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At least 1,261 records · Page 70Linked to original sources
PubMed2006

[Effect of HepG2 cells modified with CD80-IgG1 Fc fusion protein on anti-tumor immune response by lymphocytes].

AIM: To investigate the anti-tumor immune response of lymphocytes elicited by HepG2 cells modified with CD80-IgG1 Fc fragment fusion protein (CD80-Fc). METHODS: HepG2 cells were modified with CD80-Fc, then the expression of CD80 on the cell surface was analyzed by flow cytometry (FCM). After mixed lymphocyte-tumour cell reaction (MLTR) of the modified HepG2 cells and peripheral lymphocytes of healthy volunteers, the proliferation and cytotoxicity of the lymphocytes were tested by MTT colorimetry and LDH release assay,respectively. RESULTS: CD80-Fc could be efficiently bound on HepG2 cells. HepG2 cells modified with CD80-Fc fusion protein dramatically elicited proliferation and cytotoxicity of normal lymphocytes. CONCLUSION: CD80 may play an important role in anti-tumour immune response. HepG2 cells modified with CD80-Fc fusion protein can elicited potent anti-tumor immune response. This fusion protein provides a convenient means for further potential use in immunotherapy of tumor.

Animals↗
PubMed2006

[Rh antigen stability of mPEG modified red blood cells].

The objective of study was to investigate the Rh antigen stability of mPEG-modified RBC. RBC membrane protein SDS-PAGE technology was used to analyze the combination of the mPEG modified RBC membrane protein with mPEG molecules; the RBC ghost coagulation test and 4 degrees C CPD-preserved modified RBC mixed with matched blood were used to observe the stability of RBC Rh antigen camouflaged by mPEG. The results showed that the blood groups of stored mPEG-modified RBC were kept consistency before or after simulating transfusion, i.e. mixture of modified RBC with matched bloods, while the plasma hemoglobin after simulating transfusion was not only within the normal range during the storage, but also less than that before simulating transfusion even after incubation at 37 degrees C. The electrophoresis pattern stained with iodine and Coomassie blue displayed the bands of mPEG combined with RBC membrane protein and the slow mobility of membrane protein. The hemagglutination of PEGylation RBC ghosts did not take place and mPEG still covered the antigen. In conclusion, mPEG-SPA can bind the erythrocyte with its extracted membrane protein in both ghosts and living erythrocytes.

Erythrocyte Membrane↗
PubMed1991

Induction of in vivo hyporesponsiveness to contact allergens by hapten-modified Ia+ keratinocytes.

Because our previous in vitro studies of hapten-modified Ia+ keratinocytes (KC) indicated that these cells induced anergy in Ag-specific Th1 cells, we assayed such cells for their ability to induce unresponsiveness in an in vivo animal model system of delayed type hypersensitivity (allergic contact dermatitis). Naive animals that were treated with i.p. injections of FITC-modified Ia+ cultured Langerhans cells (cLC) developed allergic contact dermatitis to subsequent hapten challenge; whereas, animals treated with similar doses of FITC-Ia+ KC failed to become sensitized to epicutaneous application of FITC, as evidenced by absent ear swelling responses to a FITC challenge. Those animals that were first treated with intraperitoneal injections of hapten modified Ia+ KC could not be sensitized when they were subsequently exposed to sensitizing doses of FITC; whereas a similar first exposure to FITC-cultured Langerhans cells did not interfere with epicutaneous sensitization. This hyporesponsiveness to sensitization was hapten specific, as FITC-Ia+ KC-treated animals were hyporesponsive only to FITC but not to the irrelevant hapten, TNCB. Additionally, Ia- KC failed to induce unresponsiveness. Additional studies indicate that the hyporesponsiveness was not passively transferrable with splenocytes and was not related to the I-J MHC locus. In contrast to our in vitro studies, the unresponsiveness induced by hapten-modified Ia+ KC in vivo was transient in nature. These data indicate that hapten-modified Ia+ KC function in vivo as nonstimulatory accessory cells, by generating down-regulatory signals that can interfere with the induction of contact hypersensitivity.

Allergens↗
PubMed1976

Polyunsaturated meat and dairy products in fat-modified food patterns for hyperlipidemia.

Polyunsaturated meat and dairy products were compared with their saturated counterparts to determine their usefulness in a fat-modified diet for hyperlipidemic persons and their spouses. These polyunsaturated animal products were produced by feeding cattle a supplement of oil droplets coated with denatured protein. As a result, the polyunsaturated fatty acid content was 27 to 28 per cent of the meat fat and butterfat; saturated fatty acids (C12:0 to tc16:0) were 18 to 19 per cent. Of the eleven free-living subjects three were normocholesteremic, three had type IIa hyperlipidemia and five had type VI (IIb). In the fourteen-week study, an adjustment period of three weeks was followed by two consecutive experimental periods of four weeks each, then by a three-week follow-up period. During the adjustment period, participants continued to follow their usual eating patterns. During both experimental periods all followed the same prescribed fat modified food pattern using polyunsaturated margarine and oil. Five participants ate polyunsaturated beef and dairy products during the first experimental period and their saturated counterparts in the second; six participants ate saturated products first, then polyunsaturated. During the follow-up period, all participants selected all their own food. Serum cholesterol levels in five participants who had not previously followed a fat-modified diet were reduced by 18 per cent with polyunsaturated animal products and 11 per cent with saturated products. Serum cholesterol in six participants, previously on a fat-modified diet, was not significantly changed with polyunsaturated products. In ten of eleven participants, serum cholesterol levels were an average of 6 per cent lower with polyunsaturated products than with saturated products. It is concluded that polyunsaturated animal products are suitable for use in fat-modified food patterns for reducing hyperlipidemia, with some restrictions in the amount of polyunsaturated animal fat and with the inclusion of polyunsaturated oil and margarine.

Adult↗
PubMed1991

Evaluation of the modified Baermann's method in the laboratory diagnosis of Strongyloides stercoralis.

This study compares the modified Baermann's method with the formol-ether concentration and the direct/saline techniques in the diagnosis of Strongyloides stercoralis larvae in stool specimens. This study was conducted at Wonji-Shewa Sugar Estate located at about 110 kms. south east of Addis Abeba. Of the 718 randomly selected and examined stool specimens, 125 were found positive for Strongyloides stercoralis. Of these 98% were recovered by the modified Baermann's method, 23% by the formol-ether, and 22% by the direct saline techniques. The rate of recovery by the modified Baermann's method was significantly different (p less than 0.001) compared with those of the direct and the formol-ether concentration techniques. There was no difference (p greater than 0.1) between the direct saline and the formol-ether methods. The modified Baermann's method accounted for over 60% of the total positive findings. Furthermore, the sensitivity of the method excelled the other two techniques by four fold. Thus, the modified Baermann's method by the Merck and Sharp Dohme Company is effective, cheap and simple to use and hence recommended for routine use and epidemiological surveys.

Adolescent↗
PubMed1989

Ethanol induces the production of antibodies to acetaldehyde-modified epitopes in rats.

Rats treated with ethanol for periods of 3-27 months were found to produce an immune response to acetaldehyde-modified proteins, whereas treatment for a shorter period (3 weeks) did not lead to such a response. The reactivity towards the modified proteins was shown to be independent of the carrier protein as antibodies were reactive with modified human plasma proteins and modified bovine haemoglobin. The data presented here support the hypothesis that acetaldehyde-modified proteins may act as neoantigens in alcoholics and may play a role in the aetiology of alcoholic liver disease.

Acetaldehyde↗
PubMed1989

Radioimmunoscintigraphy and radioimmunotherapy in nude mouse models. Studies with site-specifically modified monoclonal antibodies.

Site-specific covalent modification of monoclonal antibodies at the oligosaccharide offers advantages over more conventional modification processes that involve direct attachment at tyrosine, lysine or glutamic/aspartic acid side chains. Using the site-specific modification process, attachment sites on the antibody are distal to the antigen-binding region. Thus, homogeneity of antigen-binding properties and affinity for the unmodified protein are preserved. Furthermore, higher derivatization ratios with no resultant loss of immunoreactivity can be achieved for monoclonal antibodies modified at the oligosaccharide. In vivo biodistribution and tumor localization studies in nude mouse models suggest that antibodies radiolabeled at their oligosaccharide might represent improved immunoscintigraphic reagents. In a variety of tumor xenograft models, site-specific modified 111In-labeled antibody conjugates localized to the tumor site with little non-specific localization in other tissues or organs. The degree of localization at the target site was substantially greater than that of 111In-labeled antibodies directly modified at the tyrosine side chain. Preliminary studies with 212Bi- and 90Y-labeled antibodies modified at the oligosaccharide indicate that both of these radioisotopes have immunotherapeutic potential. Because of its preferential uptake by the kidney, the use of 212Bi may be best suited for tumors localized within the peritoneal cavity, such as ovarian and colorectal carcinomas. The toxicity of 90Y at high specific activities suggests that a regimen of repeated smaller doses of this radioisotope is best suited for therapeutic use. Studies in tumor-bearing mouse models are currently underway to better define the optimal dosage and administration regimens for both of these radioisotopes when attached to site-specific modified antibodies.

Animals↗
PubMed1989

[Extracorporeal lithotripsy using the HM3 Dornier lithotriptor and the modified HM3 lithotriptor].

Extracorporeal shock waves lithotripsy is a well established procedure for the treatment of renal and ureteral calculi. From January 1985 to December 1987, 1034 patients underwent 1152 treatments with the Dornier HM3 lithotripter; from January 1988 and December 1988, 466 patients underwent 566 treatments with the modified Dornier HM3. Treatments with the original HM3 were performed mainly under general anaesthesia (97%). Only 2.4% of modified Dornier HM3 treatments have been performed under general anaesthesia; the 97.6% were treated under a combination of anxiolytic and analgesic drugs. An average of 1900 and 2300 shock waves was applied with the original HM3 and the modified one, respectively. The rate of secondary treatment increased from 10.3% to 17.4% respectively. At three month follow-up the 85.6% of the patients treated with the original HM3 and the 76.7% of those treated with the modified Dornier were free from stones. Low energy lithotripsy with the modified semi ellipsoid has proved to be equally effective as the older generators working with high shock wave pressure.

Follow-Up Studies↗
PubMed1989

[Chemical modifiers in radiotherapy].

The halogenated pyrimidine analogue bromodeoxyuridine (BrdU), which is incorporated into nuclei during DNA synthesis, has long been known to be a radiation sensitizer. Since 1965, BAR therapy (BrdU-antimetabolite-radiation therapy), in which BrdU was administered intraarterially as a radiosensitizer, has been applied to patients with malignant gliomas and the improvement in survival rate within two years has been reported. Recently, intravenous infusion of BrdU has prove to be sufficiently effective as a radiosensitizer and BrdU is still being utilized as a chemical modifier for patients with malignant gliomas. Misonidazole was developed as a hypoxic cell sensitizer and was expected to enhance the radiation response of malignant tumors. However, the clinical trial of misonidazole in patients with brain tumors showed little clinical benefit of this agent as a radiosensitizer, and therefore it is no longer used in the treatment of malignant gliomas. Synchronized chemoradiotherapy, in which alkaloid and alkyl agents are used to accumulate cells into the radiosensitive G2 and M phases, was developed for the treatment of malignant gliomas in 1976 and significant improvement in survival has been reported. However, phase II studies demonstrated that radiotherapy with alkyl agents such as BCNU and ACNU did not prolong the survival of patients with malignant gliomas as compared with radiotherapy alone, although they did increase the response rate. Since 1985, the Brain Tumor Interferon Study Group has clinically applied one of the biological response modifiers (BRM), interferon-beta (INF-beta) as a chemical modifier in patient with malignant gliomas. They have reported that the response rates in patients treated with ACNU + radiation and INF-beta + ACNU + radiation were 19.6% and 41.2%, respectively. Their results suggested that IFN-beta with ACNU was a promising regimen as a chemical modifier in radiotherapy for patients with malignant gliomas. In order to improve the rate of local control of malignant gliomas and to prolong the survival of patients, it is necessary to continue to seek effective chemical modifiers including BRMs, as well as to develop irradiation techniques.

Brain Neoplasms↗
PubMed1989

Relationships between knowledge and experience in the use of disease-modifying antirheumatic agents. A study of primary care practitioners.

The timely dissemination of new medical information is a complex and often faulty process. We surveyed primary care physicians to determine their knowledge and use of disease-modifying antirheumatic agents for the treatment of rheumatoid arthritis. Only 26.2% of patients hospitalized for rheumatoid arthritis had been treated with disease-modifying antirheumatic agents in the past, and 13.9% were presently receiving them. When responding to a clinical vignette on rheumatoid arthritis, only 12% (10/84) of practitioners would implement therapy with disease-modifying antirheumatic agents, while the majority would refer the patient to a rheumatologist. Experience with similar patients was clearly the factor that led to initiation of therapy. While 73% of practitioners were aware of the value of disease-modifying antirheumatic agents, only 14% prescribed them in the last year. These findings suggest that dissemination of information concerning disease-modifying antirheumatic agents has been successful, but the problems inherent in their use result in referral rather than initiation of therapy.

Adult↗
PubMed1988

Catalytic properties of chloroplast F1-ATPase modified at catalytic or noncatalytic sites by 2-azido adenine nucleotides.

When heat-activated F1-ATPase from chloroplasts was repeatedly exposed to Mg2+ and 2-azido-ATP, followed by separation from medium nucleotides and photolysis, a total of two sites per enzyme, both catalytic and noncatalytic, were labeled. In a coupled assay with pyruvate kinase about half the activity was lost when one site per enzyme was modified. However, increased modification resulted in no further loss of activity. In contrast, methanol-sulfite activation of the enzyme showed a loss of most of the catalytic capacity when one site per enzyme was modified. Predominant labeling of either one catalytic or one noncatalytic site caused a loss of most of the activity in either assay. An indication that the enzyme modified at one site retained some catalytic activity was verified by measurement of the [18O]Pi species formed when [gamma-18O]ATP was hydrolyzed by partially derivatized enzyme. With either catalytic or noncatalytic site modification, the distributions of [18O]Pi species formed showed that the modified enzyme had different catalytic characteristics. An interpretation is that with modification by azido nucleotides at either catalytic or noncatalytic sites, capacity for rapid catalysis is largely lost but the remaining sites retain weak modified catalytic properties.

Adenosine Diphosphate↗
PubMed1985

Stimulation of rat ovarian cell steroidogenesis by high density lipoproteins modified with tetranitromethane.

Human high density lipoprotein (devoid of apo-E) was modified by nitration of tyrosine residues with tetranitromethane. As a result of extensive cross-linking, monomeric apo-A-I was markedly depleted, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the modified HDL did not effectively bind to high-affinity sites present on dispersed rat ovarian cells and isolated rat ovarian membranes. Nonetheless, the modified HDL retained the ability to stimulate steroidogenesis by both dispersed rat ovarian cells and cultured rat granulosa cells to a degree at least equal to that of native HDL. Modified HDL stimulated luteal steroidogenesis under basal conditions and when cells were stimulated with luteinizing hormone or 8-bromo-cAMP. Although modified HDL did not effectively bind to high-affinity sites, it exhibited substantial "nonspecific" or "low-affinity" binding which was not displaceable by native HDL. These data suggest that high-affinity binding is not an essential event in the "HDL pathway" and that HDL can deliver its sterols through low-affinity cellular associations.

Animals↗
PubMed1986

Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia.

For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L-asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction.

Adolescent↗
PubMed1988

Use of the modified barium swallow in the rehabilitation of the swallowing mechanism.

Swallowing is a rapid, dynamic and complex process. Surgical treatment of head and neck malignancies produces significant alterations in the swallowing mechanism. The modified barium swallow allows assessment of these physiologic and anatomic derangements in the postoperative patient. Small amounts of liquid barium, barium paste and a cookie coated with barium are ingested by the patient and the swallowing mechanism is recorded by videofluoroscopy. Unlike the routine barium swallow in which only the esophageal stage of swallowing is studied, using the modified barium swallow all four stages of swallowing are studied with particular emphasis on the oral and pharyngeal stages. Our experience with the modified barium swallow has shown it to be a valuable adjunct in the rehabilitation of the post-surgical patient allowing the otolaryngologist and speech pathologist to identify and modify swallowing abnormalities. Presentation of specific swallowing mechanism deficits as demonstrated using the modified barium swallow will be shown and appropriate therapeutic interventions discussed.

Aged↗
PubMed1978

[Chemical modification of lysine epsilon-NH2-groups in horseradish peroxidase. Its effect on enzyme stability. Temperature dependence of thermo-inactivation constants for native and modified peroxidase].

Thermostability of horseradish peroxidase modified by acetic, propionic, butyric, valeric and succinic anhydrides and trinitrobenzolsulfonic acid (TNBS) is studied within the temperature range of 56-80 degrees C. Acylation of 4 amino groups and arylation of 3 amino groups with TNBS are found to stabilize the enzyme, while modification of 6 groups decreases the enzyme stability. Chemical modification of peroxidase does not change its pH-dependence with respect to enzyme thermostability. Thermodynamic activation parameters of irreversible thermoinactivation are determined for native and modified peroxidase. Native peroxidase has deltaH not equal to = 30+/-1 kcal/mole and deltaS not equal to = 14 e. e.; modified by acid anhydrides peroxidase has deltaH not equal to within 64-87 kcal/mole and deltaS not equal to within 110-178 e. e. depending on the nature of a modifying agent. The effect of the structure of a radical introduced into the enzyme molecule, and of a number of modified epsilon-amino groups on thermoinactivation deltaH not equal to and deltaS not equal to values is discussed.

Acylation↗
PubMed1988

The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein.

Previous studies from several laboratories have shown that thrombin is inactivated by tetranitromethane with the formation of nitrotyrosine. The inactivation is characterized by an apparently greater loss of fibrinogen-clotting activity than activity toward synthetic ester substrates, suggesting that the residues modified by tetranitromethane are involved in the interaction of thrombin with fibrinogen. This study was designed 1) to determine the effect of solvent conditions on the rate of modification and the stoichiometry of the reaction of tetranitromethane with bovine alpha-thrombin; 2) to identify the residue(s) modified; and 3) to characterize the modified enzyme with respect to its interaction with peptide nitroanilide substrates and fibrinogen. The inactivation of thrombin by tetranitromethane proceeded more rapidly in 50 mM Tris, pH 8.0, than in 50 mM sodium phosphate, 100 mM NaCl, pH 8.0. Approximately 10% fibrinogen-clotting activity remained at maximal inactivation. A study of the effect of tetranitromethane concentration on the rate of inactivation suggested that the loss of activity was the result of the modification of 1 mol of tyrosine/mol of thrombin. A similar result was obtained from the analysis of the extent of inactivation as a function of the extent of protein modification. Structural analysis of the modified protein showed substantial modification at both Tyr71 and Tyr85. Enzyme kinetic studies were performed with the modified protein and a control thrombin with N2-tosylglycylprolylarginine p-nitroanilide. H-D-phenylalanylpipecolylarginine p-nitronailide, and purified bovine fibrinogen. With all three substrates, a substantial decrease in kcat was observed, whereas there was essentially no change in Km. These results suggest that, contrary to previous suggestions, the modification of Tyr71 and Tyr85 in thrombin does not influence the binding of substrates, but rather influences active site reactivity.

Animals↗
PubMed1988

Modulation of stimulus-dependent human platelet activation by C-reactive protein modified with active oxygen species.

C-reactive protein (CRP) is one of the most characteristic acute phase proteins which appear in the serum during certain inflammatory diseases. We report here that human CRP acquired the ability to augment platelet reactivity when treated with an Fe2+ (Cu2+)-ascorbate system. CRP modified by such treatment showed no appreciable activation of platelets in the absence of platelet activators such as platelet-activating factor, thrombin, or ADP. However, in the presence of the modified-CRP, irreversible activation of platelets occurred with sub-optimal doses of platelet-activating factor and other stimulatory agents for platelets. CRP without any treatment did not show any modulating activity. Each component of the Fe2+-ascorbate system was required for modification of CRP, suggesting that CRP was modified through an oxidative process. The modification of the CRP structure was confirmed by the change in the fluorescence spectrum of 8-anilino-1-naphthalene sulfonate complexed with CRP, the increased susceptibility of CRP to proteolytic enzymes and the altered reactivity to anti-CRP mAb. We also found an inactivating system for the modified CRP in plasma. The modified human CRP did not show any modulating activity toward rabbit platelets, suggesting that the activity is species specific.

Ascorbic Acid↗
PubMed1987

Clinical comparison between original and modified distal splenorenal shunts.

This article reports on a retrospective clinical comparison between the original Warren shunt and one that we modified with Gore-Tex (expanded polytetrafluoroethylene) interposition. The former operation was performed on 35 patients between June 1969 and November 1983 and the latter on 29 patients between October 1983 and January 1986. There were no significant differences in the patients' backgrounds between the two study groups. Blood loss during surgery was significantly greater and operation time was longer in the original shunt group than in the modified shunt group. The incidence of postoperative morbidity and mortality was also significantly higher in the former group than in the latter (major complication rate: 20.0% versus 3.4%; operative death within 1 month: 5.7% versus 0%; in-hospital death: 11.4% versus 3.4%). The modified shunts had a 100% patency rate, and no variceal bleeding was evident, whereas shunt occlusion was observed in two patients and portal thrombosis in one patient of the original shunt group. The incidence of hepatic encephalopathy was 14.3% in the original shunt group and 6.9% in the modified shunt group, and the follow-up time was shorter in the latter group. A significantly greater rate of survival was achieved with the modified Warren shunts. Thus the current study seems to indicate that our modifications could be alternatives to the original distal splenorenal shunt in terms of postoperative morbidity, mortality, and survival.

Adult↗