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D Schlesinger

Publications and source records attributed to D Schlesinger.

At least 19 recordsLinked to original sources
PubMed2006

Mutation analysis in the FKRP gene provides an explanation for a rare cause of intrafamilial clinical variability in LGMD2I.

We report a limb-girdle muscular dystrophy 2I family with three affected sisters and a highly variable clinical course. FKRP gene sequencing showed that all three sisters carried a nonsense paternal mutation (W225X). The two oldest sisters with a severe phenotype carried two maternal mutations V79M and P89A. However, the youngest sister with a milder course carried the paternal and only the V79M maternal mutation, due to an intragenic recombination.

Adolescent↗
PubMed2005

A family with McLeod syndrome and calpainopathy with clinically overlapping diseases.

The authors describe a family with six patients with muscular dystrophy with a variable course. One is a compound heterozygote for CAPN3 mutations (calpainopathy) and the others have a single CAPN3 mutation. Linkage analysis and sequencing revealed a XK gene mutation (McLeod syndrome). This illustrates the variable phenotype of XK mutations and suggests the possibility that CAPN3 heterozygotes may have their condition caused by nonallelic mutations in other unrelated genes.

Adolescent↗
PubMed2002

Ocular toxoplasmosis: more than just what meets the eye.

Toxoplasma gondii is an intracellular parasite whose life cycle may include the man as an intermediate host. Close to a billion people are infected with this parasite worldwide. Ocular lesions may occur in up to 25% of those individuals infected. The infection may occur intra-uterus, through the placenta when the mother is infected during pregnancy. The parasite may also infect adults after the ingestion of contaminated food products, most notably meats or water. We have shown that although congenital and post-natal (acquired) infection results in similar ocular lesions, the immunological mechanisms behind the development of disease are different. On the other hand, contrary to published data obtained in mice, we were unable to find evidence that the T. gondii express superantigen activity for human lymphocytes. Our findings are important because they suggest that superantigen activity is not important as a pathological mechanism in human disease. Our data also suggest that, whereas the ocular lesion caused by infection after birth is the result of an excessive or dysfunctional immune response, the lesions caused by congenital infection may be due to a lack of an appropriate response to the parasite.

Animals↗
PubMed2001

Lack of evidence for superantigen activity of Toxoplasma gondii towards human T cells.

Toxoplasma gondii is an obligatory intracellular parasite whose life cycle may include man as an intermediate host. More than 500 million people are infected with this parasite worldwide. It has been previously reported that T. gondii contains a superantigen activity. The purpose of the present study was to determine if the putative superantigen activity of T. gondii would manifest towards human T cells. Peripheral blood mononuclear cells (PBMC) from individuals with no previous contact with the parasite were evaluated for proliferation as well as specific Vbeta expansion after exposure to Toxoplasma antigens. Likewise, PBMC from individuals with the congenital infection were evaluated for putative Vbeta family deletions in their T cell repertoire. We also evaluated, over a period of one year, the PBMC proliferation pattern in response to Toxoplasma antigens in patients with recently acquired infection. Some degree of proliferation in response to T. gondii was observed in the PBMC from individuals never exposed to the parasite, accompanied by specific Vbeta expansion, suggesting a superantigen effect. However, we found no specific deletion of Vbeta (or Valpha) families in the blood of congenitally infected individuals. Furthermore, PBMC from recently infected individuals followed up over a period of one year did not present a reduction of the Vbeta families that were originally expanded in response to the parasite antigens. Taken together, our data suggest that T. gondii does not have a strong superantigen activity on human T cells.

Adult↗
PubMed1994

Immunogenic and antigenic properties of an HIV-1 gp120-derived multiple chain peptide.

An HIV-1 envelope protein gp120-derived monomeric peptide (amino acid residues 419-439) and its homologous multiple chain peptide (MCP) construct were compared for immunogenicity in mice. The Abs stimulated by the MCP recognized epitopes on the MCP that were not present on the homologous monomer. The anti-419-439 MCP sera recognized a conformational determinant on the native envelope glycoprotein, as indicated by: 1) detection of native but not denatured recombinant envelope glycoprotein by ELISA and dot blot and 2) reaction with infected cell lines expressing gp120 on their surface as detected by flow cytometry. In contrast, the anti-monomer sera were highly specific for the monomer and recognized the envelope glycoprotein at lower titers. The low reactivity of the anti-monomer sera with the envelope glycoprotein was not decreased by denaturation. Reciprocally, murine antiserum to HIV-1 envelope glycoprotein gp160 recognized the MCP construct but not the homologous monomeric peptide. The data indicate that the MCP construct forms additional antigenic determinants not present on the homologous monomer, and that the anti-419-439 MCP Abs recognize a conformational determinant on the envelope glycoprotein not recognized by Abs against the homologous monomer. Furthermore, antisera against another envelope-derived MCP (amino acid residues 105-117) also recognize conformational determinants on the envelope glycoprotein, whereas antisera against the homologous monomeric peptide do not.

Amino Acid Sequence↗
PubMed1988

Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei.

The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2j mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2j mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.

Animals↗
PubMed1988

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Adrenal Glands↗
PubMed1988

Genetic polymorphism of phosphoglycolate phosphatase (PGP) (E.C.:3.2.3.18) in the Polish population.

In a sample of the Polish population of 261 unrelated adults, six types of phosphoglycolate phosphatase (PGP) were encountered. From the distribution of phenotypes obtained, the following frequency of genes was calculated: PGP1 = 0.8429, PGP2 = 0.1399 and PGP3 = 0.0172. PGP types were also determined in 12 families with 30 children and in 55 mother-child pairs. In the group of children the observed distribution of types was consistent with assumed types. The usefulness of this system in disputed paternity cases is as high as 13.52%.

Child↗
PubMed1988

Subtypes of the Gc gene (vitamin D binding protein) in the Polish population.

Gc subtypes were analyzed by isoelectric focusing on thin-layer polyacrylamide gel. In the sample of the Polish population including 278 persons, six Gc phenotypes were encountered: 1S, 1F-1S, 1F, 2-1S, 2-1F, 2 with the following frequencies: 0.342, 0.151, 0.014, 0.360, 0.072 and 0.061. Frequency of Gc1S was 0.597, Gc1F - 0.126 and Gc2 - 0.277. It was shown that a group system of the Gc protein in the Polish population was in good agreement with Hardy Weinberg equilibrium.

Adult↗
PubMed1987

Isolation of decay accelerating factor (DAF) by a two-step procedure and determination of its N-terminal sequence.

Decay-accelerating factor (DAF) from human red cell membranes was purified by a two-step procedure involving anion exchange and immunoaffinity chromatography. The DAF preparations were purified to homogeneity as judged by silver staining. In several experiments, the final product yields were approximately 23% of the total DAF present in the initial membrane extracts. The purified DAF retained its ability to inhibit the classical pathway C3-convertase and to reincorporate into cell membranes. An amino-terminal sequence was obtained by gas-phase sequencing. Rabbit antibodies to a synthetic peptide representing part of this sequence reacted with purified reduced membrane DAF by Western blotting and by a solid-phase immunoradiometric assay.

Amino Acid Sequence↗
PubMed1987

Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier.

Successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier. Tetanus toxoid (TT) has been proposed because of its safe and widespread use in humans. Paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier. Indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine made with a streptococcal peptide conjugated to TT. Our present study shows that similar results can be observed in mice preimmunized with TT 1 month before the administration of a conjugate containing TT and a Plasmodium knowlesi peptide. Analysis of the isotypic pattern of the antipeptide response showed that the immunoglobulin G1 (IgG1) subclass and especially the IgG2a and IgG2b subclasses were suppressed. In contrast, when a sporozoite peptide from Plasmodium falciparum was coupled to TT, the total antipeptide antibodies and particularly the IgG1 subclass were enhanced by preimmunization by TT. This increase of antipeptide antibodies was correlated with a greater ability of the sera to neutralize sporozoite infectivity. These results indicate that prior exposure to TT does not systematically impair the antibody response against a peptide administered as a peptide-TT conjugate.

Adjuvants, Immunologic↗
PubMed1986

Occurrence of ABO group antigens in bladder carcinoma.

Biopsies of bladder carcinoma obtained from 46 patients were tested for the presence of the group antigens, A, B and H. Lack of the antigens was confirmed in 69.6% of the samples examined. On the basis of histopathologic studies the patients were divided into three groups. The lack of the group antigens was reported in 86.4% bladder carcinoma patients; the lowest (45.5%) in the group of patients with papilloma of bladder. In cases of tumors with intermediate differentiation of tissue, the number of patients showing lack of group antigens amounted to 61.5%. Clinical observations carried out for five years suggest that the lack of group antigens is related to a recurrence of bladder carcinoma.

ABO Blood-Group System↗
PubMed1986

AK phenotypic changes observed in some hematologic diseases.

Determination of AK types in 372 patients of Hematologic Clinic, revealed in many cases changes in electrophoretic pattern of AK1 type namely the occurrence of an additional protein band. These changes were observed mostly in the acute granulocytic leukemia, lymphoblastic leukemia, and aplastic anemia. In the chronic granulocytic leukemia they were present as a rule, during the blastic crisis. Phenotypic changes were transient and the repeated examinations showed disappearance of an additional band in some patients. Etiology of the changes observed is still unclear.

Adenylate Kinase↗
PubMed1986

Inheritance of TfC subtypes in families and mother-child pairs.

Using the method of isoelectric focusing on polyacrylamide gel, TfC subtypes were determined in 90 families with 173 children in 242 mother-child pairs. The results obtained have confirmed the hypothesis that transferrin phenotypes are determined by a single autosomal locus in which multiple alleles are situated.

Child↗
PubMed1986

6-PGD types in the Polish population.

6-PGD types were examined in 467 adult, nonrelated subjects, inhabiting various regions of Poland. In the investigated sample three phenotypes were encountered: A, AB and B, having the following frequencies: 0.9191, 0.0878 and 0.0021, respectively. Frequencies of determining genes were calculated from distribution of the phenotypes with the following results: 6-PGDA = 0.954, 6-PGDB = 0.046.

Adult↗
PubMed1986

Transferrin subtypes in the Polish population.

Transferrin subtypes were determined by isoelectric focusing on a thin-layer polyacrylamide gel, using a mixture of ampholine of three pH ranges. In a sample of the Polish population numbering 361 subjects, six Tf subtypes dependent on three alleles Tfcc1, Tfcc2, Tfcc3 were encountered. They occurred with the following frequency: 0.744, 0.212, 0.044. It was found that Tf system in the Polish population was in a good agreement with Hardy Weinberg equilibrium.

Adult↗
PubMed1986

Atypical segregation in the GPT group system. Determination of types and activity of enzyme in families.

Examination of GPT system in 5418 paternity cases confirmed the elimination of maternity in 21 cases. The study of 12 probant families displayed the occurrence of opposite homozygous types in parents and children. The result obtained showed the presence of GPT0 gene in the families examined. Similar results were obtained by examining five families of alleged fathers whose paternity was eliminated on the same basis. In 12 families the activity of GPT was determined. In majority of subjects with GPT0 gene, markedly lowered activity was observed. This also concerned several homozygous subjects who were identical with their parents. The lowered activity of the enzyme is not present in all subjects with a "silent gene", and therefore, its examination cannot be used for detection of the gene.

Adult↗