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Biomedical subjects

T Kasai

Publications and source records attributed to T Kasai.

At least 181 records · Page 10Linked to original sources

Prospective evaluation of the feasibility of cisplatin-based chemotherapy for elderly lung cancer patients with normal organ functions.

A study was conducted to examine the feasibility of cisplatin-based chemotherapy in elderly patients (> or = 75 years old) with advanced non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Thirty-four patients were enrolled between September 1993 and December 1994. Patients with normal organ function and good performance status (PS) received cisplatin-based chemotherapy (cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 2 and 8 for NSCLC, or cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 2 to 4 for SCLC). Ten patients (29%) were eligible for this study, 7 with NSCLC and 3 with SCLC. Reasons for exclusion were ischemic heart disease in 14, poor PS (> or = 2) in 11, reduced creatinine clearance (Cer) in 10, abnormal electrocardiogram without ischemia in 9 and noncompliance with the protocol in 2 patients. Eight patients had two or more reasons. Nine of the 10 eligible patients were able to tolerate two or more courses of chemotherapy. All 3 patients with SCLC responded (1 complete response and 2 partial response), but only 1 of the patients with NSCLC achieved partial response. Toxicity was evaluated according to Japan Clinical Oncology Group criteria. All but one patient experienced grade 4 neutropenia, and 6 patients had infectious episodes requiring antibiotics. Grade 3 anemia and thrombocytopenia were observed in 1 and 2 patients, respectively. Non-hematological toxicities were mild. Only 10 of 34 patients (29%) satisfied our eligibility criteria and they experienced severe myelotoxicity. We conclude that chemotherapy should be given carefully to elderly patients even if they appear to have normal organ function.

Aged↗

Caseinphosphopeptides (CPP) in feces and contents in digestive tract of rats fed casein and CPP preparations.

A part of caseinphosphopeptides (CPP) formed during the digestion of casein in the small intestine of rats fed casein was not hydrolyzed in the digestive tract, but was excreted into the feces. Amino acid compositions of CPP fraction of feces for wk 1 and 2 were almost identical. The residual CPP in the feces expressed by the rate of bound phosphoserine in the CPP fraction of feces to bound phosphoserine ingested (phosphoserine-CPP/phosphoserine-ingested rate) in the ileum was the highest 4 h after the start of feeding of casein but decreased significantly after 10 h. No significant difference was observed in the rats of contents in jejunum, cecum, and colon between 4 h and 10 h after the start of feeding. No significant difference was observed in the phosphoserine-CPP/phosphoserine-ingested rate in contents of any part of the digestive tract between 50% casein and 50% CPP I (a commercial CPP product with nearly the same amino acid composition as that of casein) 4 h and 10 h after the start of feeding, except for the cecum 4 h after the start of feeding. No significant difference in phosphoserine-CPP/phosphoserine-ingested rate was observed in the contents of any part of digestive tract between the groups fed 50% casein and 5% CPP III +45% soybean protein isolate (SPI) 4 h or 10 h after the start of feeding (CPP III is a commercial CPP product containing nearly 8 times the concentration of phosphoserine as CPP I).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

A protein less sensitive to trypsin, guanidinated casein, is a potent stimulator of exocrine pancreas in rats.

Previously, we have shown that, in rats that have had bile-pancreatic juice (BPJ) diverted from the proximal small intestine for 7 days, the exocrine pancreatic secretion was enhanced after they were fed a casein, fat-free diet. This demonstrates that the pancreatic secretion is stimulated by dietary protein with a pancreatic protease-independent pathway. To examine the chemical structure of casein responsible for the enhancement of pancreatic secretion, we prepared chemically modified casein in which lysine residues were guanidinated. Secretion of protein, amylase, and chymotrypsin in the chronic BPJ-diverted rat was increased much more after the rats were fed a diet containing guanidinated casein (250 g/kg diet) than after they were fed a diet containing intact casein (250 g/kg diet). In normal rats whose diverted BPJ was returned to the duodenum, the increases in the pancreatic secretion after consuming the guanidinated casein diet were comparable to those after consuming the intact casein diet. In vitro digestibility of guanidinated casein by trypsin and chymotrypsin was much lower than that of intact casein. Also, guanidinated casein inhibited tryptic hydrolysis of benzoyl-L-arginine p-nitroanilide to a lesser extent than did intact casein as determined by an in vitro assay. These results demonstrate that guanidinated casein is less sensitive to trypsin than is intact casein and that the structure that is sensitive to trypsin is not involved in the stimulation of pancreatic secretion in diverted rats. The results evidence that masking luminal trypsin activity does not predominantly contribute to the enhancement of pancreatic secretion in 7-day BPJ-diverted rats. Also, in normal rats, the luminal protease-independent mechanism may play a role partly in increasing the pancreatic secretion by dietary protein.

Amylases↗

Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results.

A study was conducted to evaluate the impact of cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulating factor (G-CSF) on advanced thymoma or thymic cancer. Between August 1989 and December 1994, 14 patients with invasive, metastatic or recurrent thymoma or thymic cancer were treated with cisplatin (80 mg/m2, on day 1), doxorubicin (45 mg/m2, on day 1), cyclophosphamide (800 mg/m2, on day 1) and etoposide (80 mg/m2, on day 1-3) with G-CSF (90 micrograms/m2, on day 5-18) at the National Cancer Center Hospital, Tokyo. Courses were repeated every 3 or 4 weeks for a maximum of 4 cycles. Twelve patients were treated with 2 or more courses of PACE. Two patients were treated with only one course, one refused and another required emergency thoracic radiotherapy after one course of PACE. Six patients had partial responses (3 thymomas and 3 thymic cancers) but there were no complete remissions (response rates, 42.9%; 95% confidence interval, 17.7% to 71.1%). Moderate hematological toxicities were observed: grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopenia in 10, 13, 8 and 6 patients, respectively. Six patients developed infections that required antibiotics. Surgical resection or thoracic radiotherapy after PACE treatment was performed in 2 and 7 patients, respectively. The overall median survival time was 14.7 months (range, 5.9 to 59.7 months). For 9 patients who had received no prior treatment before chemotherapy, the median survival time was 8.9 months, and one patient survived for 4 years and is still alive. In conclusion, PACE with G-CSF frequently produces objective remissions in patients with advanced thymoma or thymic cancer. A large-scale intergroup study is necessary to determine the impact of this regimen on advanced thymoma and thymic cancer.

Adult↗

Plasma interleukin 8 and polymorphonuclear leukocyte elastase concentrations in patients with septic shock.

We determined the plasma concentrations of interleukin 8 (IL-8), polymorphonuclear leukocyte elastase (PMNE), and endotoxin in patients with septic shock in order to investigate the role of IL-8 and PMNE in the development of septic shock, especially in septic adult respiratory distress syndrome (ARDS). The IL-8 concentration in patients with septic shock was 6.28 +/- 9.00 ng/mL (mean +/- SD, n = 29), which was significantly higher (P < 0.0001) than the concentration in septic patients without shock (0.35 +/- 0.35 ng/mL, n = 40). There was a significant correlation between the IL-8 concentration and the PMNE concentration at the onset of septic shock (r = 0.6916, P < 0.0001). The IL-8 concentration was also significantly correlated with the endotoxin concentration (r = 0.5584, P = 0.0016). There was a significant negative correlation (r = -0.8237, P < 0.0001) between the serum PMNE concentration and the oxygenation index (PaO2/FiO2) at the onset of septic shock. These results indicate that IL-8 and PMNE are produced in large quantities when septic shock occurs, and may play a role in the development of septic ARDS.

Adult↗

Inhibitory effect of FUT-175 on the production of interleukin 8 and polymorphonuclear leukocyte elastase.

We investigated the inhibitory effects of a protease inhibitor, FUT-175, on the production of interleukin 8 (IL-8) and polymorphonuclear leukocyte elastase (PMNE) by polymorphonuclear leukocytes (PMN) and vascular endothelial cells. IL-8 production by PMN and vascular endothelial cells stimulated with lipopolysaccharide (LPS) was inhibited by FUT-175. This compound also inhibited PMNE production by PMN following LPS stimulation.

Benzamidines↗

[A case of giant bronchogenic cyst complicated with postoperative esophageal perforation].

A 42-year-old man with giant bronchogenic cyst occupied from the middle and posterior mediastinum was treated surgically. The tumor was stoutly adhered to anterior aspect of the esophagus and membranous portion of the right bronchus. In dissecting the tumor, muscular coat of the esophagus was partly severed, which was repaired interruptedly with absorbable suture material. However, esophageal perforation was detected by barium swallow on the 3rd postoperative day. Conservative therapy included intrathoracic drainage and antibiotics was successfully undertaken. It is imperative to dissect the tumor very carefully if the giant bronchogenic cyst adheres to the esophagus or other surrounding organs.

Adult↗

Antiscorbutic activity of 6-bromo-6-deoxy-L-ascorbic acid in the guinea pig.

The antiscorbutic activity of 6-bromo-6-deoxy-L-ascorbic acid (I) in guinea pigs was compared to that of ascorbic acid (AsA). The growth test results in guinea pigs did not show any significant difference between the body weight increase in the respective 2 groups given compound (I) and that in the group given AsA. Scorbutic guinea pigs were found to completely recover from the disease after administration of the compound (I). There were no significant differences in the plasma alkaline phosphatase activity and the hydroxyproline content in the tibia between the group given compound (I) and that given AsA. The total vitamin C contents in the various tissues were similar in the 2 groups given compound (I) and the C-deficient group but they were lower than the levels for the group given AsA. It was shown that antiscorbutic activity was characteristic of compound (I) and it was almost equal to the effect of AsA.

Alkaline Phosphatase↗

Blood levels of endothelin-1 and thrombomodulin in patients with disseminated intravascular coagulation and sepsis.

We evaluated the roles of plasma endothelin-1 and plasma thrombomodulin in the development of disseminated intravascular coagulation (DIC) in patients with sepsis. Plasma endothelin-1 was measured by radioimmunoassay (RIA). Plasma thrombomodulin and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay (ELISA), and serum protein C (protein C) was measured by the synthetic substrate method. Endotoxin was measured by the Endospecy test, a synthetic substrate method. A new perchloric acid method was used for the pretreatment of plasma. Blood levels of endothelin-1 and thrombomodulin were significantly higher in patients with DIC than in those without DIC (p < 0.0001). Endothelin-1 and thrombomodulin levels were positively correlated (r = 0.8645, p = 0.0001), as were endothelin-1 and TNF-alpha levels (r = 0.5441, p = 0.0002). Thrombomodulin and protein C levels were negatively correlated (r = -0.5627, p = 0.0001). Endotoxin was elevated above the normal level 14.3% (6/42) for these patients. TNF-alpha is involved in the production of endothelin-1 and thrombomodulin, which play a role in the pathogenesis of DIC and whose blood levels reflect its severity.

Adult↗

[Can improvement in therapy decrease the rate of death due to lung cancer?].

The incidence of lung cancer is increasing, and therapy for patients with this disease is not satisfactory. Surgery is done for patients with clinical (c)-stage I, II, and resectable stage IIIA non-small cell lung cancer (NSCLC). Chemotherapy, alone or in combination with radiotherapy, is given to patients with unresectable stage IV and stage III NSCLC, respectively. Chemotherapy is an important therapeutic modality for patients with small cell lung cancer (SCLC). CDDP + VP-16 (PVP) and CPA + ADM + VCR (CAV) alternating PVP regimens are standard treatment for patients with SCLC. Chemotherapy and radiotherapy are given to patients with limited disease. To develop more effective treatments, we are investigating (1) the schedule and timing of radiotherapy, (2) combination chemotherapy including new drugs, (3) dose-intensive chemotherapy, and (4) new strategies such as gene therapy. Radiotherapy is commonly used sequentially and the standard fractionation is 2 Gy/fr/day. We are studying other timings, such as concurrent and alternating, and other schedules, such as hyperfractionation and accelerated hyperfractionation. Promising new drugs include paciltaxel, docetaxel, vinorelbine, and CPT-11. These are now used in combination with platinum. To evaluate dose-intensive chemotherapy for SCLC, we are conducting a phase III study comparing CODG + G-CSF with CAV/PVP.

Carcinoma, Non-Small-Cell Lung↗

The concomitant augmentation of urokinase-type plasminogen activator and collagenase-like proteinase activities in X-ray irradiated cells of a human metastatic carcinomatous line.

The enzymatic activities of uPA, and a collagenase-like proteinase in the post-nuclear fraction of cell homogenates of a metastatic carcinomatous cell line following X-ray irradiation were examined by the use of chromogenic substrates and by casein- or gelatin-containing zymographies and electrophoretic gel stained with avidin-conjugated peroxidase. Enhanced activities were observed in these cells, while those of 5'nucleotidase and Na(+)-K(+)-ATPase were attenuated. A partial purification and characterization of the collagenase showed that it was able to hydrolyze the heat-denatured type-I collagen more efficiently than the native one. The activation of both uPA and collagenase enables an efficient degradation of matrix barrier proteins. These findings suggest that following a certain dose range of X-ray irradiation, tumor cells may increase their ability to migrate and invade through the enhancement of uPA and collagenase activities.

Amino Acid Sequence↗

Cervical spinal cord injury associated with ossification of the posterior longitudinal ligament.

Among 231 patients with cervical injuries treated over 12 years, 15 had cervical spinal cord injury associated with ossification of the posterior longitudinal ligament. All of them were male and most had injuries due to a relatively weak external force. Four of them underwent surgery. There was little difference in improvement of paralysis between the conservatively and the surgically treated group.

Aged↗

Metabolic activation of nitrodibenzofurans by rat liver in Salmonella/mutagenicity test.

The effect of metabolic activation on the mutagenicity of nitrodibenzofurans (NDF) by rat liver S9 was evaluated with S. typhimurium tester strains. Except for 1-nitrodibenzofuran (NDF), five tested NDFs were mutagenic in strains TA98 and TA98/1,8-DNP6 without S9 mix but were not mutagenic in strain TA98NR. NDFs mutagenized strain TA98NR with S9 mix, and the NAD(P)H system plus 3-methylcholanthrene-induced S9 (3-MC-S9) was the most effective. The specificity of S9 enzyme(s) participating in the activation of NDFs was different from that of endogenous enzyme(s) in strain TA98, i.e., the order of mutagenic potency of NDFs in strain TA98 without S9 mix was 2,8- = 2,7-->3-->2-->4-->1-nitrated dibenzofuran and 2-NDF and 2,8-dinitrodibenzofuran (DNDF) were more mutagenic than 3-NDF and 2,7-DNDF, respectively, in strain TA98NR with S9 mix. The mutagenic potency of 2-NDF, 4-NDF, 2,7-DNDF and 2,8-DNDF in strain TA98NR with S9 mix was stronger than those in strain TA98 without S9 mix and the cytosolic fraction of the 3-MC-S9 accounted for more of the activation than the microsomal fraction. Studies with electron donors and inhibitors indicated that xanthine oxidase and/or NAD(P)H-quinone oxido-reductase (NQOR) participated in the activation of NDFs. The mutagenic potency of NDFs in strain TA98NR with S9 mix (3-MC-S9) was reflected in the induction of NQOR by pretreatment of rats with 3-MC.

Animals↗

Quantitative EMG analysis of anticipatory postural adjustments of voluntary contraction of leg muscles in standing man.

The present experiment was undertaken to investigate the sequence of postural muscle activities involved in rapidly standing on the toes from a variety of standing positions. By varying the angle of incline of the platform on which the subject was standing, it was possible to study changes in the adaptability of the anticipatory postural muscle activity. Results showed that the initial inclination of the platform had a significant effect on the duration of soleus muscle activity and the onset and duration of tibialis anterior muscle activity. It appears that preparatory and focal motor activity can be modulated in an adaptive way according to the change in movement mechanics resulting from standing on an inclined platform.

Adult↗

T1-weighted images with ECG gating using partial flip angle spin-echo imaging.

ECG-gated spin-echo imaging can reduce vascular artefacts compared with spin-echo scans without gating. However, this method produces poor T1-weighted images because the repetition time (TR) is limited by the heart rate. We investigated the value of low flip angle spin-echo imaging for increasing T1-dependent contrast when using ECG gating. Using computer simulation, the predicted contrast increased with decreasing the flip angle, and the effect was almost saturated at a flip angle of around 40 degrees. With the application of this flip angle, the identical image contrast as a T1-weighted image (TR = 400 ms) can be obtained within the heart rate range of 65 to 75 beats/min. For clinical evaluation, the tissue contrast index values ((signal intensity in the lesion-signal intensity in the muscle)2 x 100/signal intensity in the muscle) obtained by conventional spin-echo and low flip angle spin-echo imaging were compared in 17 patients. The contrast index of low flip angle spin-echo images (74.0 +/- 52.0) was significantly higher than that of conventional spin-echo images (40.9 +/- 35.9). Thus, ECG-gated low flip angle spin-echo imaging provided better T1-dependent contrast than conventional ECG-gated spin-echo imaging. This method may be especially useful for Gd-DTPA-enhanced magnetic resonance imaging.

Aged↗

Effects of patent ductus arteriosus on left ventricular output and organ blood flows in preterm infants with respiratory distress syndrome treated with surfactant.

Thirty preterm infants (birth weight < 1500 gm) treated with Surfactant TA for the respiratory distress syndrome, who had no complicating clinical problems other than ductal patency, were studied by serial Doppler flow examinations to determine the effects of early left-to-right shunt through the patent ductus arteriosus on the left ventricular output and organ blood flows. Doppler flow variables in 15 infants with a hemodynamically significant patent ductus arteriosus (hsPDA) were compared with those in 15 subjects without hsPDA matched for age, body weight, and gestational age. Infants with hsPDA had significantly higher left ventricular output and significantly lower blood flow volume in the abdominal aorta, and lower temporal mean blood flow velocities, with concomitant increases in the relative vascular resistance in the celiac artery, superior mesenteric artery, and renal artery. Pulsatility indexes of these vessels and the anterior cerebral artery were significantly higher in the hsPDA group, but the temporal mean blood flow velocities in the anterior cerebral artery and its vascular resistance were not significantly different between the two groups. After closure of the patent ductus arterious was achieved with mefenamic acid therapy, alterations in Doppler flow variables in the hsPDA group reverted to the levels seen in the group without hsPDA. These results suggest that despite large left-to-right ductal shunting, the heart of the preterm infant is capable of mounting a compensatory increase of cardiac output sufficient to maintain unchanged cerebral blood flow, but is unable to maintain postductal organ blood flows because of decreased perfusion pressure (ductal steal) and localized increase in vascular resistance.

Blood Flow Velocity↗

Plasma endotoxin and cytokine concentrations in patients with hemorrhagic shock.

OBJECTIVES: The roles of cytokines and endotoxin in hemorrhagic shock, particularly the translocation of endotoxin and bacteria during hemorrhagic shock, were investigated. DESIGN: Prospective study. SETTING: Critical care and emergency center of a university hospital. PATIENTS: Twenty-nine patients with hemorrhagic shock and 20 healthy controls. INTERVENTIONS: Serial blood samples were collected from both study and control patients. Standard resuscitation techniques were used. MEASUREMENTS AND MAIN RESULTS: Plasma levels of endotoxin and various cytokines were determined repeatedly during hemorrhagic shock. Endotoxin was measured using an endotoxin-specific assay in addition to a new perchloric acid method for pretreatment of plasma. Cytokines were measured by commercial enzyme-linked immunosorbent assays. Plasma endotoxin concentrations remained within the normal range for 7 days after admission. Although levels of tumor necrosis factor-alpha and several interleukins increased slightly in some patients, these cytokines did not reach the levels seen in septic shock. CONCLUSIONS: Translocation of bacteria or endotoxin from the gastrointestinal tract into the bloodstream has been noted in animal experiments; however, translocation was not detected in our patients with hemorrhagic shock.

Adolescent↗