Arterial carboxyhemoglobin concentrations in elderly patients with operable non-small cell lung cancer.
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Adenocarcinoma↗
Biomedical subjects
Satoshi Suzuki
Publications and source records attributed to Satoshi Suzuki.
Expression of CYP3A4 mRNA is correlated with CYP3A4 protein level and metabolic activity in human liver.
A relatively large amount of human liver tissue was required to determine the exact activity of human hepatic CYP3A. Although, the quantity of available human liver tissue samples is limited. We measured levels of CYP3A4 mRNA by RT-PCR with a radiolabeled primer specific for CYP3A4 and compared mRNA expression with CYP3A4 protein level and metabolic activity in liver. The level of CYP3A4 mRNA was correlated with the levels of CYP3A4 protein and activity. Our results suggest that CYP3A4 protein and activity levels can be predicted from CYP3A4 mRNA levels determined by RT-PCR and using a very small amount of liver tissue.
Blotting, Western↗
Long-term treatment with probucol improves endothelial function in patients with coronary artery disease.
Recent studies have shown that endothelial function is impaired in patients with coronary artery disease (CAD). Probucol has been recognized to have antioxidant properties as well as lipid-lowering effects, and may improve endothelial function. The aim of this study was to evaluate the effects of probucol on endothelial function in patients with CAD. We evaluated endothelial function, based on flow-mediated vasodilation during reactive hyperemia (FMD), and the intima-media thickness (IMT) of the common carotid artery using high resolution ultrasonography in patients either with (CAD group, n=26) or without CAD (Control group, n=12). We measured the serum cholesterol concentration, including the low-density lipoprotein cholesterol (LDL-cholesterol) concentration, and the plasma concentrations of homocyst(e)ine and asymmetric dimethylarginine (ADMA). Measurements of FMD and serum cholesterol were repeated after 3 months of probucol (500 mg/day, n=9) or placebo (n=9) treatment in patients with CAD. The IMT was significantly greater (p < 0.001) and FMD was significantly lower (p < 0.001) in the CAD group than in the Control group. While the serum cholesterol concentration and plasma ADMA were similar in the two groups, the plasma homocyst(e)ine concentrations were higher in the CAD group than in the Control group (p < 0.01). After probucol therapy, FMD was significantly improved in the CAD group (p < 0.05). The serum LDL-cholesterol concentration did not significantly decrease after probucol treatment. Placebo treatment did not alter FMD or the serum cholesterol concentration. Our findings suggest that long-term treatment with probucol improves endothelial function in patients with CAD, an outcome independent of the LDL-cholesterol-lowering effects of probucol, and that homocyst(e)ine may be a better predictor of atherosclerosis than ADMA.
Aged↗
[A case of atypical pulmonary carcinoid accompanying skin metastasis].
A 73-year-old woman underwent cranial surgery in 1999 after receiving a diagnosis of suspected malignant meningioma. She began complaining of headache 2 years postoperatively, and around the same time, she noticed a painful skin tumor. She was then transferred to our hospital for further evaluation. The skin tumor was diagnosed by skin biopsy as an atypical metastatic carcinoid tumor. Systemic examination demonstrated a primary lesion in the left lung. Pulmonary, skin and bone biopsy samples exhibited the same pathological findings as those of the atypical pulmonary carcinoid tumor. She did not show any carcinoid symptoms. EP therapy (etoposide + carboplatin) and CAV therapy (cyclophosphamide + doxorubicin + vincristin) were administered, but there was no clinical response. The patient is currently doing well without chemotherapy and is being followed by the Outpatient Department.
Aged↗
[Case report on intra-tumor injection therapy of dendritic cells in advanced gastric cancer].
Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DCs are expected to work phagocytosis of the tumor as a localized effect. Consequently CTL induction in the tumor and the regional lymphnodes results in a systemic effect. In this study, intra-tumor DC injection therapy was performed by means of endoscopic ultrasonography (EUS) in 2 gastric cancer cases. As a result, tumor markers and ascites of one case were on the decrease. The results indicate this method can be useful in advanced cancer patients.
Dendritic Cells↗
[Verification of guideline for gastric cancer treatment based on a questionnaire].
We reported the results of a questionnaire survey of doctors and patients in relation to the guideline for gastric cancer treatment which was first published 3 years ago. The purpose of this questionnaire was to know whether the degree of recognition and availability of this guideline is satisfactory or not. The results were as follows. 1) The recognition and availability of the guideline among doctors proved satisfactory. 2) For patients who underwent gastrectomy, this guideline is still unfamiliar. Reconsideration of the guideline contents is needed in accord with the medical level from time to time. Moreover, patients must be more and more educated regarding the guideline.
Attitude of Health Personnel↗
Effects of rewarming on nuclear factor-kappaB and interleukin 8 expression in cold-preserved alveolar epithelial cells.
BACKGROUND: Nuclear factor-kappaB (NF-kappaB) and interleukin (IL)-8 play important roles in the pathophysiology of acute lung injury after lung transplantation. Because alveolar epithelium is one of the most important sites at which IL-8 production takes place after reperfusion of donor lungs, we examined the effects of cold/rewarming on NF-kappaB and IL-8 expression in alveolar epithelial cells. METHODS: A549 cells were preserved at 4 degrees C for 5 hr and then rewarmed for up to 20 hr. NF-kappaB was analyzed by electrophoretic mobility shift assay. IL-8 mRNA expression was examined by reverse transcription-polymerase chain reaction. IL-8 concentration in the cell culture medium after rewarming was measured by enzyme-linked immunosorbent assay. RESULTS: NF-kappaB was increased in the nuclear extracts as early as 30 min after rewarming. There was a marked increase in the IL-8 mRNA expression at 1 and 3 hr after rewarming. IL-8 concentration in the cell culture medium was progressively increased during 20 hr following rewarming. The cell culture medium inhibited apoptosis of neutrophils significantly. The cold/rewarming-induced IL-8 production was reduced to approximately 50% by introducing an antisense oligonucleotide for the p65 subunit of NF-kappaB and by treatment with N-acetyl-leucinyl-leucinyl-norleucinal and pyrrolidine dithiocarbamate. The effect of dexamethasone treatment was dose dependent (reduced to approximately 30% at 10-5 M dexamethasone). CONCLUSIONS: Our results indicate that rewarming of cold-preserved alveolar epithelial cells itself may be an important initiator of the inflammatory cascades, including NF-kappaB activation and IL-8 release. Inhibition of NF-kappaB would be worth trying to control unnecessary IL-8 production and the inflammatory response in the donor lungs.
Apoptosis↗
Identification of a novel 2026G-->C mutation of the MRP2 gene in a Japanese patient with Dubin-Johnson syndrome.
Dubin-Johnson syndrome is a recessive inherited disorder with conjugated hyperbilirubinemia caused by a dysfunction of multidrug resistance protein 2 (MRP2) on the canalicular membrane of hepatocytes. A mutational analysis of the MRP2 gene was carried out in three Japanese patients and their family members. In two patients, the homozygous mutations c.1901del67 and c,2272del168 were found. In the third patient, a -24C-->T polymorphism and the two mutations c.1901del67 and 2026G-->C were detected. The 2026G-->C mutation was a novel mutation in exon 16 affecting the conversion of Gly(676) to Arg(676) (G676R) in the MRP2 protein, and was not detected in fifty healthy volunteers. The G676R mutation was located in the Walker A motif of the first nucleotide binding domain in the MRP2 protein, and it was suggested that the mutation induced the dysfunction of the MRP2 protein. It was concluded that the compound heterozygosity of the two mutations of the MRP2 gene in the third patient contributed to the induction of hyperbilirubinemia in this case.
Adult↗
Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines.
Heme oxygenase-1 (HO-1) confers cytoprotection against oxidative stress. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism, which was classified into S (< 27 GT), M (27-32 GT), and L alleles (>/= 33 GT). Polymorphism in the HO-1 gene promoter was shown to be associated with susceptibility to pulmonary emphysema and restenosis after angioplasty. However, the biologic mechanism underlying these associations is still unclear. To examine this issue, we established lymphoblastoid cell lines (LCLs) from subjects possessing S/S or L/L genotypes. HO-1 mRNA expressions and HO activities induced by oxidative stress were significantly higher in LCLs with S/S than those with L/L. Furthermore, LCLs with S/S were significantly more resistant to oxidant-induced apoptosis than those with L/L. These findings suggested that the polymorphism of the HO-1 gene is associated with the strength of antiapoptotic effects of HO-1, resulting in an association with susceptibility to oxidative stress-mediated diseases.
Adult↗
Usefulness of a new Doppler index for assessing both ventricular functions and pulmonary circulation in newborn piglet with hypoxic pulmonary hypertension.
Persistent pulmonary hypertension of the newborn is a clinical syndrome associated with a variety of cardiopulmonary diseases. Serial evaluation of pulmonary circulation and cardiac function is important, but available imaging techniques have been limited. A new Doppler index combining systolic and diastolic time intervals (the Tei index, which is a simple and noninvasive measurement) has been reported to be useful for the assessment of global cardiac function in adults and children. The purpose of this study was to test the effectiveness of the Tei index in prospectively assessing ventricular function and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension. One-day-old piglets (1.1-1.6 kg) were intubated and prepared for the experiments under room air and hypoxia. A complete two-dimensional Doppler echocardiographic examination was performed. Common hemodynamic variables were measured continuously throughout the study. The right ventricle (RV) Tei index under hypoxia (fraction of inspired oxygen = 0.10) was significantly higher than the value under air ventilation (medians, 0.38 versus 0.56; p < 0.05). Moreover, there was a significant correlation between RV Tei index and mean pulmonary artery pressure and positive linear correlation between individual changes in RV Tei index and changes in mPAP (r2 = 0.799, p < 0.05). We conclude that the Tei index is useful for assessing the function of the RV and the left ventricle and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension. These results suggest that the Tei index will become an objective method of assessing patients with persistent pulmonary hypertension of the newborn.
Animals↗
Determination of sugar phosphates and nucleotides related to photosynthetic metabolism by high-performance anion-exchange liquid chromatography with fluorometric and ultraviolet detection.
A high-performance anion-exchange liquid chromatography system was constructed to identify sugar phosphates and nucleotides involved in photosynthetic metabolism. First sugar phosphates and nucleotides were separated by a gradient elution with boric acid and sodium phosphate, then they were detected by a fluorescence detector (as fluorescent derivatives with arginine) and UV detector, respectively. Eight authentic sugar phosphates and 11 authentic nucleotides could be analyzed using the system. The applicability of the system to the determination of the corresponding sugar phosphates and nucleotides in extracts from only five soybean leaf discs (8.95 cm2) was shown.
Chromatography, High Pressure Liquid↗
Dexamethasone upregulates 11beta-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells.
The actions of natural and synthetic glucocorticoids are in part determined by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). We examined whether carbenoxolone, a potent inhibitor of 11beta-HSD, would potentiate the inhibitory action of dexamethasone on interleukin-8 release from BEAS-2B cells, and whether prolonged treatment with dexamethasone at therapeutic doses would upregulate 11beta-HSD2 in the cells. We found that carbenoxolone increased the potency of dexamethasone almost 10-fold. Reverse transcription-polymerase chain reaction and Western blot revealed that BEAS-2B cells expressed 11beta-HSD2, but not 11beta-HSD1. An enzyme activity assay of the cell homogenate demonstrated only NAD+-dependent dehydrogenase activity. The Km value for cortisol in intact BEAS-2B cells was estimated to be 42 nM. When the cells were incubated with dexamethasone for up to 72 hours at increasing concentrations (10(-9) to 10(-5) M), there were considerable increases in mRNA and protein levels of 11beta-HSD2. Prolonged treatment with dexamethasone also increased the enzyme activity of 11beta-HSD in the cells in a dose- and time-dependent manner, with complete inhibition by RU38486. These results suggest that bronchial epithelial cells possess an autoregulatory system for glucocorticoids in the control of their own bioactive levels by inducing the expression of 11beta-HSD2, and that 11beta-HSD2 in the bronchial epithelium may play a role in the local regulation of inhaled glucocorticoid actions.
11-beta-Hydroxysteroid Dehydrogenase Type 2↗
Early changes in alveolar fluid clearance by nitric oxide after endotoxin instillation in rats.
Alveolar fluid clearance may be inhibited and/or stimulated under pathologic conditions. We examined the early change of alveolar fluid clearance after endotoxin instillation in adult rats. We employed electron paramagnetic resonance nitric oxide (NO) trapping technique with iron complex with N,N-diethyldithiocarbamate as an NO trapping agent. We found that lung NO signals reached the highest magnitude by 6 hours after endotoxin instillation. NO production was accompanied by increases in lung cyclic guanosine monophosphate levels. Alveolar fluid clearance decreased significantly 6 hours after the administration of the endotoxin and increased further at 24 hours. These changes were shown to be related to the function of amiloride-sensitive sodium ion channels. Treatment with gadolinium chloride and aminoguanidine significantly decreased lung NO and cyclic guanosine monophosphate levels and completely ameliorated the decrease in alveolar fluid clearance. In addition, the increase in alveolar fluid clearance at 24 hours returned to normal levels after treatment with gadolinium chloride and aminoguanidine. We found immunoreactive inducible nitric oxide synthase to be abundantly expressed in the cytoplasm of alveolar macrophages. Our results suggest that alveolar endotoxin inhibits alveolar fluid clearance at 6 hours by NO. NO is produced via inducible NO synthase in endotoxin-stimulated alveolar macrophages and was also shown to increase alveolar fluid clearance at 24 hours.
Animals↗
Decapeptide with fibroblast growth factor (FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF-5.
Earlier studies demonstrated that knock-out of fibroblast growth factor-5 gene (Fgf-5) prolonged anagen VI phase of hair cycle, resulting long hairs in the mice. We showed the activities on hair growth of the two Fgf-5 gene products, one of which, FGF-5 suppressed hair growth by inhibiting anagen proceeding and inducing the transition from anagen to catagen, and FGF-5S, a shorter polypeptide with FGF-5-antagonizing activity translated from alternatively spliced mRNA, suppressed this activity of FGF-5. As the results suggested that FGF-5 antagonist would increase hair growth, we synthesized various peptides having partial sequences of human FGF-5 and FGF-5S and determined their FGF-5 antagonist activity. Among them, a decapeptide designated P3 (95-VGIGFHLQIY-104) that aligns with receptor binding sites of FGF-1 and FGF-2 suppressed FGF-5-induced proliferation of BALB/3T3 A31 and NIH/3T3 murine fibroblasts, and FGF receptor-1c (FGFR-1c)-transfected Ba/F3 cell line (FR-Ba/F3 cells). IC50s of this peptide on these cell proliferations were 64, 28, 146 microM, respectively. On the other hand, IC50 of this peptide on binding of FGF-5 to the FGFR-1(IIIc)/Fc chimera was 483 microM. Examination in dorsal depilated mice revealed that the P3 peptide reduced the activity of FGF-5 to recover hair pigmentation and hair follicle lengths. The classification of histologically observed skin sections showed FGF-5-induced delations of anagen procedure had reduced by the P3 peptide. The anti-Ki67 antibody staining of hair follicles was inhibited by administration of FGF-5, and this inhibition by FGF-5 was recovered by administration of the P3 peptide. The P3 peptide alone did not affect hair follicle length and hair cell proliferation. These results indicate that the decapeptide antagonized FGF-5 activity in vivo, and reduced the inhibition of FGF-5 in hair growth, confirming that FGF-5 inhibitors are promising substances against hair loss and/or for promoting hair growth.
3T3 Cells↗
Right lung cancer with right aortic arch.
We report here a case of right lung cancer with right aortic arch. A 67-year-old woman with right aortic arch was found to have a 3-cm squamous cell carcinoma arising in the right middle lobe. Right middle lobectomy with lymphadenectomy was performed via right thoracotomy. Although a unique operative view required particular attention in identifying nodes in the mediastinum, we were able to perform the operation without specific techniques.
Aged↗
A rare case of a pulmonary granular cell tumor presenting as a coin lesion.
A 38-year-old man was found to show a well-defined oval-shaped homogeneous dense mass (20 x 30 mm) in the left upper lung field on chest X-ray. Left upper divisionectomy was performed under video-assisted thoracic surgery. Histology showed that the tumor cells had abundant eosinophilic granular cytoplasm, and were immunopositive for neuron-specific enolase, CD56, S-100 protein, and chromogranin. The proportion of Ki-67 positive cells was < 1%. An electron-microscopic examination showed many membrane-bound whorls in the cytoplasm. Although this was a very rare case presenting as an asymptomatic coin lesion, the histological features were the same as those demonstrated for granular cell tumor at common sites.
Adult↗
Primary intrapulmonary thymoma successfully resected with vascular reconstruction.
Primary intrapulmonary thymomas are defined as intrapulmonary tumors without an associated mediastinal component and are very rare. We report a resected case of primary intrapulmonary thymoma with dissection of mediastinal lymph nodes and vascular reconstruction. Because the tumor directly invaded the right brachiocephalic vein, the vein was reconstructed with a graft, and then adjuvant radiation was performed postoperatively. The tumor was diagnosed as a lymphocyte dominant thymoma and B2 type thymoma in the WHO classification. There has been no evidence of recurrence in 6 years. Complete resection of the tumor with vascular reconstruction and adjuvant radiation should be considered in invasive intrapulmonary thymoma.
Biopsy, Needle↗
Use of human liver S9 in the Ames test: assay of three procarcinogens using human S9 derived from multiple donors.
The purpose of the present study was to examine the inter-individual variation in the mutagenicity of chemicals using a variety of human S9 fractions. For this purpose, three procarcinogens, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), benzo[a]pyrene (BP), and dimethylnitrosamine (DMN), were selected for the Ames test and their mutagenicity was examined using human liver S9 fractions prepared from 18 different donors and one pooled liver S9 fraction prepared from 15 different donors. In addition, rat S9 fraction prepared from male rats pretreated with phenobarbital and 5,6-benzoflavone (PB/BF) was used as reference in order to examine the mutagenic differences between human and rat (PB/BF) S9 fractions. The data demonstrate a large inter-individual diversity in the mutagenic response to procarcinogens. The mutagenicity of IQ and BP in the presence of a human liver S9 fraction (lot HLS-014) was equal to that observed in the presence of rat (PB/BF) S9 fraction. The mutagenicity of IQ and BP in the presence of a pooled human liver S9 fraction was lower (90 and 95%, respectively) than that observed in the presence of rat (PB/BF) S9. On the contrary, the mutagenicity of DMN in the presence of either a selected human liver S9 fraction (lot HLS-014) or pooled fraction was 8-fold higher than that found in the presence of rat (PB/BF) S9 fraction. Human liver S9 fraction (lot HLS-014) had one of the highest cytochrome P450 enzyme activities among the 18 different donors and higher than the pooled human liver S9 fraction. These results suggest that the use of both selected human liver S9 fractions with high metabolic activity (e.g., lot HLS-014 as used in this study) and a pooled S9 fraction with moderate metabolic activity could be used as a means to evaluate the inter-individual variability in mutagenic response to chemicals and to confirm positive responses from studies completed with rodent S9.
Adult↗