Protein function. Chaperonin turned insect toxin.
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Animals↗
Biomedical subjects
K Nishimura
Publications and source records attributed to K Nishimura.
Left ventricular hypertrophy demonstrated by four-dimensional myocardiography by helical computed tomography.
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Cardiomyopathy, Hypertrophic↗
Effects of organosilicon pyrethroid-like insecticides on nerve preparations of American cockroaches and crayfish.
Quaternary organosilicon pyrethroid-like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extracellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail-current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail-current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail-current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail-current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven-fold higher than that of the alkanes with equivalent tail-current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)opt = 9.1] when other factors were similar.
Action Potentials↗
Insecticidal and binding activities of N3-substituted imidacloprid derivatives against the housefly Musca domestica and the alpha-bungarotoxin binding sites of nicotinic acetylcholine receptors.
N3-substituted imidacloprid congeners containing C1-C6 alkyl groups or various analogous groups, and their corresponding nitromethylene analogues, were used in this study. Their insecticidal activity against the housefly, Musca domestica, and their binding activity toward the nicotinic acetylcholine receptor were determined. The insecticidal test was conducted using the synergists piperonyl butoxide and propargyl propyl phenylphosphonate. The binding assay was performed with housefly head membrane preparations using radio-labelled alpha-bungarotoxin. Both insecticidal and binding activities were drastically lowered by the introduction of alkyl/allyl groups at the imidazolidine NH sites of both nitroimino and nitromethylene compounds. The binding activity of N3-substituted nitromethylene analogues was much higher than that of the corresponding nitroimino analogues. However, the insecticidal activity of both series of compounds with a given substituent was nearly identical. The insecticidal activity correlated positively with the binding activity after taking into account the structural difference of the nitroimino and nitromethylene moieties and a structural feature of the N3-substituents.
Animals↗
Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats.
Nishimura, K., Araki, N., Ohnishi, Y., and Kozaki, S. 2001. Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats. Experimental Parasitology 97, 95-101. A diet deficient in polyamines decreases the availability of dietary polyamines. We used rats infected with the Wellcome strain of Trypanosoma gambiense to examine the effects of polyamine-deficient chow (PDC) on trypanosome proliferation and symptoms of infection. Rats fed PDC showed limited increase of trypanosome and symptoms of infection and limited loss of body weight and anemia. Survival in these rats was prolonged. Before infection, the heparinized plasma concentration of spermidine in the PDC-fed rats was lower than that in control rats fed with standard chow. After infection, the content of spermidine in red blood cells increased in the control rats, but was only slightly increased in PDC-fed rats. The content of spermidine in the trypanosomes after infection was low in the PDC-fed rats. Decreases in the polyamine content of trypanosomes limited their increase. These observations suggest that a reduction in dietary polyamines may help in the regulation of trypanosome infection.
Animal Feed↗
Compact, reliable ventricular assist device as a bridge to recovery or for semipermanent use.
OBJECTIVES: The magnetically suspended centrifugal pump has gained attention as an implantable ventricular assist device for long-term use. We report recovery-oriented pump operation and results of a chronic animal experiment. METHODS: In an acute experiment in 8 sheep having microspheres injected to induce heart failure, left ventricular assist was implemented by 2 inflow cannulas, 1 each in the left atrium and left ventricle. The pressure-volume loop of the left ventricle and myocardial oxygen consumption were measured varying the assist rate. The chronic animal experiment used 10 sheep whose native heart was kept intact. Continuous hemodynamic monitoring and periodic blood sampling were conducted. RESULTS: In the acute study, myocardial oxygen consumption decreased proportionally with increasing assist rate in left atrial drainage, but was significantly less at a 100% assist rate in left ventricular drainage. External work in left ventricular drainage did not decrease until a 75% assist rate, suggesting that the left ventricle shape and size were maintained despite decreased myocardial oxygen consumption. In the chronic experiment, the pumping duration was 14 to 248 days. No thrombi or emboli in the pump or any major organ were found in sacrificed sheep after living more than 100 days. Hepatic and renal function were within an almost normal range throughout the experiment. CONCLUSION: Left ventricular blood drainage effectively reduced oxygen consumption, maintaining the shape of the left ventricle. The magnetically suspended centrifugal pump is suitable for recovery of a failing heart or semipermanent use.
Animals↗
Assessment of the effect of revascularization early after CABG using ECG-gated perfusion single-photon emission tomography.
When an arterial graft is used, reversible perfusion defects on single-photon emission tomography (SPET) perfusion images are occasionally observed early after coronary artery bypass graft surgery (CABG), owing to the restricted flow capacity. The purpose of this study was to determine whether the functional information obtained with electrocardiography (ECG)-gated perfusion SPET could be helpful in evaluating the effect of revascularization early after CABG. Twenty-three patients (18 men and 5 women, mean age 65+/-9 years) underwent stress/re-injection thallium-201 ECG-gated SPET before and 4 weeks after CABG (13 with exercise and 10 with dipyridamole). Patency of all grafts was confirmed by coronary angiography 1 month after CABG. Cardiac functional data including the left ventricular ejection fraction (LVEF) and the transient ischaemic dilatation (TID) ratio were analysed using a commercially available automated program. The conventional stress and re-injection tomograms were interpreted by means of a five-point scoring system in a nine-segment model. Stress-induced reversible 201Tl perfusion defects were present in 64% of the myocardial segments bypassed by patent arterial grafts, in contrast to 42% of the myocardial segments bypassed by patent venous grafts (chi2=7.8, P=0.005). Of the 23 patients, 12 showed improvement in summed ischaemic scores (group 1), while 11 had no change or deterioration (group 2), although all grafts were patent on postoperative catheterization. The TID ratio improved in both group 1 and group 2 before and after CABG (1.14+/-0.13 vs 0.99+/-0.07, P=0.001 and 1.09+/-0.07 vs 0.94+/-0.05, P=0.002, respectively). However, LVEF did not significantly improve in group 1 or group 2 after CABG (42.5%+/-9.9% vs 47.5%+/-11.8%, and 52.1%+/-7.5% vs 53.1%+/-5.9%, respectively). Perfusion imaging or LVEF assessment is of limited value early after CABG. The TID ratio obtained with ECG-gated perfusion SPET may be a useful marker to evaluate the effect of revascularization early after surgery.
Aged↗
Clinical value of dilatation and curettage for abnormal uterine bleeding.
Dilatation and curettage was performed under anesthesia in outpatients in 1,837 patients aged over 26 with a history of abnormal uterine bleeding not associated with pregnancy or ovulation. Fifty-one (2.8%) patients were found to have malignant disease. Of these, 47 patients had endometrial carcinoma. An additional 111 (6.0%) patients were found to have endometrial hyperplasia. The incidence of either malignant disease or endometrial hyperplasia was 9.7% in patients over the age of 40. Complications of this method were noted in 12 (0.7%) patients; only three patients needed to stay in hospital.
Adenocarcinoma↗
Natural history of endometrial hyperplasia. Study of 77 patients.
Seventy-seven patients with endometrial hyperplasia, 48 with simple hyperplasia without atypia (SH), 17 with complex hyperplasia without atypia (CH), one with simple hyperplasia with atypia (SHA), and 11 with complex hyperplasia with atypia (CHA) were prospectively followed-up by total curettage every 12 months for 3 years. Progression to carcinoma occurred in only one of the 77 patients; she showed grade 1 adenocarcinoma. The overall regression rates were 79% for SH, 100% for SHA, 94% for CH, and 55% for CHA, respectively. In patients with CHA whose disease reverted to normal endometrium, regression was most likely to occur within the first year.
Adenocarcinoma↗
Nutcracker phenomenon demonstrated by three-dimensional computed tomography.
We report a 15-year-old girl with nutcracker syndrome (NCP) in whom three-dimensional helical computed tomography (3D helical CT) was useful for diagnosis; angiographic imaging using 3D helical CT provided fine outlines of the vascular structures in NCP, i.e., a compression of the left renal vein between the aorta and the superior mesenteric artery and the abnormal acute angle between them. Thus, a 3D helical CT enables precise depiction of the anatomical characteristics of renal vasculature and, therefore, may be a useful alternative imaging technique instead of conventional examinations, such as invasive venography or digital subtraction angiography. Further study in a large number of children with vascular abnormalities would be worthwhile.
Adolescent↗
Unusual liver carcinomas with sarcomatous features: analysis of four cases.
We recently examined the clinicopathological and immunohistochemical features of four cases of primary hepatic carcinoma with sarcomatoid elements. Three of the four patients had associated ordinary hepatocellular carcinoma (HCC) and one had a sarcomatoid carcinoma with no apparent elements of HCC. The presenting symptoms were high fever and hypochondralgia in three patients, and right hypochondralgia without a high fever in one. The preoperative diagnoses were liver abscess in two patients, HCC in one, and cholangioma in one. Preoperative imaging showed necrotic change or abscess formation in the tumors. The sarcomatous elements showed a positive reaction to vimentin in three patients, but the ordinary HCC cells did not. Macroscopically, the tumors appeared as a single nodule with pericapsular growth. The prognoses of these patients were poor due to the early development of intrahepatic or distal metastases. We conclude that symptoms such as a high fever or hypochondralgia are characteristics of these tumors and that they may be histogenetically derived from a dedifferentiation of HCC, although no elements of HCC were found in one of our cases.
Aged↗
Surgical treatment for chronic pulmonary thromboembolism under cardiopulmonary bypass with selective cerebral perfusion.
The median sternotomy approach for the treatment of chronic pulmonary thromboembolism was recently improved by Daily, Jamieson, and coworkers who adopted it for use under cardiopulmonary bypass with intermittent circulatory arrest; however, we have sometimes found that the circulatory arrest time was too short to complete thromboendarterectomy. Therefore, we attempted to perform a selective cerebral perfusion technique to extend the endarterectomy time. Although we noted slight back-bleeding from the bronchial arteries, we were able to extend the endarterectomy time without causing any postoperative delirium. We conclude that the median sternotomy approach using cardiopulmonary bypass with selective cerebral perfusion may be the best option for extending the thromboendarterectomy time.
Aged↗
A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia.
Autosomal dominant hypocalcemia can be caused by activating mutations of the calcium-sensing receptor (CaSR) gene. We experienced two patients (proband and her daughter) with hypocalcemia caused by a missense mutation of the CaSR gene. The proband, aged 25, showed hypocalcemia and hypoparathyroidism from infancy. She had been diagnosed as having idiopathic hypoparathyroidism and had been treated with calcitriol. She gave birth to a female infant at age 24 years. Her daughter was found to have hypocalcemia (Ca, 6.6mg/dl), without seizure or tetany, when she was 7 months old. DNA analysis of their CaSR genes showed a novel heterozygous mutation at codon 129 (TGC-to-AGC) with substitution of cysteine for serine (C129S). Familial examination revealed that this mutation had occurred de-novo in the proband. Wild-type and niutant (C129S) CaSR cDNA were transfected into HEK293 cells, and intracellular calcium concentrations were measured with a fluorescent calcium indicator. HEK cells transfected with the C129S mutant CaSR gene showed a larger increase in intracellular calcium concentration in response to the change in the extracellular calcium concentration than HEK cells transfected with the wild-type receptor. We conclude that the C129S mutation in the CaSR gene observed in these patients causes autosomal dominant hypocalcemia.
Adult↗
Effects of hepatocyte growth factor on E-cadherin-mediated cell-cell adhesion in DU145 prostate cancer cells.
OBJECTIVES: To examine how hepatocyte growth factor (HGF) affects cell-cell adhesion junctions on scattering in prostate cancer cells. HGF is known to induce scattering (dispersion of clustered cells into single cells) in various epithelial cells, including prostate cancer cells, but the mechanisms surrounding this action are not fully understood. Cell-cell adhesion junctions are composed of E-cadherin and its associated intracellular catenins and play important roles in the maintenance of cell integrity. METHODS: The human prostate cancer cell line DU145 was used in this study. The associations and changes of various adhesion molecules with HGF treatment were investigated by inhibition assays, Western blot analysis, and immunofluorescence staining. RESULTS: In the inhibition assay, anti-E-cadherin neutralizing monoclonal antibody caused the dissociation of DU145 cells similar to the scattering with HGF treatment. The expression of E-cadherin decreased with HGF, and the expression of alpha-catenin and beta-catenin did not change by Western blot analysis. In immunofluorescence staining, HGF caused the translocation of E-cadherin from cell-cell adhesion junctions to the cytoplasm. CONCLUSIONS: These results indicate that HGF induces scattering by decreasing the expression of E-cadherin and causes its translocation to the cytoplasm of DU145 cells.
Cadherins↗
Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons.
The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 microM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 microM RH-3421 application In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.
Action Potentials↗
Trichosporon species infection in bone marrow transplanted patients.
Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.
Adult↗
First isolation of Candida dubliniensis in Rio Grande do Sul, Brazil.
Candida dubliniensis is a newly recognized species closely phylogenetically related to Candida albicans and is commonly associated with oral candidiasis in human immunodeficiency virus-positive patients. In this paper we report the isolation of three strains of C. dubliniensis, from AIDS patients, in the state of Rio Grande do Sul (Brazil). The phenotypic identification was based on germ tube emission, abundant production of chlamydospores, assimilation of sucrose but not of xylose and the inability to grow at 42 degrees C. Randomly amplified polymorphic DNA (RAPD) analysis and genomic DNA sequencing confirmed the distinct genetic nature C. dubliniensis. Topics related to the epidemiology, isolation, phenotypical and genotypical identification of C. dubliniensis are also discussed.
AIDS-Related Opportunistic Infections↗
AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.
AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.
Administration, Oral↗