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L E Spitler

Publications and source records attributed to L E Spitler.

90 records · Page 5Linked to original sources
PubMed1972

Experimental allergic encephalitis. Dissociation of cellular immunity to brain protein and disease production.

The encephalitogenic determinant of brain protein, a nonapeptide having the amino acid sequence Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys, has been characterized and synthesized. In a previous study, analogues of this encephalitogenic peptide were synthesized and some were shown to be encephalitogenic while others were not. Guinea pigs were immunized with encephalitogenic peptides having amino acid sequences different from that in the native protein. These guinea pigs did not show cellular immunity in vivo (skin reactivity) or in vitro (lymphocyte stimulation or macrophage migration inhibition) to the encephalitogenic brain protein (EP) although they did show cellular immunity to the immunizing antigenic peptide. Guinea pigs immunized with an encephalitogenic peptide having the same amino acid sequence as the brain protein, or with a nonencephalitogenic peptide having the same amino acid sequence as the native protein but lacking the terminal lysine, did develop cellular immunity to the EP. Animals immunized with EP showed cellular immunity to this protein, but not to the encephalitogenic peptides. Animals immunized with nonencephalitogenic protein (NEP), prepared by altering the tryptophan residue of EP, did not develop disease but did show cellular immunity in vitro and in vivo to the EP. Animals protected from disease by immunization with NEP similarly showed cellular immunity to EP. Thus, the results suggest a dissociation between cellular immunity to EP and the production of experimental allergic encephalitis (EAE). Animals immunized with the encephalitogenic peptides develop EAE, but do not show cellular immunity to EP, and animals immunized with NEP show cellular immunity to EP but do not develop EAE. A fresh approach to the examination of the pathogenesis of EAE is now possible through the use of these well-characterized antigens.

Amino Acid Sequence↗
PubMed1972

The Wiskott-Aldrich syndrome. Results of transfer factor therapy.

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.

Cell Migration Inhibition↗
PubMed1970

Wiskott-Aldrich syndrome, a genetically determined cellular immunologic deficiency: clinical and laboratory responses to therapy with transfer factor.

Patients with diseases associated with defects in cellular immunity, such as the Wiskott-Aldrich syndrome, characteristically have severe recurrent infections and usually succumb to overwhelming infection at an early age. This communication describes a patient with this syndrome, defective delayed hypersensitivity by skin tests and by in vitro lymphocyte response, who was treated with dialysate of peripheral blood leukocytes (transfer factor). After treatment, the clinical status of the patient improved dramatically, concomitant with the development of delayed hypersensitivity to antigens to which the donor was sensitive. In vitro tests after transfer indicated that the patient's lymphocytes, when stimulated by specific antigen, produced migration inhibitory factor without concomitant DNA synthesis. These observations dissociate skin test sensitivity and activity of migration inhibitory factor from in vitro blastogenesis. Further, the response to phytohemagglutinin remained diminished before and after therapy. While these findings represent only an individual case, the climical results suggest that investigation of the use of transfer factor appears warranted in the therapy of Wiskott-Aldrich syndrome and other genetically-determined diseases associated with impaired cellular immunity.

Antigens↗
PubMedDate not supplied

Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma.

We established short-term cell lines for 108/170 (64%) patients with metastatic melanoma. Tumor cell numbers were expanded to 10(8), then cells were irradiated, aliquoted, and cryopreserved for clinical use. Vaccines have been used to treat 69 patients with clinical follow up for 33 who had measurable metastatic disease at the time vaccine therapy was initiated (METS), and 33 who had no evidence of disease (NED) at the time of vaccine therapy following surgical resection of metastases. The protocol called for a baseline test of delayed tumor hypersensitivity (DTH), three weekly injections, a repeat of the DTH test, then monthly injections for an additional 5 months. Objective tumor responses were noted in 3/26 (12%) patients who received a minimum of three vaccinations, one complete, and two partial, with survivals of 36, 46+, and 78+ months. Only 6/64 (9.4%) had a positive DTH (>10 mm) at baseline, including three METS, all of whom progressed within 4 months and died within a year, and three who are still NED after more than 5 years. Conversion of DTH from negative to positive was documented in 18/44 (41%) patients who were tested at week 0 and 4. At a median follow up of greater than 5 years, the median overall survival (OS) was 40 months for "NED" with a 5-year survival rate of 39%, and 8.6 months with a 5-year survival rate of 10% for "METS" The 18 patients who had conversion of their DTH had a median event-free survival (EFS) of 15.8 months and 5-year EFS of 32% compared to 4.2 months and 9% for the 26 non-converters (P=0.012, two-tailed, log-rank test). Among patients who were NED when treatment started, the 12 patients whose DTH converted had a median overall survival of 61.4 months with 5-year survival of 63% compared to 9.7 months and 0% for the 13 non-converters (P=0.0026). This treatment approach is feasible, produces minimal toxicity, and is associated with long-term survival in a significant subset of patients.

Adult↗
PubMedDate not supplied

Transfer factor.

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Animals↗
PubMedDate not supplied

Experimental allergic encephalitis; treatment with drugs which alter CNS serotonin levels.

Lennon and Carnegie have proposed that the clinical symptomatology of experimental allergic encephalitis (EAE), an acute autoimmune demyelinating disease, may be due, at least in part, to an immune response directed against CNS serotonin receptors. To test this hypothesis we treated strain 13 guinea pigs, which had been immunized with guinea pig basic protein (GPBP) in complete Freund's adjuvant (CFA), with drugs known to affect central nervous system (CNS) serotonin levels. These drugs included imipramine hydrochloride, tryptophan and carbidopa which increase CNS serotonin and reserpine which decreases it. Five experiments were conducted in which all immunized animals treated with saline only died, as expected, as did all animals treated with reserpine which died even more quickly. A significant proportion of animals treated with the other three drugs, alone or in combination, survived or lived longer than controls. We conclude that survival of animals with EAE is enhanced by treatment with these drugs. We suggest that further evaluation of a possible blockade in serotonin transmission in EAE and multiple sclerosis (MS) is warrented, since, if such a blockade were demonstrated, it is possible that these drugs may have potential for therapeutic efficacy in patients with MS.

Animals↗