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)

Some rotavirus strains, including vaccine candidates, have been demonstrated to cause hepatitis in immunodeficient and malnourished mice and to grow in human liver cells. To determine whether rotavirus spreads outside the intestine in naturally infected children, we examined tissues from four immunodeficient children affected with severe combined immunodeficiency disease, acquired immunodeficiency disease syndrome, or DiGeorge syndrome. Chronic rotavirus-related diarrhea, which persisted until death, had also developed in each child. Using indirect immunoperoxidase techniques, we identified rotavirus antigen in the liver and kidney with a hyperimmune guinea pig antiserum prepared to double-shelled rotavirus particles. Similar immunostaining with an antiserum to a rotavirus nonstructural protein (NS26) provided evidence of active virus replication. The observed reactivity was eliminated specifically when serial sections were immunostained with the same antiserum that had been absorbed with either double-shelled rotavirus particles or NS26. Immunostaining was not observed in the liver of children with other diseases (alpha 1-antitrypsin deficiency, inspissated bile syndrome, and acute rejection of a transplanted liver). These findings demonstrate that rotavirus infections in children can extend beyond the intestinal tract. Further studies are warranted to determine whether extraintestinal rotavirus replication occurs in children without severe immunodeficiency, such as malnourished children.
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PMID:Extraintestinal rotavirus infections in children with immunodeficiency. 131 19

Chronic bronchitis is defined for epidemiologic and clinical purposes as the presence of productive cough for three months in each of two successive years. Based on symptoms, the term 'chronic bronchitis', therefore, does not describe one distinct disease. It is rather a collective name for the clinical manifestation of numerous different congenital or acquired chronic diseases of the trachea, the bronchi and the bronchioli. Cigarette smoking is the most consistently important (and preventable) determinant of chronic bronchitis. There are, however, other rare etiologic factors, including malformations, tumors, recurrent aspirations and bronchiectasis. The latter often occur in association with systemic disorders such as cystic fibrosis, immotile cilia syndrome, immunodeficiency, alpha 1-antitrypsin deficiency and others.
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PMID:[Chronic bronchitis: rare etiology]. 144 Apr 38

We have developed a binary transgenic mouse system that allows easy in vivo evaluation of new anti-human immunodeficiency virus type 1 (HIV-1) drugs or therapies specifically designed to target the viral transactivator protein (TAT) or long terminal repeat (LTR) functions. This approach consists of a simple genetic cross between an "activator" transgenic mouse expressing the HIV-1-tat gene exclusively to T lymphocytes and a "target" transgenic mouse bearing a silent reporter gene whose expression is under the control of the HIV-1-LTR. As expected, most of the target transgenic animals did not express the reporter gene; on the contrary, all the double-transgenic mice bearing both the activator and target transgenes strongly expressed the TAT-induced reporter gene. The choice of a secreted human alpha 1-antitrypsin variant (alpha 1-AT) as reporter gene readily permits in a single animal the quantitative determination of the plasma level of alpha 1-AT protein before and after anti-LTR or anti-TAT treatments. Such mice may be valuable as new laboratory models for the in vivo evaluation of agents with potential anti-HIV-1 activity.
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PMID:A novel transgenic mouse model for the in vivo evaluation of anti-human immunodeficiency virus type 1 drugs. 149 46

A longitudinal (10-22 month) evaluation of intestinal symptoms and function was performed in five children with symptomatic human immunodeficiency virus (HIV) infection. All received cotrimoxazole, ketoconazole, and immunoglobulins. A search for enteric pathogens and intestinal function tests were repeatedly performed in all patients. Mild episodes of diarrhea were observed in two children. One had cow's milk protein intolerance. Giardia lamblia was found in an asymptomatic carrier. Evidence for impaired intestinal function was found in all patients. These consisted of positive D-xylose and iron oral loads, increased steatorrhea, increased fecal excretion of alpha 1-antitrypsin, abnormal intestinal permeability, and increased food antibody levels. Our results suggest that severe diarrhea may be uncommon in children with HIV infection receiving antimicrobial prophylaxis, but that the intestinal function is frequently, and often markedly, impaired.
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PMID:Impaired intestinal function in symptomatic HIV infection. 186 78

The alpha 1-antitrypsin (AAT) phenotype was determined by isoelectric focusing in 215 male homosexuals and compared with those in 208 male heterosexuals. The incidence of abnormal phenotypes was 16.3% in the homosexual group which was significantly different (p less than 0.03) than the 8.7% in the heterosexual group. There was no difference in the phenotype distribution between homosexuals who were anti-human immunodeficiency virus reactive and those who were non-reactive. It suggests that investigation into the interplay of factors associated with homosexuality could include genetic as well as psychological and social factors.
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PMID:Alpha 1-antitrypsin phenotypes in homosexual men. 281 82

The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.
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PMID:Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells. 284 41

We have isolated overlapping phage genomic clones covering an area of 26 kilobases that encodes the human alpha 2-plasmin inhibitor. The alpha 2-plasmin inhibitor gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA. To our knowledge, the number of introns is the highest yet reported for a member of the serine protease inhibitor (serpin) superfamily. All introns are located in the 5'-half of the corresponding mRNA. The 5'-untranslated region and the leader sequence are interrupted by 3 introns totaling approximately equal to 6 kilobases. A "TATA box" sequence is located 17 nucleotides upstream from the proposed transcription initiation site. Multiple "GC box" sequences, G + C-rich sequences, and "CCAAT box"-like sequence, the hepatitis B virus enhancer element-like sequence and the human immunodeficiency virus enhancer-like sequence appear in the 5'-flanking region. The NH2-terminal region, which implements factor XIII-catalyzed cross-linking of alpha 2-plasmin inhibitor to fibrin, is encoded by the 4th exon. The reactive site and plasminogen-binding site, both located in the COOH-terminal region, are encoded by the 10th exon. When similar amino acids of alpha 2-plasmin inhibitor and other members of the serpin gene superfamily are aligned, the position of the 7th intron of the alpha 2-plasmin inhibitor gene aligns precisely with that of the second intron of the genes for rat angiotensinogen and human alpha 1-antitrypsin genes and is misaligned by only one nucleotide with that of the third intron of antithrombin III, suggesting that the alpha 2-plasmin inhibitor gene originates from the common ancestor of these serine protease inhibitors.
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PMID:Organization of the human alpha 2-plasmin inhibitor gene. 316 40

Lipid accumulation has been described in the duodenal lamina propria of human immunodeficiency virus (HIV)-infected patients with diarrhea and malabsorption. Using light and electron microscopy, we studied duodenal biopsies obtained from 54 consecutive HIV-infected patients by means of upper gastrointestinal endoscopy after an overnight fast. The presence of diarrhea and weight loss were recorded, and all the patients had standard stool study for ova, parasites, and bacteria. Serum levels of albumin, triglycerides, and cholesterol were obtained within one week of the endoscopy. Fecal fat and fecal alpha 1-antitrypsin clearance were measured in 11 patients. Lipid accumulation was observed in nine patients (16.6%). Fat droplets were seen in enterocytes, in their basolateral membrane spaces, and in the lamina propria. The mean serum levels of triglycerides (1.85 +/- 0.20 mmol/liter) and cholesterol (2.81 +/- 0.30 mmol/liter) were significantly lower in the patients with enteric steatosis than in patients without this anomaly (respectively, 3.38 +/- 0.39 and 3.97 +/- 0.18 mmol/liter, P < 0.001 P < 0.01). The mean amount of fecal fat in the three patients with lipid accumulation (16 +/- 1.60 g/24 hr) was significantly larger than in the eight patients without lipid accumulation (4.50 +/- 0.62 g/24 hr, P < 0.01). These findings suggest that fat malabsorption in HIV-infected individuals is due to a blockage of transport through the duodenal mucosa. The frequency of diarrhea, weight loss, or identified enteric pathogens did not differ significantly between patients with and without enteric steatosis. Both the etiology and the pathophysiology of these alterations remain to be documented.
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PMID:Association of lipid accumulation in small intestinal mucosa with decreased serum triglyceride and cholesterol levels in AIDS. 792 37

Furin is a membrane-associated calcium-dependent serine endoprotease that cleaves proproteins on the carboxyl side of the consensus sequence -Arg-X-Lys/Arg-Arg-. Using site-directed mutagenesis, a variant alpha 1-antitrypsin (alpha 1-AT) was constructed which contains in its reactive site -Arg-X-X-Arg-, the minimal sequence required for efficient processing by furin (Molloy, S. S., Bresnahan, P. A., Leppla, S. H., Klimpel, K. R., and Thomas, G. (1992) J. Biol. Chem. 267, 16396-16402). This alpha 1-AT variant, [Arg355 Arg358]alpha 1-AT (alpha 1-PDX), is greater than 3,000-fold more effective than [Arg358]alpha 1-AT (alpha 1-AT Pittsburgh, alpha 1-PIT) at inhibiting furin in vitro (K0.5 = 0.03 microgram/ml). Furthermore, the P4 Arg in alpha 1-PDX greatly attenuates the thrombin inhibitory properties of this serpin (> 300-fold) compared with alpha 1-PIT (which contains a P4 Ala), thus increasing the selectivity of alpha 1-PDX for furin. Expression studies show that alpha 1-PDX, and not alpha 1-PIT, blocks the processing of two furin substrates, pro-beta-nerve growth factor and human immunodeficiency virus (HIV)-1 gp160 in transfected cells. In addition, a syncytium assay shows that alpha 1-PDX blocks the membrane fusogenic properties of HIV-1 gp160. The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed.
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PMID:Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. 822 51

Children with human immunodeficiency virus (HIV) infection have a higher prevalence of intestinal malabsorption. Anemia is also a common feature in these children. The aims of this work were (a) to establish the prevalence of iron deficiency in HIV-infected children, (b) to test the hypothesis that iron deficiency is related to intestinal malabsorption, (c) to see whether it may contribute to anemia, and (d) to evaluate the sensitivity of oral iron load in the investigation of intestinal function. To accomplish these goals, 71 HIV-infected symptomatic children were enrolled. Iron serum values were determined before and after oral load with ferrous sulfate. The correlation between basal and post-load iron levels was evaluated by linear regression. Xylose level after oral load, fecal fat, and fecal alpha 1-antitrypsin concentration were also determined. Iron deficiency was detected in 48% of patients, and it was significantly associated with intestinal iron malabsorption. Sugar malabsorption, steatorrhea, and fecal protein loss were detected in 26, 36, and 17% of patients, respectively. Low hemoglobin levels were detected in 66% of patients. The majority of children with iron deficiency also had anemia. Preliminary data showed that oral iron administration was sufficient for raising hemoglobin in children with normal iron absorption, whereas parenteral administration was required in those with iron malabsorption. We conclude that (a) iron deficiency is a major feature of pediatric HIV infection, (b) it is related to intestinal malabsorption, and (c) it contributes to anemia. Finally, oral iron load is a sensitive test for investigating intestinal function.
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PMID:Iron deficiency and intestinal malabsorption in HIV disease. 873 98


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