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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 235 records · Page 13Linked to original sources

[Effect of CV-4151 on the cerebral hypoperfusion and production of thromboxane A2 following complete cerebral ischemia-reperfusion in dogs].

The effects of CV-4151 on post-ischemic brain hypoperfusion and thromboxane (Tx)A2 production in a canine model of total global brain ischemia were studied. Complete cerebral ischemia for 5 min was produced in adult mongrel dogs by temporary ligation of the venae cavae and aorta. In the non-treated group, cerebral blood flow (CBF) increased during the first 20 to 30 min post-ischemia followed by a gradual decline and then stayed below preischemic level; CBF at 2 hr after the reperfusion was significantly reduced to ca 77% of the pre-ischemic level. Water content in the cerebral cortex at 2 hr after the reperfusion in the non-treated group was 78.15 +/- 0.21%, higher than the content in the control group, 76.70 +/- 0.07%. The concentration of TxB2 in the sagittal sinus was significantly increased at 30 min post ischemia. CV-4151 (1.0 mg/kg, i.v.) almost completely inhibited the post-ischemic hypoperfusion, significantly inhibited the increase in water content and almost completely inhibited the production of TxB2 in the post-ischemic period and increased the production of 6-keto PGF1 alpha. OKY-046 (10 mg/kg, i.v.) had no significant effects on both post-ischemic hypoperfusion and increase in water content in the cerebral cortex. We conclude that CV-4151 ameliorates post-ischemic cerebral hypoperfusion and that this improvement is associated with decreased sagittal sinus levels of TxB2.

Animals↗

Sites of action of CS-722, a newly synthesized centrally acting muscle relaxant.

Sites of the muscle relaxant action of CS-722 were investigated in rats. Doses injected intra-4th ventricularly (i.c.v.) or intrathecally (i.t.) were determined according to measurements of CS-722 concentration in the brain stem and the spinal cord after systemic administration. When administered i.c.v. (50 and 100 micrograms) or i.t. (200 and 400 micrograms), CS-722 reduced the radio frequency decerebrate rigidity, although the effect after i.c.v. injection was transient. These results indicate that CS-722 exerts its muscle relaxant action by affecting both the supraspinal structure and the spinal cord. Spinal reflexes were not affected by CS-722 injected i.c.v. It seems that muscle relaxation is not always accompanied by impairment of the spinal reflex.

Animals↗

[Computerized database system for pure tone audiometry].

The management and storage of pure tone audiometry data creates a major problem for otolaryngological clinics. We have devised a new computerized database system to overcome this problem. The hardware involved includes multiple audiometers and computers interfaced with a glassfiber local area network (Pi-Net). The software used is database 3 plus, a popular database language and utility software package. Programs were written for data entry, data transfer, reference, entry of patient ID, and evaluation of tympanoplasty. The following benefits of the system are noted. 1) Data entry is possible at every terminal (audiometer and computer). 2) Storage capacity is sufficient for more than 10 years of operation. 3) All data can be retrieved rapidly at any terminal. Evaluations of pre- and post-tympanoplasty hearing loss are facilitated by this system. This system is very effective for follow up of hearing disorders.

Audiometry, Pure-Tone↗

Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats.

BACKGROUND: Hepatocyte growth factor (HGF) (also known as scatter factor (SF)) is a heterodimeric protein that is the most potent known complete mitogen for hepatocytes in culture. HGF is a mitogen for many epithelial cells including hepatocytes, kidney tubular epithelial cells, mammary epithelial cells, keratinocytes, etc. The protein encoded by the proto-oncogene c-met is the high affinity receptor for HGF. HGF concentration in the plasma dramatically increases after partial hepatectomy and in fulminant hepatic failure. This study describes the pharmacokinetics of HGF in the rat. EXPERIMENTAL DESIGN: Human recombinant HGF (a gift from Genentech) was radioiodinated and shown to retain biologic activity and structure. Approximately 74 ng of [125I]HGF was injected into the penile vein of male Fisher rats 5 minutes after a complete bile fistula and jugular venous catheterization were performed for blood and bile sampling. Half of the rats were subjected to 70% partial hepatectomy. RESULTS: The percentage of injected radioactivity present in the liver of control rats was 29.5% +/- 0.5% at 15 minutes and decreased to 8.6% +/- 1.0% at 120 minutes; the kidneys had 6.2% +/- 0.2% at 15 minutes, decreasing to 1.48% +/- 0.3% at 120 minutes. All the other organs examined had less than 1% of the injected radioactivity. The remaining radioactivity was present in low affinity sites in blood, bone, muscle, and skin. In control rats, radioactivity appeared in the bile within 3 minutes, reached a peak between 40 to 50 minutes, and tapered thereafter for a total 2-hour collection of 2.3% +/- 0.5%. In the partially hepatectomized rats, the HGF blood clearance was decreased (partial hepatectomy = 0.27 +/- 0.03 ml/minute; control = 0.53 +/- 0.06 ml/minute, p < 0.006), and the terminal half-life prolonged (partial hepatectomy = 124 +/- 11 minutes; control = 83 +/- 10 minutes, p < 0.03). The initial half-life for HGF, as extrapolated from the chart, was estimated at 3.8 minutes in control rats. CONCLUSIONS: Liver is the principle organ for initial uptake of [125I]HGF; disappearance from the blood suggests multicompartment kinetics with a rapid phase and a slower phase; only a portion of the hepatic uptake appears in the bile; and partial hepatectomy decreases the blood clearance of [125I]HGF. These results are correlated with previous findings bearing on the role of HGF elevation after partial hepatectomy as a stimulus for transfer of hepatocytes from G0 to G1 early in liver regeneration after partial hepatectomy.

Animals↗

[Acute aortic dissection without opacification of the false lumen on the initial aortogram: a case report].

A 50-year-old woman was admitted to the intensive care unit 40 min after the onset of severe chest and back pain with consciousness loss. Emergency computed tomography and aortography demonstrated an acute type A dissection without opacification of the false lumen. The patient was initially treated with antihypertensive drugs. Recurrent back pain and bilateral pleural effusion appeared 3 days after onset of the pain. Both the right radial and carotid pulses were reduced. Emergent operation was performed when computed tomography and aortography repeated 5 days after onset of the pain demonstrated the intimal flap in the ascending aorta with the opacified false lumen. The site of intimal tear in the proximal arch was resected and a 26 mm Dacron graft was inserted during deep hypothermia and circulatory arrest. The postoperative course was uneventful.

Aortic Dissection↗

Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can support murine pre-B cell growth.

In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.

Animals↗

Beta-chain broadens range of CD8 recognition for MHC class I molecule.

It is known that the alpha-chain of CD8 binds to a negatively charged loop composed of residues 223 to 229 on MHC class I Ag and that binding of CD8 alpha enhances Ag recognition of T cells. We have recently shown that the mouse CD8 alpha homodimer does not bind to either the HLA class I alpha 3 domain or a mutant of H-2Kb Ag containing a substitution of glutamine for methionine at residue 224, which brings this residue toward the human consensus. Here we report a complementary study of the CD8 beta-chain. The functional role of the CD8 beta-chain was analyzed by using four T cell hybridoma lines expressing mouse CD8 alpha and transfected with the mouse CD8 beta gene. As compared with the lines expressing only CD8 alpha, allorecognition of the chimeric H-2Kb Ag that contains the HLA class I alpha 3 domain was enhanced in lines expressing both CD8 alpha and -beta. This enhancement was blocked by either anti-CD8 mAb or anti-HLA class I alpha 3 domain mAb. In addition, we show that CD8 alpha beta binds the H-2Kb mutant Ag at residue 224. These results suggest that the beta-chain allows the CD8 alpha beta heterodimer to recognize the chimeric H-2Kb Ag. A model for the role of the beta-chain is presented.

Animals↗

Structural and functional analysis of monomorphic determinants recognized by monoclonal antibodies reacting with the HLA class I alpha 3 domain.

To identify mAb reacting with the HLA class I alpha 3 domain, 14 mAb recognizing monomorphic determinants expressed on HLA-A, B, and C Ag or restricted to HLA-B Ag were screened in indirect immunofluorescence with mouse L cells expressing HLA-B7/H-2Kb chimeric Ag. mAb CR1S63, CR10-215, CR11-115, and W6/32 were found to react with the HLA class I alpha 3 domain in addition to the alpha 2 domain. mAb Q1/28 and TP25.99 were found to react only with the HLA class I alpha 3 domain. The determinants recognized by the six mAb were mapped on the HLA class I alpha 3 domain by indirect immunofluorescence staining of L cells expressing H-2Kb Ag containing different segments of the HLA-B7 alpha 3 domain chimerized with the H-2Kb alpha 3 domain. mAb TP25.99 reacts with chimeric Ag containing the HLA-B7 184 to 199 stretch, mAb CR10-215 and CR11-115 react with chimeric Ag containing the HLA-B7 184 to 246 stretch, mAb CR1S63 and Q1/28 react with chimeric Ag containing the HLA-B7 184 to 256 stretch, and mAb W6/32 reacts with chimeric Ag containing the whole HLA-B7 alpha 3 domain. Functional analysis using human CD8 alpha-bearing mouse H-2Kb-specific T cell hybridoma cells (HTB-Leu2) showed that only mAb TP25.99 inhibited IL-2 production by HTB-Leu2 cells stimulated with L cells expressing KbKbB7 Ag. This inhibition may occur because of the spatial proximity of the determinant defined by mAb TP25.99 to the CD8 alpha binding loop and/or because of change(s) in the conformation of the CD8 alpha binding loop induced by the binding of mAb TP25.99 to the HLA class I molecule. Furthermore, mAb TP25.99 inhibited the cytotoxicity of CD8-dependent and CD8-independent CTL clones. These results indicate that mAb TP25.99 has unique specificity and functional characteristics. Therefore it represents a valuable probe to characterize the role of the HLA class I alpha 3 domain in immunologic phenomena.

Amino Acid Sequence↗

Enzymatic properties of the phosphorylated urokinase-type plasminogen activator isolated from a human carcinomatous cell line.

Enzymatic properties of phosphorylated urokinase plasminogen activator (P-uPA) (1) extracted from human carcinomatous cell line Detroit 562 cells were compared with those of non-phosphorylated uPA of urinary origin (nP-uPA). Using plasminogen as a substrate, the Km and Kcat of P-uPA were higher than that of nP-uPA while the Kcat/Km was lower. By zymography, a greater degree of plasminogen activation was observed. Concanavalin A reacted to both the enzymes. P-uPA had a low affinity for the inhibitors of plasminogen activator PAI-1 and PAI-2, and was inhibited only by the excess amounts of inhibitors. For PAI-1, and the KIs of P-uPA was greater and for PAI-2, KI was higher for P-uPA. These alterations by phosphorylation enable uPA to be more efficient in a focal proteolysis through plasminogen activation.

Amino Acid Sequence↗

Effectiveness of planar image and single photon emission tomography of thallium-201 compared with gallium-67 in patients with primary lung cancer.

A comparative study of planar images and single photon emission tomography (SPET) of thallium-201 chloride and gallium-67 citrate was performed in 38 patients with proven primary lung cancer to detect the primary lung tumour and to establish the presence of metastasis in the lung hilum and mediastinum. The findings of planar images and SPET were compared with the pathological findings after thoracotomy. It was shown that 201Tl studies were superior to 67Ga studies for evaluation of the primary lesion and lymph node metastases.

Aged↗

Blood flow through the ophthalmic veins during exercise in humans.

The blood from the face flows into the intracranium through the ophthalmic veins when human subjects become hyperthermic. To investigate a possible mechanism underlying this change in direction of flow, five young men were subjected to either passive body warming or exercise on a cycle ergometer, in a climatic chamber whose air temperature and relative humidity were 28 degrees C and 40%. Tympanic (Tty) and oesophageal temperatures, forehead sweat rate (msw), skin blood flow (Qsk) and blood flow through the ophthalmic vein (Qov) were measured, and the mean skin (Tsk) and mean body (Tb) temperatures were computed. Passive body warming was induced by a box-shaped body warming unit enclosing all but the subject's head. Exercise was performed either at an intensity of 60% maximal oxygen consumption or with the intensity increasing in increments. During both tests, msw and Qsk started to increase shortly after the imposition of the heat load. The Qov began to change with the venous blood flowing from the face into the intracranium and a complete reversal in the direction of Qov (from the face to the intracranium) came significantly later than the increases in msw and Qsk. The Tty at the time of flow reversal was the same in both tests. The Tsk (and hence Tb) at flow reversal was, however, significantly higher during passive body warming than during exercise. The mechanism for switching the direction of Qov appeared to have been triggered by a high temperature in the brain, and not by thermal input from the periphery of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.

The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.

Animals↗

Mechanisms of spinal reflex depressant effects of CS-722, a newly synthesized centrally acting muscle relaxant, in spinal rats.

The mechanisms of the depressant action of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized centrally acting muscle relaxant, on spinal reflexes were investigated in spinal rats. The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex. Eperisone-HCl (10 mg/kg, i.v.) and baclofen (2 mg/kg, i.v.) markedly decreased the monosynaptic and polysynaptic reflexes, with longer durations than CS-722; CS-722, eperisone and baclofen depressed the dorsal root reflex. The excitability of the motoneurone was reduced by CS-722 and eperisone. Excitability of the primary afferent fibres was reduced by CS-722, while eperisone and baclofen had no effect. Both CS-722 and eperisone did not have a depressant influence on the focal synaptic potential. These results suggest that CS-722 and eperisone but not baclofen, have a common motoneurone-membrane-stabilizing action and that this action may contribute, in part, to the spinal reflex depressant effects of CS-722 and eperisone.

Animals↗

Primary retroperitoneal plasmacytoma with tumor thrombus within the renal vein.

A case of primary retroperitoneal plasmacytoma causing a tumor thrombus within the renal vein is described. The use of radiographic techniques, including ultrasonography, computerized tomography and angiography, facilitated an accurate diagnosis. Tumor thrombi within the renal vein are rare except in cases of primary renal or adrenal neoplasms. In a patient with radiological evidence of retroperitoneal tumor and tumor thrombus within the renal vein plasmacytoma should be considered in the differential diagnosis of retroperitoneal neoplasms.

Aged↗

Antigen recognition by the T cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha.

The binding specificities and function of mouse CD8 were studied using a CD4-CD8- allospecific T cell hybridoma, chimeric class I MHC molecules, and a CD8 alpha deletion mutant. By transfecting the mouse CD8 alpha gene into a IL-2 producing, H-2Kb specific hybridoma, IL-2 production was increased when L cells expressing Kb were used as stimulators. However, no increase in IL-2 was observed when a KbKbB7 hybrid molecule, composed of the alpha 1 and alpha 2 domains of H-2Kb, and the alpha 3 domain of HLA-B7, was used as a stimulator. Comparison between T cell hybridomas that expressed full-length CD8 alpha and a deletion mutant lacking part of the cytoplasmic domain revealed identical responsiveness for H-2Kb. The data suggest that the mouse CD8 alpha homodimer does not bind to the alpha 3 domain of HLA class I molecules and that CD8 alpha acts as a co-receptor with the TCR by binding the same MHC molecule for alloantigen recognition. Our data also provide evidence that CD8 alpha signal transduction through its cytoplasmic tail by association with p56lck is not an absolute requirement for antigen recognition by T cells.

Animals↗