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81.
Summary of complementation groups of UV-sensitive CHO cell mutants isolated by large-scale screening 总被引:7,自引:0,他引:7
Busch David; Greiner Carol; Lewis Kathy; Ford Ruth; Adair Gerald; Thompson Larry 《Mutagenesis》1989,4(5):349-354
A summary is given for the lineage and complementation groupassignments of 153 UV-sensitive mutants of the CHO AA8 cellline. The distribution of mutants among six complementationgroups was highly non-random, with the great majority of theisolates belonging to groups 1 and 2. This asymmetry is consistentwith the known hemizygosity of these two linked loci in CHOcells. The relative numbers of mutants induced in group 2 wasfound to depend greatly on the type of mutagen used. Mutagenesiswith UV radiation, ethyl methanesulfonate (EMS), N-methyl-N'-nitro-N-nitroso-guanidine and 7-bromomethylbenz[a]anthraceneproduced high frequencies of group 2 mutants. In contrast, ICR170and ICR191, which are thought to produce mostly frameshift mutations,yielded very few mutants in group 2. These results are of particularimportance in light of the recent finding that the human ERCC2gene, which corrects group 2 mutants, has very strong homologywith the yeast gene RAD3. RAD3 is an essential gene for viabilityin yeast, and the low recovery of group 2 mutants using theframeshift agents strongly suggests that frameshift mutationstend to be lethal in the hamster ERCC2 locus. Several mutagen-sensitivedouble mutants were isolated in two-step selections from EMS-,mitomycin C- or UV-sensitive parental cells, including the lineUVU1, the first mammalian line with two mutations that affectUV sensitivity. The first mutation inactivated excision repair,and the second mutation appears to have affected some otherrecovery process. UVU1 should be useful for studying recoveryprocesses that are separate from nucleotide excision repair.
1To whom correspondence should be addressed 相似文献
82.
David Wesch John R. Lutzker Larry Frisch Michelle M. Dillon 《Journal of behavioral medicine》1987,10(1):91-101
This paper addresses an evaluation of an administrative decision to change the manner in which services were paid for at a Student Health Center (SHC). The impact of the change in payment was observed through monitoring the number of scheduled appointments at the SHC which the patient failed to attend, reschedule, or cancel. The impact was assessed through a comparison of the weekly no-show rates from the year prior to the change in payment practices through the year following the change. A time-series statistical package was used to analyze the no-show data. Collateral measures on the number of students attending the university, staff opinions, and usage of the SHC by different student groups were collected. Evaluations of the impact of administrative decisions on health-related behavior were discussed, in addition to a discussion of the usefulness of time-series models for this type of evaluation. 相似文献
83.
Ludwig DL Witte L Hicklin DJ Prewett M Bassi R Burtrum D Pereira DS Jimenez X Fox F Saxena B Zhou Q Ma Y Kang X Patel D Barry M Kussie P Zhu Z Russell DA Petersen WL Jury TP Gaitan-Gaitan F Moran DL Delannay X Storrs BS Tou J Zupec ME Gustafson KS McIntyre J Tarnowski SJ Bohlen P 《Human antibodies》2004,13(3):81-90
Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production. 相似文献
84.
Alterations in galectin-3 expression and distribution correlate with breast cancer progression: functional analysis of galectin-3 in breast epithelial-endothelial interactions 下载免费PDF全文
Shekhar MP Nangia-Makker P Tait L Miller F Raz A 《The American journal of pathology》2004,165(6):1931-1941
To define the role of galectin-3 in breast cancer progression, we have used a novel three-dimensional co-culture system that recapitulates in vivo reciprocal functional breast epithelial-endothelial cell-cell and cell-matrix interactions, and examined the expression of galectin-3 mRNA and protein in human breast tumors and xenografts. Galectin-3 is required for the stabilization of epithelial-endothelial interaction networks because immunoneutralization with galectin-3 antibodies abolishes the interactions in a dose-dependent manner. Co-culture of epithelial cells with endothelial cells results in increase in levels of secreted galectin-3 and presence of proteolytically processed form of galectin-3 in the conditioned media. In contrast, intracellular galectin-3 predominantly exists in the intact form. This difference in sensitivity to proteolytic processing of secreted versus intracellular galectin-3 probably arises from differences in accessibility of protease-sensitive sites, levels, and/or type of activated protease(s), and may be indicative of different functional roles for intact and processed galectin-3. To determine whether the proteolytically cleaved galectin-3 retains its ability to bind to endothelial cells, binding assays were performed with the full-length and matrix metallopeoteinase-2-cleaved recombinant galectin-3. Although a dose-dependent increase in binding to human umbilical vein endothelial cells was observed with both full-length and cleaved galectin-3, proteolytically cleaved galectin-3 displayed approximately 20-fold higher affinity for human umbilical vein endothelial cells as compared to the full-length protein. Examination of galectin-3 expression in breast tumors and xenografts revealed elevated levels of galectin-3 mRNA and protein in the luminal epithelial cells of normal and benign ducts, down-regulation in early grades of ductal carcinoma in situ (DCIS), and re-expression in peripheral tumor cells as DCIS lesions progressed to comedo-DCIS and invasive carcinomas. These data suggest that galectin-3 expression is associated with specific morphological precursor subtypes of breast cancer and undergoes a transitional shift in expression from luminal to peripheral cells as tumors progressed to comedo-DCIS or invasive carcinomas. Such a localized expression of galectin-3 in cancer cells proximal to the stroma could lead to increased invasive potential by inducing novel or better interactions with the stromal counterparts. 相似文献
85.
Kimberly Mascia Larry Borish James Patrie John Hunt C Douglas Phillips John W Steinke 《Annals of allergy, asthma & immunology》2005,94(6):652-657
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a disease of intense eosinophilic inflammation that can produce fibrosis, hyperplasia, and remodeling. OBJECTIVE: To investigate the usefulness of quantifying severity of chronic hyperplastic eosinophilic sinusitis in predicting the presence of AERD. METHODS: Data were compared between asthmatic patients who reported exacerbations after aspirin ingestion and those who did not. The primary outcome measure was severity of sinusitis using a validated computed tomography (CT) scan-based scoring system. Indices of lower airway remodeling and other markers of inflammation were also evaluated. RESULTS: Twenty-one patients with AERD were compared with 19 patients with aspirin-tolerant asthma (ATA). Patients were well matched for asthma severity as shown by their similar lung function as measured by postbronchodilator forced expiratory volume in 1 second. Patients with AERD were distinguished by their sinus CT scores (AERD patients: 16.9; 95% confidence interval [CI], 13.4-21.3; ATA patients: 6.2; 95% CI, 4.2-9.1; P < .001), and they were considerably more likely to have nasal polyps (AERD patients: 90%; ATA patients: 26%; P < .001). In addition, AERD patients demonstrated increased total lung capacity (AERD patients: 107.9%; 95% CI, 99.9%-117.6%; ATA patients: 98.0%; 95% CI, 93.7%-102.5%; P = .05), reflecting a trend toward increased air trapping. No significant differences occurred in diffusing capacity, exhaled nitric oxide, eosinophilia, or exhaled breath condensate pH. CONCLUSIONS: AERD can be distinguished from ATA by the extent of hyperplasia on CT scan and the presence of nasal polyps. We hypothesize that AERD represents a remodeling process that affects both the upper and lower airways. 相似文献
86.
Effects of physical conditioning on cardiac autonomic function in healthy middle-aged women. 总被引:4,自引:0,他引:4
Paula R Myslivecek C Ann Brown Larry A Wolfe 《Revue canadienne de physiologie appliquée》2002,27(1):1-18
The purpose of this study was to determine whether moderate exercise training affects heart rate variability (HRV) and spontaneous baroreflex (SBR) function in healthy middle-aged women. Thirty-two sedentary women aged 40-59 yr were divided into four groups depending on reproductive state (premenopausal, PrM or postmenopausal, PoM, and training group (exercise or sedentary control group). The electrocardiographic R-R interval and systolic blood pressure (finger plethysmograph) were measured at rest during paced breathing at 16 breaths/min in the left lateral decubitus, sitting, and free standing postures, and during upright cycling at 40% maximal heart rate reserve (MHRR). After initial testing, the exercise groups underwent a 12 week walking program. After training, both exercise groups (PrM and PoM) had a longer R-R interval in all conditions, a higher SBR slope in the sitting and standing posture and lower sympathetic modulation in the standing posture, than the control groups and pre-training levels. During exercise, vagal modulation was higher and sympathetic modulation was lower in both exercise groups compared to pre-training values. Vagal modulation is increased following moderate intensity aerobic conditioning in middle-aged women. 相似文献
87.
Psychological distress in high-risk youth with asthma 总被引:5,自引:0,他引:5
Gillaspy SR Hoff AL Mullins LL Van Pelt JC Chaney JM 《Journal of pediatric psychology》2002,27(4):363-371
OBJECTIVE: To examine the relationship between asthma and psychological distress among adolescents already at-risk for adjustment problems secondary to lower economic strata and educational or vocational failure. METHOD: Twenty-five high-risk adolescents with asthma and 25 high-risk controls without asthma 16 to 21 years old completed the Brief Symptom Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: Adolescents with asthma had significantly higher scores on multiple measures of psychological distress. Specifically, adolescents with asthma evidenced higher levels of anxiety, depression, and global psychological distress than those without asthma. CONCLUSIONS: High-risk adolescents with asthma may be more likely to experience psychological distress than those without asthma. Our findings suggest that asthma constitutes an additional significant independent stressor or risk factor among adolescents who already are at high risk for multiple adjustment problems. 相似文献
88.
Palmer SL Gajjar A Reddick WE Glass JO Kun LE Wu S Xiong X Mulhern RK 《Neuropsychology》2003,17(4):548-555
Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline. 相似文献
89.
Eduardo C. Salido Merry B. Passage Pauline H. Yen Larry J. Shapiro T. K. Mohandas 《Somatic Cell and Molecular Genetics》1993,19(1):65-71
The expression of mouseZfx, Rps4, Ube1x, andXist was evaluated in hamstermouse somatic cell hybrids containing either an active or an inactive mouse X chromosome using polymerase chain reaction of reverse transcribed RNA (RT-PCR). The results showed thatZfx, Rps4, andUbe1x are expressed exclusively from the active mouse X, whileXist is expressed exclusively from the inactive X. These findings confirm the pattern of X inactivation for these mouse genes reported previously based on expression in somatic tissues of F1 females from interspecific crosses. These results demonstrate the existence of differences between human and mouse X inactivation, as the corresponding human genes,ZFX, RPS4X, andUBE1 escape X inactivation. 相似文献
90.
The present experiment explored the utility of finger pulse volume (FPV) as a measure of anxiety. Subjects were exposed to either a threatening or nonthreatening situation, and indices of physiological arousal (pulse rate (PR) and FPV) and self-report of anxiety (Affect Adjective Checklist (AACL)) were collected. Results indicated that FPV was responsive to changes in experimentally induced anxiety and significantly correlated with PR and AACL, although the strength of these relationships was not substantial. Relevance for psychophysiological theory and the clinical observation of anxiety is discussed. 相似文献