Effects of a nitro compound patch on neuropathy in Churg-Strauss syndrome.
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Adrenergic beta-Agonists↗
Biomedical subjects
S Suzuki
Publications and source records attributed to S Suzuki.
Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.
We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.
Adult↗
Inhibition of hypoxia/reoxygenation-induced oxidative stress in HGF-stimulated antiapoptotic signaling: role of PI3-K and Akt kinase upon rac1.
Rac1-regulated reactive oxygen species (ROS) production has been implicated in apoptosis. In contrast, pleiotropic protein kinase Akt protects against apoptosis. However, the pro- and antiapoptotic mechanisms of rac1 and Akt, respectively, and the intersection between these mechanisms are incompletely understood. In a model of oxidative stress and apoptosis induced by hypoxia/reoxygenation (H/R) in primary hepatocytes, activation of the PI3-K Akt axis by the prosurvival hepatocyte growth factor (HGF) inhibited H/R-stimulated rac1 activation and intracellular ROS production, and suppressed apoptosis. Suppression of PI3-K or Akt activity abrogated the inhibitory effect of HGF on rac1 activity and rac1-regulated oxidative stress. Furthermore, constitutive activation of Akt or PI3-K in the absence of HGF was sufficient to phosphorylate rac1, inhibit rac1 activation, and suppress rac1-regulated ROS production. These findings demonstrate that growth factor-stimulated activation of PI3-K-Akt is necessary and sufficient to suppress intracellular oxidative stress and apoptosis by inhibiting activation of pro-apoptotic, prooxidative rac1 GTPase.
Androstadienes↗
Long-term normalization in the central nervous system, ocular manifestations, and skeletal deformities by a single systemic adenovirus injection into neonatal mice with mucopolysaccharidosis VII.
Systemic injection of an adenovirus vector into adult mice resulted in pathological improvements in multiple visceral organs of mice with mucopolysaccharidosis VII; however, no therapeutic efficacy was observed for mental retardation, skeletal deformities, corneal clouding, and retinal degeneration. In this study, an adenovirus vector expressing human beta-glucuronidase was injected into mice with mucopolysaccharidosis VII within 24 h of birth, and therapeutic efficacy was evaluated. In the brains of the mice, more than 20% of GUSB activity was maintained for at least 20 weeks after birth, and histopathological analysis showed no obvious lysosomal storage. Furthermore, no vacuolated cells were detected in corneal stroma and retinal pigment epithelium in the eyes of the mice treated in the neonatal period, while pathological improvement was not observed in adult MPSVII mice that received similar treatments. The treated mice also lacked characteristic facial skeletal deformities, and radiographic analysis demonstrated that their facial and cranial bones were morphologically normal. These results indicate that a single systemic adenovirus injection in the neonatal period could prevent the progression of mental retardation, corneal clouding, retinal degeneration, and skeletal deformities, all of which are frequently observed clinical manifestations and difficult to treat in adulthood.
Adenoviridae↗
CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis.
Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.
Adenoviridae↗
Bonding abutments to cast metal post/cores: comparison of pre-treatment effects.
Bond strengths were evaluated for (1) metal primer systems when the metal was contaminated by a dentin conditioner and (2) a dentin adhesive system when dentin was contaminated by metal primers. Disc specimens were cast in a silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy and dentin specimens were prepared by grinding the labial surface of bovine teeth. Specimens were treated with (1) metal primer alone, (2) dentin conditioner alone, (3) metal primer followed by dentin conditioner and (4) dentin conditioner followed by metal primer. A resin cement was poured into a mould over a restricted bonding area and allowed to set. Metal specimens were shear stressed to failure after thermocycling (4-60 degrees C; 20,000 cycles). Dentin specimens were stressed in the same manner after 24 h of immersion in 37 degrees C water. The results were compiled and analysed by anova. Data for dentin specimens treated with dentin conditioner only or with the combination of dentin conditioner and metal primer were not significantly different, statistically. Post-thermocycled groups indicated that bond strengths to the alloy significantly decreased (P < 0.05) when the primed metal surface was contaminated with dentin conditioner regardless of the timing of its application.
Animals↗
Cytotoxicity of bisphenol A glycidyl methacrylate on cytochrome P450-producing cells.
Of the cytochrome P450 (CYP) family of carcinogen-activating enzymes, CYP3A is the major form found in human livers. The purpose of this study was to investigate the cytotoxic effects of dental resin monomers after being metabolized by CYP3A4 and CYP3A7, using a colony formation assay and a neutral red assay. Specimen wells were plated with transfected cells derived from the Chinese hamster lung at 100 cells well(-1). The experimental group consisted of CYP-producing 3A4-10 and 3A7-40 cells, while the control group consisted of non-CYP-producing CR-119 cells. Bisphenol A (BPA) and bisphenol A glycidyl methacrylate (Bis-GMA) and a positive control (Aflatoxine Bl) were added separately to each well and cultured for 7 days. After cultivation, the number of the colonies was counted and IC50 values were determined. The data were statistically analysed by a Student's t-test. The resultant of IC50 values indicated that the monomers were not metabolically activated by CYP3A4 or CYP3A7 as compared with the control (P < 0.05). We also confirmed that these monomers act neither as activators nor as inhibitors of CYP3A4 and CYP3A7.
Aflatoxins↗
Taxol resistance and its reversal by synthetic isoprenoids in human bladder cancer cell line.
PURPOSE: We investigated the mechanism of action of reversal agents for taxol-resistance in bladder cancers. MATERIALS AND METHODS: We isolated a taxol-resistant cell line (KK47/TX30) from a human KK47 bladder cancer cell line (KK47/WT). We characterized KK47/TX30 cells and screened reversal agents for taxol-resistance. RESULTS: KK47/TX30 cells exhibited approximately 700-fold resistance to taxol and cross-resistance to Vinca alkaloids and topoisomerase II inhibitors. Western blot analysis demonstrated P-glycoprotein (P-gp) overexpression in taxol-resistant cells. Drug accumulation and efflux studies showed that the decreased taxol accumulation in the resistant cell line was due to enhanced taxol efflux. We synthesized 31 isoprenoids based on the structure of N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB), which could completely reverse multidrug resistance (MDR) as shown previously. Among those examined, trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane (N-5228) could completely reverse taxol-resistance in KK47/TX30 cells. Results of a structure-activity relationship study of isoprenoids suggested that the following structural features were important for overcoming taxol-resistance: (1) a basic structure of 8 to 10 isoprene units, (2) a cyclohexane ring or benzene ring within the framework, (3) two cationic sites in close proximity to each other, and (4) a benzyl group with 3,4-dimethoxy functionalities with moderate electron-donation. CONCLUSIONS: Taxol-resistance was primarily mediated by P-gp overexpression in KK47/TX30 cells. One of the synthetic isoprenoids, N-5228 could completely reverse taxol-resistance in KK47/TX30 cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Presence of functional domains in NADPH-dependent cytosolic 3,5,3'-Triiodo-L-thyronine (T3)-binding protein (p38CTBP) molecule: analyses with deletion mutants.
Functional domains required for NADPH-binding, T(3)-binding, protein dimerization and cytosolic retention were analyzed in NADPH-dependent cytosolic 3,5,3'-triiodothyronine (T(3))-binding protein (p38CTBP) by using the deletion mutants. Wild-type p38CTBP (amino acids; 1-314) and a series of deletion mutants (amino acids; 1-79, 1-128, 1-146, 1-216, 37-314, and 1-145 with 270-314) were bacterially induced. NADPH-dependent T(3)-binding activity was not observed in all mutant p38CTBPs studied, although wild-type p38CTBP showed high-affinity T(3)-binding activity. Wild-type p38CTBP was able to bind a CL-6B column, none of the mutant p38CTBPs showed any binding activity. Pull-down analyses demonstrated that two regions between amino acid 128 and 146, and between 216 and 270, both of which possess helical structures, were required for homodimeric p38CTBP binding. In fluoroscopic studies, GFP-tagged p38CTBP was preferentially observed in cytoplasm. However, C-terminal region-deleted p38CTBP(1-216) was not only observed in cytoplasm, but also in nucleus. These results suggest that 1) multiple regions in p38CTBP molecule are required for T(3)-binding and NADPH binding, 2) two helical structures in p38CTBP molecule may be important in the homodimer formation, and 3) C-terminal region of p38CTBP contains the function to preserve the protein in cytoplasm.
Animals↗
Neuroendoscopic surgery for intracerebral haemorrhage--comparison with traditional therapies.
Endoscopy is a new therapeutic option for hypertensive intracerebral haemorrhage. Although it has the advantages of being less invasive than craniotomy and more effective than conservative treatment, not all patients are candidates for it. Since it is important to clarify which characteristics of patients are indications for this operation, we retrospectively evaluated the role of endoscopic surgery in comparison with traditional treatments for hypertensive intracerebral haemorrhage. Seven patients were treated with endoscopic surgery in our institution between January 2000 and November 2001. Two had thalamic haemorrhage, 4 putaminal haemorrhage, and 1 intracerebral haemorrhage. The average age of patients was 55 years. Endoscopic operation was mainly selected for haematomas more than 20 ml and less than 40 ml in volume. Generally, endoscopy yielded good outcomes with GR in 50 % of patients. Adequate indications for endoscopic operation may be the following; 1) Putaminal haematoma of small-intermediate size, 2) Haematoma situated deep in the brain, e. g., thalamic haemorrhage, 3) Intraventricular haematoma, 4) High-risk patients who cannot tolerate general anaesthesia.
Adult↗
Fetomaternal interface of cytokine patterns in intrauterine infection.
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Adult↗
Renal lesions in spontaneous insulin-dependent diabetes mellitus in the nonobese diabetic mouse: acute phase of diabetes.
The nonobese diabetic mouse is a model of spontaneous insulin-dependent diabetes mellitus. The present study made longitudinal observations of renal lesions in the acute-progressive phase of diabetic mice 0, 10, 20, 30, and 40 days after onset of diabetes without insulin therapy. Plasma creatinine and blood urea nitrogen concentrations gradually increased after onset of diabetes. Kidney weight increased and plateaued at day 20. Under electron microscopy the glomeruli demonstrated only mild changes on day 40. In the proximal tubules proliferating cell nuclear antigen-positive nuclei and nuclear divisions were increased on days 10 and 20. On day 40 of diabetes, increased periodic acid-Schiff-positive granules, confirmed as lysosomal dense bodies, increased neuronal nitric oxide synthase (nNOS) positive reaction, and decreased periodic acid-Schiff staining in the brush border were observed in the proximal straight tubules. In the juxtaglomerular apparatus stratified macula densa were decreased with time in diabetes compared with the findings on day 0, and this macula densa positively reacted with nNOS. No changes in renin levels were observed. In addition, apoptotic cells were not detected. In conclusion, this research represents the first thorough characterization of acute changes in nonobese diabetic mouse kidneys. The results demonstrated renal hypertrophy and slight glomerular injury in early stages and structural alteration of the proximal straight tubules at later stages during the acute phase of diabetes. Furthermore, increased nNOS may represent one of the pathogenic factors of diabetic nephropathy.
Animals↗
Clinical and pathological features of children with Henoch-Schoenlein purpura nephritis: risk factors associated with poor prognosis.
OBJECTIVE: To clarify the risk factors related to prognosis in patients with Henoch-Schoenlein purpura nephritis (HSPN), we investigated the cases with HSPN on long-term observation. METHODS: We enrolled 114 patients who had been diagnosed with HSPN from 1974-1997. These patients were divided into 2 groups based upon features at last follow-up. One group, designated "favorable", consisted of 69 patients with normal urine and 25 patients with minor urinary abnormalities, and the second group, designated "unfavorable", consisted of 15 patients with active renal disease and 5 patients with renal failure. The clinical features, laboratory data and pathological findings were investigated in 2 groups. RESULTS: Nephrotic syndrome, decreased factor XIII activity, hypertension and renal failure at onset were more frequent in "unfavorable" than in "favorable". The rate of glomeruli with crescents, macrophage infiltrations, tubulointerstitial changes and acute exacerbation in "unfavorable" were higher than those in "favorable". There were 5 cases with renal insufficiency, and renal survival rate was 95.6% for over 15 years. CONCLUSIONS: These results suggest that the above mentioned risk factors play an important role in prognosis of the patients with active renal disease and renal failure.
Biopsy↗
Membranoproliferative glomerulonephritis associated with hereditary deficiency of the 4th component of complement.
A 10-year-old female patient was found positive for urine protein and occult blood on Japanese school urinary screening. Examination of the blood was normal except low values of the complement system with CH50 13.5 U/ml, C3 45 mg/dl and C4 3 mg/dl. Renal biopsy demonstrated a focal membranoproliferative glomerulonephritis (MPGN). As for the activity of each component of the complement in the early stage of the disease, the C4 activity was markedly declined and the activity of classical pathway component was also decreased, but the activity of alternative pathway component was normal. On the HLA examination, the patient demonstrated a C4 double null haplotype (C4A2, Q0, BQ0 phenotype). A null C4 gene at both the C4A and C4B loci was found in her mother, aunt and grandfather on the mother's side and C4B null allele in her father and her grandmother on the mother's side. The development of the disease is found in 1 case and not in the other, although both have the genetic defect and the mechanism by which the complement is activated remains unknown. Thus, there appear to be many subjects to be studied as to the relationship between the defect of C4 gene and immune competence.
Child↗
[Radiofrequency ablation for metastatic lung tumor].
BACKGROUND: Radiofrequency ablation (RFA) is a thermal ablation technique which results in coagulative necrosis. Several preliminary studies have evaluated the efficacy of RFA for liver tumor and benign prostate disease, but few studies for lung tumor. We experienced RFA for a metastatic lung tumor and it was effective. CASE: A 61-year-old woman was admitted to our hospital with chest pain. Extended thymothymomectomy with lymph node dissection was performed after diagnosis of thymic carcinoid. After 14 months, multiple small lung nodules, which had been 5-10 mm in diameter, were appeared and resected. However, 23 months after the first operation and 14 months after the second operation, multiple small lung nodules were appeared again and RFA was performed for 1 tumor without any complications. We used RITA 500 PA (RITA Medical Systems, INC.) and quadruple-hook radiofrequency probe with electrodes. Under local anaesthesia and ultrasound guidance, the probe was inserted into the target tumor and the hooks were deployed. The tumor became smaller (35 mm to 25 mm in diameter) in 2 months. CONCLUSION: RFA is an effective and minimally invasive technique to destruct local tumors.
Carcinoid Tumor↗
[Showing no increase of C-reactive protein and developing non-bacterial median chest wound dehiscence after coronary artery bypass grafting].
A 72-year-old male underwent coronary artery bypass grafting for 3 vessels disease. After the operation, the peak C-reactive protein (CRP) level was 0.85 mg/dl and CRP levels stayed very low. Forty days after the operation the patient developed a progressive median chest wound dehiscence but the bacterial cultures were negative. In spite of conventional therapies such as debridement of necrotic tissue or irrigation, the wound granulation was underdeveloped. After 6 months an epidermis had developed to cover the wound.
Aged↗
[Spontaneous regression of thymoma; report of a case].
A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.
Adult↗
Mid-term outcome after partial left ventriculectomy in pediatric patients.
From May 1998 to April 2000, we performed partial left ventriculectomy (PLV) in 3 pediatric patients with dilated cardiomyopathy (DCM). At the time of the surgery, their age ranged from eight months to three years. The first patient eventually had to receive a heart transplant, but all patients treated with PLV are alive to this day. Patient #1 was diagnosed with DCM at the age of five months, PLV was done on a semi-urgent basis at the age of eight months, when medium dose IV catecholamine therapy and mechanical ventilation were required. Fraction shortening (FS) as shown by echocardiography increased postoperatively from 8% to 15% along with marked clinical improvement. Her heart failure deteriorated three months after the surgery, and received a heart transplant in the United States when she was one year and two months old. Patient #2 developed severe heart failure two months after correction of a ventricular septal defect. Aggressive medical therapy failed to improve his condition, therefore PLV was done on an elective basis at the age of three years and five months. [The patient was initially hospitalized and underwent low dose catecholamine.] Postoperative course was well. The ventriculography one year after surgery showed an improvement of the left ventricular FS from 12% to 27% after PLV. He was still doing well at his most recent check up. Patient #3 was diagnosed with DCM as a neonate. PLV was done on an elective basis at the age of two years and five months. Her postoperative course was generally well. FS on echocardiography increased postoperatively from 10% to 25% along with marked clinical improvement. The timing of performing PLV is the most essential factor for postoperative course in our experiences. We consider that the best timing is when aggressive catecholamine infusion or mechanical ventilation is required. The mid-term outcome of PLV of pediatric patients is considered to be acceptable. We believe that PLV should be considered as a viable option for severe DCM patients.
Cardiac Surgical Procedures↗