Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-month-old shorthaired cat was presented to the Animal Hospital in Skara, Sweden, with a two-day history of lethargy, anorexia and tachypnoea. Clinical examination and laboratory investigations revealed fever, dehydration, tick infestation, neutrophilia with left shift, lymphopenia, hyperglycaemia and intracytoplasmic neutrophilic Ehrlichia inclusions. After treatment with intravenous doxycycline and lactated Ringer's solution the temperature returned to normal. Oral treatment with doxycycline continued for 20 days. The ehrlichiosis diagnosis was confirmed by serology, polymerase chain reaction and DNA sequencing. No relapse was observed during the eight-month follow-up period. The granulocytotropic Ehrlichia strain found in the cat was later characterised by analysis of the 16S rRNA gene sequence which showed 100 per cent identity to DNA sequences found in Swedish canine and equine granulocytotropic Ehrlichia strains. This is, to the best of the authors' knowledge, the first reported case of granulocytic ehrlichiosis in a cat.
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PMID:Feline granulocytic ehrlichiosis--a report of a new clinical entity and characterisation of the infectious agent. 1009 38

Pediatric cancer patients treated with multimodal therapy are at a great risk of opportunistic infections or reactivation of latent infections. Human herpesvirus-6 (HHV-6) can serve as an example of such infection, with high seroprevalence in population. In 66 children with cancer and in 45 healthy controls, age matched, the presence of DNA HHV-6 was examined in peripheral blood by the polymerase chain reaction method. HHV-6 serology was also performed. No difference has been found between patients at the time of cancer diagnosis and the group of healthy children in the presence of DNA HHV-6 in blood, 17.4 and 15.6%, respectively. During cytotoxic chemotherapy the presence of HHV-6 in peripheral blood raised to 37.1% in patients with fever. Other parameters and symptoms such as febrile neutropenia, lymphopenia, exanthem, hepatopathy, lymphadenopathy, enteritis, bone marrow aplasia, pneumonitis, and encephalitis were examined in both the HHV-6 positive and HHV-6 negative groups of pediatric cancer patients. Statistically significant differences (p < .05) were found in case of lymphopenia, exanthem, and hepatopathy. In 4 out of 66 patients (6.1%) severe HHV-6 infection has been found: in 3 patients during cytotoxic chemotherapy and in 1 at the time of cancer diagnosis. Reactivation of HHV-6 infection in pediatric cancer patients under treatment with cytotoxic chemotherapy is frequent and can lead to severe complications as described in patients after bone marrow or organ transplantation.
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PMID:Human herpesvirus-6 infection in children with cancer. 1050 18

Adenosine deaminase deficiency is an inborn error resulting in immunodeficiency. The pathogenesis of the lymphopenia is not fully understood. Intracellular increases in dATP in the absence of deamination retard DNA repair in human resting lymphocytes and results in the slow accumulation of DNA strand breaks. We focused on the relationship between DNA damage and DNA precursor pools in cultures of deoxycoformycin-treated, ADA-inhibited resting lymphocytes. The addition of 10 microM deoxyadenosine led to a substantial number of DNA strand breaks within 12 h, breaks equivalent to those which occur with about 190 rad irradiation. Addition of any of the other deoxynucleosides used partially prevented this dAdo-induced DNA damage and promoted DNA repair. However, the preventive effects did not correlate inversely with intracellular dATP levels. Resting lymphocytes have very small dNTP pools. Treatment with dAdo slightly reduced dTTP and dCTP. Three kinds of deoxynucleosides, other than dAdo, restored or raised the corresponding dNTP level but the pool imbalance was only minimally corrected. Regarding the toxic effects of dAdo in ADA deficiency, not only dATP levels but also dNTP pool balance has a crucial role in the pathogenesis. Pool sizes of dTTP, dCTP, and possibly dGTP must be maintained at normal levels, if dAdo-induced DNA damage is to be avoided.
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PMID:Protection by various deoxynucleosides against deoxyadenosine-induced DNA damage in adenosine deaminase-inactivated lymphocytes. 1060 74

Emerging evidence suggests that apoptosis is an important mechanism of tumor cell death from antineoplastic therapy. 7-hydroxystaurosporine (UCN-01) is a novel protein kinase inhibitor that increases chemotherapy-induced apoptosis in vitro and is in early phases of clinical development. In this report, we present a 68-year-old patient with chemotherapy-resistant lymphoma treated with UCN-01 and chemotherapy. He had a stage IV plasmacytoid lymphoma that failed to enter remission with high-dose EPOCH II (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) chemotherapy. Due to disease progression and transformation to large cell lymphoma in the liver and bone marrow, he received UCN-01. Four weeks later, he received "standard-dose" EPOCH because of progression, developed severe neutropenia for 9 days, and expired from Candida sepsis on day 23. At autopsy, there was no histological evidence of residual lymphoma, although PCR for immunoglobulin gene rearrangement analysis revealed a faint clonal band in two of six nodes but none in the liver. Significantly, no B cells were detected by immunohistochemistry in lymph nodes, and a polyclonal ladder pattern associated with the presence of normal B cells was not seen in the immunoglobulin gene rearrangement PCR assay. Profound peripheral lymphopenia (50 cells/microliter) was also observed. Pharmacokinetics showed UCN-01 salivary concentrations, a surrogate for free drug concentrations, to be within an effective range in vitro (45 nmol/L) as a modulator of DNA-damaging agent cytotoxicity. In vitro, UCN-01 is synergistic with multiple cytotoxic agents and increases fludarabine-induced apoptosis in a human breast cell line. These results suggest that UCN-01 sensitized the lymphoma to the cytotoxic effects of EPOCH, possibly by modulating the "threshold" for apoptosis, and may illustrate a new paradigm for reversal of drug resistance.
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PMID:Modulation of clinical drug resistance in a B cell lymphoma patient by the protein kinase inhibitor 7-hydroxystaurosporine: presentation of a novel therapeutic paradigm. 1069 May 18

Many chemotherapeutic agents function by damaging the DNA of rapidly dividing cells, leading to side effects in the bone marrow, including anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We have created an animal model of alkylation-based chemotherapy, in nontumor-bearing rats, to investigate the effect of niacin deficiency on the side effects of chemotherapy [2 x 2 design, niacin-deficient (ND) vs. pair-fed (PF) control, and ethylnitrosourea (ENU) vs. vehicle control (C)]. Weanling Long-Evans rats were fed ND diet or PF niacin replete diet for 4 wk. ENU or C treatment started after 1 wk of feeding and consisted of 12 doses delivered by gavage, every other day. At 4 wk postweaning, niacin deficiency and ENU treatment ended, the rats were fed a high-quality control diet (AIN-93M) and the recovery of blood variables was monitored. ND alone decreased growth rate and caused anemia and neutrophilia. ENU treatment alone caused anemia, lymphopenia, neutropenia and an increase in circulating reticulocytes. In combination, ND and ENU treatment synergistically decreased hematocrit. ND prevented the ENU-induced increase in reticulocyte numbers observed in control rats. ND also increased the severity of ENU-induced lymphopenia. A combination of ND and ENU abolished the neutrophilia caused by ND alone. In summary, ND significantly increased the susceptibility of young Long-Evans rats to ENU-induced bone marrow suppression, suggesting that niacin-deficient cancer patients may benefit from supplementation.
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PMID:Niacin deficiency in rats increases the severity of ethylnitrosourea-induced anemia and leukopenia. 1080 5

We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.
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PMID:Adult T cell leukemia/lymphoma with lymphopenia in a Korean. 1080 4

Infection with measles virus induces a transient immunosuppression, which occasionally results in fatal opportunistic infections. To obtain fundamental information about the mechanism, we examined peripheral blood mononuclear cells (PBMC) from acute measles patients aged from infants to 35 years old, obtained at various times from incubation periods to 103 days after onset of rash, for the number of lymphocyte subsets by flowcytometry. The data were analyzed for relationships between aging of the patients and the severity of immunosuppression. In classical measles cases, infected lymphocytes detected as a minor population during the incubation period disappeared soon after onset of rash, whereas in the cases of serious illness, the infected cells persisted longer after the rash. At the onset of rash, remarkable lymphopenia had already occurred in all measles cases with reduction in cell numbers of CD4+ T cells, CD8+ T cells, B cells, neutrophils, and monocytes. In contrast, natural killer (NK) cells were increased in number and activated, which might be a response compensatory for the lymphopenia. Apoptosis-associated molecules such as CD95(Fas) and TNF-related apoptosis-inducing ligand-receptor (TRAIL-R) were highly expressed on the cell surface of most surviving non-infected lymphocytes, and DNA fragmentation was also observed upon incubation in vitro. These results suggested that the profound lymphopenia was primarily due to extended death of non-infected blood cells caused by apoptosis. The severity and duration of the lumphopenia were age-dependent; less severe in young children whereas much severer in infants under one year of age as well as adolescents and adults. From these results, it was suggested that remarkable lymphopenia due to apoptosis of uninfected cells is one of the principal causes for immunosuppression induced by measles virus infection, and is correlated with the age-dependent severity of the disease.
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PMID:Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles patients. 1088 78

We have investigated the role of reduced glutathione (GSH) in the genetic toxicity of the rodent renal carcinogen potassium bromate (KBrO(3)). A statistically significant increase in the concentration of 8-oxodeoxyguanosine (8-oxodG) relative to deoxyguanosine was measured following incubation of calf thymus DNA with KBrO(3) and GSH or N-acetylcysteine (NACys). This was dependent on these thiols and was associated with the loss of GSH and production of oxidized glutathione. A short-lived (<6 min) intermediate was apparent which did not react with the spin trap dimethylpyrroline N-oxide. DNA oxidation was not evident when potassium chlorate (KClO(3)) or potassium iodate (KIO(3)) were used instead of KBrO(3), though GSH depletion also occurred with KIO(3), but not with KClO(3). Other reductants and thiols in combination with KBrO(3) did not cause a significant increase in DNA oxidation. DNA strand breakage was also induced by KBrO(3) in human white blood cells (5 mM) and rat kidney epithelial cells (NRK-52E, 1.5 mM). This was associated with an apparent small depletion of thiols in NRK-52E cells at 15 min and with an elevation of 8-oxodG at a delayed time of 24 h. Depletion of intra-cellular GSH by diethylmaleate in human lymphocytes decreased the amount of strand breakage induced by KBrO(3). Extracellular GSH, however, protected against DNA strand breakage by KBrO(3), possibly due to the inability of the reactive product to enter the cell. In contrast, membrane-permeant NACys enhanced KBrO(3)-induced DNA strand breakage in these cells. DNA damage by KBrO(3) is therefore largely dependent on access to intracellular GSH.
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PMID:The role of glutathione in DNA damage by potassium bromate in vitro. 1088 9

An Arab woman presented with a history of multiple foetal losses and spontaneous venous thromboembolism, which recurred on several occasions. The presence of antiphospholipid antibodies in the absence of other clinical and serological features of systemic lupus erythematosus (SLE), including negative antinuclear antibodies (ANA), confirmed the diagnosis of primary antiphospholipid syndrome (PAPS). More than 15 years after the beginning of clinical events and 10 years after diagnosis, she progressed into the immunological domain of SLE without concurrent clinical features. The patient exhibited weakly positive ANA of a speckled pattern, strongly positive anti (ds) DNA antibodies and false positive VDRL. Lymphopenia has not been observed at any stage of the follow-up. Although the evolution of PAPS into SLE has been infrequently reported, this seems to be another case suggesting that PAPS in some patients may be an early manifestation of lupus.
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PMID:Progression of primary APS (Hughes syndrome) into serological SLE: case report. 1126 37

A major hurdle to lipoplex-based systemic gene delivery is acute inflammatory toxicity. In this study, a safe, simple, and effective alternative to lipoplex administration, specifically, sequential injection of cationic liposome and plasmid DNA, was evaluated. When plasmid DNA was injected into the tail vein of mice 2-5 min after the injection of cationic liposomes, 50-80% lower levels of proinflammatory cytokines, including TNF-alpha, IL-12, and IFN-gamma, were observed compared to lipoplex injection. The sequential injection technique yielded a two- to fivefold higher level of transgene expression in the lung and was more effective in repeated dosing than lipoplex. Other types of lipoplex-associated toxicities, such as neutropenia, lymphopenia, thrombocytopenia, and complement depletion, were also significantly reduced with sequential injection. The reduction in cytokine release was observed with several different liposome formulations and appeared to be a general phenomenon.
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PMID:Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity. 1135 72


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