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E B Jensen

Publications and source records attributed to E B Jensen.

28 records · Page 2Linked to original sources

The binding of aprindine to serum proteins with statistical considerations concerning the analysis of binding data.

The binding of the potent, basic antiarrhythmic agent aprindine to serum proteins was studied in solutions of human serum albumin (HSA, lyophilized, 98% pure, KABI) and in human sera. The percentual binding in serum (90.9-96.7%) was considerably higher than in HSA solutions. The binding in serum decreased from 95-97% to 91-93% as the aprindine concentration was raised from 4 to 15 micrograms/ml. The serum binding differed significantly in sera from three normal individuals. By plotting (Formula: see text), as a function of bound drug and performing statistical analysis of the curves a striking difference between the number of primary binding sites in serum and in HSA solution was found (N1 for the HSA solution was 0.0016 and for one serum it was 0.020 "per albumin molecule".) The association constants for the primary binding sites (K1) were 4.3 X 10(6)M-1 for serum and 2.1 X 10(6)M-1 for the HSA solution. Furthermore, the analysis indicated that considerably less than one secondary binding site was present for each albumin molecule in the HSA solution. Therefore, no binding of aprindine to albumin molecules has been demonstrated and it is concluded that the entire binding of aprindine in serum as well as in 98% HSA solutions may be due to the presence of acid protein molecules. In particular, low percentual binding in HSA solutions in spite of the high association constant can be explained by a very low concentration of the binding proteins. The addition of propranolol or phenprocoumon did not cause any displacement of aprindine. In the appendix statistical problems in the analysis of the binding curves are elucidated. The experimental variance and the statistical acceptability of the binding model are discussed.

Analysis of Variance↗

Determination of membrane thickness distribution from orthogonal intercepts.

This report deals with the reconstruction of the distribution of membrane thickness T from that of orthogonal length Lo, measured in random section planes. In such planes the membrane appears as a band and the linear distance from one of its boundaries perpendicular to the opposite one is the length of the orthogonal intercept. Using a membrane model, an integral equation relating the probability density functions of orthogonal intercept length f(lo) and membrane thickness g(tau) is derived. Relations between moments are derived and the analytic solution to the problem of reconstructing g(tau) from f(lo) is given. The parametric approach by which it assumed that g(tau) has some known analytic form with unknown parameters is considered, and the use of a suggested analytic form for describing the thickness distribution of the human glomerular basement membrane is discussed.

Basement Membrane↗

The determination of naproxen by spectrofluorometry and its binding to serum proteins.

A fluorometric method for the determination of naproxen in serum, albumin solutions and protein free buffer solutions is described. The detection limit is about 10 ng/ml. Furosemide, thiopental and salicylic acid did not show any disturbing fluorescence while phenprocoumon did. The in vitro binding of naproxen in albumin solutions and serum was studied by equilibrium dialysis. A small but significant increase was found in the percentual binding in albumin solutions as compared to serum. The percentual binding was not affected by changes in the pH from 5--8. By fitting the binding data to a model assuming two classes of binding sites, association constants and binding capacities were determined. A very high affinity and a high capacity were found. The association constant for the first class of binding sites was higher for human serum albumin than for serum (8.5 versus 5.3 . 10(6) M-1). The difference in the protein binding to the first class of binding sites in human serum albumin and serum can be explained by the existence of a competitive inhibitor in serum.

Albumins↗

Renal transplantation and HLA-A,B matching. Theoretical considerations concerning pool size.

The rate of improvement in HLA matching quality with increasing pool size is predicted. The expected frequency of HLA-A,B-compatible matches increases rapidly up to approximately 47% for pool size 1,000 and from then on the increase is moderate, whereas for HLA-A,B-identical matches the increase in frequency is more constant, the expected frequencies being approximately 34 and 52% for pool sizes 1,000 and 2,500, respectively. The expected frequency of HLA-A,B fullhouse-identical matches is 33% at a pool size of 2,500. The waiting time for the first available HLA-identical kidney is estimated. For a random recipient there is a 25% chance of obtaining an HLA-identical match among the first 500 kidney donors. For two cooperating pools, it is calculated at which relative transplantation activity the kidney import to export is balanced and also the decrease in waiting time for an identical match when cooperating is estimated. The results of a kidney exchange simulation are presented and they agree well with the theoretical considerations.

ABO Blood-Group System↗

The influence of 13 clinical and immunological factors on renal graft survival: a contingency table analysis.

A statistical method which accounts for the heterogeneity of clinical materials is presented and applied to a material of necrokidney transplantations. It is concluded that the recipient sex and the period in which the transplantation was performed are the most important factors (best prognosis for female recipients, best programs for transplantations in the first periods) and that the HLA-match grade has a significant influence on graft survival for male recipients and transplantations with short cold ischemia time. The present analysis has furthermore demonstrate the heterogeneity of the material as judged by the associations between factors and the overestimation of the influence of some of the factors by direct comparisons.

ABO Blood-Group System↗

Rena transplantation and HLA-A, B matching. Theoretical considerations concerning pool size.

The rate of improvement in HLA-matching quality with increasing pool size is predicted. The frequency of HLA-A, B compatible matches increases rapidly up to approximately 47% for pool size 1000 and from then on the increase is more moderate while for HLA-A, B fullhouse-identical matches the increase in frequency is slower and more constant, the expected frequency being approximately 33% at a pool size of 2500. The import/export balance between two cooperating pools is estimated for various relative pool sizes and transplantation activities.

Gene Frequency↗

HLA-D typing by homozygous typing cells. A statistical analysis of experimental and biological variation.

Several normalization procedures have been applied to single MLC-typing experiments in order to neutralize experimental variation and hence to secure assignment of HLA-D phenotypes. The present paper concerns a statistical description and isolation of experimental and biological factors in repeated MLC-typing experiments. The statistical model used gives a meaningful description of the variables in MLC as judged by its application to MLC-typing data of HLA-identical siblings. Subsequent testing of the model in an HLA-A, -B,-C and -D-genotyped family material provides evidence that the level of typing response to selected homozygous typing cells may be influenced by factors coded for by the homologous HLA-D region. It is, however, concluded that such evidence must be accepted with caution due to the (for the present statistical purpose) suboptimal design for the HLA-D typing experiments and hence the relative insensitivity of the method. A general method for locating erroneous triplicates is devised.

Analysis of Variance↗

Expression of recombinant growth hormone in Escherichia coli: effect of the region between the Shine-Dalgarno sequence and the ATG initiation codon.

We constructed a synthetic Escherichia coli expression system in which various promoter elements can be changed easily. In this study we investigated the effect of a number of portable Shine-Dalgarno regions (SD regions) on the synthesis of two modified recombinant human growth hormones (hGH). The production of these modified hGH was measured during exponential growth and after the bacteria had reached stationary phase. The results show that the optimal distance between the SD region (AGGAGG) and the ATG start codon is approximately 11 nucleotides. However, the nucleotide sequence in this region also influences expression: 6-10 adenines result in comparable expression levels despite the varying lengths. Two overlapping SD regions reduce expression of the growth hormones considerably, whereas two potential ATG start codons do not affect expression. Having a SD-ATG region partly or totally complementary to the 5' end of the 16S ribosomal RNA does not alter translation efficiency. Estimation of the delta G values for the association between the 16S rRNA and the ribosome-binding region suggests that these are not indicators of expression efficiency.

Base Sequence↗