PJ Fairchild 《Canadian Metallurgical Quarterly》1998,4(3):182-194

Molecules encoded by the major histocompatibility complex (MHC) are polymorphic integral membrane proteins adapted to the presentation of peptide fragments of foreign antigens to antigen-specific T-cells. The diversity of infectious agents to which an immune response must be mounted poses a unique problem for receptor-ligand interactions; how can proteins whose polymorphism is necessarily limited bind an array of peptides almost infinite in its complexity? Both MHC class I and class II determinants have achieved this goal by harnessing a limited number of peptide side chains to anchor the epitope in place while exploiting conserved features of peptide structure, independent of their primary sequence. While class I molecules interact predominantly with the N- and C-termini of peptides, class II determinants form an extensive hydrogen bonding network along the length of the peptide backbone. Such a strategy ensures high-affinity binding, while selectively exposing the unique features of each ligand for recognition by the T-cell receptor.  相似文献   

    

PJ Madden 《Canadian Metallurgical Quarterly》1998,94(38):12-13

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EA Mueller  D Niese  B Mellein 《Canadian Metallurgical Quarterly》1998,30(5):1694-1696

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PJ Colletier  AS Garden  WH Morrison  H Goepfert  F Geara  KK Ang 《Canadian Metallurgical Quarterly》1998,20(8):674-681

BACKGROUND: This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy. METHODS: One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years. RESULTS: Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues. CONCLUSIONS: Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site.  相似文献   

    

PJ Bex  AB Metha  W Makous 《Canadian Metallurgical Quarterly》1998,15(4):769-776

Current models of motion perception typically describe mechanisms that operate locally to extract direction and speed information. To deal with the movement of self or objects with respect to the environment, higher-level receptive fields are presumably assembled from the outputs of such local analyzers. We find that the apparent speed of gratings viewed through four spatial apertures depends on the interaction of motion directions among the apertures, even when the motion within each aperture is identical except for direction. Specifically, local motion consistent with a global pattern of radial motion appears 32% faster than that consistent with translational or rotational motion. The enhancement of speed is not reflected in detection thresholds and persists in spite of instructions to fixate a single local aperture and ignore the global configuration. We also find that a two-dimensional pattern of motion is necessary to elicit the effect and that motion contrast alone does not produce the enhancement. These results implicate at least two serial stages of motion-information processing: a mechanism to code the local direction and speed of motion, followed by a global mechanism that integrates such signals to represent meaningful patterns of movement, depending on the configuration of the local motions.  相似文献   

    

M Zurovec  O Petrenko  R Roll  PJ Enrietto 《Canadian Metallurgical Quarterly》1998,16(24):3133-3142

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F Biagi  HJ Ellis  MA Morris  ND Parnell  PJ Ciclitira 《Canadian Metallurgical Quarterly》1998,114(2):420-1, 425

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TS Lamberg  KT Kivist?  J Laitila  K M?rtensson  PJ Neuvonen 《Canadian Metallurgical Quarterly》1998,54(9-10):761-766

OBJECTIVE: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of buspirone, a non-benzodiazepine anxiolytic agent, were investigated. METHODS: In a randomized, placebo-controlled, two-phase cross-over study, ten healthy volunteers took either 100 mg fluvoxamine or matched placebo orally once daily for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h. RESULTS: The total area under the plasma buspirone concentration-time curve was increased 2.4-fold (P < 0.05) and the peak plasma buspirone concentration 2.0-fold (P < 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone was not affected. The ratio of the total area under the plasma concentration-time curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6) by fluvoxamine (P < 0.05). The results of the six pharmacodynamic tests remained unchanged. CONCLUSION: Fluvoxamine moderately increased plasma buspirone concentrations and decreased the production of the active 1-PP metabolite of buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4-mediated first-pass metabolism of buspirone by fluvoxamine. However, this pharmacokinetic interaction was not associated with impairment of psychomotor performance and it is probably of limited clinical significance.  相似文献   

    

PJ Trotter  WI Wu  J Pedretti  R Yates  DR Voelker 《Canadian Metallurgical Quarterly》1998,273(21):13189-13196

In an effort to understand molecular mechanisms of intracellular lipid transport, we have focused upon specific events required for de novo aminophospholipid synthesis in the yeast Saccharomyces cerevisiae. A genetic system for examining the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic reticulum and its transport to and decarboxylation by PtdSer decarboxylase 2 in the Golgi/vacuole has been developed. We have isolated a mutant, denoted pstB1, that accumulates PtdSer and has diminished phosphatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity. The lesion in PtdSer metabolism is consistent with a defect in interorganelle lipid transport. A genomic DNA clone that complements the mutation was isolated, and sequencing revealed that the clone contains the STT4 gene, encoding a phosphatidylinositol 4-kinase. The pstB1 mutant exhibits a defect in Stt4p-type phosphatidylinositol 4-kinase activity, and direct gene replacement indicates that STT4 is the defective gene in the mutant. Creation of an STT4 null allele (stt4Delta::HIS3) demonstrates the gene is essential. These results provide evidence that implicates phosphoinositides in the regulation of intracellular aminophospholipid transport.  相似文献   

    

AM Hussong  PJ Curran  L Chassin 《Canadian Metallurgical Quarterly》1998,26(6):453-466

The current study examined two questions. First, do internalizing symptoms and externalizing behavior each mediate the relations between parent psychopathology (alcoholism, antisocial personality disorder, and affective disorder) and growth in adolescent heavy alcohol use? Second, are there gender differences in these mediated pathways? Using latent curve analyses, we examined these questions in a high-risk sample of 439 families (53% children of alcoholic parents; 47% female). Collapsing across gender, adolescent-reported externalizing behavior mediated both the relation between parent alcoholism and growth in heavy alcohol use and the relation between parent antisociality and growth in heavy alcohol use. Parent-reported externalizing behavior only mediated the relation between parent antisociality and growth in heavy alcohol use in males. No support was found for internalizing symptoms as a mediator of these relations. Avenues are suggested for further exploring and integrating information about different mediating processes accounting for children of alcoholics' risk for heavy alcohol use.  相似文献