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Biomedical subjects

J Jacobsen

Publications and source records attributed to J Jacobsen.

At least 127 records · Page 7Linked to original sources

Thermodynamics and kinetics of the neutral transition of human serum albumin, monitored by the spectral change of bound bilirubin.

Sectral changes in the complex of human serum albumin with bilirubin in the neutral pH range are related to conformational alterations of the protein. The transformation responds to changes in temperature and concentration of calcium ions in a similar fashion as the N-B transition of albumin. The kinetics of the structural changes are studied. The spectral shift from high to low, as well as from low to high pH, is presented in a model consisting of three relaxation steps.

Bilirubin↗

Bilirubin-albumin binding affinity and serum albumin concentration during intensive phototherapy (blue double light) in jaundiced newborn infants.

Thirty newborn infants with normal birth weights and uncomplicated hyperbilirubinaemia were studied. Twenty three of these were treated continuously for 24 h with intensive phototherapy (blue double light), and seven untreated infants served as controls. During the treatment the serum concentrations of total bilirubin and unbound bilirubin in diluted serum measured by the peroxidase method were markedly reduced. The binding affinity of bilirubin to its high affinity site on serum albumin was not affected. During the treatment a slight decrease of the serum albumin concentration occurred, and the possible causes of this observation are discussed.

Bilirubin↗

Reactivity of the thiol group in human and bovine albumin at pH 3--9, as measured by exchange with 2,2'-dithiodipyridine.

The kinetics for exchange between an aromatic disulphide and the thiol group in human and bovine albumin as well as in glutathione were investigated in the pH range 2.5--9.8. For both albumins the rate constants exhibit a maximum near pH 3, confirming the results of Svenson and Carlsson's investigation of bovine albumin [A. Svenson and J. Carlsson (1975) Biochim. Biophys Acta, 400, 433--438]. This was related to the well known N--F conformational change of the protein. At pH 5--8 the reactivity of the thiol group in both albumins and glutathione changes sharply, probably due to ionization of the thiol group. At pH above 8, however, the reactivity of the thiol group in albumins, but not in glutathione, becomes nearly independent of pH. In addition, a conformational change at pH 6.5--8.5 was studied by means of differential spectroscopy of bilirubin, liganded to human albumin. This neutral transition appeared to proceed identically in mercaptalbumin and nonmercaptalbumin. It is concluded that (a) the pK of the thiol group in albumin is significantly below that of SH in glutathione, and (b) ionization of this thiol group, Cys-34, is independent of the neutral transition.

2,2'-Dipyridyl↗

Dansylation of human serum albumin in the study of the primary binding sites of bilirubin and L-tryptophan.

Binding of bilirubin and of L-tryptophan to dansylated albumins was investigated. Dansylation of less than one lysine residue per molecule of albumin did not affect the bilirubin binding, but decreased the L-tryptophan binding, indicating that dansylation had taken place in or near the l-tryptophan-binding site. Native albumin and albumin-bilirubin 1:1 complex showed the same affinity for L-tryptophan. The results indicate that, although L-tryptophan and bilirubin are bound in the same region, perhaps in a common cavity of the albumin molecule, such a cavity is sufficiently large to contain both ligands.

Bilirubin↗

Studies of the affinity of human serum albumin for binding of bilirubin at different temperatures and ionic strength.

The association constants for the binding of bilirubin to human serum albumin (HSA) have been determined at four different temperatures by measurements of the rate of the peroxidase catalyzed oxidation of unbound bilirubin. The change of enthalpy is determined from a van't Hoff plot (ln Kass versus 1/T) to about -13.5 kcal/mol. deltaG degrees is calculated from the binding constants, and deltaS degrees is obtained from: deltaG degrees = deltaH degrees--TdeltaS degrees. The results show that the large negative deltaG degrees (--11 kcal/mol) for binding of bilirubin to HSA is a consequence of the negative deltaH degrees. The entropy was found to be about--8.5 cal/mol/degree and tends to diminish the numerical value of deltaG degrees. The binding constant has also been determined at varying ionic strength. The results show a decrease in binding for increasing salt concentration. The data from the two sets of experiments suggest that hydrogen bonds and salt linkages rather than hydrophobic interactions are the main factor in the binding of bilirubin to its primary site on HSA.

Bilirubin↗

Clinical evaluation of a novel beta-lactam antibiotic: pivmecillinam (FL 1039).

Pivmecillinam, a new penicillin-like antibiotic, is a member of the amidinopenicillanic acid group. Its mode of action differs from that of the classical penicillins and it exhibits no cross-resistance with them. Fifty-two gerontopsychiatric patients, median age 81 years, with E. coli, Klebsiella, and Proteus bacteriurias were divided into three comparable groups. In a ten week open clinical trial the patients were treated with pivmecillinam, pivampicillin or the two drugs given alternately in doses reduced in stages. The bacteriuria in all groups cleared almost completely in three days. Pivmecillinam compared favourably with pivampicillin especially at the end of the reduced medication. The alternating treatment seemed to be superior to treatment with either drug administered separately. No development of resistance was observed. No toxic effect on the liver, kidney, or bone marrow was seen in any of the three groups. In the group receiving pivmecillinam alone, no ampicillin-like skin rashes occurred.

Aged↗

[Treatment possibilities of laryngeal cancer. Surgery--radiotherapy--chemotherapy].

Treatment's possibilities of the carcinoma of larynx are presented and we especially attract notice to require a right distribution of stages in conformity with the prescriptions from the U.I.C.C. Operation's methods and radiotherapeutic possibilities are indicated. Following the author's views, it would be made primary irradiations in the stages T1 and T2, while only after the operation it would be necessary to use a radiotherapy in the stages T3 and T4. The possibility of a preoperative irradiation in the advanced stage is taken up. The problem of the reappared tumor is discussed and it is made a transition to the possibilities of the chemotherapy. The possibilities of a fractionated synchronisation of the intraarterial therapy of the tumor and a possible polychemotherapy are discussed.

Antineoplastic Agents↗