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A A Ansari

Publications and source records attributed to A A Ansari.

At least 19 recordsLinked to original sources
PubMed1992

Human T cell responses to purified pollen allergens of the grass, Lolium perenne. Analysis of relationship between structural homology and T cell recognition.

The in vitro proliferative response to purified allergens of the grass, Lolium perenne pollens was studied using PBMC from individuals allergic to grass pollens and Ag-specific T cell lines and T cell clones derived from them. The PBMC from all 10 subjects studied showed a strong response to Lol p I and most of them (8 of 10) also responded to Lol p III. Although Lol p II induced a moderate response in 4 of 10 individuals, it did not induce any response in others at all the Ag concentrations tested. However, one of the subjects (JH) responded to, besides Lol p I, both Lol p II and Lol p III equally well. Analysis of Ag-specific T cell lines and clones derived from three individuals showed varied pattern of reactivity to the Lol p allergens. Some of the Lol p III-specific T cell lines and clones were also stimulated by Lol p I and similarly, some of the Lol p I-specific T cell clones (derived from four other subjects) were stimulated by Lol p III; thus showing a two-way cross-reactivity between those T cells. In both cases, the cross-reactivity to Lol p II, when observed, was lower than that seen with Lol p I and Lol p III. Comparison of amino acid sequences of the three Lol p proteins revealed a significant level of structural similarity among them, including several segments of identical sequences. Although one of the synthetic peptides of Lol p III sharing appreciable sequence homology with other proteins stimulated PBMC from two subjects, three other peptides did not. Nevertheless, these studies indicated the possible existence of cross-reactive T cell epitope(s) among the grass pollen allergens. Based on these results, the relationship between amino acid sequence homology among the Lol p proteins and their recognition by T cells is discussed.

Allergens↗
PubMed1992

Interleukin-4 is an autocrine growth factor secreted by the L-428 Reed-Sternberg cell.

Recent evidence indicates that Reed-Sternberg (RS) cells from many cases of Hodgkin's disease have features of activated lymphocytes and that lymphokines from activated lymphocytes induce proliferation of L-428 RS cells. It is shown here that a lymphokine similar to a lymphokine secreted by activated lymphocytes is secreted by L-428 cells. This lymphokine has a molecular weight approximately equal to 68,000 daltons, identical to glycosylated recombinant interleukin-4 (rIL-4), and cross-reacts with monoclonal anti-IL-4 in Western immunoblotting. This Hodgkin's cell growth factor (HCGF) is 100% neutralized by polyclonal anti-IL-4 antibodies and competes for the IL-4 receptor. After acid-elution, the L-428 RS cell has been shown to have 3,396 +/- 120 high-affinity receptor sites/cell. HCGF competes with rIL-4 for this receptor and L-428 cells contain mRNA for IL-4. Although all evidence indicates that IL-4 is an important secreted autocrine growth factor for L-428 RS cells, anti-IL-4 has no effect on the sustained serum-free growth of these Hodgkin's cells, suggesting that either the IL-4 receptor and the IL-4 receptor-growth factor complex are protected from antibody inhibition or other mechanisms are responsible for the sustained proliferation of L-428 RS cells.

Antibodies↗
PubMed1992

Distinct in vivo functions of two macrophage subpopulations as evidenced by studies using macrophage-deficient op/op mouse.

The op/op mice totally lack macrophage growth factor colony-stimulating factor (CSF)-1 and thus, by definition are completely depleted of CSF-1-dependent functions of the macrophage cell lineage. Moreover, they possess a severe and generalized macrophage deficiency. However, residual macrophages of these mice should still have normal CSF-1-independent functions. Studies designed to elucidate this issue have revealed that op/op mice are capable of normal in vivo phagocytic function and demonstrate normal humoral and cellular response postimmunization with sheep red blood cells. However, release of monokines such as tumor necrosis factor and granulocyte CSF following administration of endotoxin is severely impaired in op/op mice as compared with littermate controls. These studies suggest that the CSF-1-dependent macrophage population (absent in the op/op mouse) is primarily responsible for regulatory functions of these cells mediated by monokines, while the CSF-1-independent macrophage population (present in the op/op mouse) is primarily responsible for the classical macrophage functions in immunity such as phagocytosis, antigen processing and presentation.

Animals↗
PubMed1992

Use of designer recombinant mitochondrial antigens in the diagnosis of primary biliary cirrhosis.

The appearance of autoantibodies against mitochondria in patients with primary biliary cirrhosis has been known for more than 25 yr. In the past, based on the biochemical complexity of the mitochondrion and the use of crude extracts for immunodiagnosis, a degree of nonspecificity in assaying for antibodies to mitochondria has been present. This problem has been largely circumvented by the cloning of the mitochondrial antigens and the identification of the E2 subunits of the pyruvate dehydrogenase complex and the branched chain 2-oxo-acid dehydrogenase complex as the major and immunodominant autoantigens of primary biliary cirrhosis. More than 90% of patients with primary biliary cirrhosis have been shown to react with one or both of these enzymes using either recombinant antigen or purified native protein. Approximately 10% of patients recognize only E2 subunits of branched chain 2-oxo-acid dehydrogenase complex and not pyruvate dehydrogenase complex. Such patients would be missed by diagnostic assay that has a low sensitivity to antibodies against E2 subunits of branched chain 2-oxo-acid dehydrogenase complex. The use of recombinant and biochemically pure antigens has permitted structural and conformational analysis of epitope mapping. We have taken advantage of the antigenic mapping studies of both primary biliary cirrhosis and branched chain 2-oxo-acid dehydrogenase complex E2 subunits and designed a molecule that expresses the immunodominant epitopes of both. Using this dual-headed molecule that coexpresses the epitope of two different antigens, we report herein a sensitive and reproducible assay for antibodies to mitochondria in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1992

The effectiveness of the Duo-Flo BioClean unit for controlling airborne antigen levels.

The Duo-Flo BioClean unit, consisting of a chamber unit with an animal rack, a HEPA filtration system, an air plenum, and a blower, was evaluated as a control unit for airborne rat antigen levels in the room housing the unit. The unit was evaluated in negative and positive pressure operating modes. In the negative mode, room air is drawn into the unit, passes over the animal cages, and is then exhausted into the room through the filters. In the positive mode, air passes through the filters, traverses the animals, and then is discharged into the room. Airborne antigen concentrations (ng/m3) and particle size distributions associated with antigen were measured during the two operating modes and prior to operation (background mode). Airborne antigen concentrations during the positive pressure operating mode were higher than during the negative pressure mode or background. Approximately 70% of airborne antigen was associated with respirable particles during background and positive pressure operating modes. A total of 36% of airborne antigen mass was associated with respirable particles during negative pressure operation. The unit is usually operated in the positive mode to protect experimental animals. This study clearly indicates that negative pressure operation would reduce the dispersion of dust-containing antigen, the exposure of room occupants to airborne antigen, and the risk to many workers of contracting animal allergy.

Air Pollutants, Occupational↗
PubMed1992

In situ detection of human cytomegalovirus immediate-early gene transcripts within cardiac myocytes of patients with HIV-associated cardiomyopathy.

OBJECTIVE: Recent clinical and echocardiographic studies have identified dilated cardiomyopathy in 10-20% of HIV-infected adults. The purpose of this study was to determine the role of cardiotropic cytomegalovirus (CMV) infection in the development of HIV-associated cardiomyopathy. DESIGN: We generated sense and antisense digoxigenin-labeled riboprobes derived from the CMV immediate-early (IE) and delayed-early (DE) genes and applied them retrospectively to endomyocardial biopsy samples and control autopsy cardiac samples from HIV-infected patients. SETTING: Tertiary care, referral hospital. PATIENTS: Twelve consecutive HIV-infected patients with global left ventricular hypokinesis demonstrated on two-dimensional echocardiography; eight randomly selected control autopsy cardiac samples from HIV-infected patients without cardiac disease during life. MEASUREMENTS AND MAIN RESULTS: Of the 12 endomyocardial biopsy specimens, six (50%) were found to have specific myocyte nuclear and perinuclear hybridization for transcripts of the CMV IE gene, consistent with non-permissive or latent infection. Similar patterns were not found in any of the eight autopsy control samples. All six patients presented with unexplained congestive heart failure and had CD4 counts less than 100 x 10(6)/l; all six biopsy samples had immunohistochemical evidence of increased myocardial major histocompatibility complex (MHC) class I expression, a finding typical of non-HIV myocarditis. None of the endomyocardial biopsy samples had characteristic CMV inclusions and no specific hybridization was noted with the DE gene riboprobe, suggesting that no active viral DNA replication was present. Only two of the six patients with myocyte hybridization with the IE riboprobe had clinical evidence of solid organ infection with CMV at the time of cardiovascular presentation. CONCLUSIONS: This study is the first to demonstrate the expression of the IE gene of CMV within myocytes from HIV-infected patients with cardiomyopathy, suggesting a non-permissive infection of myocytes without classical intranuclear inclusions. Myocyte infection may be necessary to trigger cellular and humoral-mediated cardiac injury and may be best identified using in situ hybridization techniques.

Adult↗
PubMed1992

The simian immunodeficiency virus infected macaque: a model for pediatric AIDS.

Maternal-to-infant transmission of simian immunodeficiency virus (SIV) has been demonstrated in the rhesus macaque following experimental infection of pregnant rhesus monkeys, either parenterally or by inoculation of virus into the amniotic fluid. Virus infection occurred in 3 of 12 (25%) rhesus infants born to mothers with SIV infection induced by parenteral inoculation of virus during gestation. However, these infants did not become seropositive or virus positive until they were 9-15 months old, suggesting that virus infection most likely occurred as the result of breast feeding. Infection has also been demonstrated in one rhesus infant following virus inoculation into the amniotic fluid during late gestation. These observations support the increasing evidence that intrapartum or postpartum infection may be important mechanisms for the maternal-infant transmission of HIV. The SIV-infected macaque should prove to be a useful model to evaluate the timing and mechanisms of lentivirus infection in infants, to determine maternal factors associated with transmission to the fetus or infant, and to evaluate therapeutic regimens for the prevention or treatment of pediatric AIDS.

Amnion↗
PubMed1991

Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production.

We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.

Adult↗
PubMed1991

Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1991

Sequencing of HLA-D in responders and nonresponders to short ragweed allergen, Amb a V.

We investigated the molecular basis for the striking association between HLA-DR2,Dw2 and human immune responsiveness to the Ambrosia artemisiifolia (short ragweed) pollen allergen Amb a V by sequencing the second exons of the DRB and DQB1 genes of 17 selected ragweed-allergic Caucasoid subjects. We also studied the DQA1 allelic polymorphic regions (APRs) in these patients by dot-blotting using sequence-specific oligonucleotides (SSOs). The deduced amino acid sequences of the respective class II beta and alpha polypeptides were compared, with particular emphasis on residues in the APRs that are implicated in antigen binding. No evidence for "new" HLA-DRB or DQB sequences unique to Amb a V responders were found on sequencing seven Dw2+ subjects. This suggests that the presence of a particular Dw2-associated class II molecule usually provides a necessary, but not always sufficient condition for responsiveness to Amb a V. The HLA phenotypes of three subjects suggest that they possess novel recombinant haplotypes containing either DRB1*1501 and DRB5*0101 (DR2.2-associated) or DQB1*0602 (DQ1.2-associated) sequences. In these subjects, responsiveness to Amb a V was associated with the DR2.2 but not the DQ1.2 sequences, suggesting that DR alpha beta I or DR alpha beta V class II molecules are involved in antigen presentation. We investigated whether there may be shared HLA-D-encoded responder sequences present in all responders, including some exceptional DR2- Amb a V responders. The 13 subjects producing antibody (Ab) responses to Amb a V [either from natural exposure and/or after ragweed immunotherapy (Rx)] possessed DRB1*1501, 1601, 1602, 0103, 0402, 0404, 0801, or 1101 sequences, which share the majority of their aa residues in the APRs 2-4. Some of these shared residues might be important for the binding of a common Amb a V agretope prior to presentation of the class II Amb a V complex to the T-cell receptor (Tcr). An alternative postulate is that the recognition of two different Amb a V agretopes may be determined by the beta 1 polypeptides of molecules having the DR2 and DQw3 specificities.

Alleles↗
PubMed1991

HLA-D gene studies in relation to immune responsiveness to a grass allergen Lol p III.

The grass pollen allergen Lol p III (Mr 11,000) is a well-characterized antigen that has been found useful in immunogenetic studies of human immune responsiveness. Since immune responsiveness to this allergen is associated with HLA-DR3, we investigated whether there was any sequence in the HLA-D region that would render a person "susceptible" [antibody (Ab)-positive] to the allergen. By sequence-specific oligonucleotide (SSO) slot-blot and sequence analyses of polymerase chain reaction (PCR)-amplified genomic DNA from Lol p III responder and nonresponder subjects, Ab responsiveness was found to be strongly associated with the sequence Glu-Tyr-Ser-Thr-Ser (EYSTS), present in the first polymorphic regions of DR beta I polypeptide chains of DR3, DR11 (split of DR5), and DRw6. Of the 41 grass-allergic subjects investigated, 19 had the EYSTS sequence, of whom 18 (95%) were Lol p III immunoglobulin G (IgG) Ab responders; among the 22 EYSTS- subjects, ten were Lol p III responders (P = 0.001, relative risk = 21.6). No such association was found with any polymorphic sequences in other DR beta chains, or in DQ alpha I and DQ beta I chains. These findings suggest that the EYSTS sequence is important in the presentation of an epitope of Lol p III; other sequence(s) may be involved in the presentation of other epitope(s). To our knowledge, this is the first demonstration of a strong association between a specific HLA sequence and immune responsiveness to a well-defined antigen. The paper shows that presence of the EYSTS sequence classifies subjects as Lol p III responders in 18/19 cases.

Allergens↗
PubMed1991

Studies on serum gamma-glutamyl transpeptidase in primary idiopathic hypothyroidism patients.

Variations in the levels of serum gamma-glutamyl transpeptidase (GGT) were measured in control subjects and in 39 adult primary idiopathic hypothyroidism (PIH) patients. The serum GGT activity was low in PIH patients compared to that of control subjects. A more significant correlation was found between serum GGT and T3 (r = 0.766) but not with T4 (r = 0.476). The comparison of serum GGT with TSH has revealed that those two parameters are not parallel with each other (r = -0.454). No significant correlation between serum GGT activity, age, and sex in PIH patients and control subjects was observed. The present available data indicate that measurement of serum GGT might be useful as a marker index in PIH patients.

Adult↗
PubMed1991

The identification and cloning of the murine genes encoding the liver specific F alloantigens.

The liver specific F alloantigen is a highly conserved abundant protein found in hepatic cytoplasm; smaller amounts are detected in renal tubule cells and the perikaryon cells of the central nervous system. Although the biological function of the F alloantigen is unknown, the immune response to F has been extensively studied as a murine model of tolerance and autoimmunity. Murine F exists in two allelic forms, designated F type 1 and type 2, each of approximately 43 kDa. The immune response to the allotypic form is restricted to mouse strains of I-Ak. Responding strains immunized with allotypic F break tolerance and produce precipitating antibody that reacts with both allelic forms, i.e., immunogen and self. Thus an autoantibody is produced. Using the previously isolated rat F cDNA as a probe, we report the cloning and sequencing of the two murine F allotypes. These two alleles are nearly homologous except at the extremes of the coding sequence. There are a number of regions within the F sequence that are similar to peptides that interact specifically with I-Ak. In particular, there is a sequence near the carboxy terminus, where the two allotypes differ, that has homology to the I-Ak restricted malarial antigen peptide of the ring-infected erythrocyte surface antigen (RESA).

Amino Acid Sequence↗
PubMed1991

Detection of occult simian immunodeficiency virus SIVsmm infection in asymptomatic seronegative nonhuman primates and evidence for variation in SIV gag sequence between in vivo- and in vitro-propagated virus.

Polymerase chain reaction techniques were used to identify simian immunodeficiency virus (SIV) SIVsmm gag sequences in genomic DNA isolated from peripheral blood mononuclear cells from naturally infected asymptomatic seropositive and seronegative sooty mangabeys (Cercocebus atys) and from experimentally infected but asymptomatic rhesus macaques (Macaca mulatta). The results indicate that most if not all SIV-seronegative mangabeys from the colony at the Yerkes Primate Center are in fact infected with SIVsmm despite their lack of humoral immune response, confirming previous immunological and virological observations made by our laboratory. Sequence analysis of these particular gag fragments from the mangabey revealed an average of 88% nucleotide sequence homology but 97% amino acid identity with the previously published sequence of the SIVsmmH4 clone. The significance of this finding relative to the asymptomatic state of SIV-infected mangabeys and disease-susceptible SIV-infected rhesus macaques is discussed.

Animals↗
PubMed1991

The contribution of I-Abm12 to the production of autoantibodies to dsDNA.

The development of IgG autoantibodies to dsDNA in NZBxNZW F1 (NZB/W) and NZBxSWR F1 (SNF1) mice have been linked to specific alleles of MHC class II genes contributed by the NZW and SWR parents respectively. Recently, our laboratory has shown that the introduction of the bm12 mutation into NZB mice (NZB.H-2bm12) results in mice which are phenotypically similar to NZB/W F1 mice and, in particular, develop IgG anti-dsDNA antibodies. A variety of immune abnormalities have been described in autoimmune NZB (H-2d) mice. It is, however, unclear at present, whether all these abnormalities are due to the influence or effect of a single set of linked genes or due to multiple genes. It was reasoned that NZB.H-2bm12 mice provide a unique opportunity to examine this issue. Specifically, we bred a series of five different F1 colonies of mice: (a) NZB.H-2bm12/b F1; (b) NZB.H-2bm12/d F1; (c) NZB-H-2b/d F1; (d) NZB-H-2bm12 x B6.C-2bm12 F1 (NZB/B6.H-2bm12 F1); and (e) NZB x B6.C-H-2bm12 F1 (NZB/B6.H-2d/bm12 F1) mice. All groups of mice were serially followed for the appearance of IgM and IgG anti-ssDNA and anti-dsDNA antibodies, splenic CFU-B, spontaneous secretion of IgM, FMF analysis, proteinuria and survival. We report herein that H-2bm12 genes have a dominant influence on the appearance of IgG anti-dsDNA antibodies. In contrast, antibodies to ssDNA, IgM secreting cells, CFU-B and Ly-1 B cells are linked to genes from the NZB background. Finally, we particularly note an absence of IgG antibodies to dsDNA in NZB-H-2b/d F1 mice.

Amino Acid Sequence↗
PubMed1991

Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy.

Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM.

Adult↗