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)

Inhibitors of glycoprotein processing, such as castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), have been shown previously to inhibit human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured human cells. In prior experiments, we have tested the toxicity and antiviral efficacy of castanospermine in mice infected with the Rauscher murine leukemia virus (RLV). When compared with 3'-azido-3'-deoxythymidine (AZT, zidovudine), castanospermine was less effective and more toxic. Since the 6-O-butanoyl analog of castanospermine was previously found to have a more favorable activity profile than the parent compound against HIV-1 in cultured cells, we compared the antiviral efficacy of both compounds in parallel in vitro and in vivo in the RLV system. Plaque formation in the XC assay was inhibited with a 50% inhibitory concentration (IC50) of 2.4 microM for the 6-O-butanoyl analog of castanospermine, as compared to 9 microM for castanospermine. For both compounds, concentrations resulting in significant cytotoxicity were about ten times higher. Both compounds significantly decreased HIV-1 env-induced syncytium formation in a novel in vitro assay. In RLV-exposed mice, the 6-O-butanoyl analog showed no advantage over the parent compound: both curves for toxicity as well as antiviral efficacy were super-imposable. We conclude that the 6-O-butanoyl analog of castanospermine as well as castanospermine itself are active antiviral agents in mice and that prolonged oral administration is tolerable. However, in comparison to AZT, their antiviral activity profiles are less favorable.
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PMID:Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and antiviral activity in vitro and in vivo. 198 55

Although atypical gingivitis may be an early indicator of human immunodeficiency virus (HIV) infection, dental caries and periodontal disease has not been investigated in African HIV patients. To correct this gap in the research, the prevalence of dental caries, gingival inflammation, and oral hygiene was measured in 83 male and female acquired immunodeficiency syndrome (AIDS) patients hospitalized in Kinshasa, Zaire, in 1988-89. Most patients were 21-40 years of age; the mean age was 39 years. 32% of these patients has decayed teeth, teeth were missing in 35%, and 5% had fillings. According to the Plaque Index, 69% of the AIDS patients had good oral hygiene. On the other hand, 66% (76% of females and 54% of males) has gingival inflammation, and it was considered severe in 30% of these cases. The only variable that was significantly higher among AIDS patients than healthy individuals in Kinshasa was gingivitis. The high incidence of gingivitis in AIDS patients is most likely a reflection of an impaired immune system and the susceptibility to opportunistic infections. Oral candidiasis was isolated from subgingival plaque in 94% of the cases in this series, suggesting a need for more attention to the role of Candida in the pathogenesis of HIV-related periodontal disease.
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PMID:Prevalence of dental caries, gingivitis, and oral hygiene in hospitalized AIDS cases in Kinshasa, Zaire. 240 61

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), an inhibitor of glycoprotein processing, has been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured cells. In contrast to reverse transcriptase inhibitors, castanospermine targets host enzymes. We have analyzed castanospermine in murine systems, using cultured cells as well as live animals. Plaque formation by Rauscher murine leukemia virus (RLV) was inhibited with a median inhibitory concentration (IC50) of 2 micrograms/ml. RLV-exposed BALB/c mice treated with a 20 day course of castanospermine starting 4 h postinoculation showed a dose-dependent inhibition of splenomegaly. Oral castanospermine therapy given to chronically RLV-infected mice prolonged median survival from 36 to 94 days when compared to untreated controls (p = 0.007). Castanospermine was better tolerated orally than intraperitoneally at the same dose. Toxic effects included weight loss, lethargy, and dose-dependent thrombocytopenia. At the highest intraperitoneal dose, lymphoid depletion occurred in thymus, spleen, and lymph nodes. We conclude that castanospermine is an active antiviral agent in animals and that prolonged oral administration is tolerable; however, when compared to 3'-azido-3'-deoxythymidine in the same murine system, castanospermine was less active and more toxic.
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PMID:In vivo analysis of castanospermine, a candidate antiretroviral agent. 249 48

2 intraoral lesions associated with human immunodeficiency virus (HIV) infection have recently been described: an atypical gingivitis and a rapidly progressive periodontitis. The microbiota associated with these gingival and periodontal lesions was investigated. Subgingival plaque samples were taken from 45 HIV-seropositive homosexual men and from 44 HIV-seronegative control subjects. Each sampled site was clinically and radiographically classified as HIV-associated gingivitis, HIV-associated periodontitis, healthy in an HIV-seropositive subject, or healthy, conventional gingivitis or classical periodontitis in a control subject. Plaque samples were examined by indirect immunofluorescence with polyclonal antisera to detect Bacteroides gingivalis, B. intermedius, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans. Anaerobic culturing was used to detect black-pigmented Bacteroides species, Fusobacterium species, and A. actinomycetemcomitans to confirm the immunofluorescence findings. We detected B. gingivalis, B. intermedius, F. nucleatum, and A. actinomycetemcomitans in significantly more HIV-periodontitis sites (80, 65, 59 and 61% of sites, respectively) and HIV-gingivitis sites (61, 70, 52 and 52%, respectively) than in HIV-seropositive healthy and control sites (p less than 0.05). The results indicate that the microbiota found in HIV-periodontitis is similar to that of classical periodontitis. In contrast, however, the microbiota associated with HIV-gingivitis is strikingly different from that of conventional gingivitis. The similarity in the prevalence of periodontopathic organisms in both HIV-gingivitis and HIV-periodontitis suggests that the HIV-gingivitis lesion may be a precursor to the tissue destruction observed in HIV-periodontitis. Hence, early detection and treatment of the HIV-gingivitis lesion may prevent the rapid and extensive breakdown of periodontal tissues associated with HIV-periodontitis.
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PMID:The microbiology of HIV-associated periodontal lesions. 269 96

Using the MT-4 plaque assay, differences in the plaque-forming ability among various isolates of the human immunodeficiency virus (HIV) were observed. Kinetic studies showed that these differences reflected the enhanced ability of individual HIV to replicate rapidly in T cells and cause cytopathic changes. The plaque-forming HIV all came from patients with disease; no healthy seropositive individuals had these types of isolates. Plaque formation may be a useful assay for identifying pathogenic strains of HIV.
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PMID:MT-4 plaque formation can distinguish cytopathic subtypes of the human immunodeficiency virus (HIV). 326 31

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 {arrow} AKR], virtually all the thymus and spleen cells were shown to be derived from the B6 donor; several immune functions studied in these chimeras were as follows: (a) The chimeric mice were tolerant of histocompatibility antigens of both donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen's splenomegaly assay. The tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. (b) Proliferative responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide as well as natural killer and antibody-dependent cell- mediated cytotoxicity activity of the chimeric mice was normal. (c) Plaque- forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 {arrow} AKR] and [AKR {arrow} B6] chimeras. By contrast, [B6-H-2(k)(E(k)) {arrow} AKR] H-2-compatible chimeras and [AKR {arrow} AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC, however, revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in the [B6 {arrow} AKR] chimeras. This observation favors operationally the concept of adaptive differentiation proposed by Katz et al. (44). (d) Analysis of ability of the chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-l-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB, however, was grossly deficient in [B6 {arrow} AKR] chimeras but normal in [AKR {arrow} AKR], [B6 {arrow} B6], and [E(k) {arrow} AKR] chimeras. These findings indicate that full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective.
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PMID:Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice. 698 46

Expression of human immunodeficiency virus-1 integrase in Escherichia coli, at levels that had no effect on bacterial cell growth, blocked plaque formation by bacteriophages having single-stranded genomic DNA (M13) or RNA (R17, Q beta, PRR1). Plaque formation by phages having double-stranded genomic DNA (T4, PR4) was unaffected. Integrase also inhibited infection by the phagemid M13KO7, but it had no effect on production of phage once infection by M13KO7 was established. This result indicated that integrase affects an early stage in infection. Integrase also inhibited phage production following transfection by either single-stranded or double-stranded (replicative form) M13 DNA, it blocked M13 DNA replication, as assayed by incorporation of radioactive nucleotides into DNA, and it failed to affect bacterial pilus function. These data suggest that integrase interacts in vivo with phage nucleic acid, a conclusion supported by studies in which integrase was shown to have a DNA-binding activity in its C-terminal portion. This portion of integrase was both necessary and sufficient for interference of plaque formation by M13 in the present study. Expression of the N-terminal portion of integrase at the same level as intact integrase had little effect on phage growth, indicating that expression of foreign protein in general was not responsible for the inhibitory effect. The simple bacteriophage assay described is potentially useful for identifying integrase mutants that lack single-stranded DNA binding activity.
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PMID:HIV-1 integrase blocks infection of bacteria by single-stranded DNA and RNA bacteriophages. 820 87

We selected mutants of feline immunodeficiency virus (FIV) that are resistant to 2',3'-dideoxy-2',3'-didehydrothymidine (d4T). Two mutants were selected in cultured cells with a stepwise increase in d4T concentration, resulting in mutants able to replicate in 100 microM d4T. These mutants were three- to sixfold more resistant to d4T than wild-type FIV. They were also cross-resistant to 3'-azido-3'-deoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 9-(2-phosphonylmethoxyethyl)adenine, and they were highly resistant to phosphonoformic acid (PFA). Plaque-purified mutants were isolated from each of the mutant populations. The mutant phenotype was stable, because both of the plaque-purified mutants remained d4T resistant even after three passages in the absence of d4T. One of the plaque-purified mutants, designated D4R-3c, was further characterized. Compared with wild-type reverse transcriptase (RT), RT purified from D4R-3c was 3-fold resistant to inhibition by the 5'-triphosphate of d4T, 10-fold resistant to inhibition by the 5'-triphosphate of AZT, and 6-fold resistant to PFA. D4R-3c had a single point mutation in the RT-encoding region of the pol gene at position 2474, resulting in a Val to Ile mutation at codon 47 of the FIV RT. The role of this mutation in d4T resistance was confirmed by site-directed mutagenesis.
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PMID:Mutants of feline immunodeficiency virus resistant to 2',3'-dideoxy-2',3'-didehydrothymidine. 887 67

The oral cavity is rarely reported to be a site of human immunodeficiency virus (HIV) transmission, despite detectable virus in saliva and relatively frequent prevalence of periodontal disease in HIV-infected persons yielding increased excretion of mononuclear-cell-enriched gingival fluid. To search for possible sources of HIV in saliva, and using the polymerase chain-reaction technique, we sought the presence and shedding patterns of proviral HIV-1 DNA in gingival crevicular fluid in a group of patients previously determined as HIV-1-seropositive. Periodontal status at the collection sites was monitored by several clinical parameters, including Plaque Index, Gingival Index, probing depth, and clinical attachment loss. Gingival crevicular fluid samples were collected by means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of 17 out of 35 HIV-1-infected patients. Its detection correlated significantly with higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+ cell count, the presence of blood in gingival fluid, or oral lesions. There was a significant correlation between clinical attachment loss at the sites of fluid collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline correlation between the latter and probing depth (p = 0.54) in the group of patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results of our study suggest that mononuclear cells present in gingival crevicular fluid and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and increased loss of clinical attachment.
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PMID:Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease. 1100 34

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.
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PMID:Consensus guidelines for the management of plaque psoriasis. 2225 Feb 39


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