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Y Segawa

Publications and source records attributed to Y Segawa.

At least 19 recordsLinked to original sources
PubMed2001

Effects of a novel hepatoprotective drug, ZNC-2381, on fas-induced hepatocellular caspase-3 activity and apoptosis in mice.

We examined the effects of ZNC-2381 (1-(4-aminophenyl)methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b] pyridine-2-one), a new oral hepatoprotective agent, on hepatocellular caspase-3 activity and apoptosis induced by anti-mouse Fas antibody (anti-Fas ab) in mice. Oral ZNC-2381, administered at doses of 10, 30 and 100 mg/kg 1 h before inducing hepatic injury with anti-Fas ab, dose-dependently inhibited the increase in serum alanine aminotransferase (s-ALT) activity 8 h after injection of anti-Fas ab. Increases in DNA fragmentation (nucleosome assay) and caspase-3 activity in the liver 2 h after injection of anti-Fas ab were also inhibited by ZNC-2381 in a dose-dependent manner. As shown by histopathological examination, ZNC-2381 dose-dependently inhibited the appearance of TUNEL-positive apoptotic cells in the liver. Moreover, in studies in vitro, ZNC-2381 (1- 100 micromol/l) concentration-dependently inhibited increases in DNA fragmentation and caspase-3 activity caused by anti-Fas ab in isolated mouse hepatocytes. N- Acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-cho), a caspase-3-specific inhibitor, inhibited hepatocellular apoptosis caused by anti-Fas ab both in vivo and in vitro, as well as the increase in s-ALT activity in vivo. These results demonstrate that orally administered ZNC-2381 inhibits hepatocellular apoptosis induced by anti-Fas ab and presents the progression of hepatic injury. We propose that the mechanism of action of ZNC-2381 may involve blockade of the signal transduction pathway (caspase-3) of apoptosis mediated by anti-Fas ab.

Alanine Transaminase↗
PubMed2001

Possible changes in expression of chemotaxin LECT2 mRNA in mouse liver after concanavalin A-induced hepatic injury.

The functions of leukocyte-derived chemotaxin 2 (LECT2), a novel liver-specific protein, are not well defined, especially after hepatic injury. The changes in expression of LECT2 mRNA were investigated after concanavalin A (Con A)-induced hepatic injury in mice. Serum glutamate pyruvate transaminase (s-GPT) activity and the percentage of liver DNA fragmentation, an indicator of hepatic apoptosis, increased 8 h after intravenous administration of Con A (13 mg/kg). Expression of LECT2 mRNA was reduced from 8-24 h after injection of Con A, but was detected again 48 h after recovery from hepatic injury. Expression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma mRNA was observed in liver 2 h after Con A injection. Z-Val-Ala-Asp(OMe)-CH2F (Z-VAD-FMK), a caspase inhibitor, was administered to mice to investigate whether LECT2 was involved in apoptosis of liver cells after Con A injection. Z-VAD-FMK inhibited s-GPT activity and DNA fragmentation in the liver 8 h after Con A-induced hepatic injury, but did not prevent the reduction of LECT2 mRNA, or induction of TNF-alpha and IFN-gamma mRNA expression. When the relation between expression of LECT2, TNF-alpha and IFN-gamma mRNAs was examined 8 h after Con A injection in wild-type or immunodeficient (nu-/nu-) mice, the increase in TNF-alpha and IFN-gamma mRNA expression was found to be closely related to a reduction in LECT2 mRNA expression. These results suggest that the reduction in expression of LECT2 mRNA is not directly involved in apoptosis and may be inversely related to the expression of TNF-alpha and/or IFN-gamma mRNA in the injured liver.

Alanine Transaminase↗
PubMed2000

Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity.

PURPOSE: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. METHODS AND MATERIALS: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. RESULTS: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. CONCLUSIONS: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.

Adult↗
PubMed2000

Combination of nedaplatin and vindesine for treatment of relapsed or refractory non-small-cell lung cancer.

PURPOSE: A phase II study of nedaplatin and vindesine was conducted to evaluate their efficacy and safety for treatment of relapsed or refractory non-small-cell lung cancer (NSCLC). METHODS: Between August 1996 and September 1998, 48 patients who had previously received chemotherapy, thoracic radiotherapy, and/or surgery were enrolled in the study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and an age between 20 and 79 years. Treatment consisted of nedaplatin (80 mg/m2, day 1) and vindesine (3 mg/m2, days 1 and 8) every 3 to 4 weeks. RESULTS: Of 48 patients, 7 (14.6%) exhibited an objective response. Four (50%) of eight chemotherapy-naive patients had a partial response. However, of the 40 patients who had received prior chemotherapy, a partial response was observed in only 3 (7.5%). At a median follow-up time of 85.1 weeks, the median survival time was 43.6 weeks (95% confidence interval 34.4-52.7) for patients who had received chemotherapy, with a survival rate of 40% at 1 year. Grade 3 or 4 neutropenia occurred in 43 of 48 patients (90%), and neutropenic fever was observed in 3 of the 43 patients, one of whom died of sepsis. Pharmacokinetic and pharmacodynamic analyses of platinum were performed in 43 patients during the first cycle of chemotherapy. Percent reduction in absolute neutrophil count was correlated not only with the area under the plasma ultrafilterable platinum concentration versus time curve (r = 0.41, P = 0.007) but also with the duration of ultrafilterable platinum concentration above 1 microg/ml (r = 0.41, P = 0.007). Patients with progressive disease exhibited a shorter duration of ultrafilterable platinum concentration over 1 microg/ml (P = 0.046) than those with other responses. CONCLUSION: A combination of nedaplatin and vindesine was unsatisfactory as second-line chemotherapy for NSCLC, although the combination was well tolerated. The duration of ultrafilterable platinum concentration above 1 microg/ml was an important pharmacokinetic parameter for predicting both chemotherapy-induced neutropenia and treatment outcome.

Adult↗
PubMed2000

A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: a preliminary report from the Okayama Lung Cancer Study Group.

A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status < or = 2, age < or = 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m(-2), days 1-5) and 5-fluorouracil (5-FU) (500 mg m(-2), days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily, with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for N0-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (> or = Grade 3, 58% and 60% respectively). Other toxicities of > or = Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.

Adult↗
PubMed2000

Effects of chondroitin sulfate-C on articular cartilage destruction in murine collagen-induced arthritis.

The effects of chondroitin sulfate-C (CAS 25322-46-7, Chondroitin ZS Tab) on type II collagen (CII)-induced arthritis (CIA) in mice were evaluated. DBA/1J mice were immunized with bovine CII emulsified in Freund's complete adjuvant, followed by a booster injection 21 days later. Chondroitin sulfate-C at doses of 100, 300 and 1000 mg/kg was administered orally once daily beginning 14 days before initial immunization. An arthritis index and hind paw edema were examined from day 0 to day 49, when the mice were killed by ether anesthesia for histopathological examination. The delayed-type hypersensitivity (DTH) reaction, serum anti-CII antibody titer, and histopathologic characteristics of both synovitis and destruction of articular cartilage were analyzed. Both the arthritis index and the serum anti-CII antibody titer were reduced by treatment with chondroitin sulfate-C in a dose-dependent manner. Chondroitin sulfate-C (1000 mg/kg) significantly inhibited hind paw edema, synovitis and destruction of the articular cartilage, but not DTH reaction.

Animals↗
PubMed2000

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗
PubMed2000

Carotid brainstem reflex myoclonus after hypoxic brain damage.

A patient comatose after acute anoxia developed bilaterally synchronous, periodic myoclonic jerks most prominently in the bilateral upper limbs. Although the myoclonus seemed to occur spontaneously, electrophysiological studies showed that the myoclonic jerks correlated in timing and size with arterial pulses, and was suppressed by massage over the carotid sinus. It is proposed that the present myoclonus is a variant of brainstem reflex myoclonus in which arterial pulses served as intrinsic trigger stimuli via the carotid sinus and the medullary reticular formation.

Aged↗
PubMed2000

Effects of ZNC-2381, a new oral compound, on several hepatic injury models and on hepatocellular apoptosis in mice and rats.

The hepatoprotective effect of ZNC-2381 (1-(4-aminophenyl) methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b]pyridine-2-one), a novel 2-one dihydroimidazopyridine derivative, has been evaluated in several experimental models of hepatic injury. In mice, oral ZNC-2381, administered at doses of 3, 10 or 30 mgkg(-1), 1 h before induction of hepatic injury with concanavalin A, dose-dependently inhibited increases in serum alanine aminotransferase (ALT) activity. Apoptosis of liver cells, as indicated by DNA fragmentation (nucleosome assay) and DNA-ladder formation (electrophoresis), was also inhibited dose-dependently. ZNC-2381 dose-dependently inhibited concanavalin A-induced increases in serum tumour necrosis factor (TNF)-alpha levels, and TNF-alpha mRNA expression in the liver. Oral ZNC-2381 also dose-dependently inhibited increases in serum ALT activity in mice with hepatic injury induced by Propionibacterium acnes and a bacterial lipopolysaccharide (LPS) or D-galactosamine-LPS, and in rats with D-galactosamine-induced hepatic injury. These results indicate that oral ZNC-2381 inhibits cytokine (TNF-alpha) production and cytokine-related hepatocellular apoptosis, and might thus prevent different types of hepatic injury.

Alanine Transaminase↗
PubMed2000

Diet stimulation as a synergistic factor of aggravation in a pancreatic bile duct ligation-induced rat pancreatitis model.

We evaluated the association between aggravation of pancreatitis and multiple factors enhancing pancreatic exocrine secretion using a rat model of pancreatic bile duct ligation (PBDL)-induced pancreatitis. Under fasting and non-fasting conditions, a PBDL group, a second group treated by hepatic bile duct ligation (BDL) and a third group treated by pancreatic duct ligation (PDL) were compared in terms of serum amylase (S-amylase) activity. The S-amylase activity in the PBDL group was higher than in the sham group. In the PDL group, the increase in S-amylase activity was lower than in the PBDL group. In the BDL group, no increase in S-amylase activity was observed. Diversion of pancreatic and/or bile juice in these groups resulted in no increase of S-amylase activity. Truncal vagotomy or injection of an anticholinergic drug or a cholecystokinin (CCK)1-receptor antagonist inhibited pancreatic exocrine secretion and S-amylase activity in the non-fasting PBDL group but not in the fasting PBDL group. These results suggest that retention of pancreatic juice in the pancreatic duct is necessary for the increase of S-amylase activity, and that dietary stimulation and impaired duodenal inflow of bile and pancreatic juice commonly enhance pancreatic exocrine secretion, acting synergistically as aggravating factors in pancreatitis. CCK and the vagus nerve system appears to be involved in enhancing pancreatic exocrine secretion with diet stimulation as an aggravating factor.

Amylases↗
PubMed2000

Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition.

We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the exacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our model of pancreatitis in the rat was prepared by pancreatic bile duct ligation (PBDL), which simultaneously ligated the pancreatic duct and the common bile duct. Serum amylase activity and histopathological changes in the pancreas were used as indices of pancreatitis. We also measured the volume of pancreatic juice, as well as the amylase activity and protein level of the pancreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6 times at 1-h intervals. Administration of secretin (1-3 microg/kg, s.c.) did not influence serum amylase activity in rats with PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1 microg/kg, s.c.) increased serum amylase activity and promoted vacuolation of the pancreatic acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagonist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 microg/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis. These results suggest that not secretin, which regulates the volume of pancreatic juice, but CCK, which regulates the secretion of pancreatic enzymes via the vagal system, plays an essential role in food-stimulated exacerbation after the development of pancreatitis.

Amylases↗
PubMed2000

Fasting exacerbates acute pancreatitis by occlusion of the common bile duct in rats.

We examined the effects of fasting and non-fasting on gallstone-related acute pancreatitis by the occlusion of the common bile duct (OCD). We prepared a rat OCD-induced pancreatitis model under both fasting and non-fasting conditions, and we measured amylase activity in ascites as well as production of inflammatory cytokines and chemokines. We also examined the pathology of the pancreas, myeloperoxidase (MPO) activity in some tissues and mortality rates. In the fasted OCD group, ascites containing a large amount of amylase, interleukin 1beta (IL-1beta), interleukin 6 (IL-6), and cytokine-induced neutrophil chemoattractant-1 (CINC-1) as well as marked hemorrhage and necrosis of the pancreatic acinar cells were observed. Pulmonary MPO activity increased 3.4-fold compared to the control group. In the non-fasted OCD group, there was no development of ascites. Slight necrosis of acinar cells and slight increases in pulmonary MPO activity were observed. In addition, in the fasted OCD group, the cumulative mortality rate was 50% 6 days after ligation. However, in the non-fasted OCD group, none of the animals died. These results suggest that gallstone-related severe pancreatitis depends on fasting-related structural and/or functional changes in the pancreas. Moreover, increased production of inflammatory cytokines and chemokines in ascites under fasting condition may be involved in multiple organ failure resulting from severe acute pancreatitis.

Acute Disease↗
PubMed2000

Two cases of atypical carcinoid of the thymus.

We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.

Aged↗
PubMed2000

[Combination chemotherapy consisting of ifosfamide and vindesine for non-small cell lung cancer in the elderly].

To evaluate the nature and scope of treatment for non-small cell lung cancer (NSCLC) in the elderly, we retrospectively analyzed the cases of 166 patients (aged 75 years or more) who had been treated at our hospital between 1986 and 1997. In addition, we assessed the effectiveness and feasibility of combination chemotherapy consisting of ifosfamide and vindesine for 21 elderly patients. As their initial treatment, 20 patients (12%) received surgery; 65 (39%), curative chest radiotherapy; 30 (18%), chemotherapy; and 51 (31%), best supportive care. With combination chemotherapy consisting of ifosfamide (1.6 g/m2 on hospital days 1 through 3) and vindesine (2.5 mg/m2 on days 1 and 8), the response rate was 48% and the median survival time was 13.9 months (95% confidence interval: 5.6-22.2). Grade 3 or 4 leukopenia and neutropenia developed in 76% and 86% of the patients, respectively. However, other toxicities were generally mild, and no treatment-related deaths were observed. The combination of ifosfamide with vindesine may be effective for selected elderly NSCLC patients, and warrants further clinical study.

Aged↗
PubMed1999

Psychological impact of informed consent in hospitalized cancer patients. A sequential study of anxiety and depression using the hospital anxiety and depression scale.

Patients with cancer receive an explanation of their disease and the recommended treatment when they are asked to give informed consent (IC). In the course of this process patients suffer severe distress, including anxiety and depression, but physicians tend to underestimate it. The goal of this study was to reveal the magnitude of such stress and any changes to this during the IC process by means of the Hospital Anxiety and Depression (HAD) scale, a self-assessment scale. Of 171 in-patients newly diagnosed with lung cancer, 119 were assessable for serial HAD scale scores on admission, immediately after the IC process, and at 1 and again at 2 weeks after the IC. Both anxiety and depression scores increased significantly immediately after IC. Female patients had significantly higher anxiety and depression scores than males at 1 week after the IC. The patients with poor performance status demonstrated high anxiety scores on admission and immediately after the IC, and substantial depression persisted longer in these patients. The prevalence of high scores of more than 11 (judged as adjustment disorder or more severe state) immediately after the IC was 50% for anxiety and 31% for depression. The prevalence decreased significantly within 1 or 2 weeks, but 41% and 14% of the patients still showed high anxiety and depression scores, respectively. Physicians should be aware of these facts and pay special attention to their patients' psychological distress in routine clinical practice.

Adjustment Disorders↗
PubMed1999

Clinical investigation of atypical adenomatous hyperplasia of the lung.

The clinicopathologic characteristics of atypical adenomatous hyperplasia (AAH) remain unclear. A total of 137 patients underwent resection for adenocarcinoma of the lung at our institution. Examination of resected lung tissue showed that in addition to adenocarcinoma AAH was present in 26 cases and was not present in 111 cases. All nonsmokers with AAH (n = 13) had earlier-stage disease (stage IA, IB, IIA, and IIB) and no history of respiratory disease. Among patients with stage IA disease, the relapse-free and overall survival curves for those with AAH (n = 14) tended to be better than for those without AAH (n = 40), but the difference was not statistically significant (P = 0.056 and 0.087, respectively). Concurrent presence of AAH may be a favorable prognostic indicator in patients with stage IA adenocarcinoma.

Adenocarcinoma↗