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D Todd

Publications and source records attributed to D Todd.

At least 73 records · Page 4Linked to original sources
PubMed1997

T-cell intravascular lymphomatosis (angiotropic large cell lymphoma): association with Epstein-Barr viral infection.

AIMS: Intravascular lymphomatosis (IVL) is a very rare non-Hodgkin's lymphoma characterized by proliferation of lymphoma cells in the vascular lumina without involvement of adjacent parenchymal tissue. IVL is predominantly of B-cell lineage, but occasional cases of T lineage IVL involving almost exclusively the skin have been described. A case of IVL that occurred initially in the epididymis of a patient with an antecedent nasopharyngeal carcinoma was studied to define the clinicopathological features associated with this unique presentation. METHODS AND RESULTS: This lymphoma was studied by standard histological and immunophenotyping methods. The results showed lymphoma cells confined within the blood vessels, which expressed leucocyte common antigen, and T-cell markers CD3 and UCHL-1. The T-cell origin of the IVL prompted investigations for an association with Epstein-Barr virus infection (EBV). In-situ hybridization with digoxigenin-labelled anti-sense RNA probes to EBV encoded RNA (EBER) showed strong signals in the nuclei of virtually all of the lymphoma cells. CONCLUSIONS: EBV infection of the malignant cells was demonstrated by in-situ hybridization. This case suggests that T-cell IVL may be another EBV related human neoplasm. This observation will need to be validated by further studies.

Fatal Outcome↗
PubMed1997

Sequence of porcine circovirus DNA: affinities with plant circoviruses.

The complete nucleotide sequence (1759 nt) of the ssDNA genome of porcine circovirus (PCV) was determined from a cloned dsDNA replicative form isolated from PCV-infected cells. Sequence analysis detected no significant nucleic acid or protein similarity with another animal circovirus, chicken anaemia virus (CAV) but, surprisingly, the highest protein similarity was obtained between the product of the largest predicted PCV ORF (ORF1; encoding a potential protein of 35.7 kDa) and a putative protein encoded by the plant circovirus banana bunchy top virus (BBTV). High protein similarity was also detected with the other plant circoviruses subterranean clover stunt virus (SCSV) and coconut foliar decay virus (CFDV). This region of protein identity corresponds with the putative plant circovirus replication-associated protein (Rep). The presence of a nonanucleotide sequence at the apex of a potential-stem loop structure, identical to that found in the plant circoviruses CFDV and SCSV and similar (one mismatch) to that found in the plant circovirus BBTV and in the geminiviruses, suggests that rolling-circle replication may operate during PCV DNA replication. These findings show that PCV is unique in that it bridges the gap between animal and plant circoviruses. The taxonomic relationship of PCV with other members of the Circoviridae is discussed.

Amino Acid Sequence↗
PubMed1997

Investigation of the attenuation exhibited by a molecularly cloned chicken anemia virus isolate by utilizing a chimeric virus approach.

Molecular cloning of the Cux-1 isolate of chicken anemia virus (CAV), which had been passaged 173 times in cell culture, resulted in the isolation of an attenuated strain, designated cloned isolate 10, which reverted to virulence following 10 passages in young chicks (D. Todd, T. J. Connor, V. M. Calvert, J. L. Creelan, B. M. Meehan, and M. S. McNulty, Avian Pathol. 24:171-187, 1995). The attenuated cloned isolate 10 differs from the molecularly cloned pathogenic Cux-1 isolate in that it possesses a 21-nucleotide insertion within the nontranscribed region of the CAV genome and 17 individual nucleotide substitutions dispersed throughout the genome. Comparative analyses with other published CAV sequences indicated that cloned isolate 10 was unique at nine nucleotide positions and at five amino acid positions. The molecular basis of the attenuation exhibited by cloned isolate 10 was investigated by evaluating the pathogenicities of two sets of complementary chimeric viruses. These sets were produced by transfection with chimeric double-stranded replicative-form (RF) DNA equivalents that contained DNA sequences derived from cloned isolate 10 and the pathogenic cloned Cux-1 isolate. The construction of the chimeric RFs exploited the occurrence of unique EcoRI, PstI, and BamHI restriction sites, which allowed their respective circular CAV RFs to be manipulated as three restriction fragments of 0.58, 0.93, and 0.71 kbp. Examination of the levels of anemia and gross pathology in the thymuses and bone marrows of 14 day-old specific-pathogen-free chicks following infection of 1-day-old chicks with the chimeric and cloned parental isolates indicated that nucleotide changes in each of the three genomic regions contributed towards attenuation. The significance of this result to the development and use of live attenuated CAV vaccines is discussed.

Animals↗
PubMed1996

Aggressive non-Hodgkin's lymphoma: T-cell versus B-cell.

This study is aimed to define the clinical characteristics, treatment of outcome and independent prognostic factors of 144 patients with T- and 357 B-cell non-Hodgkin's lymphomas. Entities with well-defined immunophenotype and clinical characteristics were excluded. Patients with T-cell tumours were younger. T-immunophenotype was associated with more advanced disease and presence of B symptoms. They were also less likely to have bulky disease. Primary nasal lymphomas were usually T-cell while lymphomas arising from the gastrointestinal tract and Waldeyer's ring were mostly B-cell. On univariate analysis, T-immunophenotype was associated with lower CR rate, higher relapse rate and inferior overall survival. On the other hand, multivariate analysis revealed that advanced stage, presence of B symptoms, advanced age, high serum lactate dehydrogenase level and use of non-doxorubicin-containing regimens for induction were associated with poor prognosis. Immunophenotype was not a significant independent prognostic factor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Primary B cell lymphoma of the mediastinum.

Primary B cell mediastinal lymphoma has been recognized as a distinct entity recently. This is a retrospective study to define the clinical features and treatment outcome over a 10-year period. Twenty-four consecutive patients (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum were studied. The median age was 34 years. Symptoms were mainly referrable to the chest, with superior vena cava syndrome (SVCO) present in one-third of the patients. Bulky disease was present in over half (58 per cent) and B symptoms were present in 38 per cent of patients. The overall CR rate was 70 per cent and the 5-year OS rates were 56 per cent and 72 per cent for all and CR patients respectively. Five (71 per cent) primary refractory patients and four (66 per cent) relapsed patients died despite salvage therapy. Six relapses occurred at a median of 6 months from treatment. This study showed that primary large B cell lymphoma of the mediastinum is a clinically distinct entity affecting young patients. A significant proportion attained CR and overall, more than half achieved prolonged remission, and most of the relapses occurred early. However, those who failed to attain CR or relapsed still had a poor outcome. An intensive therapy such as autologous bone marrow transplant has to be considered in this subgroup of patients.

Adolescent↗
PubMed1996

Investigation of the transfection capability of cloned tandemly-repeated chicken anaemia virus DNA fragments.

Chicken anaemia virus (CAV) is an icosahedral virus, 25 nm in diameter, which, on the basis of its circular single-stranded DNA genome, has recently been classified in the family, Circoviridae. We have investigated whether infectious, monomeric CAV DNA from recombinant plasmids containing tandemly-repeated CAV replicative form (RF) DNAs, following transfection, was generated by homologous recombination or a replicational release mechanism involving rolling circle replication (RCR) of DNA. Experiments designed to locate the virus strand origin of RCR and/or sites of recombination were performed by sequence analyses of hybrid viruses generated after transfection with cloned tandemly-repeated RFs specified by the sequence-distinct Cux-1 and 26P4 isolates. Positive transfection results obtained from 2 recombinant plasmid constructs were shown to have resulted from homologous recombination occurring at different sites within the RF sequence. Three of 5 hybrid viruses analysed were "circularised" within the same 105 bp sequence, that contains four 19bp repeats and with which promoter/enhancer activity has been associated. This region may represent a novel origin or recombination hot-spot within the CAV genome. A distinctive cruciform-loop structure within the non-coding region was shown to contain an S1 nuclease-sensitive site, detected in CAV RF and in recombinant plasmids containing RF inserts.

Base Sequence↗
PubMed1996

Apoptosis in renal cell carcinoma: detection by in situ end-labeling of fragmented DNA and correlation with other prognostic factors.

Because stage and grade of renal cell carcinoma (RCC) sometimes fail to predict the patient's outcome, additional prognostic predictors are needed. Apoptosis is a process of programmed cell death seen in both normal and neoplastic tissues, which has been shown to have prognostic significance in some tumor types. Forty-seven RCCs were studied for size, grade, stage, apoptosis, and proliferation. Fragmented DNA, a hallmark of apoptosis, was detected in situ by a process in which the fragmented DNA was labeled with a biotinylated nucleotide, which, in turn, was detected by an avidin-biotin-peroxidase labeling system. The proliferating tumor cells were detected by immunostaining with the MIB-1 antibody. The apoptotic index and proliferation index of each RCC were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1,000 tumor cells. For grade I to IV RCCs, the median proliferative index was 13, 41, 119, and 143; the median apoptotic index was 8, 12, 39, and 73. For stage I to IV RCCs, the median proliferative index was 21, 34, 70, and 144; the median apoptotic index was 8, 9, 20, and 69. There was a statistically significant correlation of tumor grade, stage, and size with both proliferative index and apoptotic index. There was a statistically significant correlation between proliferation index and apoptotic index. In conclusion, apoptosis can be easily and reliably recognized by the in situ end labeling of fragmented DNA and may help predict the outcome of RCC.

Antibodies, Monoclonal↗
PubMed1996

Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry.

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.

Adult↗
PubMed1996

Autosomal recessive lamellar ichthyosis and acute lymphoblastic leukemia.

Autosomal recessive lamellar ichthyosis (ARLI) is a congenital disorder of keratinization, the gene of which has been mapped to chromosome 14q11. This band is also the breakpoint in various chromosomal rearrangements in T cell acute lymphoblastic leukemia (ALL). We describe a patient with ARLI who developed ALL at the age of 2.5 years. High resolution banding showed no abnormality or rearrangement involving chromosome 14. To our knowledge, this is the first description of the occurrence of the two conditions in one patient.

Child, Preschool↗
PubMed1995

Essential thrombocythemia: a retrospective analysis of 39 cases.

Thirty-nine Chinese patients presenting as essential thrombocythemia (ET) were analyzed retrospectively. The median age at presentation was 69 years and the M:F ratio was 1.35:1. At diagnosis, 33 cases (84%) were asymptomatic and the diagnosis was made incidentally, while 3 cases (8%) presented with small vessel, and 2 cases (5%) with large vessel, thrombosis. One patient (3%) presented with minor bleeding. The platelet count ranged from 0.9-34 x 10(12)/l. Of 12 karyotypes done, 2 cases were abnormal, both showing the Philadelphia (Ph) chromosome. First-line therapy was radiophosphorus (32P) in 3 cases, melphalan in 20 cases, and hydroxyurea in 12 cases; 4 cases did not receive specific therapy. During the follow-up (mean = 4 years), no thrombotic or bleeding episodes were observed. One patient with the Ph chromosome underwent blastic transformation. These results indicate that bleeding and thrombosis occur significantly less in Chinese patients than in Western patients. The Ph chromosome appears to be a bad prognostic indicator. Because of the very low incidence of complications and good prognosis, the authors believe that cytoreductive therapy is best achieved by the use of hydroxyurea instead of alkylating agents or radiophorphours, as the latter agents are potentially leukemogenic.

Adult↗
PubMed1995

Identification of a 24 kDa protein expressed by chicken anaemia virus.

Antisera raised against oriented peptide conjugates were used to identify and partially characterize a 24 kDa protein product expressed by chicken anaemia virus (CAV). The peptides derived from the N and C termini of the protein were shown to react against the native protein, expressed within virus-infected cells, by immunofluorescence, immunoperoxidase and immunogold thin section electron microscopy techniques. The protein product was located by immunogold single labelling in intranuclear inclusions similar to those described previously for the 13 kDa CAV protein, which causes apoptosis. The 24 kDa protein was co-localized to the nuclear inclusions with the CAV 13 kDa protein by simultaneous dual labelling immunogold electron microscopy. Following isolation of the CAV proteins by nuclei isolation and SDS-PAGE, the antisera were used to probe for the protein by immunoblotting. The antisera recognized an expressed protein product of apparent molecular mass 30 kDa. An immunofluorescence time course study of CAV protein expression was carried out and the peptide antisera reacted against the protein at 12 h post-infection. Antisera against the 13 kDa protein reacted at similar times post-infection. This was in contrast to antisera raised against the 52 kDa capsid protein which is detectable by immunofluorescence only after 24 h. The 13 kDa and 24 kDa proteins thus appear to be early antigens produced by CAV during infection.

Amino Acid Sequence↗
PubMed1995

Treatment outcome and prognostic factors for primary nasal lymphoma.

PURPOSE: To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS: From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS: Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION: Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.

Adolescent↗
PubMed1994

The spectrum of chronic lymphoproliferative disorders in Chinese people. An analysis of 64 cases.

BACKGROUND: Chronic lymphoproliferative disorders are considered rare in Oriental patients and are thought to constitute only 2% of all leukemias in these patients, compared to 20-30% in Western patients. We conducted a retrospective analysis of Chinese patients with chronic lymphoproliferative disorders to define the frequency and spectrum of these disorders. METHODS: A consecutive series of Chinese patients with leukemia and lymphoproliferative disorders seen at two regional hospitals in Hong Kong were analyzed retrospectively. The diagnosis of chronic lymphoproliferative disorders was based on morphologic and immunologic criteria proposed by the French-American-British Cooperative Study Group. RESULTS: Sixty-four Chinese patients with chronic lymphoproliferative disorders were identified, and these patients constituted 19% of a total of 342 cases of leukemia diagnosed in 3 years. Chronic lymphocytic leukemia was the most common form, occurring at a frequency of 12.5% of all leukemias. The clinicopathologic features of these patients were similar to those of Western patients, except that Chinese patients tended to present with more advanced (Rai's Stages III and IV; Binet's Stage C) and bulky (splenomegaly > 9 cm) disease, and expressed lambda light chain about six times more frequently. Other chronic lymphoproliferative disorders identified in this study included prolymphocytic leukemia, mantle zone lymphoma, hairy cell leukemia, splenic lymphoma with villous lymphocytes, large granular lymphocyte leukemia, and Sezary syndrome. The authors did not identify any case of human T-cell lymphotropic virus-I-related lymphoproliferative disorders within the study period. CONCLUSION: In addition to providing the frequencies of various chronic lymphoproliferative disorders in southern Chinese people, this study also showed that these disorders no longer should be considered rare in this population. Inherent biologic differences between lymphoproliferative disorders in Chinese and Western patients also may exist.

Adult↗
PubMed1994

Transcriptional analysis and genome expression of chicken anaemia virus.

Strand-specific riboprobes representative of either strand of the chicken anaemia virus (CAV) replicative form (RF) DNA indicated that only one strand of the RF was transcribed to produce a major 2.0 kb transcript and that the encapsidated DNA strand was of negative sense. Primer extension analysis located a single transcriptional start site at nucleotide position 360 of the CAV sequence. Amplification, cloning and sequencing of the 3' end of the major transcript revealed the polyadenylation site at nucleotide position 21. Northern blot analysis using a series of genomic probes indicated that the 2.0 kb transcript was devoid of splicing and identified a non-transcribed region of the genome. This non-transcribed region was shown to possess promoter activity, enhancing the expression of the human growth hormone reporter gene in a transient gene expression assay. These observations suggest a simple strategy of genome expression involving a functional polycistronic message.

Animals↗