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Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 199 records · Page 11Linked to original sources

Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat.

Apoptosis may be an important mechanism of cell death in some experimental cell death models as well as in human neurodegenerative disorders. We report evidence to indicate that 1-methyl-4-phenylpyridinium ion (MPP+) induces apoptotic cell death using ventral mesencephalic and striatal co-culture; Apoptosis was defined by characteristic changes in nuclear morphology as revealed by hematoxylin-staining and DNA breaks in situ, which were demonstrated histochemically by labeling 3'-OH ends with biotinylated deoxyuridine through the action of terminal deoxynucleotidyltransferase, and DNA fragmentation, which was shown by agarose-gel electrophoresis. Apoptosis may be an important mechanism of cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression.

The molecular action of leptomycin B (LMB), an agent inducing arrest of the eukaryotic cell cycle at G1 and G2 phases, was investigated by analyzing an LMB resistance gene of Schizosaccharomyces pombe. A genomic library of an LMB-resistant mutant was screened for LMB resistance, and a DNA fragment containing an open reading frame (ORF) of 1078 amino acids was cloned on a multicopy vector. The plasmid was found to confer drug resistance specifically to LMB. Nucleotide sequencing revealed that the ORF was a mutant gene for the essential nuclear protein crm1, which had been reported to complement a cold-sensitive mutation causing deformed nuclear morphology. The gene product named crm1-N1 had two amino acid replacements (Gly-503 to Asp and Met-546 to Ile). Two allelic mutants of crm1 (crm1-809 and crm1-119) were found to be hypersensitive and resistant, respectively, to LMB. Nuclear morphology of the cold-sensitive crm1-809 mutant at the restrictive temperature was almost the same as that of the wild-type cells treated with LMB. Furthermore, a low concentration of LMB induced the intracellular accumulation of a 25-kDa protein in the wild-type cells, which was immunologically identical to the protein accumulating in the crm1-809 mutant cells. These results strongly suggest that LMB primarily inhibits the function of the crm1 gene which is required for maintaining higher order chromosome structures, correct gene expression, and cell growth in the fission yeast.

Alkaloids↗

Experimental quantitative evaluation of transvascular removal of unnecessary substances in brain edema fluid.

We developed a model by which the transvascular removal of unnecessary substances in brain edema fluid could be measured quantitatively and chronologically. Brain stab wounds were produced in Wistar rats by insertion of paired microdialysis probes in the unilateral caudatoputamen. Homovanillic acid (HVA) was administered by microdialysis from one probe, and the HVA clearance was measured by HPLC analysis of perfusate from the other probe. Using this model, we evaluated the site of removal and whether the removal processes were affected by anesthesia or an elevated plasma concentration of the substance. As a result, 1) Probenecid did not change HVA clearance although this inhibits HVA removal via subarachnoid vessels. Therefore, HVA removal in this model was considered mainly due to intraparenchymal transvascular efflux. 2) There was no alteration in HVA removal induced by anesthesia or intravenous HVA injection. Consequently, this efflux mechanism seems to be a rather stable protective process, and seems to play a considerable role in brain microenvironmental homeostasis.

Animals↗

Determination of ABO genotypes with DNA extracted from formalin-fixed, paraffin-embedded tissues.

The gene encoding the specific glycosyltransferases which catalyze the conversion of the H antigen to A or B antigens shows a slight but distinct variation in its allelic nucleotide sequence and can be divided into 6 genotypes when digested with specific restriction enzymes. We extracted DNA from formalin-fixed, paraffin-embedded tissues using SDS/proteinase K treatment followed by phenol/chloroform extraction. The sequence of nucleotides for the A, B and O genes was amplified by the polymerase chain reaction (PCR). DNA fragments of 128 bp and 200 bp could be amplified in the second round of PCR, using an aliquot of the first round PCR product as template. Degraded DNA from paraffin blocks stored for up to 10.7 years could be successfully typed. The ABO genotype was deduced from the digestion patterns with an appropriate combination of restriction enzymes and was compatible with the phenotype obtained from the blood sample.

ABO Blood-Group System↗

Necrotizing arteritis causing fatal massive intraperitoneal hemorrhage from a pancreatic pseudocyst.

We report the histopathological findings from a medicolegal autopsy case caused by sudden massive hemorrhage from a necrotic pancreatic cyst into the abdominal cavity. The histological examination revealed that the wall of the cyst was filled with hematoma and consisted of granuloma at a relative early stage, involving marginating lymphocytes, foamy lipophages, cholesterin crystals, foreign body giant cells with neutrophiles, mast cells and fibrous tissues. Since there was no epithelial lining, the lesion was diagnosed as a pseudocyst. In the wall of this pseudocyst, small arteries showed acute intense necrotizing inflammatory reactions in association with fresh thrombi. Trace of elastic fibers remained in the wall of the arteries. Since the small veins in the wall showed varix-like changes without necrosis or inflammation, it is proposed that the lethal bleeding was caused by rupture of the small arteries that exhibited severe arteritis.

Acute Disease↗

Post-harvest degradation of carotenoid glucose esters in saffron.

It has been found that an indoor cultivation system of Crocus sativus L. is more favorable with regard to the quality of saffron, as compared to the usual cultivation in an open field. Carotenoid glucose esters increase from the period before blooming and reach the maximum in the full blooming period, and are sensitive for the presence of oxygen, light irradiation, and beta-glucosidase. Moreover, it is evident that storage of saffron at -20 degrees C promotes the constant supply of saffron with a homogeneous pharmacological activity.

Carbohydrate Conformation↗

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma-free hemoglobin on renal vascular responsiveness to vasoactive substances in isolated perfused rat kidney.

The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma-free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances were examined in isolated perfused rat kidneys. The kidneys isolated from rats were perfused with 6% PHP, 6% SFH, and 6% hydroxyethylstarch (HES) solution at a constant flow rate. Vascular responsiveness to acetylcholine (ACh), nitroglycerin (NG), norepinephrine (NE), and angiotensin-II (ANG-II) was examined by measuring the perfusion pressure (PP). Effects of inhibition of endothelium-derived relaxing factor (EDRF) by NG-monomethyl L-arginine (L-NMMA) on NE-induced and ANG-II-induced renal vascular responses were examined. ACh and NG induced a dose-dependent decrease in perfusion pressure (PP) in all groups. NE and ANG-II induced an increase in PP in all groups, but NE-induced and ANG-II-induced responses in the PHP-perfused and SFH-perfused groups were significantly larger than those in the HES-perfused group. L-NMMA did not alter vascular responsiveness to NE and ANG-II. These results indicate that PHP and SFH do not inhibit EDRF induced by ACh, but hemoglobin moiety per se does augment the vascular responsiveness to NE and ANG-II in the isolated perfused rat kidney.

Acetylcholine↗

Effect of interleukin 1 receptor antagonist on the blood-aqueous barrier after intraocular lens implantation.

Interleukin 1 (IL-1) possesses as an intercellular signal a wide spectrum of inflammatory, metabolic, haematopoetic, immunological, and reparative properties and can be a mediator not only of host defence but also of disease. Reduction of IL-1 can decrease the inflammatory host response. A human recombinant IL-1 receptor antagonist (IL-1ra) was used to block IL-1 after intraocular lens implantation in rabbits. Seventeen rabbits underwent intercapsular phacoemulsification and posterior chamber lens implantation. A 100 micrograms dose (0.1 ml) of IL-1ra (1 mg/ml) was injected into the anterior chamber at the end of surgery in seven rabbits. The 10 rabbits serving as the controls received no IL-1ra. Postoperatively, all rabbits were observed with a slit-lamp, and the aqueous flare intensity was measured with a laser flare cell meter at 12 hours, 1, 2, 3, and 4 days and thereafter at 1, 2, 3, and 4 weeks. Aqueous flare intensity was significantly lower on days 2 and 3, and fibrin deposition much less marked in the eyes treated with IL-1ra, compared with the controls. The results suggest that IL-1 is involved in the postoperative inflammation that occurs after intraocular lens implantation and the use of the IL-1ra would be valuable for reducing this problem.

Animals↗

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects.

BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.

Acetaldehyde↗

Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.

The methanol extract of the aerial part of Andrographis paniculata Nees showed potent cell differentiation-inducing activity on mouse myeloid leukemia (M1) cells. From the ethyl acetate-soluble fraction of the methanol extract, six new diterpenoids of ent-labdane type, 14-epi-andrographolide (3), isoandrographolide (4), 14-deoxy-12-methoxyandrographolide (7), 12-epi-14-deoxy-12-methoxyandrographolide (8), 14-deoxy-12-hydroxyandrographolide (9) and 14-deoxy-11-hydroxyandrographolide (10) as well as two new diterpene glucosides, 14-deoxy-11,12-didehydroandrographi-side (12) and 6'-acetylneoandrographolide (14), and four new diterpene dimers, bis-andrograpolides A (15), B (16), C (17) and D (18), were isolated along with six known compounds. The structures of the diterpenoids were determined by means of spectral methods. Some of these compounds showed potent cell differentiation-inducing activity towards M1 cells.

Animals↗

Inhibitory effect of a selective thromboxane synthetase inhibitor, OKY-046, on acetaldehyde-induced bronchoconstriction in asthmatic patients.

We recently reported that inhaled acetaldehyde causes bronchoconstriction indirectly via histamine release in patients with asthma. The purpose of this study was to investigate a role of thromboxane A2 in acetaldehyde-induced bronchoconstriction in asthmatic airways. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects who were treated with placebo or OKY-046, a selective thromboxane A2 synthetase inhibitor, of 200 mg twice a day for 3 days, and 200 mg on the fourth day (test day) in a double-blind, randomized, placebo-controlled, crossover fashion. Percentage decreases in FEV1 caused by 20 and 40 mg/ml of acetaldehyde inhalation were significantly (p < 0.05 and p < 0.01, respectively) prevented by the pretreatment with OKY-046. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV1 (PC20-Ac-CHO) was significantly (p < 0.01) greater with the OKY-046 pretreatment (72.2 [1.1] mg/ml) than with the placebo pretreatment (19.8 [1.2] mg/ml). We conclude that thromboxane A2 is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A2 may play an important role in endogenous histamine-induced bronchoconstriction caused by acetaldehyde in asthmatic airways. We believe that this is a first report on the interaction between endogenous histamine and thromboxane A2 in asthmatic subjects.

Acetaldehyde↗

Effects of 5-(N,N-hexamethylene)amiloride on action potentials, intracellular Na, and pH of guinea pig ventricular muscle in vitro.

We examined the effects of 5-(N,N-hexamethylene)amiloride (one of the Na(+)-H+ exchange blockers, HMA) and amiloride (AM) on action potentials (APs), intracellular Na+ activity, and pH using conventional and double-barreled ion-selective microelectrodes in guinea pig papillary muscle in vitro. Papillary muscle preparations were superfused with HEPES-buffered solution, and intracellular Na+ (aiNa+) and H+ (intracellular pH, pHi) activities were measured in quiescent preparations without stimulation. HMA at a concentration of 1 microM began to induce prolongation of action potential duration (APD) and at concentrations > 10 microM induced a decrease in action potential amplitude (APA), depolarization of resting membrane potential (RMP), prolongation of APD and depression of the maximum upstroke velocity (Vmax). HMA exerted dose-, time-, and rate-dependent reduction in Vmax. AM began to prolong APD at a concentration of 10 microM and at 1 mM induced depolarization of RMP, decreased Vmax and induced significant prolongation of APD. HMA (100 microM) induced a decrease in aiNa+ by 2-3 mM, but exerted no effects on pHi in normal Tyrode's solution. Under conditions of intracellular acidosis induced by exposure to K(+)-free solution, HMA produced a further decrease in pHi. Our results provide direct evidence that HMA has a depressant action on cardiac Na+ channels and prolongs AP at concentrations that presumably affect Na(+)-H+ exchange in cardiac muscle.

Acidosis↗

Increased heart rate and blood pressure response, and occurrence of arrhythmias in elderly swimmers.

Changes in the heart rate (HR) and blood pressure, and the occurrence of arrhythmias after swimming were examined in 52 members of swimming classes aged 40 to 76 years. After swimming 25 m twice at a usual intensity, HR increased markedly in the subjects to 87 +/- 11% of predicted maximal HR, while the rate of perceived exertion was modest. The systolic blood pressure (SBP) also increased significantly, and SBP of 200 mmHg or higher was exclusively observed in subjects 60 years or older. After entering the pool, immersing the face and swimming, 28 subjects (54%) developed various arrhythmias. Premature ventricular contraction (PVC) was provoked or aggravated by swimming in 19 subjects. The incidence of PVC provocation or aggravation increased as SBP at rest or age increased. Swimming causes marked rise in HR and SBP in elderly subjects, and frequently provokes or aggravates PVC in older subjects and/or in subjects with higher SBP at rest.

Adult↗

[A case of prostatic adenocarcinoma with pulmonary metastases--diagnosis by transbronchial lung biopsy and immunohistochemistry].

Metastatic pulmonary adenocarcinoma was found in a 79-year-old man, who had symptoms of general malaise and poor appetite. An extensive work-up including a transurethral resection of the prostate, failed to establish the primary site of the malignancy. By administering chlormadinone acetate for prostatic hypertrophy, the pulmonary metastases improved dramatically. The tumor cells in the lung, which had previously been obtained by transbronchial lung biopsy, stained positive for prostatic acid phosphatase and prostatic specific antigen. These data suggested that prostatic carcinoma had metastasized to the lung. The prostatic carcinoma was finally confirmed at autopsy.

Acid Phosphatase↗

[A case of liver cirrhosis presenting with right pleural fluid without ascites].

A 80-year-old man was admitted to our hospital complaining of appetite loss, dry cough, and dyspnea on exertion. Chest X-ray film showed massive right pleural effusion. On physical examination, the right thorax was dull to percussion, and breath sounds of the right lung field were diminished. Examination of the cardiovascular system was unremarkable. Hepatosplenomegaly and ascites were not evident. The character of the pleural fluid was transudative. Cytological findings were negative and culture of the pleural fluid was normal. First, the pleural fluid was diminished by thoracic drainage. But, after the cessation of drainage, the pleural fluid soon reaccumulated. Abdominal ultrasonography showed typical liver cirrhosis pattern without ascites. An intraperitoneal injection of 99mTc-sulfur colloid was followed by positive uptake of radioactivity in the right pleural cavity from 1 hour after the injection, demonstrating the existence of a direct perito-pleural communication. Thus, the diagnosis of liver cirrhosis presenting with right pleural fluid, without ascites was made. This case indicates that the absence of ascites cannot exclude cirrhosis as the etiologic cause of pleural effusion.

Aged↗

[Evaluation of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

We investigated the utility of intraoperative peritoneal lavage smears and gastric wall brushing smears for diagnosis of peritoneal dissemination and serosal involvement during gastric cancer surgery. One hundred fifty-three patients with gastric cancer were examined; 138 who underwent gastric resection and 15 who did not. The incidence of cancer cell positivity determined by these methods was 8.0% in resected cases, and 80.0% in unresected cases. According to macroscopic serosal invasion, the incidence of positive cytology was 0% for S0, 15.4% for S1, 13.0% for S2, and 38.7% for S3. According to microscopic wall invasion, the incidence of positivity was 0% for m and sm, 6.3% for mp, 0% for ss, and 22.2% for se and si. In terms of macroscopic peritoneal dissemination, the incidence of positivity was 2.6% for P0, 28.6% for P1, 42.9% for P2, and 90.0% for P3. These results suggest that peritoneal lavage smears and gastric wall brushing smears are useful for predicting the spread of peritoneal dissemination. Thus, further study of intraoperative fast-smear cytology seems warranted.

Gastrectomy↗

Inhibitory effect of aerosol administration of a sulfidopeptide leukotriene antagonist on bronchoconstriction induced by antigen inhalation in guinea pigs.

The effects of inhalation of the sulfidopeptide leukotriene antagonist AS-35 (9-[(4-Acetyl-3-hydroxy-2-n-propyl-phenoxy)methyl]-3-(1H- tetrazol-5-yl)-4H-pyrido [1,2-a]pyrimidin-4-one, CAS 108427-72-1) on bronchoconstriction induced by aerosol antigen, histamine, and leukotriene C4, D4 (LTC4, D4) were investigated in anesthetized and artificially ventilated guinea pigs. The increase in pressure at the airway opening (P(ao)) was measured as an index representing the grade of bronchial response. The bronchoconstriction induced by aerosol antigen was suppressed dose-dependently by pretreatment with inhaled AS-35 (0.1 mg and 1 mg) through a pressurized meter-dosed inhaler in the passively sensitized animals pretreated with diphenhydramine hydrochloride. But the histamine-induced bronchoconstriction was not altered by the pretreatment with AS-35 inhalation. On the other hand, LTC4- and LTD4-induced bronchoconstriction was inhibited by the pretreatment with aerosol AS-35 in a dose-dependent manner. The deposited dose of inhaled AS-35 in the peripheral airways was 3.5 micrograms and 6.5 micrograms when 0.1 mg and 1 mg of the drug was inhaled, respectively. These results suggest that sulfidopeptide leukotrienes (s-LTs) play an important role in the allergic bronchoconstriction in guinea pigs pretreated with antihistamine, and AS-35 inhalation may be beneficial in the treatment of asthma.

Administration, Inhalation↗