PubMed Health⌕ Search

Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 505 records · Page 28Linked to original sources

Factors influencing survival in carcinoma of the ovary. Study from a well-defined Swedish population.

Prognostic factors were studied in 770 cases of carcinoma of the ovary treated at Radiumhemmet during 1974 to 1979. Centralization of the treatment in a well-defined population with complete follow-up permits a nonselective study of the disease. The analysis was made separately for early and late stages. For the early cases, histology and grading were the most dominant prognostic factors. For the most advanced cases successful surgical treatment, either primary or secondary, showed significant relation to survival. Successful secondary surgery could be achieved in twice as many cases where radiotherapy was included in the treatment. Even for the advanced cases, the stage but not the histology was of prognostic significance. The major difficulties in evaluating treatment of ovarian cancer, especially in advanced cases, are associated with the multiplicity of sites of the disease and the prognostic factors that may contribute independently to the outcome.

Adult↗

Efficient secretion and purification of human insulin-like growth factor I with a gene fusion vector in Staphylococci.

A novel approach for production of small polypeptides, using a staphylococcal protein A vector, is described. This system is used to express, secrete and purify human insulin-like growth factor I (IGF-I). A fusion protein consisting of protein A and IGF-I is recovered in high yield by passing the culture medium through an IgG affinity column. Using site-specific mutagenesis an acid labile asp-pro cleavage site was introduced at the fusion point between the two proteins. The protein A "tail" can thereby be removed from the affinity purified fusion protein by chemical cleavage releasing biologically active IGF-I molecules.

Escherichia coli↗

The effect of inhibition of thromboxane synthesis in experimental thrombosis and hemostasis.

The effect of a selective inhibitor of thromboxane synthesis (dazoxiben) was evaluated in different acute models for thrombosis and hemostasis. Dazoxiben significantly reduced the thrombogenicity of the modified human umbilical vein (Dardik Biograft) inserted in the carotid artery position in sheep. The effect was evident concerning patency, thrombus weight and platelet accumulation at the distal anastomosis. This paralleled a decreased production of thromboxane in both anastomoses and the midgraft region. Dazoxiben did not reduce either the frequency of jugular vein thrombosis (induced by a combination of endothelial damage and flow restriction) or arteriolar microembolism after laser injury in rabbits. Neither did it influence initial hemostasis as evaluated by measuring the hemostatic plug formation in the rabbit mesenteric microcirculation. It is concluded that thromboxane synthesis inhibition may be of value when attempting to improve the performance of small diameter vascular prostheses, the data obtained indicating a low risk for hemorrhagic complications.

6-Ketoprostaglandin F1 alpha↗

Immobilization and purification of enzymes with staphylococcal protein A gene fusion vectors.

Two improved plasmid vectors, containing the gene coding for staphylococcal protein A and adapted for gene fusions, have been constructed. These vectors allow fusion of any gene to the protein A moiety, giving fusion proteins which can be purified, in a one-step procedure by IgG affinity chromatography. One vector, pRIT2, is designed for temperature-inducible expression of intracellular fusion proteins in Escherichia coli and the other pRIT5, is a shuttle vector designed for secretion. The latter gives a periplasmatic fusion protein in E. coli and an extracellular protein in Gram-positive hosts such as Staphylococcus aureus. The usefulness of these vectors is exemplified by fusion of the protein A gene and the E. coli genes encoding the enzymes beta-galactosidase and alkaline phosphatase. High amounts of intact fusion protein are produced which can be immobilized on IgG-Sepharose in high yield (95-100%) without loss of enzymatic activity. Efficient secretion in both E. coli and S. aureus, was obtained for the alkaline phosphatase hybrid, in contrast to beta-galactosidase which was only expressed efficiently using the intracellular system. More than 80% of the protein A alkaline-phosphatase hybrid protein can be eluted from IgG affinity columns without loss of enzymatic activity.

Alkaline Phosphatase↗

Tissue polypeptide antigen (TPA) as a prognostic aid in human prostatic carcinoma.

Serum levels of tissue polypeptide antigen (TPA) and prostatic acid phosphatase (PAP) in serum, the presence or absence of skeletal metastases, tumor grade, patient age, and erythrocyte sedimentation rate (ESR) were determined in 50 patients with prostatic adenocarcinoma before onset of any therapy. Crude survival rates were estimated for a 5-year period after the time of diagnosis. The prognostic value was estimated by means of the log rank test and multivariate life table analysis. The TPA, PAP, tumor stage, and ESR all appeared to be useful as prognostic markers. Tumor grade and patient age were not significantly related to crude survival. The TPA proved to be the most reliable prognostic marker in single test estimates as well as in a multivariate life table analysis (p less than 0.01).

Acid Phosphatase↗

Curettage of benign lesions of bone. Factors related to recurrence.

In a retrospective study of 155 patients with different types of benign lesions of bone, the rate of recurrence following simple curettage was analysed in relation to sex, age, histological type, the location and the size of the tumour, and the type of bone graft used at operation. All patients were followed for a minimum of 2 years, 131 (85%) for 5 years and 101 (65%) for 10 years or more. The overall rate of recurrence was 23%. All recurrences except one were within 6 years of the initial operation, 80% within 3 years and 49% within 1 year. The overall rate of cure using curettage as the sole treatment, although repeated several times in some cases, was 95%. Only 5% of the patients required more extensive surgery, such as local resection (6 cases) and amputation (1 case), to control the tumour. The histological type and the sex of the patient proved to be the only factors statistically related to recurrence, although with solitary cysts the age of the patient was also relevant. Significantly higher recurrence occurred with giant cell tumours and aneurysmal bone cysts, in females, and with solitary cysts in patients under 9 years of age. This study of histologically different benign lesions treated in a uniform manner at a single centre shows that the rate of recurrence is strongly related to the type of tumour. The choice of treatment in patients with benign lesions of bone should be dictated by the histological appearance of the lesion. More extensive surgical procedures may not be necessary but other measures may be used in addition to curettage.

Adolescent↗

Chondronectin: physical and chemical properties.

Chondronectin, the chondrocyte attachment factor, was purified from chicken serum and characterized as to its physical and chemical properties. From sedimentation equilibrium data it was found to have a native molecular weight of 175,800 +/- 800 and a subunit molecular weight of 55,540 +/- 800 in the presence of guanidinium chloride and cysteine, suggesting a trimeric structure linked by disulfide bonds. As visualized by electron microscopy after rotary shadowing, the protein appears compact and globular. The amino acid and carbohydrate compositions of chondronectin are distinct from fibronectin, the fibroblast attachment factor, and laminin, the epithelial cell attachment factor. The activity of chondronectin in promoting attachment of chondrocytes is stable to digestion by collagenase, elastase, and neuraminidase, but is destroyed by trypsin treatment. The data suggest that chondronectin is structurally and chemically distinct from fibronectin and laminin.

Amino Acids↗

Effects of progesterone, progestogens, and danazol on the specific cortisol binding in human plasma.

The interaction of medroxyprogesterone acetate (MPA) with cortisol binding to corticosteroid-binding globulin (CBG) was studied with the use of an aqueous two-phase system with polyethylene glycol and dextran for equilibrium partition. Competitive binding analyses were also performed for progesterone (P), levonorgestrel, norethisterone, danazol, and tamoxifen. P and danazol were found to exert cortisol displacing activity, whereas MPA and the other tested compounds had no such effect. The glucocorticoid effects reported for MPA could not be explained by displacement. In general, P serum concentrations are lower than those of cortisol, and most binding sites on CBG are occupied by the glucocorticoid. At high P levels displacement and an increase in free cortisol may occur. Danazol displacement of cortisol is hampered by its pronounced albumin binding. In conclusion, none of the tested compounds should increase free and biologically active cortisol during normal clinical treatment.

Binding, Competitive↗

Irradiation therapy with multiple small fractions per day in urinary bladder cancer.

In a clinical trial 168 patients with carcinoma of the bladder, T2-T4, were randomized to one of two treatments; 1 Gy 3 times a day to a total of 84 Gy or 2 Gy once a day to a total of 64 Gy. Local eradication of the tumour in the bladder cystoscopically and cytologically at 6 months after completion of treatment and patient survival were analyzed. The results favoured significantly the patients treated with 84 Gy. All patients were followed 5-9 years. The survival was significantly improved in patients with T3 lesions treated with 84 Gy (p less than 0.01). Complications in the bowel requiring surgical treatment were not significantly different between the two groups of patients. The results indicate a therapeutic gain by hyperfractionated radiotherapy in comparison to conventional fractionated radiotherapy.

Aged↗

Influence of reduced oxygen availability on cerebral metabolic changes during bicuculline-induced seizures in rats.

The objective of the present work was to study cerebral energy metabolism at threshold levels of hypoxia, i.e., degrees of hypoxia that abolish cerebral electrical activity, in the "normal" and in the epileptic brain. Seizures were induced by intravenous bicuculline and cerebral oxygen availability was reduced by a combination of lowered PO2 and reduced blood pressure to give a transformation of the burst suppression pattern to either one with single spikes or overt EEG flattening. Nonepileptic control animals were exposed to degrees of hypoxia that gave either a markedly depressed EEG pattern with sparse slow waves or EEG flattening. Epileptic and nonepileptic groups proved comparable in terms of calculated oxygen availability and cerebral oxygen consumption at the threshold of "transmission failure." At levels of hypoxia that markedly attenuated or completely abolished seizure discharge, the cerebral metabolic changes were more marked than in comparable nonepileptic animals. These changes comprised an imminent severe perturbation of cerebral cortical phosphorylation potential, a pronounced lactic acidosis with a precipitous redox change, and a marked accumulation of ammonia. The more labile energy balance of the epileptic brain may indicate that the "seizure state" either increases cellular energy demands in spite of the electrical silence or reduces the efficiency of ATP production at the prevailing oxygen availability. It is conceivable that energy failure elicited by complicating hypoxia can aggravate or precipitate brain cell damage in epilepsy.

Animals↗

Electron contamination from different materials in high energy photon beams.

Relative lateral electron surface dose distributions from filters and air in high energy photon beams were determined using the Fermi-Eyges theory of multiple scattering. The model includes transmission and angular scattering in materials and in air. Backscatter from the phantom was also estimated. The variation of surface dose with different parameters such as atomic number, thickness and position of material, field size and photon energy was investigated. The calculated data show good agreement with experiment. For 60Co gamma rays, electron filters of medium atomic number give the lowest surface dose, whereas for higher energies a low to medium atomic number material should be used, especially for short material-phantom distances and large field sizes. The contribution to surface dose can be reduced by over 30% by placing a thin foil of high atomic number after a low to medium atomic number filter, thus scattering some electrons from the beam. For 60Co gamma rays the air is often the dominant source of contaminating electrons because of high multiple scatter loss at this energy, while for higher photon energies the beam flattening filter is the main electron source because of the small emission angle of the electrons and the small scattering power at high energies.

Cobalt Radioisotopes↗

Death by graft-versus-host disease associated with HLA mismatch, high recipient age, low marrow cell dose, and splenectomy.

In 65 recipients of marrow from HLA-identical siblings, the death rate from graft-versus-host disease (GVHD) at 1 year was 13%, which was significantly less when compared with 50% among 10 recipients of marrow from HLA-non-identical donors (P less than 0.001 log-rank test). Among recipients of HLA-matched marrow the following was found: patients below 17 years of age had a death rate from GVHD of 4% compared with 32% in elder patients (P less than 0.01). In patients who received greater than or equal to 3 X 10(8) marrow cells/kg 3% died of GVHD compared with 31% in those receiving fewer marrow cells (P less than 0.02). Furthermore, death by GVHD was 11% among nonsplenectomized patients compared with 60% in splenectomized patients (P less than 0.001). Among all children, and among nonsplenectomized patients, those receiving less than 3 X 10(8) marrow cells/kg had a significantly increased death rate by GVHD. The number of T cells or T cell subsets in the marrow graft was not correlated with GVHD or death by GVHD.

Actuarial Analysis↗

Prognostic value of B-cell mitogen-induced and spontaneous thymidine uptake in vitro in chronic B-lymphocytic leukaemia cells.

Blood lymphocytes from 50 patients with chronic B-lymphocytic leukaemia (B-CLL) were cultured in vitro with and without the polyclonal B-cell activators (PBA) dextran sulphate (DxS), lipopolysaccharide from E. coli (LPS), and Epstein Barr virus (EBV). Patients with blood lymphocytes that showed a high spontaneous or PBA-induced 3H-thymidine uptake in 4 d cultures had a significantly shorter therapy-free survival than patients whose lymphocytes showed a low thymidine uptake. The DxS-induced cellular thymidine uptake was the most powerful predictor of prognosis. Eighteen patients with leukaemic cells responding to DxS stimulation had a median therapy-free survival of 17 months and a probability of 5 year therapy-free survival of less than 0.1, whereas for 30 patients with DxS unresponsive cells the corresponding figures were greater than 120 months and greater than 0.7, respectively (log rank, P less than 0.0001). A multivariate Cox's regression analysis revealed that the DxS-induced leukaemic cell response was of greater prognostic importance than clinical features such as blood counts and staging according to Rai and Binet. Therefore PBA-induced leukaemic cell thymidine uptake seems valuable in the prediction of prognosis in B-CLL.

Adult↗

An assessment of the extent of antigenic analogy between physiologically bound C3 and C3 denatured by sodium dodecyl sulphate.

Three previously defined antigenic subsets of C3 (C3(S), C3(D) alpha and C3(D)beta) clearly distinguish native C3 from C3 that has been denatured in the presence of sodium dodecyl sulphate (C3-SDS): C3-SDS expresses antigens of all 3 subsets, while native C3 only expressed C3(S) antigens. The radioimmunometric assessment performed in this study revealed that 90% of the C3(S) and C3(D)alpha and 70% of the C3(D)beta antigens demonstrable in C3-SDS also was expressed by physiologically bound C3b on sheep erythrocytes. The antigenic properties of bound C3b were not shared by soluble C3b, which (like soluble C3) only expressed C3(S) antigens, nor did soluble C3b 'spontaneously' released from complement-treated target cells express antigens other than C3(S). We therefore conclude that the expression of C3(D) antigens, under physiological conditions of activation, reflects a conformational modification unique for bound C3b and occurring to an extent comparable to that of C3 in the presence of a strong denaturant. Additional studies further revealed that the antigenic profile of bound C3b is determined by a heterogeneous population of molecules differing in their relative expression of the C3(S), C3(D)alpha and C3(D)beta subsets.

Animals↗

Non-invasive detection of carotid bifurcation disease by continuous-wave Doppler with spectral analysis.

The diagnostic accuracy of 5 MHz continuous-wave (C-W) Doppler with spectral analysis for detecting carotid bifurcation disease was evaluated. In a first phase of the study, normal confidence intervals for peak frequency data and spectrum width were established and Doppler spectrum abnormalities were separated into three types (spectral broadening with preserved window, spectral broadening without window, sequence of abnormalities including inverted Doppler spectrum). In a second phase the diagnostic accuracy of these variables was tested on 86 carotid arteries as independently compared with angiography. Whereas both peak frequency data and spectrum distribution findings were invariably abnormal in stenoses greater than or equal to 60%, spectrum distribution findings were more accurate in 30-59% stenosis. Using spectrum distribution criteria, sensitivity and specificity for stenosis greater than or equal to 30% were 94.6% and 90.7% respectively. All variables were insensitive for stenoses less than 30% lumen diameter reduction.

Adult↗

Density distribution of chronic myeloid leukaemia and normal colony-forming cells in diffusion chambers (CFU-D) and agar (CFU-GM).

The density distribution in Percoll gradients of clonogenic cells forming colonies in diffusion chambers (CFU-D) or in agar culture (CFU-GM) was studied in chronic myeloid leukaemia (CML). The density distribution of CFU-GM in CML was homogeneous with peaks within 1.058-1.061 g/ml, which is slightly lower than normal. CFU-D, on the other hand, showed heterogeneous distributions both in CML and in normal controls. Two separable populations of CFU-D were recognized, one with the same or lower density than CFU-GM that formed almost exclusively neutrophilic colonies in diffusion chambers, and a second population concentrating in the density range 1.068-1.075 g/ml which primarily formed macrophage colonies. The second population contained colony-forming cells derived from both Fc-receptor positive and Fc-receptor negative precursor cells, suggesting that at least some colonies in diffusion chambers arise from Fc-receptor positive granulopoietic cells of intermediate maturity and/or monocytes. The concentration of CFU-D in peripheral blood was increased 40- to 100-fold in 2 patients currently off treatment who had increased WBC counts.

Agar↗

Molecular cloning of Bacillus sphaericus penicillin V amidase gene and its expression in Escherichia coli and Bacillus subtilis.

The Bacillus sphaericus gene coding for penicillin V amidase, which catalyzes the hydrolysis of penicillin V to yield 6-aminopenicillanic acid and phenoxyacetic acid, has been isolated by molecular cloning in Escherichia coli. The gene is contained within a 2.2-kilobase HindIII-PstI fragment and is expressed when transferred into E. coli and Bacillus subtilis. The expression in B. subtilis carrying the recombinant plasmid is approximately two times higher than in the original B. sphaericus strain. A comparison of the purified enzyme from B. sphaericus and the expressed gene product in E. coli minicells suggests that the native enzyme consists of four identical subunits, each with a molecular weight of 35,000.

Amidohydrolases↗

Maternal and cord serum levels of tissue polypeptide antigen (TPA) in normal pregnancies.

The tumor antigen and cytoskeleton protein tissue polypeptide antigen (TPA) have been determined in maternal serum throughout pregnancy. TPA levels in serum from pregnant women (n = 70) were not different from those in nonpregnant women (n = 61) until pregnancy week 28, from which time levels increased until parturition. Duplex pregnancies (n = 7) had higher serum TPA concentrations than simplex pregnancies, which was significant in pregnancy weeks 28 (p less than 0.014) and 32 (p = 0.05). Maternal serum TPA concentrations did not change during abortion or parturition and the mixed umbilical blood concentration of TPA equaled that in the mother's serum just after parturition. The correlation between placenta weight and maternal serum TPA levels was significant (p = 0.025). The decline of TPA after labor indicated a t1/2 for serum TPA of 7.5 days.

Abortion, Induced↗