The aim of the present study was to examine the activity of superoxide dismutse (SOD) and the level of fetal hemoglobin (HbF) in hydroxyrea (HU) -treated Eβ thalassaemia. We measured SOD level, HbF, mean corpuscular volume (MCV), packed cell volume (PCV) and hemoglobin (Hb) in Eβ thalassaemia patients treated with HU (dose 30mg/kg/day) for 90 consecutive days. There was an increase in HbF synthesis without any increase in Hb in HU-treated patients. The decreased SOD level in long-tem HU therapy in Eβ thalassaemic patients suggests that HU plays some role in inhibiting the superoxide radical generation in thalassamic erythrocytes. HU may act as an inhibitor of oxidative damage of red cells in E thalassaemia.

抄録全体を表示

Glioblastoma multiform is the most common malignant tumor of the human central nervous system and is resistant to classical antitumor treatments. Retinoic acid (RA), which has proven effective in the treatment of acute promyelocytic leukemia, has been used in clinical trials on glioma tumors with moderate effect. In this study, we examined the effect of all-trans retinoic acid (ATRA) on Bcl-2 protein expression in human glioma cell lines (A-172, T98G, YKG-1) using flow cytometry and immunohistochemistry. Bcl-2 protein was expressed in all glioma cell lines tested (27-48%) . There was a significant decrease in Bcl-2 protein expression after incubation with ATRA in the YKG-1 cell line. In these cells, Bcl-2 localized to the cytoplasm of the perinuclear region, but when treated with ATRA no Bcl-2 protein was evident and there was a reduction in the number of stress fibers observed. These findings suggest that the growth inhibitory effects of ATRA maybe mediated via the down-regulation of Bcl-2, an antagonist of apoptotic cell death, and via changes in the cytoskeleton.

抄録全体を表示

To assess the salvage effect on ischemic myocardium we studied 42 patients with ischemic heart disease by adenosine triphosphate (ATP) stress thallium (Tl) -²⁰¹ and ¹²³I-β-methyl-phenylpentadecanoic acid (I-BMIPP) dual single-photon emission computed tomography (SPECT) imaging before and one month after revascularization. We analyzed : (1) the QTc (corrected QT) interval dispersion ; (2) the redistribution in ATP-SPECT before revascularization ; and (3) the Tl/BMIPP discrepancy before and one month after revascularization. BMIPP and Tl-²⁰¹ defects were scored in 9 segments of the left ventricle. The total defect score (TDS) was defined as the sum of the defect scores. Results : (1) There were correlations between both the QTc dispersion (QTD) and the TDS of the ATP-SPECT before and after revascularization. (2) Revascularization decreased the ATP-induced QTc dispersion and improved left ventricular ejection fraction (LVEF) (from 54.3 ± 14.1 to 63.1 ± 19.2, p <.0001) in redistribution (on Ti-SPECT perfusion imaging) (+) patients before revascularization, compared with no significant change in redistribution (-) patients. (3) Before revascularization there was a significant increase in the QTc dispersion during ATP infusion in the group in which Tl/BMIPP discrepancy was prolonged compared to the group in which the Tl/BMIPP discrepancy improved (69 ± 22 versus 78 ± 25, p= .0003) . Conclusions : These findings suggest that ATP-induced changes in the QTD may aid in evaluation of the salvage effect on the ischemic myocardium after revascularization.

抄録全体を表示

To determine the correlation between histologic features in Helicobacter pylori (H. pylori) -positive patients with hemorrhagic gastric ulcer and the inhibition of gastric acid secretion resulting from continuous intravenous infusion of ranitidine followed by oral administration of omeprazole. Subjects included 27 H. pylori-positive patients with hemorrhagic gastric ulcers (22 men, 5 women; mean age=55.1±13.2 years) . Intra-gastric pH was monitored during continuous intravenous infusion with ranitidine (200 mg per day), and after oral administration of omeprazole for 3 or 4 days. The percentage of time for which the pH was maintained above 3 or 4 (pH 3 holding time and pH 4 holding time, respectively) and the mean pH, were measured. Histologic features in biopsy specimens were graded according to the updated Sydney System. With continuous intravenous ranitidine infusion, pH 3 and pH 4 holding times, as well as the mean pH, were significantly lower for patients with a score of 1 for glandular atrophy in the gastric corpus, than in patients with scores of 0 or 2 and above (P=0.006, P=0.011 and P=0.038, respectively) . Values were also significantly lower for patients with a score of 1 for intestinal metaplasia in the gastric antrum than for patients with scores of 0 or 2 and above (P<0.001, P=0.001 and P=0.001, respectively) . The values during oral administration of omeprazole showed no correlation with histologic features. Inhibition of gastric acid secretion during continuous infusion with ranitidine varies in H. pylori-positive patients with hemorrhagic gastric ulcers and correlates with the degree of atrophy in the gastric mucosa.

抄録全体を表示

Immunohistochemical staining of E-cadherin and thymidine phosphorylase (TP) were performed on paraffin-embedded blocks from needle biopsy specimens of prostate cancer. Specimens were obtained from 20 patients (mean age : 72.9 years, range : 65-94 years) who underwent prostate needle biopsy under transrectal ultrasound guide in 1998. Prostate cancer was suspected in patients when a high serum prostate-specific antigen (PSA) level was observed and suspicious findings from a digital transrectal examination (DRE) or transrectal prostate ultrasonograph (TRUS) were obtained. The immunohistochemical staining results were compared with the Gleason score and clinical stage of the disease. Although a high level of expression of E-cadherin was observed in all patients with prostatic hypertrophy or prostatitis, a reduction in E-cadherin expression was seen with an increase in Gleason score and clinical stage of the disease, indicating a correlation of E-cadherin expression with both parameters. Non-cancerous epithelial cells had very high TP expression levels, while cancer tissue demonstrated a metachromatic pattern. There was considerable heterogeneity in the topographic distribution of TP expression, indicating that there was no significant correlation with either the Gleason score or clinical stage. There was no evidence of a common expression pattern between E-cadherin and TP. TP was highly expressed in stroma, irrespective of the differentiated state of the cancer, this resulted in inconsistent staining, while E-cadherin showed expression levels that correlated with the Gleason score. These findings indicate that TP expression level is not suitable to use as a single indicator of malignancy in prostate cancer. E-cadherin may be considered to be a marker of malignant phenotype in prostate cancer due to the presence of a significant correlation of expression levels with the Gleason score and clinical stage of disease. Moreover, immunostaining proved to be feasible using stored paraffin-embedded blocks. However based on the results of the present study, it could not be said that E-cadherin has a greater diagnostic value in the prediction of prognosis than the Gleason score.

抄録全体を表示

The influence of macrolide antibiotics, josamycin (JS), roxithromycin (RXM) and azithromycin (AZ), on co-stimulatory molecule expression was examined using an in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with 8.0μg/ml of keyhole limpet haemocyanin (KLH) were cultured in the presence of 100.0μg/ ml of KLH and various concentrations of antibiotics for 72 hours. RXM and AZ, but not JS, inhibited cell activation induced by antigenic stimulation when the cells were cultured in the presence of more than 5.0 μg/ml of agents. Addition of RXM and AZ to cell cultures did not cause suppression of the proliferative response of spleen cells to anti-CD3 monoclonal antibody stimulation even when the cells were cultured in the presence of 10.0μg/ml of agents. The influence of these macrolide antibiotics on co-stimulatory molecule expression on spleen cells in response to antigenic stimulation was examined. Addition of RXM and AZ, but not JS, at a concentration of 5.0μg/ml into cultures markedly suppressed expression of the co-stimulatory molecules, CD40, CD80 and CD86, which are enhanced by antigenic stimulation in vitro.

抄録全体を表示

During endotoxic shock, two endogenous cannabinoids, anandamide (ANA) and 2-arachidonoyl glycerol (2-AG), can be generated by activated macrophages and platelets and are thought to play a crucial role in the induction of shock-related hypotension. In vitro, the cell wall components of both Gram-positive and Gram-negative bacteria, can activate macrophages and release ANA. The aim of this study was to investigate whether cell wall components from Gram-positive bacteria could stimulate the release of ANA in an experimental animal model. Male Wistar rats were anesthetized and received an intravenous injection of lipoteichoic acid (LTA) and peptidoglycan (PepG) from Staphylococcus aureus. Mean arterial blood pressure (MAP) was monitored and blood samples were taken at 30 min and 360 min to measure ANA levels and other biochemical markers of multiple organ dysfunction syndrome (MODS) . The administration of LTA and PepG resulted in a significant increase in the serum concentration of ANA (360 min, n=4-6; P<0.05) and a biphasic fall in MAP from 103±1 mmHg (time 0) to 50±4 mmHg (360 min, n=5 ; P<0.05) . Furthermore, LTA+PepG was able to induce MODS as evidenced by a decrease in arterial oxygen tension (lung), an increase in serum levels of glutamate-pyruvate- and glutamate-oxaloacetatetransaminases (liver), and an increase in creatinine and blood urea nitrogen (kidney) . These results, together with those of previous studies, imply that ANA is an endogenous mediator of shock-induced hypotension, in response to both endotoxin and Gram-positive bacteria.

抄録全体を表示

In acute pancreatitis, tissue destruction, from neutrophil infiltration of the pancreas and other organs, is thought to be inhibited by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in the rat. Rats fed a low-protein diet for 11 days received a daily intraperitoneal dose of DL-ethionine (20 mg/ 100 g) for the last 4 days. To evaluate its preventive potential, IS-741 (10 mg / kg s.c.) was administered every 8 h beginning on the first day of the low-protein diet. In another group, IS-741 was administered as described above, beginning with the second ethionine injection, this time to evaluate the therapeutic effect on ethionine-induced pancreatitis. The rats were killed 24 h after the final ethionine injection. Blood was sampled to measure concentrations of the inflammatory cytokines, interleukin-6 and -8. The pancreas was weighed, DNA and protein levels were determined, and neutrophil infiltration was assessed by the myeloperoxidase assay. The pancreas was also examined histologically. Pancreatic sections from saline-treated controls showed considerable infiltration by inflammatory cells, and acinar cell necrosis was widespread. The histologic severity of acute pancreatitis was alleviated by the administration of IS-741. Pancreatic weight and DNA content in rats treated with IS-741 were significantly higher than in control rats. Interleukin-6 concentrations were undetectable at baseline in all groups while those of interleukin-8 were higher in controls, compared to rats treated with IS-741. Preventive or therapeutic administration of IS-741 ameliorated acute pancreatitis induced in rats by DL-ethionine, and may become a useful drug to treat patients with this condition.

抄録全体を表示

The purpose of this study was to compare the antioxidant effect of several extracts from tomato, carrot, or red sweet pepper on FeCl₃ inducedlipid peroxidation in bovine retinal homogenate. Ethyl acetate was used to prepare an A-fraction which contained carotenoids and vitamin E. After removal of A-fractions, B-fractions containing flavonoids, were extracted from the precipitates with n-butanol, and the residual C-fraction was extracted with water. The concentration of lycopene in tomato extract, β-carotene in carrot, and capsanthin in red sweet pepper was determined by HPLC. Phosphatidylcholine hydroperoxide (PC-OOH) in retinal homogenate was analyzed by HPLC as the endpoint biomarker. After 60 min incubation with or without addition of FeCl₃, the oxidized and baseline controls were 10.7 ± 0.8 and 2.6 ± 0.2 pmol PC-OOH/mg protein respectively. Standards of lycopene (10 μM), β-carotene (10μM), or capsanthin (1 μM) did not inhibit PC-OOH production by FeCl₃. However, the A-fraction of carrot and the B-fraction of red sweet pepper significantly inhibited PC-OOH production, (7.88 ± 0.59 pmol/mg protein and 5.94 ± 0.28 pmol/mg protein respectively), whilst the C-fraction was not effective. When the A or B-fractions were combined with 10 ACM vitamin E, the individual effects were enhanced. These results demonstrate that vegetable extracts containing antioxidants such as carotenoids; flavonoids and vitamins reduce retinal lipid peroxidation, especially, the B-fraction of red sweet pepper, which showed strong antioxidant activity. Therefore, a diet rich in these compounds may help slow age-related macular degeneration.

抄録全体を表示

The purpose of this study was to investigate the location of equivalent current dipoles estimated by the scalp-skull-brain/dipole tracing (S SB/DT) method during complex and simple tasks. The complex task involved self paced right hand grasping followed by elbow flexion, whereas the simple task involved right middle finger flexion. The movement-related cortical potential was recorded with scalp electroencephalogram surface electrodes (international 10/20 system) . The negative slope, one of the components of the movement-related cortical potential, was recorded from -40 ms to the onset of electromyogram activity of finger flexion muscles during simple tasks. The negative slope was also recorded during complex and sequential tasks from -120 ms to the onset of electromyogram activity. During the simple task dipoles were recorded in both the contralateral primary motor area and the contralateral somatosensory area. For complex and sequential tasks dipoles were recorded in the bilateral supplementary motor area, contralateral primary motor cortex and the contralateral somatosensory area. These results suggest that dipoles in the bilateral supplementary motor cortex, contralateral primary motor cortex and contralateral somatosensory cortex may be activated simultaneously and produce movement-related cortical potential in humans. These results also indicate that the somatosensory cortex may receive inputs from the motor cortex directly before the onset of movement.

抄録全体を表示

We report a case of chromophobe renal cell carcinoma coincident with a malignant gastric gastrointestinal stromal tumor in a 71-year-old Japanese man. Although the occurrence of two coincidental malignant neoplasms is not rare, there are no documented case reports of chromophobe renal cell carcinoma (RCC) combined with gastric gastrointestinal stromal tumor (GIST) . Histopathologically, this RCC showed characteristic features of the chromophobe subtype, despite being negative for colloid iron staining, which is one of the hallmarks of chromophobe RCC. Immunohistochemical analysis of the GIST revealed that the spindle-shaped neoplastic cells were positive for CD34 and CD 117, but negative for smooth muscle actin and S 100. These results are indicative of an 'uncommitted' subtype of GIST. In addition, we extracted genomic DNA from paraffin-embedded sections of the gastric GIST and sequencing revealed a 6 by in-frame deletion in exon 11 of the c-kit gene, a gene that is frequently mutated in GIST. Although the significance of the coincidence of chromophobe RCC with gastric GIST is currently unknown, it will be interesting to investigate whether the molecular basis of oncogenesis is shared between these neoplasms.

抄録全体を表示