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Biomedical subjects

A H Johnson

Publications and source records attributed to A H Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1987

A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the alloxan-induced diabetic rat and rabbit.

1. Hyperlipidaemia is associated with diabetes mellitus. 2. A comparison of cholesterol synthesis and utilization in alloxan-induced diabetic rats and rabbits revealed that interspecies differences existed only in the response of the key enzymes regulating cholesterol utilization, namely cholesterol 7 alpha-hydroxylase and ACAT in the liver and intestine respectively. 3. The activity of cholesterol 7 alpha-hydroxylase was enhanced in diabetic rats but was markedly reduced in diabetic rabbits. 4. Intestinal ACAT activity, though unchanged in diabetic rats was reduced in diabetic rabbits. 5. Such species differences in cholesterol utilization may underlie the different degree of susceptibility to hypercholesterolaemia that exists between these two species.

Animals↗
PubMed1987

A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit.

1. The rat and rabbit are amongst the animal models most widely used in the study of human atherosclerosis, a disease state correlating with disturbances in cholesterol metabolism. 2. In order to relate the key regulatory enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit to their differing degree of susceptibility to atherosclerosis, enzyme levels and their properties were determined in liver and intestine of both species. 3. Hepatic HMG CoA reductase and cholesterol 7 alpha-hydroxylase levels were significantly higher in the rat than in the rabbit, while intestinal HMG CoA reductase activity in the two species was comparable. Conversely, the capacity to esterify cholesterol as measured by ACAT activities was considerably greater in both sites in the rabbit compared to the rat. 4. The data suggest that differences in the key regulatory enzymes of cholesterol metabolism in both liver and intestine may reflect different methods of cholesterol utilization in the two species.

Animals↗
PubMed1987

Forest decline: modeling the effect of climate in tree rings.

Tree rings provide an historical record of forest growth that reflects changes with time in site factors including, competition, tree and stand age, fire and other disturbances, and climate. Statistical methods can be used to factor out climatic influences on radial growth to yield a climate response model that can indicate whether declines in forest productivity are related to the modeled climatic variables or to other influences such as atmospheric pollutants. A general method, based on ordinary least squares, is presented for creating climatic response models for forest decline studies. The crux of the method is model verification, whereby the time-stability of the model is tested before it is used to forecast tree-ring variations during a period of decline. Three studies are described that employ monthly mean temperatures to predict tree-ring indices in declining red spruce (Picea rubens Sarg.) stands in the Appalachian Mountains of North America. The results indicate that, since 1960, red spruce trees at most of the sites sampled have undergone a period of growth decline that is unrelated to changes in mean monthly temperature. However, an association between annual ring width and unusual departures from the mean summer and winter temperatures during both present and past periods of decline suggests that climatic effects are implicated to some degree in the current decline.

Journal Article↗
PubMed1987

Unique HLA-D region heterogeneity in American blacks.

American blacks and whites show heterogeneity in serologically detected and lymphocyte-defined HLA-D region antigen frequencies. Also, alterations in linkage relationships are seen in DR and DQ specificities. Since homozygous typing cells probably identify a cluster of specificities that are usually found in linkage disequilibrium in a given population, it is not surprising that blacks have unique HLA-D types. The significance of the observed differences in the function of class II molecules is being investigated.

Black People↗
PubMed1986

Recognition of a hybrid HLA-DP-associated determinant by a human T lymphocyte clone.

Alloreactive, human T cell clones were derived from an HLA-DPw1-specific primed lymphocyte typing cell line by limiting dilution. The specificities of the clones were analyzed with allogeneic stimulator cells and in family segregation studies. One clone, TLC 56.94, recognized some, but not all, DPw1-positive stimulator cells and in two families, failed to proliferate in response to stimulatory cells from DPw1-homozygous individuals. The simplest explanation for these results is that TLC 56.94 recognizes a hybrid alloantigen produced by transcomplementation or transassociation between an element of DPw1 and some other gene product.

Antibodies, Monoclonal↗
PubMed1986

The association of impaired neutrophil chemotaxis with postoperative surgical sepsis.

Postoperative sepsis remains a major problem in current surgical practice. This study assesses the predictive role of neutrophil chemotaxis in the development of sepsis in surgical patients. Neutrophil chemotaxis was measured in 30 cancer patients undergoing gastrointestinal surgery and in 26 healthy age and sex-matched controls. Neutrophil chemotaxis was significantly reduced (P less than 0.02) in the patients (mean 79.2 micron +/- 2.7 s.e.m.) compared with the controls (mean 86.8 micron +/- 1.9 s.e.m.). In the entire patient group neutrophil chemotaxis did not change to any appreciable extent following surgery. However, in the seven patients who developed postoperative septic complications, chemotaxis, which was similar to control levels in the pre-operative stage, declined significantly following surgery. Pre-operative values for the septic group of patients are 92.4 micron +/- 4.02 s.e.m.. These declined to 73.4 micron +/- 3.15 s.e.m. (P less than 0.05) and to 68.2 micron +/- 2.89 s.e.m. (P less than 0.05), 5-8 days (early) and 10-14 days (late) postoperatively respectively. Neutrophil chemotaxis in the non-septic group of patients did not alter over this same period. The data suggest that the onset of postoperative sepsis in patients is accompanied by impairment of chemotactic properties in their neutrophils. However, it is also evident that measurement of this variable in patients before operation does not help to define an 'at risk' group for the development of postoperative sepsis.

Aged↗
PubMed1986

Human allospecific TLCs generated against HLA antigens associated with DR1 through DRw8. I. Growth and specificity analysis.

To study the fine specificity of the HLA-D region, a panel of human T-lymphocyte clones (TLCs) was generated against alloantigens associated with HLA-DR1 through DRw8. HLA-DR-homozygous peripheral blood lymphocytes (PBLs) were stimulated with DR-heterozygous PBLs in primary mixed lymphocyte cultures for 4 days. Blasts were cloned by limiting dilution at 0.3 cells/well in the presence of 20% T-cell growth factor and irradiated stimulator cells. Viable clones were subsequently tested in proliferation assays against the original stimulator and a limited panel of stimulators bearing relevant DR specificities. Initial primings produced approximately 800 clones; some recognized DR-associated antigens, 70 recognized only their original stimulator, and approximately 50% were nonresponsive. Analysis on extended stimulator panels revealed alloantigenic complexity within similar DR-associated antigens as recognized by TLCs. The data are consistent with evidence that extreme heterogeneity exists within the HLA-D region.

Clone Cells↗
PubMed1986

Human allospecific TLCs generated against HLA antigens associated with DR1 through DRw8. II. Population analyses and blocking studies with monoclonal antibodies.

Serologic, cellular, and molecular evidence supports the concept of extreme complexity within the HLA-D region. To study the complexity and fine specificity of the HLA-D region at the level of T-cell recognition, a panel of T-cell clones was generated against alloantigens associated with HLA-DR1 through -DRw8. After initial screening of more than 800 clones, 89 representative lines were selected for extensive testing against 204 unrelated stimulator cells. Clone-by-clone correlation analyses were performed to test whether any clones recognized similar or identical epitopes. In addition, clonal reactivity patterns were correlated with known HLA specificities. Twelve clusters of clones were identified with similar reactivity patterns using clone-by-clone correlation analysis. Some groups were significantly correlated with specificities associated with various D-region haplotypes; others had no significant correlation with any defined D-region specificity. Five general types of clones obtained in our study can be categorized as follows: Those recognizing epitopes clearly demonstrating a primary association with the classically defined D-region molecules against which the clones were primed. Clones recognizing epitopes associated with one of the priming antigens and also with another unrelated D-region specificity. Clones detecting epitopes which showed significant correlation with D-region molecules totally different from those against which they were originally primed. Clones with limited reactivity in population studies and no correlation with defined D-region molecules. Clones recognizing class I-associated epitopes.

Antibodies, Monoclonal↗
PubMed1986

Clonal analysis of HLA-DPw1 (SB1) associated allodeterminants: recognition of novel epitopes and evidence for quantitative variation in class II antigen expression.

Alloreactive human T-lymphocyte clones were derived from the SB1 HLA-DPw1)-specific, primed lymphocyte typing cell line SB1A used in the Ninth International Histocompatibility Workshop. The clones from two separate subclonings were analyzed for their proliferative patterns in panel experiments with cells from unrelated individuals and in family segregation analyses. While only one clone gave a perfect correlation with the DPw1 specificity, the maturity of clones recognized multiple specificities apparently associated with but not identical to HLA-DPw1. Most clones defined "splits" or subsets of DPw1 and some also displayed "extra" reactions with DPw1-negative stimulator cells. Further evidence was also found that, of the molecules bearing epitopic subsets associated with DPw1, some may be selectively expressed on the cell surface whereas the surface density of other DPw1-associated antigens may be varied. Thus, the HLA-DP region appears to encode a complex array of alloantigens and is in this regard similar to the HLA-DR region.

B-Lymphocytes↗
PubMed1986

Recognition of an HLA-DPw1 specific alloantiserum raised by planned immunization.

This study reports identification of the first alloantiserum specific for a single HLA-DP allele and presents valuable technical information for the serological detection of the HLA-DP gene product. Serological detection of the HLA-DP gene products was undertaken by analyzing a large number of alloantisera against an HLA-DP characterized, monocyte depleted, B-lymphocyte reference panel. After absorption of contaminating DR antibodies, one alloantiserum (SOW) which had been raised by planned immunization, was shown to have a correlation coefficient of 0.91 with DPw1 as defined by primed lymphocytes. No association was seen with any other HLA-A,-B,-C,-D,-DR, or -DQ specificity in either population or family studies. The HLA-DP typing of the serum donor and immunizing recipient support the conclusion. Evidence is presented which suggests that expression of the DP molecule is not stable, at least as detected by conventional microcytotoxicity techniques.

Antigen-Antibody Complex↗
PubMed1986

Failure of oestradiol administration to induce fatty liver haemorrhagic syndrome in the laying hen.

Studies were carried out to investigate whether the administration of oestradiol to laying hens induced fatty liver-haemorrhagic syndrome (FLHS). Short term oestradiol administration (up to 6 d) significantly increased liver size and plasma lipid concentration but had no effect on liver lipid concentration or hepatic lipogenic enzyme activities. Longer-term hormone treatment (up to 28 d) again significantly increased liver size and plasma lipid concentration. Liver lipid concentration was substantially reduced and lipogenic enzyme activity significantly reduced in oestradiol-treated birds. These effects had some similarities to those seen in oestrogenised immature birds and were additive to the effects of endogenous oestrogen in the laying bird. There were no deaths from FLHS and oestradiol treatment did not cause liver haemorrhages or affect egg production.

Animals↗
PubMed1986

Goitrous Hashimoto's thyroiditis. Lack of association with HLA antigens.

We studied HLA antigen frequency in 54 carefully selected patients with goitrous Hashimoto's thyroiditis. All had an appropriate clinical course, positive family history, antithyroid antibodies and/or a needle biopsy indicating chronic lymphocytic thyroiditis. We found no statistically significant association with any HLA-A, -B, -C or DR specificity.

Female↗
PubMed1985

Hereditary malignant melanoma is not linked to the HLA complex on chromosome 6.

Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re-analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (theta) less than 40%. Data on family members' status regarding dysplastic nevi (DN), a well-characterized precursor of hereditary CMM, were available for our 11 families and 7 previously-reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub-groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects' CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously-published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex.

Chromosomes, Human, 6-12 and X↗
PubMed1985

Localization of C4 genes within the HLA complex by molecular genotyping.

Segregation of the complement component, C4, was analyzed in six families that each included an individual who inherited an HLA haplotype where a crossover event had occurred in the region between HLA-B and HLA-DR. Two cDNA clones corresponding to the C4 gene were utilized as probes in Southern blot analysis of DNA from members of each family. Restriction fragment length polymorphisms (RFLP) were observed and were assigned to haplotypes. In one family RFLP, hybridizing with the C4 probes, segregrated with HLA-B, and in four families RFLP segregated with HLA-DR; one family was not informative in this respect. These analyses have made it possible to localize the genes for C4 between HLA-B and HLA-DR by molecular genotyping and to characterize three different genomic configurations of C4 genes by limited restriction mapping.

Chromosome Mapping↗
PubMed1985

Measles-specific T cell clones derived from a twin with multiple sclerosis: genetic restriction studies.

The association between multiple sclerosis (MS) and HLA-DR2 suggests that the disease may be associated with an aberrant immune response, likely directed against an antigen of either viral or host origin. We have used measles virus-specific T cell clones derived from a patient with MS to study genetic restriction patterns of antigen presentation by macrophage-enriched (E-) populations. Twenty-two clones proliferated in response to measles-infected Vero cells but not to mumps-infected or uninfected Veros. E- cells from both the autologous subject and her healthy, measles nonresponder identical twin were capable of presenting antigen to all clones. Studies with E- cells obtained from a panel of cell donors demonstrated clones which recognized antigen in association with D2/DR2, DR4, subgroups of DR4, and SB3. Three clones recognized antigen only in association with the autologous or twin's cells, but not with other sets of HLA-matched E-cells obtained from healthy donors or from other patients with MS. These studies indicate that the differing responses to measles virus demonstrated by these two identical twins are not explained by alterations in the interactions between antigen-presenting cells and T cells. Furthermore, at the clonal level, no preferential role is seen for HLA-DR2 as the restricting element for presentation of measles virus to these clones.

Antigen-Presenting Cells↗
PubMed1984

The detection of HLA-DR, MB and MT determinants on purified class II molecules by inhibition of microcytotoxicity.

An assay has been developed which makes it possible to determine the HLA allospecificities carried by molecules in purified fractions of detergent lysates from EBV-transformed human lymphocytes. It is based on inhibition of the standard microlymphocytotoxic test used for identifying HLA class I and II antigens with alloantisera. Soluble cell membrane products from EBV-transformed cell lines homozygous for the HLA region gave specific inhibition of standard typing antisera. The test requires preincubation of microliter volumes of soluble antigen preparations maintained in 0.05% NP-40 with selected antisera prior to adding EBV-transformed cells as target cells. It was possible using this assay to follow isolation of the structurally related human class II molecules bearing the MB and DR specificities. Detergent lysates of cells were fractionated on affinity columns prepared from monoclonal antibodies directed against distinct class II antigens. Eluates from these columns contained the expected DR and MB specificities. The assay is easy to perform, highly reproducible and allows multiple determinations.

Antibodies, Monoclonal↗