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At least 235 records · Page 13Linked to original sources
PubMed1996

Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party.

In patients with non-metastatic but inoperable non-small cell lung cancer that is locally too extensive for radical radiotherapy (RT), but who have good performance status, it is important to determine whether thoracic RT should be the minimum that is required to palliate thoracic symptoms or whether treatment should be more intensive, with the aim of prolonging survival. A total of 509 such patients from 11 centres in the UK between November 1989 and October 1992 were admitted to a trial comparing palliative versus more intensive RT with respect to survival and quality of life. They were allocated at random to receive thoracic RT with either 17 Gy in two fractions (F2) 1 week apart (255 patients) or 39 Gy in 13 fractions (F13) 5 days per week (254 patients). Survival was better in the F13 group, the median survival periods being 7 months in the F2 group compared with 9 months in the F13 group, and the survival rates 31% and 36% at one year and 9% and 12% at 2 years, respectively (hazard ratio = 0.82; 95% CI0.69-0.99). There was a suggestion of a trend towards greater benefit in fitter patients. Metastases appeared earlier in the F2 group. As recorded by patients using the Rotterdam Symptom Checklist, the commonest symptoms on admission were cough, shortness of breath, tiredness, lack of energy, worrying and chest pain. These were more rapidly palliated by the F2 regimen. Psychological distress was generally lower in the F13 group. Three patients (two F13, one F2) exhibited evidence of myelopathy. As recorded by patients using a diary card, 76% of the F2 compared with 81% of the F13 patients had dysphagia associated with their RT. This was transient, lasting for a median of 6.5 days in the F2 group compared with 14 days in the F13 group. In conclusion, the F2 regimen had a more rapid palliative effect. In the F13 group, although treatment-related dysphagia was worse, survival was longer.

Aged↗
PubMed2003

Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction.

We have previously isolated a lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal agent, by affinity chromatography on a CNBr-activated Sepharose 4B bound TS-2 monoclonal antibody (mAb) that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. In the current study, we compared the cytokine-inducing and anti-tumor activities of OK-PSA, a TS-2-binding fraction, with those of OK-PTF, a TS-2-unbinding fraction, in order to determine the efficacy of OK-PSA for clinical use in affinity chromatography using TS-2. In the in vitro experiments using human peripheral blood mononuclear cells (PBMCs), OK-PSA markedly induced Th1-type cytokines, while interleukin (IL)-6 and IL-10, Th2-type cytokines, were induced by OK-PTF. Th1-cytokine induction by OK-PTF was not dose-dependent and was suppressed when PBMCs were treated with a high concentration of OK-PTF. In a mouse model, Th1 cytokines were also induced by OK-PSA and Th2 cytokines were induced by OK-PTF. Th2 cytokine-inducing activity of OK-PTF was accelerated in tumor-bearing mice relative to that in healthy mice. Although the anti-tumor effect of OK-PTF was statistically significant, it was much weaker than that of OK-PSA. A significant difference between the anti-tumor effect of OK-PSA and that of OK-PTF was observed (P<0.05). Finally, OK-PSA elicited its cytokine-inducing effect via Toll-like receptor (TLR) 4, whereas OK-PTF-induced signaling was mediated by both TLR2 and TLR4. These findings strongly suggested that the affinity chromatography using TS-2 is a useful strategy to separate the effective component for cancer therapy (OK-PSA) from other components.

Animals↗
PubMed2002

Distribution of gamma-glutamyl-beta-alanylhistidine isopeptide in the macromolecular fractions of commercial meat extracts and correlation with the color of the macromolecular fractions.

The measurement of gamma-glutamyl-beta-alanylhistidine isopeptide in the macromolecular fraction of various commercial meat extracts indicated that all of the commercial meat extracts tested contained the isopeptide, in concentrations ranging from 0.04 to 0.87 micromol/g of dry matter. This variation was suggested to be due to the differences between the processes of extraction and the differences in the initial amounts of carnosine. A positive correlation between the content of gamma-glutamyl-beta-alanylhistidine and the color of the macromolecular fraction was observed. These results suggested that gamma-glutamyl-beta-alanylhistidine is widely distributed in meat products and that the content can be used as an index of protein denaturation during the heating process.

Amino Acids↗
PubMed1992

A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party.

Two policies of palliative thoracic radiotherapy for NSCLC have been compared in a randomised multicentre controlled trial aimed at simplifying the palliative treatment of patients with poor performance status. A total of 235 patients were entered. They had inoperable, microscopically confirmed disease, too advanced for 'curative' radiotherapy. Their main symptoms were related to the primary intrathoracic tumour even if metastases were present, and they had a poor performance status. Patients were allocated at random to regimens of either 17 Gy given in two fractions of 8.5 Gy 1 week apart (F2 regimen, 117 patients), or a single fraction of 10 Gy (F1 regimen, 118 patients). Two patients (one in each group) were excluded from all analyses because they were found to have had previously treated malignant disease and had been admitted in error. On admission, 95% of the 233 eligible patients had cough, 47% haemoptysis, 59% chest pain, 64% anorexia, and 16% dysphagia. As assessed by the clinicians, these symptoms were palliated in high proportions of patients, ranging in the F2 group from 48% for cough to 75% for haemoptysis, and in the F1 group from 55% for anorexia to 72% for haemoptysis and chest pain. For all five symptoms the median duration of palliation was 50% or more of survival. All these results were similar in the two treatment groups. In contrast, on daily assessment by the patients using a diary card, those treated with the F2 regimen experienced substantially more dysphagia, which was recorded in 56% of the patients compared with 23% in the F1 group (difference 33%: 95% confidence interval 17-48%). The median survival from randomisation was 100 days in the F2 group and 122 days in the F1 group. The F1 regimen, as it requires only a single attendance for treatment, is recommended as a palliative regimen for patients with inoperable NSCLC and a poor performance status.

Carcinoma, Non-Small-Cell Lung↗
PubMed1986

Studies on an antineoplastic fraction from human urine. Characterization of the major protein in this fraction.

A fraction has been isolated from human urine which exhibits antiproliferative activity against human tumour cell lines without affecting the growth of several normal diploid cell lines or tumour cells of mouse or hamster origin. The major protein present in this fraction has been characterized and tentatively designated antineoplastic urinary protein (ANUP). An S020,W value of 3.69 S was obtained by sedimentation velocity analysis, and a subunit molecular mass of 16 300 Da was obtained by sedimentation equilibrium and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Centrifugation data also indicated that the protein self-associates. The amino acid analysis of ANUP was consistent with its low pI (4.2) as determined by chromatofocusing analysis. Furthermore, the amino acid composition exhibited some features similar to collagen, as shown by high levels of proline and glycine, the absence of cysteine, and the presence of low levels of hydroxyproline.

Amino Acids↗
PubMedDate not supplied

Stability of rat lung and liver microsomal cytochrome P-450 enzyme activities to storage: purified microsomal fraction, postmitochondrial fraction, and whole tissue.

The ability to maintain cytochrome P-450 enzyme levels in stored tissue samples is necessary in order to properly utilize this enzyme system in toxicological and environmental health studies. The stability of enzyme activities associated with microsomal cytochrome P-450 was investigated to determine the best way to handle large numbers of samples and postmortem or biopsy lung and liver tissue. Long-term storage in cold buffer resulted in diminished activities in purified microsomes and whole tissue. Benzo[a]pyrene hydroxylase and 7-ethoxycoumarin deethylase, however, were stable when the purified microsomal fraction, postmitochondrial fraction, or whole tissue was stored at -80 degrees C, but care should be exercised in the freezing and thawing procedures.

Animals↗
PubMed1959

Studies on fractions of methanol extracts of tubercle bacilli. I. Fractions which increase resistance to infection.

Fractionation procedures yielding partially purified vaccine preparations from a 60 degrees C. methanol extract of tubercle bacilli have been described. Some of the preparations have the characteristics of lipopolysaccharides. Certain ones have been found capable of increasing resistance to experimental tuberculosis in albino mice of the Rockefeller Swiss strain. The levels of resistance elicited by these preparations are equivalent to those following vaccination with BCG (Phipps) in this strain of mice as reported by other authors. The admixture of two of the crude fractions in amounts as small as 0.05 mg. each per dose per mouse affords an even greater increase in resistance. Neither of these substances alone in larger doses can approach this degree of efficacy in mouse protection experiments. The protective activity appears to involve the stimulation of two supplementary mechanisms, one providing a peak resistance between 1 and 3 weeks post vaccination but falling off to a lower level thereafter, the other not responding fully until approximately 6 weeks but continuing undiminished through a 12 week post-vaccination period. The first of these peaks corresponds to an increase in resistance against staphylococci as well as tubercle bacilli. The possibility that the term "broad specificity," rather than "non-specificity," might best describe this phenomenon permits the implication of classical immune mechanisms.

Animals↗
PubMed1960

Studies on fractions of methanol extracts of tubercle bacilli. II. Toxic and allergenic properties of fractions employed as antituberculous vaccine.

Fractions of methanol extract which had been previously demonstrated to increase the resistance of mice to experimental tuberculosis have been subjected to an examination of their toxic and allergenic properties. The criteria for toxicity were: (a) production of inflammatory skin reactions in guinea pigs; (b) induction of weight loss in mice by intraperitoneal injection; and (c) depression of resistance to staphylococcus infections in mice. Allergenicity of a preparation was investigated by (a) its ability to evoke a hypersensitive skin response in guinea pigs previously sensitized with whole tubercle bacilli; and (b) its capacity to induce hypersensitivity to one or more of its components when injected under appropriate conditions into guinea pigs. Fraction F I, a preparation precipitated from methanol extract by slow concentration at 45 degrees C., was found to possess some toxicity and some allergenicity by all of the criteria employed. Subfraction F I-P, precipitated from aqueous suspensions of F I by 33 per cent ethanol and 0.5 per cent NaCl, was apparently the F I component responsible for these activities. The saline-ethanol-soluble subfraction, F I-S, was neither toxic nor allergenic by the tests performed. These findings were considered of particular interest inasmuch as F I-S, despite its small yield, had been shown earlier to be the most active single substance used as vaccine to increase resistance to experimental tuberculosis in mice.

Allergens↗
PubMed1980

Isolation and characterization of sulfated glycoproteins from the brush border fraction and the soluble fraction of rabbit small intestine.

The brush border fraction (Fr. P2) and the calcium chloride (10 mM)-soluble fraction (Fr. S) were separated from the small intestinal mucosa of rabbit. Sulfated glycoproteins, P-SGP and S-SGP, were then purified from Fr. P2 and Fr. S by zone electrophoresis and gel filtration, respectively. P-SGP and S-SGP were both electrophoretically homogeneous, although their mobilities differed from each other. P-SGP and S-SGP contained 61.8 and 35.% protein, 31.8 and 55.0% carbohdyrate, and 1.1 and 2.7% sulfate, respectively. The major constituent sugars in P-SGP and S-SGP were galactose and glucosamine, while mannose, sialic acid, and L-fucose were minor components. In addition, galactosamine was a major sugar in S-SGP, but a minor one in P-SGP. The major amino acids of the protein moiety of P-SGP were glutamic acid, aspartic acid, glycine, and alanine, while those of S-SGP were threonine, proline, glutamic acid, aspartic acid, serine, and glycine.

Amino Acids↗
PubMedDate not supplied

Comparison of left ventricular ejection fraction and regional contractility fraction pre and post coronary angiography.

Thirty patients [four normals, eight with mild and 18 with severe coronary artery disease (CAD)] were studied to evaluate left ventricular function type and post coronary angiography. The end diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF) and the regional contractility fractions (RCF) of eight ventricular segments were evaluated by left ventriculography. The RCF's were analyzed, in addition to the EF's to ascertain the effect of contrast material upon normal and scarred or ischemic segments of the left ventricle, and to rule out spurious findings in the EF due to coexistent reciprocal changes in RCF's. There was good correlation (r = .45 to .97 and p less than .01 to less than .001) in the above parameters of left ventricular function in patients with and without CAD before and after angiography. Thus, although intraventricular and intracoronary injections of contrast material produce transient changes in myocardial contractility, in a clinical setting left ventriculography may be performed prior to or following coronary angiography without danger of spurious results in normals and in patients with CAD.

Adult↗
PubMed1986

Phosphate-activated glutaminase in the crude mitochondrial fraction (P2 fraction) from human brain cortex.

The kinetics and other properties of phosphate-activated glutaminase have for the first time been studied in the crude mitochondrial fraction (P2 fraction) from human brain. The enzyme is for unexplained reasons inactivated postmortem. The enzyme activity decreases by storing the tissue or homogenate at 37 degrees C. The inactivation is not caused by formation of a dialysable inhibiting compound. No large proteolytic degradation has occurred, since the phosphate-activated glutaminase-like immunoreactive band did not disappear during the storage. The molecular weight of the subunit of the enzyme as determined by immunoblots of sodium dodecyl sulfate-treated homogenates from human brain is estimated to be approximately 64 K. The enzyme has been shown to have a pH optimum of 8.6; it is activated by phosphate, inhibited by glutamate, and partially inhibited by ammonia. Double-inverse plots of enzyme activity against phosphate are concave-upward, and more so in the presence of an inhibitor. The inhibition by glutamate appears to be noncompetitive with the substrate glutamine, and competitive with the activator phosphate. These kinetic properties are not significantly different from our earlier observations concerning phosphate-activated glutaminase from pig brain and pig kidney.

Cerebral Cortex↗
PubMed1976

Studies about the adjuvant activity of saponin fractions in foot and mouth disease vaccine. III. Comparison of the irritant, adjuvant and hemolytic activities of six commercial saponins and their hemolytic fractions obtained by chromatography on sephadex G 100.

12 experimental vaccines were prepared to compare the irritant and adjuvant activity in cattle of 6 commercial saponin preparations and their hemolytic fractions. It is still not known if a single substance is responsible for the irritant, adjuvant and hemolytic activities of the saponin preparations. The quantities of saponin added were standardised on the base of a constant hemolytic activity rather than on a weight of powder per dose of vaccine base. A FMD vaccine was used to reveal the adjuvant activity. It was concluded that the irritation is related to the hemolytic activity and not to the weight of powder. Irritation is slightly reduced when a toxic effect appears. The adjuvant activity was higher for untreated saponin preparations with high hemolytic activity used at low dose and for one of the chromatographic saponin fractions. The adjuvant activity is reduced when toxic effect appear. Toxicity of less hemolytic saponins used at high dose is removed by chromatography. Highly hemolytic saponins used at low dose become toxic after chromatographic treatment.

Adjuvants, Immunologic↗
PubMed1977

[Immunochemical study of the antigenic structure of microbes of the genus Bordetella. 5. Fractionation of the extracts of the parapertussis microbes and the study of the immunochemical and biochemical properties of the isolated fractions].

Fractions responsible for the main part of the serological and immunogenic activity differing by the set of antigens were isolated from the salt extracts of parapertussis microbes by gel-filtration on Sephadex G-100, ion exchange chromatography on DEAE-cellulose, and preparative electrophoresis in agar. Fractions, disclosing a sufficiently high serological activity and possessing the immunological properties, but containing the minimal set (2--3 out of 7) antigens, which were included in the initial extract, were isolated in the agar gel in the use of the preparative electrophoresis method.

Antigens, Bacterial↗
PubMed1987

Interstitial cell heterogeneity in rat testes. II. Purification of cells by Percoll and metrizamide gradient centrifugation with preferential localization of gonadotropin binding sites in light cell fraction and hormone-induced steroidogenesis in heavier cell fraction.

The ability of 125I-labeled human chorionic gonadotropin (125I-labeled hCG) to bind and stimulate steroidogenesis was studied in light cells (density, 1.053-1.065 g/cm3) and heavier cells (density, 1.090-1.110 g/cm3) purified from collagenase-dispersed rat testicular interstitial cells by unit gravity sedimentation (Bhalla, V.K., Rajan, V.P., Burgett, A.C., and Sohal, G.S. (1987) J. Biol. Chem. 262, 5313-5321). Preferential localization of gonadotropin binding sites was demonstrated on light cells, and the heavier cells produced testosterone in response to hCG without occupancy of high affinity (Kd = 2.02 X 10(-10) M) binding sites. In this study, established methods for interstitial cell purification involving gradient centrifugation were utilized to demonstrate the cell heterogeneity. Light cells bound hCG with high affinity (Kd = 3 X 10(-10) M) without manifestation of steroidogenic response. The heavier cells responded to hCG with elicitation of steroidogenesis, but the occupancy was negligible. Stimulation of steroidogenesis by hCG in heavier cells was dose and time dependent. Dibutyryl and bromo cyclic AMP (1 mM) also promoted steroidogenesis comparable to a level stimulated by the tropic hormone (700% stimulation). The concept of spare receptors was tested in purified cell fractions. Upon cell purification, no saturable high affinity binding sites were observed in the heavier cell fraction. Autoradiographic analyses at the electron microscopical level supported this conclusion. Our data suggest that target cell activation is not preceded by hormone occupancy of high affinity binding sites. A model for defining the functional domains of the physiological receptor for hCG is presented.

Animals↗
PubMed1978

Studies on column fractionation of immune cells. VII. Electrophoretic mobility and functional behavior of mouse spleen cells after fractionation on a weakly basic ion exchanger.

After passing normal mouse spleen cells through columns of a weakly basic ion-exchanger, the percentage of cells with B cell-typical electrophoretic mobility (EPM) is 90% after fractionation at pH 8.0 and 10--20% at pH 5.0. However, the characterization of fractionated cells with regard to theta-antigen as well as graft-versus-host reaction shows that separation of T- and B-lymphocytes had not occurred. After incubation of the separated cells for 2 h at 37 degrees C the EPM returned to that of unseparated cells. It appears that the net charge of T- and B-lymphocytes is changeable depending on pH, temperature and separation material.

Animals↗
PubMed1986

Stability of acetaldehyde fractions with various hemoglobin fractions.

The stabilities of 14C-acetaldehyde with various hemoglobin fractions (HbA1a + b, HbA1a, and HbA0) were examined by determining amounts of adducts remaining after dialysis at 4 degrees C for various time intervals. Significant differences were found in the stabilities of adducts formed with various hemoglobin fractions. Acetaldehyde adducts formed with HbA1a + b were more stable to dialysis than adducts formed with HbA0 or HbA1c (7-8% of total adducts formed with HbA1a + b were stable to dialysis, compared with 4-5% stable adducts formed with either HbA0 or HbA1c). While only 37-57% of the trichloroacetic acid (TCA) precipitable adducts from HbA0 or HbA1c samples were stable to dialysis, 72-75% of TCA precipitable adducts from HbA1a + b were retained after dialysis. Posttranslational modification of hemoglobin by phosphorylated glycolytic intermediates appears to alter the physical properties of hemoglobin following further modification with acetaldehyde. In view of the increased amounts of glycosylated proteins found in patients with diabetes, these observations may be relevant to the pathogenesis of the sequelae of diabetes and/or alcoholism and the influence of one chronic illness on the other.

Acetaldehyde↗
PubMed1985

[Rational dose fractionation schedule 1. Each fractional dose].

The dose per fraction which will produce the maximum therapeutic ratio in clinical radiotherapy is discussed, using the data on the variation of the oxygen enhancement ratio with dose size and the difference in the dose response curves between tumor cell lines and late effects in normal tissues. Isoeffect doses for late injury increased more than that for tumor response with decreasing dose per fraction. When late effects in normal tissues are dose-limiting for radiotherapy, the highest therapeutic ratio (normal tissue tolerance dose/dose for a given probability of local tumor control) would be obtained when the dose/fraction is equal to the flexure dose. Lengthening the interfraction interval to allow complete repair of sublethal injury in the normal tissues responsible for late effects may allow some repopulation of tumor cells. In this case it may be necessary to increase the dose/fraction slightly above the flexure dose.

Cell Survival↗