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101.
The effect of the glycosidic torsion angle on 13C and 15N shifts of the sugar and base moieties of guanosine nucleotides was investigated by comparing the sites in two model G-tetrad oligodeoxynucleotides that contain guanosine residues alternately with syn and anti bases. The sugar puckering has been shown to be C2'-endo for both cases. It was observed that, for the instances with syn bases, the C1' through C4' carbons showed shifts that may be distinguished from those normally found in B-DNA-like structures. C1', C3' and C4' moved to lower field, while C2' moved to higher field. Effects of the change in glycosidic torsion angle were also seen in the shifts of base carbons and nitrogens in the five-membered ring portion of the base. Characterization of the shift variation associated with this conformational change may be useful in developing the use of 13C shifts as a tool in conformational analysis of oligonucleotides. 相似文献
102.
LS Palmer GJ Andros M Maizels WE Kaplan CF Firlit 《Canadian Metallurgical Quarterly》1997,49(4):604-608
OBJECTIVES: To evaluate the management approach for vesicoureteral reflux (reflux) into a solitary kidney. METHODS: Outcomes of all children with solitary kidneys and reflux managed between 1981 and 1996 were reviewed. Solitary kidneys were documented by nuclear renography and ultrasonography; reflux was graded after cystography. Management consisted of observation and antimicrobial prophylaxis or surgery by ureteroneocystostomy or subureteric injection of polytetrafluoroethylene (STING). Follow-up ranged from 3 months to 14 years and included serial cystography, sonography, and serum creatinine measurement. RESULTS: Twenty-one patients with a median follow-up of 26 months were identified. Etiologies included contralateral renal agenesis (14 children), multicystic dysplastic kidney (5 children), or nonfunctioning ureteropelvic junction obstruction (2 children). Low-grade (I to II) reflux was identified in 6 children, and high grade (III to V) was identified in 15. Reflux resolved in 20 patients. Five children with low-grade reflux were managed without surgery and demonstrated reflux resolution after a mean of 20.5 months. Renal function deteriorated in only 1 child. Ureteroneocystostomy was performed in 13 children with grades III to V reflux, and STING was performed in 1 child with grade II reflux. Every surgical patient maintained stable renal function and was infection-free during a mean follow-up of 56 months. Management by observation in 2 children with grades IV to V reflux resulted in spontaneous resolution in one and stable grade IV in the other. CONCLUSIONS: Reflux into the solitary functioning kidney may be managed by the same strategies used to manage unilateral reflux in children with two normally functioning kidneys: low-grade reflux by observation/ chemoprophylaxis until spontaneous resolution occurs, and higher grades by surgery to protect renal function; however, chemoprophylaxis and serial imaging may be used until well-defined indications for surgery are satisfied. Renal function should be monitored diligently. 相似文献
103.
PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder. 相似文献
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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
108.
The semisynthesis of eel[L-alpha-aminosuberic acid]calcitonin (elcatonin) was accomplished by alpha-chymotrypsin-catalyzed coupling of two peptide segments in a single reaction without the protection of any functional group. The eel calcitonin-(10-32)-peptide was prepared by a gene manipulation. The esters of cyclic desamino nonapeptide (segment 1-9) were synthesized by the conventional solution method including a thermolysin-mediated resolution of DL-alpha-aminosuberic acid via one-step tripeptide synthesis leading to the 7-9 sequence. The main aim of this work was to determine the conditions for protease-catalyzed segment condensation while avoiding a concurrent cleavage of other proteolytically labile peptide bonds in the hormone. The alpha-chymotrypsin condensation strategy under usual conditions led to a complicated mixture of split products with an insignificant amount of the required peptide. When the coupling reaction was carried out at 0 degrees C, the reaction resulted in a satisfactory yield of elcatonin with the complete conversion of the acyl donor (1-9 segment) accompanied by negligible concurrent peptide bond digestion. The same strategy was employed for the preparation of analogous dicarba salmon calcitonin using a synthetic elcatonin-(10-32)-peptide. Both calcitonin analogs exhibited hypocalcemic activity corresponding to the international standard of elcatonin. We demonstrate in this work a peptide synthesis based on the combination of genetic engineering, chemical synthesis and proteinase-catalyzed segment condensation. This approach enables effective incorporation of an unnatural amino acid into calcitonins without the side-chain protection. 相似文献
109.
Hepatic expression of ErbB3 is repressed by insulin in a pathway sensitive to PI-3 kinase inhibitors
ErbB3 is an epidermal growth factor receptor-related type I tyrosine kinase receptor capable, in conjunction with ErbB2 or epidermal growth factor receptor, of transmitting proliferative and differentiative signals in a variety of cell types. We previously showed that ErbB3 messenger RNA and protein increase in cultured hepatocytes during the first 12 h in culture, as does the binding of heregulin beta1, a ligand for ErbB3. Insulin inhibits the increase in heregulin beta1 binding, as well as the increase in ErbB3 messenger RNA and protein. Two models of insulin deficiency in vivo (diabetes and fasting) demonstrated elevated levels of hepatic ErbB3 protein, strengthening the relevance of our observations in vitro. Using chemical activators or antagonists, we sought to identify the signaling pathways that link insulin to ErbB3 expression. The PI-3 kinase inhibitors, wortmannin and LY294002, completely blocked the inhibition of ErbB3 protein expression by insulin, suggesting a role for PI-3 kinase in the regulation of this growth factor receptor. Rapamycin, an inhibitor of p70 S6 kinase, an enzyme downstream of PI-3 kinase, failed to block the effect of insulin on ErbB3 expression. These results suggest a complex regulatory paradign for ErbB3 that includes PI-3 kinase and may be linked, via insulin, to the metabolic status of the animal. 相似文献
110.
G Pantaleo H Soudeyns JF Demarest M Vaccarezza C Graziosi S Paolucci MB Daucher OJ Cohen F Denis WE Biddison RP Sekaly AS Fauci 《Canadian Metallurgical Quarterly》1997,27(12):3166-3173
Down-regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective down-regulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection. 相似文献