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A H Johnson

Publications and source records attributed to A H Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Point mutations define positions in HLA-DR3 molecules that affect antigen presentation.

Allelic differences in major histocompatibility complex (MHC)-encoded class II molecules affect both the binding of immunogenic peptides to class II molecules and the recognition of MHC molecule-peptide complexes by T cells. As yet, there has been no extensive mapping of these functions to the fine structure of human class II molecules. To determine sites on the HLA-DR3 molecule involved in antigen presentation to T cells, we used monoclonal antibodies specific for HLA-DR3 to immunoselect mutants of a B-lymphoblastoid line. We located the sites of single amino acid substitutions in the HLA-DR3 molecule and correlated these structural changes with patterns of recognition by HLA-DR3-restricted, antigen-specific T cells, allospecific T cells, and allospecific anti-DR3 monoclonal antibodies. We analyzed seven mutations. One mutation, at position 74 in domain 1 of the DR beta chain, affected recognition by all T cells tested, whereas others, at positions 9, 45, 73, 151, and 204 of the DR beta chain and position 115 of the DR alpha chain, altered recognition by some T cells, but not others. Each of the substitutions resulted in a unique pattern of T-cell stimulation. In addition, each T-cell clone recognized a different subset of the mutants. These results indicate that different residues of the DR3 molecule are involved in presentation of antigen to different DR3-restricted T cells. These studies further show that substitutions which most likely affect peptide binding alter recognition of DR3 molecules by an alloreactive T-cell clone and some allospecific antibodies.

Alleles↗
PubMed1990

Cholesterol metabolism in alloxan-induced diabetic rabbits.

The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P less than 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P less than 0.01), hepatic HMG-CoA reductase (P less than 0.05) and ACAT (P less than 0.001), and phenol 2-monooxygenase (P less than 0.01). The poorly controlled animals were hypercholesterolemic (P less than 0.01), and this was reflected in the very-low-density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated.

Alloxan↗
PubMed1990

Lipoprotein composition in the alloxan-diabetic rabbit.

This study investigates the lipoprotein abnormalities in the alloxan-diabetic rabbit maintained on a standard chow diet. Poorly-controlled diabetic rabbits had elevated levels of triglyceride and phospholipid (reflected in all lipoprotein fractions) and cholesterol (reflected in the very low density and high density lipoprotein fractions) compared with well-controlled and non-diabetic rabbits. The importance of diabetic control in these changes was emphasized by the observation of a positive correlation between weight loss and serum triglyceride (rs = 0.62, p less than 0.02), cholesterol (rs = 0.65, p less than 0.01) and phospholipid (rs = 0.56, p less than 0.05). The lipoprotein fractions of the poorly-controlled rabbits were enriched with triglyceride.

Animals↗
PubMed1990

Hansen's disease update.

The incidence of Hansen's disease has increased with most new cases appearing in California and Florida. The bulk of this increase can be attributed to the immigration of patients from countries where the disease is endemic. Because many immigrants from Caribbean basin countries settle in Florida, it is especially important for physicians here to be able to recognize this disease. An asymptomatic macule or patch may be the first recognizable feature. Alternatively, patients may present with an acute inflammatory episode known as a "reaction". Dapsone, rifampin, clofazimine, thalidomide and prednisone are useful in treatment. With early recognition and treatment, potentially disabling neurological and ophthalmological sequelae can be avoided. Consultation with or referral to either the Miami Regional Hansen's Disease Center or the Gillis W. Long Hansen's Disease Center in Carville, La., may be helpful.

Humans↗
PubMed1989

Human T cell recognition of polymorphic epitopes from malaria circumsporozoite protein.

Lymphocytes obtained from forty individuals living in a malaria endemic area of West Africa were tested for in vitro proliferative responses to peptides representing variant regions of the immunodominant T cell domain of the circumsporozoite protein (amino acids 326 to 345, referred to as Th2R, and 361 to 380, referred to as Th3R) from three distinct strains of Plasmodium falciparum. A total of 83% of the individuals responded to at least one of the six peptides tested, confirming that these epitopes are immunodominant. A much greater number of individuals than expected by chance (32% of the responders to Th2R and 27% of the responders to Th3R) reacted to all three of the variant peptides for that epitope, indicating interdependency of the T cell responses, suggestive of cross-reactivity. Nevertheless, some subjects' T cells were clearly able to distinguish each variant peptide from the others. Using EBV transformed B cells, lymphocytes from 10 of the individuals were HLA typed. In this small group, HLA DRw13 was associated with a positive response to any of the peptides, whereas there was a negative association between DQw3 and response to any of the peptides. These results, although limited by the small sample size, suggest that recognition of T epitopes may be Ir gene linked. Our findings suggest that it may be possible to broaden the immunogenicity of an anti-sporozoite malaria vaccine.

Adult↗
PubMed1989

Epitopes within the HLA-B5,B35 cross-reacting group.

The HLA-B5,B35 cross-reacting group is a large and serologically complex antigen family which includes the World Health Organization-recognized specificities HLA-B5,B51,Bw52,B35,Bw53,B18,Bw70,Bw71, and Bw72. In addition, several variants of antigens in this cross-reacting group have been described in the past but have not yet gained official recognition. A genetic basis for the complexity and the protein and molecular bases of this highly cross-reactive and polymorphic cross-reacting group have yet to be established. The potential contributions of shared amino acid sequences, the occurrence of multiple epitopes on a single HLA-B molecule, and the presence of new HLA-C antigens have been difficult to resolve. To address this issue, we have carefully examined the serologic reactions of more than 900 allo- and monoclonal antibodies (Tenth International Workshop, Third Asia-Oceanic Workshop, and local reagents) versus lymphocytes from 92 individuals of diverse ethnic origin (North American Caucasians, North American blacks, Amerindians, Middle Eastern Caucasians), 84 of whom were informative for the HLA-B5,B35 cross-reacting group and related antigens. Our results demonstrate that the HLA-B5,B35 gene products share different combinations of distinct epitopes. We have constructed a model for the evolution of this cross-reacting group by assigning polarity to distinct diversification steps utilizing principles of maximum parsimony.

Antibodies, Monoclonal↗
PubMed1989

The DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci.

The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population, in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a DQw4 allelic product. This study characterizes the DR subregion of that haplotype. cDNA sequence analysis has revealed a DR beta gene which differs at several positions from previously described DR3 beta 1 genes. It is postulated that a gene-conversion-like event with a DRw52 beta gene as donor has generated some of these differences. The haplotype carries a DRw52a allele as defined by oligonucleotide hybridization studies. DNA restriction fragment analysis using a family and several unrelated individuals has allowed us to identify DR alpha and beta fragments associated with the DR3(w18),DQw4 haplotype. The most striking observation is that the DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci. Several genetic mechanisms including reciprocal recombination, gene conversion, and point mutation were involved in generating the differences between these haplotypes. Once established, the DR3(w18),DQw4 haplotype appears to be relatively stable in the population.

Amino Acid Sequence↗
PubMed1989

Lack of common haplotype among four family members with late-onset Kaposi's sarcoma.

Kaposi's sarcoma is associated with an increased frequency of HLA-DR5. The hypothesized model of a susceptibility gene in linkage disequilibrium with DR5 may be tested by haplotype analysis in familial Kaposi's sarcoma. Our finding of no common haplotype among afflicted members of a family provides evidence against the hypothesized linkage.

Aged↗
PubMed1988

Polymorphism of the HLA-DR1 haplotype in American blacks. Identification of a DR1 beta-chain determinant recognized in the mixed lymphocyte reaction.

Mixed lymphocyte typing provides an exquisitely sensitive means of detecting the polymorphism of HLA class II molecules. By using this technique, the differences between divergent human populations become apparent. This study describes a DR1 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR1 individuals are DQw1 and type as Dw1 by using mixed lymphocyte typing, approximately 50% of DR1, DQw1 positive American blacks express an undefined Dw specificity. The DR beta polypeptide encoded by a DR1,Dw-cell differs from a previously described DR1,Dw1 beta sequence by two amino acid replacements at positions 85 and 86 in the first domain. One silent nucleotide substitution has also been identified. DQ alpha and beta first domain cDNA sequences from this haplotype are identical with previously described DQ sequences from a DR1,Dw1 cell. This relatively minor change in amino acid sequence of the DR molecule appears to produce the undefined HLA-D specificity in this haplotype. The variant DR1 sequence is shared with a DR beta-chain from the DR2,DwMN2 haplotype suggesting that a gene conversion-like mechanism has generated this difference.

Amino Acid Sequence↗
PubMed1988

Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination.

The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a serologically undefined DQ allelic product. DNA restriction fragment analysis with the use of several unrelated individuals and an informative family has allowed us to identify unique DQ alpha- and beta-fragments associated with the DR3, DQw- haplotype. Based on fragment size, the DQ alpha genes of the DR3, DQw- and DRw8, DQw- haplotypes are similar as are the DQ beta genes of DR3, DQw-; DRw8, DQw-; and DR4, DQw- haplotypes. In addition, a DX beta gene polymorphism has been identified which is associated with some DR3 haplotypes including the American black DR3, DQw- haplotype. cDNA sequence analysis has revealed a DQw2-like alpha gene and a DQ beta gene which is similar to that previously described for a DR4, DQw- haplotype. It is postulated that recombination between DQ alpha and DQ beta genes and between the DQ and DX subregions has generated the various DR3 haplotypes and has played an important role in creating diversity in the HLA-D region.

Amino Acid Sequence↗
PubMed1988

Human allospecific TLCs generated against HLA antigens associated with DR1 through DRw8. III. Family segregation analyses.

We have studied the complexity and fine specificity of the HLA-D region using a panel of T lymphocyte clones generated against alloantigens associated with HLA-DR1 through DRw8. After extensive testing in population studies, 89 clones were tested in proliferation assays with 14 families. Segregation patterns were analyzed for haplotype associations by calculating sequential lod scores to test the likelihood that genes encoding epitopes detected by TLCs were linked to HLA genes. Four general categories were identified: (1) clonal responses that segregated with the same HLA-D region haplotype in all informative pedigrees; (2) clonal responses that segregated with HLA in all pedigrees but not always with the same haplotype; (3) clonal responses that segregated with HLA in some families but failed to segregate in others or produced equivocal results; (4) clonal responses that did not segregate with HLA haplotypes.

Cell Line↗
PubMed1988

Measles virus-specific human T cell clones: studies of alloreactivity and antigenic cross-reactivity.

Cross-reactivity between altered self and foreign major histocompatibility complex (MHC) may be of etiologic importance in autoimmune disease. We have studied 29 measles virus-specific cloned and uncloned T cell lines from a patient with multiple sclerosis (MS) and from a normal subject. Two of the T cell clones derived from the normal subject reacted with foreign MHC determinants. No cross-reactivity between measles virus and either myelin basic protein (BP) or galactocerebroside (GC) was detected. T cell clones which are specific for nominal antigen and which also recognize alloantigen were detected with much smaller frequency than that reported in murine systems. Our data do not support a role for alloreactive measles-specific T cells, nor for cross-reactivity between measles virus and either BP or GC, in the pathogenesis of MS.

Antigens, Viral↗
PubMed1988

Climate and red spruce growth and decline in the northern Appalachians.

Between the mid-1960s and mid-1980s, red spruce (Picea rubens Sarg.) died at unusual rates on the mountains of New York and western New England. We determined the relationship between standardized tree ring widths and monthly climate data for calibration and verification periods from 1856 to 1981 and found that after about 1960, there was a distinct shift in the temperature variables related to standardized ring widths in vigorous spruce. The beginning of widespread spruce mortality, regionwide growth decreases, and the shift in response to climate in the early 1960s corresponds to the onset of a decade of unusually cold winters and several consecutive years when severe winter damage was noted across the Northeast in this species. We suggest that the episodes of winter damage are an important initiating and synchronizing factor in the red spruce decline.

Journal Article↗
PubMed1988

The effect of physician personality on laboratory test ordering for hypertensive patients.

Laboratory tests are responsible for a large percentage of health care expenses in the United States. In a retrospective study of the outpatient test ordering by residents for hypertensive patients between the years 1980 and 1986 at the Department of Family Medicine at the Medical University of South Carolina, we found great variability in laboratory test ordering as well as an association between personality as measured by the Myers-Briggs Type Indicator (MBTI) and test ordering. Introverts ordered more than extroverts, and intuitives ordered more than sensors. This association was confirmed by a multiple regression analysis controlling for potential confounders of test ordering, such as severity of disease, the presence of coexisting diabetes mellitus, the demographic characteristics of the patient population, and the number of initial evaluations for hypertension. Elucidation of a relationship between resident personality and laboratory test ordering has important implications for planning intervention strategies to reduce excessive laboratory test ordering in ambulatory care.

Clinical Laboratory Techniques↗