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A case report of the successful treatment of recurrent aphthous stomatitis with some preparations of orally administered transfer factor.

A patient with severe disabling recurrent aphthous stomatitis (RAS) was treated with four different preparations of oral human transfer factor (TF), as well as placebo, following a double-blind protocol. Two of the TF preparations had a significant effect upon the course of the patient's illness by prolonging the interval between attacks and decreasing the severity of attacks. No side effects attributable to any of the preparations were noted by the patient. Thus, some but not all preparations of human transfer factor given orally are an effective therapy for RAS.

Administration, Oral↗

A study of estrogen metabolic clearance rates and transfer factors.

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E(2)) and estrone (E(1)) during 2-hr and 12-hr infusions. When estradiol-(3)H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-(3)H levels increased slowly throughout the infusion. When estrone-(3)H was infused, constancy of estrone-(3)H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios C(E1E2) and C(E2E1) continually changed and transfer factors could not be calculated. The apparent "MCR'S" calculated on the basis of the 2-hr studies expressed as liters/24 hr per m(2) +/-SD were: "MCR(E1)" (women) 980 +/-94, (men) 1170 +/-95; "MCR(E2)" (women) 615 +/-17, (men) 830 +/-30. The estradiol "MCR's" differed significantly between men and women. "MCR(E2)" was the same using either estradiol-(14)C or -(3)H and was unchanged by the infusion of 170 mug of estradiol daily. Postmenopausal women had estrogen "MCR's" in the same range as premenopausal women. Excess glucocorticoids increased the "MCR(E2)."

Adult↗

The effect of transfer factor on lymph node morphology in murine toxoplasmosis.

Mice were infected intraperitoneally with a low virulence strain of Toxoplasma gondii (TO) and transfer factor (TF) was prepared from the spleens of infected (TFT) and uninfected control mice (TFC). Three experimental groups of 12 mice were given either saline, TFC or TFT, by intraperitoneal injection. After 24 h half of each group of these animals were infected by intraperitoneal injection of TO cysts. In three separate experiments animals were killed at 11, 28 and 35 days and the flank and axillary nodes removed for histological examination. There was generalized lymph node enlargement with cortical and paracortical expansion. In most animals there was diffuse infiltration of the nodes by clusters of histiocytes. Administration of TFC alone led to a mild increase in node size at 11 and 28 days. Administration of TFT alone had a moderate stimulatory effect on the mouse lymph nodes with a significant increase in size at 11 days due predominantly to expansion of the paracortex. Administration of TFT and TFC followed by inoculation of TO led to an increased and more consistent histiocyte response and an increased number of paracortical T blasts compared with animals given TO alone. TFT and TFC had no demonstrable protective effect in experimental murine toxoplasmosis as assessed by quantitation of toxoplasma brain cysts. The effect of transfer factor was not antigen specific in this system.

Animals↗

Transfer factor in mycosis fungoides: a case report on a patient "cured".

A report is given of the successful treatment with transfer factor as an additional therapeutic agent of a patient in the tumour stage of mycosis fungoides who had not responded to conventional treatment with nitrogen mustard, methotrexate, or grenz rays alone. Besides twelve injections of transfer factor, the patient received X-irradiation, 1 400 r (50 kV 1 mm Al) in all, to three tumours. The combined treatment induced sustained remissions. When that patient died from a coronary infarct 5 years after treatment began, autopsy showed no evidence of mycosis fungoides at all.

Humans↗

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

B-Lymphocytes↗

The effect of transfer factor on spontaneous shedding of sheep red blood cell binding receptors of T lymphocytes in vitro.

Many effects of transfer factor can be used for testing of its activity in vitro. Its effect on rosette formation has been utilized in two methods: the enhancement of rosetting of trypsin-treated T lymphocytes and the increase of 'active' rosettes depressed under some immunopathological conditions. 'Active' rosetting lymphocytes of healthy blood donors if kept at 37 degrees C for 4 hr shed partly their sheep red blood cell-binding receptors into the culture medium supplemented with 25% fetal calf serum. The adding of the negative skin test-converting fraction of dialysable leucocyte extracts inhibits the decrease of the number of rosettes. Possible explanations for the observed phenomenon are: transfer factor increases the rate of receptor synthesis, it causes uncovering or redistribution of the receptors, or it stabilizes otherwise shed membrane structures.

Animals↗

Transfer factor in mycosis fungoides: three years experience.

13 patients with clinically and histologically verified mycosis fungoides were treated with transfer factor as additional therapy to the hitherto conventional treatment after this had failed. After approximately 3 years, complete remission was present in 3 patients, 4 patients were significantly improved and registered as being in partial remission, while the condition was registered as no change in 3 patients. 1 patient was found worse, 1 patient had died after discontinuation of therapy and 1 patient was out of the study. In this case treatment was withdrawn because of the development of contact urticaria to nitrogen mustard, her basic therapy. The number of T lymphocytes, which was low prior to treatment, increased to normal values during the therapeutic period. During the first year a decrease in serum IgE was noted. The results of the clinical evaluation seem to indicate that transfer factor may be of value as an additional therapeutic agent in mycosis fungoides. Controlled investigations are needed and are in progress.

Adolescent↗

[Transfer factor. Properties and possible therapeutic applications (author's transl)].

Transfer factor (TF) is a dialysable and ultrafilterable extract from human leukocytes. It contains only substances with a molecular weight of less than 10 000. Several biological activities of TF are so far known. These refer to the transfer of specific cellular immunity from one individual to another and a stimulating effect, probably of an unspecific nature, on the cellular immune system. So far, favorable therapeutic results have been obtained in chronic candidiasis and a few other chronic infectious diseases, in the Wiskott-Aldrich syndrome and possibly also in some special malignant tumors. The small number of treatments does not permit any firm conclusions to be drawn.

Arthritis, Rheumatoid↗

Double-blind trial of the use of transfer factor in the treatment of Crohn's disease.

We have undertaken a double-blind controlled trial of the use of transfer factor in Crohn's disease. Thirty-three patients with known Crohn's disease completed the trial in which half the patients had three injections of transfer factor and the other half were given saline. After six months there was no significant difference in the clinical condition of either of the two groups compared with before receiving treatment. There was also no difference in their in vitro lymphocyte function, although a number of patients exhibited altered responsiveness to skin testing with tuberculin or streptokinase/streptodornase. A signficant fall on Crohn's disease activity index score occurred over the initial 'acclimatising period' before the trial was started, probably related to overcoming initial introspection and the placebo effect of being part of a trial.

Adult↗

An investigation into the antigen-specificity of transfer factor in its stimulatory action on lymphocyte transformation.

Dialysable transfer factor (TF) was prepared from the buffy-coat cells of donors with known cell-mediated reactivity to tuberculin (PPD), streptococcal protein (SKSD) and diphtheria toxoid (DT). The effect of such preparations on the transformation by these antigens of lymphocytes from tuberculin-negative donors was investigated. Transformation was determined as incorporation of tritiated thymidine. The concentrations of SKSD and DT were adjusted for different lymphocyte donors so as to give, in the absence of TF, a low index of transformation (less than 10-fold) comparable to that obtained with PPD. TF from tuberculin-positive donors stimulated antigen-induced transformation by on average approximately 2-fold whereas TF from tuberculin-negative donors generally had little effect. This was so not for PPD as antigen but also for SKSD and DT, and sensitivity of TF donor to SKSD of DT was not a determining factor. TF also frequently increased background transformation in the absence of antigen. Although a small effect, this ability tended to reflect the activity of TF in the presence of antigen. It is concluded that neither the whole nor any significant part of this enhancement of transformation can be ascribed to an antigen-specific factor. Tuberculin-positive donors apparently yield a higher level of non-specific factor and possible reasons for this are discussed. The factor active in transformation may be responsbile for the TF phenomenon in vivo.

Antigens, Bacterial↗

Effect of different fractions of dialyzable leukocyte extract--transfer factor--on the chemiluminescence of human phagocytes.

The chemiluminescence (CL) inducing effect of the fractions of dialyzable leukocyte extract (DLE)--transfer factor--from tonsil leukocytes was tested on the phagocytes of human whole blood. The fractionation of DLE by Sephadex G-25 results in three main fractions: I, II, III. We found only fraction II having a direct CL inducing effect on the non-stimulated cells. Fraction II increased further the CL of phagocytes which were stimulated by zymosan (Mannozym). Fractions I and III were ineffective. We suggest that in the complex "transfer factor" effects of DLE, the stimulation of the peripheral phagocytes of blood-by the oligopeptides of fraction II may have an important role.

Humans↗

[The current position of the transfer factor investigation (author's transl)].

This critical review has attempted to describe the current knowledge about the preparation and characterisation of transfer factor, the biological assays, and the tendency to therapy of patients with immunodeficiencies, chronic infectious diseases, and neoplastic diseases on the basic of results of the two last years. Hypotheses for the mechanism of functional activities of transfer factor are discussed.

Antibody Specificity↗

Transfer factor and its protective effect against herpesvirus infections of marmosets.

Using skin test response and lymphocyte blastogenesis as indicators of cell-mediated immunity, we have been able to demonstrate in vivo transfer of cell-mediated immunity to marmosets both with dialyzable transfer factor (TFd) prepared from a human donor and transfer factor (TF) from baboon whole cell lysates. We were able to protect marmosets with TFd from fatal Herpesvirus hominis type 1 (HVH-1) disease. When TFd was administered prior to challenge with HVH-1, 50% of the marmosets survived. Of the untreated control animals and those first treated on day 0 or postinfection, 100% succumbed to disseminated HVH-1 disease. In addition, when TF prepared from TFd-treated marmosets which had survived HVH-1 disease, was given to other marmosets, it conferred protection from subsequent HVH-1 challenge.

Animals↗

[Treatment of extrinsic bronchial asthma with transfer factor].

A group of 90 external asthmatics with cellular immunodeficiency or not was studied and treated during 10 months with transfer factor or double blind placebo. Total immunoglobulin serum studies (A, G, M and E), spontaneous rosette and intradermal tests, were made a month before the treatment's beginning and a month after the ending of the treatment. The patients were clinically evaluated every day in accordance to the intensity and the frequency of their crisis and with the immunological point of view of the tests made. There was not significant differences between the study groups treated with the transfer factor or not. Adverse reactions were not noticed.

Adjuvants, Immunologic↗

"Transfer factor" therapy in infectious diseases.

The world literature on transfer factor treatment in infectious diseases was examined. Even with the limits due to the incomplete knowledge of the substances, its use is worthy of further study in the field of infectious diseases.

Candidiasis, Cutaneous↗

Fine structure of lymphocytes from an immune deficient child before and after administration of transfer factor.

Lymphocytes from a male infant delivered by Cesarean section and placed into a germ-free environment were examined by electron microscopy (EM). The child had a sex-linked severe combined immunodeficiency. The lymphocytes were atypical, having sparse cytoplasm with little rough endoplasmic reticulum (ER) but abundant smooth ER. The nuclear membrane was pulled away from the nuclear space, and no evidence of nuclear pores or aggregated ribosomes was found. Mitochondria were intact. Repeated injections of the subject during the 9-month period with KLH, typhoid vaccine, and diphtheria toxoid yielded no significant observable change in the fine structure of the lymphocytes. At 11 months, the subject was given transfer factor. Following repeated injections of this material, the original cell type was still present but a new type of lymphocyte was also observed by EM examination. The new cell type resembled a more normal lymphocyte. It had a higher density of cytoplasmic material, in comparison with cells prior to administration of transfer factor. It was smaller in size with some aggregated ribosomes, had detectable amounts of rough ER, and more intact nuclear membranes. This new type of lymphocyte may represent a small population of B lymphocytes perhaps stimulated by T cells made immunocompetent by transfer factor.

Cell Nucleus↗

HLA haplotypes and long survival in childhood acute lymphoblastic leukaemia treated with transfer factor.

Association between HLA haplotypes and long survival was investigated in 116 children with acute lymphoblastic leukaemia. It was found that patients with A2 B12 and/or A2 B40 haplotypes survived longer than patients wtihout these two haplotypes. Since all children were treated with transfer factor obtained from their relatives, it is suggested that children possessing A2 B12 or A2 B40 haplotypes may respond better to this type of immunotherapy.

Acute Disease↗