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

In December 1991, US blood centers reported an unusual increase in donations that tested falsely reactive for antibodies to two or more (multiple false positive) of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type I (HTLV-I), and hepatitis C virus. Many of these donations were from people who had recently received the 1991-1992 influenza vaccine, raising the possibility that this vaccine had somehow specifically caused the problem of multiple false reactivity. A case-control study of 101 affected donors and 191 matched controls found that recent receipt of any brand of influenza vaccine was significantly associated with testing multiple false positive (p < 0.05), as was a history of recent acute illness (p < 0.05) and of allergies (p < 0.05). Surveillance for monthly rates of multiple reactive donations from May 1990 through December 1992 linked the seasonal cluster of multiple false-positive donations to the use of viral screening test kits thought to react nonspecifically to donor immunoglobulin M. There was no similar increase in multiple false-positive donations during the 1992-1993 influenza vaccination season after the HIV-1 and hepatitis C virus tests were replaced; however, the number of donations that were falsely reactive for only HTLV-I almost doubled, indicating that false reactivity was not specifically associated with the 1991-1992 influenza vaccine. Retesting of affected donors found that the duration of HTLV-I and hepatitis C virus false reactivity was 3-6 months. The cluster of multiple false-positive donations in 1991 was most likely caused by the test kits used, rather than by the influenza vaccine.
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PMID:Multiple false reactions in viral antibody screening assays after influenza vaccination. 753 79

Binding and signaling proteins based on Escherichia coli alkaline phosphatase (AP; EC 3.1.3.1) were designed for the detection of antibodies. Hybrid proteins were constructed by using wild-type AP and point mutants of AP [Asp-101 --> Ser (D101S) and Asp-153 --> Gly (D153G)]. The binding function of the hybrid proteins is provided by a peptide epitope inserted between amino acids 407 and 408 in AP. Binding of anti-epitope antibodies to the hybrid proteins modulates the enzyme activity of the hybrids; upon antibody binding, enzyme activity can increase to as much as 300% of the level of activity in the absence of antibody or can decrease as much as 40%, depending on the presence or absence of the point mutations in AP. The fact that modulation is altered from inhibition to activation by single amino acid changes in the active site of AP suggests that the mechanism for modulation is due to structural alterations upon antibody binding. Modulation is a general phenomenon. The properties of the system are demonstrated by using two epitopes, one from the V3 loop of human immunodeficiency virus type 1 gp120 protein and one from hepatitis C virus core protein, and corresponding monoclonal antibodies. The trend of modulation is consistent for all hybrids; those in wild-type AP are inhibited by antibody, while those in the AP mutants are activated by antibody. This demonstrates that modulation of enzyme activity of the AP-epitope hybrid proteins is not specific to either a particular epitope sequence or a particular antibody-epitope combination.
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PMID:A molecular sensor system based on genetically engineered alkaline phosphatase. 754 Nov 35

The prevalence of hepatitis C virus (HCV) infection amongst a group of intravenous drug users (IVDUs) resident in West Suffolk (East Anglia, England) was investigated and compared with the prevalence of infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV). In addition, both the level of HCV persistence, as defined by detection of viral RNA, and the HCV genotypes present in this population were determined. It was found that HCV antibodies were present in 59% of those tested; by comparison 22% had antibodies to HBV and 1% antibodies to HIV. HCV RNA was found in 44% of those with HCV antibody. HCV genotype 1 was the most prevalent within this population although both genotypes 2 and 3 were also represented.
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PMID:Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities. 754 93

Liver function and antibodies to hepatitis C virus and to human immunodeficiency virus-1 were examined in 195 Japanese patients with hemophilia. One hundred and seventy-three were positive for antibody to HCV and 61 for antibody to human immunodeficiency virus-1. In 63 patients, we examined HCV genotypes according to the double polymerase chain reaction method. Forty cases (63%) were infected with hepatitis C virus with a single genotype, including type 1a in five, type 1b in 21, type 2a in seven and type 2b in seven; 16 (25%) were infected with double genotypes, including types 1a + 1b in 14, types 1b + 2a in one and types 1b+2b in one; and four (6%) were infected with triple genotypes, including types 1a + 1b + 2b in two. Genotype could not be determined in three patients by this method. In the 191 nonhemophiliac patients with chronic hepatitis C, HCV genotyping was as follows: type 1a in 0, type 1b in 121, type 2a in 40 and type 2b in 10 of 171 cases (89.5%) with single infection and types 1b + 2a in five and types 2a + 2b in one of six (5.5%) with double infection. In the remaining 14 patients, genotype could not be determined. Frequent transfusion of domestic and/or imported coagulation factor concentrates probably caused the high incidence of HCV infection with rare or mixed genotypes in Japanese hemophiliacs.
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PMID:Hepatitis C virus infection and genotypes in Japanese hemophiliacs. 754 74

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.
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PMID:HCV infection in patients with primary defects of immunoglobulin production. 755 76

The immunologic defect in X-linked immunodeficiency and hyperimmunoglobulinemia M (HIM) are related to defective expression of the CD40 ligand (CD40L). We have studied two female patients with HIM to evaluate the role of CD40/CD40L in the pathogenesis of impaired immunoglobulin switching. In addition to recurrent infections characteristic of humoral immunodeficiencies, the two patients had chronic hepatitis caused by type C virus. Phenotypic characterization of peripheral blood mononuclear cells showed a similar picture in both patients, with a reduction in the absolute numbers of CD4 cells and increased numbers of CD8 and CD3/DR cells. B cells (CD19+) were reduced in one patient, but CD40 was expressed on all CD19+ cells in both patients. The expression of CD40L was normal on peripheral blood mononuclear cells from the two patients with HIM on both resting and stimulated cells. The combination of anti-CD40 and cytokines (interleukin-2, interleukin-4, and interleukin-10) was able to restore proliferative capacity to anti-IgM. Peripheral blood mononuclear cells from the two patients with HIM showed a high spontaneous production of IgM in vitro and no production of IgG or IgE. Our data suggest that the defect of isotype switching in female patients with HIM is not related to defective expression of the CD40/CD40L receptor system. A possible role for chronic hepatitis C virus infection in the pathogenesis of the disease is suggested by the detection of specific production of anti-hepatitis C virus IgM.
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PMID:Immunodeficiency with hyperimmunoglobulinemia M in two female patients is not associated with abnormalities of CD40 or CD40 ligand expression. 756 Jun 43

The Central African Republic is located in tropical Africa, where both the human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are highly endemic. The exact prevalence of hepatitis C virus (HCV) and hepatitis E virus (HEV) markers in this country is unknown. The aim of the study was to determine, according to HIV and HBV serostatus, the prevalence of these markers in young sexually active adults in the Central African Republic. One hundred and fifty-seven consecutive patients attending the National Centre for Sexually Transmitted Diseases in Bangui were included. The following serological markers were examined: (i) anti-HIV1 and anti-HIV2 antibodies; (ii) markers of HBV infection; (iii) anti-HCV antibodies; (iv) anti-HEV antibodies. Anti-HIV1 antibodies were found in 31 of the 157 patients (20%). The prevalence of anti-HBc antibodies, reflecting exposure to HBV, was 140/157 (89%) and 45 had detectable anti-HBs antibodies. Twenty-two patients (14%) were chronic carriers of hepatitis B surface antigen (HBsAg), but only one was HBe antigen-positive. Anti-HCV antibodies were found in 8 persons (5%) and anti-HEV antibodies in 38 (24%). No difference was found in the prevalence of these markers according to the presence or absence of anti-HIV antibodies. This study confirms the high rate of HIV infection, HBV exposure and chronic carriage of HBsAg in sexually active young adults in the Central African Republic. A high prevalence of HCV markers was found in this population, similar to that reported in neighbouring countries, together with a high rate of HEV markers, suggesting that HEV is endemic in this region.
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PMID:High prevalence of hepatitis B, C, and E markers in young sexually active adults from the Central African Republic. 756 2

Serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphotropic virus type 1 (HTLV-1), and human immunodeficiency viruses (HIV-1 and HIV-2) were studied in 53 Saudi children (31 males, 22 females; 1-12 years of age) receiving cycled cancer chemotherapy and in 168 healthy Saudi children taken as control. Exposure to HBV in the patients was similar to that in the control (6 per cent HBsAg in patients v. 7 per cent in the control; 19 per cent exposure rate in patients v. 20 per cent in control). None of our patients was vaccinated against HBV prior to chemotherapy. The fact that among the 10 HBV exposed patients five patients were anti-HBs-positive is in favour of vaccinating Saudi oncology patients against HBV prior to chemotherapy. In contrast to the situation with HBV the prevalence of anti-HCV in the patients (11 per cent) was significantly higher than that in the control (1 per cent) (P = 0.003). None of our patients or the control were anti-HTLV-1 or anti-HIV-positive. The results of this study stress the need for an awareness of HCV problem in Saudi oncology patients. Strict measures of screening blood donors for all blood-borne viruses and, in particular, for HCV in addition to the use of disposable equipment in management of cancer patients are items that should be implemented as soon as possible.
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PMID:Infection with hepatitis viruses (B and C) and human retroviruses (HTLV-1 and HIV) in Saudi children receiving cycled cancer chemotherapy. 756 71

In a prospective study, 102 hospital patients with liver disease were evaluated in West Cameroon, Africa. Blood donors, pregnant women and patients without liver disease served as controls. A total of 757 individuals were tested for markers of hepatitis A, B, C and D and for immunological markers (autoantibodies, procollagen III, alpha-foetoprotein, CA50 antigen, alpha-1-antitrypsin and antibodies to human immunodeficiency virus types 1 and 2). One-third of the liver disease patients had focal lesions on ultrasound examination. Histologically, 20 cases of cirrhosis, 14 cases of chronic hepatitis, 15 hepatocellular carcinomas and 17 cases of acute hepatitis were detected. All hepatic patients and virtually all controls had had a previous hepatitis A virus infection. Over 85% of adult patients and controls had at least one marker of hepatitis B virus infection. Over 30% of patients with liver disease had markers of possible hepatitis B virus replication. Antihepatitis C virus antibody was present in 18% of hepatic patients and in 6% of controls. Hepatitis C virus infection seems to play an important role in the development of chronic liver pathology; 40% of cirrhotic patients had a combined hepatitis B and C virus infection. Serum autoantibodies were frequently found and were not correlated with the presence of autoimmune liver disease.
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PMID:Liver pathology in rural south-west Cameroon. 757 Aug 83

Surgeons routinely work with potentially infectious materials. The risk of acquiring a disease from one percutaneous exposure is 0.3-0.4% for human immunodeficiency virus (HIV) 6-30% for hepatitis B virus (HBV) and 2.7-10% for hepatitis C virus (HCV). Rates of blood contacts vary but may reach up to 11.9 per 100 h in the operating room. Residents are at highest risk, and obstetrics and gynaecology surgeons suffered the highest rate of exposures (10%) as a group. Contributing risk factors include trauma or emergency orthopaedic procedures, high patient blood loss, long procedures and holding tissue by hand while suturing. However, across occupations, nurses and other health workers experience greater risks than surgeons regarding potentially infectious exposures. Preventive measures such as the HBV vaccine and protective devices (i.e. self-capping needles, needle-free i.v. systems and improved barrier materials) have reduced the occupational risk of acquiring a blood-borne infection, which allows attention to be given to the psychosocial risks which may be more significant, yet are often overlooked. Doctors are at greater risk of divorce, alcoholism, substance abuse and suicide than are members of comparable professional groups. One study found that general surgeons had the highest rates of suicide of all doctors. According to family surveys, surgeons tend to be oblivious to the effects of work stressors, and may benefit from greater self-awareness; sharing of feelings and responsibilities with colleagues, family and patients; being willing to delegate work to others; setting work limits; and broadening perspectives in their approach to work.
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PMID:Occupational health in surgery: risks extend beyond the operating room. 757 89


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