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)

Bloom syndrome (BS) is an autosomal recessive disorder characterized by small stature, immunodeficiency, chromosomal instability, and a predisposition to different types of cancer. Although extremely rare in the general population, BS is seen in about 1 in 48,000 Ashkenazi Jews. Mutation analysis of seven Ashkenazi BS probands has shown that all were homozygous for the same mutation in the BLM gene: 2281delATCTGAinsTAGATTC, also known as blmAsh. This finding, along with the increased incidence of BS among Ashkenazi Jews, suggests a founder effect for BS in this population. The purpose of this study was to determine the frequency of blmAsh mutation carriers in a randomly sampled Ashkenazi Jewish population in Israel. The initial study group included 1,613 Ashkenazi Jews who were referred for routine DNA screening tests (cystic fibrosis, Gaucher, Canavan, fragile X). None had a family history of BS. A group of 552 non-Ashkenazi Jews served as controls. Mutation analysis was performed by PCR amplification followed by analysis of a specific BstN1 restriction site, created by the blmAsh mutation. All positive carriers were confirmed by direct sequencing. Sixteen blmAsh carriers were detected among 1,613 Ashkenazi Jews (1 in 101), compared to none among 552 non-Ashkenazi individuals. In this study, Ashkenazi Jews of biparental Polish descent had a significantly higher proportion of the blmAsh mutation (1 in 37) compared to Ashkenazi Jews of non-Polish descent. These results provide further evidence that a founder effect is responsible for the increased incidence of Bloom syndrome among Ashkenazi Jews, particularly those of Polish descent.
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PMID:High frequency of a common Bloom syndrome Ashkenazi mutation among Jews of Polish origin. 1046 6

Several problems limit the application of gene transfer to correct the cystic fibrosis (CF) Cl(-) transport defect in airway epithelia. These include inefficient transduction with vectors applied to the apical surface, a low rate of division by airway epithelial cells, failure of transgene expression to persist, and immune responses to vectors or vector-encoded proteins. To address these issues, we used a feline immunodeficiency virus-based (FIV-based) vector. FIV vector formulated with a calcium chelator transduced fully differentiated, nondividing human airway epithelia when applied to the apical surface. FIV-based vector encoding the cystic fibrosis transmembrane conductance regulator cDNA corrected the Cl(-) transport defect in differentiated CF airway epithelia for the life of the culture (>3 months). When this approach was applied in vivo, FIV vector expressing beta-galactosidase transduced 1-14% of adult rabbit airway epithelia. Transduced cells were present in the conducting airways, bronchioles, and alveoli. Importantly, gene expression persisted, and cells with progenitor capacity were targeted. FIV-based lentiviral vectors may be useful for the treatment of genetic lung diseases such as CF. This article may have been published online in advance of the print edition.
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PMID:Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect. 1058 10

Pneumocystis carinii (P. carinii) cysts were identified in bronchoalveolar lavage fluid from a 15-week-old child newly diagnosed with cystic fibrosis who presented with bronchitis, pneumonia, and weight loss. The child was not infected with human immunodeficiency virus (HIV), and there was no evidence of impaired immunity or exposure to individuals with known or suspected P. carinii disease. Culture of the lavage fluid also revealed pathogens typical of lung disease associated with cystic fibrosis. It is suspected that the presence of P. carinii in this patient represented a new acquisition, as has been described in immunocompetent infants and children. Whether P. carinii infection complicated cystic fibrosis-associated lung disease in this patient is unknown.
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PMID:Pneumocystis carinii isolated from lung lavage fluid in an infant with cystic fibrosis. 1068 45

Despite a marked increase in the prescription of oral nutritional supplements (ONS) in the community (Department of Health, 1991-7), there is still uncertainty about the value of their use in patients with different diseases. To answer questions about the effects on ONS on body weight and structure, spontaneous food intake and body function, a critical systematic review was undertaken (Stratton & Elia, 1999a). Eighty-four trials were reviewed (forty-five randomized, thirty-nine non-randomized: 2,570 patients; diagnoses including chronic obstructive pulmonary disease, Crohn's disease, cystic fibrosis, human immunodeficiency virus and acquired immune deficiency syndrome and cancer). Most studies (83 %) were conducted in patients living at home. The supplements were typically mixed macronutrients in liquid form, providing < 0.42-10.5 MJ/d for 1 week-2 years. The studies reviewed in patients with predominantly chronic conditions living in the community suggested that: (1) ONS produce demonstrable clinical (including functional) benefits, but the nature and extent of these benefits varies with the underlying chronic condition; (2) ONS increase total energy intake with > 50 % of the energy from ONS typically additional to that from habitual food intake; (3) improvements in body weight, total energy intake and body function following ONS appear to occur more frequently in individuals with a BMI < 20 kg/m2 than in those with a BMI > 20 kg/m2.
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PMID:Summary of a systematic review on oral nutritional supplement use in the community. 1099 76

Chronic liver disease is a major complication of cystic fibrosis. Its incidence and severity show marked heterogeneity, even among the homogeneous group of homozygous DeltaF508 patients, suggesting that environmental or genetic factors other than the deletion DeltaF508 may influence the development of cystic fibrosis related liver disease. We investigated whether the allelic variants of mannose binding lectin, an important protein of the immune system, could be associated with the presence of cirrhosis in a population of 216 homogeneous homozygous DeltaF508 patients. Analysis of the data shows that the presence of cirrhosis in cystic fibrosis patients is significantly associated with a mutated mannose binding lectin genotype (homozygous or compound heterozygous for mannose binding lectin variants). The modulating role of mannose binding lectin in the occurrence of cirrhosis in cystic fibrosis could be explained by the fact that hepatotoxic damage from viruses or bacteria might be increased by the immunodeficiency associated with mannose binding lectin variants and might facilitate the degradation of liver status. These data highlight the crucial role of mannose binding lectin in the clinical outcome of cystic fibrosis, as it has recently been shown that the mannose binding lectin gene is a modulating gene of the respiratory involvement in cystic fibrosis patients.
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PMID:The mannose binding lectin gene influences the severity of chronic liver disease in cystic fibrosis. 1133 66

The local increase in the secretion of extracellular proteases, allowing cleavage of the extracellular matrix and thereby facilitating the infiltration of T cells, monocytes and neutrophils, is a hallmark of chronic inflammation and autoimmunity. In pulmonary genetic diseases, such as emphysema and cystic fibrosis, proteases can also favour the development of local immunodeficiency by degrading key regulators of the immune response, such as CD4, CD8, IgG, ICAM-1 and C3b receptors. Since several infectious agents can give rise to severe pulmonary disorders associated with opportunistic infections, we sought to determine whether an increase in proteolytic activity occurred during infection with porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of a new disease in swine characterized by severe respiratory problems in young pigs. Piglets were infected with the virus and bronchoalveolar lavages were collected at various times post-infection to measure the net proteolytic activity. It was shown that PRRSV infection leads to a significant increase in proteolytic activity in pulmonary fluids. Maximal activity was found at 7 and 14 days post-infection, with a return towards normal levels at day 42. Zymographic analyses showed a significant increase in the secretion of matrix metalloproteases (MMPs) 2 and 9, two enzymes involved in tissue remodelling. Histological analyses showed a correlation between the increase in proteolytic activity and the appearance of lesions that were characterized by massive lymphomononuclear cell infiltration. These results suggest that virus infection of the lungs can lead to a transient increase in proteolytic activity that could favour opportunistic infection.
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PMID:Increased proteolytic activity and matrix metalloprotease expression in lungs during infection by porcine reproductive and respiratory syndrome virus. 1136 68

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by deficient antibody production. The cause of this immunodeficiency is unknown; several in vitro studies have revealed a significant number of alterations that could explain the hypogammaglobulinemia present in this syndrome. Among those described are primary B cell alterations, numerical and functional T cell abnormalities, and defects in the interaction between accessory cells. The alteration typical of CVI is the failure of B lymphocytes to differentiate from antibody-producing cells, resulting in deficient immunoglobulin secretion. Among the T cell abnormalities described are a diminished proliferative response to mitogens and antigens, alterations in the level of production of several cytokines, especially reduction in the production of IL-2, diminished antigen-specific T cells and increase basal apoptosis after stimulation. Antigen presenting cells, monocytes and dendritic cells can also present alterations and contribute to deficient antigen response. The clinical manifestations of these patients is variable; most present recurrent bacterial infections due to encapsulated bacteria, especially sinusitis, otitis, bronchitis, and pneumonias. A few patients can present mycobacterial or fungal infection and occasionally Pneumocystis carinii. Viral infection is uncommon in these patients although some suffer recurrent herpes zoster infection. Clinical features of septicemia and central nervous system infections are less frequent. The incidence of digestive tract infections in these patients is high. The most common cause of diarrhea is Giardia lamblia; Salmonella, Shigella and Campylobacter are also common pathogens. Autoimmune disease is also more prevalent in these patients than in the general population. The most frequently associated diseases are hemolytic anemia, idiopathic thrombocytopenic purpura and autoimmune neutropenia. Cancer is also frequently associated with CVI, the most common forms being lymphoproliferative syndromes, especially non-Hodgkin's lymphoma. Granulomas are a unusual manifestation in some patients with CVI; their localization varies but the most commonly affected organs are the spleen and lungs. Some authors have compared these granulomas with those characterizing sarcoidosis, especially when appearing in the lung. Diagnosis of CVI is usually by exclusion of other diseases, such as cystic fibrosis, immotile cilia syndrome or allergic processes. CVI should be suspected in all patients with recurrent bacterial infections especially those localized in the respiratory tract. Other primary immunodeficiencies which present clinical findings similar to CVI and which should be ruled out are selective IgG subclass deficiency, IgA deficiency and selective deficiency in the response to polysaccharide antigens with normal immunoglobulin levels. The serum hypogammaglobulinemia present in all patients with CVI provides the diagnostic key. The age at which clinical manifestations appear, the absence of familial antecedents and the presence of circulating B lymphocytes form the basis of the differential diagnosis between X-linked agammaglobulinemia and autosomal recessive forms. The treatment of choice of patients with CVI is treatment with human gamma-globulin. Currently, the most common route of administration is intravenous; these molecules have a half-life of approximately 21 days and a high degree of safety concerning the possible transmission of viral infections. Adverse reactions are generally few and clinically unimportant. The most frequently used doses oscillate between 200 and 400 mg/kg body weight every 2-4 weeks. Both the dose and its frequency should be personalized for each patient. Early diagnosis of patients with CVI, application of treatment with appropriate antibiotics for infections and treatment with gamma-globulins prevent long-term complications of this disease and dramatically improve the quality of life and life expectancy of these patients.
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PMID:[Common variable immunodeficiency. Review]. 1143 84

Sclerosing cholangitis in childhood is a heterogeneous condition, which has different aetiologies. Sclerosing cholangitis may be inherited and diagnosed in the neonatal period (neonatal sclerosing cholangitis); it may present later with features of autoimmunity (autoimmune sclerosing cholangitis); or it may be associated with a variety of disorders, including Langerhans cell histiocytosis, immunodeficiency, psoriasis, cystic fibrosis, reticulum cell sarcoma and sickle cell anaemia. In contrast to the experience in adult patients, sclerosing cholangitis occurring as an individual disease (primary sclerosing cholangitis) is rare. The initiating events and possible pathogenic mechanisms differ in the various forms of sclerosing cholangitis and are still obscure. Treatment and prognosis depend on the type of sclerosing cholangitis present.
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PMID:Sclerosing cholangitis in the paediatric patient. 1149 76

The objective of this study was to develop an anthropometry-based prediction model for the assessment of bone mineral content (BMC) in children. Dual-energy X-ray absorptiometry (DXA) was used to measure whole-body BMC in a heterogeneous cohort of 982 healthy children, aged 5-18 years, from three ethnic groups (407 European- American [EA], 285 black, and 290 Mexican-American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean +/- SD for the measured/predicted in ratio was 1.000 +/- 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted In ratio = 1.000 +/- 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole-body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty-nine patients had Z scores less than -1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than -2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.
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PMID:Z score prediction model for assessment of bone mineral content in pediatric diseases. 1154 35

The child with recurrent chest infections presents the clinician with a difficult diagnostic challenge. Does the child have a simply-managed cause for their symptoms, such as recurrent viral respiratory infections or asthma, or is there evidence of a more serious underlying pathology, such as bronchiectasis? Many different disorders present in this way, including cystic fibrosis, a range of immunodeficiency syndromes, and congenital abnormalities of the respiratory tract. In some affected children, lung damage follows a single severe pneumonia: in others it is the result of inhalation of food or a foreign body. The assessment of these children is demanding: it requires close attention to the history and examination, and in selected cases, extensive investigations. Early and accurate diagnosis is essential to ensure that optimal treatment is given and to minimise the risk of progressive or irreversible lung damage. The aim of this chapter is to examine the causes of recurrent chest infections and to describe how this complex group of children should be assessed and investigated.
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PMID:Assessment of the child with recurrent chest infections. 1199 2


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