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S Wold

Publications and source records attributed to S Wold.

13 recordsLinked to original sources
PubMed1992

Chemical purity and mutagenicity: case study of a drug in development.

During a routine Ames assay of a potential antipsychotic drug candidate, the compound appeared to be a frameshift mutagen in Salmonella typhimurium strains TA98 and TA1538. Additional testing indicated the mutagenic activity was due to one or more contaminants incurred during synthesis. While the compound was initially shown to be greater than 98% pure by high-performance liquid chromatography, the presence of small amounts (0.01-0.1%) of a highly mutagenic impurity produced positive mutagenicity results. The need to assess for chemical purity before discontinuing development of drug candidates found positive in the Ames assay is discussed.

Aminoquinolines↗
PubMed1990

Peptide QSAR on substance P analogues, enkephalins and bradykinins containing L- and D-amino acids.

Peptide QSARs are constructed for substance P analogues, enkephalins (two examples) and bradykinins containing both L- and D-amino acids. As descriptors in the QSARs, the previously developed descriptors z1 (hydrophobicity), z2 (bulk) and z3 (electronic effect) are used together with a qualitative variable coding for variation in chirality. Two parametrizations of the peptide sequences are tested. In the first no chiral description is used at all, and in the second chirality is described by the qualitative variable. It is concluded that for the current series of peptides, the biological response to variation in amino acid sequence and chirality can be modelled.

Amino Acid Sequence↗
PubMed1979

Classification of fungi by means of pyrolysis-gas chromatography-pattern recognition.

Repetitive samples of three strains of the mould Penicillium were subjected to pyrolysis-gas chromatography (Py-GC). From the chromatograms, 26 peak heights were used in a subsequent SIMCA pattern recognition analysis. This data analysis gives a marked improvement in the classification of the samples (100% correct, 85% unique) in comparison with the traditional analysis based on the average chromatogram of each class (92% correct, 45% unique). The data analytical method is described in detail using the Py-GC data as an illustration.

Analysis of Variance↗
PubMed1978

Structure-activity study of beta-adrenergic agents using the SIMCA method of pattern recognition.

The SIMCA method of pattern recognition (PaRC) was used to analyze structure-activity data for a series of phenethylamine agonists and antagonists of the beta-adrenergic receptor. On the basis of physicochemical substituent parameters the SIMCA method classified correctly 100% of the agonists and 88% of the antagonists. In addition, parameters derived from the class models were correlated with the biological activities of the agonists and antagonists, respectively. Test compounds not included in the initial data analysis were classified and their activities estimated. The applicability of pattern recognition in structure-activity studies in general is discussed.

Adenylyl Cyclase Inhibitors↗
PubMed1978

A structure-carcinogenicity study of 4-nitroquinoline 1-oxides using the SIMCA method of pattern recognition.

Structure-carcinogenicity data for a series of 4-nitro- and 4-hydroxyaminoquinoline 1-oxides were analyzed using the SIMCA method of pattern recognition. Using physicochemically based substituent constants to describe each compound, a principal components model was derived for the carcinogens. This model was 82% successful in predicting the carcinogenic potential of the compounds. For the 6-substituted compounds, a significant relationship between those structural parameters associated with carcinogenic potential and ability to stimulate unscheduled DNA synthesis was observed. In addition, other problems unique to the classification of carcinogens were discussed.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1977

Trace-element concentrations in blood samples from welders of stainless steel or aluminium and a reference group.

The concentrations of 17 trace elements (e.g., copper, cobalt, iron, manganese, chromium, silicon and magnesium) were determined in whole blood samples of 81 persons working with different welding methods on stainless steel or aluminium and 68 nonwelders. Inorganic spark source mass spectrometry was used for the chemical analyses. The data were analyzed by the SIMCA method for pattern recognition (discriminant analysis). No differences were found between the five groups, either in the average levels of the trace elements or in the correlation structures between the trace elements. Thus no blood concentration data on the analyzed elements and collected from a single person contained any information with respect to exposure to the welding fumes investigated.

Aluminum↗
PubMed1976

Comparison of graphical and computerized methods for calculating binding parameters for two strongly bound drugs to human serum albumin.

The determination of drug-protein binding parameters (n's and K's) can lead to important information on the required therapeutic dosage regimen and possible clinical complications associated with competitive displacement of one drug by a concurrently administered agent. Graphical and computer estimates of the data are often incorrectly formulated, and and seldom are adequate data obtained at low binding ratios. Commonly used graphical procedures, inadequately formulated computer methods, and a statistically correct computer method were used to compare results obtained from a circular dichroic examination of dicumarol-human serum albumin and fenoprofen-human serum albumin interactions. Literature binding constants for dicumarol-albumin range from 1 X 10(5) to 30 times that figure, and it is shown here that a wide range in parameter estimates may be obtained depending on the method of data analysis. The parameter estimates in the case of fenoprofen-albumin are even more variable.

Binding Sites↗
PubMedDate not supplied

Plasma levels and clinical effects of thioridazine and thiothixene.

The effects of thioridazine and thiothixene were studied by a double-blind technique on 40 schizophrenic patients. The doses were adjusted for optimal clinical and therapeutic effects and side effects were rated after three and eight weeks of treatment. No statistically significant differences were observed between the two drugs or between either of the two drugs and the previous medication. Plasma levels were estimated by a fluorometric technique after three and eight weeks of treatment. No correlation was found between plasma levels and clinical effects for either thioridazine or thiothixene. Plasma levels of both drugs were clearly correlated to dosage after three weeks of treatment. After eight weeks this correlation persisted for thioridazine but not for thiothixene. By that time plasma levels of thiothixene had decreased to about 30 per cent of the initial value, indicating strong enzyme induction.

Adult↗