Sandra Reichstetter - Academia.edu (original) (raw)

Papers by Sandra Reichstetter

Pharmaceutical Research, Dec 7, 2012

Purpose-To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoact... more Purpose-To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP). Methods-VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP

Tissue Antigens, 1999

DQalpha and DQbeta trans heterodimeric HLA-DQ molecules form in individuals heterozygous for the ... more DQalpha and DQbeta trans heterodimeric HLA-DQ molecules form in individuals heterozygous for the DQ2 and DQ8 specificities. Unique functions and disease associations have been postulated for such trans-dimers, which may be different from cis-encoded DQ molecules encoded by the corresponding haplotypes. We analyzed the ability of the trans-dimer encoded by HLA-DQA1*0501/DQB1*0302 to bind a peptide antigen which interacts with DQ molecules encoded by both parental haplotypes. Markedly impaired binding was observed, consistent with both the use of different anchor residues and with changes in levels of DQ cis-dimer availability for peptide binding interactions.

Immunogenetics, 1994

HLA class II antigens are highly polymorphic molecules expressed on the surface as glycosylated ~... more HLA class II antigens are highly polymorphic molecules expressed on the surface as glycosylated ~ heterodimers (Kappes and Strominger 1988). The expression of class II molecules is regulated by complex mechanisms involving cisand trans-acting elements (for review see Benoist and Mathis (1990); Glimcher and Kara 1992). A limited number of highly conserved cis-acting upstream regulatory elements are critical for both constitutive and inducible expression. Recently, Andersen and co-workers (1991) have recognized the existence of an allelic polymorphism in the 5' regulatory region of the DQB1 gene. Functional studies indicated that this allelic polymorphism is associated with differences in transcriptional activity and affinity for DNA-binding proteins. Furthermore, mutations in the W and X box may be responsible for the lack of expression seen for the DQB2 gene (Shewey et al. 1992). In addition, allelic polymorphism in the upstream regulatory region can also be detected for HLA-DQA1 and -DRA (Del Pozzo et al. 1992; Pinet et al. 1991; Morzycka-Wroblewska et al. 1993, Kimura and Sasazuki 1992). The specific requirements for tissueand locus-specific expression of HLA class II genes are still under debate. Thus, we have analyzed allelic variability in the upstream regulatory region of the DQB1 gene in more detail in order to identify regions of possible functional importance for locusspecific regulation. The designation of HLA alleles was carried out according to the Nomenclature for Factors of the HLA System 1991 (Bodmer et al. 1992). DQB1 upstream regulatory regions were named after their linked DQB1

Human Immunology, Apr 1, 1996

Immunology, Mar 1, 2006

Alloreactivity is one of the most serious problems in organ transplantation. It has been hypothes... more Alloreactivity is one of the most serious problems in organ transplantation. It has been hypothesized that pre-existing alloreactive T cells are actually cross-reacting cells that have been primed by the autologous major histocompatibility complex (MHC) and a specific peptide. CD8+ cytotoxic T lymphocytes that are alloreactive and recognize a virus-peptide that is presented by the autologous MHC have been reported. Here we demonstrate a cross-reactivity that exists between DQ0602 restricted, herpes simplex type 2 VP16 40–50 specific CD4+ T-cell clones, which can be alloreactive to DQ0601. Though most of the DQ0602 restricted T-cell clones we isolated from two different donors were not alloreactive, weakly cross-reacting T-cell clones could be isolated from both donors. Two strongly cross-reacting T-cell clones with high affinity interaction of their T-cell receptor (TCR) with both DQ0602/VP16 40–50 and DQ0601 could be isolated from one donor. DNA sequencing of the a fragment of the Vβ gene used in their TCR confirmed that these two T cells indeed are two independent clones. These clones are cytotoxic and produce cytokines of a T helper 2-like pattern. Possible implications in a DR-matched transplantation setting are discussed.

Journal of Immunology, Apr 1, 2009

Formulation of peptides in a nanocarrier made up of protected-graft-copolymer (PGC) can greatly e... more Formulation of peptides in a nanocarrier made up of protected-graft-copolymer (PGC) can greatly enhance pharmacokinetics and biodistribution of the peptides in vivo. Glucagon-like peptide 1 (GLP-1) is β-cell protective and decreases the severity symptoms of diabetes in Type 2 and streptozotocin models. We hypothesized that PGC-formulated GLP-1 can prevent Type 1 diabetes in NOD mice. 4-5 week old female NOD mice [n=25] were treated for eight weeks with 3mg/kg PGC-formulated GLP-1 administered s.c. either once or three times per week. After the treatment period, the mice were monitored for signs of diabetes until they reached 36 weeks of age. A group of NOD mice treated with anti-CD3 antibodies (0.5mg/kg i.p. once at treatment week 0 and once at treatment week 1) was used as a positive control for diabetes prevention. At 36 weeks of age, 48% of the mice treated with saline had developed diabetes. Anti-CD3 treatment prevented 50% of the diabetes cases in the mice with only 24% of the mice in this group having developed diabetes at 36 weeks of age. Once a week GLP-1 treatment (3mg/kg s.c.) was as effective in preventing diabetes as anti-CD3 treatment with only 28% of mice being diabetic at 36 weeks of age. Surprisingly, there was no difference between the three times per week GLP-1 treatment group (3mg/kg s.c.) and the saline control: 54.1% of the mice treated three times per week became diabetic, which was not statistically significantly different form the 48% diabetes incidence in the saline group.

Human Immunology, Dec 1, 1996

Sequence variability in the upstream regulatory regions (URR) of HLA class II genes has been desc... more Sequence variability in the upstream regulatory regions (URR) of HLA class II genes has been described as an additional mechanism of diversity in these polymorphic genes. For HLA-DQBl, 12 URR variants have been identified previously by sequence analysis of approx. 600 bp located immediately upstream of the first exon of the DQBl gene. To investigate the distribution of these promoter alleles and their linkage with the structural portion of the DQBZ gene, a population-based study was carried out. Sequence information was utilized to develop 25 sequence-specific oligonucleotide probes to analyze enzymatically amplified locus-specific DNA. Supplemented with one sequence-specific primer pair to differentiate QBPI-6.2 from-6.3, all known 12 QBPl alleles could be identified. Subsequently, 215 healthy, unrelated German controls were investigated for the distribution and linkage of DQBl and QBPl alleles. A total of 10 out ABBREVIATIONS PCR polymerase chain reaction QBPl DQBl promoter sso sequence-specific oligonucleotide

Human Immunology, Jul 1, 1999

Antigen-specific T cell recognition is dependent on the functional density of the TCR-ligand, whi... more Antigen-specific T cell recognition is dependent on the functional density of the TCR-ligand, which consists of specific MHC molecules and a specifically bound peptide. We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4ϩ, DQA1*0501/DQB1*0201 (DQ2.1)restricted, HSV-2-specific T cell clone. Using antigen peptide analogs with different mutations of known DQ2anchor residues, T cell response was reduced in an peptide-affinity and-concentration specific manner. The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate T cell proliferation and the poorest binding peptide induced an even weaker T cell response. MHC class II density on the APC was modified using DQ2 homo-and heterozygous B-LCLs as APCs, however this variation of MHC concentration had no effect on T cell proliferation. We interpret this as a reflection of a low threshold for activation of the T cell clone, in which peptide-MHC avidity is the overriding determinant of the strength of ligand signal.

Human Immunology, Mar 1, 2002

Three different HLA-DQ0602 restricted T-lymphocyte clones (clones 5, 44, and 48) specific for two... more Three different HLA-DQ0602 restricted T-lymphocyte clones (clones 5, 44, and 48) specific for two different Herpes simplex virus type 2 (HSV-2) VP16 peptides were used in a series of proliferation assays with BLS-1 cell lines expressing mutated HLA-DQ0604 molecules as APC. Up to four residues in the peptide-binding region of DQ0604 were replaced by the respective DQ0602 residue. For all three clones, residue ␤70 played a crucial role in TCR recognition; ␤30 and ␤57 were important, although ␤86 was less significant. Clone 5 and 48, specific to the HSV-2 VP16 369-379 peptide, responded to the same mutated DQ0604 molecules. Both clones could be stimulated only when the antigen presenting DQ molecule contained the DQ0602-like Gly at position ␤70. Stimulation of clone 44, which recognized a different HSV-2 VP16 epitope (VP16 40-50), was less restricted. Molecular homology modeling showed that the ␤70Arg of DQ0604 partially covered the peptide around P5/P6. Interactions of ␤70 with residues from the antigen-peptide and polymorphic residues at positions ␤30 and ␤57 can modulate this effect. Supported by molecular modeling data, we conclude that the distinct molecular topography of DQ0602 is not contributed by a single residue, but rather the interactions of various polymorphic DQ residues with particular antigenic peptides.

Economics of Contemporary Russia, 2020

The work is devoted to the improvement of the existing system of strategic management of the Russ... more The work is devoted to the improvement of the existing system of strategic management of the Russian oil and gas complex using the program-target method, which is one of the most effective tools of world management practice. The directions for improving the management system of the oil and gas complex of Russia were determined on the basis of the analysis and identified shortcomings of the existing hierarchy of documents of the strategic planning of the development of the oil and gas complex. It was found that the current system of strategic planning of the oil and gas sector is characterized by a large number of documents of various levels, often outdated, adopted with a significant time lag, which are not coordinated with each other in time, goals, objectives, indicators, activities and resources. Documents of the industry level are developed only within the framework of goal-setting, in the absence of the specification of these documents in the forecasts, programs and plans, cons...

Tissue Antigens, 1999

Human Immunology, 1995

An understanding of the regulation of HLA class II genes is crucial in immune response, transplan... more An understanding of the regulation of HLA class II genes is crucial in immune response, transplantation and susceptibility to autoimmune diseases. We have previously reported allelic polymorphisms in the conserved consensus motifs in the promoter region of DRB genes. In addition, we observed significant (up to 4-fold) differences in strengths of promoters of DRBI genes from different DR haplotype

Autoimmunity, 2000

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive ... more Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p = 0.003, and 69 vs. 27%, p < 0.00, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-I patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRB1*03-DQB1* 02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1*13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD.

Bioorganic & Medicinal Chemistry, 1996

Formula 1 depicts a generalized structure of the capsular polysaccharides of four serotypes of th... more Formula 1 depicts a generalized structure of the capsular polysaccharides of four serotypes of the opportunistic microorganism Cryptococcus neoformans, which appears as one of the major infections in the late stages of development of AIDS. Syntheses are now described of two tetrasaccharides with corresponding structures. These are methyl O-α- d-mannopyranosyl-(1→3)-[O-β-d-xylopyranosyl-(1→2)]-O-α-d-mannopyranosyl-(1→3)- α-d-mannopyranoside and methyl O-α-d-mannopyranosyl-(1→3)-[O-β-d-glucopyranosyluronic acid-(1→2)]-O-α-d-mannopyranosyl-(1→3)-α-d-mannopyranoside.

ABSTRACT Background. Microchimerism after liver transplantation is a readily observed phenomenon.... more ABSTRACT Background. Microchimerism after liver transplantation is a readily observed phenomenon. The immunological implications, however, remain unclear. Moreover, methodological approaches and their detection limits in the study of allogeneic microchimerism have not been studied in detail. Methods. Therefore, the aim of this study was to evaluate the single-step and nested formats of the polymerase chain reaction/sequence-specific priming(PCR-SSP) approach under standardized conditions. For that purpose, a panel of recombinant plasmid clones was generated by PCR cloning. The panel contained the allelic sequences of the second exon of DRB1 covering all DR specificities on a low-resolution level. Using this panel, limiting dilution assays for various DR sequences in the presence and absence of competitor DNA were carried out to determine the minimal number of copies required for detection by single-step and nested PCR-SSP. Subsequently, 22 liver transplant recipients were analyzed in a retrospective study for the presence of allogeneic microchimerism by nested PCR-SSP. Results. Although at least 10 copies of template DNA could be detected by nested PCR-SSP overall, single-step PCR-SSP was on average 102 to 103 times less sensitive. Upon the addition of human competitor DNA, the detection limits decreased on average by a factor of 10. In addition, sequence-specific differences in amplification efficiency could be appreciated. Using nested PCR-SSP, peripheral blood allogeneic microchimerism could be observed in 17 of 22 HLA-DR-mismatched liver recipients. Recombinants representing recipient DRB1 specificities were used to exclude false-positive results by lack of cross-reactivities of the donor-specific primers and to evaluate negative results due to sample-related reduced amplification efficiencies in microchimerism-negative recipients. In donor/recipient combinations that differed by at least one DR specificity, allogeneic microchimerism was seen in 87.5% of the cases. In five chimerism-negative cases, sample-related problems were detected in two cases. Conclusion. The optimization and standardization of the detection of genomic HLA sequences at low copy number may be greatly facilitated using a clonal reference system. Furthermore, a clonal reference system may be used to conduct cross-priming experiments to exclude false-positive results and may allow the determination of sample-specific detection limits for donor-derived HLA-DR specificities in chimerism-negative patients. Our evaluation of the PCR-SSP approach for the study of allogeneic microchimerism indicated that nested PCR-SSP provides the most sensitive format when HLA sequences are targeted. Yet, the detection sensitivity may vary between individual alleles and specificities. Allogeneic microchimerism in liver recipients can be observed in the majority of patients. However, the detection may be subject to the degree of mismatching, the HLA-DR alleles involved, and sample-related impaired PCR amplification efficiency.

Human Immunology, 1996

The Journal of Immunology, Apr 1, 2009

Pharmaceutical Research, Dec 7, 2012

Tissue Antigens, 1999

Immunogenetics, 1994

Human Immunology, Apr 1, 1996

Immunology, Mar 1, 2006

Journal of Immunology, Apr 1, 2009

Human Immunology, Dec 1, 1996

Human Immunology, Jul 1, 1999

Human Immunology, Mar 1, 2002

Economics of Contemporary Russia, 2020

Tissue Antigens, 1999

Human Immunology, 1995

Autoimmunity, 2000

Bioorganic & Medicinal Chemistry, 1996

Human Immunology, 1996

The Journal of Immunology, Apr 1, 2009