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J Street

Publications and source records attributed to J Street.

At least 37 records · Page 2Linked to original sources

Identification of HLA-A*0224: implications for PCR-SSP HLA typing.

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.

Base Sequence↗

Identification, sequencing and serology of HLA-B*3527.

We describe a variant HLA-B*35 allele (B*3527) that was detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP) in an individual on the Welsh Bone Marrow Donor registry. B*3527 differs from B*3501 by a single base (G/A) at position 302 that encodes an amino acid change of Ser to Asn at position 77 in the Bw6 epitope. Serological studies using 38 B35-, 4 Bw6- and 7 Bw4-reactive sera indicated that the B*3527 product was indistinguishable from the B35 specificity, and that the substitution did not significantly affect the Bw6 epitope. A family study determined the B*3527 bearing haplotype as: HLA-A*29, B*3527, Cw*0401, DRB1*0404, DRB4*0101/0103, DQA1*03, DQB1*0302, BFS, C4A3, C4B1. The phenotype and gene frequencies in the local Welsh population were<0.01% and <0.00005%, respectively.

Alleles↗

HLA-B*4703: sequence confirmation, serology and distribution.

This study has confirmed the nucleotide sequence of exons 2 and 3 of the B*4703 allele, discovered by an unusual HLA-B47 and Bw6 serological pattern, in two subjects of Black/Japanese and Caribbean Black descent. Titration studies on 25 HLA-B47 cross-reactive sera, stimulated by B13, B27, B44 and B60, and nine Bw6 antisera/monoclonal antibodies, showed that the B*4703 product can be distinguished from the established HLA-B47 specificity. The phenotypes of these donors and an International Cell Exchange donor suggests an association between B*4703 and Cw*0701/ 06 in Black subjects. No examples of B*4703 (or B*4702) were found in 10,194 PCR-SSP HLA-A,B typed Welsh Bone Marrow Donor Registry panel members indicating a phenotype frequency of <0.0098% in this primarily Northern European Caucasoid population.

Alleles↗

Molecular, serological and population studies of the alleles and products of HLA-B*41.

The HLA-B41 specificity was first identified over 25 years ago and, although both serological and biochemical studies have suggested its subdivision, it is only recently that two HLA-B*41 alleles (B*4101 and B*4102) have been identified and sequenced. We designed three oligonucleotide primers, combined in two mixtures to define these alleles by PCR using sequence-specific primers (PCR-SSP) in a random normal population of 9,464 HLA-A, B, DR, DQ typed Northern European Caucasoid donors from the Welsh Bone Marrow Donor Registry. The HLA-B41 phenotype frequency was 0.835%, and of the 79 HLA-B41 subjects 22 (27.85%) were B*4101 and 57 (72.15%) were B*4102. The phenotype frequencies of B*4101 and B*4102 were 0.232 and 0.602%, respectively, and the gene frequencies were 0.00116 and 0.00301, respectively. Formal two-locus linkage disequilibrium (LD) analysis demonstrated significant associations between B*4101 and A30 and DR11, and between B*4102 and A66 and DR13. LD analysis of three loci showed significant associations between B*4101, DR7, DQ2 and B*4101, DR11, DQ7 (DQB1*0301/0304) and between HLA-A3, B*4102, DR13; A66, B*4102, DR7; A66, B*4102, DR13; B*4102, DR13, DQ6 and B*4102, DR13, DQ7. Examination of the HLA phenotypes (including HLA-C) of the B*41 subjects, together with the LD analysis findings, suggested four different HLA haplotypes bearing B*4101 and five B*4102 haplotypes. The most frequent B*4101 haplotype was: HLA- A30 or other A allele, Cw*1701, B*4101, DRB1*1102, DQB1*0301 and the most freqent B*4102 haplotype was: A*6601 or A3 or other A allele, Cw*1701, B*4102, DRB1*1303, DQB1*0301. In addition, the well-known association of A66 with B41 was between A*6601 and B*4102, and although both B*41 alleles were commonly in association with Cw*1701, B*4101 was found with Cw*07. One-dimensional isoelectric focusing (1D-IEF) analysis of HLA-B proteins from 2 B*4101 and 2 B*4102 subjects clearly showed that the B41.1 and B41.2 1D-IEF variants, identified in the 10th International Histocompatibility Workshop, corresponded to B*4101 and B*4102 products, respectively. Serological titration studies, with 59 lymphocytotoxic pregnancy antisera, containing an HLA-B41 component and stimulated by up to five different HLA-B specificities, were unable to differentiate the two groups of B*41 subjects. This suggests that partition of the HLA-B41 specificity will not normally be achieved by classical serological methods. It is suggested that the previous alleged serological subdivision of HLA-B41 was founded on the unwitting use of antisera detecting the HLA-Cw*17 products.

Alleles↗

A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.

BACKGROUND AND METHODS: There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale. RESULTS: After adjustment for base-line differences, the chiropractic group had less severe symptoms than the booklet group at four weeks (P=0.02), and there was a trend toward less severe symptoms in the physical therapy group (P=0.06). However, these differences were small and not significant after transformations of the data to adjust for their non-normal distribution. Differences in the extent of dysfunction among the groups were small and approached significance only at one year, with greater dysfunction in the booklet group than in the other two groups (P=0.05). For all outcomes, there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain. About 75 percent of the subjects in the therapy groups rated their care as very good or excellent, as compared with about 30 percent of the subjects in the booklet group (P<0.001). Over a two-year period, the mean costs of care were $437 for the physical-therapy group, $429 for the chiropractic group, and $153 for the booklet group. CONCLUSIONS: For patients with low back pain, the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs, and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet. Whether the limited benefits of these treatments are worth the additional costs is open to question.

Adult↗

Laparoscopic surgery for abdominal aortic aneurysms. Technical elements of the procedure and a preliminary report of the first 22 patients.

BACKGROUND: Laparoscopic surgery for infrarenal aortic aneurysms is based on the principle of retropertoneal exclusion of the aneurysms sac with aortofemoral or aortoiliac bypass. METHODS: Of 22 patients who met the selection criteria, 20 successfully underwent laparoscopic aortic surgery at Morristown Memorial Hospital between February and October 1997. Technical elements and steps of this operation are described and illustrated. RESULTS: Within 30 days of surgery, 2 patients died and 9 had various major and minor perioperative complications. As a group, the laparoscopic patients had less postoperative pain, needed fewer hours of ventilator support, had shorter intensive care unit (ICU) and hospital lengths of stay, and resumed diet and normal activity earlier than the historical norms of patients undergoing transabdominal or retroperitoneal aortic resections at the same institution. CONCLUSIONS: These early observations suggest that the laparoscopic treatment of infrarenal abdominal aneurysms may have several significant potential benefits. Long-term results and randomized prospective studies with patients matched by risk stratification will be needed to confirm these impressions.

Aged↗

Molecular, serological and population studies on a novel HLA-B allele--HLA-B*5002.

A novel HLA-B allele (B*5002), detected as a discrepancy between serological and PCR-SSP HLA-A and B phenotyping of bone marrow panel donors, was identified by nucleotide sequencing of exons 2 and 3. Titration studies on 39 HLA-B12/B21 cross-reactive antisera showed that the serological specificity of HLA-B*5002 was HLA-B45. PCR-SSP testing of 287 serologically defined HLA-B45-positive subjects from a panel of 12,411 donors, together with HLA-B*45 and B*5002 frequency data on 4,342 PCR-SSP typed subjects, indicated that 4.53% of serologically defined HLA-B45-positive subjects possess HLA-B*5002 and not HLA-B*4501. The phenotype frequency of HLA-B*5002 was 0.08954%; gene frequency was 0.00045 (n=16,753). In 73.3% of instances B*5002 appeared to be present on a haplotype with DRB1*0406 and DQB1*0402, 54.6% of which possessed A*2301. The B*5002, DRB1*0406, DQB1*0402 haplotype represents 52.4% of all haplotypes with DRB1*04 and DQB1*04 and 78.6% of haplotypes possessing DRB1*0406 and DQB1*0402.

Alleles↗

HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales.

Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele - A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05), for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/DQ and HLA-A/B/DR and B/DR/DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and A1, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient's extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.

Adolescent↗

A new HLA-B44 variant (B44BO [B*4408]) identified by serology.

Using HLA serology, we detected a new variant of HLA-B44- B44BO- in two families. This antigen reacts with B44 antisera and is negative with over one-third of B12 (B44, B45) sera but reacts with 50% antisera with a B62 component, especially if they contain anti-B57. The variant, B*4408, differs from the common B*4402 by 4 nucleotide substitutions in exon 2: 193, 206 and 209, which produce changes in the the alpha 1 domain at positions 41, 45 and 46 (TKE in B*4402 and AMA in B44BO); and nucleotide 213, a silent substitution. At each of these positions, B*4408 is identical to B*46 B*57 and may B*15 alleles. As anticipated from its predicted iso-electric point (5.71), one-dimensional isoelectric focusing studies showed that B44BO focuses at the same position as B*4402. The sequence and serological reactivity of this rare antigen allowed the identification of two likely epitopes shared by two different groups of HLA-B antigens.

Alleles↗

HLA-A9 antibodies and epitopes.

Fifty pregnancy alloantisera directed towards HLA-A23 and/or A24 antigens were investigated serologically in titration studies against the three sequenced HLA-A9 specificities, A23 (A*2301), A24 (A*2402) and A2403 (A*2403). The reaction patterns of the antisera fell into five categories which allowed the three HLA-A9 specificities to be easily differentiated. Based on the various titre cytotoxicity scores of the antisera five possible antibody specificities were defined: anti-A23; -A24; -A23/24; -A24/2403 and anti-A23/24/2403. One antiserum crossreacted with HLA-A1 and A24. Inspection of the amino acid sequences of 136 HLA-A, B and C molecules allowed the prediction of five unique epitopes corresponding to these antibody specificities, a possible epitope unique to A2403 and confirmation of a likely epitope shared by A1 and A24. These, together with the previously suggested epitopes HLA-A9/ A2/A28 and A1/A23/A24 together with the presence of Bw4 on the three HLA-A9 antigens suggests that the HLA-A9 family of antigens is characterized by a minimum of nine serologically definable epitopes.

Antibodies↗

Distribution of the HLA-A9 antigen family (A23, A24 and A2403).

Characterization of 50 local anti-HLA-A9 (A23 and/or A24) sera against the HLA-A2403 antigen allowed the retrospective assignment of A2403 and the verification of A23 and A24 specificities in a panel of 9196 volunteer bone marrow donors. The six A2403 positive subjects identified were confirmed by PCR using four sequence-specific primer mixtures. Population analysis showed the distribution and HLA-A/B linkage disequilibrium of HLA-A23 and A24 to be typical of a Northern European Caucasoid population. HLA-A2403 has a phenotype frequency of 0.00065 (gene frequency-0.00033) and is in linkage disequilibrium with HLA-B63 and possibly B35.

Bone Marrow↗

Serological and molecular identification of an HLA-B8 variant, HLA-B8Jon (B*0802).

The serological and molecular characteristics of the first HLA-B8 variant (B8Jon), located on a haplotype bearing HLA-A1, -B8Jon, -Cw*07, DRB1*0301, DQA1*05, DQB1*0201, BfS, C4AQ0, C4B1 and the microsatellite alleles D6S265-3, 258-11, 105-8, 299-1 and 202-2 are identified and described. This new HLA-B antigen was distinguished from the usual B8 by its lack of reactivity with Bw6 and most Bw4 antisera, together with its failure to react with most antisera cross-reactive with HLA-B8. B8Jon gives a 'weaker' response than HLA-B8 in titration studies with B8 antisera. It cannot be differentiated from the usual B8 by one-dimensional iso-electric focusing. Time course studies, absorption analyses and serological tests on 17 Bw4 antibodies suggest that B8Jon possesses an unusually 'weak' Bw4 epitope. Studies on the Bw4 sequence motif by PCR, using sequence-specific primers, indicate that B8Jon has a Bw4 sequence in common with other HLA-B alleles, including B*4402-B*4405, rather than the Bw6 motif found on the familiar HLA-B8 molecule.

DNA↗

Immunoglobulin allotype frequencies in responders and nonresponders to the Rh(D) antigen.

Immunoglobulin allotype frequencies were determined in well characterised groups of responders (n = 160) and non-responders (n = 32) to Rh(D) antigen immunisation. Allotype frequencies in these groups were compared with frequencies in a normal control population (n = 500). No significant differences in allotype frequencies were observed between the responder and non-responder groups, or when these two groups where compared with a normal control population. These results suggest that the immunoglobulin heavy-chain genes do not influence the anti-Rh(D) immune response.

Female↗

Serological identification of a new HLA-B7 variant antigen--HLA-B7QUI.

A new HLA-B antigen, HLA-B7Qui that appears to be a variant of HLA-B7 has been identified. This antigen, which is HLA-Bw6 associated, reacts with approximately two-thirds of cytotoxic antisera stimulated by HLA-B7 or B27 that lack a B27 or B7 component, respectively. All anti-B7 + 27 antisera (stimulated by either B7 or B27) react with B7Qui as do most B22-stimulated sera possessing a B7 component. However, sera stimulated by B60, with or without a B7 component, fail to react with B7Qui. Family studies show the B7Qui allele to be unique to the haplotype-HLA-A32 CW6 B7Qui Bf*S C4A*6 C4B*1 DR11 DQ7 (GLO2). Six Caucasoid subjects on the panel of 6861 HLA-typed potential bone marrow donors have this antigen (phenotype frequency, 0.08745%; gene frequency, 0.04473%). Work undertaken during the 11th International Histocompatibility Workshop (Reekers et al., 1992) showed that B7Qui has the same isoelectric point as HLA-B702 and HLA-B703 (Bpot) and that B7Qui is distinct from the HLA-B7 variants B703, B7SL, BDT, B7 x 40, BRI, and B41v.

Female↗

Response of inbred mice to infection with a new isolate of Trypanosoma musculi.

A new isolate of Trypanosoma musculi has been derived from organisms recovered from Mus spretus captured in Lisbon, Portugal. The time-course and profiles of infection with this isolate in inbred mice have been compared with those obtained with the existing Partinico II isolate. Infections with the Portuguese isolate are less intense, and controlled more quickly than those with the Partinico isolate. As with the latter, there are marked mouse strain-dependent influences on infection with the Portuguese isolate, but these strain-dependent characteristics differ considerably with each isolate. For example, NIH mice were the most susceptible to the Partinico II isolate, but virtually refractory to the Portuguese isolate. Mice exposed to infection with one isolate show complete immunity to both homologous and heterologous challenge infections. These striking interactions between host and parasite genotype are discussed in terms of immunological influences on infection.

Animals↗