Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human leukemia cell lines are powerful tools in the study of leukemogenesis, particularly for rare but recurrent subtypes such as acute myeloid leukemia (AML) with the t(16;21)(p11.2;q22) and FUS-ERG fusion. Four AML cell lines carrying a t(16;21)(p11.2;q22) have been described previously. We report a novel AML cell line, designated JIH-4, for which karyotypic analysis demonstrated a single abnormality, t(16;21)(p11.2;q22). The FUS-ERG fusion transcript was identified by reverse transcriptase polymerase chain reaction (RT-PCR). Neither Epstein-Barr virus nor mycoplasma was detected in JIH-4 cells. The morphology and immunoprofile of JIH-4 cells display typical features of myelogenous lineage, and short tandem-repeat PCR comparison with the donor patient's bone marrow cells confirm the cell line's authenticity. Tumor masses were found in 50% of inoculated mice 83 days after subcutaneous injection with JIH-4 cells. Our results confirm that JIH-4 cells are derived from the donor patient's leukemia cells and support using the JIH-4 cell line as a valuable tool in the study of leukemogenesis.
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PMID:Establishment and characterization of a novel acute myeloid leukemia cell line, JIH-4, carrying a t(16;21)(p11.2;q22) and expressing the FUS-ERG fusion. 2153 42

A novel phosphoramidate nucleotide prodrug of the anticancer nucleoside analogue 5-fluoro-2'-deoxyuridine (5-FdUrd) was synthesized and evaluated for its cytostatic activity. Whereas 5-FdUrd substantially lost its cytostatic potential in thymidine kinase (TK)-deficient murine leukaemia L1210 and human lymphocyte CEM cell cultures, NUC-3073 markedly kept its antiproliferative activity in TK-deficient tumour cells, and thus is largely independent of intracellular TK activity to exert its cytostatic action. NUC-3073 was found to inhibit thymidylate synthase (TS) in the TK-deficient and wild-type cell lines at drug concentrations that correlated well with its cytostatic activity in these cells. NUC-3073 does not seem to be susceptible to inactivation by catabolic enzymes such as thymidine phosphorylase (TP) and uridine phosphorylase (UP). These findings are in line with our observations that 5-FdUrd, but not NUC-3073, substantially loses its cytostatic potential in the presence of TP-expressing mycoplasmas in the tumour cell cultures. Therefore, we propose NUC-3073 as a novel 5-FdUrd phosphoramidate prodrug that (i) may circumvent potential resistance mechanisms of tumour cells (e.g. decreased TK activity) and (ii) is not degraded by catabolic enzymes such as TP which is often upregulated in tumour cells or expressed in mycoplasma-infected tumour tissue.
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PMID:The cytostatic activity of NUC-3073, a phosphoramidate prodrug of 5-fluoro-2'-deoxyuridine, is independent of activation by thymidine kinase and insensitive to degradation by phosphorolytic enzymes. 2165 73

A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) anti-sera and PCR, we determined if additional prostate cancer or other cell lines contain XMRV or MLV-related viruses. Our study included a total of 72 cell lines, which included 58 of the 60 human cancer cell lines used in anticancer drug screens and maintained at the NCI-Frederick (NCI-60). We have identified gammaretroviruses in two additional prostate cancer cell lines: LAPC4 and VCaP, and show that these viruses are replication competent. Viral genome sequencing identified the virus in LAPC4 and VCaP as nearly identical to another known xenotropic MLV, Bxv-1. We also identified a gammaretrovirus in the non-small-cell lung carcinoma cell line EKVX. Prostate cancer cell lines appear to have a propensity for infection with murine gammaretroviruses, and we propose that this may be in part due to cell line establishment by xenograft passage in immunocompromised mice. It is unclear if infection with these viruses is necessary for cell line establishment, or what confounding role they may play in experiments performed with these commonly used lines. Importantly, our results suggest a need for regular screening of cancer cell lines for retroviral "contamination", much like routine mycoplasma testing.
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PMID:Identification of replication competent murine gammaretroviruses in commonly used prostate cancer cell lines. 2169 4

Pyrolysis mass spectrometry (PyMS) was used to produce biochemical fingerprints from replicate frozen cell cultures of mouse macrophage hybridoma 2C11-12, human leukaemia K562, baby hamster kidney BHK 21/C13, and mouse tumour BW-O, and a fresh culture of Chinese hamster ovary CHO cells. The dimensionality of these data was reduced by the unsupervised feature extraction pattern recognition technique of auto-associative neural networks. The clusters observed were compared with the groups obtained from the more conventional statistical approaches of hierarchical cluster analysis. It was observed that frozen and fresh cell line cultures gave very different pyrolysis mass spectra. When only the frozen animal cells were analysed by PyMS, auto-associative artificial neural networks (ANNs) were employed to discriminate between them successfully. Furthermore, very similar classifications were observed when the same spectral data were analysed using hierarchical cluster analysis. We demonstrate that this approach can detect the contamination of cell lines with low numbers of bacteria and fungi; this approach could plausibly be extended for the rapid detection of mycoplasma infection in animal cell lines. The major advantages that PyMS offers over more conventional methods used to type cell lines and to screen for microbial infection, such as DNA fingerprinting, are its speed, sensitivity and the ability to analyse hundreds of samples per day. We conclude that the combination of PyMS and ANNs can provide a rapid and accurate discriminatory technique for the authentication of animal cell line cultures.
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PMID:Rapid authentication of animal cell lines using pyrolysis mass spectrometry and auto-associative artificial neural networks. 2235 55

Ninety-six feral cats from Prince Edward Island were used to determine the prevalence of selected infectious agents. The prevalence rates were 5.2% for feline immunodeficiency virus, 3.1% for feline leukemia virus, 3.1% for Mycoplasma haemofelis, 8.4% for Candidatus Mycoplasma haemominutum, 2.1% for Bartonella spp. and 29.8% for exposure to Toxoplasma gondii. Oocysts of T. gondii were detected in 1.3% of the fecal samples that were collected. Gender and retroviral status of the cats were significantly correlated with hemoplasma infections. Use of a flea comb showed that 9.6% of the cats had fleas; however, flea infestation was not associated with any of the infectious agents.
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PMID:Infectious disease prevalence in a feral cat population on Prince Edward Island, Canada. 2237 97

'Candidatus Mycoplasma haemominutum' (CMhm) is a hemotropic mycoplasma (aka hemoplasma) of domestic cats and wild felids. In a transmission study, we exposed eight specified pathogen-free cats to blood from Iberian lynxes (Lynx pardinus) infected with CMhm. The cats were coinfected with feline leukemia virus (FeLV) from an Iberian lynx or with a prototype FeLV. The goal of the present study was to quantify the humoral immune response to CMhm and to identify potential target tissues and sequestration sites. Antibodies were measured by a recombinant antigen-based enzyme-linked immunosorbent assay, and blood and tissue loads were quantified using real-time PCR. Seven out of eight cats became CMhm-infected; all of these cats seroconverted between 3 and 13 weeks after inoculation. Antibody levels correlated with the CMhm blood loads. The peak CMhm blood loads were inversely correlated with the incubation period. PCR-positive results were found in all 24 tissues tested but not for all samples. Although all tissues were PCR-positive in one cat euthanized ten weeks after infection, many tissues tested negative in six cats euthanized at week 20 after infection. In several cats, the spleen, lung, liver, heart and aorta contained more copies than expected given the tissue's blood supply, but most tissues contained fewer copies than expected. In conclusion, this is the first study to quantify the humoral immune response and tissue loads in CMhm-FeLV-coinfected cats. The tissue loads appeared to correlate with the duration of infection and with the blood loads, but no evidence of significant CMhm tissue sequestration was found.
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PMID:Quantification of the humoral immune response and hemoplasma blood and tissue loads in cats coinfected with 'Candidatus Mycoplasma haemominutum' and feline leukemia virus. 2258 83

The diagnosis of feline haemoplasmosis has improved over the years, with several techniques enabling a clear and specific diagnosis, and where polymerase chain reaction (PCR) is considered as the 'gold standard'. The aim of this study was to survey the prevalence of feline haemoplasmas in 320 cats from the north-central region of Portugal by the use of real-time PCR, as well as to evaluate any associations between infection, clinical presentation and risk factors. The overall prevalence of infection by feline haemoplasmas was 43.43% (139/320), where 41.56% (133/320) corresponded to Candidatus Mycoplasma haemominutum (CMhm), 12.81% (41/320) to Mycoplasma haemofelis (Mhf), 4.38% (14/320) to Candidatus Mycoplasma haematoparvum and 1.25% (4/320) to Candidatus Mycoplasma turicensis. Almost 13% (47/320) of the samples were co-infected, with the most common co-infection being CMhm and Mhf (23.74%). Infection was found statistically significant with feline immunodeficiency/feline leukaemia virus status (P = 0.034), but no significant association was found for breed, sex, fertility status (neutered/spayed/entire), age, clinical status, living conditions (in/outdoor), anaemia status, or the presence/absence of ticks or fleas. Cats from north-central Portugal are infected with all the known feline haemoplasma species, with CMhm being the most common one. Prevalence of all feline haemoplasmas was higher than that reported previously in cats from other European countries, but similar to that described in Portugal for dogs. These data provide a better perspective regarding Mycoplasma species infection in Europe, and new information that helps us better understand feline haemoplasmosis.
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PMID:Prevalence and co-infection of haemotropic mycoplasmas in Portuguese cats by real-time polymerase chain reaction. 2348 54

Haemotropic mycoplasmas (haemoplasmas) are small epierythrocytic bacteria that have the potential to cause severe, life-threatening haemolytic anaemia. The aim of the current study was to evaluate feline haemoplasma prevalence using real-time polymerase chain reaction (PCR) from a convenience sample of New Zealand domestic cats, including blood film examination and a risk factor analysis. DNA was extracted from 200 blood samples submitted to a diagnostic laboratory for routine haematology over a 12-month period. Species-specific real-time PCR assays identified 62 cats that were positive for haemoplasma DNA, giving an overall prevalence of 31%. Twelve of the positive cats had dual infections. The prevalence of the three feline haemoplasmas was 25% for 'Candidatus Mycoplasma haemominutum', 7.5% for Mycoplasma haemofelis and 4.5% for 'Candidatus Mycoplasma turicensis' (CMt). All samples were positive for an internal control (feline 28S rDNA) by real-time PCR. Sensitivity and specificity of blood smear examination for haemoplasma infection in this study was 9.7% and 97.8%, respectively. Retroviral infection was tested using the Idexx Snap Feline Triple test on all samples. Twenty cats (10%) were feline immunodeficiency virus (FIV) positive and 11 cats (5.5%) were feline leukaemia virus (FeLV) positive. Statistical comparisons, using multivariate logistic regression, indicated that positive FIV status, male gender and non-pedigree breed were significantly (P <0.05) associated with haemoplasma infection, with odds ratios of 10.16, 5.04 and 3.03, respectively. The results of this study demonstrate the prevalence of the three main feline haemoplasma species in New Zealand for the first time, with prevalences correlating with previous overseas studies. This is the first report of CMt in New Zealand.
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PMID:Prevalence and risk factor analysis of feline haemoplasma infection in New Zealand domestic cats using a real-time PCR assay. 2366 10

We measured seasonal changes in body mass and pathogen exposure in wild Pallas' cats (Felis [Otocolobus] manul) in the Daurian Steppe of Russia in 2010-11. Pallas' cats lost about 30% of body mass over winter. Tests for antibodies to 15 potential pathogens showed that Pallas' cats were exposed to four pathogens. Two of 16 cats had antibodies to Toxoplasma gondii. Two had antibodies to Mycoplasma sp., and one each had antibodies to Influenza A virus and Feline leukemia virus. The percentage of antibody-positive wild Pallas' cats was lower than results reported for other wild felids in the Russian Far East.
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PMID:Detection of seasonal weight loss and a serologic survey of potential pathogens in wild Pallas' cats (Felis [Otocolobus] manul) of the Daurian Steppe, Russia. 2448 81

Animal hoarders accumulate animals in over-crowded conditions without adequate nutrition, sanitation, and veterinary care. As a result, animals rescued from hoarding frequently have a variety of medical conditions including respiratory infections, gastrointestinal disease, parasitism, malnutrition, and other evidence of neglect. The purpose of this study was to characterize the infectious diseases carried by clinically affected cats and to determine the prevalence of retroviral infections among cats in large-scale cat hoarding investigations. Records were reviewed retrospectively from four large-scale seizures of cats from failed sanctuaries from November 2009 through March 2012. The number of cats seized in each case ranged from 387 to 697. Cats were screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) in all four cases and for dermatophytosis in one case. A subset of cats exhibiting signs of upper respiratory disease or diarrhea had been tested for infections by PCR and fecal flotation for treatment planning. Mycoplasma felis (78%), calicivirus (78%), and Streptococcus equi subspecies zooepidemicus (55%) were the most common respiratory infections. Feline enteric coronavirus (88%), Giardia (56%), Clostridium perfringens (49%), and Tritrichomonas foetus (39%) were most common in cats with diarrhea. The seroprevalence of FeLV and FIV were 8% and 8%, respectively. In the one case in which cats with lesions suspicious for dermatophytosis were cultured for Microsporum canis, 69/76 lesional cats were culture-positive; of these, half were believed to be truly infected and half were believed to be fomite carriers. Cats from large-scale hoarding cases had high risk for enteric and respiratory infections, retroviruses, and dermatophytosis. Case responders should be prepared for mass treatment of infectious diseases and should implement protocols to prevent transmission of feline or zoonotic infections during the emergency response and when transferring the rescued cats to other shelters or to adopters.
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PMID:Infectious diseases in large-scale cat hoarding investigations. 2493 62


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