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D H Wright

Publications and source records attributed to D H Wright.

At least 19 recordsLinked to original sources

Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt's lymphoma.

Epstein-Barr virus (EBV)-infected cells may sustain three distinct forms of virus latency. In lymphoblastoid cell lines, six EBV-encoded nuclear antigens (EBNA1, 2, 3A, 3B, 3C, -LP), three latent membrane proteins (LMP1, 2A, 2B), and two nuclear RNAs (EBERs) are expressed. This form of latency, termed latency III, is also encountered in some posttransplant lymphoproliferative disorders. In EBV-positive cases of Hodgkin's disease, the EBERs, EBNA1, and the LMPs are expressed (latency II), whereas in Burkitt's lymphoma (BL) only the EBERs and EBNA1 have been detected (latency I). We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology. Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases. Also, the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases, indicating entry into the lytic cycle. A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines. Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors.

Adolescent

HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy.

CD is a gluten-sensitive enteropathy, strongly associated with expression of the DQA1*0501, DQB1*0201 genotype. CD patients have an increased risk of malignancy, particularly EATCL. However, it is controversial as to whether adults with EATCL represent a subgroup of patients with CD or should be regarded as a distinct entity. To investigate the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype frequencies were compared with those observed in 151 unrelated control individuals. A total of 83 (91%) of 91 CD patients were of DQA1*0501, DQB1*0201 genotype (pc < 10(-6), RR = 522.2), compared with 40 (93%) of 43 EATCL patients (pc < 10(-6), RR = 44.2) with amplifiable DNA versus 35 (23%) of 151 controls. DRB1*03 frequencies were also elevated in both patient groups (79 of 91 in CD [87%; pc < 10(-6), RR = 24.5] and 38 of 40 in EATCL [95%; pc < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results confirm previous studies of HLA associations in CD and also suggest that EATCL arises in individuals with the DQA1*0501, DQB1*0201 CD-predisposing genotype. However, the frequency of DRB1*03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%) compared with both control individuals (3 of 151, 2%; pc < 10(-6), RR = 32.9) and uncomplicated CD patients (6 of 91, 7%; pc = 0.04, RR = 9.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The major complications of coeliac disease.

Neoplasms constitute the major complication of coeliac disease, and high-grade T-cell lymphoma of the small intestine (enteropathy-associated T-cell lymphoma) is the most common neoplasm in this category. HLA genotyping indicates that in patients with enteropathy-associated T-cell lymphoma have the coeliac disease associated DQA1*0501, DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for lymphoma development. Molecular biological and immunohistochemical studies have shown that the intestinal mucosa distant from the tumour contains clonal populations of small T cells, often of the same clone as the high-grade T-cell lymphoma. These findings suggest that enteropathy-associated T-cell lymphoma arises in the setting of coeliac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumour, which is usually the cause of the presenting symptoms. Most cases of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same disease process. If the ulceration occurs at a time when the neoplastic T-cells are of a low grade, morphological recognition of tumour cells in the ulcers may be impossible. Carcinoma of the pharynx and oesophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with coeliac disease. The increased risk of carcinoma of the oesophagus may be related to vitamin A deficiency. A number of reports have indicated an increased prevalence of various types of chronic hepatitis in patients with coeliac disease, but no coherent view of the cause of this association has emerged. Similarly, patients with coeliac disease have been reported to have various forms of fibrosing lung disease of uncertain causation. In recent years, there have been several reports, mainly from Italy, of a syndrome of epilepsy and bilateral brain calcification occurring in coeliac patients. The pathogenesis of this condition is not known and its prevalence in other communities is uncertain. Splenic atrophy occurs frequently in patients with coeliac disease and is related to the severity of the disease and degree of dietary control. Splenic atrophy predisposes to infection with capsulated bacteria, although mortality studies indicate that infection with these organisms is not a major cause of death in patients with coeliac disease.

Brain

Acromial angle on radiographs of the shoulder: correlation with the impingement syndrome and rotator cuff tears.

OBJECTIVE: This study was undertaken to determine the reproducibility of measurements of an acromial angle on radiographs and to correlate those measurements with the presence of the impingement syndrome and rotator cuff tears. MATERIALS AND METHODS: Ninety-nine shoulders in 95 patients who had an arch radiograph and had undergone shoulder arthroscopy were included in this retrospective study. The acromial angle was measured on the arch view of the shoulder independently by three observers who were blinded to the name, history, and arthroscopic results. The angle was measured at the intersection of lines drawn along the inferior cortex of the anterior and posterior portions of the acromion. Interobserver variability was determined by the intercorrelation coefficient (a test of reproducibility of quantitative measurements). The average of the three measurements for each patient was correlated with the preoperative diagnosis and the arthroscopic findings. RESULTS: A correlation was found between increasing severity of cuff disease as determined on arthroscopy and increasing acromial angle (p < .01). In 67 patients (70 shoulders) with impingement, patients with a full-thickness tear (29%) accounted for 43% of those with an angle of 30 degrees or greater. The average acromial angle for patients with impingement was greater than that for either patients with instability or patients with trauma (p < .05 for both). An angle of 25 degrees or greater was measured in 63% of patients with impingement but in only 18% of those with instability. The average acromial angle in patients with impingement and an intact rotator cuff was also greater than the average angle in patients with instability (p = .001). The interobserver variability had an intercorrelation coefficient of 0.90. CONCLUSION: The acromial angle is an objective and fairly reproducible measure of anterior acromial shape. The angle is useful in identifying patients with a greater likelihood of having a rotator cuff tear and in distinguishing patients with primary impingement from those with instability.

Acromion

Bucket-handle tears of the medial and lateral menisci of the knee: value of MR imaging in detecting displaced fragments.

OBJECTIVE: A bucket-handle tear of a meniscus is a longitudinal tear with an attached fragment displaced away from the meniscus. Several MR findings of bucket-handle tears have been reported previously. However, the sensitivity of MR for detecting the displaced fragment is unknown. We determined the sensitivity of MR for detecting a displaced bucket-handle tear and determined how the sensitivity varied with tears of different sizes. We also evaluated whether the three findings of a displaced fragment differed in frequency between medial and lateral tears. MATERIALS AND METHODS: We retrospectively evaluated the MR examinations of 39 patients with arthroscopically proven bucket-handle tears for signs of a displaced meniscal fragment. Thirty-two patients had medial meniscal bucket-handle tears, and seven had lateral tears. Two observers evaluated each examination independently, with discrepancies resolved by consensus of a third reader. Each observer evaluated for three findings of a bucket-handle tear: a double posterior cruciate ligament sign, a flipped meniscus sign, or a fragment in the intercondylar notch. A double posterior cruciate ligament sign is present when the meniscal fragment is displaced anterior to the posterior cruciate ligament, resembling two ligaments. A flipped meniscus sign occurs when the fragment is flipped anteriorly so the anterior horn of the meniscus appears to be enlarged. We tested for differences between menisci in the sensitivity for each sign using Pearson's chi-squared test or Fisher's exact test. We compared the sensitivity of MR for identifying fragments when the tear involved one third, two thirds, or the entire meniscus using Spearman's rank correlation. RESULTS: Overall sensitivity for a displaced fragment was only 0.64. When the bucket-handle tear involved the entire meniscus, the displaced fragment could be seen in 84% of the menisci. The double posterior cruciate ligament sign was seen in 53% of the medial and none of the lateral bucket-handle tears (p = .01). The flipped meniscus sign was noted in 44% of medial and 29% of lateral menisci (p = .68), and a fragment was identified in the intercondylar notch in 66% of medial and 43% of lateral menisci (p = .40). CONCLUSION: MR is sensitive for detecting meniscal fragments in large bucket-handle tears, but is less so in small tears. The flipped meniscus sign and presence of a fragment in the notch were comparably useful findings of a displaced fragment in both medial and lateral menisci. The double posterior cruciate ligament sign was noted only in medial bucket-handle tears.

Adult

Microwave antigen retrieval in immunocytochemistry: a study of 80 antibodies.

AIMS: To evaluate the effect of microwave irradiation on the staining quality of a range of commonly used primary antibodies in archival, formalin fixed, paraffin wax embedded material, with emphasis on antibodies that have previously worked successfully only on frozen tissue. METHODS: Immunocytochemistry (streptavidin-biotin complex technique) was performed on histological sections of a range of normal and pathological tissues, after varying treatment with microwave irradiation. The staining quality of each antibody was compared with that achieved without prior treatment of the sections or after enzyme predigestion. RESULTS: Microwave irradiation permitted successful immunostaining with 20 antibodies that stained only frozen tissues before. The staining characteristics of 21 antibodies that were already known to stain formalin fixed, paraffin wax embedded material were improved. Another 39 antibodies did not show enhanced staining with microwave irradiation. The method preserves tissue morphology and produces more consistent staining than that achieved by enzyme predigestion with many antibodies. Microwave irradiation may also allow some primary antibodies to be used at higher working dilutions. The citrate buffer used in this study avoids the necessity of exposure to heavy metal salts. CONCLUSIONS: Microwave antigen retrieval represents an important technical advance within immunocytochemistry that will greatly increase the range of antibodies which can be used to study formalin fixed, paraffin wax embedded tissues.

Antibodies, Monoclonal

Cytogenetic and molecular studies of t(14;18) and t(14;19) in nodal and extranodal B-cell lymphoma.

We have examined 107 cases of B-cell lymphoma for the t(14;18) translocation, characteristically described in follicular lymphoma. B-Cell lymphomas of extranodal origin, and in particular malignancies derived from mucosa-associated lymphoid tissue (MALT), were compared with node-based lymphomas of follicular and diffuse morphology. Cytogenetic techniques were supplemented by molecular analysis using probes which recognize both the major and the minor breakpoint regions of the bcl-2 gene located on chromosome 18 (q21). t(14;18) was detected in 55 per cent of follicular and 27 per cent of diffuse B-cell lymphomas thought to be of follicle centre cell origin. Cytogenetics and molecular analysis proved equally effective in demonstrating the translocation. t(14;18) was not observed in the 36 extranodal lymphomas examined, of which 20 were characterized histologically as lymphomas of MALT, using either technique. In addition, 30 cases demonstrated only a germline band when probed with a bcl-3 probe specific for t(14;19), a translocation observed in chronic lymphocytic leukaemia (CLL). Cytogenetic abnormalities were detected in all cases of extranodal lymphoma, although no consistent abnormality was observed. Numerical abnormalities of chromosomes 3, 6, 16, and 18; structural abnormalities of chromosomes 2, 6, 8, and 9; and small marker chromosomes were frequently seen. This study provides data which suggest that different genetic events are involved in the development of lymphoma of MALT from those giving rise to follicle centre cell lymphomas.

Autoradiography

Epstein-Barr virus latent membrane protein expression by Hodgkin and Reed-Sternberg-like cells in acute infectious mononucleosis.

In the light of reports of latent membrane protein (LMP) expression by Hodgkin and Reed-Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen (four cases) from 14 patients with acute infectious mononucleosis (IM) have been examined for the presence of HRS-like cells and immunostained with an antibody to LMP. Sections of the tonsils and one lymph node were also stained with a panel of antibodies which characterize HRS cells of Hodgkin's disease. The tonsils contained abundant HRS-like cells, mainly adjacent to the crypts, which were highlighted by strong LMP expression. The immunophenotype of these cells closely, but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph nodes and spleens showed the typical changes of acute IM but only few LMP-positive HRS-like cells were present in the cervical lymph nodes and hardly any were present in the inguinal nodes and spleen. These findings suggest that tonsillar crypt squamous epithelium may play a role in the formation of LMP-positive HRS-like cells; these cells could be progenitors of Hodgkin's disease HRS cells and, if so, this might explain the restricted sites of presentation of Hodgkin's disease.

Acute Disease

Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells.

We have performed an immunohistochemical study of immunoblastic T cell lymphoma and enteropathy-associated T cell lymphoma for alpha-1 anti-trypsin and CD30. Cytoplasmic staining for alpha 1 anti-trypsin is present in the malignant cells in both types of T cell neoplasm which also express CD30, a marker of lymphoid activation. Peripheral blood T lymphocytes on stimulation with mitogen also show granular cytoplasmic expression of alpha 1 anti-trypsin. Time course studies show that this parallels the expression of CD30. Alpha 1 anti-trypsin expression appears therefore to be associated with activation in T cells. Further studies of sub-fractionated T lymphocytes in vitro suggest that the expression of alpha 1 anti-trypsin on activation is not restricted to an individual lymphocyte subset.

Antigens, CD

The morphological spectrum of monocytoid B-cell lymphoma and its relationship to lymphomas of mucosa-associated lymphoid tissue.

We report 10 cases of monocytoid B-cell lymphoma, five of which had extranodal lymphomas of mucosa-associated lymphoid tissue (MALT) type. In one patient the MALT lymphoma in the salivary gland was microscopic. In another, the small bowel lymphoma, which preceded the monocytoid B-cell lymphoma by 11 years, showed different clonal immunoglobulin gene rearrangements. Attention is drawn to the extreme degree of plasmacytic differentiation and epithelioid cell infiltration that may occur in monocytoid B-cell lymphoma. In addition to the cytological and immunophenotypic likeness of monocytoid B-cells and centrocyte-like cells, monocytoid B-cell and MALT lymphomas share a number of micro-anatomical and behavioural characteristics. These include the sharp separation of the monocytoid B-cells and plasma cells, follicular colonization and progression to high-grade lymphoma. It is suggested that the frequent association of monocytoid B-cell lymphoma with Sjögren's syndrome may be due to the fact that the salivary glands drain to cervical lymph nodes that are part of the systemic, rather than the mucosal, lymphocyte circulation pathway.

Aged

CD43 expression in B cell lymphoma.

AIMS: To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. METHODS: The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. RESULTS: Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CONCLUSION: CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas.

Antibodies, Monoclonal

Alpha-1 antitrypsin gene exon use in stimulated lymphocytes.

AIMS: To investigate the expression of mRNA transcripts containing exon A or B in lymphocyte cultures. METHODS: An in situ hybridisation technique, using synthetic, biotinylated oligonucleotide probes was deployed to allow the demonstration of exon A, exon B, or the normal hepatocyte message containing exon C. RESULTS: Lymphocytes used the same alternative splicing technique as monocytes in the generation of their alpha-1 antitrypsin message. They also provided data on the frequency of exon A and B expression in cells from different subjects. Most circulating granulocytes failed to show the alpha-1 antitrypsin message, suggesting that this protein is synthesised in the marrow and represents a stored protein component in polymorph and circulating nuclear lymphocytes. CONCLUSIONS: In situ hybridisation is a sensitive technique for the detection of individual gene exon use in cell populations. Lymphocytes show the same promoter use as that described for monocytes.

Antisense Elements (Genetics)

Follicular colonization in thyroid lymphoma.

The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin-embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category.

Base Sequence

Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes?

Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness.

Biopsy

Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.

Thirty-five cases of Hodgkin's disease (HD) were analysed for the presence of Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) DNA. EBV genomes were detected in 11/35 cases while none of the cases was positive for HHV-6. Ten of the EBV-positive cases were subsequently analysed using a probe for the terminal region of the virus; the results suggested that the EBV-infected cells were clonally expanded. EBV subtypes specific DNA amplification was used to demonstrate that EBV subtype A, and not subtype B was present in the EBV-positive cases. The age distribution of the EBV-positive cases indicated a statistically significant trend for an increase in positivity with increasing age. This is the first indication that EBV is significantly associated with any subset of HD patients.

Adolescent

Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups.

Adolescent