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91.
C Yost GH Farr SB Pierce DM Ferkey MM Chen D Kimelman 《Canadian Metallurgical Quarterly》1998,93(6):1031-1041
Dorsal accumulation of beta-catenin in early Xenopus embryos is required for body axis formation. Recent evidence indicates that beta-catenin is dorsally stabilized by the localized inhibition of the kinase Xgsk-3, utilizing a novel Wnt ligand-independent mechanism. Using a two-hybrid screen, we identified GBP, a maternal Xgsk-3-binding protein that is homologous to a T cell protooncogene in three well-conserved domains. GBP inhibits in vivo phosphorylation by Xgsk-3, and ectopic GBP expression induces an axis by stabilizing beta-catenin within Xenopus embryos. Importantly, antisense oligonucleotide depletion of the maternal GBP mRNA demonstrates that GBP is required for the establishment of the dorsal-ventral axis in Xenopus embryos. Our results define a family of GSK-3-binding proteins with roles in development and cell proliferation. 相似文献
92.
A Nasim MM Thompson RD Sayers JR Boyle C Maltezos G Fishwick A Bolia PR Bell 《Canadian Metallurgical Quarterly》1998,12(6):522-528
BACKGROUND: Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms. OBJECTIVES: Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival. METHODS: During a 10-year period (1986-1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection. RESULTS: Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P = .960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P = .95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P = .0011) and the site of the recurrence (P = .02). Timing was defined as early (< or =365 days from the time of diagnosis to recurrence) or late (> or =365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection--intensive or minimal--did not significantly affect survival (P = .18). CONCLUSIONS: There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients. 相似文献
93.
MM Hudson CA Poquette J Lee CA Greenwald A Shah X Luo EI Thompson JA Wilimas LE Kun WM Crist 《Canadian Metallurgical Quarterly》1998,16(11):3592-3600
PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection. 相似文献
94.
RR Bell MM Soliman VK Nonavinakere DM Hammerbeck JL Early 《Canadian Metallurgical Quarterly》1997,90(2-3):107-114
Ovalbumin-sensitized (50 mg/kg, i.p.) male Hartley-guinea-pigs (550-610 g; n = 6) were treated 14 days later intratracheally with saline, cadmium (Cd 0.3 mg), selenium (Se 0.3 mg or 0.06 mg) or Se (0.06 mg) with Cd (0.3 mg). After 24 h, baseline dynamic-lung-compliance (Cdynl) and pulmonary-resistance (Rp), and percent change after ovalbumin-aerosol-challenge (10 mg/ml, 60 s) were assessed. Cadmium or Se (0.3 mg), Se (0.06 mg) and/or Cd (0.3 mg) decreased Cdynl (P < 0.05). Selenium (0.3 mg) increased Rp (P < 0.05). Ovalbumin-challenge decreased Cdynl and increased Rp in all groups. Analysis of bronchoalveolar-lavage-fluid (BALF) displayed increased activities of lactate-dehydrogenase (LDH), beta-glucuronidase (beta-G), alkaline-phosphatase (AP), and protein due to 0.3 mg Se, 0.3 mg Cd alone or with 0.06 mg Se (P < 0.05). Findings indicated that, 0.3 mg Se is more detrimental than 0.3 mg Cd to lung-dynamics despite a modest protection by 0.06 mg Se against Cd illustrated by an ameliorated Cdynl and lower protein in BALF. 相似文献
95.
HI McFarland AA Lobito MM Johnson JT Nyswaner JA Frank GR Palardy N Tresser CP Genain JP Mueller LA Matis MJ Lenardo 《Canadian Metallurgical Quarterly》1999,162(4):2384-2390
Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis. 相似文献
96.
97.
DM Parry MM MacCollin MI Kaiser-Kupfer K Pulaski HS Nicholson M Bolesta R Eldridge JF Gusella 《Canadian Metallurgical Quarterly》1996,59(3):529-539
Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P < or = .05) for nearly every variable. Patients with nonsense or frameshift mutations were younger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study. 相似文献
98.
99.
Ten patients with newly diagnosed B-chronic lymphocytic leukaemia were treated with cladribin orally for five days every four weeks with a median of four series. This is the first reported clinical study where a purine analogue is administered orally. The tumour reducing effect was fast. Eight out of 10 patients responded with a partial or clinical complete remission. Two of these were in molecular biological complete remission. With an observation time of 22 months we have seen no serious side effects so far. A randomized study (including a long term follow up) between chlorambucil, fludarabin and cladribin is needed to clarify the future role of cladribin in B-CLL treatment. 相似文献
100.
MM Khananashvili 《Canadian Metallurgical Quarterly》1998,(8):13-16
Experiments on animals (rodents, beasts, primates) and observation in man have ascertained that psychogenic stress is the most important defensive state of living organisms, which is constantly involved in order to maintain their interaction with external psychogenic factors. Three types of stress should be distinguished, these include normostress, hypostress, and hyperstress. Normostress has definite limits within which optimal responses, which are typical for an individual are realized. Hyperstress develops as a defensive response to extremely strong (extraordinary) stimuli. Hypostress can be observed in the retarded development of self-regulation mechanisms. All three types of stress are provided by a fundamental property of living organisms--the self-regulation mechanism, which realizes the keeping back of normostress constancy, or return of hyper- and hypostress to the normostress status. And only if an extreme deficit of self-regulation mechanisms takes place, hyper(hypo)stress could become a condition for the development of pathology. 相似文献