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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Simulation of a subsurface vertical flow constructed wetland for CSO treatment.

Constructed wetlands (CWs) have proved to be a highly effective measure to reduce the ecological impact of combined sewer overflows (CSOs) on receiving waters. Due to the stochastic nature of the loading regime and the multitude of environmental influences, assessment of the performance of such plants requires detailed mathematical modelling. A multi-component reactive transport module (CW2D) was applied to simulate the flow, transport and degradation processes occurring in a CW for CSO treatment. CW2D was originally developed to simulate the treatment of municipal wastewater in subsurface flow CWs. Loading and operational conditions in CSO treatment differ fundamentally from the conditions occurring for wastewater treatment. Despite these differences, first results from the simulation of lab-scale experiments show, that the model is generally applicable to this type of plant. Modelling of adsorption, degradation processes, and influent fractionation, however, require further research.

Biodegradation, Environmental↗
PubMed2005

Eye signs that alert the clinician to a diagnosis of AIDS.

One of the hallmarks of progressive immune deficiency is a steady decline in the absolute number of CD4+ T-lymphocytes. As the immune response thus becomes suppressed, opportunistic systemic infections such as protozoal (Pneumocystis carinii pneumonia, disseminated toxoplasmosis), viral (Cytomegalovirus pneumonitis and colitis and persistent invasive herpes simplex lesions), fungal (cryptococcossis and esophageal candidiasis) and bacterial infections (atypical mycobacterial and extrapulmonary tuberculosis) set in to claim their toll. Ocular complications occur in about 75% of AIDS patients and may be divided into four categories: Retinal microangiopathy, Opportunistic infections, Tumours, Neuro-ophthalmological lesions. Only the most frequently occurring manifestations will be highlighted.

AIDS-Related Opportunistic Infections↗
PubMed2004

Peptide immunogens designed to enhance immune responses against human immunodeficiency virus (HIV) mutant strains: a plausible means of preventing viral persistence.

A major problem impeding the development of an effective HIV-1 vaccine is the rapid antigenic variability that occurs throughout the viral genome but is most pronounced in the envelope (env) gene and env gene products. The high number of errors made by the reverse transcriptase (RT) enzyme and the absence of an RT proofreading mechanism during HIV-1 replication leads to new antigenic variants that escape current immunological attack. In turn, accumulation of escape mutants leads to a persistent infection. It has been hypothesized through many means including mathematical modeling that preventing HIV persistence necessitates a vaccine that enhances immunity against a sufficiently large fraction of mutant stains. To this extent we have developed a 4 branched--and an 8 branched--multiple epitope immunogen (MEI) that in theory represent 6.7x10(7) and 1.8x10(16) envelope V3 loop sequences respectively. Both MEI constructs were recognized by antibodies in sera from AIDS and/or HIV-1 positive patients from South Africa and Puerto Rico. The immunogens also induced immune responses in MF1 mice and New Zealand White rabbits with the octameric MEI proving to be a more effective antigen. This data supports our hypothesis that synthetic peptides designed to represent the variable regions of HIV-1 envelope should induce immunity against a large quantity of mutant strains.

AIDS Vaccines↗
PubMed2004

[Gastrointestinal stromal tumor of the abdominal wall. An unusual localization of a rare tumor].

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We describe here for the first time a patient with a huge GIST of the abdominal wall without any relation to the gastrointestinal tract, omentum, or mesentery. With regard to the size of 24 cm and a low mitotic index, this GIST is considered an intermediate risk for metastasis. Radical surgical resection was performed with negative pathologic resection margins. The classic immunohistochemical phenotype of the tumor described facilitates the differential diagnosis to exclude abdominal desmoid tumor and solitary fibrous tumor (SFT). In the case of metastasis, therapeutic nihilism no longer seems justified with the availability of imatinib, a tyrosine kinase inhibitor, which shows encouraging results in the therapy of metastatic GIST.

Abdominal Neoplasms↗
PubMed2004

Liver transplant for the septuagenarians: importance of patient selection.

With the increasing success of liver transplantation (OLT), more patients above 70 years of age are being considered for OLT. There is not enough data about the predictors for survival in this patient population. We retrospectively analyzed the medical records of 33 patients at least 70 years of age who received 34 OLT from July 1995 to July 2002. There were 16 women and 17 men of mean age 73.7 years. Etiologies of end-stage liver disease (ESLD) were: HCV (17/33, 52%), cryptogenic cirrhosis (8/33, 24%), PBC (3/33, 9%), Laennec's cirrhosis (2/33, 6%), and others (3/33, 9%). According to the UNOS classification, 15/34 (44%) were status 3, 16/34 (47%) status 2, and 3/34 (9%) status 1. Among 13/33 patients who died (39%), 1-year and 3-year survival rates were 78.79% and 71.43%, respectively. Based on UNOS criteria, 4/15 (26%) were status 3; 6/16 (37%), status 2; and 3/3 (100%), status 1 (P value = .04 for status 1 patients). There was no statistical differences between the scores using the Model for End-Stage Liver Disease (MELD) among those who died (MELD (19) versus MELD (17.35) respectively (P = .50). There was a statistically significant difference in cold ischemia time (CIT) and warm ischemia time (WIT) between those who died (P = .024 and.010, respectively). These results suggest that in this group of patients UNOS status classification, CIT and WIT correlate with survival. The sample size was too small to derive a conclusion about the association with the MELD score.

Adult↗
PubMed2004

Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.

The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia. Distributions of genotypes at all loci and in all populations fit Hardy-Weinberg equilibrium expectations. There was not a single allele predominant at any of the loci in these populations, with the exception of A*3002 [allele frequency (AF) = 0.233] in Zambians and Cw*1601 (AF = 0.283) in Malians. This distribution was consistent with balancing selection for all class I loci in all populations, which was evidenced by the homozygosity F statistic that was less than that expected under neutrality. Only in the A locus in Zambians and the C locus in Malians, the AF distribution was very close to neutrality expectations. There were six instances in which there were significant deviations of allele distributions from neutrality in the direction of balancing selection. All allelic lineages from each of the class I loci were found in all the African populations. Several alleles of these loci have intermediate frequencies (AF = 0.020-0.150) and seem to appear only in the African populations. Most of these alleles are widely distributed in the African continent and their origin may predate the separation of linguistic groups. In contrast to native American and other populations, the African populations do not seem to show extensive allelic diversification within lineages, with the exception of the groups of alleles A*02, A*30, B*57, and B*58. The alleles of human leukocyte antigen (HLA)-B are in strong linkage disequilibrium (LD) with alleles of the C locus, and the sets of B/C haplotypes are found in several populations. The associations between A alleles with C-blocks are weaker, and only a few A/B/C haplotypes (A*0201-B*4501-Cw*1601; A*2301-B*1503-Cw*0202; A*7401-B* 1503-Cw*0202; A*2902-B*4201-Cw*1701; A*3001-B*4201-Cw*1701; and A*3601-B*5301-Cw*0401) are found in multiple populations with intermediate frequencies [haplotype frequency (HF) = 0.010-0.100]. The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci. Comparison of the genetic distances measured by the distribution of alleles at the HLA class I loci in the sub-Saharan populations included in this and other studies indicate that the Luo population from western Kenya has the closest distance with virtually all sub-Saharan population so far studied for HLA-A, a finding consistent with the putative origin of modern humans in East Africa. In all African populations, the genetic distances between each other are greater than those observed between European populations. The remarkable current allelic and haplotypic diversity in the HLA system as well as their variable distribution in different sub-Saharan populations is probably the result of evolutionary forces and environments that have acted on each individual population or in their ancestors. In this regard, the genetic diversity of the HLA system in African populations poses practical challenges for the design of T-cell vaccines and for the transplantation medical community to find HLA-matched unrelated donors for patients in need of an allogeneic transplant.

Africa South of the Sahara↗
PubMed2004

Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.

Type 2N von Willebrand disease (VWD) is characterized by a markedly decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). The FVIII binding site has been localized within the first 272 amino acid residues of mature VWF, encoded by exons 18-23. Two substitutions in exon 18 of VWF gene, inducing candidate mutations Y795C and C804F were identified in the heterozygous state in two French patients who also displayed the frequent R854Q mutation in exon 20. Expression studies in Cos-7 cells showed that these abnormalities, which implicate cysteine residues, induced secretion, multimerization and FVIII binding defects of corresponding recombinant VWF. Results from transfection experiments with R854Q, performed to reproduce the hybrid VWF present in patient plasma, were in agreement with those obtained for patient's plasma VWF. These findings confirm the importance of the VWF D' domain in FVIII binding. In addition, this work shows that exon 18 should preferentially be sequenced in type 2N VWD patients when the frequent R854Q mutation in exon 20 has been excluded or detected in the heterozygous state.

Adult↗
PubMed2004

Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome).

ADAMTS13, the specific von Willebrand factor (VWF)-cleaving metalloprotease, prevents the spontaneous formation of platelet thrombi in the microcirculation by degrading the highly adhesive ultralarge VWF multimers into smaller forms. ADAMTS13 severe enzymatic deficiency and mutations have been described in the congenital thrombotic thrombocytopenic purpura (TTP or Upshaw-Schulman syndrome), a rare and severe disease related to multivisceral microvascular thrombosis. We investigated six French families with congenital TTP for ADAMTS13 enzymatic activity and gene mutations. Six probands with congenital TTP and their family were tested for ADAMTS13 activity in plasma using a two-site immunoradiometric assay and for ADAMTS13 gene mutations using polymerase chain reaction and sequencing. ADAMTS13 activity was severely deficient (< 5%) in the six probands and one mildly symptomatic sibling but normal (> 50%) in all the parents and the asymptomatic siblings. Ten novel candidate ADAMTS13 mutations were identified in all families, showing either a compound heterozygous or a homozygous status in all probands plus the previous sibling and a heterozygous status in the parents. The mutations were spread all over the gene, involving the metalloprotease domain (I79M, S203P, R268P), the disintegrin domain (29 bp deletion in intron/exon 8), the cystein-rich domain (acceptor splice exon 12, R507Q), the spacer domain (A596V), the 3rd TSP1 repeat (C758R), the 5th TSP1 repeat (C908S) and the 8th TSP1 repeat (R1096stop). This study emphasizes the role of ADAMTS13 mutations in the pathogenesis of congenital TTP and suggests that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process.

ADAM Proteins↗
PubMed2003

Sirolimus therapy in orthotopic liver transplant recipients with calcineurin inhibitor related chronic renal insufficiency.

UNLABELLED: Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. Our clinical experience has revealed sirolimus to be an effective agent in treating renal insufficiency related to calcineurin inhibitor toxicity. METHODS: We performed a retrospective review of the medical records of OLT recipients suffering from chronic renal insufficiency and treated with sirolimus at the University of Miami. RESULTS: Fourteen patients (nine men and five women) of mean age 57 years who had been treated with tacrolimus for at least 30 days were converted to sirolimus after developing nephrotoxicity. Mean creatinine clearances collected on day 0, 30, 60, and 90 after conversion were 40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of acute cellular rejection were not increased during the sirolimus conversion. CONCLUSION: This retrospective review suggests that OLT patients suffering from tacrolimus-related renal insufficiency successfully converted to sirolimus may benefit from this therapy.

Creatinine↗
PubMed2003

Peptide immunogens based on the envelope region of HIV-1 are recognized by HIV/AIDS patient polyclonal antibodies and induce strong humoral immune responses in mice and rabbits.

Peptide immunogens produced by novel synthesis techniques and based on envelope proteins have repeatedly proven successful in inducing anti-HIV and anti-SIV responses in addition to producing anti-peptide immunity [Vaccine 12 (8) (1994) 736; AIDS Res. Hum. Retroviruses 14 (9) (1998) 751; Vaccine (2002) 2680]. We report here the design and evaluation of synthetic peptide constructs mimicking the variability of the third variable (V3) loop, or representing the conservation of the CD4 region of HIV-1 envelope. Three peptides based on the V3 region of HIV-1 subtype C gp120 and designated multiple epitope immunogens (MEI) differ in that one was randomly branched containing a spacer (b-MEI-s), another conjugated to a tetrameric lysine core (MEIV3b(4)) and the third conjugated to poly-L-lysine (poly-L-MEI). The method of synthesis employed produced peptides that were either linear, dimeric or tetramerically branched thereby providing differing levels of conformation. In addition the peptides also differed in their levels of variability. A fourth peptide designated B138 was based on a conserved region of HIV-1 envelope. The aim of this work was to evaluate the effect of variability and level of conformation on the immunogenicity of variable region peptides (MEI's) when compared to that of a known immunogenic and conserved region peptide (B138). Anti-peptide humoral immunity induced in BALB/c mice and New Zealand White rabbits produced antigen-recognizing antibody titres of </=5000 in enzyme linked immunosorbent assays (ELISA) and stimulation indices (SI) of 7 in cell proliferation assays. Plasma polyclonal antibodies collected from HIV/AIDS patients (from South Africa, Botswana and Puerto Rico) recognized the peptide constructs at antibody titres of </=5000. As demonstrated by mouse, rabbit and human antibody and proliferation responses, the immunogenicity and antigenicity of the peptides varied, with MEIV3b(4) responding better than the other three, at times even surpassing the conserved region peptide B138.

AIDS Vaccines↗
PubMed2002

Gap formation and soft phonon mode in the Holstein model.

We investigate electron-phonon coupling in many-electron systems using the dynamical mean-field theory in combination with the numerical renormalization group. This nonperturbative method reveals significant precursor effects to the gap formation at intermediate coupling strengths. The emergence of a soft phonon mode and very strong lattice fluctuations can be understood in terms of Kondo-like physics due to the development of a double-well structure in the effective potential for the ions.

Journal Article↗
PubMed2002

Producing a highly immunogenic synthetic vaccine construct active against HIV-1 subtype C.

A synthetic peptide immunogen designated the multiple epitope immunogen (MEI), based on the principle neutralizing domain (PND) of the third variable region (V3) of the HIV-1 subtype C surface envelope protein was prepared by combining two different modes of synthesis [Vaccine 12 (8) (1994) 736; AIDS Res. Hum. Retroviruses 14 (9) (1998) 751; J. Biol. Chem. 263 (4) (1988) 1719]. The MEI induced strong humoral immune responses (titers of >100) in Swiss White and Balb/c mice and antibodies from individuals with HIV/AIDS recognize the immunogen at similar antibody titers. Anti-MEI antibodies were detected by ELISA (using HIV-1 and the immunogen as antigen) and confirmed by proliferation assays (stimulation indices of >5).

AIDS Vaccines↗
PubMed2002

Plasminogen activation by blood monocytes and alveolar macrophages in primary pulmonary hypertension.

The pathophysiology of primary pulmonary hypertension (PPH) remains poorly understood. Vascular wall remodeling and endothelial dysfunction reflected by modifications in plasma fibrinolytic proteins and von Willebrand factor have been well documented in PPH. We hypothesize that endothelial mediators, produced in excess in PPH patients, may stimulate migrating mononuclear cells and thereby modulate alveolar macrophage function; in particular, the plasminogen activation system. Components of the fibrinolytic system were therefore studied in plasma, blood monocytes and alveolar macrophages obtained from bronchoalveolar lavage in 10 patients with PPH and in four controls. Compared with controls, PPH patients had elevated plasma levels of tissue-type plasminogen activator (15.6 +/- 9.9 versus 5.5 +/- 3 ng/ml) and plasminogen activator inhibitor-1 (27.8 +/- 23 versus 16.4 +/- 12 ng/ml). In contrast, binding and activation of plasminogen by single-chain urokinase-type plasminogen activator (scu-PA) at the surface of blood monocytes and alveolar macrophages were not different from those of control values. Dissociation constants (K(d)) for binding of scu-PA and plasminogen to alveolar macrophages were similar in both PPH (4.7 +/- 1.5 and 0.88 +/- 0.3 micromol/l, respectively) and control (6.7 +/- 0.1 and 1.02 +/- 0.12 micromol/l, respectively) groups. These results indicate that in PPH patients the fibrinolytic activity of alveolar macrophages is normal, whereas endothelial fibrinolytic proteins are abnormally elevated in plasma.

Adult↗
PubMed2002

Generation of von Willebrand factor epitope libraries expressed in E. coli.

The von Willebrand factor (VWF) subunit is composed of several domains, often coinciding with structural regions, characterized through their specific interaction with a ligand. Since several monoclonal antibodies (MoAbs) have been shown to functionally interfere with one of the specific interactions, we have created libraries of bacterial clones expressing peptidic sequences of VWF to map antibodies directed against this protein. Randomly cleaved fragments of VWF cDNA have been cloned in a plasmid designed for the expression of small peptides as part of larger fusion proteins. The NovaTope system is a useful procedure for protein analysis, allowing screening of epitopes composed of contiguous amino acid residues. To map MoAbs with conformational discontinuous epitopes displayed on small as well as large peptidic domains, this technique had to be widely modified to obtain two VWF peptide libraries expressing two ranges of peptide length (15-70 and 100-300 amino acids). Screening with six MoAbs with an epitope in a known region was performed to control both libraries. Four MoAbs were mapped through the characterization of overlapping sequences for 5-10 different positively expressed clones respectively. Two of these mapped MoAbs had no known inhibitory effect and bind reduced VWF only. The fact that the two other MoAbs mapped VWF functional interactions with ligands, platelet GPIIb/IIIa and Factor VIII, respectively, demonstrate that our libraries are valuable tools to determine conformational epitopes.

Antibodies, Monoclonal↗