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Biomedical subjects

A H Johnson

Publications and source records attributed to A H Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cellular crossreactivity. Implications for solid organ transplantation matching.

This study evaluates the cellular crossreactivity among DR11, DR13, and DR8 molecules using TLC reagents generated in reciprocal priming combinations where the responder and stimulator cells express different microvariants of DR11. The large majority of T lymphocyte clones (TLC) derived from such stimulation detect not only the product of the specific DR11 allele expressed by the stimulator but also detect subsets of DR molecules that span serologic specificities. Thus, TLC generated in response to DR(alpha,beta1*1102) detect DR(alpha,beta1*1103) and products of specific DR13, DR8, DR2 and DR4 alleles. Whereas, TLC generated in response to DR(alpha,beta1*1104) detect DR(alpha,beta1*1101), DR(alpha,beta1*1103), and products encoded by specific DR8 and DR2 but not DR13 or DR4 alleles. Since DR11 microvariants cannot be identified serologically, this type of mismatch certainly occurs frequently between DR11 serologically matched donors and recipients. Particularly affected are populations, such as the African American population, that exhibit extensive HLA diversity and exhibit different frequencies of HLA alleles compared with those of the majority of serologically matched cadaveric donors. Rapid methods of DNA-based HLA typing now makes it feasible to utilize this methodology for allele level identificaiton of recipient and donor alleles. Based on the strength of the alloproliferative responses and on the recognition patterns of the TLC reported here, we suggest that retransplant patients might benefit by excluding subsequent donors expressing DR molecules that in vitro demonstrate strong cellular crossreactivity with DR molecules expressed by the previous donor(s) as well as those DR molecules shared with the previous donor(s). Since such a matching schema has the potential to improve retransplant allograft survival, particularly in patients from minority population groups, it should be evaluated clinically.

Alleles↗
PubMed1996

Increased esterification of cholesterol and transfer of cholesteryl ester to apo B-containing lipoproteins in Type 2 diabetes: relationship to serum lipoproteins A-I and A-II.

This study examines the activity of two key enzymes of reverse cholesterol transport, cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 patients with non-insulin dependent diabetes mellitus (NIDDM) and 21 control subjects. Serum CETP was assessed by measuring plasma-mediated cholesteryl ester transfer between pooled exogenous lipoprotein with endogenous LCAT inhibited--an estimate of CETP mass. CETP activity was determined as cholesteryl ester transfer in the presence of the patients' lipoproteins and LCAT (endogenous assay). LCAT activity was determined in the same assay. There was no significant difference in CETP mass between the diabetic and non-diabetic subjects and there was no correlation between CETP mass and LCAT activity. Using the endogenous lipoprotein assay, CETP was elevated in serum from diabetic patients compared to control subjects (10.05 +/- 1.89 vs. 5.50 +/- 0.53 nmol/ml/h P < 0.05). LCAT was also increased in the diabetic patients (53.63 +/- 4.70 vs. 41.22 +/- 3.40 nmol/ml/h P < 0.05). Serum free cholesterol from diabetic and control subjects correlated with CETP activity measured using endogenous lipoprotein assay (r = 0.77, P < 0.001 and r = 0.82, P < 0.001), and also with LCAT activity (r = 0.76, P < 0.01 and r = 0.79, P < 0.01). There was a negative correlation between CETP activity with the endogenous lipoprotein assay and serum high density lipoprotein (HDL) cholesterol in the diabetic patients (r = -0.38, P < 0.01), but not in control subjects. In a subgroup of 10 control subjects, there was a positive correlation between LCAT activity and apolipoprotein (apo) A-I (r = 0.49, P < 0.05) and apo A-II (r = 0.51, P < 0.05) and also between CETP activity (endogenous assay) and apo A-I (r = 0.87, P = 0.001) and apo A-II (r = 0.63, P < 0.05). No relationship was observed between CETP activity and apo A-I or apo A-II in the diabetic subjects. Thus, serum CETP mass was normal in Type 2 diabetes but CETP activity (endogenous assay) was increased and was related to free cholesterol levels and LCAT activity in both diabetic and non-diabetic subjects.

Adult↗
PubMed1996

Molecular and serological characterization of HLA-B71 in association with different class I haplotypes or in different ethnic groups.

The HLA-B70 antigen is among the most common antigens present in African Americans; however, monospecific serologic reagents defining B70 and its subtypes, B71 and B72, are rare. We have recently reported the molecular characterization of a B71 allele (B*1510) from an African American individual carrying the haplotype HLA-A30, Cw3, B71(w6). In order to better define the degree of polymorphism of molecules carrying the B71 serological specificity in the human population, we have used serology, cDNA sequencing, and PCR/SSOP typing to characterize B71 alleles from additional individuals from different ethnic populations and carrying different class I haplotypes. All carried either B*1510 or B*1518 alleles. Other HLA-B alleles isolated from these individuals (B*5001, B*4901, B*3501, B*3701) were identical to previously reported sequences except for a novel B41 allele (B*4102) identified in one Hispanic individual. This allele has concurrently been identified by Rufer and colleagues in Caucasian individuals. The B*4102 allele differs from B*4101 at codons 95 (Leu/Trp) and 97 (Ser/Arg). In addition, the B*4102 allele differs from B*4101 by two silent substitutions at codons 94 (ACC/ACT) and 99 (TAC/TAT). Since the polymorphic sequence present in B*4102 is also present in other HLA-B alleles (e.g.., B*2707, B*4002, B*0702), it may represent a gene conversion cassette. The allelic diversity at the class I loci and the scarcity of monospecific alloantisera support the importance of the application of molecular based methods to identify HLA class I alleles in matching unrelated donor/recipient pairs for bone marrow transplantation.

Alleles↗
PubMed1996

Novel HLA-B alleles, B*8201, B*3515 and B*5106, add to the complexity of serologic identification of HLA types.

Three class I alleles, B*8201, B*3515 and B*5106, have been described using DNA and cDNA sequencing. The B*8201 allele is most structurally related to B*5602, differing from it by 14 nucleotide substitutions resulting in 5 amino acid differences. The other two alleles, B*3515 and B*5106, differ from their most closely related HLA-B alleles by 2-3 nucleotide substitutions resulting in 1-2 amino acid substitutions, respectively. The majority of nucleotide substitutions marking these new alleles are observed in other HLA-B alleles suggesting that gene conversion and/or reciprocal recombination have created this diversity. All of the amino acid substitutions are predicted to alter the antigen binding site of the HLA-B molecule. The newly defined HLA-B allelic products were originally defined by their unusual serologic reactivity patterns. The B*8201 allelic product is serologically typed as a B "blank" or as a variant of B22 or B45. These patterns and the serologic reactivity of the other newly described allelic products are consistent with the protein sequence homology among specific HLA-B molecules. While serology remains a powerful tool for detecting HLA diversity, alleles generated by events resulting in the sharing of HLA sequence polymorphisms among alleles at a locus will continue to create complexity in the interpretation of typing results.

Alleles↗
PubMed1996

T cell responses to the paramyxovirus simian virus 5: studies in multiple sclerosis and normal populations.

A recent study suggested that a significant portion of the oligoclonal IgG found in multiple sclerosis (MS) cerebrospinal fluid may be removed by absorption with simian virus 5 (SV5). We have now evaluated the proliferative responses to SV5 generated by peripheral blood mononuclear cells from normal adult subjects and from patients with MS. Positive responses were detected in 16 of 16 subjects in each group. The magnitude of the response was not significantly different in the two groups. There was no correlation between the level of response and the presence or absence of HLA-DR2. No cross-reactivity with SV5 was demonstrated by panels of human T cell clones directed against myelin basic protein or measles virus. More than 60% of normal individuals between 10 and 16 years of age also generated positive T cell proliferative responses to SV5, while fewer than 25% of subjects below the age of 6 generated positive responses. Intermediate percentages of positive responders were detected in subjects 6-9 years of age. We conclude that the adult human population has been widely exposed to this organism and that initial exposure generally occurs in the early to middle school-age years.

Adolescent↗
PubMed1995

Microvariation creates significant functional differences in the DR3 molecules.

Two DR3 molecules differ by four amino acids whose side chains point into the DR antigen-binding groove. To begin to assess the role of microvariation on DR3 function, DRB1*0302 residues were replaced with DRB1*0301 residues at beta-chain positions 26, 47, 86, and 47 plus 86. Murine fibroblast cell lines expressing DR(alpha, beta 1*0301), DR(alpha, beta 1*0302), and the four mutant 0302 molecules were examined for alloproliferative DR(alpha, beta 1*0302)-specific TLC stimulation and peptide binding. Changing position 26 had the most profound effect on T-cell recognition (seven of nine TLCs did not respond). Two TLCs did not respond to the mutant 0302V86 molecule and four TLCs that did respond to this mutant lost responsiveness when positions 47 and 86 were mutated together. These data suggest that each of these variant residues, including position 47, influence T-cell recognition. Surprisingly, none of the mutations had an effect on the absolute binding of HA 307-319 (DR[alpha, beta 1*0302] specific) and HSP 3-13 (DR[alpha, beta 1*0301] specific); however, the mutant 0302 molecules changed at position 86 (glycine to valine) consistently bound HA 307-319 at significantly higher levels than DR(alpha, beta 1*0302). These data for position 86 are in contrast to other DR molecules and indicate that peptide contact residues for a specific DR molecule cannot be predicted based on binding results obtained with other DR molecules. These data suggest that each of these variant groove residues, although not accessible to the TCR, contribute to the significant functional differences between the DR3 microvariants through subtle influences on the DR3-peptide complex.

Amino Acid Sequence↗
PubMed1995

Effects of mist acidity and ambient ozone removal on montane red spruce.

Recent forest studies have established that high-elevation (> 900 m) populations of red spruce (Picea rubens Sarg.) in the northeastern USA are declining. Because it has been suggested that changes in air quality are responsible for the decline, we examined the effects of acidic mists and ozone on several biochemical and growth parameters in mature montane red spruce. We used branch-sized environmental chambers to introduce mists of controlled composition and exclude ambient clouds and ozone from individual branches within a tree. Mists consisting of distilled water increased the end-of-season pigment concentration and shoot length of enclosed branches relative to ambient or artificial mists. Needle and twig weights and starch concentrations were not significantly altered by the acidic mist treatments. Removal of ambient ozone had no apparent effect on the variables measured.

Journal Article↗
PubMed1995

Cerebral perfusion pressure: management protocol and clinical results.

Early results using cerebral perfusion pressure (CPP) management techniques in persons with traumatic brain injury indicate that treatment directed at CPP is superior to traditional techniques focused on intracranial pressure (ICP) management. The authors have continued to refine management techniques directed at CPP maintenance. One hundred fifty-eight patients with Glasgow Coma Scale (GCS) scores of 7 or lower were managed using vascular volume expansion, cerebrospinal fluid drainage via ventriculostomy, systemic vasopressors (phenylephrine or norepinephrine), and mannitol to maintain a minimum CPP of at least 70 mm Hg. Detailed outcomes and follow-up data bases were maintained. Barbiturates, hyperventilation, and hypothermia were not used. Cerebral perfusion pressure averaged 83 +/- 14 mm Hg; ICP averaged 27 +/- 12 mm Hg; and mean systemic arterial blood pressure averaged 109 +/- 14 mm Hg. Cerebrospinal fluid drainage averaged 100 +/- 98 cc per day. Intake (6040 +/- 4150 cc per day) was carefully titrated to output (5460 +/- 4000 cc per day); mannitol averaged 188 +/- 247 g per day. Approximately 40% of these patients required vasopressor support. Patients requiring vasopressor support had lower GCS scores than those not requiring vasopressors (4.7 +/- 1.3 vs. 5.4 +/- 1.2, respectively). Patients with vasopressor support required larger amounts of mannitol, and their admission ICP was 28.7 +/- 20.7 versus 17.5 +/- 8.6 mm Hg for the nonvasopressor group. Although the death rate in the former group was higher, the outcome quality of the survivors was the same (Glasgow Outcome Scale scores 4.3 +/- 0.9 vs. 4.5 +/- 0.7). Surgical mass lesion patients had outcomes equal to those of the closed head-injury group. Mortality ranged from 52% of patients with a GCS score of 3 to 12% of those with a GCS score of 7; overall mortality was 29% across GCS categories. Favorable outcomes ranged from 35% of patients with a GCS score of 3 to 75% of those with a GCS score of 7. Only 2% of the patients in the series remained vegatative and if patients survived, the likelihood of their having a favorable recovery was approximately 80%. These results are significantly better than other reported series across GCS categories in comparisons of death rates, survival versus dead or vegetative, or favorable versus nonfavorable outcome classifications (Mantel-Haenszel chi 2, p < 0.001). Better management could have improved outcome in as many as 35% to 50% of the deaths.

Adolescent↗
PubMed1994

Detection of malignancy-associated metabolites in the sera of cancer patients by electron capture gas chromatography.

A reliable test that detects malignancy and indicates response to therapy is needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a selective analytical technique that is sensitive to 15 fmol quantities of metabolites, was used to analyse derivatised acidic chloroform extracts of sera from patients with biopsy-proven cancer, non-malignant infectious and non-infectious disease, and healthy controls. Two peaks designated P1 and P10, not found in serum from healthy controls (n = 7) or patients with non-malignant disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer patients. P1 and P10 were later shown by chemical and mass spectral studies to be carboxylic acids. When one or both of these peaks were detected in the sera of non-treated patients they were always associated with malignancy. In patients responding to therapy, a reduction or disappearance of these peaks was observed. Further, it was noted that P10 persisted or increased in sera of patients with progressive cancer not responding to therapy. We conclude that this test has potential in diagnosis and for following the response of the disease to therapy.

Adenocarcinoma↗
PubMed1994

Effect of elevated temperatures on carbon dioxide exchange in Picea rubens.

We examined some of the physiological reasons that may underlie past and expected future migrations of red spruce (Picea rubens Sarg.) by evaluating the effects of high temperatures on photosynthesis and respiration of trees growing on Whiteface Mountain, NY. At temperatures of 35-40 degrees C, the trees exhibited a zero or negative carbon balance. Higher temperatures resulted in cellular disorganization and death. Temperatures around 30 degrees C resulted in reduced CO(2) uptake, a condition that could decrease future reproductive output and competitive stature. We conclude that thermal intolerance explains, at least in part, the absence of red spruce at low elevations and latitudes where temperatures of >/= 30 degrees C occur. We suggest that the thermosensitivity of this species is important with respect to global climate trends and migration patterns.

Journal Article↗
PubMed1993

Molecular characterization of HLA-B71 from an African American individual.

We have sequenced a cDNA clone encoding an HLA-B71 (B70) allele from an African American individual. Serologic definition of B70 allelic products is very difficult due to extensive cross-reactivity of the alloantisera with B35, B15, and B5 antigens. The new sequence most closely resembles the sequence of B*1503, differing only by three amino acids at positions 63, 67, and 116. The B71 sequence differs from alleles of the B15 antigenic group (serologically defined as B62) by 7-8 amino acids and from members of the B35 family by 10 to 12 amino acids. B71 may represent an evolutionary intermediate, sharing elements common to both B35 and B15 allelic groups.

Alleles↗
PubMed1993

Midwinter needle temperature and winter injury of montane red spruce.

To assess the role of solar warming and associated temperature fluctuations in the winter injury of sun-exposed red spruce foliage, we used fine wire thermocouples to monitor midwinter needle temperature in the upper canopy of mature red spruce trees over two winters. In 1989-1990, 15-min mean temperatures were recorded for six needles in a single tree. In 1990-1991, 10-min mean temperatures of six needles in one tree, and 1-min mean temperatures of seven needles in a second tree were recorded during rapid temperature changes. Warming was more frequent and greatest on terminal shoots of branches with a south to southwest aspect. The maximum rise above ambient air temperature exceeded 20 degrees C, and the maximum one minute decrease in temperature was 9 degrees C, with maximum rates of 0.8 and 0.6 degrees C min(-1) sustained over 10- and 15-min intervals, respectively. These data demonstrate that red spruce is subject to rapid temperature fluctuations similar to those known to produce visible injury in American aborvitae, a much hardier species. We concluded that solar warming to temperatures above the freezing point was unlikely to result in dehardening and subsequent freezing injury, because warming was infrequent, of short duration, and did not always raise needle temperature above the freezing point. Parts of branches and some individual shoots were frequently covered by snow or rime that may have prevented injury by reducing the frequency or intensity of needle temperature fluctuations. Radiation load on exposed shoots may have been increased by reflection of short wave radiation from snow and rime deposits on surrounding surfaces, which would exacerbate temperature fluctuations.

Journal Article↗
PubMed1993

Combinatorial diversity in DR2 haplotypes.

Sequence analysis has identified multiple alleles at two loci that encode for the DR2 specificity. The loci, DRB1 and DRB5, are in linkage disequilibrium which can extend to alleles of the DQ loci. Serologic, cellular, and sequence-specific oligonucleotide probe (SSOP) typing techniques have been used to identify the DR2 haplotypes. In this report, we have characterized by SSOP typing and cDNA/DNA sequence analyses the combinatorial diversity of DR2 haplotypes. Cells were selected on the basis of unique serologic reactivity, unique associations of alleles of DR and DQ loci, and/or presence in populations which have not been extensively characterized for HLA diversity. An asymmetric polymerase chain reaction (PCR) amplification was applied to rapidly screen unique cells and to characterize DNA sequence in conjunction with more conventional cDNA sequence analysis. The sequence data confirm the lack of a DRB5 locus in the DR2"LUM" specificity, the unexpected association of DRB1*1602 and DRB5*010 alleles in a nonCaucasoid population, and the association of the allele DRB1*1503 with DRB5*0101 in black African, African American and native American individuals. The DRB1*1503 and DRB5*0101 alleles were identified in an unusual haplotype, DR2,DQ2. The combinatorial diversity of the DR2 haplotypes is extended by these studies in nonCaucasoid populations.

Alleles↗