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Biomedical subjects

M Shapira

Publications and source records attributed to M Shapira.

At least 73 records · Page 4Linked to original sources
PubMed1984

Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin.

Four peptides have been synthesized, corresponding to different regions of the H3 influenza hemagglutinin, that are related to antigenic sites "A" and "B" of the molecule. The peptides consisted of the following sequences: 139-146, which forms the "loop" in the native hemagglutinin molecule, with either glycine or aspartic acid at position 144; 147-164, which contains part of antigenic determinant "B"; and 138-164, which comprises both the loop and the area 147-164. The peptides were conjugated to tetanus toxoid and used for immunization of rabbits and mice. All four conjugates elicited an immune response against the homologous peptides, but only the peptides 138-164 and 147-164 gave rise to antibodies that recognized and bound to the intact virus. Protection of mice against challenge infection with A/Eng/42/72 virus was achieved only by immunization with the conjugate (138-164)-TT, which led to partial protective effect. These data emphasize the role of molecular structure in determining the antigenic properties of synthetic peptides and indicate that the length of the peptide could be crucial for enforcing the right folding required to mimic the native structure.

Animals↗
PubMed1984

Unusual association of insulin-dependent diabetes mellitus with congenital myasthenia gravis and autoimmune thyroid disease.

A 26-year-old woman with congenital myasthenia gravis and antibodies to the acetylcholine receptor developed overt insulin-dependent diabetes with positive islet cell antibodies and thyroid microsomal and gastric parietal cell antibodies. Her younger sister has been an insulin-dependent diabetic since the age of 7 years, and the mother has nongoitrous hypothyroidism. In the same period the woman in question developed a transient chemical hyperthyroidism. HLA typing of the family members showed that the diabetes was probably associated with an HLA AW30, BW38, DR4 haplotype, found in both sisters and in their father, and that the thyroid disease was associated with the A29, B7, DR6 haplotype found in the patient and in her mother. This familial HLA pattern may indicate that each autoimmune manifestation in the patient is due to a different susceptible gene associated with the HLA system.

Adult↗
PubMed1983

Synthetic vaccines.

Explore the source record for details and available documents.

Adjuvants, Immunologic↗
PubMed1982

Anti-influenza response achieved by immunization with a synthetic conjugate.

The peptide corresponding to sequence 91--108 of the hemagglutinin of type A H3N2 influenza virus has been synthesized by the solid-phase peptide synthesis method and covalently attached to several macromolecular carriers. The conjugate with tetanus toxoid was used for immunization of rabbits and mice. The immunoglobulin fraction of the rabbit antiserum showed the presence and antipeptide antibodies by both agar gel diffusion and radioimmunoassay. In the latter assay, the antibodies showed marked crossreactivity with the intact virus of the A/Texas/77 strain. The antibodies were also capable of inhibiting the hemagglutination of chicken erythrocytes by the virus; the highest hemagglutination inhibition titer (1:32) was achieved with a serum-resistant strain of A/Texas/77. When the in vitro virus plaque formation assay was used with monolayers of Madin--Darby canine kidney (MDCK) cells, the number of plaques was reduced on interaction with the immunoglobulin fraction of the antiserum, which was effective up to a dilution of 1:32. Preliminary results indicate that C3H/DiSn mice immunized with the peptide--tetanus toxoid conjugate are partially protected against a further challenge with A/Texas mouse-adapted influenza virus. The results are thus indicative of the efficacy of the synthetic material in eliciting anti-influenza immune response.

Animals↗
PubMed1981

A therapeutic trial of 15 (R)-15-methyl prostaglandin E2 in rheumatoid arthritis patients with gastroduodenal lesions.

Thirteen patients who had rheumatoid arthritis and gastroduodenal lesion (erosions, ulcers) received 200 micrograms/d of 15(R)-15-methyl prostaglandin E2 (MPGE2) for one month in a controlled, randomized, double-blind crossover study. The patients continued their usual arthritis medications. Serial assessments were made with endoscopy and multiple antral biopsies. Seven patients improved on MPGE2 and 3 improved on placebo. Two patients worsened on MPGE2 compared with 3 on placebo. No dramatic benefit was observed after one month of therapy with MPGE2, although a moderate benefit could have been missed in a small study of this type. Our experience with this study suggests that future studies in rheumatoid arthritis should first establish the natural history of lesions in a given group of patients, that a cross-over design may actually hamper interpretation and that therapy should be more prolonged.

Adult↗
PubMedDate not supplied

Sequence analysis and transcriptional activation of heat shock protein 83 of Leishmania mexicana amazonensis.

Changes in environmental temperature regulate the differential expression of genes during Leishmania stage differentiation. Therefore, molecular analysis of the heat shock proteins (HSPs) in these parasites is of interest as a model for thermoregulation of gene expression. Sequences of the HSP83 repetitive unit in the genome of Leishmania mexicana amazonensis, including both the coding and intergenic regions, are described. The 5' boundary of the message was mapped by S1 analysis, to potential AG splice sites located 293, 295 and 321 nucleotides upstream of the first ATG. A high degree of conservation (84%) is present between the coding sequence of HSP83 from L. mexicana amazonensis and similar sequences from Trypanosoma cruzi. The intergenic leishmanial sequences, however, were not homologous to similar sequences from HSP83 of trypanosomes, or from HSP70 of Leishmania major. A search for sequences that resemble eukaryote thermoregulated promoters was made and several regions with dyad symmetry were detected. However, only one of these regions was partially homologous with the consensus heat shock element present upstream of all eukaryotic HSPs studied to date.

Amino Acid Sequence↗
PubMedDate not supplied

Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases.

Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) following BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. The latter working hypothesis suggested that effective BMT procedures may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell transplantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality.

Acute Disease↗
PubMedDate not supplied

Genetic manipulations of cholinergic communication reveal trans-acting control mechanisms over acetylcholine receptors.

Several approaches have been developed for genetic modulations of receptor expression. These initiated with gene cloning and heterologous expression in microinjected Xenopus oocytes, and proceeded through transgenic expression and genomic disruption of receptor genes in mice. In addition, antisense treatments have reduced receptor levels in a transient, reversible manner. Integration of foreign DNA with host genomic sequences yields both cis- and trans-acting responses. These may depend on the DNA integration site, host cells condition and most importantly, the affected signal transduction circuit. For example, acetylcholinesterase (AChE) overexpression in microinjected Xenopus tadpoles has been shown to upregulate alpha-bungarotoxin binding levels, indicating trans-acting control conferring overproduction of muscle nicotinic acetylcholine receptors. In transgenic mice expressing human AChE, the hypothermic response to oxotremorine was suppressed, reflecting modified levels of brain muscarinic receptors. To dissociate the feedback processes occurring in transfected cells from responses related to DNA integration, we examined the endogenous expression of the alpha 7 neuronal nicotinic acetylcholine receptor in PC12 cells transfected with DNA vectors carrying alternative splicing variants of human AChE mRNA. Our findings demonstrate suppression of alpha 7 receptor levels associated with the accumulation of foreign DNA in the transfected cells. Acetylcholine receptor levels thus depend on multiple elements, each of which should be considered when genetic interventions are employed.

Acetylcholinesterase↗