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101.
The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the numbering system for the T. brucei enzyme, in their aligned sequences, the T. cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and 126. T. brucei triosephosphate isomerase has cysteine residues at positions 14, 40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity of wild type triosephosphate isomerase from T. cruzi and T. brucei to the reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes, respectively. Triosephosphate isomerases that have cysteine residues at positions 40 and 126, but lack a cysteine residue at position 14 are insensitive to methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At stoichiometric concentrations, the reagents inhibited the three enzymes as a consequence of structural alterations as measured by binding of 8-anilino-1-napthalenesulfonic acid to previously buried hydrophobic regions. However, the times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T. cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The effect of pH on the action of the sulfhydryl reagents and molecular modeling showed no differences in the solvent accessibility of Cys14. As Cys14 forms part of the dimer interface, the data indicate that, in the three enzymes, barriers of different magnitude hinder the interaction between the sulfhydryl reagents and Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its dimer interface more susceptible for perturbation. 相似文献
102.
BACKGROUND: Circulatory support with mechanical devices often leads to bleeding and tamponade. METHODS: We report a series of three patients that required mechanical circulatory support for postcardiotomy ventricular dysfunction. RESULTS: Late tamponade occurred in each patient with different clinical presentations. Early postoperative bleeding occurred in 2 patients. There was no active bleeding in any of the 3 patients. Transesophageal echocardiography was not helpful in making the diagnosis. CONCLUSION: Late tamponade, which may be the result of hematoma with earlier bleeding, can present as dyspnea, hypoxia, or forms of hemodynamic collapse. Exploratory media sternotomy is required to definitively make the diagnosis and to evacuate the hematoma. 相似文献
103.
104.
Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling
CE Johnston MD White M Wu GK Bristow GG Giesbrecht 《Canadian Metallurgical Quarterly》1996,80(2):422-429
Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation. 相似文献
105.
GM Kacl I Bicik AW Sch?nenberger P Steiner B Romanowski JF Debatin GK von Schulthess 《Canadian Metallurgical Quarterly》1998,8(7):1173-1178
The purpose of this review was to give an answer to the question whether there are convincing data to support the hypothesis of an amino acid imbalance as one possible mechanism to explain overtraining syndrome. Animal studies point to an enhanced synthesis of the neurotransmitter 5-hydroxytryptamine through an amino acid imbalance at the blood-brain barrier with a preferable tryptophan uptake into the brain, resulting in premature fatigue. Human studies, however, show contradictory results, mainly because of nonstandardized methodology, so that a final conclusion cannot be made at present. BCAA supplementation in addition to standard carbohydrate ingestion during sustained exercise seems to be of no eminent advantage to delay fatigue. The overall results concerning the BCAA hypothesis to explain overtraining are inconclusive and require more controlled experimental research. 相似文献
106.
SM Mandala RA Thornton J Milligan M Rosenbach M Garcia-Calvo HG Bull G Harris GK Abruzzo AM Flattery CJ Gill K Bartizal S Dreikorn MB Kurtz 《Canadian Metallurgical Quarterly》1998,273(24):14942-14949
Rustmicin is a 14-membered macrolide previously identified as an inhibitor of plant pathogenic fungi by a mechanism that was not defined. We discovered that rustmicin inhibits inositol phosphoceramide synthase, resulting in the accumulation of ceramide and the loss of all of the complex sphingolipids. Rustmicin has potent fungicidal activity against clinically important human pathogens that is correlated with its sphingolipid inhibition. It is especially potent against Cryptococcus neoformans, where it inhibits growth and sphingolipid synthesis at concentrations <1 ng/ml and inhibits the enzyme with an IC50 of 70 pM. This inhibition of the membrane-bound enzyme is reversible; moreover, rustmicin is nearly equipotent against the solubilized enzyme. Rustmicin was efficacious in a mouse model for cryptococcosis, but it was less active than predicted from its in vitro potency against this pathogen. Stability and drug efflux were identified as two factors limiting rustmicin's activity. In the presence of serum, rustmicin rapidly epimerizes at the C-2 position and is converted to a gamma-lactone, a product that is devoid of activity. Rustmicin was also found to be a remarkably good substrate for the Saccharomyces cerevisiae multidrug efflux pump encoded by PDR5. 相似文献
107.
Administration of 2-acetylaminofluorene (2-AAF) given before partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Our objective in this study was to examine the oval cell response and associated alpha-fetoprotein (AFP) gene expression by combining 2-AAF with selective damage of centrilobular regions (carbon tetrachloride [CCl4]) or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a more enhanced oval cell response and AFP gene expression than periportal damage. Conversely, more intense proliferation of intraportal bile duct epithelia was seen with 2-AAF/AA than with 2-AAF/CCl4. The oval cell response and AFP gene expression was ranked as 2-AAF/ CCl4 > or = 2-AAF/PHx > 2-AAF/AA. AFP mRNA expression was also examined in an acute AA and CCl4 injury. We found very little AFP gene expression compared with the 2-AAF/hepatic injury models. To see a true oval cell response, the hepatocytes must be inhibited from proliferating. In addition, the results presented with the 2-AA/AA model suggest that the periportal matrix may be as important as the cells that populate the area. 相似文献
108.
GK Bejjani B Sullivan E Salas-Lopez J Abello DC Wright A Jurjus LN Sekhar 《Canadian Metallurgical Quarterly》1998,43(4):842-52; discussion 852-3
INTRODUCTION: The infratemporal fossa (ITF) gives passage to most major cerebral vessels and cranial nerves. Dissection of the ITF is essential in many of the lateral cranial base approaches and in exposure of the high cervical internal carotid artery (ICA). We reviewed the surgical anatomy of this region. METHODS: Direct foraminal measurements were made in seven dry skulls (14 sides), and the relationship of these foramina to each other and various landmarks were determined. Ten ITF dissections were performed using a preauricular subtemporal-infratemporal approach. Preliminary dissections of the extracranial great vessels and structures larger than 1 cm were performed using standard macroscopic surgical techniques. Dissection of all structures less than 1 cm was conducted using microsurgical techniques and instruments, including the operating microscope. The anatomic relationships of the muscles, nerves, arteries, and veins were carefully recorded, with special emphasis regarding the relationship of these structures to the styloid diaphragm. The dissection was purely extradural. RESULTS: The styloid diaphragm was identified in all specimens. It divides the ITF into the prestyloid region and the retrostyloid region. The prestyloid region contains the parotid gland and associated structures, including the facial nerve and external carotid artery. The retrostyloid region contains major vascular structures (ICA, internal jugular vein) and the initial exocranial portion of the lower Cranial Nerves IX through XII. Landmarks were identified for the different cranial nerves. The bifurcation of the main trunk of the facial nerve was an average of 21 mm medial to the cartilaginous pointer and an average of 31 mm medial to the tragus of the ear. The glossopharyngeal nerve was found posterior and lateral to stylopharyngeus muscle in nine cases and medial in only one. The vagus nerve was consistently found in the angle formed posteriorly by the ICA and the internal jugular vein. The spinal accessory nerve crossed anterior to the internal jugular vein in five cases and posterior in another five cases. It could be located as it entered the medial surface of the sternocleidomastoid muscle 28 mm (mean) below the mastoid tip. The hypoglossal nerve was most consistently identified as it crossed under the sternocleidomastoid branch of the occipital artery 25 mm posterior to the angle of the mandible and 52 mm anterior and inferior to the mastoid tip. CONCLUSION: The styloid diaphragm divides the ITF into prestyloid and retrostyloid regions and covers the high cervical ICA. Using landmarks for the exocranial portion of the lower cranial nerves is useful it identifying them and avoiding injury during approaches to the high cervical ICA, the upper cervical spine, and the ITF. 相似文献
109.
RL Riepl B Reichardt CJ Auernhammer G Beier J Schopohl GK Stalla P Lehnert 《Canadian Metallurgical Quarterly》1996,42(3):371-377
1. Morphine suppresses the release of pancreatic polypeptide, a hormone under vagal cholinergic control. The intention of the study was to detect whether the mu-opiate receptor agonist loperamide is also able to inhibit pancreatic polypeptide release, and to define its site of action. 2. In groups of healthy subjects (n = 6 each) stimulation of pancreatic polypeptide was assessed in five different tests: (i) insulin-hypoglycaemia; (ii) modified sham feeding; (iii) intravenous infusion of the cholecystokinin analogue ceruletide; (iv) injection of corticotropin releasing hormone; (v) infusion of the muscarinic acetylcholine agonist bethanechol. All tests were performed after oral application of either a placebo or loperamide (16 mg), tests (ii) and (iii) were repeated with loperamide in smaller doses (2 and 6 mg), with loperamide plus naloxone, with naloxone alone, and with infusion of atropine. Plasma concentrations of pancreatic polypeptide were measured radioimmunologically. 3. Release of pancreatic polypeptide in test (i) to (iv) was completely blocked by 16 mg loperamide, whereas bethanechol-stimulated release (test 5) was not influenced. Tests (ii) and (iii) showed that the inhibition was dose-dependent and could be attenuated by naloxone. The inhibitory effect of loperamide was comparable with that of atropine. 4. We conclude that loperamide causes a dose-dependent inhibition of pancreatic polypeptide release mediated by vagal-cholinergic pathways, but does not have an atropine-like peripheral action. 相似文献
110.