Search PubMed⌕ Search

Biomedical subjects

A H Johnson

Publications and source records attributed to A H Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1984

Recombination within the HLA-D region. Correlation of molecular genotyping with functional data.

Molecular genotyping of the HLA-D/DR region in a family correlated with serologic and cellular typing data. It was further possible to predict a subtle difference in SB region-related functions from such molecular studies. A family that included an individual who inherited an HLA haplotype with a paternal recombination between HLA-B and the HLA-D/DR region was identified by classic HLA typing techniques. Segregation of HLA-D/DR region genes in this family was studied by Southern blot analysis using cDNA probes for DR alpha, DR beta, DC alpha, DC beta, and SB beta. Restriction enzyme fragment polymorphisms observed for every gene tested were in concordance with assigned HLA haplotypes (including the individual known to have inherited a paternal recombinant haplotype) with one exception: two HLA identical siblings were observed to have different SB beta restriction fragment patterns. Further testing revealed that one individual inherited a maternal HLA haplotype recombinant between the HLA-D/DR region and SB beta. Although both maternal SB alleles typed as SB4, allelic differences could be detected cellularly by primed lymphocytes and by the differential expression of a class II cell surface antigen using monoclonal antibody. Therefore, predicted and nonpredicted recombinant haplotypes were detected in a family by molecular genotyping.

DNA Restriction Enzymes↗
PubMed1984

Human helper T-cell clones that recognize different influenza hemagglutinin determinants are restricted by different HLA-D region epitopes.

Human T-lymphocyte clones ( TLCs ) were generated against the hemagglutinin (HA) of A/Texas/1/77 influenza virus by limiting dilution. TLCs were then screened for antigen specificity on chemically synthesized peptides representing the HA1 molecule. It has been hypothesized that different T cells that recognize the identical antigenic determinant are controlled by (restricted by) the same class II epitope. Two TLCs , HA1.4 and HA1.7, both recognized the same HA peptide and in proliferation studies exhibited identical restriction patterns. Two other clones, HA 1.9 and HA 2.43, recognized different HA determinants and also had distinct restriction patterns. Proliferation inhibition studies with monoclonal antibodies against human class II molecules demonstrated three unique patterns of blocking with the clones, suggesting that clones may be restricted to a unique class II epitope depending on the HA determinant recognized. These data can be interpreted as supporting the argument that human immune responses to influenza hemagglutinin are under Ir gene control exerted at the level of the viral antigenic determinant recognized in association with particular D-region restricting elements. The determinant selection and clonal deletion theories are compared for their capacity to best explain these findings.

Antibodies, Monoclonal↗
PubMed1984

Lymphocyte lactate dehydrogenase isoenzymes in association with depressed mitogen responsiveness.

Purified lymphocyte preparations from cancer patients were less responsive to the mitogen phytohaemagglutinin (PHA) than were lymphocytes from healthy donors as measured by [3H]-thymidine uptake over periods in culture up to 96 hours. The uptake of radiolabel was paralleled by total cellular lactate production. The isoenzymic composition of lactate dehydrogenase (LD) in lymphocytes from healthy individuals was altered following PHA stimulation with increasing proportions of LD-1 and LD-2 throughout the culture period. This phenomenon was markedly reduced in lymphocytes from cancer patients. This defect in lymphocytes from cancer patients is thought to reflect an impaired capacity to accomplish an early mitogen-induced enhancement of glucose metabolism, which is a prerequisite for lymphocyte proliferation.

Aged↗
PubMed1983

SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones.

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.

Antigens, Viral↗
PubMed1983

A comparison of lysosomal acid hydrolase activities in human gastric antrum and in different regions of the porcine stomach.

Lysosomes are known to be implicated in many disease states in both humans and animals. In order to assess the possible role of lysosomes in the aetiology of human gastric ulceration, lysosomal enzyme levels and some of their properties were determined in human gastric antrum and in three discrete porcine gastric regions. Of the four regions investigated, the strongest similarity emerged between the enzymes of the porcine pyloric gland area and those of the human antrum. These data suggest that the pyloric gland is an appropriate model tissue for a comparative in vitro study of lysosomal involvement in human gastric ulceration.

Acid Phosphatase↗
PubMed1983

HLA and B-lymphocyte alloantigens in Gila River Indians.

HLA-A, B, C, DR, and MB and MT B-lymphocyte alloantigens were tested in 249 Pima and Papago Indians from Arizona. Frequencies of A and B locus antigens in Pimas were similar to published values for other North American Indians, as well as previous reports from Pimas. Cw3 was the most frequent C locus antigen found and DR5 was the most frequent DR antigen. Another B-cell specificity, DuB31, behaved as a DR allele and had a phenotype frequency of .717. This study is the first report of MB and MT frequencies in a North American Indian population, and the pattern of association with some DR antigens appears to be different from that observed in Europeans. MT3 had a phenotype frequency of .583, but was not associated with DR4, 7, 9, which suggests an undefined DR allele associated with MT3.

Adolescent↗
PubMed1983

In vitro lymphocyte proliferation response to therapeutic insulin components. Evidence for genetic control by the human major histocompatibility complex.

Genes in the major histocompatibility complex of mice and guinea pigs control immunologic responsiveness to insulins from other animal species. In order to determine if similar genetic control exists in man, we have examined lymphocyte proliferation responses to components of therapeutic insulins by employing lymphocytes from diabetic patients that receive insulin. Distinct groups of individuals demonstrated positive lymphocyte proliferative responses to beef insulin, beef and pork insulin, beef proinsulin, pork proinsulin, and protamine. Lymphocytes from the patient population were typed for the HLA-A, B, C, and DR antigens. An increased frequency of certain HLA antigens was found in those individuals that responded to the following therapeutic insulin components: beef, HLA-DR4; beef and pork, HLA-DR3; beef proinsulin, HLA-BW4, CW2, CW5, DR2, and DR5; protamine, HLA-CW3, CW5, and DR7. The results demonstrate that the human immune system recognized the structural differences between human and beef and/or pork insulin. These differences are two amino acids in the A chain, alpha loop, of beef insulin and the single terminal amino acid, alanine, which is common to pork and beef insulins. Positive responses to both beef proinsulin and pork proinsulin demonstrated the capability of restricted recognition of more complex proteins represented by the C-peptide in these insulin preparations. Lymphocyte proliferative responses to protamine were also restricted, which suggests a genetic control to this antigen. The association of these responses with HLA alloantigens strongly suggests that genes within the human major histocompatibility complex control recognition and lymphocyte response to therapeutic insulin components.

Adult↗
PubMed1982

Abnormal cardiac enzyme responses after strenuous exercise: alternative diagnostic aids.

Serial estimations of activities of creatine kinase and its MB isoenzyme, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and of concentrations of alpha(1)-acid glycoprotein were performed in 15 healthy well-trained male marathon runners. Estimations were made initially within three days before a race and then one, 24, and 96 hours after the race. Technetium-99m pyrophosphate myocardial scintigraphy was carried out at the initial prerace assessment and repeated 48 to 96 hours after the race. None of the subjects developed cardiac symptoms during or after the race.Activities of creatine kinase and creatine kinase MB became maximal 24 hours after the race. One and 96 hours after the race two and five subjects, respectively, showed amounts of creatine kinase MB totalling 5% or more of total creatine kinase. Lactate dehydrogenase activity peaked at one hour after the race, and activities of aspartate and alanine aminotransferases peaked at 24 and 96 hours after the race, respectively. Activities of all these enzymes showed a significant increase from prerace values during the rest of the study. Electrocardiographic features noted were similar to those reported elsewhere in athletes under similar conditions. They included first-degree heart block, incomplete right bundle-branch block, left ventricular hypertrophy, pseudoischaemic T-wave changes, and early repolarisation of variant ST-segment elevations in precordial leads. Technetium-99m pyrophosphate myocardial scintigraphy did not show evidence of myocardial damage before or after the race. Alpha(1)-acid glycoprotein concentrations were normal throughout.These data suggest that reliance on standard enzyme estimations and electrocardiographic criteria may yield false-positive indicators of myocardial injury during prolonged strenuous exercise. Technetium-99m pyrophosphate scintigraphy and alpha(1)-acid glycoprotein measurements offer additional information and may usefully be employed in evaluating circulatory collapse associated with such exercise.

Adult↗
PubMed1982

Antigen-specific human T-lymphocyte clones. Genetic restriction of influenza virus-specific responses to HLA-D region genes.

Human T lymphocytes, primed in vitro to influenza virus, were cloned by limiting dilution and expanded using medium containing interleukin 2 and feeder cells. A detailed analysis of the genetic requirements for induction of T-cell proliferation was conducted using a panel of cells from unrelated donors and two families who had previously been extensively phenotyped for HLA region antigens. Clones obtained from a Dw1, Dw3 individual required Dw1,DR1 histocompatibility for successful presentation of viral antigens by antigen-presenting cells. The antigen-presenting ability segregated with HLA-B,D,DR in an informative HLA-A/B recombinant individual. In contrast, some TLCs responded to antigen presented by cells that did not share known HLA antigens, and in one informative family, reactivity did not segregate with HLA. None of the T-cell clones reacted to allogeneic cells in the absence of antigen, suggesting that the TLCs do not bear receptors that recognize both influenza virus and alloantigen. In antibody-blocking studies, Dw1, DR1-restricted clones were blocked by all monoclonal anti-DR framework antibodies. The non-HLA-restricted TLCs were blocked by some, but not all, of the anti-DR framework monoclonal antibodies. These results confirm and extend the role of HLA-D region gene products in antigen presentation and also provide evidence that yet undefined cell interaction products, which may include hybrid structure, are able to participate in antigen-specific proliferative responses by human T cells.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibodies specific for human polymorphic cell surface antigens. I. Evaluation of methodologies. Report on a workshop.

Five techniques, the direct and the antiglobulin enhanced cytotoxicity assays, indirect immunofluorescence, the enzyme-linked immunosorbent assay, and the radioimmunoassay, were evaluated in a workshop to determine their utility in studies of the interactions of monoclonal antibodies with HLA antigens expressed on lymphocytes. Several well-defined antibodies, both cytotoxic and noncytotoxic, were tested against well-characterized human lymphoid cells. All the methods suffer from some deficiency. The enhanced cytotoxicity assay, however, is most useful as a routine screening tool because of its ease and simplicity; whereas, the enzyme-linked immunosorbent assay is most useful when dissection of antigenic structure is sought because it yields information on the quantities of the antigenic determinants expressed on the cell surface without requiring radioactive reagents.

Antibodies, Monoclonal↗
PubMed1982

Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones.

Human peripheral blood lymphocytes from an HLA-Dw1,3 individual were primed in vitro with influenza A virus (A/Texas/1-77/x-49) and subsequently cloned by limiting dilution in TCGF. Of the 96 TLCs originally obtained, nine were characterized in detail. TLCs were antigen specific, responding to influenza A virus, not to influenza B, TGAL, GAT, tetanus toxoid, or KLH, and only when antigen was presented by cells unable to form rosettes with AET-treated SRBC. Presentation of antigen by unseparated PBL often resulted in significant "back stimulation," probably via production of growth factors. The MHC requirements for the induction of TLC proliferation were analyzed. Of four representative clones analyzed, three required Dw1;DR1 compatibility for successful presentation of viral antigens by a panel of antigen-presenting cells. In contrast, one TLC showed an unusual pattern of response that could not be correlated to a particular HLA haplotype. Monoclonal anti-T cell antibody analysis of the surface phenotype of two TLCs maintained in continuous culture for 5 mo indicated that they were OKT3+, 4+, and 8-, consistent with an inducer/helper phenotype. To confirm the clonal nature of TLCs, data on the functional properties of TLC subclones are also presented.

Clone Cells↗
PubMed1981

HLA-A2 and type 2 (insulin independent) diabetes mellitus in Pima Indians: an association of allele frequency with age.

In Pima Indians with Type 2 (insulin independent) diabetes mellitus, HLA-A2 allele frequencies were inversely associated with age, (0.72, 0.59, and 0.52 in those less than 35, 35 to 54, and 55 years old and over, respectively). This suggests that there may be a gene closely linked with the HLA-A locus which plays a role in the expression of diabetes in the Pimas by contributing to an earlier age of onset. HLA-A2 was found in 65% non-diabetic and 81% of 191 diabetic subjects (relative risk = 2.2).

Adult↗
PubMed1981

HLA antigens and immunoglobulin allotypes in patients with malignant melanoma.

HLA antigens and Gm, A2m, and Km allotypes were examined in Caucasian patients with malignant melanoma. No significant associations were found for any of the HLA antigens tested. Significant association was found with Gm(2), and the relative risk for individuals with this marker was calculated at 1.9. The data indicate that Caucasians positive for Gm(2) are almost twice as likely to develop malignant melanoma as those without this marker.

HLA Antigens↗