SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A study has been made of compatibility among four F-like factors of genetic transfer (pAP22-4, pAP38, pAP39 and pAP41) labeled separately by transpozones Tn1 and Tn9. It has been established that pAP38 transfer factor is compatible with plasmids pAP22-4, pAP39 and pAP412, while pAP41 transfer factor is compatible with plasmids pAP22-4 and pAP38 but is incompatible with plasmid pAP39.
Results of therapeutic trials of transfer factor in a number of laboratories suggest clinical benefit and enhancement of immunological reactivity in patients with primary or secondary immunodeficiency diseases. Long term follow-up of 32 patients with the Wiskott-Aldrich syndrome suggested that transfer factor caused conversion of immunologic reactivity, apparent clinical benefit, and prolonged survival in some, but not in all patients. In 18 patients with disseminated (Stage III) malignant melanoma treated with surgery and transfer factor, survival was better than would ordinarily be expected for disseminated disease (78% with mean follow-up of 2 years). A randomized trial has been initiated which will answer the question of the efficacy of transfer factor as surgical adjuvant therapy in malignant melanoma. Studies in human subjects suggested that transfer factor does not cause enhancement of reactivity in normal subjects, when evaluated in a controlled, double-blind fashion. Similar controlled studies in immunodeficient patients are necessary to ascertain whether transfer factor does cause enhancement of immune responses in these patients. Based on these observations, a guinea pig model was developed in which transfer factor caused abrogation of tolerance to ABA-Tyrosine.
Transfer factor, a dialyzable lymphocyte extract that may act as an immune stimulator by transferring antigen-specific immunity between genetically dissimilar individuals, was administered in a prospective, randomized study to patients with non-small cell bronchogenic carcinoma. Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection, and, when indicated by the presence of mediastinal lymph node involvement, mediastinal irradiation were randomized into two groups. Group 1 (n = 28) received 1 mL of pooled transfer factor at 3-month intervals after operation; group 2 (n = 35 ) served as controls and received saline solution. There were no statistically significant differences between the two groups with respect to age, sex, tumor histology, stage of disease, or extent of resection. One patient was lost to follow-up at 96 months; follow-up was complete in all others through July 1990. In patients receiving transfer factor, the 2-, 5-, and 10-year survival rates were 82%, 64%, and 43% respectively, whereas in controls they were 63%, 43%, and 23%. Survival in patients receiving transfer factor was consistently better than in those receiving placebo. Furthermore, survival in patients receiving transfer factor was greater at all stages of disease for both adenocarcinoma and squamous cell carcinoma. Although these long-term results were not statistically significant using survival analysis with covariates (p = 0.08), they confirm our previously reported short-term findings suggesting that administration of transfer factor, either through nonspecific immune stimulation, enhancement of cell-mediated immunity, or an as yet undefined mechanism, can improve survival in patients with bronchogenic carcinoma.
The objective of this study was to utilize transfer factor to stimulate cell-mediated immunity to specific tumor antigens in cancer patients. Thirty-five selected patients with advanced recurrent cancer, who were not suitable for further conventional therapy, were treated with transfer factor. Transfer factor was prepared from cohabitants of the patients and administered at 2-week intervals. This immunotherapeutic approach produced a clinical effect in 13 patients in terms of regression of tumor (1), arrest of metastatic disease (14), or pain relief (14). Conversion of dermal reactivity to specific tumor antigens was observed during periods of clinical improvement. Despite continued immunotherapy, the duration of clinical improvement was short (2 weeks to 12 months). Seven of the 11 patients not responding to therapy exhibited serum blocking of lymphocyte responsiveness. In 11 patients there is insufficient data to evaluate the clinical effectiveness of this therapy. The results suggest that transfer factor can stimulate specific cell-mediated immunity in cancer patients and produce a clinical effect on tumor under certain circumstances.
Transfer factor therapy was applied in three patients with severe atopic dermatitis and given at regular intervals for 1 1/2 years. Clinically, slight improvements were seen, attacks of impetigo ceased and admissions to hospital were not necessary. However, IgE concentrations in serum remained constantly high in all cases and the absolute number of T and B lymphocytes was continuously subnormal despite treatment. The in vitro cellular reactivity to PPD as assayed by a leucocyte migration test was not significantly altered in the patients, although a slight increase was found early on in the therapy. Finally, a serum factor inhibiting leucocyte migration and appearing simultaneously with attacks of impetigo disappeared during treatment. In conclusion, no convincing effect of transfer factor therapy was encountered in immune parameters and no major alterations were found in the status of the patients' atopic dermatitis.
Five anergic patients with chronic mucocutaneous candidiasis were given transfer factor from donors with positive delayed reactions to Candida. In each recipient, the delayed skin reactions of the transfer factor donors appeared in the recipients and no recipient developed reactivities not possessed by the donor. Prior to injection of transfer factor, in vitro stimulation of the patients' lymphocytes with antigens did not result in MIF production, however, after transfer factor this response was positive. Therapy with transfer factor alone did not have therapeutic benefit, however, in 2 patients treatment with amphotericin-B followed by transfer factor has produced cutaneous remissions of 18 months.
Dialysed transfer factor, prepared from the leucocytes of a donor whose warts had undergone recent spontaneous regression, was used in the treatment of a child with the Wiskott--Aldrich syndrome. The child then had a spontaneous regression at multiple warty areas. A similar relationship was seen in four otherwise healthy patients in a pilot study. A randomized double-blind study of thirty patients failed to confirm a causal relationship between the transfer factor therapy (equivalent to 2-1 X 10(8) leucocytes) and wart regressions. The need for randomized trials of transfer factor therapy for diseases with a variable natural history is emphasized.
AIMS: The atopic dermatitis is an chronic inflammatory illness of the skin. It exists an interrelation complex of factors gene, environmental, and psychological that contribute to the development and severity of the illness. The immunol aberrations significant is the answer increased of IgE specific antibodies toward antigens common, the liberation is increased of immunol mediators by the basophils and mast cells, eosinophils peripheral and local, besides enlarges the biphasic activity Th1/Th2 with liberation of cytokines (IL-4, IL-5, IL-13), GM-C5F, and decrease of IFN-gamma by the cells Th1. Leung to report a knowledge upon the bases immunopathologies of it atopic dermatitis has immunopathologies clinical important for the diagnosis and processing. Alternatives multiples of processing by the same complexity of the illness exist. OBJECTIVE: To compare the security and the clinical efficacy of the thalidomide and the factor of transfer in the atopic dermatitis severe. MATERIAL AND METHOD: Were studied patient with diagnosis of atopic dermatitis severe in agreement with the criterions of Hanifin and Rajka that they entered to the service of Allergy and Immunology Clinical of the Hospital Regional Lic. Adolfo López Mateos (public hospital). They were included 19 patient (women 12 and men 7, with age average 30 +/- 4 years). They were distributed in two groups. The first group of 5 patient administration thalidomide 200 mg/d during six months. The second group am administered the factor of transfer a total of 15 units by road oral during six months. Studies of laboratory for appraisal were requested immunology and metabolic pretreatment and pretreatment. RESULTS: In the group A dealt with thalidomide 5 patient and the group B dealt with FT, both presented a statistically significant decrease, as for the extension of the wounds (p < 0.01), and 1 am observed greater reduction in the intensity of the symptoms, the SCORAD total (p < 0.001 and p < 0.001 respectively) with statistical difference among them. None presented alterations immunologies and metabolic secondary to the use of the two drugs and not there was the need to suspend the processing. During the period of study, the patient were maintained controlled to the allergic rhinitis and the asthma. DISCUSSION: In the atopic dermatitis by its secondary clinical complexity to the multifactors etiologic, the alternatives of processing utilized in the present study are an option the security and efficacy, I am observed better clinical.
Plasmid DNA from Escherichia coli strains harboring drug resistance either of the infectious or noninfectious kind has been separated by CsCl centrifugation of crude cell lysates in the presence of ethidium bromide and examined by electron microscopy. Plasmid deoxyribonucleic acid (DNA) from an S(+) strain (which has the property of noninfectious streptomycin-sulfonamide resistance) consists of a monomolecular covalently closed circular species of 2.7 mum in contour length (5.6 x 10(6) atomic mass units; amu). DNA from a strain carrying a transfer factor, termed Delta, but no determinant for drug resistance, is a monomolecular covalently closed circular species of 29.3 mum in contour length (61 x 10(6) amu). DNA from either Delta(+)A(+) or Delta(+)S(+) strains, (which are respectively ampicillin or streptomycin-sulfonamide resistant, and can transfer this drug resistance), shows a bimodal distribution of molecules of contour lengths 2.7 mum and 29.3 mum, whereas DNA from a (Delta-T)(+) strain (showing infectious tetracycline resistance) contains only one species of molecule measuring 32.3 mum (67 x 10(6) amu). We conclude that ampicillin resistance is carried by a DNA molecule (the A determinant) of 2.7 mum, and streptomycin-sulfonamide resistance is carried by an independent molecule (the S determinant) of similar size. These molecules are not able to effect their own transfer, but can be transmitted to other cells due to the simultaneous presence of the transfer factor, Delta, which also constitutes an independent molecule, of size 29.3 mum. In general, there appears to be little recombination or integration of the A or S molecules into that of Delta, although a small proportion (5-10%) of recombinant molecules cannot be excluded. In contrast, the third drug-resistance determinant, that for tetracycline resistance (denoted as T), is integrated in the Delta molecule to form the composite structure Delta-T of size 32.3 mum, which determines infectious tetracycline resistance. The Delta(+)A(+) and Delta(+)S(+) strains are defined as harboring plasmid aggregates, and the (Delta-T)(+) strain is defined as carrying a plasmid cointegrate; the properties of all three strains are characteristic of strains harboring R factors. These results are compatible with the previously published genetic data. The number of Delta molecules per cell appears to be equal to the chromosomal number irrespective of growth phase, and this plasmid can thus be defined as stringently regulated in DNA replication. In contrast, S and A exist as multiple copies, probably in at least a 10-fold excess of chromosomal copy number. S and A can thus be defined as relaxed in the regulation of their DNA replication.
12 patients with Wiskott-Aldrich syndrome were treated with therapeutic doses of transfer factor in an attempt to induce cellular immunity. Clinical improvement was noted after transfer factor therapy in 7 of the 12 patients treated. Because this disease has a variable course and temporary spontaneous improvement can occur, the observed improvement cannot necessarily be attributed to the transfer factor. However, in two patients repeated remissions consistently followed transfer factor administration on repeated occasions. This included freedom from infections, regression of splenomegaly, and clearing of eczema. An unexpected finding was a decrease in bleeding in 3 of the 10 patients who had bleeding. Conversion of skin reactivity was obtained in all seven patients who clinically seemed to respond to transfer factor. In vitro studies performed after the administration of transfer factor demonstrated that the lymphocytes of the patients now produced migration inhibitory factor in response to appropriate test antigens, but did not undergo increased radioactive thymidine incorporation in response to the same antigens. A defect in the monocyte IgG receptors has been found in certain patients with the disease, and the current study shows that all patients with defective monocyte IgG receptors responded to transfer factor, whereas only one patient with normal receptors showed any response. This test may thus prove to be useful in predicting the results of transfer factor therapy in patients with Wiskott-Aldrich syndrome, although evaluation of a larger series of patients will be necessary to confirm this point. We conclude that cellular immunity can be induced, that there appears to be clinical benefit in certain patients with Wiskott-Aldrich syndrome by the use of transfer factor, and that this mode of therapy warrents trial in these patients and others with defects of cellular immunity.
Thirteen patients with subacute sclerosing panencephalitis (S.S.P.E.) at different stages of the disease were admitted for transfer factor treatment. The transfer factor was prepared from non-selected blood bank donors. The activity of the transfer factor was tested in patients with diseases other than S.S.P.E. and was found to be either clinically or immunologically active. Regardless of the number of transfer factor units applied a significant influence on the course of the disease was not apparant. The observed intermittant improvement of 3 patients was considered as spontaneous remission which is known to occur occasionally in S.S.P.E. The humoral and cellular immune response before and after transfer factor therapy did not reveal significant changes which could be correlated with transfer factor therapy.
Transfer factor-containing dialysates from mice that were either high or low responders to GAT10, GLA5, or ovalbumin were assayed for their ability to transfer delayed hypersensitivity to murine recipients of either high or low responder phenotype. Dialysates from high responder strains contained transfer factor that would transfer delayed hypersensitivity to both high and low responder recipients. These transfers were not restricted by disparities at the MHC or Igh loci. Identically prepared materials from low responder donors contained little or no transfer factor activity and would not transfer delayed hypersensitivity to either high or low responder recipients. Thus, administration of transfer factor transfers the high responder phenotype to low responder recipients. The data also suggest that production of transfer factor is regulated by Ir genes but that the immunologic activities of transfer factor are not.
Problems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis. One potential immunotherapeutic agent is transfer factors. Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients. In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis. When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNFalpha) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNFalpha and iNOS, and low DTH. Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects. We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNFalpha and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival. This beneficial effect was dose dependent. Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone.
Transfer factor specific for herpes simplex virus (HSV) type 1 (TFHSV-1) was prepared from splenic cells of HSV-1 immunized mice. Protection was transferred with TFHSV-1 to nonimmune mouse recipients. The TFHSV-1 injected mice had a higher survival rate after lethal HSV-1 challenge as compared to mice injected with a nonspecific transfer factor (P less than 0.05). 51Cr-labelled leukocyte adherence inhibition (51-Cr-LAI) test was used to demonstrate the specific activity of transfer factor in vitro. Only leukocytes incubated with TFHSV-1 exhibited significant adherence inhibition (P less than 0.01) to HSV-1 antigen, but not to control antigen. Specific activity component of TFHSV-1 (STFc) was separated by affinity adsorption with the antigen. Activity of STFc in 51Cr-LAI test was significantly higher than that of TFHSV-1 (P less than 0.01). Ratio activity of STFc in protective host immunity was 16 times as much as that of TFHSV-1. STFc was analysed by high performance liquid chromatography, thin layer chromatography and isoelectric focusing in the polyacrylamide gel. Results revealed that STFc appeared to be a polypeptide with a molecular weight of about 12,870 dalton.
Passive transfer of delayed hypersensitivity was achieved, with normal transfer factor, in patients with Hodgkin's disease in remission. The cellular immune responses of the recipients improved. It is suggested that, in addition to specific effect the transfer factor (or factors) has a nonspecific effect causing improvement in the state of delayed hypersensitivity of the recipient in general. The average number of E-rosette T lymphocytes was 46.3% after the transfer factor treatment in Hodgkin's disease. The control patients with Hodgkin's disease, not receiving transfer factor, had a value of 37.8%. Removal of 4.9 X 10(9) to 1.08 X 10(10) lymphocytes did not diminish the delayed hypersensitivity of the donor. Side effects attributable to transfer factor were not seen.
Current data suggests that the transferring of immunologically specific information by transfer factor molecules requires interaction with a cell that has been genetically programmed to be antigen reactive but at the time of interaction is unprimed. Contact with transfer factor molecules would allow a naive recipient, on a first encounter with antigen, to make a secondary rather than a primary immunological response. Transfer factor molecules for each and every antigenic determinant are thus necessary. Transfer factors made from animals or humans are capable of transferring antigen specificity across a species barrier. Even primitive species have cells from which one can make transfer factors. The molecules are, therefore, well conserved and it is reasonable to suggest that they are important for normal immunological functioning. Proposed mechanisms of action must explain the fact that transfer factors obtained from the cells of high responder animals are capable of transferring delayed hypersensitivity to low responder animals while the reverse is not true. Transfer factor molecules are likely to interact with the variable regions of the alpha and/or beta chain of T cell receptors to change their avidity and affinity for antigen in a way that otherwise would only occur after an encounter with antigen.
Transfer factors against two heterologous antigens, Herpesvirus saimiri and owl monkey kidney cells, were replicated in vitro in a human lymphoblastoid cell line (LDV/7) and injected into rhesus and owl monkeys. Transfer of immunity was demonstrated by the leukocyte migration inhibition assay. This study suggests that heterologous transfer factor, replicated in vitro, can transfer cellular immunity against membrane antigens in rhesus and owl monkeys.
The differences between lung transfer factor values measured in supine and standing positions were correlated with pulmonary artery pressures in 61 patients with chronic obstructive lung disease and in 34 patients with recurrent pulmonary embolism. No significant correlation was found. The postural change of transfer factor cannot be used as a noninvasive indicator of pulmonary artery pressure in these diseases.