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Biomedical subjects

M Blank

Publications and source records attributed to M Blank.

At least 109 records · Page 6Linked to original sources
PubMed1998

Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black population.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.

Alleles↗
PubMed1998

Differential distribution of beta-dystroglycan in rabbit and rat retina.

The distribution of the dystrophin-associated glycoprotein complex was investigated in rabbit and rat retina by using the monoclonal antibody 43DAG/8D5, which specifically recognizes beta-dystroglycan, a central component of the complex. In cryostat sections of retinae from both species, the authors observed staining of blood vessels, continuous labeling around the vitreal border, and strong immunoreactivity in the outer plexiform layer (OPL). Electron microscopy showed that the immunoreactivity associated with the vitreal border of the retina was the result of a subcellular concentration of beta-dystroglycan in the endfeet of Müller glial cells. A similar concentration was observed in endfeet of perivascular astrocytes in the region of contact with the capillary basal lamina. In the OPL, beta-dystroglycan was associated with the terminals of both rods and cones. The label was almost exclusively found outside the synaptic area and was particularly strong in the extensions of the photoreceptor terminals protruding into the OPL. In the OPL of the rabbit retina, the authors found additional immunoreactivity associated with the tips of postsynaptic horizontal and bipolar cell processes. These results show that the dystrophin-associated glycoprotein complex is subcellularly concentrated in photoreceptor terminals and glial cell endfeet, and that the rabbit retina differs from the rat retina by the additional expression of this complex in bipolar and horizontal cells.

Animals↗
PubMed1998

Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome.

BACKGROUND: The antiphospholipid syndrome (APS) entails a prothrombotic state associated with the presence of anticardiolipin antibodies (aCL). aCL were shown to promote endothelial cell and platelet activation and to induce an APS-like syndrome in mice when administered intravenously. Recent data suggest that aCL target the plasma cofactor beta2-glycoprotein I (beta2GPI) rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-beta2GPI antibodies obtained from one patient possess pathogenic properties. METHODS AND RESULTS: Three beta2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS. The three antibodies were shown to bind beta2GPI immobilized on irradiated plates, yet only ILA-1 bound beta2GPI coated onto nonirradiated plates. Furthermore, when using the anti-beta2GPI enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase beta2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4 induced significant expression of adhesion molecules when preincubated with human umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to pregnant BALB/c mice induced clinical findings consistent with APS (increased fetal resorptions, reduced platelet counts, and prolonged activated partial thromboplastin time), whereas both ILA-4 and the control human IgM did not produce similar effects. CONCLUSIONS: The results of the study demonstrate the differential effects of various populations of anti-beta2GPI antibodies on endothelial cell activation and on experimental APS.

Adult↗
PubMed1998

Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin-3 and granulocyte-macrophage colony-stimulating factor expression.

OBJECTIVE: To evaluate the immunomodulatory potential of ciprofloxacin in mice with experimental antiphospholipid syndrome (APS). METHODS: Ciprofloxacin or ceftazidime (control antibiotic) was given to mice with experimentally induced APS. The titers of autoantibodies, levels of cytokines, and number of cytokine-producing cells were determined by enzyme-linked immunosorbent assay. Myeloid progenitor cells were determined by granulocyte-macrophage colony-forming unit, and interleukin-3 (IL-3) messenger RNA (mRNA) was tested by Northern analysis. RESULTS: A decrease in the incidence of pregnancy loss and an improvement in the clinical manifestations of APS were noted in the mice treated with ciprofloxacin, compared with the mice given ceftazidime. The effect of ciprofloxacin was found to be associated with increased serum levels of IL-3 and with increased IL-3 mRNA transcription in the splenocytes. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was documented by elevated titers in the sera and elevated numbers of colony-forming cells in the bone marrow. CONCLUSION: Ciprofloxacin prevents the manifestations of experimental APS. This effect may be associated with increased IL-3 levels and GM-CSF expression.

Adjuvants, Immunologic↗
PubMed1998

Virtual cisternoscopy of intracranial vessels: a novel visualization technique using virtual reality.

This paper introduces a different visualization method which we call "virtual cisternoscopy" using 3D MRA data sets. Virtual cisternoscopy uses well known tools, such as perspective volume rendering (pVR), fly-through techniques, and interactive visualization and combines them to a new approach featuring motion to resolve spatial relationships of intracranial vessels and vascular malformations. With a dedicated flight protocol extraluminal topography of intracranial arteries was analyzed using pVR. For evaluation of difficult vascular malformations extraluminal views are necessary. Therefore, movies of pVR views were produced simulating virtual tracks of neurosurgical flexible endoscopes, by flying around the intracranial vessels and vascular malformations within the cisterns. Endoluminal views were acquired additionally for precise evaluation of cases with complex vessel topography. Two healthy volunteers and three patients were examined. Comparing MIP and pVR images relevant advantages of pVR were found, such as depth information, perspective, lighting, and color. In contrast to MIP and source images of the MRA data set, virtual cisternoscopy of an aneurysm of the left middle cerebral artery demonstrated clearly an early origin of an artery in the region of the aneurysm neck/sac. In this case only virtual cisternoscopy led to the correct therapeutical decision. In a newborn, the type of a vein of Galen aneurysmal malformation could only be evaluated reliably by means of virtual cisternoscopy. The third case of a patient with a clipped aneurysm was evaluated more easily with virtual cisternoscopy than with DSA. In conclusion, virtual cisternoscopy may improve the pretherapeutic visualization of intracranial vascular malformations.

Adult↗
PubMed1998

Increased prevalence of autoantibodies in celiac disease.

Several features suggest an immune mechanism operates in celiac disease. Information on the autoantibody repertoire in this condition is lacking. The purpose of the study was to investigate the reactivity of celiac patients sera to various autoantigens widely distributed in the human intestine. Seventy children, celiacs and controls, were evaluated for serum autoantibodies using ELISA and immunofluorescence. Celiac patients had increased prevalence of serum anti-single-stranded DNA (14%), anti-double-stranded DNA (23%), anti-cardiolipin (14%), and anti-endomysial autoantibodies (63%). The relevance of this finding on the extraintestinal manifestations of celiac disease or the coexistence of autoimmune conditions and celiac disease remains to be determined.

Autoantibodies↗
PubMed1998

Anti-DNA and antiphospholipid antibodies in IVIG preparations: in vivo study in naive mice.

Intravenous immunoglobulins (IVIG) are therapeutic preparations of pooled normal polyspecific immunoglobulin G. We investigated the presence and the in vivo pathogenic potential of autoantibodies against phospholipids and DNA in several commercial IVIG preparations. The presence of autoantibodies and their antiidiotypic antibodies in the IVIG preparations was detected by ELISA. Naive mice were actively immunized with either IVIG preparations or pathogenic monoclonal antibodies (mAbs) against cardiolipin (CL) or DNA, in an attempt to induce autoimmune conditions. The mice were tested for the presence of mouse autoantibodies (auto-Abs) and for clinical parameters of autoimmune diseases. We found high levels of auto-Abs against a panel of phospholipids and DNA, as well as their antiidiotypic Abs, in all the IVIGs. Affinity studies pointed to a lower affinity of auto-Abs of IVIG origin to their respective antigens compared to pathogenic mAbs. Mice immunized with pathogenic anti-CL mAb had high levels of antiphospholipid auto-Abs, accompanied by thrombocytopenia, prolonged aPTT, and an increased fetal resorption rate. Mice immunized with pathogenic anti-DNA mAb had elevated anti-DNA and anti-CL auto-Abs, along with a high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. Following immunization with IgGs from IVIG batches, mice developed high levels of auto-Abs against phospholipids and DNA, similar to mice immunized with pathogenic anti-DNA or anti-CL mAbs, but none of the mice expressed the clinical manifestations compatible with the presence of these autoantibodies. We conclude that commercial IVIG preparations contain high levels of antiphospholipid and anti-DNA auto-Abs, as well as their antiidiotypic Abs. Although these Abs induced the generation of mouse auto-Abs upon active immunization, following idiotypic manipulation they did not prove to be pathogenic in vivo.

Animals↗
PubMed1998

Immunomodulation of experimental antiphospholipid syndrome.

The various therapeutic modalities which are found to be beneficial in experimental antiphospholipid syndrome include: bone marrow transplantation, anti-CD4 monoclonal antibodies, bromocriptine, intravenous immunoglobulins and anti-idiotypes, interleukin-3, and various anti-coagulant and anti-aggregate agents. The advantage of animal models is the ability to evaluate experimental treatments that cannot be tested directly on patients. In this paper, we review the effect of these agents on animal models of antiphospholipid syndrome, their mechanisms of action, and their clinical implications.

Animals↗
PubMed1998

Cloning and functional expression of the human GlcNAc-1-P transferase, the enzyme for the committed step of the dolichol cycle, by heterologous complementation in Saccharomyces cerevisiae.

The gene for the human dolichol cycle GlcNAc-1-P transferase (ALG7/GPT) was cloned by screening a human lung fibroblast cDNA library. The library was constructed in a Saccharomyces cerevisiae expression vector, and the positive clone was identified by complementation of the conditional lethal S.cerevisiae strain YPH-A7-GAL. This strain was constructed by replacing the endogenous promoter of the GPT-gene by the stringently regulated GAL1-promoter. This construct allows to specifically suppress the endogenous enzyme activity. The insert of the positive clone displayed an open reading frame of 1200 nucleotides, coding for a putative protein of 400 amino acids with a calculated molecular weight of 44.7 kDa. The deduced protein sequence shows a homology of over 90% when compared with other mammalian GPT sequences, thus resembling the close phylogenetic relationship between mammalian species. This homology however decreases to 40-50% when compared to more distantly related organisms such as S.cerevisiae , Schizosaccharomyces pombe , or Leishmania amazonensis . Biochemical characterization of the recombinant protein showed that it is functionally expressed in the S.cerevisiae strain YPH-A7-GAL. GlcNAc- and GlcNAc2-PP-Dolichol biosynthesis could be shown with isolated S.cerevisiae membranes from cells harboring the recombinant plasmid and grown on glucose thus suppressing transcription of the endogenous gene. Synthesis could be stimulated by dolicholphosphate and was inhibited by tunicamycin. These results show that we have cloned the human GlcNAc-1-P transferase by heterologous complementation in S. cerevisiae, a strategy that may be useful for the cloning and characterization of glycosyltransferases from a variety of organisms.

Amino Acid Sequence↗
PubMed1998

Characterization of murine monoclonal anti-endothelial cell antibodies (AECA) produced by idiotypic manipulation with human AECA.

The IgG fraction of human anti-endothelial cell antibodies (AECA) obtained from a patient with Wegener's granulomatosis was used as immunogen to raise AECA mAb in mice selected among those which developed vasculitis-like lesions after immunization. Three mAb (BGM, 3C8 and 7G2), selected by cyto-ELISA and flow cytometry analyses, featured a specific reactivity with human umbilical vein endothelial cells (HUVEC) and the mouse endothelial cell line H5V; on the contrary, HEp2 cells, the murine melanoma B16 cell line, the extracellular matrix as well as several other antigens tested were not recognized. BGM mAb, an IgG3 precipitating a 70 kDa structure from HUVEC, was able to induce endothelial cells to secrete amounts of IL-6 significantly higher than irrelevant controls or mAb binding different endothelial antigens (i.e. CD31, CD29, ICAM-1 and HLA class I). BGM mAb induced significant levels of antibody-dependent cell cytotoxicity (13 +/- 2.5 versus 0.6 +/- 0.03%). To the best of our knowledge, BGM is the first murine mAb specific for human endothelial cells generated by idiotypic manipulation; secondly, its biological properties further support the notion of a pathogenic role for AECA in autoimmune-mediated diseases.

Animals↗
PubMed1998

Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus.

OBJECTIVE: To examine the effect of diets with different polyunsaturated fatty acid contents, including linseed oil which contains 70% omega-3 fatty acids, on autoantibody production in idiotype induced mouse model of systemic lupus erythematosus (SLE). METHODS: Five different fats were fed to mice with induced SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and histological examination of kidneys were carried out. RESULTS: SLE mice fed linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less severe kidney damage than mice fed other diets, including fish oil. CONCLUSION: Use of linseed oil may attenuate the severity of SLE and this diet may be recommended for other auto-immune diseases as well.

Animals↗
PubMed1998

Anti-endothelial cell antibodies in the sera of hyperprolactinemic women.

Prolactin (PRL) is closely associated with autoimmune diseases in animal models and humans, and several disease-related autoantibodies were reported in increased titers in patients with hyperprolactinemia (HPRL). We studied the presence of anti-endothelial cell antibodies (AECA) and other autoantibodies in sera of female patients with HPRL. Sera from 25 HPRL patients and 10 healthy female controls were tested for AECA (against both macrovascular and microvascular endothelial cell antigens), anti-dsDNA, and anti-cardiolipin (anti-CL) using ELISA. Sera were considered positive for the autoantibody when the optical density (OD) value was more than 3 s.d. above the mean of the OD in normal controls. Sera from 13 patients were obtained repeatedly during dopaminergic anti-PRL treatment, to relate PRL level or anti-PRL treatment with the autoantibody levels. Elevated micro and/or macrovascular AECA were observed in sera from 19/25 patients (76%). Elevated titers of anti-CL Abs, all beta2-GPI-dependent, and low levels of anti-dsDNA antibodies (Abs) were also observed in the HPRL patients. Inhibition studies showed that the affinity purified AECAs bound the endothelial cell (EC) antigens in a dose-dependent manner. Titers of AECA as well as anti-DNA and anti-CL autoantibodies did not correlate with PRL level nor with the use or duration of anti-PRL treatment. None of the HPRL patients presented clinical manifestations of autoimmune disease. We conclude that elevated levels of AECA as well as anti-DNA and anti-CL autoantibodies are frequent in hyperprolactinemia. Our results further support the association of PRL and autoimmunity, and may point to a relationship between AECA-associated diseases and HRPL. The presence of autoantibodies in patients with HPRL might portend an increased risk for future development of autoimmune disease.

Antibodies, Anticardiolipin↗
PubMed1998

Immunomodulation of murine experimental SLE-like disease by interferon-gamma.

The objective of this study was to assess the impact of murine recombinant IFN-gamma and anti-IFN-gamma monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16/6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-gamma, anti-IFN-gamma mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-gamma, intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-gamma treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-gamma treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-gamma treated mice. IFN-gamma upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-gamma administration can aggravate the clinical and laboratory outcome of 16/6 id induced lupus in BALB/c mice.

Animals↗
PubMed1998

The pathogenic 16/6 idiotype in patients with silica associated systemic lupus erythematosus (SLE) and uranium miners with increased risk for development of SLE.

OBJECTIVE: To investigate the prevalence of the 16/6 idiotype (16/6 Id), a major cross reactive idiotype of anti-DNA antibodies involved in the pathogenesis of experimental lupus, in subjects with an exogenous risk for the development of systemic lupus erythematosus (SLE). METHODS: The titer of 16/6 Id was determined by ELISA in sera of uranium miners exposed to heavy quartz dust: 15 developed definite and 12 probable SLE, 34 had clinical symptoms, and 27 had only serological signs (medium to high titer anti-dsDNA antibodies) of possible connective tissue disease (CTD) development. RESULTS: The prevalence of 16/6 Id was higher in all groups compared to healthy blood donors. It was 18.5% in miners with SLE (definite and probable) and 22.2-26.5% in miners with clinical and/or serological signs for developing CTD. All 16/6 Id positive miners were positive for anti-dsDNA antibodies and other autoantibodies associated with CTD. The prevalence of 16/6 Id in anti-dsDNA positive miners correlated slightly with CTD/SLE symptoms: 55.6% in patients with SLE, 47.4% in miners with possible CTD/SLE, and 22.2% in miners without CTD symptoms. Further, at short term followup, disease progressed in 2 miners of the 16/6 Id positive, but not in 16/6 Id negative miners. CONCLUSION: The detection of 16/6 Id in miners exposed to quartz dust may indicate a higher risk for development of SLE, warranting further studies of the role of 16/6 Id in the development of SLE in a cohort with the same sex, ethnicity, geographic region, and occupation.

Aged↗
PubMed1998

Antiphospholipid syndrome in pregnancy--animal models and clinical implications.

The antiphospholipid (APS) syndrome frequently includes severe pregnancy complications such as fetal wastage and recurrent spontaneous abortions. Animal models for APS in pregnancy can provide both an understanding of the pathogenic mechanisms of anti-phospholipid antibodies (aPL), and aid in the evaluation of various therapeutic modalities in APS. Animal models for APS include both spontaneously developed diseases, as is the case for secondary APS in mice with another autoimmune disease, and induced models of APS. The latter includes either passive induction of disease by antibodies infusion, or active induction via manipulation of the idiotypic network. This article summarizes the literature reports of animal models of APS in pregnancy, deal with the various possible mechanisms of action of aPL in pregnancy, and discuss the treatment options of women having pregnancy complications of APS.

Abortion, Spontaneous↗
PubMed1997

Subcellular concentration of beta-dystroglycan in photoreceptors and glial cells of the chick retina.

Mutations in the dystrophin-glycoprotein complex cause muscle degeneration and dysfunctions in the central nervous system, including an impaired synaptic transmission in the outer plexiform layer (OPL) of the retina. To investigate the basis for this ocular phenotype, we analyzed the distribution of beta-dystroglycan, a central member of the dystrophin-glycoprotein complex, in the chick retina by using the 43DAG/8D5 monoclonal antibody. This antibody reacted specifically with chick beta-dystroglycan, as indicated by its staining of the neuromuscular junction, and its reactivity with a single 43-kilodalton band in Western blots. In the retina, beta-dystroglycan was highly concentrated in the OPL and at the vitreal border of the retina, around the inner limiting membrane. Mechanically isolated and flat-mounted inner limiting membranes were stained by the anti-beta-dystroglycan antibody, and this immunoreactivity could be extracted by detergent, indicating that beta-dystroglycan is associated with membranous structures bound to the basal lamina. Consistently, electron microscopy showed a concentration of beta-dystroglycan in the endfeet of Müller glial cells exclusively in the region of direct contact to the inner limiting membrane. In the OPL, beta-dystroglycan immunoreactivity was concentrated in the distal extensions of rod and cone terminals protruding into the outer plexiform layer. There, beta-dystroglycan codistributed with the alpha1beta subunit of the N-type voltage-gated calcium channel. By contrast to previous reports, we did not detect beta-dystroglycan directly associated with the synaptic regions of conventional or ribbon synapses of the retina. These results show that in the retina beta-dystroglycan is exclusively expressed by photoreceptors and glial cells and that beta-dystroglycan is highly concentrated in subcellular regions of glial cell endfeet and photoreceptor terminals. Moreover, the colocalization of beta-dystroglycan with N-type calcium channels in the outer plexiform layer indicates that both proteins might be part of a macromolecular complex.

Agrin↗
PubMed1997

Electromagnetic field exposure induces rapid, transitory heat shock factor activation in human cells.

Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal growth temperatures results in heat shock factor 1 activation and heat shock element binding, a sequence of events that mediates the stress-induced transcription of the stress gene HSP70 and increased synthesis of the stress response protein hsp70kD. Thus, the events mediating the electromagnetic field-stimulated stress response appear to be similar to those reported for other physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) and could well be the general mechanism of interaction of electromagnetic fields with cells.

Binding Sites↗