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Biomedical subjects

N Nakajima

Publications and source records attributed to N Nakajima.

At least 19 recordsLinked to original sources
PubMed1992

Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist.

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.

Administration, Inhalation↗
PubMed1992

Purification and characterization of a cystatin-type cysteine proteinase inhibitor in the human hair shaft.

We found a cysteine proteinase inhibitor in human hair shaft extract treated with 0.01 M Tris HCl buffer, pH 8.0. A yield of 0.2 mg of purified cysteine proteinase inhibitor was obtained from 86 g of hair shaft. The cysteine proteinase inhibitor had a molecular mass of 13 kDa as determined by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was more stable to heat and pH than most proteins and had a pI of 4.7. Immunologically, its antigenicity was the same as that of cystatin A, but differed from that of cystatin B and C, and kininogen. The amino-acid sequence of the first 30 residues from the NH terminus of the inhibitor was identical to that of cystatin A from human epidermis. Hair shaft cysteine proteinase inhibitor is thus considered to be identical to epidermal cystatin A.

Cystatins↗
PubMed1992

Purification and characterization of two fibrinolytic enzymes from Bothrops jararaca (jararaca) venom.

Two fibrinolytic enzymes, jararafibrase I and jararafibrase II, were purified from Bothrops jararaca venom. The purified jararafibrase I and jararafibrase II ran as single protein bands on analytical polyacrylamide gel electrophoresis and had mol. wts of 47,000 +/- 2000 and 21,400 +/- 500, respectively, by SDS-polyacrylamide gel electrophoresis. The isoelectric points of jararafibrase I and jararafibrase II were 4.6 and 6.5, respectively. The specific activities of jararafibrase I and jararafibrase II were 2.2 units/mg protein and 6.3 units/mg protein, respectively. Both enzymes exhibited no detectable plasminogen activating activity. The activity of the enzymes was completely inhibited by 1,10-phenanthroline and ethylenediaminetetraacetate, suggesting that both enzymes were metalloproteinases. Jararafibrase I and jararafibrase II had single-chain protein compositions, and the amino acid sequence up to the 49th amino acid from the NH2-terminal of jararafibrase II was: Leu-Pro-Glu-His-Gln-Arg-Tyr-Ile-Glu-Leu-Phe-Ile-Val-Val-Asp-His-Gly-Met- Phe-Met-Lys-Tyr-Asn-Gly-Asn-Ser-Asp-Lys-Ile-Arg-Arg-Arg-Ile-His-Gln- Met-Val-Asn-Ile-Met-Lys-X-Ala-Tyr-Arg-Tyr-Leu-Tyr-Ile-(X = not confirmed).

Amino Acid Sequence↗
PubMed1992

Effect of various polyamino acids and D- and L-amino acids on the blood fibrinolytic system.

1. Comparative additional effects of 24 commercially obtained amino acids and their derivatives were studied by the whole blood clot lysis time (WBCLT) method. D-Arg and L-Lys (greater than 50 micrograms/ml) activated the fibrinolytic system, and poly-L-Glu (mol. wt 6000-90,000) (less than 50 micrograms/ml) were less effective. 2. Poly-L-Arg, poly-L-Lys and poly-(Lys-Ala-Glu-Tyr) accelerated the TPA inhibition in the presence of human plasma. 3. For in vivo experiments, 5 mg of poly-L-Glu were given intravenously to 10 rats. 4. The shortening of WBCLT and elevation of EFA (P less than 0.01) were found after 1 hr administration. 5. The main enzymes which increased in plasma were proved to be the endogenous plasminogen activators with mol. wt higher than 70,000, by zymography.

Amino Acid Sequence↗
PubMed1992

Fibrinolysis relating substances in marine creatures.

1. Extracts with physiological saline solution were obtained from about 20 species of invertebrates and seaweed. Tosyl-L-Arg-MeOH hydrolysing and fibrin plate lytic activity were detected in the invertebrates Stichopus japonicus, Crassost gigas, Tapes japonica, and Kintai-gai as well as the seaweed Codiales codium. 2. These activities were all labile against heat (at 65 degrees C for 1 hr). Except for the extract from Stichopus japonicus, lytic activities against fibrin plates with and without plasminogen were similar. 3. The extract from S. japonicus showed plasminogen activating potency as well as the existence of urokinase (UK) activity enhancing factor. 4. On the other hand, the extract of the seaweed Hizikia fusiformis showed a strong UK inhibiting activity. 5. A fraction of fibrinolytic enzyme was obtained from the extract of S. japonicus by absorption to the celite affinity chromatography. It was orally administered to rabbits at a dosage of 40 mg/kg/day. 6. Fibrinolytic activity was determined periodically on the eugloblin fraction of plasma samples collected from these animals. 7. As compared with the pretreatment value, the activity increased about 2 times (P less than 0.01) and 3 times (P less than 0.005) after 4 and 8 weeks, respectively, of the treatment. 8. After 8 weeks of treatment, the kidney of treated rabbits was extracted with 2 M KCl. The activity of tissue plasminogen activator (free-type TPA) was revealed to be enhanced significantly (P less than 0.001) in the extracts. 9. The fibrinolytic enzyme increased in the blood was recognized by zymography to be mainly the UK type plasminogen activator with mol. wt of 53,000.

Animals↗
PubMed1992

Endothelium-dependent vasodilation by LP-805, a novel vasodilating agent, on rat thoracic aorta.

1. In rat aortae with [E(+)-tissue] and without [E(-)-tissue] intact endothelium, LP-805 relaxed the preparations precontracted with 35.9 mM K+ and its action in E(+)-tissues was more potent than that in E(-)-tissues. Moreover, the inhibitory action of glibenclamide in E(-)-tissues was more potent than that in E(+)-tissues. 2. The relaxing action of LP-805 on E(+)-tissues treated with NG-nitro-L-arginine methyl ester (10 microM), a potent inhibitor of nitric oxide synthesis, was the same as that in E(-)-tissues. 3. Methylene blue (10 microM) also inhibited the LP-805 induced relaxation in E(+)-tissues. 4. Indomethacin (10 microM) had no effect on LP-805-induced relaxation in E(+)-tissues. 5. These results suggest that the vasorelaxant action of LP-805 involves the mechanism which causes the release of nitric oxide (NO) from vascular endothelium.

Animals↗
PubMed1992

Effects of LP-805, a novel vasorelaxant agent, a potassium channel opener, on rat thoracic aorta.

1. In rat thoracic aorta, LP-805 (0.1-10 microM) caused the marked reduction of NE-induced maximum response and relaxed the low K+ (less than 35.9 mM)-induced contraction, in a concentration-dependent manner, but failed to relax the high K+ (65.9 mM)-induced contraction. 2. Glibenclamide (0.3-1 microM) caused a parallel shift of concentration-response curve produced by LP-805 for 25.9 mM K(+)-induced contraction and prevented the LP-805-induced reduction in maximum response evoked by NE in a concentration-dependent manner. 3. Glibenclamide (10 microM) prevented the LP-805 (10 microM)-induced decrease in cytosolic Ca2+ levels which was increased by 1 microM NE or 25.9 mM K+. 4. LP-805 (10 microM) increased basal 86Rb efflux, which was completely inhibited by 10 microM glibenclamide. 5. The results suggest that LP-805 causes a vasorelaxation as a consequence of the decrease in cytosolic Ca2+ levels due to the increase in K+ efflux via opening ATP-dependent K+ channels.

Animals↗
PubMed1992

Clinical experience of mitral valve reconstruction with artificial chordae implantation.

To expand the application of mitral valve reconstruction for pure mitral regurgitation due to diffuse leaflet prolapse, we have employed artificial chordae implantation using GPEP strips in 9 patients and 4-0 PTFE sutures in 20 patients since November 1986. The total number of GPEP strips implanted was 20 with a range from 1 to 4 (average 2.2 per patient) and 45 pairs of PTFE sutures with a range from 1 to 6 (average 2.3 per patient). There was one hospital death (3.4%). All other patients survived operation without valve-related complications except 1 patient who required reoperation for failure of mitral valve reconstruction. In 27 survivors free from reoperation, the amount of mitral regurgitation assessed postoperatively was none or trivial in 19 patients, mild in 7 and moderate in 1. All 27 patients improved to NYHA functional class I or II. So far, our results were no less acceptable than those with conventional procedures for mitral valve prolapse.

Adolescent↗
PubMed1992

Type A aortic dissection: evaluation with ultrafast CT.

The authors examined 17 patients with type A aortic dissection with ultrafast computed tomography (CT). Forty sections with 1-cm intervals, from the aortic arch to the aortic bifurcation, were scanned serially without breath holding within only 74 seconds. Except for two thrombosed dissections, all intimal flaps in the ascending aorta were demonstrated, and 14 (93%) of the 15 surgically proved intimal tears were depicted. An intimal tear in the aortic arch was missed. Since conventional scanning tends not to depict type A aortic dissection, millisecond-order ultrafast CT scanning has the potential to become the modality of choice for imaging of aortic dissection.

Adult↗
PubMed1992

[Mitral valve surgery for patients after undergoing percutaneous transvenous mitral commissurotomy (PTMC)--investigation on indication of PTMC based on the intraoperative findings].

Ten patients underwent open heart surgery for mitral valve after PTMC because of post PTMC MS (n = 4) and MR (n = 6) out of 150 patients undergoing PTMC in our hospital between June 1987 and October 1991. Intraoperative findings of 4 patients with residual mitral stenosis included severe thickening, stiffening and calcification on anterior and posterior leaflets, commissures and subvalvular apparatus. Mitral valve repair was possible in 2 and mitral valve replacement (MVR) was necessary in the other 2. In all 6 cases who massive mitral regurgitation after PTMC, in repairable tears in the mitral leaflets necessitated MVR. Since in these cases changes in the leaflets were less severe than those of the commissures or subvalvular apparatus, surgical repair could have been possible if open mitral commissurotomy (OMC) was done primarily. Patients selection for PTMC versus OMC based on precise morphological evaluation of mitral valve would reduce occurrence of massive MR resulting in surgical replacement.

Adult↗
PubMed1992

[The effects of protease inhibitor upon the ischemia-reperfusion injury].

The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[The controversy on the treatment of aortic dissection].

It is obvious that there are many controversies regarding to the treatment of aortic dissection. In this report, we discuss following points such as 1) classification, 2) thrombosed type dissection, and 3) simultaneous graft replacement of ascending and aortic arch with the reconstruction of cervical branches. From the patho-morphological status, dissection will be classified into two types, localized and extended types. From the anatomical and surgical points of view, it will be also classified as 1) ascending-arch, 2) descending-thoracoabdominal, and 3) abdominal. With the combination of these two, dissection will be classified more clearly. The thrombosed type will be incorporated into localized type. We have experienced 76 cases of this dissection, and clinical features and outcome by medical treatment only are presented. The simultaneous reconstruction of ascending aorta and aortic arch for the dissection at ascending-arch type was undertaken in total of 35 patients. The surgical results as well as follow up data are presented and the benefit of this extended procedure is presented as well.

Aortic Dissection↗
PubMed1992

[The experimental and clinical study of hyperthermia with thermosensitizer for gastric cancer patients with peritoneal seeding].

We examined experimentally and clinically the effect of misonidazole (MISO), a hypoxic cell radiosensitizer, in combination with hyperthermia. First, tissue blood flow and tumor growth of xenoplanted human gastric cancer in nude mice were measured after treatment with MISO 500 mg/kg ip plus hyperthermia at 40.5, 42.0 and 43.5 degrees C. Also clinically, 17 advanced gastric cancer patients with peritoneal seeding underwent intraperitoneal hyperthermic perfusion (IPHP). They were given MISO 1.45 g/m2 po twice (12 hours and 5 hours before IPHP). And plasma MISO levels were measured. MISO plus hyperthermia produced a more prolonged decrease of the tumor blood flow than hyperthermia alone. At 43.5 degrees C, TbF recovered 2 days after the treatment. MISO plus hyperthermia also made tumor growth delay more marked than hyperthermia alone. In gastric cancer patients treated with MISO plus IPHP, T 1/2 of serum MISO was 7.7 hours and the AUC was 1,087 micrograms.hr/ml. There were no side effects observed which were caused by MISO. Thus MISO can be an effective thermosensitizer when used in combination with hyperthermia.

Animals↗
PubMed1992

[Clinical statistics on operations for inpatients at Department of Urology, Tokai University Hospital 1975-1989].

Operations on inpatients during the 15-year period from 1975 to 1989 were analyzed statistically. A total of 3,791 operations were performed at our Department of Urology, including 717 operations on the kidney, 316 operations on the ureter, 583 operations on the bladder, 811 operations on the prostate, 136 operations on the urethra, 1,097 operations on the scrotum, 43 operations on the adrenal gland, 19 operations on the retroperitoneal space and 69 operations on other organs.

Adolescent↗
PubMed1992

[An experimental study of myonephropathic metabolic syndrome (MNMS)].

We have attempted to establish dog experimental model similar to clinical MNMS. Thirty-five dogs were divided into four groups; G-1: Ligation of abdominal aorta. (N = 5), G-2: Ligations as above for 6 hours and reperfusion. (N = 12), G-3: Same as G-2+ligation of superior epigastric arteries (N = 13), G-4: Same as G-2+transection of abdominal muscles (N = 5). Biochemicals, electrolytes and blood gas analysis in artery and vein were measured before, 6 hours after clamp, 5 minutes, 1 hour, 6 hours after reperfusion. Skeletal muscle PCO2, pH of lower leg were continuously measured. In G-1, no dog showed MNMS, in G-2, half of the dogs developed MNMS, in G-3, MNMS developed 9, but not in 4. In G-4, 4 dogs died during aortic cross-clamping. Satisfactory results were obtained in G-3. From the results of statistical analysis, the measurement of GOT, LDH, CPK, Cr and tissue PCO2, pH showed high significance between MNMS (+) and (-), and had correlation with K, BE, pH of artery and vein after reperfusion. Therefore, we consider that above factors are appropriate predictors for MNMS.

Acidosis↗
PubMed1992

Continuous monitoring of blood oxygen saturation of internal jugular vein as a useful indicator for selective cerebral perfusion during aortic arch replacement.

We continuously monitored blood oxygen saturation in the internal jugular vein during selective cerebral perfusion for aortic arch operations and evaluated its efficacy as an indicator of cerebral oxygen metabolism. The selective cerebral perfusion method was applied in 11 patients who underwent operations for aortic arch replacement. Blood oxygen saturation in the internal jugular vein was continuously monitored at the bulbus jugularis with a fiberoptic catheter during the operation. Perfusion flow of 500 ml/min was continued for 134.7 +/- 14.9 minutes under moderate hypothermia at 25 degrees C, and bilateral temporal arterial pressure was 40 to 60 mm Hg. Blood gas data were used to estimate oxygen consumption, oxygen extraction ratio, and lactate uptake in the cerebrum. No patients had postoperative cerebral complications. Cerebral oxygen consumption was 2.93 +/- 0.4 ml/min/100 gm under general anesthesia at 36 degrees C. While selective cerebral perfusion at 25 degrees C decreased consumption to 0.92 +/- 0.39 ml/min/100 gm, it fell to about 30% of its former value. Blood oxygen tension in the internal jugular vein showed no significant correlation with rectal temperature. Selective cerebral perfusion did not significantly affect cerebral lactate uptake. In contrast, blood oxygen saturation in the internal jugular vein was significantly affected by temperature and cerebral flow during selective cerebral perfusion, and blood oxygen saturation in the internal jugular vein correlated closely with cerebral oxygen extraction ratio (r = 0.91). Cerebral oxygen metabolism was thus well maintained, and continuous monitoring of blood oxygen saturation in the internal jugular vein was found to serve as a useful indicator under selective cerebral perfusion during operations for aortic arch replacement.

Adult↗
PubMed1991

Characterization of the lymphoproliferative diseases in the skin by DNA analysis.

Various samples from lymphoproliferative diseases in the skin were analyzed by Southern blotting technique with probes from the T cell receptor gene, immunoglobulin genes, and human T cell leukemia virus-I genome. Samples were taken from 10 mycosis fungoides (MF) patients, 1 parapsoriasis en plaque patient, 10 Adult T cell leukemia/lymphoma (ATL) patients, 1 cutaneous T cell lymphoma (CTCL) patient, 4 lymphomatoid papulosis (LP) patients, 4 B cell lymphoma patients, and 2 actinic reticuloid (AR) patients. In MF, the monoclonality of the T cells became detectable first in the skin when plaques develop to tumors then in lymph nodes, and finally in the blood lymphocytes, indicating this disease develops from local (skin) malignancy to systemic malignancy. In parapsoriasis en plaque, no monoclonality was detected in any sample. We could distinguish cutaneous ATL from the carrier state by detecting the T cell monoclonality and HTLV-I integration with these probes. One patient with CTCL showed detectable T cell monoclonality; 1 out of 4 patients with LP did the same. Four samples from patients with B cell lymphoma revealed detectable monoclonal rearrangement of immunoglobulin heavy and light chain genes. In AR, no monoclonality was detected in any sample. From these data, we conclude that DNA analysis is useful in determining the monoclonality, cell origin, and distribution of monoclonal cells from skin samples.

Antibodies, Monoclonal↗