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)

The life-or-death decision of immune cells makes an essential contribution to immune-system development and the regulation of immune responses. A new family of cell-survival regulators expressed in lymphocytes, termed immune-associated nucleotide-binding proteins (IANs) [also known as GTPase of immunity-associated proteins (GIMAPs)], has been described. The IAN/GIMAP family consists of GTP-binding proteins that share a unique primary structure and whose expression is finely regulated by T-cell receptor signals. Recent studies have shown that IAN/GIMAP family proteins crucially regulate the survival of T cells during development, selection and homeostasis, and are possibly linked to the onset of T-lymphopenia, leukemia and autoimmunity. IAN/GIMAP family proteins might also take part in mitochondrial regulation of lymphocyte apoptosis by interacting with Bcl-2 family proteins.
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PMID:The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins. 1719 32

Feline haematology profiles of patients presented to the University of Bristol Small Animal Hospital from January 2000 to October 2005 were evaluated for thrombocytosis (defined as a platelets count of >700x10(9)/l and confirmed on smear evaluation). Thrombocytosis was found in 79 cats (4.64% of the hospital feline population), with values ranging from 703 to 1895x10(9)/l. Signalment, clinical presentation, concurrence of other haematological abnormalities, diagnoses and outcome were evaluated in 51 cases in which complete medical records were available. Other variables (feline immunodeficiency virus/feline leukaemia virus status, thyroxine level, haemoplasma PCR, toxoplasma antibody titres) were also evaluated. No association was found between the presence of thrombocytosis and breed or gender. Gastrointestinal signs were the most common clinical presentation. Lymphopenia was the most common concurrent haematological abnormality. Based on final diagnosis reached, cats were grouped both according to the DAMNITV classification and according to the body system affected. Amongst the DAMNITV classification, inflammatory/infectious conditions were most commonly associated with thrombocytosis. According to body systems, gastrointestinal involvement was most represented, followed by endocrine cases. No association was found between the severity of thrombocytosis and outcome.
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PMID:Thrombocytosis in cats: a retrospective study of 51 cases (2000-2005). 1738 28

Alemtuzumab is a humanized monoclonal antibody directed against lymphocytes through the CD-52 receptor, an antigen being found on > 95% of peripheral blood lymphocytes and monocytes, and to a smaller extent on granulocytes. It is an effective immunotherapeutic agent in patients with malignancies such as non-Hodgkin lymphoma, B cell chronic lymphocytic leukemia and T cell pro- lymphocytic leukemia. Adverse side effects are increasingly recognized in patients receiving alemtuzumab, mainly including fever, rigors, nausea/vomiting, skin rash; other severe alemtuzumab-related reactions have also been described, such as lymphopenia and neutropenia leading to both opportunistic (e.g. cytomegalovirus) and non-opportunistic infections. Digestive complications have more rarely been described, i.e.: gastroenteritis and peritonitis. We recently observed a case of particular interest as the patient with T cell prolymphocytic leukaemia treated with alemtuzumab, exhibited symptomatic reactivation of CMV infection and developed subsequently typhlitis.
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PMID:Typhlitis as a complication of alemtuzumab therapy. 1756 96

Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) is a serious opportunistic infection in children and adolescents with cancer. It was the most common cause of death among children receiving chemotherapy prior to the inclusion of PCP prophylaxis as part of standard care for children with leukemia. The incidence of PCP has decreased significantly since initiation of prophylaxis; however, breakthrough cases continue to occur. Hematologic malignancies, brain tumors necessitating prolonged corticosteroid therapy, hematopoietic stem cell transplantation, prolonged neutropenia, and lymphopenia are the most important risk factors for PCP in children not infected with HIV. Of children with leukemia, 15-20% may develop PCP in the absence of prophylaxis. Infection with P. jiroveci occurs early in life in most individuals. However, clinically apparent disease occurs almost exclusively in immunocompromised persons. Dyspnea, cough, hypoxia, and fever are the most common presenting symptoms of PCP. Chest radiography and high-resolution CT scans of the chest demonstrate a characteristic ground-glass pattern. Induced sputum analysis and bronchoalveolar lavage are the diagnostic procedures of choice. Gomori's methenamine-silver stain, Geimsa or Wright's stain, and monoclonal immunofluorescent antibody stains are most commonly used to make a diagnosis. However, identification of P. jiroveci DNA using polymerase chain reaction assays in bronchoalveolar lavage fluid is more sensitive. Trimethoprim-sulfamethoxazole (TMP-SMZ; cotrimoxazole) is the recommended drug for the treatment of PCP. Patients who are intolerant of TMP-SMZ or who have not responded to treatment after 5-7 days of therapy with TMP-SMZ should be treated with pentamidine. A short course of corticosteroids is recommended for moderate to severe cases of PCP within the first 72 hours after diagnosis. Mutations in the dihydropteroate synthetase gene may confer resistance to TMP-SMZ; however, the clinical relevance of these mutations is not well established. TMP-SMZ is the most commonly used agent for prophylaxis. Myelosuppression is the most important adverse effect of TMP-SMZ and the most frequent cause for choosing alternative prophylactic agents in children undergoing chemotherapy. Alternative agents for chemoprophylaxis include dapsone, aerosolized pentamidine, and atovaquone. Alternative prophylactic agents must be used in patients developing myelosuppression secondary to TMP-SMZ or dapsone.
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PMID:Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. 1792 2

Nosocomial infection is a frequent event with potentially lethal consequences. We reviewed the literature on the predictive factors for mortality related to nosocomial infection in pediatric medicine. Electronic searches in English, Spanish and Portuguese of the PubMed/MEDLINE, LILACS and Cochrane Collaboration Databases was performed, focusing on studies that had been published from 1996 to 2006. The key words were: nosocomial infection and mortality and pediatrics/neonate/ newborn/child/infant/adolescent. The risk factors found to be associated with mortality were: nosocomial infection itself, leukemia, lymphopenia, neutropenia, corticosteroid therapy, multiple organ failure, previous antimicrobial therapy, catheter use duration, candidemia, cancer, bacteremia, age over 60, invasive procedures, mechanical ventilation, transport out of the pediatric intensive care unit, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia infections, acute physiology and chronic health evaluation (APACHE) II scores over 15. Among these factors, the only one that can be minimized is inadequate antimicrobial treatment, which has proven to be an important contributor to hospital mortality in critically-ill patients. There is room for further prognosis research on this matter to determine local differences. Such research requires appropriate epidemiological design and statistical analysis so that pediatric death due to nosocomial infection can be reduced and health care quality improved in pediatric hospitals.
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PMID:Pediatric mortality due to nosocomial infection: a critical approach. 1796 79

Purine nucleoside phosphorylase (PNP) was recognized more than 30 years ago as a potential target for the treatment of patients with T-cell malignancies when an inherited deficiency of PNP was reported to be associated with a profound T-cell lymphopenia. The biochemical basis for this T-cell deficiency was subsequently shown to be related to the accumulation of plasma 2'-deoxyguanosine (dGuo) and intracellular dGuo triphosphate (dGTP). These observations have led to a search for PNP inhibitors that would be useful clinically in the management of T cell-derived malignancies. The most potent inhibitor of PNP described to date is forodesine, a rationally designed, transition-state analogue inhibitor. The preclinical and clinical pharmacology of forodesine showed its effectiveness in inhibiting PNP and augmenting dGuo levels in plasma. Increased dGTP concentrations in leukemia cells of different lineages provides strong support for the potential use of this agent in the treatment of patients with hematologic malignancies of both T- and B-cell origin.
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PMID:Pharmacology and mechanism of action of forodesine, a T-cell targeted agent. 1808 47

Feline leukemia virus (FeLV) was not detected in Florida pumas (Puma concolor coryi) in almost 20 yr of surveillance; however, the finding of two FeLV antigen-positive pumas during the 2002-2003 capture season led to an investigation of FeLV in the population. Between January 1990 and April 2007, the proportion of pumas testing FeLV antibody positive increased, with antibody-positive pumas concentrated in the northern portion of puma range. Five of 131 (4%) pumas sampled between July 2000 and April 2007 were viremic, with all cases clustered in Okaloacoochee Slough (OKS). Clinical signs and clinical pathology at capture were absent or included lymphadenopathy, moderate-to-severe anemia, and lymphopenia. All viremic pumas died; causes of death were septicemia (n=2), intraspecific aggression (n=2), and anemia/dehydration (n=1). Outcome after FeLV exposure in pumas was similar to that in domestic cats, with evidence of regressive, latent, and persistent infections. Management of the epizootic included vaccination, and as of April 2007, 52 free-ranging pumas had received one or more inoculations. Vaccinations were concentrated in OKS and in a band between OKS and the remainder of the puma population. There have been no new cases since July 2004; however, the potential for reintroduction of the virus remains.
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PMID:Epizootiology and management of feline leukemia virus in the Florida puma. 1868 39

Allogeneic stem cell transplantation remains a curative treatment for haematological malignancies resistant to other treatment approaches through the unique graft-versus-leukaemia effect (GvL). However, the lack of specificity of this response results in the targeting of normal tissue, and the morbidity and mortality associated with graft-versus-host disease (GvHD). Further improvements in exploiting the GvL effect to prevent relapse in high-risk leukaemias while minimizing toxicity have focused on the use of targeted anti-leukaemic immunotherapy. These strategies include the use of vaccines against minor histocompatibility antigens (HA-1, HA-2 and H-Y) and leukaemia-specific antigens (proteinase 3, Wilms' tumour 1 and BCR-ABL), and the adoptive transfer of leukaemia-specific T cells. The unique post-transplant milieu, which is characterized by lymphopenia, regulatory T-cell depletion and the release of growth factors, offers the opportunity to promote the expansion of engrafted T cells and enhance the specific GvL response. Techniques to reduce regulatory T-cell control over T-cell responses to leukaemia antigens could further enhance GvL reactivity. Finally, these approaches to increase GvL effects would be facilitated by transplant approaches to deplete GvHD alloresponses selectively while preserving GvL reactivity.
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PMID:Characterizing and optimizing immune responses to leukaemia antigens after allogeneic stem cell transplantation. 1879 Apr 48

Beagle dogs inhaled graded exposure levels of insoluble plutonium dioxide ((239)PuO(2)) aerosols in one of three monodisperse particle sizes at the Lovelace Respiratory Research Institute (LRRI) to study the life-span health effects of different degrees of alpha-particle dose non-uniformity in the lung. The primary noncarcinogenic effects seen were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, and radiation pneumonitis and pulmonary fibrosis. Radiation pneumonitis/ pulmonary fibrosis occurred from 105 days to more than 11 years after exposure, with the lowest associated alpha-particle dose being 5.9 Gy. The primary carcinogenic effects also occurred almost exclusively in the lung because of the short range of the alpha-particle emissions. The earliest lung cancer was observed at 1086 days after the inhalation exposure. The most common type seen was papillary adenocarcinoma followed by bronchioloalveolar carcinoma. These lung cancer results indicate that a more uniform distribution of alpha-particle dose within the lung has an equal or possibly greater risk of neoplasia than less uniform distributions of alpha-particle dose. The results are consistent with a linear relationship between dose and response, but these data do not directly address the response expected at low dose levels. No primary tumors were found in the tracheobronchial and mediastinal lymph nodes despite the high alpha-particle radiation doses to these lymph nodes, and no cases of leukemia were observed.
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PMID:Radiotoxicity of inhaled (239)PuO(2) in dogs. 1913 39

We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.
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PMID:Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors. 1964 71


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