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Biomedical subjects

J Street

Publications and source records attributed to J Street.

At least 19 recordsLinked to original sources
PubMed2006

A high-resolution polymerase chain reaction-sequence-specific primer HLA-B*27 typing set and its application in routine HLA-B27 testing.

We designed a set of 35 polymerase chain reaction sequence-specific primers (PCR-SSP) in 29 SSP mixtures to assign 29 HLA-B*27 4-digit level alleles (B*2701-B*2721 and B*2723-B*2730). This was used in conjunction with our 41 PCR-SSP primer mixture low-resolution HLA-B typing set to fully differentiate B*27 from all other HLA-B alleles. Successful typing set validation used 521 B*27 samples covering 13 (B*2701-B*2710 and B*2712, B*2717, B*2723) alleles. The distribution of B*27 alleles was determined in a random population of 4020 local blood donors and the use of PCR-SSP B*27 typing in our routine flow cytometry-based HLA-B27/B2708 typing strategy is described.

Alleles↗
PubMed2006

Identification of a novel HLA-A allele (A*1115) in the UK National External Quality Assessment Schemes for Histocompatibility and Immunogenetics' Educational Cell Exchange.

The novel allele, HLA-A*1115, was identified in an 'Educational Scheme' sample (ED03/03 - from a north-western European Caucasoid blood donor) distributed by the UK National External Quality Assessment Schemes for Histocompatibility and Immunogenetics. ED03/03 was typed by serology, the polymerase chain reaction using sequence-specific primers and sequence-based typing. A*1115 is most similar to A*110101 with a single mismatch (G to C) at constant position 565, leading to a conservative amino acid change from valine (GTG) to leucine (CTG) at codon 165 in the alpha(2) domain. This substitution has not been reported for any other HLA class I allele so far. The HLA-A*1115-bearing haplotype was B*350101; Cw*040101; DRB1*140101; DRB3*020201; DQA1*010401; DQB1*0503; DPA1*0103/07; DPB1*030101. Extensive serological typing indicated that this allele essentially encodes a 'normal' HLA-A11 specificity.

Alleles↗
PubMed2003

Immunogenetics of two new HLA alleles: A*0108 and B*4031.

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.

Gene Frequency↗
PubMed2003

Observations on the HLA-A2403 specificity.

We found HLA-A*2423 in a subject possessing the HLA-A2403 specificity. Consequently we delineated the A*24 alleles of 41 subjects previously assigned as 'A2403' by serology and/or 'low-resolution' PCR-SSP (allele group: A*2403/10/18/22/23/33) and found that 36 were A*2403, 3 were A*2410 and 2 were A*2433. The A*2410 and A*2433 subjects also typed as A2403. Several likely A*2410/23/33-bearing haplotypes were identified and the frequency of the A*2403/10/18/22/23/33 alleles was determined in 26,826 Welsh blood donors. We suggest that HLA-A9/A24 antibodies against epitope(s) involving 166D and 167G will fail to react with all A*2403/10/18/22/23/33 products. As it is this 'short' A9/A24 serological reactivity that defines HLA-A2403 all these products will be serologically designated as HLA-A2403.

HLA-A Antigens↗
PubMed2003

Immunogenetics of two new HLA-B alleles: B*4414 and B*5708.

Two new alleles, HLA-B*4414 and B*5708, were identified in north-western European Caucasoid blood donors. B*4414 differed from B*440201 by two nucleotide substitutions in exon 3 [positions 66 (T to C) and 69 (G to A)] producing two amino acid differences between the B*440201 and B*4414 specificities (tyrosine to histidine at codon 113 and aspartic acid to asparagine at codon 114). B*5708 differed from B*570101 by a single substitution (G to C) at position 247 in exon 2 causing an amino acid difference between B*570101 and B*5708 products of arginine to proline at codon 83. The likely haplotypes bearing these alleles were identified. Both alleles occurred once in approximately 25,000 random blood donors so both have a frequency of approximately 0.00002 (carriage frequency 0.004%). B*4414 and B*5708 specificities both gave 'short' serological reactivity for their expected specificities and Bw4. The likely reasons for this are discussed in relation to the epitopes of B44 and B57.

HLA-B Antigens↗
PubMed2003

Immunogenetics of the rare HLA-B allele B*4408.

The nucleotide sequence of exons 2 and 3 of B*4408 has been confirmed. This allele has now been found in five, apparently unrelated, north-western European Caucasoid subjects, residing in Wales, on HLA haplotypes bearing: A*0201, Cw*0501 with DRB1*0401, DQA1*03, DQB1*0301 in four instances and DRB1*0701, DQA1*0201, DQB1*0202 in one instance. The unique serological reactivity of 'HLA-B44BO' was established using up to nine B*4408 subjects and was easily identified using a variety of B44 and B62 antisera. The phenotype and gene frequencies of B*4408, in a sample of 40 473 subjects residing in Wales, were 0.01235% and 0.00006, respectively.

HLA-B Antigens↗
PubMed2003

Immunogenetics of a new HLA-B null allele, HLA-B*4423N.

The second example of an HLA-B*44 null allele (B*4423N) was identified by discrepancies between serological and polymerase chain reaction-sequence-specific primer (PCR-SSP) typing in two north-western European Caucasoid unrelated stem cell donor volunteers. HLA-B*4423N was identical to B*440201 except for a single nucleotide substitution at position 493 in exon 3, resulting in a premature stop codon at bases 493-495 (TAG rather than CAG at codon 141). As expected, comprehensive serological testing using 54 antisera, directed towards B44 or Bw4, failed to identify the HLA-B44 (Bw4) specificity. The B*4423N-bearing haplotype was identified as A*0201, Cw*0501, DRB1*0408, DRB4*01, DQA1*03, DQB1*0304 and the frequency of B*4423N estimated as 0.00006 (carriage frequency 0.0121%) in 16 533 subjects resident in Wales.

Europe↗
PubMed2002

Immunogenetic study of a new HLA allele, B*2723.

A novel HLA-B*27 allele (B*2723) detected by irregular serological and PCR-SSP typing results was identified by nucleotide sequencing of exons 2 and 3. B*2723 differs from B*27052 by nine nucleotides which encode seven amino acid changes at positions 63 (Glu to Asn), 67 (Cys to Phe), 69 (Ala to Thr), 70 (Lys to Asn), 71 (Ala to Thr), 74 (Asp to Tyr) and 77 (Asp to Ser) in the alpha1 helix. All these substitutions are possessed by B*35 alleles suggesting that B*2723 was created by a gene conversion-like event involving B*27052 and a B*35 allele. Using the HLA-A*26 and DRB1*12 alleles of the B*2723-bearing haplotype as 'markers', two further examples of B*2723 were found in 29,851 blood donors. Therefore, B*2723 has a 'minimum' gene frequency of 0.000034 (phenotype frequency 0.0067%) in blood donors resident in Wales. In all three families, B*2723 was present on a haplotype with: A*26; Cw*0202; DRB1*1201/6/7; DRB3*02; DQA1*05; DQB1*0301. The B*2723 product failed to react with HLA-B27 antisera and reacted weakly or not at all with Bw4 antisera. Lack of the ECAKA motif at amino acid positions 63, 67, 69-71 probably accounts for lack of the B27 specificity while the amino acid combination 74Y, 77S, 80T, 81L may cause aberrant Bw4 reactivity.

Amino Acid Sequence↗
PubMed2002

Dipyridamole may be used safely in patients with ischaemic heart disease.

It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease. The published literature, periodic safety update reports, the randomised controlled trials of antiplatelet agents in stroke prevention and those including dipyridamole in cardiovascular indications, have been reviewed and analysed. The early reports of serious adverse cardiac effect attributable to dipyridamole occurred in patients with severe coronary artery disease using dipyridamole as a stress test adjunct to cardiac imaging. The randomised controlled trials databases show no evidence of mortality and only isolated cases of significant cardiac morbidity attributable to dipyridamole at recommended oral doses in patients with ischaemic heart disease. We conclude that patients with cerebrovascular and mild to moderate concomitant ischaemic heart disease may be treated safely with dipyridamole for the secondary prevention of stroke.

Dipyridamole↗
PubMed2001

Randomized trial comparing traditional Chinese medical acupuncture, therapeutic massage, and self-care education for chronic low back pain.

BACKGROUND: Because the value of popular forms of alternative care for chronic back pain remains uncertain, we compared the effectiveness of acupuncture, therapeutic massage, and self-care education for persistent back pain. METHODS: We randomized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture (n = 94), therapeutic massage (n = 78), or self-care educational materials (n = 90). Up to 10 massage or acupuncture visits were permitted over 10 weeks. Symptoms (0-10 scale) and dysfunction (0-23 scale) were assessed by telephone interviewers masked to treatment group. Follow-up was available for 95% of patients after 4, 10, and 52 weeks, and none withdrew for adverse effects. RESULTS: Treatment groups were compared after adjustment for prerandomization covariates using an intent-to-treat analysis. At 10 weeks, massage was superior to self-care on the symptom scale (3.41 vs 4.71, respectively; P =.01) and the disability scale (5.88 vs 8.92, respectively; P<.001). Massage was also superior to acupuncture on the disability scale (5.89 vs 8.25, respectively; P =.01). After 1 year, massage was not better than self-care but was better than acupuncture (symptom scale: 3.08 vs 4.74, respectively; P =.002; dysfunction scale: 6.29 vs 8.21, respectively; P =.05). The massage group used the least medications (P<.05) and had the lowest costs of subsequent care. CONCLUSIONS: Therapeutic massage was effective for persistent low back pain, apparently providing long-lasting benefits. Traditional Chinese Medical acupuncture was relatively ineffective. Massage might be an effective alternative to conventional medical care for persistent back pain.

Acupuncture Therapy↗
PubMed2001

Sequence, genetics and serology of a new HLA-B allele: B*4903.

A new HLA-B allele - B*4903 - was detected by the polymerase chain reaction using sequence-specific priming (PCR-SSP), in a Caucasoid bone marrow panel donor, that differs from B*4901 by 8 nucleotides at positions 141, 142, 144, 165, 167, 193, 206 and 213 in exon 2. These substitutions all occur in HLA-B*51 and B*52 alleles and encode 4 amino acid substitutions at positions 24 (Thr to Ala), 32 (Leu to Gln), 41 (Thr to Ala) and 45 (Lys to Thr). This suggests that B*4903 occurred following a gene conversion-like event involving B*4901 and probably a B*51 allele. HLA-B*4903 was identified on a haplotype with: HLA-A*0201; Cw*07; DRB1*1302/34; DRB3*0301; DQA1*0102; DQB1*0604; BfS; C4A3; C4BQ0 and encodes a unique serological specificity which was characterised by the reactivity of 55 antisera directed towards at least four predicted epitopes. No further examples of B*4903 were found in 15,796 consecutive HLA PCR-SSP typed donors from the Welsh Bone Marrow Donor Registry, indicating that this allele has a phenotype frequency of <0.01% and a gene frequency of <0.00004.

Antilymphocyte Serum↗
PubMed2000

Molecular, serological and genetic studies on two new HLA-DRB1 alleles--HLA-DRB1*0704 and HLA-DRB1*1507.

Two new HLA-DRB1 alleles (DRB1*0704 and DRB1*1507) were detected during routine polymerase chain reaction (PCR)-based typing of two Caucasoid bone marrow panel donors due to apparent DRB1* "blanks" being associated with unexpected DRB4, DRB5 and DQB1 alleles. HLA-DRB1*0704 differed from DRB1*0701 by five consecutive nucleotides at positions 217 to 221 of exon 2 encoding two amino acids substitutions of tyrosine to asparagine at codons 77 and valine to tyrosine at codon 78. DRB1*1507 differed from DRB1*1501 by a single nucleotide at position 127 encoding an amino acid substitution of phenylalanine to tyrosine at codon 47. Their specificities were unequivocally assigned by serology as HLA-DR7 and DR15, respectively, and family and population studies allowed their likely HLA-A,B,C,DR,DQ and complement (Bf, C4A, C4B) bearing haplotypes to be identified. No further examples were found in 19,113 HLA-DR,DQ typed donors from the Welsh Bone Marrow Donor Registry indicating that both these alleles have a phenotype frequency of <0.01% and a gene frequency of <0.00003.

Alleles↗
PubMed2000

Is human fracture hematoma inherently angiogenic?

This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.

Adult↗
PubMed2000

Is provisional stenting the effective option? The WIDEST study (Wiktor stent in de novo stenosis). Widest Trial Investigators' Group.

AIM: To compare the immediate and late outcomes of patients treated by a policy of routine stent implantation with routine balloon angioplasty and the use of stents only when an ideal result has not been obtained. METHODS: A nine centre, multinational, randomised study of 300 patients with coronary artery disease thought suitable for treatment of a single lesion by balloon angioplasty or stent implantation. Only new lesions in patients who had not undergone previous bypass surgery were included, and totally occluded vessels were excluded. RESULTS: The initial procedure was considered successful in 96% of patients. There was more complete angiographic restoration of luminal diameter in patients treated by elective stent (minimum lumen diameter (MLD) 2.68 mm for stent v 2.27 mm for balloon; p < 0.007), but analysis of the subgroup of balloon angioplasty patients who crossed over to stenting showed that they achieved similar results to the elective stent group. Late luminal loss was greater in stented patients than in those undergoing balloon angioplasty only, and by six months the angiographic benefit of stenting had disappeared (MLD 1.90 mm for stent group v 2.00 mm for balloon angioplasty). Angiographic and clinical results in the balloon angioplasty group were assisted by the high crossover rate (30.1%). Both groups had similar symptom relief, with 58.9% of patients improving by two or more angina grades. The need for further revascularisation was also similar in the two groups at one year (18.2% in the stented group v 17.1% in the balloon angioplasty group). Haemorrhagic complications at the local arterial entry site were more common than expected and were distributed equally between the patients receiving full anticoagulation and those receiving antiplatelet treatment only. The results of both Wiktor stent placement and balloon angioplasty were similar to the findings in the stent group in previous randomised studies (Benestent II, STRESS). CONCLUSIONS: Provisional stenting appears to offer the same longer term outcome as elective stenting in this selected group of patients. Improvement in the results of conventional balloon angioplasty in the past 10 years means that a policy of obtaining an ideal result without the use of stents appears to be practicable in many of these patients, with consequent cost savings.

Adult↗