiazem, and verapamil. When gingival fibroblasts were co-cultured with RAW264 (macrophage-like) cells, lipopolysaccharide (LPS) caused the concentration-dependent death of fibroblasts. Nifedipine significantly inhibited the LPS-induced cell death. Although neither LPS nor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitroso-hydrazino)-ethanamine, a nitric oxide donor, directly caused fibroblast death, 3-morpholino-sydnonimine (SIN-1), a peroxynitrite donor, induced fibroblast death, regardless of the presence of RAW cells. The cell death induced by SIN-1 was not affected by nifedipine treatment. LPS stimulation caused an increase in the immunoreactivity of inducible nitric oxide synthase (iNOS) and in the nitrite concentration in the incubation medium of RAW cells. The induction of iNOS was completely prevented by the incubation with nifedipine. The inhibition by nifedipine of nitrite production in RAW cells was also observed after treatment with nicardipine, but not with either diltiazem or verapamil. Therefore, the inhibition by nifedipine of both adherence- and LPS-stimulated macrophage-induced death of fibroblasts may be the mechanism of gingival overgrowth seen during chronic treatment with Ca(2+) channel blockers.

Animals↗

Hepatitis C virus core protein activates nuclear factor kappa B-dependent signaling through tumor necrosis factor receptor-associated factor.

Hepatitis C virus (HCV) core protein, a viral nucleocapsid, has been shown to affect various intracellular events including the nuclear factor kappaB (NF-kappaB) signaling supposedly associated with inflammatory response, cell proliferation, and apoptosis. In order to elucidate the effect of HCV core protein on the NF-kappaB signaling in HeLa and HepG2 cells, a reporter assay was utilized. HCV core protein significantly activated NF-kappaB signaling in a dose-dependent manner not only in HeLa and HepG2 cells transiently transfected with core protein expression plasmid, but also in HeLa cells induced to express core protein under the control of doxycycline. HCV core protein increased the DNA binding affinity of NF-kappaB in the electrophoretic mobility shift assay. Acetyl salicylic acid, an IKKbeta-specific inhibitor, and dominant negative form of IKKbeta significantly blocked NF-kappaB activation by HCV core protein, suggesting HCV core protein activates the NF-kappaB pathway mainly through IKKbeta. Moreover, the dominant negative forms of TRAF2/6 significantly blocked activation of the pathway by HCV core protein, suggesting HCV core protein mimics proinflammatory cytokine activation of the NF-kappaB pathway through TRAF2/6. In fact, HCV core protein activated interleukin-1beta promoter mainly through NF-kappaB pathway. Therefore, this function of HCV core protein may play an important role in the inflammatory reaction induced by this hepatotropic virus.

Cell Line↗

Cloning and characterization of an inhibitor of apoptosis protein (IAP) from Bombyx mori.

We cloned a novel inhibitor of apoptosis protein (IAP) family member, BmIAP, from Bombyx mori BmN cells. BmIAP contains two baculoviral IAP repeat (BIR) domains followed by a RING domain. BmIAP shares striking amino acid sequence similarity with lepidopteran IAPs, SfIAP and TnIAP, and with two baculoviral IAPs, CpIAP and OpIAP, suggesting evolutionary conservation. BmIAP blocks programmed cell death (apoptosis) in Spodoptera frugiperda Sf-21 cells induced by p35 deficient Autographa californica nucleopolyhedrovirus (AcMNPV). This anti-apoptotic function requires both the BIR domains and RING domain of BmIAP. In mammalian cells, BmIAP inhibits Bax induced but not Fas induced apoptosis. Further biochemical data suggest that BmIAP is a specific inhibitor of mammalian caspase-9, an initiator caspase in the mitochondria/cytochrome-c pathway, but not the downstream effector proteases, caspase-3 and caspase-7. These results suggest that suppression of apoptosis by lepidopteran IAPs in insect cells may involve inhibition of an upstream initiator caspase in the conserved mitochondria/cytochrome-c pathway for apoptosis.

Amino Acid Sequence↗

Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells.

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-beta. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 microg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells.

Blotting, Western↗

Preoperative assessment of vascularity by color Doppler ultrasonography in human rectal carcinoma.

PURPOSE: Although angiogenesis assessed by immunostaining endothelial cells (microvessel density) is a well-known prognostic factor in a wide variety of human solid tumors, preoperative determination of microvessel density seems to be difficult in rectal carcinoma. Thus, we performed transanal color Doppler ultrasonography in 46 patients with rectal carcinoma to assess preoperative angiogenic status and compare it with microvessel density in surgical specimens. METHODS: Time-averaged maximal velocity, peak systolic velocity, number of vascular points, and vascular point index were conducted by color Doppler ultrasonography in 46 patients with rectal carcinoma. Number of vascular points was defined as the number of vessels with pulsation in the section of tumor. Vascular point index was defined as the average number of vascular points divided by the area assessed by color Doppler ultrasonography in the section of tumor. The profiles of number of vascular points were similar to those assessed by microangiography in five rectal carcinomas. RESULTS: Vascular point index significantly correlated with microvessel density (P < 0.0001). No significant correlation was found between microvessel density and time-averaged maximal velocity or peak systolic velocity. Vascular point index was also a better indicator of lymph node metastasis and venous invasion than microvessel density. In addition, 11 of 46 cases with postoperative hematogenous metastasis (23.9 percent) were observed prospectively. Vascular point index may be a best predictor for hematogenous metastasis from rectal carcinoma compared with peak systolic velocity, time-averaged maximal velocity, and microvessel density by receiver operating characteristic analysis. CONCLUSION: These results suggest that preoperative quantification of angiogenesis using color Doppler ultrasonography will provide quick and useful information in the management of rectal carcinoma.

Blood Flow Velocity↗

A case of solitary fibrous tumor of the meninges.

We report a rare case of solitary fibrous tumor (SFT) of the meninges of the posterior fossa presenting as an intracerebellar hemorrhage. A 29-year-old woman was admitted with sudden-onset severe headache, nausea, and vomiting. A computed tomographic (CT) scan of the brain revealed an intracerebellar hemorrhage 3.5cm in diameter. Gadolinium-enhanced magnetic resonance imaging (MRI) showed a heterogeneous enhancement mass. A posterior craniotomy found a firm, highly vascular tumor attached to the meninges. Histologically, the tumor showed mostly sclerotic tissues with spindle cells. In few areas, the tumor had a more compact arrangement of spindle-shaped cells with vascular spaces and highly cellular components. Immunohistochemical study revealed strong CD-34 immunopositivity in many tumor cells. The tumor was diagnosed as SFT of the meninges. We report the clinical and histological features of this newly described tumor with a heterogeneous component.

Adult↗

Combined resection of distal aortic arch for T4N0 non-small-cell lung cancer with aortic arch invasion.

Three men age: 39-51 years (mean: 43.3 years) with T4N0 lung cancer infiltrating the distal aortic arch underwent combined resection of the left upper lobe, distal aortic arch, and left subclavian artery using partial extracorponeal circulation. Selective cerebral perfusion was used in 2. One underwent induction therapy (CDDP + VP - 16 x 2 + radiation 30 Gy), and all underwent adjuvant therapy. No postoperative complications or postoperative death occurred. Average ICU stay was 2.3 days. All patients are alive without local recurrence. Two were disease-free 37 and 26 months after surgery, and 1 had adrenal gland metastasis 8 months after surgery. Extended resection of the aortic arch in lung cancer is thus feasible and worthwhile in patients with T4N0 non-small-cell lung cancer.

Aorta, Thoracic↗

Ultrasonic integrated backscatter in early assessment of myocardial injury during open heart surgery.

OBJECTIVES: The recovery of cyclic variation of ultrasonic integrated backscatter in myocardial ischemia provides early assessment of myocardial injury and is useful in assessing myocardial injury during open heart surgery. METHODS: We studied 25 patients with valvular disease undergoing cardiac surgery--7 with aortic stenosis, 7 with aortic regurgitation, 6 with mitral stenosis, and 5 with mitral regurgitation. All underwent transesophageal echocardiography (before aortic cross-clamping: T-pre and 60 minutes after aortic declamping: T-60). The short-axis view at the papillary muscle level of the left ventricle was recorded and anterior areas were assessed. RESULTS: The magnitude of cyclic variation at T-pre and T-60 was 9.4 +/- 2.5 dB and 8.8 +/- 3.0 dB, and the ratio was 97 +/- 32%. Fractional shortening at T-pre and at T-60 was 27 +/- 7% and 20 +/- 9%, and the ratio was 79 +/- 44%. Recovery of magnitude was ahead of recovery of fractional shortening. The percent recovery of magnitude at T-60 did not correlate with aortic cross-clamping time (p = 0.91), postoperative peak creatine kinase-MB (p = 0.4), or catecholamine dosage (p = 0.13), but correlated with preoperative left ventricular mass index (p < 0.01). In patients with aortic stenosis, the percent recovery of magnitude at T-60 (66 +/- 4%) was significantly lower than in those with other types of valvular disease. CONCLUSIONS: The recovery of magnitude of cyclic variation of ultrasonic integrated backscatter provides early assessment of myocardial injury, particularly in severely hypertrophied hearts, during reperfusion after aortic declamping in open heart surgery.

Adult↗

Assessment of prognostic factors in follicular lymphoma patients.

Prognostic factors, including clinical, biological, and histological parameters, were assessed for 94 patients with follicular lymphomas at our institute. Follicular lymphomas constituted 7.7% (94/1208) of malignant lymphomas in this study. Eighteen patients were diagnosed with stage I follicular lymphoma, 20 with stage II, 23 with stage III, and 33 with stage IV. The cases of follicular lymphoma were subclassified as: follicular small cleaved cell lymphoma (FSC) in 20 cases, follicular mixed cell lymphoma (FMX) in 59 cases, and follicular large cell lymphoma (FLC) in 15 cases. The patients comprised 49 men and 45 women with a median age of 54 years (range, 25-84 years). The complete response rate was 76.5%, and the median survival time was 13 years. The expected 10-year overall survival and event-free survival rates were 61.9% and 38.2%, respectively. Univariate analysis identified the factors associated with poor survival as elevated serum lactate dehydrogenase (LDH) level (P < .0001), age of >60 (P < .0001), Ann Arbor stage III/IV (P < .01), and Eastern Cooperative Oncology Group performance status (PS) of 2 to 4 (P = .048). Multivariate analysis showed that LDH, age, and PS were independent predictors. After application of the International Prognostic Index (IPI), the 10-year survival rates for the low-risk, low-intermediate risk, high-intermediate risk and high-risk groups were 80.4%, 48.7%, 21.9%, and 0.0%, respectively. The differences among these groups were significant at P < .01. The IPI for aggressive non-Hodgkin's lymphoma was found to be applicable to survival prediction for Japanese follicular lymphoma patients.

Adult↗

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications.

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.

Adult↗

Change in post-exercise vagal reactivation with exercise training and detraining in young men.

We studied the effects of aerobic exercise training and detraining in humans on post-exercise vagal reactivation. Ten healthy untrained men trained for 8 weeks using a cycle ergometer [70% of initial maximal oxygen uptake (VO2max) for 1 h, 3-4 days.week-1] and then did not exercise for the next 4 weeks. Post-exercise vagal reactivation was evaluated as the time constant of the beat-by-beat decrease in heart rate during the 30 s (t30) immediately following 4 min exercise at 80% of ventilatory threshold (VT). The VO2max and the oxygen uptake at VT had significantly increased after the 8 weeks training programme (P < 0.0001, P < 0.001, respectively). The t30 had shortened after training, and values after 4 weeks and 8 weeks of training were significantly shorter than the initial t30 (P < 0.05, P < 0.01, respectively). The change in the t30 after 8 weeks of training closely and inversely correlated with the initial t30 (r = -0.965, P < 0.0001). The reduced t30 was prolonged significantly after 2 weeks of detraining, and had returned almost to the baseline level after a further 2 weeks of detraining. These results suggest that aerobic exercise training of moderate intensity accelerates post-exercise vagal reactivation, but that the accelerated function regresses within a few weeks of detraining.

Adult↗

Left hemihepatectomy with microsurgical reconstruction of the right-sided hepatic vasculature. A strategy for preserving hepatic function in patients with proximal bile duct cancer.

BACKGROUND: Right hemihepatectomy (RH) for proximal bile duct cancer occasionally results in liver failure. We report the feasibility of left hemihepatectomy (LH) with vascular reconstruction (VR) of the right-sided hilar vessels to preserve hepatic reserve. METHODS: Among 110 patients with proximal bile duct cancer (PBC) treated between January 1980 and December 1998, 11 patients underwent LH with VR of eight portal veins and nine hepatic arteries, and 14 underwent RH with VR of four portal veins and one hepatic artery. Microsurgical techniques were used in 80% (8/10) of the hepatic arterial reconstructions. RESULTS: Although operation time was significantly longer in the LH group, hospital mortality, blood loss and incidence of histologically cancer positive margin at the bilioenteric anastomotic site were similar in the two groups. Peak serum liver enzyme concentration was significantly higher in the LH group with longer inflow occlusion time, whereas peak serum total bilirubin concentration was significantly higher in the RH group, which had smaller liver remnant. No liver abscess occurred in any patients who underwent microvascular reconstructions. The cumulative survival of the LH group was worse than that of the RH group, in which the proportion of vascular invasion was lower, but not significantly. CONCLUSION: LH with right-sided microvascular reconstruction is technically possible and a feasible option when RH is likely to result in postoperative liver failure.

Bile Duct Neoplasms↗

Solid and papillary tumor of the pancreas complicating agenesis of the dorsal pancreas.

We report the first documented case of a solid and papillary tumor of the pancreas (SPT) complicating agenesis of the dorsal pancreas. A 28-year-old female patient was referred to our hospital for a pancreatic tumor detected at a local hospital. The laboratory findings were all within normal limits. Diagnostic images revealed absence of the dorsal pancreas and the presence of a tumor located in the head of the pancreas. The tumor was solid, well demarcated, noncalcified, and hypovascular. Fine-needle aspiration cytology revealed that larger cell clumps often had a branching papillary appearance, with multiple layers of tumor cells surrounding central vascular stalks; a preoperative diagnosis of SPT was made. At surgery, on February 10, 1999, the tumor was found to have clear margins, and it showed no signs of direct invasion of adjacent structures. No metastases were found in the liver or the local lymph nodes. Accordingly, partial resection of the pancreas, including the entire tumor, was performed, and, thus, almost the entire head of the pancreas could be saved. Microscopic examination of the resected specimen yielded findings compatible with SPT. No recurrences, and no impairment of pancreatic endocrine or exocrine function have been noted since the operation.

Adult↗

Complete cure of malignant lymphoma of the stomach with a huge adrenal lesion achieved by preoperative chemotherapy and surgery: report of a case.

We report herein the case of a 53-year-old woman with malignant lymphoma of the stomach who was successfully treated by preoperative chemotherapy and surgery. The patient consulted our hospital with the chief complaint of upper abdominal pain. Endoscopy demonstrated a protruding lesion at the antral posterior wall of the stomach, and a post-biopsy pathological diagnosis of diffuse large cell type B-cell lymphoma was established. Moreover, abdominal ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a tumor measuring approximately 10cm in diameter in the left adrenal gland. A total of three courses of chemotherapy using the CHOP regimen were given preoperatively. The CHOP regimen consisted of 100mg of prednisolone administered for 8 days together with 1.9mg of vincristine, 1,000mg of cyclophosphamide, and 60mg of epirubicin administered intravenously on the first day. This resulted in tumor shrinkage, and a distal gastrectomy, lymph node dissection, and left adrenalectomy were subsequently performed. Since the pathological findings of the resected tissue specimen demonstrated complete elimination of the malignant lymphoma, this combination of procedures was defined as having resulted in a complete response. The postoperative course of this patient was uneventful. She is still alive without any sign of tumor recurrence 6 years after her operation, and is being followed up at the outpatient clinic.

Adrenal Gland Neoplasms↗

An element downstream of the transcription start site is required for activation of Bombyx mori nucleopolyhedrovirus bro-c promoter.

Bombyx mori nucleopolyhedrovirus (BmNPV) contains five baculovirus repeated ORF (bro) genes. We have previously reported that all of these genes (bro-a, b, c, d and e) are transcribed as early genes and require viral factor(s) for their expression. In this study, we investigated the mechanism of promoter activation of the bro-c gene. Transient expression assays using genomic libraries of BmNPV indicated that the baculoviral trans-regulator IE-1 is responsible for activating the bro-c promoter. To identify essential site(s) for promoter activation, mutations were introduced to the promoter region of bro-c. Interestingly, it was shown that the pentanucleotide sequence CACGC located 30 nucleotides downstream of the RNA start site was essential for bro-c promoter activation. In addition, the RNA start site and the spacing between the RNA start site and CACGC were also required for promoter activation. By introducing a CACGC sequence into the corresponding region of the bro-b promoter, which is not normally trans-activated by IE-1, we demonstrated that this pentanucleotide motif has the ability to confer trans-activation by IE-1 on a promoter. Gel retardation experiments also showed a sequence-specific DNA binding protein induced by baculovirus infection interacts with the CACGC motif.

Animals↗