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PubMed1978

Immunological properties of fractionated avian erythroid nuclei.

Chicken reticulocyte (polychromatic primitive erythrocyte) and erythrocyte chromatin was fractionated by ultrasound shearing and salt precipitation into three fractions differing in their activities to support the in vitro RNA synthesis. The transcriptionally active fraction of chicken reticulocyte chromatin which represented only about 0.5% of the total nuclear DNA contained essentially all the chromatin-associated endogenous RNA. Approximately 2% of this endogenous reticulocyte RNA hybridized to globin cDNA probe and could be translated in vitro into polypeptides which coelectrophoresed with the in vitro translation product of isolated chicken globin mRNA or chicken globin marker. Each of the three fractions had a characteristic distribution of chromosomal proteins and endogenous RNA. Polyacrylamide gel electrophoresis of the chromosomal proteins showed differences in their distribution among individual fractions of the same cell type and among corresponding fractions of reticulocyte or erythrocyte chromatin. Antisera produced against dehistonized reticulocyte chromatin were specific for reticulocyte but not erythrocyte chromatin. When reacted with each of the differentially templating chromatin fractions, it was found that reticulocyte-specific antibodies were highly reactive with the template-active fraction of reticulocytes, but essentially nonreactive with any other reticulocyte fraction. This same antiserum was not significantly reactive toward any erythrocyte fraction. The antigenicity of the template-active fraction of reticulocytes was abolished after pronase or DNase II digestion, but only partially diminished after DNase I digestion.

Animals↗
PubMed2004

Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials.

BACKGROUND: Recent randomised studies reported that single fraction radiotherapy was as effective as multifraction radiotherapy in relieving pain due to bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications such as pathological fracture and spinal cord compression by single fraction radiotherapy. OBJECTIVES: To undertake a systematic review and meta-analysis of single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications. SEARCH STRATEGY: Trials were identified through MEDLINE, EMBASE, Cancerlit, reference lists of relevant articles and conference proceedings. Relevant data was extracted. SELECTION CRITERIA: Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain DATA COLLECTION AND ANALYSIS: The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. MAIN RESULTS: Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 - 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95%CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95%CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95%CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95%CI 0.72-2.75]). Repeated analyses excluding dropout patients gave similar results. REVIEWERS' CONCLUSIONS: Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.

Bone Neoplasms↗
PubMed2006

Average attributable fractions: a coherent theory for apportioning excess risk to individual risk factors and subpopulations.

The attributable fraction in a population and the attributable fraction in exposed are different epidemiologic measures for quantifying the contribution of a risk factor to the risk of disease. While the attributable fraction in a population depends on both the relative risk of disease and the risk of being exposed in the population, the attributable fraction in exposed depends only on the relative risk. Similar relationships apply to the combined attributable fraction in a population and in exposed, respectively, for quantifying the total contribution of a group of risk factors. Eide and Gefeller (1995) showed how the sequential and average attributable fractions could be applied to quantify the contributions of the individual risk factors to a combined attributable fraction in a population. The present paper shows how this methodology can be extended to the combined attributable fraction in exposed. The resulting average attributable fractions in exposed are compared to other proposed methods. The relationship between the average attributable fractions in a population and in exposed is outlined, thus establishing a coherent theory for apportioning attributable fractions in individuals, groups of individuals and populations, to single risk factors or groups of risk factors like modifiable versus nonmodifiable factors.

Adolescent↗
PubMed1987

Morphologic and functional heterogeneity among rat alveolar macrophage fractions isolated by centrifugation on density gradients.

Lavaged rat bronchoalveolar cells were separated into four different density fractions (I-IV) by centrifugation through a discontinuous Percoll gradient. Maximum cell size was found in the lowest density fraction (I) and minimal cell size in the highest density fraction (IV), showing an inverse correlation with cell density. These fractions contained alveolar macrophages (AM) in the proportion of 97% or more by morphologic criteria, while phagocytic AM was approximately 80% in each fraction. Although the proportion of Ia antigen-positive AM was low in each fraction, it was elevated after incubation with supernatants from concanavalin A (Con A) stimulated spleen cell cultures, with greater Ia expression in higher density fractions. Differences in these fractions were also noted in several functions, including Fc receptor activity, chemotactic migration, tumoricidal activity, and interleukin 1 (IL-1) production, all of which were greater in higher density fractions (III and IV). Con A-induced T cell proliferation was, however, suppressed by these higher density fractions, whereas only an intermediate density fraction (II) enhanced T cell responses. These results indicate morphologic and functional heterogeneity among rat AM.

Animals↗
PubMed1991

Tyrosine phosphorylation and immunodetection of vinculin in growth cone particle (GCP) fraction and in GCP-cytoskeletal subfractions.

The growth cone, the motile tip of developing neuronal processes, is considered responsible for the exact guidance of axons and synaptogenesis. High activity of tyrosine kinases in growth cones may contribute to the functions of growth cones. Our previous work revealed that vinculin is one of the endogenous substrates for intrinsic tyrosine kinases in the growth cone particle (GCP) fraction isolated from fetal rat brain. In the present study, we examined tyrosine phosphorylation and immunoblot analysis of vinculin in various fractions from fetal rat brains and adult synaptosomal fraction. Tyrosine phosphorylation of vinculin in the GCP fraction was more prominent than in any other fraction from fetal brain or synaptosomes from adult. Compared to other fractions, however, the enrichment of vinculin in the GCP fraction was not observed. Tyrosine phosphorylation of vinculin in the fraction was inhibited by genistein, a specific tyrosine kinase inhibitor. Although vinculin was also phosphorylated by protein kinase C in the GCP fraction, it incorporated a much smaller amount of 32P than MARCKS protein or GAP-43. The cytoskeletal subfraction from the GCP fraction contained a considerable amount of vinculin and it was one of the major substrates for tyrosine kinases in the GCP cytoskeleton. The membrane skeleton from the GCP fraction contained a low amount of vinculin but showed high kinase activity that phosphorylated vinculin. Taken together, our results suggest that tyrosine phosphorylation of vinculin contributes to the cytoskeletal organization of growth cones.

Animals↗
PubMed2006

Effect of cationic flaxseed protein hydrolysate fractions on the in vitro structure and activity of calmodulin-dependent endothelial nitric oxide synthase.

The objective of this study was to determine the in vitro effects of cationic flaxseed protein hydrolysate fractions on calmodulin (CaM) structure as well as the activity of CaM-dependent endothelial nitric oxide synthase (eNOS). Flaxseed protein isolate was hydrolyzed with alcalase, and two peptide fractions were isolated by cation-exchange chromatography. Fraction I, eluted first from the column, and fraction II contained 42% and 51% contents of basic amino acids, respectively. Fractions I and II reduced the activity of CaM-dependent eNOS through a mostly mixed-type inhibition mode. Fraction II was at least ten times more effective as an eNOS inhibitor when compared to fraction I, as evident from the IC(50) (concentration of protein hydrolysate that reduced eNOS activity by 50%) values. Fluorescence spectroscopy showed that the tyrosine residues in CaM were increasingly exposed upon addition of fraction I, while the opposite was the case when fraction II was added. Circular dichroism studies showed that fractions I and II reduced the alpha-helix content but increased the rigidity of the active calcium/CaM complex. We concluded that ability of the protein hydrolysate fractions to change the secondary and tertiary structures of CaM may explain their ability to reduce activity of CaM-dependent eNOS.

Calmodulin↗
PubMed1994

The fractional-order dynamics of brainstem vestibulo-oculomotor neurons.

The vestibulo-ocular reflex (VOR) and other oculomotor subsystems such as pursuit and saccades are ultimately mediated in the brainstem by premotor neurons in the vestibular and prepositus nuclei that relay eye movement commands to extraocular motoneurons. The premotor neurons receive vestibular signals from canal afferents. Canal afferent frequency responses have a component that can be characterized as a fractional-order differentiation (dkx/dtk where k is a nonnegative real number). This article extends the use of fractional calculus to describe the dynamics of motor and premotor neurons. It suggests that the oculomotor integrator, which converts eye velocity into eye position commands, may be of fractional order. This order is less than one, and the velocity commands have order one or greater, so the resulting net output of motor and premotor neurons can be described as fractional differentiation relative to eye position. The fractional derivative dynamics of motor and premotor neurons may serve to compensate fractional integral dynamics of the eye. Fractional differentiation can be used to account for the constant phase shift across frequencies, and the apparent decrease in time constant as VOR and pursuit frequency increases, that are observed for motor and premotor neurons. Fractional integration can reproduce the time course of motor and premotor neuron saccade-related activity, and the complex dynamics of the eye. Insight into the nature of fractional dynamics can be gained through simulations in which fractional-order differentiators and integrators are approximated by sums of integer-order high-pass and low-pass filters, respectively. Fractional dynamics may be applicable not only to the oculomotor system, but to motor control systems in general.

Brain Stem↗
PubMed1992

The effects of insulin, cycloheximide and phalloidin on the content of actin and p35 in extracts prepared from the nuclear fraction of Krebs II ascites cells.

The nuclear fraction isolated from Krebs II ascites cells following cell disruption by nitrogen cavitation was separated into four fractions by salt/detergent extraction: NP-40 soluble fraction, 130 mM KCl extract, DOC/Triton x 100 soluble fraction and salt/detergent treated nuclei. The protein composition of the individual fractions was studied by SDS-PAGE and the relative amounts of actin and a 35 kDa protein (p35) were measured from gel scans. There was a time-dependent shift of actin from the 130 mM KCl extract to the NP-40 soluble fraction upon storage of the nuclear fraction on ice, indicating a progressive depolymerization of microfilaments. Compared with actin there was a slower release of p35 into the NP-40 soluble fraction. The results suggest that p35 is not integrated in the microfilament network. Phalloidin, which stabilizes the microfilaments, enriched the amount of both proteins in the 130 mM KCl extracts, together with a series of other proteins in the range 50-205 kDa. The presence of phalloidin also resulted in a large increase in the actin content in both the DOC/Triton x 100 extract and the fraction containing salt/detergent treated nuclei. Incubation of cells with insulin and/or cycloheximide enriched the amount of actin in the 130 mM KCl fraction. The results show that short term incubation of cells with phalloidin, insulin or cycloheximide increases the actin content of the nuclear fraction and also affects the presence of several other proteins.

Actins↗
PubMed1987

The effect of serum fractions on single-cell mouse embryos in vitro.

To examine the effect of various fractions of human fetal cord serum (HCS) on mouse embryos cultured in vitro, heat-inactivated HCS was separated by ultrafiltration into five distinct fractions: Fractions A, MW greater than 30,000; B, MW 30,000-10,000; C, MW 10,000-5,000; D, MW 5,000-1,000; and E, MW less than 1,000. Seven hundred twenty-eight single-cell embryos were cultured in TYH-280 medium supplemented with 8 mg/ml bovine serum albumin (BSA) and a 20% concentration of Fraction A, B, C, D, or E, whole HCS, or BSA alone. Embryos cultured with Fraction A or E or whole HCS demonstrated a significantly reduced growth rate (P less than 0.01), while embryos cultured with Fraction D demonstrated a significantly increased growth rate (P less than 0.01). Additionally, 649 single-cell embryos were cultured in medium which was supplemented with 8 mg BSA/ml and a 0, 1, 2, or 5% concentration of Fraction A or E. Fraction E displayed toxicity even at a 1% concentration (P less than 0.01), while Fraction A demonstrated growth inhibition at a 5% concentration (P less than 0.05) but increased the hatching rate at a 1% concentration (P less than 0.01). Finally, 635 single-cell embryos were cultured with four distinct fractions of HCS obtained from a Sephacryl S-200 column: Fractions I, MW 100,000; II, MW 70,000-100,000; III, MW 30,000-70,000; and IV, low molecular weight (less than 5,000).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial.

PURPOSE: The aim of this study was to evaluate if the combination of micronized purified flavonoid fraction with short-term routine antibiotic and anti-inflammatory therapy was better at reducing the intensity of postoperative symptoms and wound bleeding after a Milligan-Morgan's open hemorrhoidectomy than antibiotic and anti-inflammatory treatment alone. METHODS: Fifty patients were randomly assigned to receive routine antibiotic and anti-inflammatory treatment alone (control patients) or a combination of micronized purified flavonoid fraction with identical antibiotic and anti-inflammatory treatment (micronized purified flavonoid fraction patients). The evolution of symptoms (pain, tenesmus, pruritus, and bleeding) during the postoperative period was assessed by means of patients' self-questionnaires. Each symptom was scored on a graded severity scale from 0 to 3, daily during the first three days of the immediate postoperative period, then at regular intervals (about every 14 days) until postoperative day 60. A global score for evaluation of each postoperative symptom and bleeding was used. The global score for each symptom was the sum of scores for each patient over the study period. The global score for each symptom was compared between the two groups with the Mann-Whitney U test. RESULTS: No significant differences in age, gender distribution, and stage of disease between the two groups were noticed at baseline. Posthemorrhoidectomy symptoms were relieved more rapidly in the micronized purified flavonoid fraction group; during the first three postoperative days, the global score for each symptom was significantly more reduced in the micronized purified flavonoid fraction group. The global scores for each symptom are as follows: pain after 3 days, 6.16 (SD = 1.9) in the control group vs. 3.48 (SD = 1.8) in the micronized purified flavonoid fraction group (P < 0.0001); tenesmus, 5.36 (SD = 1.8) in the control group vs. 1.48 (SD = 1.5) in the micronized purified flavonoid fraction group (P < 0.0001); pruritus, 4.04 (SD = 1.9) in the control group vs. 1.84 (SD = 1.4) in the micronized purified flavonoid fraction group (P < 0.0001); bleeding, 4.4 (SD = 2.1) in the control group vs. 2.0 (SD = 1.3) in the micronized purified flavonoid fraction group (P < 0.0001). A significant difference (P < 0.0001) between groups was also shown in favor of micronized purified flavonoid fraction patients when global scores were calculated over the entire study period (60 days). CONCLUSION: Micronized purified flavonoid fraction used in combination with short-term antibiotic and anti-inflammatory treatment can reduce both the duration and extent of postoperative symptoms and wound bleeding following hemorrhoidectomy.

Adult↗
PubMed1977

Circular dichroism of glycopeptide fractions from alpha1-acid glycoprotein, thyroglobulin, and ovalbumin.

Using sequential pronase digestions, glycopeptide fractions were prepared from human alpha1-acid glycoprotein, hen egg ovalbumin, and bovine thyroglobulin, two types of glycopeptides being obtained from the latter. The fractions were characterized on the basis of hexose, hexosamine, sialic acid, and peptide content. The glycopeptide fraction from alpha1-acid glycoprotein is complex (i.e., the carbohydrate moiety contains mannose, galactose, N-acetylglucosamine, and sailic acid), as is one of the glycopeptide fractions from thyroglobulin (type I). The glycopeptide fraction from ovalbumin and the type II glycopeptide fractions from thyroglobulin are simple (i.e., the carbohydrate moiety contains only mannose and N-acetylglucosamine). The circular dichroic spectra of the two complex glycopeptide fractions and the ovalbumin glycopeptide fraction were similar and were characterized by a negative extremum between 207.5 nm and 211 nm with magnitudes in the range of --6400 deg-cm2-dmol-1 to --7200 deg-cm2-dmol-1 (referred to the molar concentration of N-acetylated sugars). The thyroglubulin type II glycopeptide fraction exhibited a circular dichroic spectrum with an extremum of --29 200 deg-cm2-dmol-1 at 205 nm. Removal of sialic acid from the complex glycopeptide fractions greatly increased the (negative) magnitude of ellipticity at the extremum. The circular dichroic spectra of the complex of glycopeptide fractions were reasonably additive using the spectra of monomeric sialic acid and the asialo-derivatives. This demonstrates that the contributions of sialic acid to the circular dichroic spectrum are nearly additive. The implications of this observation are that covalent attachment of these terminal residues to the oligosaccharides does not lead to strong interactions with other chromophores nor to positioning in particularly asymmetric environment. In contrast, the magnitudes of the observed ellipticity extrema in the circular dichroic spectra of the asialo-derivatives, in which N-acetylglucosamine is the major chromophore, are much greater than can be accounted for on the basis of monomeric contributions (i.e., free N-acetylglucosamine). This finding shows that the optical activity of N-acetyl-glucosamine is greatly influenced by the formation of the carbohydrate core in glycoproteins and suggests the possible formation of secondary structure in the carbohydrate moiety.

Amino Acids↗
PubMed1982

Amino acid composition of gliadin fractions which may be toxic to individuals with coeliac disease.

Fraction 9, prepared by chromatography of a peptic-tryptic-pancreatinic digest of gliadin on S.P. Sephadex C-25, was re-chromatographed on Q.A.E. Sephadex A-25 and subfractions 9-1 and 9-2 further purified on S.P. Sephadex C-25. Sub-fractions 9-1 and 9-2 and the purified sub-fractions 9-1B and 9-2B appeared to be toxic to patients with coeliac disease on the basis of causing a reduction in D-xylose absorption. Amino acid analysis of undigested residues from sub-fractions 9-1B and 9-2B obtained after 'in vitro' digestion with remission coeliac mucosa contained mainly glutamine/glutamic acid and proline with some serine, leucine, phenylalanine and glycine. Another fraction (fraction 3) of wheat gliadin prepared by peptic-tryptic digestion and ion-exchange chromatography on S.P. Sephadex, previously shown to produce a skin-reaction in adults with coeliac disease, has been further purified by ion exchange chromatography, isoelectric focusing and gel filtration. The sub-fractions were submitted to amino acid analysis and the results compared with those from the undigested residues above. Isoelectric focusing of fraction 3 of the P.T. digest and its sub-fractions showed the presence of peptides of pI approximately 4.8 and 5.6 with only small amounts of peptides on either side of this region. Mucosal digestion of fractions of peptic-tryptic-pancreatinic gliadin digests 'in vitro' appears to be a promising method for the elucidation of the primary structure of that section of the gliadin which may be responsible for the lesion in coeliac disease. The evaluation of higher molecular mass peptic-tryptic digests by intradermal skin tests could also be useful for the preliminary screening of fractions for feeding tests, but this approach seems less likely to indicate the toxic region of the gliadin molecule.

Adult↗
PubMed1986

Cell fractions from rat rib growth cartilage. Biochemical characterization of matrix molecules.

In an attempt to isolate and characterize the putative target cells for growth hormone, chondrocytes were isolated from rat rib growth cartilage and fractionated by centrifugation in a discontinuous Percoll gradient. This resulted in three cell fractions with differing properties. The fraction with the lowest density consisted mainly of large, lipid-containing cells which became flattened in subsequent culture. The cells in this fraction were fair collagen producers but synthesized only minor amounts of proteoglycans and apparently no proteoglycan aggregates. These cells probably originate in the hypertrophy zone of the growth plate. The fraction with highest density, on the other hand, consisted of small cells which upon cell culture became polygonal and surrounded with refractile matrix. They synthesized less collagen, but more proteoglycans than the low-density fraction. The proportion of proteoglycan aggregates was rather low (10-20%) but otherwise the proteoglycans were similar to those synthesized by other chondrocytes. This cell fraction was tentatively identified as cells from the upper part of the growth plate. Finally, the middle fraction was heterogeneous, consisting of cells of varying shape. This fraction synthesized large amounts of both collagen and proteoglycans. In all three cell fractions, type II collagen predominated. There were also minor amounts of (1a, 2a, 3a) collagen, and, in the two denser fractions, of type I collagen.

Animals↗
PubMed1991

Separation of Alternaria into protein and carbohydrate fractions with phenyl sepharose.

To evaluate the contribution of high carbohydrate-containing fractions to the allergen content of Alternaria, samples of an Alternaria extract were bound to a phenyl Sepharose column and eluted with Tris buffer containing 4, 2, and 1 mol/L of NaCl and then distilled water. The fractions were dialyzed and lyophilized. The 4 mol/L fraction accounted for 79% of the dry weight and most of the carbohydrate content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the fractions demonstrated significant interfraction differences with the largest number of silver-stained bands in the H2O fraction. Although individual differences in skin reactivity to the fractions were present, geometric means of histamine equivalent pricks were approximately the same with only a 0.5 log dilution higher potency for the 1 mol/L and H2O fractions. The 50% IgE ELISA-inhibition concentration was 100 micrograms/ml for the 1 mol/L and distilled water fractions and 10 micrograms/ml for the other fractions. Since the 4 mol/L fraction accounted for most of the dry weight and had the highest carbohydrate to protein ratio (5.8), purification of Alternaria extracts by removal of carbohydrate fractions may result in significant loss of allergenic material.

Adolescent↗
PubMed1993

Effect of small doses per fraction in rat spinal cord: influence of initial vs. final top-up doses.

Previous data suggested that the linear-quadratic (LQ) model underestimated the sparing effect of small doses per fraction on the radiation tolerance of rat cervical spinal cord when 24 h was allowed between fractions for repair. In these experiments, animals had been given initial top-up doses consisting of 3 daily fractions of 9 Gy to represent 75% tolerance, followed by small fractionated doses in 1, 10, 20, 30 and 40 fractions given once daily. The end-point was forelimb paralysis secondary to white matter necrosis. To assess the possible perturbation of the initial top-up doses on the biological system, an experiment was performed with the small fractionated doses given initially, followed by the same top-up (final top-up) doses. The ED50s for 1, 10, 20, 30 and 40 fractions followed by final top-up doses were 9.5 +/- 0.3, 22.6 +/- 0.6, 32.4 +/- 0.6, 37.7 +/- 0.8 and 41.7 +/- 0.9 Gy, respectively; the corresponding ED50s obtained from the initial top-up experiment were 10.0 +/- 0.4, 20.7 +/- 0.5, 30.0 +/- 0.8, 37.0 +/- 0.8 and 39.9 +/- 0.7 Gy for 1, 10, 20, 30 and 40 fractions, respectively. Using the direct method of analysis and assuming complete repair between fractions, data from both experiments were not adequately described by the LQ model, which gave small alpha/beta values of 0.97 Gy for the initial top-up experiment and 1.23 Gy for the final top-up experiment, in contrast to an alpha/beta value of 2.41 Gy for the experiment with full course fractionation, fraction sizes down to 2 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Radiotherapy of the rhabdomyosarcoma R1H of the rat: the influence of the number of fractions on tumor and skin response.

The influence of the number of fractions on tumor and skin response to fractionated irradiation was studied. R1H rhabdomyosarcomas of the rat (volume doubling time 3 days) were irradiated with 6, 18, 30, or 42 fractions in 6 weeks. Total doses of 45, 60, or 75 Gy were applied in each fractionation scheme, that is, the dose per fraction ranged from 1.07 to 12.5 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. A clearcut reduction of skin damage was observed with increasing number of fractions, whereas the tumor response was found to be the same whether the dose was given in 6, 18, 30, or 42 fractions. Thus, the fractionation regimens were more effective than expected from calculations based on single-dose in situ survival curves. This result can be explained by assuming that the clonogenic tumor cells become less hypoxic with increasing number of fractions. Since normal tissue damage decreases with increasing number of fractions, the therapeutic gain may be improved by applying a greater number of fractions.

Animals↗
PubMed1996

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)

OBJECTIVES: This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. BACKGROUND: Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. METHODS: The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. RESULTS: In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). CONCLUSIONS: In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.

Aged↗
PubMed2005

Persistent organic pollutants in soil density fractions: distribution and sorption strength.

The sorption strength of persistent organic pollutants in soils may vary among different soil organic matter (SOM) pools. We hypothesized that polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were unevenly distributed and had different soil organic carbon (SOC)-water partition coefficients (K(OC)) among soil density fractions. We determined the concentrations and K(OC) values of 20 PAHs and 12 PCBs in bulk samples and three density fractions (light, <2.0, medium, 2.0-2.4, and heavy, >2.4 g cm(-3)) of 11 urban topsoils (0-5 cm) from Bayreuth, Germany. The K(OC) values were determined using sequential extraction with methanol-water mixtures (35% and 65% methanol) at 60 degrees C. The sum of 20 PAH concentrations in bulk soil ranged 0.4-186 mg kg(-1), and that of 12 PCB concentrations 1.2-158 microg kg(-1). The concentrations of all PAHs and PCBs decreased in the order light>medium>heavy fraction. When normalized to the SOC concentrations, PAH concentrations were significantly higher in the heavy than in the other density fractions. The K(OC) values of the PAHs in density fractions were 3-20 times higher than those of the PCBs with similar octanol-water partition coefficients (K(OW)). The K(OC) values of individual PAHs and PCBs varied up to a factor of 1000 among the studied soils and density fractions. The K(OC) values of 5- and 6-ring PAHs tended to be highest in the heavy fraction, coinciding with their enrichment in this fraction. For the other PAHs and all PCBs, the K(OC) values did not differ among the density fractions. Thus, there is no relationship between sorption strength and distribution among density fractions, indicating that density fractionation is not a suitable tool to distinguish among differently reactive PAH and PCB pools in soils.

Absorption↗