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Biomedical subjects

S Hori

Publications and source records attributed to S Hori.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on guinea pig respiratory mechanics.

This study characterized the in vitro pharmacological properties of a newly developed endothelin receptor antagonist, N-butanesulfonyl-[N-(3, 5-dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-(D)- alanyl]-( L)-valineamide sodium salt (IRL 3630A), and its in vivo effects on respiratory mechanics were determined. IRL 3630A showed highly balanced affinities to human endothelin ET(A) and ET(B) receptors, giving apparent K(i) values of 1.5 and 1.2 nM, respectively. This compound also potently antagonized the endothelin-1-induced intracellular Ca(2+) increases in both embryonic bovine tracheal (EBTr) cells expressing endothelin ET(A) receptors and human Girardi heart (hGH) cells expressing endothelin ET(B) receptors. In guinea pig isolated tracheas having both endothelin ET(A) and ET(B) receptors, IRL 3630A greatly inhibited endothelin-1-induced contraction (pA(2)=7.1), which was partially or scarcely suppressed by the endothelin ET(A) receptor antagonist cyclo[-(D)-Trp-(D)-Asp-(L)-Pro-(D)-Val-(L)-Leu-] (BQ-123) or the endothelin ET(B) receptor antagonist N-(3, 5-dimethylbenzoyl)-N-methyl-3-(4-phenyl)-(D)-phenylalanyl-(L)-t ryptop han (IRL 2500), respectively. Bolus i.v. injections of IRL 3630A administered into anaesthetized guinea pigs at 10 and 30 microg/kg inhibited endothelin-1 (1.3 microg/kg)-induced changes in respiratory resistance and compliance in a dose dependent manner, whereas both sodium 2-benzo[1, 3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4, 5-trimethoxy-benzyl)-but-2-enoate (an endothelin ET(A) receptor antagonist: PD 156707) and IRL 2500 at doses of up to 30 microg/kg did not affect endothelin-1-induced changes in respiratory mechanics, reflecting the in vitro results. IRL 3630A is thus an effective bifunctional endothelin receptor antagonist, and will be useful in clarifying the role of endothelin in pulmonary diseases such as bronchial asthma.

Airway Resistance↗
PubMed2000

Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study.

BACKGROUND: A rapid 30-minute assay of circulating smooth-muscle myosin heavy-chain protein has been developed as a biochemical diagnostic tool for aortic dissection. OBJECTIVE: To determine the sensitivity and specificity of this assay. DESIGN: Cross-sectional study. SETTING: 8 major cardiovascular centers in Japan. PATIENTS: 95 patients with acute aortic dissection, 48 patients with acute myocardial infarction, and 131 healthy volunteers. MEASUREMENTS: Levels of circulating smooth-muscle myosin heavy-chain protein. RESULTS: Patients with acute aortic dissection who presented within 3 hours after onset had elevated levels of circulating smooth-muscle myosin heavy-chain protein. In these patients, the assay had a sensitivity of 90.9%, a specificity of 98% compared with healthy volunteers, and a specificity of 83% compared with patients who had acute myocardial infarction; the clinical decision limit was 2.5 microgram/L. All patients with proximal lesions had elevated levels of smooth-muscle myosin heavy-chain protein, and only patients with distal lesions had decreased levels (<2.5 microgram/L). CONCLUSIONS: Levels of smooth-muscle myosin heavy-chain protein can be used to diagnose aortic dissection soon after symptom onset. The assay had the greatest diagnostic value in patients with proximal lesions.

Aged↗
PubMed2000

Specific depletion of preformed IgM natural antibodies by administration of anti-mu monoclonal antibody suppresses hyperacute rejection of pig to baboon renal xenografts.

BACKGROUND: The elimination of circulating anti-porcine preformed antibodies is crucial for avoiding hyperacute vascular rejection (HAVR) of primarily vascularized xenograft in discordant pig to baboon model. Previously described methods used for eliminating natural antibodies, however, constantly removed both anti-porcine IgM and IgG antibodies, as well as often complement proteins. To study specifically the role of preformed anti-porcine IgM antibodies, a specific anti-IgM monoclonal antibody (mAb) has been designed and evaluated in vivo. METHODS: Iterative injections of anti-IgM mAb (LO-BM2) at high dose (20 mg/kg) depleted to undetectable level the circulating IgM and therefore anti-porcine IgM antibodies but did not change the concentration of anti-pig IgG antibodies. The serum concentration of IgM and IgG antibodies was assessed by ELISA and the level of anti-pig natural IgM and IgG antibodies by flow cytometry (FC). Anti-rat sensitization was assessed by specific ELISA as well as the serum concentration of LO-BM2. RESULTS: Iterative injections of LO-BM2 allowed to specifically eliminate the anti-porcine IgM antibodies to undetectable levels at ELISA. Despite a normal serum level of anti-porcine IgG and complement proteins, HAVR was avoided. Without immunosuppression, the specific elimination of preformed anti-porcine IgM prolonged the survival of a renal xenograft in baboon up to 6 days, whereas without IgM antibody elimination, the renal xenografts were hyperacutely rejected within hours. The lost of activity of LO-BM2 after 10 days was concomitant to an IgM and IgG antibody rebound, which caused an acute vascular rejection of the xenograft. CONCLUSION: Specific elimination of natural anti-porcine IgM antibodies allows to avoid HAVR of a pig to baboon renal xenograft, whereas anti-porcine IgG antibodies and complement proteins were present in the serum. This result confirms previous in vitro reports and demonstrates for the first time in vivo that preformed IgM antibodies alone are responsible for HAVR, while preformed anti-porcine IgG antibodies are unable alone to cause HAVR. Anti-IgM therapy appears as an important tool to transiently but completely eliminates xeno-IgM antibodies in vivo.

Animals↗
PubMed2000

A feasibility study of chemosensitivity assay by adhesive tumor cell culture system using biopsy specimens for gastric cancer.

BACKGROUND AND OBJECTIVES: The adhesive tumor cell culture system (ATCCS) is known to produce high colony-forming efficiency. We, therefore, studied the feasibility of ATCCS for gastric cancer by use of biopsy specimens and the relationship between the results of ATCCS and histological effects of anticancer drugs. METHODS: Tumor specimens extracted by gastroendoscopic biopsy were sufficient for obtaining the result of sensitivity to at least one drug in 24 out of 30 (80%) patients. Twenty patients were administered 5-fluorouracil (5-FU) for 14 days prior to surgery, and the results of ATCCS were compared with histological changes of the resected specimens. RESULTS: The histological response rate was found to be 100% (4/4) when the 90% inhibition concentration (IC90) of 5-FU was less than 0.24 microg/ml (sensitive) and was 0% (0/3) when IC90 was greater than 0.40 microg/ml (resistant). CONCLUSIONS: Although lacking in statistical significance, the results suggest that the drug to which the tumor revealed sensitivity in the ATCCS would produce histological effects and the drug to which the tumor was resistant would have no histological effect.

Aged↗
PubMed2000

Attempted gene therapy for intractable pain: dexamethasone-mediated exogenous control of beta-endorphin secretion in genetically modified cells and intrathecal transplantation.

For optimal neural transplantation using gene engineering, it might be important to control the expression of the transfected gene extrinsically as required. This strategy could be very useful for the treatment of intractable pain that responds to opioids. For this purpose, we established a genetically modified embryonal carcinoma cell line (P19) in which the expression of beta-endorphin (beta-EP) could be controlled by the addition of dexamethasone. To obtain extrinsic control, we transfected the cells with pMAMneo containing mouse MMTV-LTR as a promoter and cDNA of the artificial beta-EP. The upregulation of beta-EP, through the activation of MMTV by the administration of dexamethasone, was confirmed in vitro. Then we transplanted these cells into the subarachonoid space in rats and evaluated the analgesic potential of these cells in vivo by hot plate test and formalin test. In the rats that received beta-EP-producing cells, we observed prominent analgesic effects after the transplantation for a month. The administration of naloxone blocked these effects. Intraperitoneal injection of 100 mg/kg dexamethasone further enhanced these effects by up to two times. These data indicate obvious analgesic effects of the cells after the transplantation and the possible exogenous upregulation of transfected beta-EP gene expression in vivo. The application of this technique might provide a new therapeutic approach to various neurological diseases.

Animals↗
PubMed2000

Neoadjuvant intraarterial infusion chemotherapy in patients with stage IB2-IIIB cervical cancer.

OBJECTIVES: The purpose of this study was determine the effect of neoadjuvant intraarterial chemotherapy (NAIC) on the prognosis of patients with locally advanced cervical cancer. METHODS: From January 1992 to December 1997, 26 previously untreated patients with stage IB2-IIIB cervical cancer were enrolled in the study. NAIC was administered for more than two courses every 3 weeks using a combination of 17.5 mg/m(2) bleomycin, 7 mg/m(2) mitomycin-C, and 75 mg/m(2) cisplatin via the bilateral internal iliac artery. Pathologic findings were evaluated with histologic examinations of surgical specimens. A nonrandomized control group of 120 patients who underwent conventional treatment between 1980 and 1991 was used for comparison. RESULTS: Nineteen (73.1%) of the 26 patients responded to initial chemotherapy, permitting a radical hysterectomy with pelvic lymphadenectomy in 14 patients. The remaining 5 patients received radiotherapy. One of 7 nonresponders was able to undergo radical surgery. Pathologic complete responses were found in 4 of the 15 patients who underwent radical surgery. The incidence of lymph node metastasis, parametrial infiltration, and vascular space involvement in the 15 patients who received NAIC followed by radical surgery was significantly lower than that in the control group (13.3, 6.7, and 13.3% vs 54.2, 43.8, and 60.4%). The overall 5-year estimated survival rate was significantly higher for all 26 patients who received NAIC (80.0%) than for the control group (59.6%). In stage II and III, the 5-year survival rate for patients who received NAIC was significantly higher than that in the control group (83.3 and 77.8% vs 68.1 and 49.8%). CONCLUSIONS: These preliminary results suggest that NAIC is able to eliminate effectively the pathologic risk factors in the pelvic cavity, to improve the operability in patients with stage IIIB cervical cancer, considered inoperable, and to improve the prognosis of patients with locally advanced cervical cancer.

Adenocarcinoma↗
PubMed2000

Ca2+ and electrolyte mobilization following agonist application to the pancreatic beta cell line HIT.

We have investigated intracellular Ca2+ mobilization in oscillations of cytoplasmic Ca2+ in response to glucagon-like peptide 1 (GLP-1) and glucose in clonal HIT insulinoma cells with a confocal laser-scanning microscope (CLSM). We also used electron probe X-ray microanalysis to determine the GLP-1- and glucose-induced changes in electrolyte levels in the cytoplasm and insulin granules of the cells. GLP-1 produced 10- to 35-s duration oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i), both with and without Ca2+ in the extracellular solution, suggesting that Ca2+ is mobilized from intracellular Ca2+ stores, namely secretory granules. Glucose caused 1- to 3-min duration oscillatory increases in [Ca2+]i when the extracellular solution contained Ca2+. When the cells were cultured without Ca2+ (no Ca2+ added, 1 mM EGTA), an oscillatory [Ca2+]i increase of amplitude and short duration (12-35 s) was produced by 11 mM glucose, and the oscillation was inhibited by ruthenium red. X-ray microanalysis showed that stimulation with glucose increased the total Ca concentration in the cytoplasm and decreased it in the insulin granules with and without Ca2+ in the extracellular solution. The application of glucose significantly decreased K, and increased Na and C1 in the cytoplasm when the extracellular solution contained Ca2+. Our result also suggests that the [Ca2+]i oscillation induced by glucose is involved in the release of Ca2+ from intracellular Ca2+ stores through the ryanodine receptor, which is blocked by ruthenium red, and/or through the inositol trisphosphate receptor that may be present in the membrane of insulin granules.

Animals↗
PubMed2000

Localization of endothelin A receptors in the rat pituitary TSH cells: light- and electron-microscopic immunohistochemical studies.

Endothelins modulate hormonal secretion in the pituitary gland. Intense signaling of endothelin A receptors (ET(A)R) has been detected by in situ hybridization, binding assay and receptor autoradiography. We used light- and electron-microscopic immunohistochemistry of ET(A)R with polyclonal antibody against a synthetic peptide corresponding to the carboxyl terminus (403-427) of human ET(A)R. Immunoreactivity was observed in 6-8% of anterior pituitary cells, which were rather large polygonal or stellate cells. These cells were often clustered. Double-staining immunofluorescence showed that the ET(A)R-positive cells immunoreacted with antibody against the beta-subunit of thyroid-stimulating hormone (TSH), but not adrenocorticotropic hormone (ACTH) or lutenizing hormone beta (LHbeta). Pre- and postembedding electron-microscopic immunohistochemistry showed that ET(A)R-positive cells had vacuolated or parallel-lined rough endoplasmic reticulum (rER) and numerous round granules in their periphery and the elongated processes. By pre-embedding immunohistochemistry, diaminobenzidine tetrahydrochloride (DAB) products were shown to be mostly located around the granules and occasionally underneath the plasma membrane. By postembedding immunohistochemistry, granules in the ET(A)R-positive cells were 90-150 nm in diameter, and colloidal gold particles due to ET(A)R were associated with about 10% of these granules. These results indicate that ET(A) receptors are associated mostly with the secretory granules of TSH cells.

Adrenocorticotropic Hormone↗
PubMed2000

Discrepancies among megatrials.

The validity of meta-analyses has recently been examined by comparing their results with those of megatrials on the same topic. We investigated the reliability of this gold standard by identifying megatrials, defined as ones involving more than 1000 subjects, in the recent issue of the Cochrane Library and in the article by LeLorier et al. (N Engl J Med 1997;337:536-42). In the former set, 289 pairs of megatrials were identified which studied the same patient-intervention-outcome combinations. Of these, 210 (73%, 95% CI: 67-77%) reported odds ratios or weighted mean differences that were not statistically significantly different from each other. The agreement of statistical conclusions regarding outcomes was a quadratic weighted kappa of 0.40 (95% CI: 0.29-0.51). The article by LeLorier et al. yielded 133 comparisons, of which 97 (73%, 95% CI: 64-79%) reported mutually compatible odds ratios. The agreement of statistical conclusions was a kappa of 0.33 (95% CI: 0.18-0.47). Agreement among megatrials was approximately as large as that reported between meta-analyses and megatrials. These findings suggest that taking megatrials as the gold standard can be problematic and that there is no substitute for clear and hard thinking for any study, be it a meta-analysis or a megatrial.

Humans↗
PubMed2000

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury.

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Journal Article↗
PubMed2000

Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-alpha or basic fibroblast growth factor.

Glioblastoma multiforme is a highly malignant tumor that is extremely refractory to therapy. One reason is its highly invasive nature into brain tissue. Metalloproteinases and their inhibitors, plasminogen activators (PA) and their inhibitors and cathepsins are thought to be involved in invasion by tumor cells. In this study, we determined if the urokinase-type plasminogen activator (uPA) and/or the urokinase-type plasminogen activator receptor (uPAR) were responsible for the invasion activity of a human glioma cell line. We determined the invasion activity of a human glioma U251 cell line using an in vitro invasion assay system. A 2.4- to 5.8-fold increase in invasion activity was observed in the presence of basic fibroblast growth factor (bFGF) or transforming growth factor (TGF)-alpha. Northern blot analysis showed that bFCF and TGF-alpha treatment was associated with increases in cellular mRNA levels of uPA and uPAR. Zymographic activity correlated to mRNA levels of uPA and uPAR. Addition of an anti-uPAR monoclonal antibody significantly inhibited the invasion activity induced by bFGF- and TGF-alpha. Irsogladine, an inhibitor of uPA synthesis, also blocked the invasion activity. These observations suggest that uPA and its receptor have a role in the invasion process of human gliomas.

Fibroblast Growth Factor 2↗
PubMed2000

Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma.

Human pancreatic cancer is a lethal malignancy, and the lesions show a very high incidence of point mutations of the K-ras oncogene. These alterations can be used as potential targets for specific ribozyme (Rz)-mediated growth suppression of the cancer cells. We designed an anti-K-ras Rz against mutant K-ras gene transcripts (codon 12, GGT to GTT) and generated a recombinant adenovirus (rAd) to express the Rz (rAd/anti-K-ras Rz). More than 95% of Capan-1 human pancreatic cells were infected with rAd/anti-K-ras Rz when treated with the virus at 200 plaque-forming units/cell. The virus, rAd/anti-K-ras Rz, significantly suppressed mutant K-ras gene expression and inhibited the growth of Capan-1 cells. At 3 days postinfection, we observed maximum growth suppression of the cells, characteristic morphological changes of apoptosis such as nuclear condensation and oligonucleosomal DNA fragmentation, and suppression of bcl-2 oncoprotein. These changes were not found in control virus-infected cells. Our results indicated that the virus rAd/anti-K-ras Rz specifically down-regulated the K-ras/bcl-2 pathway and induced apoptotic changes in Capan-1 pancreatic carcinoma cells. High-efficiency adenovirus-mediated delivery of anti-K-ras Rz could become a significant gene therapy strategy against human pancreatic cancer.

Adenoviridae↗
PubMed2000

Paraplegia caused by painless acute aortic dissection.

OBJECTIVES: Painless acute aortic dissection in which paraplegia is the only presenting sign is rare, with limited reported cases. CASE REPORT: The authors report a patient with painless acute aortic dissection who presented with sudden onset paraplegia. Ischemic diseases of the spinal cord were suspected as the cause. MRI revealed extensive acute aortic dissection with an intramural hematoma. The patient was treated conservatively by strictly controlling his blood pressure. The treatment was successful, although the motor function of the lower extremities could not be rescued. Although 3% to 5% of patients with acute aortic dissection present with paraplegia as a result of spinal cord infarction, most of these patients experience severe pain prior to presentation. CONCLUSION: Painless acute aortic dissection in which paraplegia is the only presenting sign is very rare. However, aortic diseases, including acute aortic dissection, should always be considered as a differential diagnosis of patients with sudden onset, painless paraplegia.

Acute Disease↗
PubMed2000

Determination of triazine herbicides in foods with liquid chromatography mass spectrometry.

Eight residual triazine herbicides and three metribuzin metabolites in foods were determined by liquid chromatography mass spectrometry (LC-MS) with an atmospheric pressure chemical ionization (APCI) interface, under both positive and negative ion modes. Herbicides were extracted with acetonitrile, and no cleanup procedure was adopted in this method. Four foods were spiked with eight herbicides and three metabolites at 0.05 ppm. The average recoveries of these herbicides usually ranged from 82 to 99% and the relative standard deviations were usually around 10%. These results suggest that LC-MS with APCI can be used to determine residues of triazine herbicides in foods.

Chromatography, Liquid↗
PubMed2000

A novel hemocyte-specific membrane protein of Sarcophaga (flesh fly).

Extensive tissue remodeling takes place during metamorphosis of holometabolous insects. It has been shown that hemocytes play crucial roles in the recognition and elimination of apoptotic cells and larval tissue fragments produced during metamorphosis. We report the immunoaffinity purification, cDNA cloning, and characterization of a prepupal hemocyte membrane protein of Sarcophaga (flesh fly) with a molecular mass of 120 kDa. This protein is a novel type I transmembrane protein with 18 repeats of an epidermal growth factor-like domain in the predicted extracellular region. Expression of the protein was restricted exclusively to prepupal hemocytes. This protein is suggested to be a scavenger receptor for tissue remodeling.

Amino Acid Sequence↗