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G Grimsley

Publications and source records attributed to G Grimsley.

7 recordsLinked to original sources
PubMed1992

Sequence differences between HLA-B and TNF distinguish different MHC ancestral haplotypes.

The HLA-B locus is extremely polymorphic. We have sequenced a region, CL, telomeric of HLA-B that also shows a high degree of allelic variation which we have shown previously by RFLP analysis. The polymorphism can be accounted for by sequence variation in duplicated, reiterated sequence elements called geometric elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted. It is possible, using the polymerase chain reaction, to amplify these elements in genomic DNA from ancestral haplotypes for which sequence data of the CL region are not available and to obtain gel patterns which are characteristic of different ancestral haplotypes. The most striking feature of the data is the fact that the majority of the CL patterns are haplospecific; i.e. have a particular pattern that is unique for a particular ancestral haplotype and can be used to type these ancestral haplotypes. At least 12 different allelic patterns have been identified within a panel of 29 cell lines representing 16 ancestral haplotypes. For these 16 ancestral haplotypes, all examples of each haplotype have the same CL pattern. The haplotypic nature of the patterns confirms that ancestral haplotypes are conserved chromosomal segments and that coding and non-coding sequences are identical by descent from a remote ancestor.

Base Sequence↗
PubMed1990

Correction of human immunodeficiency virus-associated depression of delayed-type hypersensitivity (DTH) after zidovudine therapy: DTH, CD4+ T-cell numbers, and epidermal Langerhans cell density are independent variables.

Twenty-four patients with various degrees of human immunodeficiency virus (HIV)-associated immunodeficiency were treated with zidovudine for up to 6 months. Nineteen of these patients had persistent depression of delayed-type hypersensitivity (DTH) responses prior to commencing therapy. In 11 of these 19 patients (58%) there was sustained improvement of DTH responses with the maximal effect occurring at approximately 3 months after therapy was started. DTH declined after 3 months but remained significantly higher than baseline at 6 months. Patients who did not have a sustained increase in DTH responses had more severe disease than those that did. Blood CD4+ T-cell counts increased in the majority of patients on zidovudine therapy, but varied independently of DTH responses. Epidermal Langerhans cell density was lower in HIV-infected patients than controls but also varied independently of DTH responses before and after zidovudine therapy. We suggest that sequential measurement of DTH responses is a valuable means of monitoring the restoration of cell-mediated immune responses by zidovudine in some HIV-infected patients. Our findings also demonstrate the need to define the processes involved in the restoration of DTH responses as this may lead to new approaches to the therapeutic manipulation of cell-mediated immune responses in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

MHC supratypes as markers of null and defective C4 alleles in a Thai/Chinese population: relevance to disease susceptibility.

Deficiency alleles at the C4 loci within the MHC are associated with autoimmune diseases in Caucasoids and possibly other races. We therefore studied the relationship between relevant C4 alleles and other MHC markers in a random Thai/Chinese population. Over 90 per cent of C4AQO occurs within two supratypes (HLA Aw33, B44, C4AQO, B1, BfS, DR7 and Aw33, B17, C4AQO, B1, BfF DR x where x is an unassigned DR antigen). These two supratypes have minimum population frequencies of 6 and 3 per cent, respectively. Almost 70 per cent of C4BQO is contained within the supratype HLA Aw33 (11), B17, C4A3, BQO, BfS, DR3. At least 8 per cent of the Thai/Chinese population bear this supratype. Essentially all subjects with C4A6 also have HLA A1, B17, C4B1, BfS, and DR7. Approximately 6 per cent of Thai/Chinese have this supratype which is also found in Caucasoids. Partial C4 deficiency is common in Thai/Chinese as well as Caucasoids, can be inferred from examination of HLA phenotypes and may contribute to susceptibility to some diseases.

Alleles↗
PubMed1986

Increased binding of D-penicillamine to monocytes in rheumatoid arthritis.

Long-term therapy of D-penicillamine (D-Pen) for rheumatoid arthritis (RA) is associated with a fall in rheumatoid factor, but many patients develop autoantibodies. In vitro binding of D-Pen to human peripheral blood monocytes was examined in 37 patients with RA and 75 healthy subjects. Mononuclear cells were reacted with D-Pen coupled to a fluorescein isothiocyanate-bovine serum albumin (BSA) conjugate in the presence of sodium azide and BSA, and analyzed by flow cytometry. Patients showed significantly higher D-Pen binding to monocytes than did healthy subjects. The proportion of monocytes binding D-Pen increased with age in the patients but not in healthy subjects. None of 6 patients who had D-Pen-induced autoimmune side effects was associated with increased D-Pen binding though patients with therapeutic responses showed high D-Pen binding. These results suggest that D-Pen binding to monocytes may be important in mediating therapy and inducing autoimmune side effects.

Adult↗
PubMed1976

Myasthenia gravis: the role of immunological deficiency.

To evaluate further the association between myasthenia gravis and humoral immune deficiency, 92 sera from myasthenic patients were tested so as to determine titers against commensal E. coli, isohemagglutinin titers, and IgG and IgM concentrations. Results were compared with those obtained from normals, disease controls, and W27 positive arthropathy. On the basis of these three investigations it is concluded that subtle immunodeficiency is common in myasthenia gravis, and it is suggested that an immune defect might explain such diverse associations as thymic disease, HL-A antigens, and various autoimmune phenomena.

Agglutinins↗