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)

A series of 23 Amaryllidaceae isoquinoline alkaloids and related synthetic analogues were isolated or synthesized and subsequently evaluated in cell culture against the RNA-containing flaviviruses (Japanese encephalitis, yellow fever, and dengue viruses), bunyaviruses (Punta Toro, sandfly fever, and Rift Valley fever viruses), alphavirus (Venezuelan equine encephalomyelitis virus), lentivirus (human immunodeficiency virus-type 1) and the DNA-containing vaccinia virus. Narciclasine [1], lycoricidine [2], pancratistatin [4], 7-deoxypancratistatin [5], and acetates 6-8, isonarciclasine [13a], cis-dihydronarciclasine [14a], trans-dihydronarciclasine [15a], their 7-deoxy analogues 13b-15b, lycorines 16 and 17, and pretazettine [18] exhibited consistent in vitro activity against all three flaviviruses and against the bunyaviruses, Punta Toro and Rift Valley fever virus. Activity against sandfly fever virus was only observed with 7-deoxy analogues. In most cases, however, selectivity of the active compounds was low, with toxicity in uninfected cells (TC50) occurring at concentrations within 10-fold that of the viral inhibitory concentrations (IC50). No activity was observed against human immunodeficiency virus-type 1, Venezuelan equine encephalomyelitis virus, or vaccinia viruses. Pancratistatin [4] and its 7-deoxy analogue 5 were evaluated in two murine Japanese encephalitis mouse models (differing in viral dose challenge, among other factors). In two experiments (low LD50 viral challenge, variant I), prophylactic administration of 4 at 4 and 6 mg/kg/day (2% EtOH/saline, sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 100% and 90%, respectively. In the same model, prophylactic administration of 5 at 40 mg/kg/day in hydroxypropylcellulose (sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 80%. In a second variant (high LD50 viral challenge), administration of 4 at 6 mg/kg/day (ip, twice daily for 9 days, day -1 to +7) resulted in a 50% survival rate. In all cases, there was no survival in the diluent-treated control mice. Thus, 4 and 5 demonstrated activity in mice infected with Japanese encephalitis virus but only at near toxic concentrations. To our knowledge, however, this represents a rare demonstration of chemotherapeutic efficacy (by a substance other than an interferon inducer) in a Japanese-encephalitis-virus-infected mouse model.
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PMID:Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances. 133 40

Ten, hitherto unreported, analogues of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (2a, ribamidine) and methyl carboximidate 5 have been synthesized. These include the N-cyano (2b), N-alkyl (2c-e), N-amino acid (2f-h), N,N'-disubstituted (6, 7a,b), and the N-methylated carboxamide (1f) analogues of ribavirin. In addition, a new facile synthesis of carboxamidine 2a was also developed. All compounds were evaluated for biological activity against the following RNA viruses: Punta Toro (PT) and sandfly fever (SF) viruses (bunyaviruses); Japanese encephalitis (JE), yellow fever (YF), and dengue-4 viruses (flaviviruses); parainfluenza type 3 (PIV3), respiratory syncytial virus (RSV), and measles viruses (paramyxoviruses); influenza A and influenza B viruses (orthomyxoviruses); Venezuelan equine encephalomyelitis virus (VEE, alphavirus); human immunodeficiency virus type-1 (HIV-1, lentivirus); the DNA-containing vaccinia (VV) virus (poxvirus); and adeno type 5 (Ad5) viruses. All of the compounds except for 2b and 7a,b exhibited activity against the bunyaviruses such as that observed with 2a; however, higher IC50 values were generally observed. Glycine analogue 2f showed activity in PT-virus-infected mice in terms of increased survivors and decreased markers of viral pathogenicity. Carboxamidine 2a, carboximidate 5, and dimethyl amidine 6 exhibited activity against dengue type-4 virus. Monomethyl amidine 2c demonstrated activity against RSV, PIV3, and, to a lesser extent, influenza A and B. Activity of 2c generally required higher IC50 values than unsubstituted 2a. The latter exhibited hitherto unreported activity against RSV; therapeutic indices for 2a against RSV and PIV3 were greater than 64 and greater than 21. No substantial in vitro activity was observed for any of the compounds tested against Ad5, measles, JE, YF, VEE, or HIV-1. In addition, evidence is presented which argues in favor of a distinct antiviral mechanism of action for carboxamidines, e.g. 6, in contrast to a role as a carboxamide precursor.
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PMID:Synthesis and antiviral evaluation of N-carboxamidine-substituted analogues of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride. 150 8

Many agents are associated with bone marrow failure, including toxins, inherited metabolic defects, ionizing radiation, and viral infection. In most cases, the etiologic agent is unknown. Many of these unclassified cases have symptomatic, immunologic, or epidemiologic similarities to viral infections. Viruses from different taxonomic families have been implicated in bone marrow failure syndromes, and they appear to cause hematosuppression by a variety of mechanisms. Some of the viruses involved in relatively well characterized suppressive interactions will be reviewed, including parovovirus B19, dengue, hepatitis viruses, Epstein-Barr virus, cytomegalovirus and the human immunodeficiency virus.
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PMID:Viruses and bone marrow failure. 165 29

The prevalence of antibodies to hepatitis C virus (anti-HCV) was investigated among different populations in Taiwan, where anti-HCV was detected in 0.8% (24/2,994) of adult volunteer blood donors, 0.1% (1/1,305) of youngsters and children, 12.5% (8/64) of adult volunteer blood donors with elevated alanine aminotransferase (ALT), 36.5% (23/63) of hemodialysis patients, 4.1% (13/318) of male homosexuals, 25.4% (16/63) of cases positive for antibodies to human immunodeficiency virus (anti-HIV), 82.2% (578/703) of intravenous drug users (IVDUs), and 10.3% (23/223) of female prostitutes (FPs). Among patients with chronic liver diseases including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC), the overall prevalence rate for anti-HCV was 34.1% (42/123), and a higher prevalence was noted in hepatitis B surface antigen (HBsAg)-negative cases than in HBsAg-positive cases. The prevalence of anti-HCV in volunteer blood donors and high prevalence found in IVDUs, hemodialysis patients, anti-HIV positive cases, and FPs are consistent with those results from other countries. These findings suggest that hepatitis C virus (HCV) infection is transmitted by both blood-borne and sexual contact routes. Among flavivirus infections, anti-HCV was detected in 0.3% (1/289) and 1.3% (4/310) of Japanese encephalitis and dengue fever patients, respectively. In conclusion, in Taiwan, an area with high endemicity of hepatitis B virus (HBV) infection, the epidemiological status of HCV infection is similar to that observed in other countries, and no serum cross-reactivity was noticed between HCV and flavivirus infections.
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PMID:Prevalence of antibodies to hepatitis C virus (anti-HCV) in different populations in Taiwan. 165 45

Antibody-dependent enhancement of infection (ADE) is an in vitro serological phenomenon--or a group of phenomena--in which viral infection of susceptible cells is modified by the addition of virus-reactive antibody. Evidence suggests that ADE reflects immunologic processes that occur in vivo. Various severe and even fatal viral conditions of humans and animals, including dengue shock syndrome, the "early-death phenomenon" in experimental infections of immune animals, and other vaccine- and immunoglobulin-modified conditions, have been attributed to ADE by some researchers. ADE has caused great concern in relation to the development of vaccines against dengue virus and human immunodeficiency virus. More data are urgently needed on the mechanisms and determinants of ADE and on its alleged role in disease pathogenesis and in vaccine-associated phenomena.
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PMID:Antibody-dependent enhancement of infection and the pathogenesis of viral disease. 781 70

The use of riboprobes for the detection of RNA viral sequences is analyzed. Subgenomic fragments of cDNA from poliovirus type 2, dengue virus type 4 and human immunodeficiency virus type 1, were inserted downstream SP6 and/or T7 promoters in the transcription vectors pGEM-4z or pSP64. RNAs obtained by in vitro transcription in the presence of UTP infinity (32P) were used as probes for the detection of RNA viral sequences from infected cell lines in slot and Northern blot assays. The poliovirus riboprobe (P2-221) was able to detect specific viral sequences; thus, it could be used for the detection of the virus in serum, as well as in residual waters. The human immunodeficiency virus riboprobe (HIV-378), detected viral sequences poly A+RNA from infected cells; thus it can be used as a confirmatory test or as a tool in basic research. Finally, the dengue virus riboprobes (D4-2819 and D4-1134) detected specifically dengue 4 virus; however the sensitivity of the detection could be significantly improved amplifying viral sequences by the polymerase chain reaction (PCR) prior to probe hybridization.
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PMID:[Riboprobes: an alternative in the detection of viral sequences]. 807 29

Emerging and reemerging infections are attracting greater attention from the public health and medical communities. Pathologists and other physicians are increasingly aware of the importance of the subspecialty of infectious disease pathology as a tool for diagnosis, surveillance, and research of emerging infections. In this communication, we describe the role that infectious disease pathologists have played during the last 2 years in broadening our understanding of selected emerging infections, including such examples as new variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, leptospirosis, microsporidiosis, Ebola hemorrhagic fever, and cyclosporiasis. The significance of providing pathology services, especially the autopsy, to patients with potentially hazardous communicable diseases is discussed with the supposition that it is unethical to exclude or withhold health care from a patient based on his or her underlying disease or on risk factors for acquiring a disease. The increasing occurrence of infectious diseases imported into the United States and other nations, including human immunodeficiency virus-1 group O, dengue fever, tuberculosis, malaria, diphtheria and cholera in immigrants and travelers, and Ebola virus in nonhuman primates, emphasizes the necessity for pathologists of having competence with infectious disease pathology. It is critical that new generations of pathologists not only be trained in the subspecialty of infectious disease pathology, but that they also be willing participants in the diagnosis and investigation of infectious diseases. The lack of training programs for infectious disease pathologists, as well as the deficiency in infectious disease pathology support for ongoing and future epidemiologic investigations and research, has led to the broadening of pathology services and initiation of a dedicated section of Infectious Disease Pathology at one of the nation's premier public health institutions, the Centers for Disease Control and Prevention in Atlanta, Ga. Together with preexisting groups of medical and veterinary infectious disease pathologists at universities, the Armed Forces Institute of Pathology, the US Army Medical Research Institute of Infectious Diseases, and the National Institutes of Health, this new program will significantly strengthen the capability of the United States to respond to future challenges of emerging and reemerging infections, both in this country and abroad.
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PMID:Emerging and reemerging infections. Progress and challenges in the subspecialty of infectious disease pathology. 927 4

Metabolites isolated from marine invertebrates, callipeltin A, crambescidin, ptilomycalin A, celeromycalin, gymnochrome B, gymnochrome D and isogymnochrome D previously shown bioactive on either herpes simplex virus 1 or human immunodeficiency virus, were tested on a new in vitro bioassay using the dengue virus 1. Only gymnochrome D and isogymnochrome D isolated from the living fossil crinoid Gymnocrinus richeri are highly potent dengue antiviral agents.
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PMID:In vitro antiviral activity on dengue virus of marine natural products. 953 59

This study presents the disability-adjusted life years (DALYs), a non-monetary economic measure of impact, lost to dengue in Puerto Rico for the period 1984-1994. Data on the number of reported cases, cases with hemorrhagic manifestations, hospitalizations, and deaths were obtained from a surveillance system maintained at the Dengue Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (San Juan, PR). The reported cases were divided into two age groups (0-15 years old and >15 years old), and then multiplied by predetermined factors (10 for 0-15 years; 27 for >15 years) to allow for age-related under-reporting of cases. Severity of dengue was modeled by classifying cases into three groups: dengue fever, dengue with severe manifestations, and hospitalized cases. Each group was assigned a different number of days lost because of dengue-related disability. Dengue caused an average of 658 DALYs per year per million population (SE = 114, range = 145-1,519). A multivariate sensitivity analysis, which simultaneously altered the values of six input variables, produced a mean of 580 DALYs/year/million population, with a maximum average of 1,021 DALYs/year/million population, and a maximum, single-year estimate for 1994 of 2,153 DALYs/million population. The most important input was the number of days lost to classic dengue. The DALYs/year/million population lost to dengue in Puerto Rico are much greater than previous estimates concerning the impact of dengue hemorrhagic fever alone. The loss to dengue is similar to the losses per million population in the Latin American and Caribbean region attributed to any of the following diseases or disease clusters; the childhood cluster (polio, measles, pertussis, diphtheria, tetanus), meningitis, hepatitis, or malaria. The loss is also of the same order of magnitude as any one of the following: tuberculosis, sexually transmitted diseases (excluding human immunodeficiency virus), tropical cluster (e.g., Chagas' disease, leishmaniasis), or intestinal helminths. The results objectively suggest that when governments and international funding agencies allocate resources for research and control, dengue should be given a priority equal to many other infectious diseases that are generally considered more important.
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PMID:Using disability-adjusted life years to assess the economic impact of dengue in Puerto Rico: 1984-1994. 971 44

Ross River virus (RRV) is an indigenous Australian arthropod-borne alphavirus responsible for epidemic polyarthritis (EPA), myalgia, and lethargy in humans. Macrophages and monocytes have been associated with human RRV disease, and previous studies have shown that RRV is capable of infecting macrophages via both a natural virus receptor and by Fc receptor-mediated antibody-dependent enhancement (ADE). Similar to other viruses, such as human immunodeficiency virus and dengue virus, ADE infection results in dramatic RRV growth increases for in vitro macrophage cultures. This study demonstrates that RRV could resist lipopolysaccharide (LPS)-induced antiviral activity in macrophage cultures when infection was via the ADE pathway. Investigation of this infection pathway found that RRV was able to suppress the transcription and translation of key antiviral genes (tumor necrosis factor and inducible nitric oxide synthase) in LPS-stimulated macrophages by disrupting the transcription into mRNA of the genes coding for the associated transcription factors IRF-1 and NF-kappaB. The transcription of non-antiviral control genes was not perturbed by RRV-ADE infection, and de novo protein synthesis also was not significantly affected in RRV-ADE infected cells. The ADE pathway of infection allowed RRV to specifically target antiviral genes in macrophages, resulting in unrestricted virus replication. As ADE has been observed for several virus families and associated with disease and adverse vaccination outcomes, these findings may have broad relevance to viral disease formation and antiviral vaccination strategies.
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PMID:Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. 1095 37


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