[Study of specific mRNA expression by peripheral monocytes of patients with diffuse panbronchitis using cDNA representational difference analysis (RDA)].
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Anti-Bacterial Agents↗
Biomedical subjects
T Takada
Publications and source records attributed to T Takada.
Fas/APO-1-mediated apoptosis of human renal cell carcinoma.
We have investigated the Fas-mediated apoptosis of cultured human renal cell carcinoma OUR-10. OUR-10 cells express Fas antigen on their cell surface and showed apoptotic cell death by stimulation with anti-Fas agonistic antibody. Cell proliferation of OUR-10 was reduced to 62% by the addition of anti-Fas antibody. The cytotoxic effect of anti-Fas antibody on OUR-10 was augmented by the pretreatment of these cells with interferon-gamma, not with interferon-alpha or with interleukin-2. Flow cytometry demonstrated that preculture of Our-10 cells with interferon-gamma increased the cell surface Fas antigen. Immunohistochemical analysis of resected tissues from the patients with renal cancer revealed stronger expression of Fas antigen on the surface of cancer cells than that of normal cells. These data suggest that Fas may be one of the possible targets for a novel approach to human kidney cancer, and the efficiency of this Fas-mediated treatment for kidney cancer could be augmented by the treatment with interferon-gamma.
Apoptosis↗
Characterization of a 115-kDa protein that binds to SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in Chinese hamster ovary cells.
SH-PTP2, a non-transmembrane-type protein-tyrosine phosphatase with two Src homology 2 domains, was previously shown to play a positive signaling role in the insulin-induced activation of Ras and mitogen-activated protein kinase. SH-PTP2 was shown to associate with a 115-kDa tyrosine-phosphorylated protein (pp115), as well as with insulin receptor substrate 1, in insulin-stimulated Chinese hamster ovary cells that overexpress human insulin receptors (CHO-IR cells). In vivo and in vitro binding experiments revealed that SH-PTP2 bound to pp115 through one or both of its SH2 domains. The pp115 protein was partially purified from insulin-stimulated CHO-IR cells that overexpress a catalytically inactive SH-PTP2 by a combination of immunoaffinity and lectin-affinity chromatography. A monoclonal antibody to pp115 was then generated by injecting the partially purified protein into mice. Experiments with this monoclonal antibody revealed that pp115 is a transmembrane protein with a domain exposed on the cell surface and that it binds to SH-PTP2 in response to insulin. The insulin receptor kinase appeared to phosphorylate pp115 on tyrosine residues both in vivo and in vitro. The extent of tyrosine phosphorylation of pp115 associated with SH-PTP2 was greatly increased in CHO-IR cells that overexpress catalytically inactive SH-PTP2 compared with that observed in CHO-IR cells overexpressing wild-type SH-PTP2. Furthermore, recombinant SH-PTP2 preferentially dephosphorylated pp115 in vitro, indicating that SH-PTP2 may catalyze the dephosphorylation of phosphotyrosine residues in pp115 after it binds to this protein. These results suggest that pp115 may act as a transmembrane anchor to which SH-PTP2 binds in response to insulin. Furthermore, pp115 may be a physiological substrate for both the insulin receptor kinase and SH-PTP2.
Animals↗
Controlling substrate preference and transglycosylation activity of neopullulanase by manipulating steric constraint and hydrophobicity in active center.
The substrate specificity and the transglycosylation activity of neopullulanase was altered by site-directed mutagenesis on the basis of information from a three-dimensional structure predicted by computer-aided molecular modeling. According to the predicted three-dimensional structure of the enzyme-substrate complex, it was most likely that Ile-358 affected the substrate preference of the enzyme. Replacing Ile-358 with Trp, which has a bulky side chain, reduced the acceptability of alpha-(1-->6)-branched oligo- and polysaccharides as substrates. The characteristics of the I358W-mutated enzyme were quite different from those of wild-type neopullulanase and rather similar to those of typical starch-saccharifying alpha-amylase. In contrast, replacing Ile-358 with Val, which has a smaller side chain, increased the preference for alpha-(1-->6)-branched oligosaccharides and pullulan as substrates. The transglycosylation activity of neopullulanase appeared to be controlled by manipulating the hydrophobicity around the attacking water molecule, which is most likely used to cleave the glucosidic linkage in the hydrolysis reaction. We predicted three residues, Tyr-377, Met-375, and Ser-422, which were located on the entrance path of the water molecule might be involved. The transglycosylation activity of neopullulanase was increased by replacing one of the three residues with more hydrophobic amino acid residues; Y377F, M375L, and S422V. In contrast, the transglycosylation activity of the enzyme was decreased by replacing Tyr-377 with hydrophilic amino acid residues, Asp or Ser.
Amino Acid Sequence↗
Mutagenic activation of N-nitrosobis(2-oxopropyl)amine by pancreatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs.
CONCLUSION: The results suggest that systemic administration (s.c. and i.p.) of BOP induces liver damage due to BOP itself and/or its metabolites which might be formed in the liver and that interaction of BOP itself in the pancreatic duct with pancreatic juice plays an important role for pancreatic duct tumorigenicity. METHODS: Mutagenic activation and pancreatic duct tumorigenicity of N-nitrosobis (2-oxopropyl)amine (BOP) administered s.c., i.p., and i.d. were studied in dogs. RESULTS: Following i.p. administration of BOP, N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP), but not BOP, were detected in pancreatic juice, while following i.d. administration, only BOP was detected. The pancreatic juice of one dog that received 100 mg of BOP i.d. showed positive mutagenicity towards Salmonella typhimurium TA100, but the pancreatic juice of two dogs that received 100 mg of BOP i.p. was not mutagenic. BOP showed clear mutagenicity in the presence of pancreatic juice from untreated dogs, but the pancreatic juice could not activate HPOP and BHP to mutagens. BOP administered sc for 2 wk (total dose: 600 mg) induced clinical toxicity, nausea, vomiting, and loss of appetite at 10 wk. BOP administered i.p. for 4 mo (total dose: 2000 mg) induced liver damage at 6 mo, but no pancreatic injury. BOP administered i.d. for 6.5 or 12 mo (total dose: 2500 or 4700 mg, respectively) induced papillary hyperplasia and dysplasia of duct epithelial cells and ductal proliferation with fibrosis.
Animals↗
The reduction and redistribution of plantar pressures using foot orthoses in diabetic patients.
High pressures on the soles of the feet of diabetic patients cause plantar ulcerations, and reduction of this pressure is important in the treatment and prevention of such ulcers. The effects of foot orthoses on the distribution of plantar pressures were investigated using a pressure-sensitive insole containing 960 sensor elements in seven diabetic patients (13 feet) with diabetic ulcers or past histories of diabetic ulcers. Plantar pressures at the foot-insole interface and their distribution were measured in a stable standing position wearing the patients' own shoes, with and without foot orthoses. The preorthotic peak pressure was 130.6 +/- 41.9 kPA (mean +/- S.D.), while the postorthotic peak pressure was reduced to 52.6 +/- 17.9 kPa (P < 0.001 vs. preorthotic). The mean reduction of pressure was 56.3%. The preorthotic contact area was 330.2 +/- 48.4 pressure-sensitive elements and the postorthotic contact area was increased to 517.2 +/- 105.5 elements (P < 0.001), with a mean increase of 62.7%. The marked reduction in plantar pressures at the foot-insole interface by pressure redistribution indicates that this new pressure measurement system is very useful for the design of such orthoses.
Adult↗
Indications for the choledochoscopic removal of intrahepatic stones based on the biliary anatomy.
BACKGROUND: Choledochoscopic treatment has been used primarily to remove intrahepatic stones. However, failure in removing such stones can occasionally occur, resulting in the need for additional surgery. The aim of this study was to clarify the clinical indications and limitations of choledocoscopic treatment for the removal of intrahepatic stones. METHODS: A review of the records of 86 patients treated for intrahepatic stones between April 1974 and December 1993 formed the basis of this study. These patients were evaluated based on their bile-duct findings (no strictures, mild strictures, or severe strictures), the site of the stones (left hepatic lobe, right hepatic lobe, and the bilateral lobes), and the presence of variations in the posterior segmental bile-duct drainage. RESULTS: Complete removal of stones was achieved in 59 patients (69%). Further, choledochoscopic removal was mainly successful in patients with no strictures or, to a lesser degree, with mild strictures; whereas stone removal was impossible in all patients (19) with severe strictures (P < 0.0001). As for the site of the stones, no statistical differences were seen among the three groups. Regarding the presence of drainage variations of the segmental bile duct, removal of the stones was more difficult in patients with variations than in those without variations (P < 0.01). With respect to long-term clinical outcomes, of the 59 successful patients, only 2 (3%) developed recurring stones. CONCLUSION: Based on these findings, choledochoscopic treatment should be indicated for patients who have no, or only mild, bile-duct strictures and who mainifest normal segmental bile-duct drainage.
Bile Ducts↗
Somatosensory evoked potentials recorded from the posterior pharynx to stimulation of the median nerve and cauda equina.
Somatosensory evoked potentials (ppSEPs) in response to stimulation of the median nerve at the wrist and the cauda equina at the epidural space (the L4 level) were recorded from the posterior wall of the pharynx in 15 patients who underwent spinal surgery under general anesthesia, using disc electrodes attached to the endotracheal tube, and compared with segmental spinal cord potentials (seg-SCPs) that were recorded simultaneously from the posterior epidural space (PES). ppSEPs consisted of the initially positive spike (P9) followed by slow positive (P13) and negative (N22) waves. The P13 and N22 of ppSEPs had phase reversal relationship with the P2 and N2 recorded from the PES, respectively. The peak latencies of P9 (9.40 +/- 0.7 ms) (mean +/- SD), P13 (13.1 +/- 0.9 ms), and N22 (22.0 +/- 2.1 ms) of ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs, respectively, ppSEPs were recorded more clearly with a reference electrode on the dorsal surface of the neck than with the reference electrode at the earlobe or back of the hand. The threshold and maximal stimulus intensities were also similar between the ppSEPs and seg-SCPs. Thus, the P9, P13, and N22 components of ppSEPs were thought to have the same origin as the P1, N1 and P2 of seg-SCPs, respectively. Therefore, the P9, P13 and N22 of ppSEPs may reflect incoming volleys through the root, synchronized activities of the interneurons and primary afferent depolarizations (PAD), respectively. ppSEPs in response to cauda equina stimulation showed that the latencies of the two initial components (4.6 +/- 0.4 and 6.4 +/- 0.6 ms) corresponded to those of the SCPs recorded from the PES (4.6 +/- 0.3 and 6.3 +/- 0.5 ms), suggesting that these potentials reflect impulses conducting through the spinal cord, similar to epidurally recorded SCPs.
Adult↗
Immunosuppression by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies of free and vascularized skin allograft rejection.
Immunosuppression by anti-adhesion molecule antibody of free or vascularized skin allograft rejection was investigated in rats. Lewis (LEW, RT11) rats were used as donors and Fisher (F344, RT11v1) rats as the recipients. When F344 rats were treated intraperitoneally (i.p.) with anti-intercellular adhesion molecule-1 (ICAM-1) mAb (1A29) (3 mg/kg/day) and anti-leukocyte function-associated antigen-1 (LFA-1) mAb (WT.1) (3 mg/kg/day) one day prior to grafting and daily after grafting for nine days, free skin graft survival was prolonged only slightly compared with that in control rats which were injected i.p. with a daily dose of 6 mg/kg of anti-TNP mAbs (H1-6-2) one day prior to grafting and daily after grafting for nine days. (Mean survival time [MST] of the free skin graft was 11.2 +/- 0.6 days in the control group and 13.4 +/- 0.3 days in the 1A29 + WT-1 treated group [p < 0.01], respectively.) On the other hand, the vascularized graft survival was prolonged significantly in anti-ICAM-1/LFA-1 mAbs-treated F344 rats as compared with that in control rats. (The mean vascularized graft survival time was 14.2 +/- 0.7 days in the control group and 21.5 +/- 1.9 days in 1A29 + WT-1 treated group [p < 0.002]). Our results suggest that interaction with ICAM-1 and LFA-1 is more important in the rejection of vascularized skin allografts than that of free skin allografts.
Animals↗
Physical and clinical evaluation of a 2,048 x 2,048-matrix image intensifier TV digital imaging system in bone radiography.
RATIONALE AND OBJECTIVES: To evaluate the potential utility of a 2,048 x 2,048-matrix image intensifier television digital radiography (DR) system versus a conventional screen-film (S-F) system for bone radiography. METHODS: Basic imaging properties were evaluated including resolution properties, Wiener spectra, and detectabilities of low-contrast signals. DR images were obtained with the same exposure (iso-dose) or one-third the exposure (low-dose) used with the S-F system. The visibility of pathologic details of metastatic disease on bone radiographs of 27 patients was evaluated subjectively by six radiologists. RESULTS: Resolution properties of the DR system were slightly superior to those of the S-F system at low-frequency range, but the S-F system showed considerably higher resolution properties at the high-frequency range. The noise levels for iso-dose DR were slightly greater than those for S-F imaging at low spatial frequency; however, low-dose digital radiographs showed higher noise levels. Visibility of details of diagnostic features on bone radiographs was similar with both systems, but the low-dose digital radiographs were slightly inferior. CONCLUSION: High-resolution image intensifier television DR systems may be clinically useful for bone radiography.
Bone Neoplasms↗
Periodicity and prediction of mania onsets in biopolar I affective disorders.
In studying the periodicity of mania onsets, cycle-oriented diagrams were made of the clinical course from 257 manic episodes analyzed retrospectively in 34 bipolar I manic-depressive patients for a period of about 5 years. Using these diagrams, the frequent period of mania onsets located in one-quarter of the follow-up period was pre-estimated, and the accordance ratio during a 25 month follow-up period was analyzed. The accordance ratio in all subjects was 39% (11/28) for the first episode and 35% (7/20) for the second episode. These ratios were not significantly different from the expected level (25%). The number of subjects was limited to 11 patients (10 rapid and 1 non-rapid cyclers) whose number of episodes used for the determination of the index cycle was eight or more. The accordance ratio was 64% (7/11) and 60% (6/10) for the first and second episodes, respectively. Their levels were significantly higher than those expected. Periodicity of mania onsets existed at least in rapid cyclers with abundant past data.
Adult↗
A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion.
Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important roles in growth factor and cytokine signal transduction pathways. A protein of approximately 115 to 120 kDa that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts (SR-3Y1 cells), and the corresponding cDNA was cloned. The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells. Thus, SHPS-1 may be a direct substrate for both tyrosine kinases, such as the insulin receptor kinase or Src, and a specific docking protein for SH2-domain-containing PTPases. In addition, we suggest that SHPS-1 may be a potential substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling.
Amino Acid Sequence↗
[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].
The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.
Adult↗
[Preoperative chemoradiation therapy for lower rectal cancer].
To identify appropriate candidates with rectal cancer for preoperative chemoradiation therapy, the local recurrence rate and clinicopathological characteristics of 232 patients with rectal cancer undergoing curative resection in our department were investigated. The local recurrence rates were 3.8%, 10.8% and 16.5% in the Rs, Ra and Rb lesions, respectively. Regarding lower (Rb) rectal cancer, depth of lesion (> a1) and nodal metastasis consisted of high factors for local recurrence. Basing on these results, entry criteria for preoperative chemoradiation therapy were established, and concurrent chemoradiation therapy with fluorouracil and cisplatin was delivered preoperatively in 9 primary cases of locally advanced rectal cancer and 3 cases with local recurrence. A partial response was obtained in 7 of 12 cases with a response rate of 58%, size-reduction of the distant metastatic lesions was found in 2 cases, and clinical symptoms were improved in all cases. The histological responses of the 6 resected cases were Grade 2 in 2 cases and Grade 1b in 4 cases. The toxicities of this chemoradiation regimen were well tolerable. As a postoperative complication, infection of the perineal wound was most frequent. Preoperative chemoradiation therapy with the present regimen would be a useful adjuvant treatment for advanced lower rectal cancer.
Aged↗
[Evaluation of percutaneous microwave hepatic tumor coagulation therapy (PMTC) under general anesthesia from viewpoint of quality of life (QOL)].
We evaluated clinical benefits (QOL and local control rate) of percutaneous microwave coagulation therapy conducted with general anesthesia. Five cases with hepatic tumor (3 cases with hepatocellular carcinoma, 2 cases with metastatic hepatic tumor) were enrolled. The day following treatment all patients were virtually free of complaints with performance status ranging 0 to 1, and they were discharged from the hospital within 1 week. Four of five cases could be controlled solely with this treatment: one case showed local relapse, the tumor size of which exceeded 3 cm. PMTC may be one of the most beneficial local treatments for malignant hepatic tumor, since it shortens hospital stay with a good QOL status, and is applicable to metastatic tumor.
Aged↗
Infrared thermometry for rapid, noninvasive detection of reflux of spermatic vein in varicocele.
PURPOSE: We evaluated infrared thermometry for measurement of reflux of blood via the internal spermatic vein. MATERIALS AND METHODS: The change in scrotal temperature in patients with varicoceles and controls with different positions was measured with an infrared thermometer. RESULTS: Scrotal neck temperature in the patients increased during Valsalva's maneuver with upright position (mean plus or minus standard deviation 34.62 +/- 1.20 to 36.05 +/- 1.42C), while no statistically significant increase occurred in the controls (32.91 +/- 0.92 to 33.42 +/- 1.15C). Two weeks after high ligation of the internal spermatic vein the scrotal temperature in the patients decreased to the same level (0.59 +/- 0.84C) as in the controls. Using this method 2 subclinical varicoceles were also found on the right side in patients with a left varicocele. CONCLUSIONS: Infrared thermometry is noninvasive, rapid and simple for documenting varicoceles, including subclinical disease.
Adult↗
[Recovery from descending necrotizing mediastinitis and multiple organic failure after seven months of mechanical ventilation].
A 61-year-old man with a history of hypertension and diabetes mellitus had a tooth extracted. Nine days later, he was admitted to the hospital with complaints of high fever, dyspnea, and anterior chest pain. Physical examination revealed a drowsy man with a fever of 38.2 degrees C, blood pressure of 66/44 mmHg, and marked redness and swelling from the neck to anterior part of the chest. Laboratory examination indicated severe infection and multiple organ failure, consisting of cardiac, respiratory, renal, and hepatic failure, with disseminated intravascular coagulation. Chest X-ray and CT-scan films showed abscesses extending from the neck to the mediastinum, and bilateral pleural effusion. Immediately, he was treated with catecholamines, furosemide, mechanical ventilation with a high concentration of oxygen, continuous drainage, repeated skin incisions, and broad-spectrum antibiotics. In addition, steroid pulse therapy was administered for persistent respiratory failure. On the 28th hospital day, a fistula developed between the trachea and the mediastinum, and an intratracheal tube had to be inserted through the fistula. On the 212 th hospital day, after intravenous hyperalimentation, continuous intravenous insulin infusion, and administration of broad-spectrum antibiotics, catecholamines, and furosemide, the patient was weaned from mechanical ventilation. A restrictive ventilatory defect due to ankylosis and atrophy of underused muscles was noted after weaning, but the PaO2 was high with a low dose of oxygen (1 to 2 l/min), and 21 months later, the blood gases were normal while the patient was breathing room air. As of January, 1996, he was undergoing rehabilitation to promote his recovery from ankylosis, muscle atrophy, and speech dysfunction.
Catecholamines↗
[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].
Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.
Administration, Oral↗