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Biomedical subjects

P Dunn

Publications and source records attributed to P Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement.

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.

Acute Disease↗
PubMed2006

AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples.

The roles of CEBPalpha mutations and its cooperating mutations in the relapse of acute myeloid leukemia (AML) are not clear. CEBPalpha mutations were analyzed on 149 patients with de novo AML at both diagnosis and relapse. Twenty-two patients (14.8%) had the mutations at diagnosis, two patients had N-terminal nonsense mutations alone, one had homozygous inframe duplication at the bZIP domain, and 19 patients had both N-terminal and bZIP mutations. Twenty patients relapsed with identical mutant patterns, two lost CEBPalpha mutations and none acquired the mutations at relapse. Cloning analysis showed that the N-terminal and C-terminal mutations occurred on separate cloned alleles and also on the same alleles in most of the diagnosis and relapse samples. Losing one of the two or more mutations on the same allele or acquiring the other mutation on the allele original carrying single mutation were observed not infrequently in the paired samples analyzed. Seven patients with CEBPalpha mutations had cooperating mutations with FLT3/ITD, FLT3/TKD or N-ras but not K-ras mutations. Our study showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis retained the identical mutant patterns but frequently changed in the allelic distribution at relapse.

Adolescent↗
PubMed2005

Equal tension in all four strands of a semitendinosus graft with a low profile tibial fixation device (Cobra LFD).

The article introduces a novel tibia fixation device, the Cobra Ligament Fixation Device (Cobra LFD), for anterior cruciate ligament reconstruction. The Cobra LFD has a low profile and is hooked upon the cortical bone of tibia. It is useful either for primary ACL reconstruction or for ACL revision surgery, mainly for fixation of hamstring grafts. Fixation in the cortical bone is of great importance, in particular for revision cases. Besides technical aspects, we also present the 4-year follow-up of 15 cases of ACL revision surgery, where the Cobra LFD has been used for the tibia fixation.

Adult↗
PubMed2005

Pseudo-Gaucher cells in mycobacterial infection: a report of two cases.

This report describes two cases of mycobacterial infection with pseudo-Gaucher cells. Both patients had no clinical evidence of inherited Gaucher disease. The first case was a patient with AIDS and Mycobacterium avium intracellulare involving the lung, spleen, and bone marrow. The bone marrow aspirates showed many histiocytes with needle-like inclusions. Acid fast staining showed that these histiocytes contained acid fast bacilli. Bone marrow biopsies revealed granulomatous lesions with aggregates of foamy histiocytes. The second case was an alcoholic patient with Mycobacteriumkanasassi infection involving the lung and lymph nodes. The lymph node aspirates showed infiltration of the same cells with acid fast bacilli in the cytoplasm.

AIDS-Related Opportunistic Infections↗
PubMed2005

Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes simplex virus HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dose-dependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.

3-Iodobenzylguanidine↗
PubMed2004

Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia.

The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, P<0.001). FLT3/ITD(+) patients progressed to AML more rapidly than FLT3/ITD(-) patients (2.5+/-0.5 vs 11.9+/-1.5 months, P=0.114). FLT3/ITD(+) patients had a significantly shorter survival than FLT3/ITD(-) patients (5.6+/-1.3 vs 18.0+/-1.7 months, P=0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (P<0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.

Acute Disease↗
PubMed2003

All- trans-retinoic acid-induced erythema nodosum in patients with acute promyelocytic leukemia.

Erythema nodosum associated with all- trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is very rare. We describe four patients with classic APL who developed erythema nodosum during ATRA therapy. Fever and subsequent multiple painful erythematous nodules over extremities developed on D11, D16, D17, and D19, respectively, after ATRA therapy. The skin biopsy taken from each patient was consistent with erythema nodosum. All patients received short course of steroids. Fever subsided rapidly and the skin lesions regressed completely. All patients achieved complete remission without withdrawal of ATRA. ATRA seemed to be the most possible etiology of erythema nodosum in our patients. Short-term use of steroid is very effective in ATRA-induced erythema nodosum.

Adult↗
PubMed2003

A new allele, HLA-DRB4*010304.

We report here the identification of a novel DRB4*01 allele, DRB4*010304, found in a patient waiting for a liver transplantation. The new allele was detected during a routine DNA-based HLA typing. Sequencing confirmed that the new allele is identical to DRB4*01030101 at exon 2 except for position 216 where the new allele has a T instead of a C.

Alleles↗
PubMed2003

Survival of avian influenza virus H7N2 in SPF chickens and their environments.

The survival or clearance of the avian influenza virus (AIV) of subtype H7N2 in its chicken host was evaluated using experimentally infected specific pathogen free (SPF) chickens of different age groups. Birds of different ages were successfully infected with infectious doses ranging between 10(4.7) and 10(5.7) ELD50 per bird. In infected birds, the infective virus was undetectable usually by the third week following exposure. The infectivity or inactivation time of the H7N2 AIV in various environmental conditions was studied using chicken manure, heat, ethanol, pH, and disinfectants. The H7N2 AIV was effectively inactivated by field chicken manure in less than a week at an ambient temperature of 15-20 degrees C. At a pH 2, heating at 56 degrees C, and exposure to 70% ethanol or a specific disinfectant, the AIV infectivity was destroyed in less than 30 min.

Animals↗
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

Genomic organisation and developmentally regulated expression of an apicomplexan aspartyl proteinase.

The cDNA for an aspartyl proteinase, termed eimepsin, was isolated from an Eimeria tenella sporulated oocyst library and the deduced amino acid sequence found to be almost identical to a previously described aspartyl proteinase from E. acervulina (97.4% amino acid identity). An E. tenella cosmid clone covering the entire eimepsin gene was cloned and characterised. Sequencing revealed that the eimepsin gene spans 2.9 kb and consists of 18 exons and 17 introns. The 5' flanking region sequence of the gene contains a putative transcriptional promoter sequence (TATAAA box) and three potential transcription initiator sites (Inr sites). Expression of eimepsin at the mRNA and protein level is developmentally regulated during oocyst sporulation. The eimepsin transcript was detected in unsporulated oocysts and increased in abundance during the early part of sporulation when the oocyst undergoes nuclear division and blast formation. Thereafter, the level of the eimepsin transcript decreases and in the excysted sporozoite, no eimepsin-specific RNA was detected. Expression of eimepsin lags behind transcript expression by some hours, and the protein accumulates in the oocyst during sporocyst and sporozoite formation.

Amino Acid Sequence↗
PubMed2001

Clonality analysis using X-chromosome inactivation patterns by HUMARA-PCR assay in female controls and patients with idiopathic thrombocytosis in Taiwan.

OBJECTIVE: Analysis of X-chromosome inactivation patterns (XCIPs) is a useful tool in the diagnosis of clonal disorders. The human androgen receptor (HUMARA) locus is especially useful for clonality study. The present study was conducted 1) to determine the heterozygosity rate for HUMARA locus in Taiwanese women, 2) to determine the frequency of excessive skewing in different cell types, and 3) to determine the utility of XCIPs in the differential diagnosis of thrombocytosis. PATIENTS AND METHODS: XCIPs by HUMARA-PCR assay were performed on purified granulocytes and T cells from 73 female patients presenting with idiopathic persistent thrombocytosis (IT), 10 patients with reactive thrombocytosis (RT), and 46 bone marrow samples from female controls. XCIPs of buccal mucosa cells were also compared with those of T cells in 57 patients with IT. The percentage of clonal granulocytes was calculated after correcting for the degree of Lyonization in T cells. RESULTS: The heterozygosity rate for the HUMARA gene was 89.1% in Taiwanese females. The median age of informative IT patients and controls was 59 (18-92) and 58 (19-89), respectively. Excessive skewing (allele ratio <0.33) was more frequent in granulocytes than in T cells in both controls (12/43 vs 9/43, p = 0.080) and IT patients (56/64 vs 25/64, p < 0.001). XCIPs were the same for both buccal mucosa and T cells in 43 patients but were different in 14 patients. Of the 43 informative controls, 31 had a polyclonal pattern; an ambiguous pattern was found in nine; and the remaining three, aged 71, 73, and 80, respectively, had a clonal pattern. A clonal pattern was found in 42 IT patients, a polyclonal pattern in 12, and an ambiguous pattern in 10 of the 64 IT patients. The frequency of clonal, polyclonal, and ambiguous patterns in the 40 IT patients with age < or = 65 was 55.0%, 30.0%, and 15.0%, respectively. None of the IT patients aged >65 had a polyclonal disease. IT patients aged >65 had a significantly higher frequency of clonal pattern (p = 0.030) and a significantly lower frequency of polyclonal pattern (p = 0.002) than those with age <65. Of the eight heterozygous patients with RT, one aged 80 exhibited a clonal pattern, and the remaining seven had a polyclonal pattern. CONCLUSIONS: The present study on Taiwanese females showed a heterozygosity rate of 89.1% for the HUMARA gene. Our results confirmed that IT is a heterogeneous disorder in terms of clonality. Twenty-three percent of IT patients exhibited a greater than 20% difference in allele expression for buccal mucosa and T cells. Presence of a clonal XCIP in young patients with IT can serve as a positive marker for the diagnosis of clonal thrombocytosis, and elderly patients with polyclonal XCIPs are unlikely to have essential thrombocythemia.

Adolescent↗
PubMed2001

Ticlopidine-induced thrombotic thrombocytopenic purpura: two case reports treated with plasma exchange plus steroids.

Thrombotic thrombocytopenic purpura (TTP) has a high mortality rate if left untreated with plasma exchange promptly. We report two cases of ticlopidine-induced TTP, which lesser dosages of ticlopidine (200-250 mg/day) were prescribed and were treated with plasma exchange (PE) plus steroids. The first case was treated successfully, but the second case did not respond to our treatment and died of a progressive disease complicated with pneumonia. In sum, we recommend careful use of ticlopidine, regardless of the dosages prescribe and regardless of how long the drug is used. Moreover, the adverse effect of ticlopidine should be closely monitored.

Aged↗
PubMed2001

Development of rheumatoid arthritis in a patient with pernicious anemia: case report.

Very few cases of rheumatoid arthritis combined with pernicious anemia have been reported in the world literature and none in the Chinese literature. A 62-year-old female initially presented with anemia. Pernicious anemia was diagnosed by characteristic blood and bone marrow morphology. Laboratory data showed a deficiency of vitamin B12 and positive anti-gastric parietal cell antibodies. Her anemia improved after vitamin B12 therapy. Painful swelling of multiple joints developed 6 years later. The clinical presentation supported a diagnosis of rheumatoid arthritis. We report herein a rare case of rheumatoid arthritis and pernicious anemia in the same ethnic Chinese patient. We also review the literature and discuss a possible association between a non-organ-specific autoimmune disease, rheumatoid arthritis, and an organ-specific autoimmune disease, pernicious anemia.

Anemia, Pernicious↗
PubMed2000

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗