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Biomedical subjects

T M Haqqi

Publications and source records attributed to T M Haqqi.

At least 37 records · Page 2Linked to original sources
PubMed1993

The effect of circulating serum factors from patients with systemic lupus erythematosus on protein kinase A (PKA) activity and PKA-dependent protein phosphorylation in T lymphocytes.

T lymphocytes from subjects with active systemic lupus erythematosus (SLE) exhibit reduced cAMP-inducible, protein kinase A (PKA)-dependent phosphorylation of several intracellular substrates compared with healthy and disease controls. To ascertain whether the persistent T cell activation observed during active SLE can result in impaired PKA-dependent protein phosphorylation, normal T cells were activated in vitro by monoclonal anti-CD3-epsilon antibody and recombinant IL1-alpha (rIL1-alpha) for 24 hr. T cell activation, verified by IL2 mRNA, IL2 receptor-alpha (IL2R-alpha) mRNA, and IL2R-beta mRNA expression, did not diminish cAMP-inducible, PKA-dependent protein phosphorylation. We also tested the hypothesis that circulating factors present in active SLE serum can decrease cAMP-inducible total PKA phosphotransferase activity and PKA-dependent protein phosphorylation in normal T lymphocytes. T cells cultured for 24 hr in medium supplemented with 10% active SLE sera (from subjects who exhibited the defect of PKA-dependent protein phosphorylation) exhibited similar total PKA phosphotransferase activity and substrate phosphorylation as cells cultured in normal AB serum. Moreover, the addition of interferon-alpha (IFN-alpha) and/or immune complexes (IC) did not diminish either total PKA activity or PKA-dependent substrate phosphorylation. Lastly, we found that the defect of PKA-dependent protein phosphorylation in active SLE T cells could not be reversed by culturing the cells in culture medium supplemented with 10% AB serum for 24 hr. In conclusion, (a) deficient cAMP-inducible, PKA-dependent phosphorylation in SLE T cells is not reversible by culturing cells in vitro; (b) there is no evidence to support the concept that serum factors, including IC and IFN-alpha, can induce a defect of PKA-dependent protein phosphorylation in normal T cells.

Adult↗
PubMed1993

Chemical carcinogens increase IL-1 alpha and IL-6 gene transcripts in human keratinocytes.

Using reverse transcriptase-linked polymerase chain reaction, the effect of polycyclic aromatic hydrocarbons (PAHs) on IL-1 alpha, IL-1 beta and IL-6 gene expression in cultured human keratinocytes was studied. Exposure to beta-naphthoflavone and benz(a)anthracene resulted in a higher copy number of IL-1 alpha and IL-6 mRNA while lower level of IL-1 beta mRNA was detected in these cells. These data suggest that, like ultraviolet B (UVB) radiation, ubiquitous environmental carcinogenic PAHs are potent inducers of IL-1 alpha and IL-6 cytokines and, unlike UVB, they downregulate IL-1 beta in human keratinocytes.

Base Sequence↗
PubMed1992

Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice.

We have used PCR to study the expression of T-cell antigen receptor beta RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B10.Q mice (H-2q) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few V beta transcripts--V beta 2, -6, -7, -8.2, -9, -10, and -15. V beta 6 and -8.2 were expressed predominantly (six out of seven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for V beta 6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collagen-induced arthritis there is a restrictive usage of TCR V beta elements and that V beta 6 and -8.2 are probably used preferentially.

Animals↗
PubMed1989

RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes.

We have identified an inbred strain of mouse, RIII S/J (H-2r), that has the largest known deletion of the TCR V beta genes by screening with mAb and TCR V beta specific probes. Upon screening of PBL with mAb F23.1, which is specific for V beta 8 TCR, RIII S/J was found to be negative. On further screening with mAb KJ 23a, which is specific for V beta 17a TCR, RIII S/J was completely negative. We next tested RIII S/J with mAb 44-22-1, which is specific for V beta 6 TCR, and found it also to be negative. The (B10 X RIII)F1 mice showed a 50% expression of V beta 6 gene, indicating a genomic rather than a clonal deletion. mAb KJ25, detecting V beta 3, was positive in RIII S/J, denoting the downstream boundary for the deletion. Southern blot analysis of liver DNA using TCR V beta-specific probes confirmed the deletion of V beta 8 gene subfamily and V beta 5 gene subfamily, along with V beta 9, V beta 11, V beta 12, and V beta 13 genes similar to the known TCR V beta deletion mutants (SWR, SJL, C57L, and C57Br). In addition, RIII S/J is missing V beta 6, V beta 15, and V beta 17 genes. Our mapping of the deletion indicates that RIII S/J has lost approximately 130 kb of V beta chromosome and with it 13 V beta genes out of the known 21 V beta genes of the TCR. The deletion is marked by the presence of V beta 10 gene upstream and V beta 3 gene downstream.

Animals↗
PubMed1989

Identification of T-cell receptor V beta deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collagen-induced arthritis.

Our laboratory is involved in investigating the role of T-cell receptor (Tcr) in collagen-induced arthritis (CIA). During these studies we found AU/ssJ (H-2q) mice to be resistant to CIA like SWR (H-2q), as compared with other H-2q strains with wild-type Tcr like DBA/1 and B10.Q. Upon screening with monoclonal antibodies F23.1 and KJ23a, AU/ssJ was found to be F23.1 negative (V beta 8 Tcr negative) and KJ23a positive (V beta 17a Tcr positive). Southern blot analysis on liver DNA using specific Tcr-V beta probes confirmed the deletion of V beta 8 gene family and also showed that AU/ssJ mice have deletions of V beta 9, V beta 13, V beta 12, and V beta 11 genes of Tcr. Further, these mice show a restriction fragment length polymorphism pattern with V beta 10, V beta 6, and V beta 17 probes similar to SWR mice as compared with B10 mice. Since SWR and AU/ssJ are from different backgrounds, these studies indicate that specific variable region beta chain genes of Tcr are crucial for susceptibility to CIA in mice. Furthermore, these studies identify an additional inbred strain which has also deleted 50% of its Tcr-V beta genes.

Animals↗
PubMed1988

Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice.

Arthritis was induced by immunization of type II collagen in adjuvant in mice from H-2q-bearing crosses between SWR (H-2q/q) and B10 (H-2b/b mice), two strains known to be resistant to collagen-induced arthritis (CIA). The resistance of B10 is known to be due to its MHC haplotype, but it was postulated that the resistance of SWR mice which expresses the susceptible MHC haplotype could be due to the deletion of close to 50% of the V beta genes of the T cell receptor (TCR) in them. 17% of the F1 hybrids, 33% of the SWR backcrosses, 68% of the B10 backcrosses, and 52% of the F2 hybrids developed arthritis on follow-up to 5 mo after primary immunization with collagen. There was no significant difference in anti-type II collagen antibody titers between the arthritic and nonarthritic mice in each of these crosses. The segregation of the TCR genes with arthritis was determined in the F2 population by typing with F23.1 mAb that reacts with T cells using V beta 8 subfamily genes in their TCRs. SWR mice are F23.1- as V beta 8 genes are deleted in them. All six of arthritic mice homozygous for H-2q, and thus with an H-2 haplotype similar to SWR mice, expressed the F23.1 marker. These studies indicate that for complete susceptibility to collagen-induced arthritis, not only is a susceptible MHC haplotype (H-2q) important, but possibly also the presence of a subset of T cells using certain specific V beta genes in their TCRs. Other background genes may, however, modulate the severity of arthritis.

Animals↗
PubMed1983

Studies with chlorambucil. I. Effect on lactate dehydrogenase in the testes of albino rabbits treated with multiple doses of chlorambucil.

Treatment with multiple sub-lethal doses of chlorambucil resulted in lower activity levels and specific activity of LDH and low protein content in the testes of albino rabbits. Electrophoretic analysis and assay of individual isozymes eluted from DEAE-Sephadex A-50 indicated that this loss in activity was related to the differential and/or selective action of chlorambucil on LDH4, which was affected most, while LDH3 and LDH5 were affected to a lesser degree. Kinetic inhibitory studies on purified rabbit muscle LDH in vitro revealed that chlorambucil in the reaction mixture binds to non-active enzyme sites resulting in non-competitive irreversible inhibition of LDH.

Animals↗
PubMed1982

Testicular damage and change in serum LDH isozyme pattern induced by multiple sub-lethal doses of apholate in albino rats.

Treatment with apholate caused degenerative changes in the testes of albino rats. No histological changes were observed in Leydig cells. LDH-X activity was present in the serum of treated rats and absent in controls. Electrophoresis indicates that the activity band present in serum was similar to the activity band found in testes. A colorimetric method for assaying LDH-X activity is reported.

Animals↗
PubMedDate not supplied

Sister-chromatid exchanges and chromosomal aberrations in lymphocytes of male albino rats treated with an alkylating agent, apholate (NSC 26, 812; ENT 26, 316).

A lymphocyte culture system was used to study the frequency of chromosomal aberrations and SCEs at various time intervals after an intraperitoneal injection of apholate (0.5 mg/kg b.w.) in male albino rats. Treatment with apholate increased the frequency of chromosomal aberrations significantly (P less than 0.001). The majority of chromosomal aberrations were single chromatid breaks, although other aberrations were also present. The distribution of chromatid breaks was non-random and the large chromosomes were affected to a greater extent. SCEs frequency in lymphocytes of apholate-treated rats was more than 5-fold higher in comparison to controls. The highest number of chromosomal aberrations and SCEs/rat was recorded at 48 h post-treatment, after which there was a gradual decline in both SCE and chromosomal aberration frequency. The results indicate that apholate is a mutagenic compound and it may also be carcinogenic.

Animals↗