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At least 991 records · Page 55Linked to original sources
PubMed1980

[Selection of a statistical model for the evaluation of the reliability of the results of toxicological analyses. II. Selection of our statistical model for the evaluation].

Part II presents a statistical model devised by the authors for evaluating toxicological analyses results. The model includes: 1. Establishment of a reference value, basing on our own measurements taken by two independent analytical methods. 2. Selection of laboratories -- basing on the deviation of the obtained values from reference ones. 3. On consideration of variance analysis, t-student's test and differences test, subsequent quality controls and particular laboratories have been evaluated.

Analysis of Variance↗
PubMed1995

Selective use of an alternative stop codon and polyadenylation signal within intron sequences leads to a truncated topoisomerase II alpha messenger RNA and protein in human HL-60 leukemia cells selected for resistance to mitoxantrone.

Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replication and a target for many of the clinically useful antineoplastic agents. In a mitoxantrone-selected human leukemia cell line, HL-60/MX2, cellular topoisomerase II (topo II) catalytic activity is decreased, in association with the finding of reduced nuclear topo II alpha and beta protein levels. In addition, HL-60/MX2 cells contain a novel M(r) 160,000 topo II alpha-related protein that localizes predominantly to the cell cytoplasm (W. G. Harker et al., Biochemistry, 30: 9953-9961, 1991). In these studies, we have investigated the molecular mechanisms underlying the altered expression of the topo II alpha protein(s) in these cells. Three topo II alpha mRNAs, 7.2, 6.3, and 4.8 kb, were identified in the HL-60/MX2 cells, with the 6.3 and 4.8 kb transcripts being present in roughly equivalent amounts, while the 7.2-kb mRNA represents < 7% of the total topo II alpha-specific mRNA. Portions of the 3'-coding and 3'-untranslated regions were found to be missing from the 7.2- and 4.8-kb topo II alpha mRNAs by Northern blot analysis. Sequences encoding the 3' regions of the normal and truncated forms of the topo II alpha enzyme were obtained from the HL-60/MX2 cells through the use of a 3'-rapid amplification of cDNA ends strategy. Approximately 1321 nucleotides are missing from the 3'-coding and 3'-untranslated regions of the 4.8-kb mRNA and are replaced by 122 nucleotides that contain an in-frame stop codon and consensus polyadenylation signal. The translation product of the truncated 4388-bp topo II alpha transcript would have a predicted M(r) of 157,850, with 108 COOH-terminal amino acids being replaced by 13 novel residues. Immunoblot analysis confirmed that amino acids in the COOH-terminal region of topo II alpha were missing from the M(r) 160,000 HL-60/MX2 protein, and antisera generated to a synthetic peptide representing the 13 unique amino acids identified a M(r) 160,000 protein in nuclear extracts from these cells. PCR evaluation of the organization of the 3' region of the topo II alpha gene revealed that the 4.8-kb mRNA found in HL-60/MX2 cells diverges from that of the 6.3-kb mRNA at a consensus exon-intron splice donor site. The 122-bp novel nucleotides identified in the truncated transcript appear to originate from an adjacent intron as a result of altered RNA processing. These studies suggest that as a result of the disruption of the carboxy terminus of the topo II alpha protein and the putative nuclear targeting sequences identified therein, cellular localization of the protein is altered, which may confer a growth advantage for the HL-60/MX2 cells in the presence of mitoxantrone.

Amino Acid Sequence↗
PubMed1994

[Postmortem findings in swine: non-selected submissions from hog cholera protection areas of 1992 versus selected submissions of 1991-1992].

This article presents a survey of death-causes of all spontaneously died pigs, n = 851, from a restricted area in the province of South Holland during a 2 1/2 months lasting hog-cholera epizoötic in 1992. 23 pigs from 5 submissions showed a positive IFT against hog-cholera virus. Those animals and pigs from sero-positive farms were excluded from this survey. The results of the post-mortems were compared with the post-mortem findings of the normally submitted, selected, animals in 1991 and 1992, n = 904 + 745, from the western parts of the Netherlands, in which the above mentioned province is situated. By means of classification of the animals in age-classes and of the post-mortem findings to disease or diseased organsystem, insight is gained in the prevalence of the various causes of death per age-class. No distinct differences were found between the findings in the groups of animals from 1991 and 1992. In the group of the hog-cholera-period comparatively more animals belonged to the neonatal and suckling period. In contrast to 1991-1992 the number of weaned and fattening pigs in the hog-cholera-group was lower. In both groups 40% of the death-causes was due to diseases of the digestive tract and 30% was a result of respiratory-tract infections. The third main cause of death in both groups was septicaemia and related diseases as endocarditis, pleuritis, peritonitis, polyserositis and polyarthritis. Comparison of the prevalence of infectious diseases per organsystem in successive age-classes demonstrated a similar tendency in the hog-cholera-group as in the year-groups 1991 and 1992.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors.

A number of nuclear receptors are capable of binding to specific DNA sequences known as response elements that correspond to two 5'-PuG(G/T)TCA motifs. We have systematically compared the selectivity of DNA sequence recognition by the estrogen receptor and the retinoic acid receptor (RAR) and retinoid X receptor (RXR), using a variety of synthetic oligonucleotides related to natural response elements. The importance of the spacing and relative orientation of the PuG(G/T)TCA motifs as well as the possible role of the flanking sequences were investigated for each receptor. We find that the three receptors have different response element preferences and that their intrinsic DNA binding properties cannot be simply ascribed to spacing or orientation rules. For example, RARs bind with similar efficiencies to response elements containing directly repeated PuGTTCA motifs separated by 2, 3, 4, or 5 base pairs, and RXRs bind to response elements in which the directly repeated motifs are separated by 1, 2, and 5 base pairs. The actual sequence of the repeated motifs and the nature of their flanking bases appear to be important parameters in determining RAR and RXR binding efficiencies. The possibility that the binding specificity of nuclear receptors can be modified by interactions with other proteins, in particular other nuclear receptors, is discussed in relation to the patterns of transcriptional activation observed with either endogenous or transiently expressed receptors on chimeric promoters containing various response elements.

Animals↗
PubMed1995

Effects on metabolic rate and fuel selection of a selective beta-3 agonist (ICI D7114) in healthy lean men.

METHOD: ICI D7114 is a selective beta-3 agonist which in some animals increases metabolic rate, promotes weight loss and improves glucose tolerance. To investigate its potential usefulness in humans, 16 healthy young men (mean age 28.9 +/- 8.0 years; body mass index 22.5 +/- 1.6 kg/m2) were given ICI D7114 (150 mg/day, 2.08 +/- 0.24 mg/kg body weight) or placebo for 14 days in a double-blind randomised parallel group trial. Energy expenditure (EE) and substrate oxidation were assessed by continuous whole-body indirect calorimetry on Day 0 (before dosing), on day 1 (acute effect) and on Day 14 (chronic effect). RESULTS: Analysis of covariance indicated no significant effects on EE 4 h post-dose (Day 1, +2.4%, NS; Day 14, +1.0%, NS). There was no chronic effect on either the lowest 1 h of sleeping EE (+2.2%, NS) or 24 h EE (+0.7%, NS). There was a marginally significant chronic stimulation of basal metabolic rate (+3.6%, P = 0.042). ICI D7114 had no significant influence on protein, fat or carbohydrate oxidation. Tolerability and safety data showed that there were no increases in resting heart rate or blood pressure; no change in plasma potassium or reports of tremor; no haematological or biochemical abnormalities and no adverse events. CONCLUSION: We conclude that over 14 days ICI D7114 at a dose level of 150 mg/day has no biologically significant effect on EE in healthy, lean men.

Adolescent↗
PubMed1977

[The effect of biocides on the microflora of soils and their degradation. I. The selection of suitable biocides and ways of selective influences in soil-microorganisms (author's transl)].

The influence of 544 biocides on soil-microflora was investigated by a special plate-test and by a soil-test. Fungi were particularly sensitive to active substances. They were more inhibited by a greater number of substances, by lower concentrations and by a larger time-interval than bacteria. A differentiated sensitivity of fungi becomes apparent. The pseudomonads, a species of Agrobacter (AIA), flavobacteria and some coryneforme bacteria were relatively resistant. Actinomyces responded similar to fungi. The plate-test is suitable as preliminary test for the selection of substances retarding the degradation of straw. These organisms already favoured by treatments with active substance locate in higher quantities in such soils where the biological balance was disturbed in after the injection. Therefore, the effect of the active substance exceeds that of the injection. The displacement-effect by bacteria resistant to active substances and little active against cellulose plays a minor role in opposite to bacteria active against cellulose, because bacteria don't develop any homogeneous protective coat. A priority effect is therefore excluded.

Bacteria↗
PubMed1977

[Proximal selective vagotomy. Statistical review approximately 200 cases of selective vagotomy. Preventive note].

Gastric resection for the correction of duodenal hyperacidity in patients suffering from duodenal ulcer has always seemed out of proportion to the objective which is simply that of the clinical and anatomopathological cure of a small lesion. Vagotomy, particularly proximal selective v. offers the surgeon a rational approach to duodenal ulcer. This is also seen in the series of the F. Ponti Surgery Division of the Ca' Granda General Hospital of Milan.

Duodenal Ulcer↗
PubMed1997

Selective damage to the cerebellar vermis in chronic alcoholism: a contribution from neurotoxicology to an old problem of selective vulnerability.

The curiously consistent localization of cerebellar cortical damage in chronic alcoholism is re-evaluated in the light of selective damage, with a similar topography in the cerebellar vermal region, in superficial siderosis in man and in experimental animals exposed to certain toxic substances. Attention is drawn to the capacity for Purkinje cell dendrites and Bergmann glia to extract materials from the CSF, and to the close anatomical relationships of the susceptible lobules I-II, IX and X to the roof of the IVth ventricle and to the cistern of the great cerebral veins. This restriction of damage to vermis and paravermis may reflect some compartmentalization of CSF flow within leptomeninges, consistently increasing exposure of these cerebellar surfaces to materials circulating in the CSF. In other circumstances when this pattern of damage is encountered it raises the question as to whether other environmental agents, gaining access to the CSF, may be similarly distributed.

Alcoholism↗