Biomedical subjects

P G Sørensen

Publications and source records attributed to P G Sørensen.

At least 19 recordsLinked to original sources

PubMed2005

Preparation and characterization of Boron carbide nanoparticles for use as a novel agent in T cell-guided boron neutron capture therapy.

Boron carbide nanoparticles are proposed as a system for T cell-guided boron neutron capture therapy. Nanoparticles were produced by ball milling in various atmospheres of commercially available boron carbide. The physical and chemical properties of the particles were investigated using transmission electron microscopy, photon correlation spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, vibrational spectroscopy, gel electrophoresis and chemical assays and reveal profound changes in surface chemistry and structural characteristics. In vitro thermal neutron irradiation of B16 melanoma cells incubated with sub-100 nm nanoparticles (381.5 microg/g (10)B) induces complete cell death. The nanoparticles alone induce no toxicity.

Animals↗

PubMed2001

Full-scale model of glycolysis in Saccharomyces cerevisiae.

We present a powerful, general method of fitting a model of a biochemical pathway to experimental substrate concentrations and dynamical properties measured at a stationary state, when the mechanism is largely known but kinetic parameters are lacking. Rate constants and maximum velocities are calculated from the experimental data by simple algebra without integration of kinetic equations. Using this direct approach, we fit a comprehensive model of glycolysis and glycolytic oscillations in intact yeast cells to data measured on a suspension of living cells of Saccharomyces cerevisiae near a Hopf bifurcation, and to a large set of stationary concentrations and other data estimated from comparable batch experiments. The resulting model agrees with almost all experimentally known stationary concentrations and metabolic fluxes, with the frequency of oscillation and with the majority of other experimentally known kinetic and dynamical variables. The functional forms of the rate equations have not been optimized.

Glycolysis↗

PubMed2001

Synchronization of glycolytic oscillations in a yeast cell population.

The mechanism of active phase synchronization in a suspension of oscillatory yeast cells has remained a puzzle for almost half a century. The difficulty of the problem stems from the fact that the synchronization phenomenon involves the entire metabolic network of glycolysis and fermentation, and consequently it cannot be addressed at the level of a single enzyme or a single chemical species. In this paper it is shown how this system in a CSTR (continuous flow stirred tank reactor) can be modelled quantitatively as a population of Stuart-Landau oscillators interacting by exchange of metabolites through the extracellular medium, thus reducing the complexity of the problem without sacrificing the biochemical realism. The parameters of the model can be derived by a systematic expansion from any full-scale model of the yeast cell kinetics with a supercritical Hopf bifurcation. Some parameter values can also be obtained directly from analysis of perturbation experiments. In the mean-field limit, equations for the study of populations having a distribution of frequencies are used to simulate the effect of the inherent variations between cells.

Algorithms↗

PubMed2000

Increased urinary albumin excretion rate in breast cancer patients.

A high frequency of slightly increased urinary albumin excretion (UAE) has been reported in patients with malignancies. Earlier studies have indicated a prognostic significance of UAE in some malignant diseases. We measured urinary albumin in 24-h urine samples in 44 patients with newly diagnosed early breast cancer and in 22 patients with relapse of metastatic breast cancer disease. The prevalence of microalbuminuria ( > or = 20 microg/min) was 20.5% in patients with early breast cancer and 54.5% in patients with metastatic disease. Median UAE was significantly higher in patients with metastatic breast cancer compared with the early breast cancer group (20.5 microg/min vs. 9.2 microg/min; p < 0.01). In patients with metastatic breast cancer, univariate survival analysis revealed a significantly lower survival rate in patients with microalbuminuria compared with the normoalbuminuric group (p <0.001). The present study demonstrates a high frequency of microalbuminuria in patients with breast cancer. Increased UAE was most prevalent in patients with metastatic disease. Our results also suggest that UAE may be a prognostic marker in metastatic breast cancer. Further prospective studies with a larger number of patients and controls are needed to test the validity of these observations.

Adult↗

PubMed1999

Sustained oscillations in living cells.

Glycolytic oscillations in yeast have been studied for many years simply by adding a glucose pulse to a suspension of cells and measuring the resulting transient oscillations of NADH. Here we show, using a suspension of yeast cells, that living cells can be kept in a well defined oscillating state indefinitely when starved cells, glucose and cyanide are pumped into a cuvette with outflow of surplus liquid. Our results show that the transitions between stationary and oscillatory behaviour are uniquely described mathematically by the Hopf bifurcation. This result characterizes the dynamical properties close to the transition point. Our perturbation experiments show that the cells remain strongly coupled very close to the transition. Therefore, the transition takes place in each of the cells and is not a desynchronization phenomenon. With these two observations, a study of the kinetic details of glycolysis, as it actually takes place in a living cell, is possible using experiments designed in the framework of nonlinear dynamics. Acetaldehyde is known to synchronize the oscillations. Our results show that glucose is another messenger substance, as long as the glucose transporter is not saturated.

Acetaldehyde↗

PubMed1999

Clinical significance of urinary albumin excretion in patients with non-Hodgkin's lymphoma.

Slightly increased urinary albumin excretion rates (UAE) have been reported in patients with various types of human cancer. We measured UAE in 24 h urine samples from 48 untreated patients with non-Hodgkin's lymphoma at diagnosis. In patients with a pretreatment UAE >/=20 microgram/min, post-treatment value of UAE was determined following completion of the last treatment. The median UAE was 15.0 microgram/min and the prevalence of microalbuminuria (UAE >/=20 microgram/min) was 39.6%. Increased UAE was significantly associated with Ann Arbor stage, performance status, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). The median posttreatment value of UAE was significantly lower than the pretreatment value (P < 0.0001). Our data suggest a clinical and prognostic significance of UAE in patients with non-Hodgkin's lymphoma.

Adolescent↗

PubMed1998

Sustained oscillations in glycolysis: an experimental and theoretical study of chaotic and complex periodic behavior and of quenching of simple oscillations.

We report sustained oscillations in glycolysis conducted in an open system (a continuous-flow, stirred tank reactor; CSTR) with inflow of yeast extract as well as glucose. Depending on the operating conditions, we observe simple or complex periodic oscillations or chaos. We report the response of the system to instantaneous additions of small amounts of several substrates as functions of the amount added and the phase of the addition. We simulate oscillations and perturbations by a kinetic model based on the mechanism of glycolysis in a CSTR. We find that the response to particular perturbations forms an efficient tool for elucidating the mechanism of biochemical oscillations.

Journal Article↗

PubMed1997

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis.

The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but the combinations are expected to be equally effective. A disadvantage of the cisplatin-based regimen is that patients need to be admitted to the hospital. The carboplatin regimen can be administered to outpatients. We tested both combinations administered every 3 weeks in a randomized phase III study in patients with previously untreated epithelial ovarian cancer. An interim analysis for toxicity was performed in 145 patients shortly after study closure. We observed a difference in the incidence of nausea, vomiting, and neurotoxicity favoring the women treated with the carboplatin regimen, but this regimen caused more myelotoxicity. Maturation of the study is awaited before survival data can be analyzed and final conclusions can be drawn.

Adult↗

PubMed1995

Activities of carbohydrate and amino acid metabolizing enzymes from liver of mink (Mustela vison) and preliminary observations on steady state kinetics of the enzymes.

The activity and some kinetic parameters of the key enzymes of the glycolysis, the gluconeogenesis and the amino acid catabolism from the liver of male and female mink have been determined and compared to the corresponding activities from rat and cat. The activities of glucose-6-phosphatase and pyruvate kinase are dependent on sex, both being higher in females. Except for pyruvate carboxylase the glycolytic and the gluconeogenic enzyme activities of the mink are higher than those of rat and cat; especially the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are markedly higher. The activities of glutamate dehydrogenase and glutamate oxaloacetate transaminase are smaller than the corresponding activities of rat but higher than those of cat. The results suggest that mink has a high capacity for gluconeogenesis compared to rat.

Amino Acids↗

PubMed1991

[Significant extrapulmonary manifestations of sarcoidosis].

Sarcoidosis is a granulomatous multisystem disorder of unknown genesis. Although the course is most often benign and self-limiting, serious or life-threatening extrapulmonary manifestations may occur when heart, central nervous system, kidney or the haemopoietic system are involved. In these cases, corticosteroid treatment is necessary to suppress the inflammation, prevent fibrosis in vital organs, and improve the general condition.

Adrenal Cortex Hormones↗

PubMed1990

[Diffuse fibrosing alveolitis and primary biliary cirrhosis].

Diffuse fibrosing alveolitis (DFA) is a disease with progressive, diffuse fibrosis in the interstitial tissue of the pulmonary parenchyma. As a rule, diffuse fibrosing alveolitis is limited to the lungs alone but it may occur as a partial manifestation of a systemic disease. A case report is presented here where diffuse fibrosing alveolitis was encountered in a patient with primary biliary cirrhosis. The pulmonary symptoms dominated the clinical picture and investigation revealed the autoimmune condition.

Autoimmune Diseases↗

PubMed1990

Determination of T1- and T2-relaxation times in the spleen of patients with splenomegaly.

Twenty-nine patients with known splenomegaly and seven healthy volunteers were examined. The T1 and T2 relaxation times were read out from a region of interest centrally in the spleen. Even though different mean T1 and T2 relaxation times were found between the groups, the great scatter and the considerable overlap between the groups makes the contribution of relaxation time measurements to the differential diagnosis of splenomegaly of limited value.

Diagnosis, Differential↗

PubMed1990

Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease.

We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage.

Anemia↗

PubMed1990

Prolonged T1 relaxation of the hemopoietic bone marrow in patients with chronic leukemia.

Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior iliac crest (within 72 hours of the MR examination) in order to provide data on bone marrow cellularity and differential counts. The patients with chronic leukemia all showed a significant prolongation of the T1 relaxation times compared with the normal range for hemopoietic bone marrow.

Adult↗

PubMed1989

Tallysomycin S10b--a phase I trial.

Tallysomycin S10b is a new bleomycin analogue. In animal studies it has shown the same degree of antineoplastic activity as bleomycin; however in contrast to that of bleomycin, its dose-limiting effect in animal systems is renal toxicity and its pulmonary toxicity is less pronounced. A total of 16 patients received tallysomycin S10b at three exploratory levels: 3 patients were given a dose of 1.25 mg/m2, 9 received 2.5 mg/m2 and 4 were given 5 mg/m2 as i.v. bolus injections twice weekly. Before treatment and every 3 weeks, plain chest X-rays, pulmonary function tests, renography and 51Cr-EDTA clearance were carried out. No renal toxicity was found in any of the treatment groups. In the first two groups no changes in chest X-rays were observed during treatment, whereas in the third group a decrease in single-breath carbon monoxide diffusion capacity (DLCO) was seen in one patient until the treatment was discontinued. Two of four patients receiving 5 mg/m2 developed interstitial pneumonitis at total doses of 104 and 160 mg, respectively. During the trial no haematologic or hepatic changes occurred due to the drug. The frequency of occurrence of skin changes, stomatitis and fever increased with the cumulative dose of tallysomycin S10b, and these side effects were similar to those seen with bleomycin. No tumor regression was seen during the trial. In contrast to the findings in previous animal studies, we found that the dose-limiting effect was pulmonary and not renal toxicity. The recommended dose for further phase II trials is 2.5 mg/m2 twice weekly, with careful monitoring of the pulmonary function.

Adult↗

PubMed1989

Enhanced pulmonary toxicity in smokers with germ-cell cancer treated with cis-platinum, vinblastine and bleomycin: a long-term follow-up.

The long-term effects of bleomycin on pulmonary function were studied. Thirty-four patients with germ-cell cancer were followed for an average of 64 months (range 43-98 months). All had obtained complete remission during treatment and none had relapsed at the follow-up examination. Pulmonary function was tested by measurements of total lung capacity (TLC), vital capacity (VC), forced expiratory volume in one second (FEV1) and single breath diffusion capacity for carbon monoxide (TLCO). TLC and VC were significantly reduced by the treatment (P less than 0.05), but normalized during the follow-up. TLCO was initially reduced to a predicted median of 83%. In the smokers the initial TLCO was at a predicted median of 79%, while in non-smokers a median of 88% was predicted. During the first 2 months of treatment, TLCO increased both in smokers and non-smokers to predicted medians of 90% and 91%. Subsequently, however, a significant decrease to 72% was noted in the smokers, while the non-smokers had only an insignificant decrease to 84%. The decrease in TLCO was irreversible but not progressive. We conclude that bleomycin treatment is associated with a long-term sustained reduction in TLCO. The changes were most pronounced in the smokers.

Adult↗

PubMed1989

The effect of thoracic irradiation for cancer of the breast on ventilation, perfusion and pulmonary permeability. A one-year follow-up.

Regional and overall lung function was studied in 14 women during a one-year follow-up after postmastectomy irradiation for cancer of the breast. The dose was 40 Gy in the chest wall and 20-40 Gy in the apex of the lung. Immediately after irradiation there was a slight increase in pulmonary clearance of 99TCm-DTPA compared to baseline values. This increase, however, was not restricted to the field of irradiation. Three months after irradiation there were regional defects in the ventilation and perfusion scintigrams in 11 of the patients. At the same time there was a greater decrease in total lung capacity, vital capacity and diffusion capacity for CO than in ventilation and perfusion. One year after irradiation the lung function impairment had only insignificantly regressed. It is concluded that local lung irradiation may cause persistent regional and generalized lung function impairment. The early increase in pulmonary clearance of 99Tcm-DTPA could not be used as a predictor of subsequent lung function impairment.

Adult↗

PubMed1988

Size adaptation of Turing prepatterns.

Spontaneous pattern formation may arise in biological systems as primary and secondary bifurcations to nonlinear parabolic partial differential equations describing chemical reaction-diffusion systems. Such Turing prepatterns have a specified geometry as long as D/R2 (the diffusion coefficient of the morphogen D divided by the square of a characteristic length) is confined to a (usually) limited interval. As real biochemical systems like cleaving eggs or early embryos vary considerably in size, Turing prepatterns are unable to maintain a specified prepattern-geometry, unless D/R2 is varied as well. We show, that actual biochemical control systems may vary Dapp/R2, where Dapp (kappa) is an apparent diffusion constant, dependent on enzyme regulated rate constants, and that such simple control systems allow Turing structures to adapt to size variations of at least a factor 10(3) (linearly), not only in large connected cell systems, but in single cells as well.

Diffusion↗