Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an elderly patient with paroxysmal nocturnal haemoglobinuria (PNH), having recurrent enterocolitis and haemolytic attacks associated with cellular immunodeficiency. On admission, the patient had normal neutrophil count and function but a decreased T-cell count, decreased mitogenic reactions, and a negative tuberculin test. Granulocyte colony-stimulating factor (G-CSF) was administered, resulting in an increased T-cell count, normalization of T-cell function, increased blood levels of helper T cell (Th)1 and Th2 cytokines and improvement in the enterocolitis and haemolytic attacks. This suggests that G-CSF may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.
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PMID:A patient with paroxysmal nocturnal haemoglobinuria in whom granulocyte colony-stimulating factor administration resulted in improvement of recurrent enterocolitis and its associated haemolytic attacks. 1243 72

We describe the treatment of a 10-year-old girl with autosomal recessive Dyskeratosis congenita (DC), neutropenia, thrombocytopenia and combined immunodeficiency by nonmyeloablative hematopoietic stem cell transplantation. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day (days -5, -4, -3) and 2 Gy TBI (0.07 Gy/min; day 0). For graft-versus-host disease (GVHD) prophylaxis a course of intravenous MMF and CSA was administered. At 2 years after transplantation of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells from a healthy 11-year-old HLA-identical brother, peripheral blood counts and T- and B-cell functions have completely normalized and donor chimerism was 100% in all cell lineages. No GVHD occurred. Neurological examination and lung function remained normal. The current transplantation regimen appears suitable, safe and efficacious in patients with DC.
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PMID:Nonmyeloablative allogeneic hematopoietic stem cell transplantation for treatment of Dyskeratosis congenita. 1263 34

A human immunodeficiency virus-infected boy with Scedosporium apiospermum otomastoiditis and a girl with diabetes mellitus and Mucor sinusitis and orbital cellulitis had life-threatening disease progression despite antifungal treatment. Interferon-gamma and granulocyte-macrophage or granulocyte colony-stimulating factor were added, with good functional outcome in both children. Adjunctive therapy with interferon-gamma, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor can be considered for refractory invasive fungal infections.
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PMID:Interferon-gamma and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. 1529 29

Lentiviral vectors are capable of efficiently transducing nondividing and slowly dividing cells, including hematopoietic stem cells, resulting in stable integration and sustained transgene expression. We constructed human immunodeficiency virus type 1-based self-inactivating lentiviral vectors to express either wild-type or an O6-benzylguanine (O6-beG)-resistant mutant form of the human O6-alkylguanine-DNA methyltransferase (MGMT; DNA-O6-methylguanine:[protein]-L-cysteine S-methyltransferase, EC 2.1.1.63) and transduced K562 and granulocyte colony-stimulating factor-mobilized human peripheral blood CD34+ cells. After transduction, K562 cells expressed high levels of MGMT as determined by Western blot, immunocytochemistry, and biochemical assay. A colony-forming survival assay showed significant protection against O6-beG plus 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) or temozolomide (TMZ) toxicity. Similarly, a single transduction of CD34+ cells resulted in a 13- to 14-fold increase in the level of MGMT expression. In comparison with non-transduced cells, mutant MGMTP140K-transduced CD34+ cells showed significant resistance against the combined toxicity of O6-beG with either TMZ or BCNU: there was an approximately 9-fold increase in the survival of colony-forming cells as indicated by the IC50 values after O6-beG plus TMZ treatment and an approximately 5-fold increase in the case of O6-beG plus BCNU treatment. These results show that lentivirus-mediated expression of MGMTP140K can efficiently protect the hematopoietic compartment against the combined toxicity of O6-beG plus TMZ or BCNU.
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PMID:Lentivirus-mediated expression of mutant MGMTP140K protects human CD34+ cells against the combined toxicity of O6-benzylguanine and 1,3-bis(2-chloroethyl)-nitrosourea or temozolomide. 1531 33

The effects of hematopoietic stem cell (HSC) mobilization on Kaposi's sarcoma-associated herpesvirus (KSHV) were evaluated in three KSHV and human immunodeficiency virus type 1 co-infected subjects. KSHV DNA was not detected in purified CD34+ cell preparations from the period of filgrastim treatment. However, two of 3 subjects had transiently increased cell-free plasma KSHV DNA during filgrastim treatment. Peak plasma KSHV DNA (2,600 and 4,300 copies/mL) occurred on day 4 and declined to below the limit of detection by day 7. These findings suggest that, although CD34+ cell preparations do not have evidence of KSHV infection, HSC mobilization may stimulate KSHV replication in other cellular compartments that contribute to KSHV viremia.
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PMID:Stimulation of Kaposi's sarcoma-associated herpesvirus viremia during hematopoietic stem cell mobilization with filgrastim. 1555 Dec 82

The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.
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PMID:FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity. 1609 4

The relationship between infectious complications and neutropenia was evaluated in recipients of interferon-based therapy for hepatitis C followed at The Ottawa Hospital Viral Hepatitis Clinic from June 2000 to May 2005. One hundred ninety-two patients received 211 courses of therapy (5707 person-weeks of therapy). No patients received granulocyte colony-stimulating factor. Sixty-seven infectious complications occurred in 57 patients (1.17 infections per 100 person-weeks of therapy). The median time to infection was 17 weeks after the start of therapy. Age, sex, weight, race, human immunodeficiency virus status, stage and grade of biopsy, and type of interferon were not correlated with infection rate by Cox regression analysis. The rates of total, fungal, viral, and bacterial infections did not correlate with nadir neutrophil count or magnitude of decrease from baseline. Neutrophil count is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C. Reduction in interferon dose and/or dosing with granulocyte colony-stimulating factor in those with neutropenia is not supported by this analysis.
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PMID:Rate of infectious complications during interferon-based therapy for hepatitis C is not related to neutropenia. 1670 70

The aim of hematopoietic stem cell transplantation (HSCT) is to cure patients of malignancies, autoimmune diseases, and immunodeficiency disorders by redirecting the immune system: the often described graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Unfortunately, fulfillment of this goal is often hampered by relapse of the underlying disease, graft-versus-host disease (GVHD), or severe opportunistic infections, which account for the majority of post-transplantation deaths. Moreover, studies of long-term survivors of transplantation indicate an accelerated immune aging due to the transplantation procedure itself, preceding chemo- or radiotherapy, and acute and chronic GVHD. Significant advances have been made towards overcoming these obstacles by enhancing immune reconstitution with hematopoietic growth factors (HGFs) such as granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) or through the application of cytokines. In addition, there are approaches to promote the thymic-dependent development of naive T cells, which are prepared for the interaction with a multitude of pathogens. Examples are the application of keratinocyte growth factor (KGF), neuroendocrine hormones such as growth hormone or prolactin, sex hormone ablation, or the invention of a three-dimensional artificial thymus based on a cytomatrix. Might these measures result in a higher rate of healthy and fully recovered patients? Here we review progress in each of these areas.
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PMID:Hematopoietic growth factors including keratinocyte growth factor in allogeneic and autologous stem cell transplantation. 1763 Nov 84

In the era of highly active antiretroviral therapy (HAART), the prognosis for acquired immunodeficiency syndrome-related lymphomas (ARL) seems to be similar to that for aggressive B-cell lymphomas in human immunodeficiency virus (HIV)-negative patients. This improvement in prognosis might lead to a modification of the classic prognostic factors for ARL. We evaluated the prognostic factors for response and survival in a series of HIV-infected patients with systemic non-Hodgkin's lymphoma (NHL) in the HAART era. Forty patients with systemic NHL treated with a CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) and HAART were studied. The main clinicopathologic and laboratory parameters were recorded in each case. Patients were scheduled to receive cycles of CHOP therapy, and all received granulocyte colony-stimulating factor. In addition, 9 patients received rituximab (375 mg/m2). The complete remission (CR) rate was 62.5% (n = 25). No prognostic factors influencing CR attainment were found. The 5-year disease-free survival (DFS) probability (95% confidence interval [CI]) was 73% (54%-92%). The median overall survival (OS) time was 69.17 months, and the 5-year OS rate (95% CI) was 51% (35%-67%). A disease stage of III to IV was the only parameter with prognostic influence on DFS. The factors influencing OS were an International Prognostic Index >2, an Eastern Cooperative Ecology Group (ECOG) score >2, and a disease stage of III to IV. Patients with an advanced stage had a lower OS probability in a multivariate analysis (odds ratio, 4.24; 95% CI, 1.24- 14.57). Advanced stage was the main prognostic factor predicting survival in ARL treated with CHOP and HAART.
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PMID:Advanced stage is the most important prognostic factor for survival in patients with systemic acquired immunodeficiency syndrome-related non-Hodgkin's Lymphoma treated with CHOP and highly active antiretroviral therapy. 1805 41

Biomarkers for treatment response would facilitate the testing of urgently needed new anti-tuberculous drugs. The present study investigated the profiles of 30 proinflammatory, anti-inflammatory and angiogenic factors [epidermal growth factor, eotaxin, fractalkine, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, interferon-gamma, interferon-inducible protein-10, Krebs von den Lungen-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, sCD40L, transforming growth factor-alpha, tumour necrosis factor-alpha and vascular endothelial growth factor] in the plasma of 12 healthy tuberculin skin test-positive community controls and 20 human immunodeficiency virus-negative patients with active tuberculosis (TB) and identified potential biomarkers for early treatment response. We showed differences in the level of circulating cytokines between healthy controls and TB patients, but also between fast responders and slow responders to anti-tuberculosis treatment. The general discriminant analysis based on pre-treatment and week 1 measurements identified 10 sets of three-variable models that could classify fast and slow responders with up to 83% accuracy. Overall, this study shows the potential of cytokines as indicators of anti-tuberculosis treatment response.
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PMID:Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis. 1919 52


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