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101.
Inhibition of sickle beta-chain (betaS)-dependent polymerization by nonhuman alpha-chains. A superinhibitory mouse-horse chimeric alpha-chain 总被引:1,自引:0,他引:1
P Nacharaju RP Roy SP White RL Nagel AS Acharya 《Canadian Metallurgical Quarterly》1997,272(44):27869-27876
Horse alpha-chain inhibits sickle beta-chain-dependent polymerization; however, its inhibitory potential is not as high as that of mouse alpha-chain. Horse alpha-(1-30) and alpha-(31-141) segments make, respectively, minor and major contributions to the inhibitory potential of horse alpha-chain. The sum of the inhibitory potential of the two segments does not account for the inhibitory potential of the full-length horse alpha-chain. Although the polymerization inhibitory potential of horse alpha-chain is lower than mouse alpha-chain, the inhibitory potential of horse alpha-(31-141) is comparable to that of mouse alpha-(31-141). When mouse alpha-(1-30) is stitched to horse alpha-(31-141), the product is a chimeric alpha-chain with an inhibitory potential greater than mouse alpha-chain. In contrast, the stitching of horse alpha-(1-30) with mouse alpha-(31-141) had no additional inhibitory potential. Molecular modeling studies of HbS containing the mouse-horse chimeric alpha-chain indicate altered side-chain interactions at the alpha1beta1 interface when compared with HbS. In addition, the AB/GH corner perturbations facilitate a different stereochemistry for the interaction of the epsilon-amino group of Lys-16(alpha) with the beta-carboxyl group of Asp-116(alpha), resulting in a decrease in the accessibility of the side chain of Lys-16(alpha) to the solvent. Based on molecular modeling, we speculate that these perturbations by themselves, or in synergy with the altered conformational aspects of the alpha1beta1 interactions, represent the molecular basis of the superinhibitory potential of the mouse-horse chimeric alpha-chains. 相似文献
102.
We have studied omphalopagus conjoined twins with a diamniotic monochorionic placenta. Although conjoined twins usually present in a single amniotic sac, one other example of diamniotic placenta has been reported in omphalopagus twins [Weston et al., 1990: Am J Med Genet 37:558-561]. Most theories concerning the pathogenesis of conjoined twinning exclude the possibility of diamniotic placentation. However, Spencer [1992: Teratology 45:591-602] recently elaborated a model for conjoined twinning based on duplication of organizing centers (primitive streaks) during gastrulation. We have considered the fate of embryonic membranes according to this model of omphalopagus twinning and show that diamniotic placentation is a predictable outcome. 相似文献
103.
CS Sommardahl RP Woychik WE Sweeney ED Avner JE Wilkinson 《Canadian Metallurgical Quarterly》1997,11(6):728-733
Studies on conscious Sprague-Dawley rats using intracerebral dialysis in live animals combined with high-performance liquid chromatography with electrochemical detection showed that administration of apomorphine into the nucleus accumbens decreased the levels of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the extracellular space of the dorsal striatum throughout the observation period and produced a transient reduction in the level of homovanillic acid in the dialysate from this structure. The studies demonstrated that reversible exclusion of the nucleus accumbens with procaine produced a transient increase in the levels of dopamine metabolites, without an increase in serotonin metabolites, in the extracellular space of the dorsal striatum. These results demonstrate that the nucleus accumbens affects dopamine metabolism in the striatum, this being mediated by the dopamine-reactive system in the nucleus accumbens. 相似文献
104.
EL Nazarenko RP Gorshkova VA Zubkov AS Shashkov EP Ivanova IuS Ovodov 《Canadian Metallurgical Quarterly》1993,19(7):733-739
An acidic polysaccharide from Alteromonas sp. 4MC17 is built up of trisaccharide repeating units containing D-glucose, D-mannose and D-galacturonic acid residues. On the basis of methylation studies, 1H and 13C NMR-spectroscopy data, including two-dimensional homonuclear correlation spectroscopy and nuclear Overhauser effects, the following structure was suggested for the polysaccharide repeating unit: -->4)-beta-D-Glcp-(1-->4)-beta-D-GalpA-(1-->4)-beta-D-Manp-( 1-->. 相似文献
105.
Because changes in intracellular Ca2+ affect progression through the mitotic cell cycle, we investigated the role of Ca2+-binding proteins in regulating cell cycle progression. Evidence was found demonstrating that the activation of Ca2+/calmodulin-dependent protein kinase (CaM kinase) inhibits cell cycle progression in small cell lung carcinoma (SCLC) cells. We also demonstrated that SCLC cells express both CaM kinase type II (CaMKII) and CaM kinase type IV (CaMKIV). Five independent SCLC cell lines expressed proteins reactive with antibody to the CaMKII beta subunit, but none expressed detectable proteins reactive with antibody to the CaMKII alpha subunit. All SCLC cell lines tested expressed both the alpha and beta isoforms of CaMKIV. Immunoprecipitation of CaMKII from SCLC cells yielded multiple proteins that autophosphorylated in the presence of Ca2+ / calmodulin. Autophosphorylation was inhibited by the CaMKII(281-302) peptide, which corresponds to the CaMKII autoinhibitory domain, and by 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), a specific CaM kinase antagonist. Influx of Ca2+ through voltage-gated Ca2+ channels stimulated phosphorylation of CaMKII in SCLC cells, and this was inhibited by KN-62. Incubation of SCLC cells of KN-62 potently inhibited DNA synthesis, and slowed progression through S phase. Similar anti-proliferative effects of KN-62 occurred in SK-N-SH human neuroblastoma cells, which express both CaMKII and CaMKIV, and in K562 human chronic myelogenous leukemia cells, which express CaMKII but not CaMKIV. The expression of both CaMKII and CaMKIV by SCLC cells, and the sensitivity of these cells to the anti-proliferative effects of KN-62, suggest a role for CaM kinase in regulating SCLC proliferation. 相似文献
106.
The neuroprotective properties of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) and the non-NMDA antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX) and alpha-methyl-4-carboxyphenylglycine (MCPG) were evaluated against neuronal injury produced by the intraspinal injection of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Forty-nine animals were divided into eight groups in order to evaluate the effects of different drug combinations: (a) NMDA; (b) NMDA + MCPG; (c) NMDA + NBQX; (d) NMDA + MK-801; (e) AMPA; (f) AMPA + MCPG; (g) AMPA + MK-801; and (h) AMPA + NBQX. Drugs were microinjected into spinal segments T12-L3 through a micropipette attached to a Hamilton microliter syringe. Spinal cords were evaluated after a survival period of 48 h at which time NMDA and AMPA were found to produce morphological changes over the concentration ranges of 125-500 mM and 75-500 microM, respectively. Neuronal loss following injections of NMDA + MK-801 or AMPA + NBQX was significantly less than that following injections of NMDA or AMPA alone. By contrast, neuronal loss following co-injections of NMDA or AMPA with inappropriate antagonists, i.e., NMDA + NBQX/MCPG or AMPA + MCPG/MK-801, was not significantly different from that produced by NMDA or AMPA. The results suggest that elevations in spinal levels of glutamate followed by prolonged activation of NMDA and AMPA receptor subtypes initiate an excitotoxic cascade resulting in neuronal injury. Blockade of NMDA and AMPA effects by MK-801 and NBQX respectively confirms the well documented neuroprotective effects of these drugs and lends support to the potential importance of NMDA and especially AMPA receptor antagonists as therapeutic agents in the treatment of acute spinal cord injury. 相似文献
107.
ET Crosby RM Cooper MJ Douglas DJ Doyle OR Hung P Labrecque H Muir MF Murphy RP Preston DK Rose L Roy 《Canadian Metallurgical Quarterly》1998,45(8):757-776
PURPOSE: To review the current literature and generate recommendations on the role of newer technology in the management of the unanticipated difficult airway. METHODS: A literature search using key words and filters of English language and English abstracted publications from 1990-96 contained in the Medline, Current Contents and Biological Abstracts databases was carried out. The literature was reviewed and condensed and a series of evidence-based recommendations were evolved. CONCLUSIONS: The unanticipated difficult airway occurs with a low but consistent incidence in anaesthesia practice. Difficult direct laryngoscopy occurs in 1.5-8.5% of general anaesthetics and difficult intubation occurs with a similar incidence. Failed intubation occurs in 0.13-0.3% general anaesthetics. Current techniques for predicting difficulty with laryngoscopy and intubation are sensitive, non-specific and have a low positive predictive value. Assessment techniques which utilize multiple characteristics to derive a risk factor tend to be more accurate predictors. Devices such as the laryngeal mask, lighted stylet and rigid fibreoptic laryngoscopes, in the setting of unanticipated difficult airway, are effective in establishing a patient airway, may reduce morbidity and are occasionally lifesaving. Evidence supports their use in this setting as either alternatives to facemask and bag ventilation, when it is inadequate to support oxygenation, or to the direct laryngoscope, when tracheal intubation has failed. Specifically, the laryngeal mask and Combitube have proved to be effective in establishing and maintaining a patent airway in "cannot ventilate" situations. The lighted stylet and Bullard (rigid) fibreoptic scope are effective in many instances where the direct laryngoscope has failed to facilitate tracheal intubation. The data also support integration of these devices into strategies to manage difficult airway as the new standard of care. Training programmes should ensure graduate physicians are trained in the use of these alternatives. Continuing medical education courses should allow physicians in practice the opportunity to train with these alternative devices. 相似文献
108.
RP Millman CL Rosenberg CC Carlisle NR Kramer DM Kahn AE Bonitati 《Canadian Metallurgical Quarterly》1998,113(4):992-996
Twenty-four patients who failed uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) had an adjustable oral (Herbst) appliance made to treat the persistent apnea. Six patients discontinued the device prior to sleep evaluation. Eighteen patients had polysomnographic evaluations at baseline, post-UPPP, and with the Herbst appliance in place. The apnea-hypopnea index baseline (AHI) and arterial oxygen saturation (SaO2) nadir were 42.3+/-6.1 and 83.6+/-1.8%, respectively. There was no significant change in either parameter with surgery. With the oral appliance, the AHI fell to 15.3+/-4.4 (p < or = 0.01) and the SaO2 nadir increased to 87.9+/-1.2% (p < or = 0.05). Ten of the patients had control of the OSA with the Herbst appliance with a fall in the AHI to < 10. There were, in addition, two partial responders as defined by an AHI of <20 and a >50% fall in AHI compared with baseline and post-UPPP values. All but one of the responders and partial responders had complete resolution of subjective symptoms of daytime sleepiness with the appliance. An adjustable oral appliance appears to be an effective mode of therapy to control OSA after an unsuccessful UPPP. 相似文献
109.
Rous sarcoma virus (RSV) and murine leukemia virus (MLV) are examples of distantly related retroviruses that normally do not encounter one another in nature. Their Gag proteins direct particle assembly at the plasma membrane but possess very little sequence similarity. As expected, coexpression of these two Gag proteins did not result in particles that contain both. However, when the N-terminal membrane-binding domain of each molecule was replaced with that of the Src oncoprotein, which is also targeted to the cytoplasmic face of the plasma membrane, efficient copackaging was observed in genetic complementation and coimmunoprecipitation assays. We hypothesize that the RSV and MLV Gag proteins normally use distinct locations on the plasma membrane for particle assembly but otherwise have assembly domains that are sufficiently similar in function (but not sequence) to allow heterologous interactions when these proteins are redirected to a common membrane location. 相似文献
110.