Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which cells expressing HIV envelope glycoproteins progress from binding CD4+ cells to syncytia formation is not entirely understood. The purpose of these investigations was to use physical and biochemical tools (temperature shifts, soluble CD4, protease inhibitors, and a battery of anti-CD4 monoclonal antibodies) to isolate discrete steps during syncytia formation. Previously (Fu et al., J Virol 1993;67:3818), we found that preincubation of cells stably expressing HIV-1 gp 160 (TF228.1.16) with CD4+ SupT1 cells at 16 degrees C, a temperature that is nonpermissive for syncytia formation, resulted in an increased rate of syncytia formation when the cocultures were shifted to the syncytia-permissive temperature of 37 degrees C. We have since found that syncytia formation is further enhanced by shifting the cocultures from 16 to 4 degrees C prior to incubation at 37 degrees C. Together, these data suggest that two discrete states, which we term the first and second activation intermediates (FAI and SAI), are involved in syncytia formation. We have found that acquisition of the FAI (by preincubation at 16 degree C) is sensitive to some serine protease inhibitors (PI), soluble CD4 (sCD4), shedding of gp120, and anti-CD4 monoclonal antibodies (MAb) directed toward the CDR-1/2 and CDR-3 regions of domain 1 on CD4. Expression of the FAI (formation of syncytia by shifting from 16 to 37 degrees C) remains sensitive to sCD4, shedding of gp120, and MAb directed toward CDR-1/2 but is less sensitive to MAb that bind CDR-3 and is insensitive to PI. Similarly, acquisition of the SAI (shifting cocultures from 16 to 4 degrees C), is sensitive to sCD4, shedding of gp120, and MAb directed toward CDR-1/2. In contrast, expression of the SAI (shifting cocultures from 16 to 4 to 37 degrees C) is sensitive only to MAb directed toward CDR-1/2 and cannot be blocked by sCD4, shedding of gp120, or PI. These data allow us to propose that syncytia formation, mediated by HIV-1 envelope glycoproteins, proceeds by a multistep cascade.
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PMID:Characterization of CD4-gp120 activation intermediates during human immunodeficiency virus type 1 syncytium formation. 889 Nov 9

Three thousand and fifty-two infections with opportunist mycobacteria were reported to the PHLS Communicable Disease Surveillance Centre from 1982 to 1994. The commonest reported species was Mycobacterium avium-intracellulare (MAI), followed by M. kansasii and M. malmoense. The annual totals of opportunist mycobacteria increased steadily over this period, mostly, but not exclusively, due to an increase in reports of MAI associated with HIV infection. There were also increases in reports of MAI not associated with HIV infection, and in reports of M. malmoense. The increase in reports of opportunist mycobacteria was seen throughout England and Wales, but underreporting of MAI infection in the National Health Service Thames regions appears to have increased in recent years. Continued referral of isolates of opportunist mycobacteria to one of the PHLS regional centres for mycobacteriology or the Mycobacterium Reference Unit, and reporting to CDSC, is essential for the surveillance of these infections.
Commun Dis Rep CDR Rev 1996 Oct 11
PMID:Opportunist mycobacteria in England and Wales: 1982 to 1994. 891 89

The number of HIV infections prevalent in the United Kingdom (UK) at the end of 1994 have been estimated. Estimates of the future annual incidence and prevalence of AIDS and severe HIV disease have been calculated for the UK by combining recently published projections for Scotland with projections produced for England and Wales adjusted to account for Northern Ireland. The number of HIV infections prevalent in the UK at the end of 1994 was estimated to be about 23,000, 36% of them undiagnosed. It was estimated that 52% of prevalent infections were in homo/bisexual men, and 32% were in people exposed through heterosexual intercourse. Between 2100 and 2190 new cases of AIDS are expected to be reported in the UK each year from 1995 to 1999. It is predicted that a 30% rise in the number of cases exposed through heterosexual intercourse and a 17% rise in cases who inject drugs will be balanced by a 7% fall in cases among homo/bisexual men. Prevalent AIDS cases in the UK are expected to rise by 15%, from 3740 at the end of 1995 to 4290 at the end of 1999. The number of people expected to be living with severe HIV disease, including AIDS, will also rise by about 15%, from 7545 at the end of 1995 to 8650 at the end of 1999.
Commun Dis Rep CDR Rev 1996 Dec 06
PMID:AIDS and severe HIV disease: combined predictions for the United Kingdom to 1999. 899 May 77

Individuals seropositive for human immunodeficiency virus type 1 (HIV) express elevated levels of autoantibodies (AAbs) directed against recombinant T-cell receptors (TCRs) and synthetic peptide epitopes duplicating beta chain markers. We performed longitudinal studies of anti-TCR AAbs in HIV-1-infected individuals, making comparisons with uninfected sera and sera from other individuals infected with a nonviral agent. We determined levels of autoantibodies by titration using enzyme-linked immunosorbent assay (ELISA) and developed a means for characterizing "autoantibody CDR recognition spectrotypes" for individual sera. Antibody levels against certain defined synthetic epitopes were substantially elevated in HIV-infected subjects relative to reactivities by control groups. Individual sera showed relatively high AAb levels to a subset of CDR1 peptide epitopes. Two patients who subsequently developed AIDS showed particular reactivity to Vbeta2.1, 8.1, 10.1, and 22.1 epitopes. Our results show that production AAbs to TCR Vbeta epitopes is a general consequence of HIV infection. The response is individual but shows some restriction and shifts in AAb subpopulations often occur with time.
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PMID:Analysis of autoantibodies to T-cell receptors among HIV-infected individuals: epitope analysis and time course. 900 Apr 86

Emergence of resistance of Candida albicans to antifungal triazoles is increasingly recognized as an important cause of refractory mucosal candidiasis in HIV-infected patients. Recently, CDR1, which is thought to be analogous to the human MDR-1 P-glycoprotein, has been cloned in C. albicans. It has been proposed that its expression is partially responsible for fluconazole resistance in C. albicans. This gene is characterized by the presence of an ATP binding cassette (ABC) region and is distinct from the BENr gene which does not encode such a functional domain. As the molecular basis for fluconazole resistance appears to be multifactorial, we considered that there may be other ATP binding cassette-containing MDR genes that may potentially contribute to antifungal azole resistance in C. albicans. We therefore sought to identify potential target sequences that may be derived from candidate genes that share homology with the ATP binding cassette region of the human MDR-1 P-glycoprotein. Degenerate oligonucleotide primers based on the known sequence from the ATP binding cassette region of the human MDR-1 P-glycoprotein were used to amplify PCR products within the range of 100 bp in length from C. albicans isolates (3 fluconazole-susceptible and 3 fluconazole-resistant). Sequence analysis of individually subcloned PCR products, derived from the six isolates revealed 34 sequences in total. The results of our study identified 14 clones (with at least one per isolate) with a high degree of homology to the ATP binding cassette of the human MDR-1 P-glycoprotein. The BLAST search did not disclose homology of these new sequences to the C. albicans CDR1 gene, suggesting that C. albicans may possess more than one MDR-like gene. We conclude that C. albicans may possess one or more additional genes encoding ATP binding cassette MDR-like proteins that are distinct from CDR 1 and which could participate in the development of fluconazole resistance.
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PMID:New evidence that Candida albicans possesses additional ATP-binding cassette MDR-like genes: implications for antifungal azole resistance. 914 73

Health districts in England, Wales, and Northern Ireland were surveyed in 1996 to collect summary information about people with diagnosed HIV infection who received care under the statutory services in 1995. The survey provided demographic and epidemiological information about the prevalent caseload by area of residence, and the extent to which patients with diagnosed HIV infection travelled to obtain care related to it. A total of 13362 people with diagnosed HIV infection were reported to be resident and treated in England, Wales, or Northern Ireland in 1995. Forty-four per cent of these were treated outside the health district where they lived, with regional specialist centres attracting patients from wider areas. At least 13% received care from more than one treatment centre. This national survey of prevalent diagnosed HIV infections provided public health specialists with information relevant to their own localities without compromising confidentiality. This information complements surveillance data from confidential AIDS case diagnosis reports, laboratory reports of HIV infections, and the unlinked anonymous HIV prevalence monitoring programme, all of which contribute to the assessment and projection of demands on health and social services, and provide evidence on which to develop and direct national and local health campaigns.
Commun Dis Rep CDR Rev 1997 May 30
PMID:Results from the 1995 survey of prevalent clinically diagnosed HIV infection in England, Wales, and Northern Ireland. 918 80

Accurate estimates of expected survival times and survival rates of AIDS patients are important both for estimating the prognosis of individuals and for monitoring the progress of the HIV/AIDS epidemic as new treatments are introduced. They are also needed for projecting future numbers of AIDS cases. Data on reported AIDS cases held at the PHLS AIDS Centre at the Communicable Disease Surveillance Centre and the Scottish Centre for Infection and Environmental Health confirmed the time, age, and reporting delay effects identified in earlier analyses of the United Kingdom AIDS database. The duration of survival after AIDS is diagnosed has improved since the epidemic began--median survival was 10.6 months in cases diagnosed before 1987 and has been at least 18.4 months in cases diagnosed each year since then. People who are diagnosed younger live longer--median survival fell from 21.6 months at age 15 to 29 to 12.6 months at age 45 or over. Delay in reporting AIDS cases adversely affects survival estimates for cases reported in recent years. Survival was longer in cases reported over a year after diagnosis of AIDS--23.7 months compared with 16.9 months in those reported less than a year after diagnosis. The experience of the hospital, measured by its cumulative AIDS caseload, was an important factor in the survival of men who have sex with men presenting with Kaposi's sarcoma alone or 'other' diagnoses--survival was shorter for cases reported from smaller centres. Men who have sex with men with Pneumocystis carinii pneumonia alone or other opportunistic infections alone who were known to be HIV positive before being diagnosed with AIDS had a shorter survival after being diagnosed than those who were unaware of their HIV infection. This supports the hypothesis that treatment for HIV infection and prophylaxis may extend the period before AIDS develops but reduce the period between developing AIDS and dying.
Commun Dis Rep CDR Rev 1997 Jun 27
PMID:Survival of adults with AIDS in the United Kingdom. 921 23

A profile of sexually transmitted diseases (STDs) and HIV infections among teenagers in England and Wales was obtained from reports of newly diagnosed STDs among teenagers attending genitourinary medicine (GUM) clinics in 1995, laboratory reports of newly diagnosed HIV infections between 1985 when reporting began and the end of 1995, and the prevalence of HIV (unlinked anonymous programme) among teenagers attending genitourinary medicine clinics and antenatal clinics in 1994 and 1995. STD reports were analysed by sex, age group, and place of residence of patients--whether in the NHS Thames regions or elsewhere in England and Wales. High rates of STDs were reported in teenagers, particularly in girls. The incidences of gonorrhoea, chlamydia infection, and first attack genital wart infections were higher in teenage girls than in any other age group. Boys under 16 years of age had substantially higher rates of infection with all STDs in the Thames regions than elsewhere. Rates of gonorrhoea in teenagers of both sexes in the Thames regions were more than twice those in the rest of the country. Infection rates for genital herpes, and chlamydia in girls, were also higher in the Thames regions, although the geographical differences were less marked. The seroprevalence of HIV among heterosexual teenagers was very low. In contrast, 226 HIV infections among teenage boys had probably been acquired through sexual intercourse with other males. Unlinked anonymous testing revealed HIV antibody in 7.5% of routinely collected serology specimens taken from teenage homosexual or bisexual males attending GUM clinics in London. The high rates of STDs among teenage girls and all teenagers in the Thames regions make these groups a high priority for sexual health promotion, with special consideration given to homo/bisexual male teenagers. Detailed surveillance of risk factors for STDs, and further studies of teenage sexual behaviour will help to effectively target resources to improve the sexual health of teenagers in England and Wales.
Commun Dis Rep CDR Rev 1997 Nov 14
PMID:Sexually transmitted diseases among teenagers in England and Wales. 939 59

A retrospective cohort study was performed to examine the extent and clinical significance of misclassification associated with using the current United States AIDS case defining category of an initial CD4 count < or = 200 cells x 10(6)/l (< or = 200) compared with a definition requiring two consecutive counts below this level. The main outcomes examined were the probability of subsequent CD4 counts > 200 x 10(6)/l (> 200) and progression times to AIDS and death. Of the 2025 predominantly male homosexual HIV-positive patients attending two hospital based HIV clinics with initial CD4 cell counts < or = 200, 1524 (75%) subsequently had consecutive counts < or = 200, but only half did so at the next CD4 count. Ten per cent had either no further or only non-consecutive counts < or = 200, and 15% had only one CD4 count available for analysis. The cumulative proportion of patients with a CD4 count > 200 at one year after a first count of < or = 200 was about twice (39%) that observed among the subgroup with at least two consecutive counts < or = 200 (19%). The times from the initial counts of < or = 200 to AIDS and death were also shorter by six months and two months, respectively, in the subgroup with two or more consecutive counts < or = 200. A significant proportion of patients will be prematurely classified as having a CD4 cell count < or = 200 if a single CD4 count below this level is accepted. A definition of two consecutive counts < or = 200 should be adopted in preference to a single count < or = 200 for natural history studies and clinical trials, in which precise estimates of the time to or from a defined CD4 threshold are important. In surveillance programmes, however, such an approach may be impractical because of missing or infrequent serial CD4 counts, although adjustments can be made based on these estimates of premature misclassification.
Commun Dis Rep CDR Rev 1997 Nov 14
PMID:CD4 cell counts of 200 x 10(6)/1 or below in natural history studies and surveillance: is one enough or are two better? 939 60

Fluconazole-resistant Candida albicans, a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as a cause of candidiasis in patients receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses of a series of C. albicans isolates from an MT patient who developed disseminated candidiasis caused by an azole-resistant strain 2 weeks after initiation of fluconazole prophylaxis (K. A. Marr, T. C. White, J. A. H. vanBurik, and R. A. Bowden, Clin. Infect. Dis. 25:908-910, 1997). DNA sequence analysis of the gene (ERG11) for the azole target enzyme, lanosterol demethylase, revealed no difference between sensitive and resistant isolates. A sterol biosynthesis assay revealed no difference in sterol intermediates between the sensitive and resistant isolates. Northern blotting, performed to quantify mRNA levels of genes encoding enzymes in the ergosterol biosynthesis pathway (ERG7, ERG9, and ERG11) and genes encoding efflux pumps (MDR1, ABC1, YCF, and CDR), revealed that azole resistance in this series is associated with increased mRNA levels for members of the ATP binding cassette (ABC) transporter superfamily, CDR genes. Serial growth of resistant isolates in azole-free media resulted in an increased susceptibility to azole drugs and corresponding decreased mRNA levels for the CDR genes. These results suggest that C. albicans can become transiently resistant to azole drugs rapidly after exposure to fluconazole, in association with increased expression of ABC transporter efflux pumps.
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PMID:Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. 975 59


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