Initial nursing impression in patients with chest discomfort.
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Chest Pain↗
Biomedical subjects
C Peterson
Publications and source records attributed to C Peterson.
High-frequency transformation of human repair-deficient cell lines by an Epstein-Barr virus-based cDNA expression vector.
We constructed a human cDNA expression vector by combining an episomal Epstein-Barr virus (EBV) vector with the expression cassette from the transient-expression vector, pCDM8. This new vector, designated pEBS7, exhibited high-level expression of reporter genes in normal and repair-deficient xeroderma pigmentosum cell lines. Reconstruction experiments indicated that marker genes diluted to a frequency of 10(-5) can be rescued on a single transfection dish. Moreover, derivative cell lines that constitutively express the gene encoding EBV nuclear antigen 1 exhibited a tenfold enhancement in the frequency of rescue of marker genes. The feasibility of preparing large-scale directional or nondirectional cDNA libraries in pEBS7 was demonstrated and reconstruction experiments indicated that marker genes could be rescued from either library with equal efficiency. These results establish a high-efficiency system for the isolation of genes by direct phenotypic selection in human mutant cell lines.
Antigens, Viral↗
Increased spectrin proteolysis in fibroblasts from aged and Alzheimer donors.
Since calcium homeostasis is altered in cultured skin fibroblasts from aged and Alzheimer donors, the present study examined the degradation of spectrin, a substrate of the calcium dependent protease calpain. Spectrin proteolysis was estimated as the percentage of spectrin breakdown products (e.g., 150 + 155 kDa bands) per total spectrin immunoreactivity. In the baseline condition (e.g., unstimulated fibroblasts), spectrin breakdown was 53% greater in cells from aged donors when compared to cells from either young or Alzheimer donors. Compared to unstimulated cells, serum increased spectrin breakdown in cells from aged (22.4%) or Alzheimer (92.1%) donors but was ineffective in cells from young donors. Thus, when compared to young donors (100%), serum stimulation increased spectrin proteolysis by 183.9% (aged) or 231.7% (Alzheimer) after serum stimulation. Treatment of unstimulated cells with carbonyl cyanide 4-trifluoromethoxy-phenylhydrazone (FCCP), an uncoupler of mitochondrial function, increased spectrin degradation by 360.6% (young), 242.4% (aged) or 239.7% (Alzheimer) when compared to unstimulated cells of the same group. The combination of FCCP and serum stimulation enhanced spectrin breakdown in cells from aged (123.6%) and Alzheimer (154.0%) donors when compared to young cells (100%). Thus, changes in the regulation of calcium dependent proteases may contribute to decreased cell spreading and may play a role in the altered cytoskeletal dynamics characteristic of Alzheimer's disease.
Aged↗
The spontaneous resolution of cystic hygromas and early fetal growth delay in fetuses with trisomy 18.
The spontaneous resolution of cystic hygromas in fetuses with trisomy 18 may be due to a delay in lymphatic-vascular anastomosis. The severity of growth delay with trisomy 18 appears to be variable in time of onset and extent.
Adult↗
Intraindividual variation in 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute lymphoblastic leukaemia.
Intraindividual variation in 6-mercaptopurine (6-MP) kinetics has been little studied. It has now been examined in 18 children with acute lymphoblastic leukaemia (ALL). On 2 to 4 occasions in each patient drug concentrations in plasma and red cells were followed for 4 h after administration by means of HPLC. The mean individual coefficient of variation (C.V.) in AUC was 57.9% and it was not related to dose or concentration. The variation was the same in plasma and in red cells. It is concluded that regular monitoring of 6-mercaptopurine concentration would identify periods when a patient deviates strongly from the mean range. Both undertreatment and concentration-dependent toxicity could then be corrected.
Administration, Oral↗
Cytotoxicity of human phagocytes studied in vitro in a novel model based on neutral red absorbtion.
The aim of these investigations was to establish a model for the study of neutrophil (NEU) and monocyte (MO) mediated cytotoxicity (TOX), and to study the protective actions of model protease inhibitor, peroxide scavengers and glucocorticoids in this model. Confluent human fibroblasts were used as target cells (T) and NEU and MO were used as effector cells (E), ratio E/T was 5-10:1. After triggering E with PMA (16-48 nM) for about 24 hours, remaining viable T were detected by incorporation of Neutral Red (NR). Oxidant-induced TOX was performed with H2O2 and t-BuOOH. In contrast to MO TOX, NEU TOX was inhibited by antiprotease and scavengers. On the other hand, MO TOX was inhibited by glucocorticosteroids. This indicates different TOX mechanisms by NEU and MO.
Absorption↗
The effect of trisomy 18 on transverse cerebellar diameter.
The transverse cerebellar diameter was measured in 19 fetuses with trisomy 18. Eleven of the cerebellar measurements (57.9%) were greater than 2 SD below the mean for the patient's gestational age. If fetal biometry rather than last menstrual period were used to determine gestational age, four of the 19 (21.0%) cerebellar measurements were greater than 2 SD below the mean. Both intrauterine growth retardation and intrinsic central nervous system abnormalities associated with trisomy 18 appeared to affect cerebellar size.
Cerebellum↗
The transverse cerebellar diameter in the second trimester is unaffected by Down syndrome.
Cerebellar hypoplasia is a consistent finding in necropsy studies of children and adults affected by Down syndrome. The transverse cerebellar diameter was measured in 23 second-trimester fetuses with Down syndrome. All the measurements were within the normal range for gestational age.
Cerebellum↗
Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia.
Blood eosinophil count, serum concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), and peak expiratory flow (PEF) rate were studied in 23 patients with severe labile asthma characterized by eosinophilia at the start and end of a treatment period of 5 weeks. The mean blood eosinophil count was 808 x 10(6)/L at the start of the treatment period. Serum ECP and EPX were significantly raised compared with that of the references, whereas the mean serum MPO level was normal. The mean PEF was significantly and negatively correlated to both blood eosinophil count and serum ECP and EPX, but the predominant correlation was that between blood eosinophil count and PEF. At the end of the treatment period, PEF had increased and the blood eosinophil count and serum ECP and EPX were reduced when these values were compared with the values at the start of the treatment period. There was a significant and negative correlation of mean PEF to serum ECP but not to the blood eosinophil count. In individual subjects, the decreases in the blood eosinophil counts and serum EPX were significantly correlated to the individual increases of mean PEF. In conclusion, the present investigation indicates that in patients with asthma and pronounced eosinophilia, the lung function of the patients was principally related to the number of circulating eosinophils, whereas, when their eosinophilia was reduced to moderate levels, the patient's lung function was closer related to the activity of the eosinophils.
Adolescent↗
Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma.
Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts.
Adult↗
Secretion of granule proteins from eosinophils and neutrophils is increased in asthma.
The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03). The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.
Adult↗
A longitudinal analysis of young children's cohesion and noun specification in narratives.
The early production of nine cohesive devices during narration about personal experience was examined in an 18-month longitudinal study of 10 children between approximately age 2;0 and 3;6. The specification of noun phrases and types of noun errors were also explored. The number of cohesive ties increased with both age and MLU, due to increased pronominal reference and conjunctions (while clausal and verbal ellipsis decreased). Specific cohesive devices also were acquired at different MLU levels. Most noun phrases were non-problematic and errors declined with increasing age and MLU; specifically, noun omissions declined. However, when new nouns were introduced, approximately one out of five were ambiguous throughout the study. Thus, children's narratives become more comprehensible with age as cohesive links increase, and noun errors decrease, but at 3;6 children are still having difficulty properly managing the introduction of novel nouns.
Child Language↗
Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression.
Sublines from the small cell lung cancer (SCLC) cell lines U1285 and U1690, denoted U1285-100, U1285-250, U1690-40 and U1690-150, were adapted to grow in the continuous presence of 100, 250, 40 and 150 ng ml-1 doxorubicin (Dox), respectively. The Dox resistance was accompanied by cross-resistance to vincristine (Vcr), Vp-16 and for U1285-100 also to cisplatinum. Sublines of U1690-40 and U1285-100, cultured in absence of Dox for 4 months were only partially reversed with respect to Dox resistance. Neither the parental nor the most Dox resistance sublines had detectable levels of mdr 1 RNA but a small fraction of cells in all cell lines stained weakly positive for P-glycoprotein (P-gp). Verapamil (Ver) at 5 microM reversed the Dox resistance completely and partly in the U1690 and U1285 sublines, respectively, but did not increase the cellular accumulation of Dox. The cytoplasmic free Ca2+ concentration (Ca2+i) was close to 100 nM in both parental cell lines but elevated in the U1285-100 and U1690-40 sublines by 21 and 44%, respectively, and in U1285-250 and U1690-150 by 51 and 91%, respectively. The partly reverted sublines still showed significant but smaller elevations in Ca2+i of 10-30%. Ver was without acute or long term effects of Ca2+i in the U1285-100 and U1690-40 sublines. Selection for Dox resistance in SCLC may thus result in atypical multidrug-resistance characterised by absence of P-gp overexpression and atypical cross-resistance. Although Ver did not seem to affect Dox accumulation it may still work as a resistance modulator.(ABSTRACT TRUNCATED AT 250 WORDS)
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Trace analysis of methotrexate and 7-hydroxymethotrexate in human plasma and urine by a novel high-performance liquid chromatographic method.
A new high-performance liquid chromatographic method for the quantitative determination of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7-OHMTX) in blood plasma and urine was developed. The method utilized a solid-phase extraction procedure (Certify II cartridges) for the simultaneous isolation of MTX and 7-OHMTX. Chromatographic separation was achieved using a C18 reversed-phase column with isocratic elution. The eluent was irradiated with UV light of 254 nm, which converted MTX and 7-OHMTX by photolytic oxidation to fluorescent products. The limits of detection of MTX and 7-OHMTX in plasma were approximately 0.2 and 1 nmol/L, respectively. The intraday variability in the quantitation of MTX and 7-OHMTX was less than 8% down to 1 nmol/L and 4.6 nmol/L, respectively. Both MTX and 7-OHMTX could be detected in plasma from a patient being treated for rheumatoid arthritis 1 week after the last dose (10 mg orally).
Chromatography, High Pressure Liquid↗
Lipoproteins, malignancy, and anticancer agents.
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Antineoplastic Agents↗
On shortening the Expanded Attributional Style Questionnaire.
Whitley (in press) described a short form of the Expanded Attributional Style Questionnaire (EASQ). The EASQ was created to remedy the unsatisfactory psychometric properties of the Attributional Style Questionnaire; therefore, the benefits of a short form must be balanced with the possible costs, lower reliability and, hence, lower validity. Data from eight different samples using the EASQ (N = 963) suggest that the best items on the EASQ differ from sample to sample and from dimension to dimension. Further, reliabilities are reduced according to the predictions of the Spearman-Brown formula. Implications of these findings for attributional style research are discussed.
Journal Article↗
Pharmacokinetic optimisation of anticancer therapy.
It is obvious that there are great problems with pharmacokinetic individualization of anticancer therapy. The strong relationship between dose intensity (total dose/unit time) and response revealed in clinical trials with some tumours provides a strong support for studies seeking relationships between the individual plasma pharmacokinetic profile and response to treatment. Unfortunately, studies that define a therapeutic window are sparse, and trials that prospectively test such models are even rarer. Thus, for most cancer drugs, it is not possible to give any definite advice on how to use pharmacokinetic determinations to establish individualised therapy, and there is therefore a definite need for such studies. It is important, however, that attempts to establish relationships between drug concentrations and therapeutic effects be founded on a sound theoretical base. When drugs, mainly antimetabolites, are extensively metabolised intracellularly and interact with intracellular processes about which there are data showing a strong interindividual heterogeneity, such data must be considered when designing pharmacokinetic investigations. Cytarabine and fluorouracil are good examples of this. The monitoring of intracellular drug/metabolite concentrations or of the direct biochemical events in the tumour cells seems to be a promising approach with such drugs. It also needs to be emphasised that pharmacokinetically guided individualization cannot be achieved before a therapeutic window is established, i.e. a knowledge of the relationship between drug concentration and clinical effects. The investigators in this field accept a great responsibility when clinical studies are undertaken: a poorly designed study showing no benefit from pharmacokinetically guided individualization can impair the possibilities of performing more adequate studies in the future.
Antineoplastic Agents↗
Effects of ondansetron on chemotherapy-induced acute and delayed emesis--a pilot study.
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Adult↗