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Biomedical subjects

G Grimsley

Publications and source records attributed to G Grimsley.

12 recordsLinked to original sources
PubMed1996

Analysis of the major histocompatibility complex microsatellite CL1 in different human haplotypes.

Characterization of the region between HLA-B and the TNF loci in the human MHC revealed the presence of duplicated loci, named CL1 and CL2, that included repeat sequences. Development and use of a PCR typing methodology that amplified both CL microsatellites simultaneously indicated that PCR product patterns analysed on native agarose gels were allelic (Abraham et al., 1992). The purpose of the current study was to determine the molecular explanation for the unique patterns achieved. Sequence analysis of the CL1 locus from 32 chromosomes representing 10 ancestral haplotypes indicated that six alleles were present. The CL microsatellites also provided an opportunity to study the evolutionary relationships between MHC haplotypes from different racial groups. Sequence comparison of closely related ancestral haplotypes from different racial groups suggested that the CL1 microsatellite has not changed in the period since divergence.

B-Lymphocytes↗
PubMed1995

How to measure and predict the molar absorption coefficient of a protein.

The molar absorption coefficient, epsilon, of a protein is usually based on concentrations measured by dry weight, nitrogen, or amino acid analysis. The studies reported here suggest that the Edelhoch method is the best method for measuring epsilon for a protein. (This method is described by Gill and von Hippel [1989, Anal Biochem 182:319-326] and is based on data from Edelhoch [1967, Biochemistry 6:1948-1954]). The absorbance of a protein at 280 nm depends on the content of Trp, Tyr, and cystine (disulfide bonds). The average epsilon values for these chromophores in a sample of 18 well-characterized proteins have been estimated, and the epsilon values in water, propanol, 6 M guanidine hydrochloride (GdnHCl), and 8 M urea have been measured. For Trp, the average epsilon values for the proteins are less than the epsilon values measured in any of the solvents. For Tyr, the average epsilon values for the proteins are intermediate between those measured in 6 M GdnHCl and those measured in propanol. Based on a sample of 116 measured epsilon values for 80 proteins, the epsilon at 280 nm of a folded protein in water, epsilon (280), can best be predicted with this equation: epsilon (280) (M-1 cm-1) = (#Trp)(5,500) + (#Tyr)(1,490) + (#cystine)(125) These epsilon (280) values are quite reliable for proteins containing Trp residues, and less reliable for proteins that do not. However, the Edelhoch method is convenient and accurate, and the best approach is to measure rather than predict epsilon.

1-Propanol↗
PubMed1993

A region centromeric of the major histocompatibility complex class I region is as highly polymorphic as HLA-B. Implications for recombination.

Two hallmarks of the MHC are the high degree of polymorphism apparent at multiple loci and "linkage disequilibrium." The data presented here suggest that a consequence of selection at a particular locus may be the inhibition of recombination through the accumulation of DNA sequence polymorphisms. Equivalent 6.4 kb regions from a locus, CL1, located approximately 25-30 kb centromeric of HLA-B, were sequenced for three ancestral haplotypes: A1,B8,DR3; A30,B18,DR3; and A1,B57,DR7. Comparison of the sequences indicated that the level of DNA sequence polymorphism was high when compared with the TNF region; approximately 80 single nucleotide differences were found when comparing any two sequences. In addition, multiple deletions/insertions were present. We believe that the degree of polymorphism within the CL interval may be adequate to at least partially inhibit recombination between the haplotypes studied.

Base Sequence↗
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↗
PubMed1984

Comparison of delayed type hypersensitivity and T subsets in random and homosexual populations in western Australia.

Random and homosexual populations were tested for delayed type hypersensitivity (DTH) (Multitest) reactivity and T cell subsets. In the random population DTH reactivity was stronger in males irrespective of age. Reactivity in the homosexuals was generally even stronger especially with respect to tuberculin. As a group, male homosexuals had low OKT 4/8 ratios when compared with sex and age matched controls. Analysis of DTH and T cell subset results in the random group showed an association between anergy and low OKT 4/8 ratios. It is concluded that homosexuals demonstrate some alteration of cell mediated immunity and therefore may be at risk of various infections.

Adult↗
PubMed1980

Immunological status may predict clinical outcome in BCG treated melanoma.

Twenty-seven patients with surgically resected stage II or III malignant melanoma were treated with bacillus Calmette-Guérin (BCG) and followed prospectively to determine whether relapse could be predicted. Peripheral blood mononuclear (lymphocyte plus monocyte) counts (PBM), T and B cell counts, phytohaemagglutinin (PHA) cytotoxicity, PHA transformation, antibody-dependent cell-mediated cytotoxicity (ADCC) and serum immunoglobulin concentrations were studied before and during therapy. Patients ultimately classified as having a poor clinical outcome (inoperable recurrence) were compared with those with a more favourable outcome. Prior to therapy, poor outcome patients had lower PBM and T cell counts but there was some overlap. After three months, these differences were more pronounced. Low PHA cytotoxicity was also associated with poor outcome; again the differences were more apparent at 3 months than prior to therapy. These results suggest that PBM, T cell counts and PHA cytotoxicity may predict poor outcome some months before inoperable recurrence in apparent clinically.

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↗