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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 379 records · Page 21Linked to original sources

Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat.

The effects of helodermin, a basic 35-amino acid peptide isolated from the venom of a lizard salivary gland, on arterial blood pressure and heart rate were examined in the rat, focusing on the possibility that activation of ATP sensitive K+ (K(ATP)) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). Helodermin produced hypotension in a dose-dependent manner with approximately similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a levcromakalim-produced decrease in arterial blood pressure. Oxyhemoglobin did not affect helodermin-induced hypotension, whereas it shortened the duration of acetylcholine (ACh)-produced hypotension. These findings suggest that helodermin-produced hypotension is partly attributable to the activation of glibenclamide-sensitive K+ channels (K(ATP) channels), which presumably exist on arterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)/nitric oxide does not seem to play an important role in the peptide-produced hypotension.

Animals↗

123I-MIBG SPECT of Merkel cell carcinoma.

131I-MIBG may be useful in the detection of neuroendocrine tumours. Merkel cell carcinoma is a neuroendocrine tumour of the skin. We evaluated a patient with Merkel cell carcinoma using 123I-MIBG single photon emission computed tomography (SPECT) which demonstrated tumour accumulation of the radiotracer in the right eyelid. This result suggests that 123I-MIBG SPECT may be useful in the evaluation of Merkel cell carcinoma.

3-Iodobenzylguanidine↗

Positive and negative thymocyte selection.

T cells differentiate from CD4-CD8- (DN) precursor to mature CD4+ or CD8+ (SP) thymocytes through the CD4+CD8+ (DP) stage. Immature thymocytes express pre-TCR complex composed of pT alpha and TCR beta chains, which plays a role in allelic exclusion of TCR beta and promotion from DN to DP transition. During the DP stage, thymocytes are subjected for selection, either expansion/differentiation into SP cells (positive selection) or deletion (negative selection). The level of TCR signals, which is mainly affected by the avidity between TCR and self-peptide/MHC and the contribution of coreceptors (CD4, CD8), determines the fate of thymocytes. The difference of avidity may result in distinct kinetics when signaling machinery assembles with TCR. As TCR signals increase either by high expression of TCR/coreceptors or higher avidity, the fate of thymocytes changes from default death (no selection) to positive selection and then negative selection. Although signaling pathways to discriminate these selections are largely unknown, ZAP-70 and Lck are important for both processes, whereas calcineurin and MAPK pathway play crucial roles in positive selection. TCR signals also affect the CD4/CD8 lineage commitment. The requirements for the two lineages are different. Differentiation of CD4 SP thymocytes requires stronger TCR signals, while special signals such as Notch-mediated signal are necessary for development of CD8+ cells.

Animals↗

A delayed hemolytic transfusion reaction (DHTR) with multiple alloantibodies (Anti-E, Jka, Dia, Fyb, and S) induced by E-antigen-negative, crossmatch-compatible blood.

We describe the case of a 44-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of two pregnancies and a blood transfusion, the details of which were unknown. At the time of her first vascular surgery on November 15, 1989, she received 1200 ml of crossmatch-compatible concentrated red blood cells (CRC). Before the first operation, screening for anti-RBC antibodies (Ab) was negative. At the time of the second admission on Feburary 15, 1996, anti-E Abs were detected by indirect antiglobulin test. She received 560 ml of E-antigen-negative, crossmatch-compatible, CRC for treatment of anemia on March 1 and 2, 1996. After this transfusion, total bilirubin (1.6 mg/dl) and lactate dehydrogenase (1355 IU/ml) were elevated on March 12, 1996. She had no evidence of clinical hemolysis. We suspected DHTR from these data, and therefore screened for anti-RBC Abs. Anti-E, Jka, Dia, Fyb, and S Abs were detected in blood samples obtained from the patient on March 12, 1996. Anti-E, Jka Dia, and S Abs were present more than 1 month and anti-Fyb Ab was disappeared at 18 days after transfusion.

Adult↗

The plasma FK506-binding protein 12 level is related to acute cellular rejection in small bowel transplantation.

Since FK506 binding protein (FKBP12) inhibits dose-dependently the immunosuppressive activity of FK506 in vitro, plasma FKBP12 levels were measured after rat small bowel transplantation (SBTx). The mean plasma FKBP12 level in untreated recipients increased significantly at the onset of acute cellular rejection (ACR) compared to that in FK506-treated recipients without rejection at the same time after SBTx (P < 0.05). In both groups, however, the mean plasma FKBP12 level did not increase at 1 day after SBTx. These results suggest that plasma FKBP levels may be affected by ACR, but not by ischemia-reperfusion injury. Therefore, the plasma FKBP12 level should be considered as one of the parameters related to the immunosuppressive activity of FK506 in SBTx.

Animals↗

Endogenous tumor necrosis factor and doxorubicin sensitivity in leukemic patients.

Sensitivity to doxorubicin (DOX) and expression of intracellular endogenous TNF (enTNF) or manganous superoxide dismutase (MnSOD) activity were found to be inversely correlated in leukemic cells from 19 patients (6 acute lymphoblastic leukemia, 13 acute myeloblastic leukemia). In a case with acquired resistance to chemotherapy which included DOX, enTNF expression and MnSOD activity were increased. Furthermore, in 14 cases treated with a regimen including an anthracycline, 4 cases which failed to respond to chemotherapy showed relatively high amounts of enTNF expression. After TNF antisense cDNA was transfected into leukemic cells isolated from 5 patients, sensitivity of transfectants to DOX increased 1.4- to 2.5-fold. Overall, we found enTNF to act as a resistance factor against DOX in leukemia which may predict response to DOX.

Antibiotics, Antineoplastic↗

Vascular and non-vascular ligands for L-selectin.

Ligands for L-selectin are expressed not only on vascular endothelial cells but also in the extravascular tissues. In this article, we summarize the current understanding of the "vascular" ligands for L-selectin. We also describe identification of "non-vascular" ligands for L-selectin and discuss their possible biological significance.

Animals↗

Persistent distension and enhanced diffusive extravasation of tumor vessels improved uniform tumor targeting of radioimmunoconjugate in mice administered with angiotensin II and kininase inhibitor.

Induced hypertension with angiotensin II (AT-II) and the inhibition of kininase with enalapril maleate may increase the tumor targeting of radiolabeled monoclonal antibodies (MAbs). We previously found that short-period infusion of 2.0 microg/kg/min of AT-II enhanced tumor targeting of MAb without an impact on normal tissue distribution. In this study, we aimed to optimize the manipulation with these agents, and examine the possible mechanism of their effects on MAb distribution. Effect of the manipulation on tissue circulation was assessed in mice bearing colon cancer xenografts by 201Tl and 99mTc-human serum albumin (HSA) as markers of tissue blood flow and tissue blood volume and/or vascular permeability. A dose finding study of enalapril ranging from 3 to 300 microg showed that 30 microg of enalapril in combination with AT-II infusion produced the best improvement in tumor uptake of 99Tc-HSA without altering 201Tl distribution, suggesting that the increase of vascular permeability was caused by enalapril. AT-II infusion for longer than 1 h affected renal blood flow and caused subcutaneous edema. Tumor uptake of (111)In-A7, a murine IgG1, was 1.62-fold improved 72 h postinjection (P < 0.001) and intratumoral distribution became uniform with 2.0 microg/kg/min of AT-II for 1 h and 30 microg of enalapril. Vessels in manipulated tumors were distended even 48 h after the cessation of AT-II infusion. In conclusion, it was suggested that persistent distension of tumor vessels and the increase of diffusive extravasation of MAb caused by short-period-induced hypertension and inhibition of bradykinin degradation produced favorable effect for the MAb distribution in tumors.

Angiotensin II↗

[The significance of telomerase activity in patients with gastric cancer].

The activation of telomerase is one of step in carcinogenesis. Therefore, it indicates that the detection of telomerase activity in tissues is useful for cancer diagnosis. TRAP assay developed by Kim et al. is sensitive enough to detect telomerase activity from a telomerase expressing cell. Using TRAP assay kit provided by Oncor Inc., we estimated quantitatively the telomerase activity from benign (atrophic gastritis), premalignant (intestinal metaplasia), and malignant tissues in the stomach. Telomerase activity in gastric cancer tissues was significantly higher than that in tissues which are characterized histologically as intestinal metaplasia or atrophic gastritis. In addition, to exclude interference with TRAP assay by telomerase or PCR inhibitor when telomerase activity was not observed in cancer tissues, the use of internal control (ITAS or TSNT) and dilution of samples should be performed.

Biomarkers, Tumor↗

Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay.

UNLABELLED: The purpose of the present study was to evaluate the degree of cytological radiation damage to lymphocytes after 131I therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by 131I in vivo should result in augmentation of the cells with micronuclei. METHODS: We studied 25 patients with differentiated thyroid carcinoma who were treated with 3.7 GBq of 131I. Isolated lymphocytes collected from patients 1 wk after therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. The micronucleus number of micronuclei per 500 binucleated cells were scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. In an in vitro study, lymphocytes from three patients at least 3 mo after therapy were exposed to doses varying from 0.25 to 1 Gy and studied with the same method. RESULTS: The mean number (mean +/- s.d.) of micronuclei after treatment was significantly increased (p < 0.05) as compared to control subjects (15.7 +/- 2.7 vs. 5.4 +/- 1.4). Since there was an interval ranging from 6 to 20 mo (mean 11.8 mo) between the present and the last radioiodine therapy, no significant effect on the frequency of micronucleus with cumulative radiation exposure of 131I to lymphocytes was detected. Internal radiation absorbed doses estimated for 25 patients were 0.33 +/- 0.09 Gy in this external irradiation study. CONCLUSION: The relatively low frequency of lymphocyte micronuclei induced by 131I in vivo and lack of significant effect on the frequency of lymphocyte micronuclei with cumulative 131I supported the contention that short-term nonstochastic damage of this therapy with 3.7 GBq of 131I in thyroid cancer patients is minimal and reversible.

Female↗

[Gene delivery into human cancer cells via transferrin receptor].

At present, vectors widely used for gene transduction are retroviruses and adenoviruses. However, the transduction using these vectors are primarily conducted ex vivo. The direct in vivo gene delivery method to target tumor cells are required. Trials to augment specificity of gene targeting to tumor cells have been in progress including approaches to use modified virus particles by gene technology instead of wild type particles or to take advantage of ligand-receptor or antibody-antigen systems by allowing vector DNAs to bind these ligand and antibodies. Transferrin receptor (TfR) is widely distributed on actively proliferating cells and is therefore an appropriate target for in vivo gene delivery into those cells. We developed a simple method to conjugate biotinylated double-stranded DNA to biotinylated Tf via streptavidin and demonstrated successful transduction of the conjugate into TfR-positive human cancer cells. The present method may provide a novel technique for gene transduction, which may be used especially to transfer various DNA vectors into cells specifically expressing TfR, in vivo as well as in vitro.

Adenoviridae↗

[A study of post-operative delirium in elderly patients].

We investigated the post-operative delirium in elderly patients of over 65 years of age. This investigation consisted of two studies, a prospective study and a retrospective study. In the prospective study, we evaluated the incidence of post-operative delirium and the incidence of post-operative delirium was estimated pre-operatively using State-Trait Anxiety Inventory (STAI) and Mini Mental State Examination (MMSE) in 24 patients scheduled for elective surgery under general anesthesia in the period from Nov. 1995 to Oct. 1996. In the retrospective study, we selected patients with post-operative delirium from 1600 patients who had undergone scheduled and emergency operation under general anesthesia in the same period as in the prospective study and analyzed the incidence of post-operative delirium and background of these patients. Twenty four patients in the prospective study were excluded from the retrospective study. In the prospective study, although post-operative delirium was observed in 2 cases (8.3%), no specific changes were observed in anxiety state and the ability of recognition. In the retrospective study, post-operative delirium was observed in 22 cases (1.37%). In these patients, several factors such as blood transfusion, emergency operation, dehydration, thrombosis of the superior mesenteric artery, history of ischemic heart disease, brain infarction and atrial fibrillation were thought to be major risk factors triggering post-operative delirium. In this study we could not conclude that STAI or MMSE are useful to estimate the incidence of post-operative delirium preoperatively. However, our result suggests that we should be careful about the incidence of post-operative delirium in elderly patients with pre-operative risk factors as mentioned above.

Aged↗

[Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,282 strains of 11 bacterial species isolated at all institutions between October and December 1995. The results were as follows: 1. Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae. Their activities against Enterococcus faecalis were comparable to that of ABPC. Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest antibacterial activity against Haemophilus influenzae, followed by MEPM. The antibacterial activities of the other carbapenems were comparable to those of FMOX and CTM. 3. The carbapenems showed high activities against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents. The carbapenems also exhibited greater antibacterial activities against Serratia marcescens than the other beta-lactam antibacterial agents, but some resistant strains were detected. 4. The antibacterial activities of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ, AZT, AMK.

Carbapenems↗

[Recurring intradiploic epidermoid cyst of the skull: a case report].

We report a case of a 65-year-old man with intradipolic epidermoid cyst of the frontal bone. The patient presented with headache and swelling of the forehead. Skull x-ray showed massive destruction of the frontal bone. Magnetic resonance imaging (MRI) revealed an epidural mass without any encroachment of the dura mater. The cystic tumor was removed followed by cranipolasty with methylmethacrylate. Four years later, the tumor recurred in the same region. At the second surgery the bony defect was again replaced with methylemthacrylate plate. Four years after the second operation, the tumor reemerged with some subcutaneous fluid retention. At the third surgery, the remaining tumor capsule was removed as much as possible except for that part which adhered to the superior sagittal sinus. The authors discuss the relationship of tumor recurrence with utilization of methylmethacrylate for cranioplasty in this type of tumor.

Bone Cements↗

Antibody response of cattle experimentally inoculated with parainfluenza type-3 live vaccine in a post-tracheal position.

One of the major viral respiratory diseases of cattle is parainfluenza type-3 virus infection. Attenuated live virus vaccines have been used in most countries. An experimental attempt was made to clarify the antibody response of cattle inoculated with a live vaccine in a post-tracheal position by a spray method. A significantly higher titers of antibodies in both hemagglutination inhibition and neutralization were obtained in the serum samples of animals vaccinated in this manner than those vaccinated by intramuscular injection or intranasal instillation.

Administration, Inhalation↗