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Biomedical subjects

K Arndt

Publications and source records attributed to K Arndt.

At least 19 recordsLinked to original sources
PubMed1996

Implicit rationing criteria in non-small-cell lung cancer treatment.

Data collected from lung cancer patients attending the Victoria Clinic of the British Columbia Cancer Agency are used to investigate how resources are rationed in the treatment of non-small-cell lung cancer (NSCLC). An ordered logit model is estimated to analyse empirically the relationship between treatment selection and: tumour stage, size and differentiation; the Feinstein index; Karnofsky performance status (KPS); and the patient's age, gender and marital and smoking status. Implicit rationing is found to occur with respect to all of these factors except the Feinstein index, gender and marital status. With respect to age, KPS and smoker status the main empirical results are: (a) an increase in age from 50 to 85 reduces the expected treatment expenditure by 50-70%, depending on the patient's KPS and smoker status; (b) patients with a KPS less than 80 and of 80, receive 30-46% and 75-85%, respectively, of the expected treatment expenditure for patients with a KPS of 90 or 100, depending on age and smoker status; (c) the expected treatment expenditure for active smokers is about 71-86% of the expenditure for non- or former smokers depending on age and KPS.

Age Factors↗
PubMed1988

Mechanism of inhibition of hepatic bioactivation of paracetamol by dimethyl sulfoxide.

Prior work has shown that DMSO inhibits paracetamol hepatotoxicity. In this paper we show that DMSO and its reduced metabolite dimethyl sulfide (DMS) can inhibit in vitro hepatic dimethylnitrosamine N-demethylase. We also show that DMSO can inhibit in vivo production of glutathione conjugates of paracetamol. Glutathione is known to conjugate the bioactivated form of paracetamol. Also, the isozyme of cytochrome P-450 responsible for dimethylnitrosomine N-demethylase, cytochrome P-450j, is thought responsible for paracetamol bioactivation. We therefore propose that DMSO inhibits paracetamol hepatotoxicity due to inhibition of cytochrome P-450j-dependent paracetamol bioactivation by DMSO and its metabolite DMS.

Acetaminophen↗
PubMed1986

Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982.

We analyzed the data on 15,438 consecutive medical inpatients monitored by the Boston Collaborative Drug Surveillance Program from June 1975 to June 1982 to determine the rates of allergic cutaneous reactions to drugs introduced since 1975 and to confirm and extend findings from an earlier study of the preceding 22,227 patients. There were 358 reactions occurring in 347 patients, for an overall reaction rate among patients of 2.2%. Each patient received a mean of eight different drugs. Rashes were attributed to 51 drugs, and 75% of the allergic cutaneous reactions were attributed to antibiotics, blood products, and inhaled mucolytics. Amoxicillin (51.4 reactions per 1000 patients exposed), trimethoprim-sulfamethoxazole (33.8/1000), and ampicillin (33.2/1000) had the highest reaction rates. Drug-specific reaction rates ranged from zero to 51.4 per 1000 and were determined for 180 drugs or drug groups. These results provide physicians with quantitative data that will be helpful in clinical decision making when drug-induced exanthems, urticaria, or generalized pruritus occurs.

Anti-Bacterial Agents↗
PubMed1986

GCN4 protein, a positive transcription factor in yeast, binds general control promoters at all 5' TGACTC 3' sequences.

The GCN4 gene is required for the general amino acid control derepression response in yeast. GCN4 protein protects a repeated sequence motif in the 5'-untranslated region of HIS4, HIS3, ILV1, and ILV2 genes subject to general control. At low concentrations of GCN4, only certain repeats in these genes are bound. The repeats differ slightly from the 5' TGACTC 3' consensus core sequence, and the selective binding of some sites at low GCN4 concentrations is related to the relative affinity of these sites to GCN4. Using purified GCN4 protein obtained from an overproducing strain of Escherichia coli, we were able to obtain complete protection of all of the repeat elements in these four genes at high GCN4 concentrations. Analysis of the relative binding constant to the 15 repeated sequences protected by GCN4 shows that the optimal binding site for GCN4 is 5' RRTGACTC 3' followed by a short stretch of thymidines. Another protein, present mostly in yeast nuclear extracts, binds to the HIS4 promoter at a site overlapping one of the GCN4 binding sites. This protein is displaced from its binding site at high GCN4 concentrations.

Binding Sites↗
PubMed1985

Lambda phage cro repressor interaction with its operator DNA: 2'-deoxy-5-fluorouracil OR3 analogues.

The experiments here show that chemically synthesized DNA containing fluorine at selected sites can be used to test specific predictions of a model for cro repressor--operator interaction. This is done by observation of the perturbation to the fluorine-19 NMR spectra of analogues of OR3 synthesized with 2'-deoxy-5-fluorouracil at specific positions in the DNA helix. Although the three-dimensional structure of the cro repressor from phage lambda has been determined by Matthews and co-workers [Anderson, W., Ohlendorf, D., Takeda, Y., & Matthews, B. (1981) Nature (London) 290, 754-758], direct structural observations on the complex of the protein with its specific DNA recognition sequence, OR3, are limited. From that structure of the protein, alone, a model of its complex to DNA was built by fitting B-form DNA, with some distortion [Ohlendorf, D., Anderson, W., Fisher, R., Takeda, Y., & Matthews, B. (1982) Nature (London) 298, 718-723]. That model proposes that the cro repressor contacts only one side of this DNA double helix and a number of specific protein--DNA contacts. To test the model, 2'-deoxy-5-fluorouracil was used to place the fluorine-19 nuclear spin-label on the side of the DNA contacting the cro repressor and on the opposite side facing away from the cro repressor. The results presented here are consistent with the prediction that lambda phage cro repressor contacts only one side of the DNA double helix.

Bacteriophage lambda↗
PubMed1984

Correlation of lac operator DNA imino proton exchange kinetics with its function.

The kinetics for imino hydrogen exchange, at individual base pairs in the DNA sequence corresponding to the lactose operon operator of Escherichia coli, has been examined by NMR saturation recovery measurements as a function of temperature. Three 17-base-pair subsections of the lac operator DNA were chemically synthesized for these studies. The results support our previous observations in the 36-base-pair complete lac operator DNA fragment that has been used in our previous NMR studies. The results indicate faster opening kinetics at a GTG/CAC that is also the site of operator mutations leading to the highest level of constitutive beta-galactosidase synthesis. The GTG/CAC sequence occurs frequently and often symmetrically in prokaryotic and eukaryotic DNA sites where one anticipates specific protein interaction for gene regulation or recombination.

DNA, Bacterial↗
PubMed1983

Possible molecular detent in the DNA structure at regulatory sequences.

A common feature that appears in a number of DNA sites where proteins interact is the sequence GTG/CAC. In the lac operator this sequence leads to a region with a higher imino proton exchange rate well below the optical melting temperature. It is suggested that this reflects a structural feature recognized by proteins that bind specific sites on the DNA molecule.

Base Sequence↗
PubMed1982

lac repressor-lac operator interaction: NMR observations.

We show here the changes in the NMR spectra of the Escherichia coli lac repressor when bound to isolated lac operator DNA. The observations focus on the aromatic residues--four tyrosines and a single histidine--in the amino-terminal DNA binding domain of the lac repressor. There is a good correlation between chemical shift changes seen by 19F NMR when compared with 1 H NMR of otherwise identical repressor--DNA complexes. The results suggest that the tyrosines do not intercalate in the DNA. The NMR spectral changes with similarly sized DNA fragments, not containing the lac operator DNA sequence, are different. Thus, the amino-terminal domain of the lac repressor is independently capable of discriminating between lac operator and nonspecific DNA sequences. There can be two amino-terminal fragments per operator in the specific complex.

Amino Acid Sequence↗
PubMed1982

[In vitro testing of yeast resistance to antimycotic substances].

Investigations have been carried out in order to clarify the antibiotic susceptibility determination of yeasts. 291 yeast strains of different species were tested for sensitivity to 7 antimycotics: amphotericin B, flucytosin, nystatin, pimaricin, clotrimazol, econazol and miconazol. Additionally to the evaluation of inhibition zone diameters and MIC-values the influence of pH was examined. 1. The dependence of inhibition zone diameters upon pH-values varies due to the antimycotic tested. For standardizing purposes the pH 6.0 is proposed; moreover, further experimental parameters, such as nutrient composition, agar depth, cell density, incubation time and -temperature, have to be normed. 2. The relation between inhibition zone size and logarythmic MIC does not fit a linear regression analysis when all species are considered together. Therefore regression functions have to be calculated selecting the individual species. In case of the antimycotics amphotericin B, nystatin and pimaricin the low scattering of the MIC-values does not allow regression analysis. 3. A quantitative susceptibility determination of yeasts--particularly to the fungistatical substances with systemic applicability, flucytosin and miconazol, -- is advocated by the results of the MIC-tests.

Antifungal Agents↗
PubMed1978

The natural history of recurrent facial-oral infection with herpes simplex virus.

Fifty-seven episodes of facial-oral infections with herpes simplex virus (HSV) (cold sores) were studied in 41 ambulatory patients. Patients were examined within 24 hr of the onset of symptoms and for five consecutive days. Clinical parameters were assessed, lesion size was measured, and daily cultures for virus were performed. HSV was isolated in 61% of the episodes and was HSV type 1 in all cases. Serum neutralizing antibody to HSV was measured initially and 21 days after the onset of symptoms. All patients had antibody initially, but a fourfold or greater rise in titer was seen in only four patients. Lesion size and stage of healing were compared in patients with virus-positive episodes and those with virus-negative episodes. These two groups were found to be clinically distinct. Virus-positive lesions were larger, and the rate of healing was slower. This finding provides the first clinical correlation associated with the presence of HSV in cold sores.

Adolescent↗