Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A derivative of 5'-noraristeromycin epimeric at the 5'-nor center ((-)-3) has been prepared enantiospecifically in three steps from (+)-((1R,4S)-4-hydroxy-2-cyclopenten- 1-yl acetate. Compound (-)-3 was evaluated for antiviral activity against a large number of viruses and found to display marked activity against varicella-zoster virus, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, reovirus, and cytomegalovirus. A similar antiviral activity spectrum was shown by the S-adenosylhomocysteine hydrolase inhibitors neplanocin A and carbocyclic 3-deazaadenosine. While equally potent as neplanocin A against most of the viruses tested, compound (-)-3 was significantly less cytotoxic. The results of this study suggest that (-)-3 should be pursued for the treatment of those virus infections [that is, pox (VV), rhabdo (VSV), paramyxo (parainfluenza), and reo] that appear to be exquisitively sensitive to the compound.
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PMID:An epimer of 5'-noraristeromycin and its antiviral properties. 817 16

By using an ovine interferon-tau (IFN-tau) cDNA probe, four recombinant phages were isolated from a rabbit genomic library and sequenced from nucleotides -450 to 1,300 relative to the CAP site. Each of the four rabbit genes contains an open reading frame of 595 nucleotides and code for proteins that exhibit structural characteristics of the interferon-omega (IFN-omega) family. They display more than 98% identity in their coding regions. The deduced amino acid sequences share > 96% sequence similarity. In contrast, the 5' and 3' noncoding regions have diverged considerably (approximately 50% identity). Amino acid comparisons of rabbit IFN-omega with IFN-omega of other species reveal the highest degree of identity with human (72%), followed by porcine (68%) IFN-omega. Rabbit IFN-omega displays only 57% sequence similarity with ovine IFN-tau. The coding regions of the four genes subcloned in a cytomegalovirus eukaryotic expression vector and transfected in monkey COS-7 cells direct the production of proteins that protect bovine and rabbit cells against vesicular stomatitis virus infection, thus demonstrating that these genes encode fully active IFN proteins. The expression of these genes was studied in Sendai-induced rabbit leukocytes. A single band of poly(A)+RNA hybridized with a rabbit IFN-omega probe under stringent conditions, whereas no IFN-omega transcript was detected with RNA isolated from uninduced leukocytes. Southern blot analysis suggest the existence of at least eight IFN-omega genes or pseudogenes in the rabbit genome.
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PMID:Cloning and structural analysis of four genes encoding interferon-omega in rabbit. 830 Nov 51

Immunostimulating complexes (ISCOMs), containing lipids, the saponin Quil A, and proteinaceous antigens, have been proven to vaccinate effectively CD8+ cytolytic T cells in vivo. However, conventional ISCOM technology is restricted to hydrophobic proteins or fatty acid-derivatized proteins or peptides. We therefore analysed whether Quil A-containing liposomes are an effective vehicle to shuttle hydrophilic proteins or peptides into the MHC class I pathway of antigen presentation resulting in the in vivo induction of antigen-specific cytolytic T cells (CTL). Liposomes were formed by a lipid dry-down method followed by resuspension with an aqueous solution containing protein/peptide and Quil A and then an extrusion step. Quil A-containing liposomes are an effective means to elicit a CD8+ CTL response to peptide antigen in vivo. CTL could be raised in C57B1/6 mice against ovalbumin (OVA) peptide 257-264 and vesicular stomatitis virus nucleoprotein 52-59, as well as in Balb/c mice against listeriolysin peptide 91-99 and cytomegalovirus pp89 168-176, demonstrating the versatility of this approach. The elicited response was peptide-specific, peptide dose-dependent and Quil A was necessary. Vaccination with liposomes entrapping the whole ovalbumin molecule or an extended (OVA) peptide 254-276 also yielded a CTL responsive to the immunodominant OVA peptide 256-264, implying cellular internalization and correct processing. Thus Quil A-containing liposomes appear to be a versatile vehicle to vaccinate CD8+ T cells in vivo; in addition, they could rapidly enhance the understanding of subunit vaccines and rules of antigen processing and peptide-MHC class I binding.
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PMID:Vaccination with immunodominant peptides encapsulated in Quil A-containing liposomes induces peptide-specific primary CD8+ cytotoxic T cells. 830 44

Two women and two men were infected with the human immunodeficiency virus type 1 (HIV-1) transmitted by renal transplantation from i.v. drug-addicted donors in 1984. The four recipients were treated with cyclosporine and methylprednisolone (one patient only for three months because of early graft failure). Two patients died 66 and 74 months after transplantation, one of endocarditis and one of cerebral hemorrhage. Despite several infections including urinary tract infection (n = 8), peritonitis (n = 1), shunt infection (n = 1), bronchitis (n = 1), salmonellosis (n = 1), herpes stomatitis (n = 2), herpes zoster (n = 1), and cytomegalovirus (n = 1), and despite treatment of several rejection episodes (n = 8), none of them had or has infections typical of the acquired immunodeficiency syndrome (AIDS). However, two patients developed cervical lymphadenopathy and one autoimmune thrombocytopenia 15-20 months after HIV-1 infection. Their T helper cell counts (355/microliters to 75/microliters) and helper/suppressor T cell ratios (1.0-0.2) are distinctly lowered. One patient has membranous glomerulopathy with virus-like particles within and on the outside of the basement membrane and tubuloreticular inclusions in glomerular endothelial cells. We evaluated the case reports of 53 patients with HIV-infection caused by an infected transplant or by blood transfusions during or shortly after transplantation. The cumulative incidence of AIDS was significantly lower in 40 transplant patients with an immunosuppressive regimen including cyclosporine than in 13 transplant patients receiving immunosuppressive treatment without cyclosporine (5-year cumulative risk of AIDS: 31% versus 90%, P = 0.001).
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PMID:The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation--data on four cases and review of the literature. 821 77

A series of new polyanions was synthesized via gamma-polymerization, in aqueous micellar solution, of omega-unsaturated anionic surfactants whose polar head was derived from amino acids or dipeptides. The obtained polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1, HIV-2) and various other RNA and DNA viruses. All the test compounds proved active against HIV-1 and HIV-2, their 50% inhibitory concentration (IC50) being in the range of 0.04-7.5 micrograms/mL, while they were not toxic to the host cells (CEM-4 or MT-4) at concentrations up to 100 micrograms/mL or higher. The HIV-inhibitory effect increased with the hydrophilic character of the amino acid moiety. The compounds were found to interact with both the viral envelope glycoprotein gp120 and the cellular CD4 receptor, thus blocking virus-cell binding and virus-induced syncytium formation. These polyanions also proved active against human cytomegalovirus at about the same IC50 as for HIV. In addition, they were also active, albeit at somewhat higher IC50 values (0.8-20 micrograms/mL), against other enveloped viruses such as respiratory syncytial virus and arenaviruses (Junin and Tacaribe). At yet higher IC50 values ( > or = 20 micrograms/mL), some of the compounds showed activity against influenza A virus. No activity was observed with any of the compounds against vesicular stomatitis virus, Sindbis virus, Semliki forest virus, influenza B, parainfluenza type 3, and the nonenveloped viruses Coxsackie type B4, polio type 1, and reovirus type 1.
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PMID:Polyanion inhibitors of human immunodeficiency virus and other viruses. Part 2. Polymerized anionic surfactants derived from amino acids and dipeptides. 864 2

Experimental analyses of the acute cytotoxic T lymphocyte (CTL) response to viruses have focused on studying these infections in immunologically naive hosts. In the natural environment, however, viral CTL responses occur in hosts that are already immune to other infectious agents. To address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific CTL precursor cells (pCTL) not only using the usual experimental paradigm where mice undergo acute infections with a single virus, and in mice immune to a single virus, but also in immune mice after challenge with various heterologous viruses. As determined by limiting dilution assays, the pCTL frequency (p/f) per CD8+ T cell specific for lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), or vaccinia virus (VV) increased during the acute infections, peaking at days 7-8 with frequencies as high as 1/27-1/74. Acute viral infections such as these elicit major expansions in the CD8+ T cell number, which has been reported to undergo apoptosis and decline after most of the viral antigen has been cleared. Although the decline in the total number of virus-specific pCTL after their peak in the acute infection was substantial, for all three viruses the virus-specific p/f per CD8+ T cell decreased only two- to fourfold and remained at these high levels with little fluctuation for well over a year. The ratios of the three immunodominant peptide-specific to total LCMV-specific clones remained unchanged between days 7 and 8 of acute infection and long-term memory, suggesting that the apoptotic events did not discriminate on the basis of T cell receptor specificity, but instead nonspecifically eliminated a large proportion of the activated T cells. However, when one to five heterologous viruses (LCMV, PV, VV, murine cytomegalovirus, and vesicular stomatitis virus) were sequentially introduced into this otherwise stable memory pool, the stability of the memory pool was disrupted. With each successive infection, after the immune system had returned to homeostasis, the memory p/f specific to viruses from earlier infections declined. Reductions in memory p/f were observed in all tested immunological compartments (spleen, peripheral blood, lymph nodes, and peritoneal cavity), and on average in the spleen revealed a 3 +/- 0.4-fold decrease in p/f after one additional viral infection and an 8.4 +/- 3-fold decrease after two additional viral infections. Thus, subsequent challenges with heterologous antigens, which themselves induce memory CTL, may contribute to the waning of CTL memory pool to earlier viruses as the immune system accommodates ever-increasing numbers of new memory cells within a limited lymphoid population. This demonstrates that virus infections do not occur in immunological isolation, and that CD8+ T cell responses are continually being modulated by other infectious agents.
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PMID:Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections. 867 69

The design, synthesis, and antiviral activities of 6'-homoneplanocin A (HNPA, 3) and its congeners having nucleobases other than adenine, such as 3-deazaadenine (4), guanine (5), thymine (6), and cytosine (7), were described. Starting from the known cyclopentenone derivative 8, the optically active (mesyloxy)cyclopentene derivative 15 was prepared, which was condensed with nucleobases then deprotected to give target compounds 3-7. Of these compounds, HNPA showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. HNPA proved particularly active against human cytomegalovirus, vaccinia virus, parainfluenza virus, vesicular stomatitis virus, and arenaviruses, which is compatible with an antiviral action targeted at S-adenosylhomocysteine hydrolase. HNPA appears to be a promising candidate drug for the treatment of these viruses.
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PMID:New neplanocin analogues. 6. Synthesis and potent antiviral activity of 6'-homoneplanocin A1. 869 33

Persistent mucocutaneous ulcers in AIDS represent a variety of disease entities. The purpose of this study was to characterize clinicopathologic features of persistent oral ulcers associated with cytomegalovirus and herpes simplex virus in AIDS. Forty-seven persons infected with HIV with persistent ulcers (mean, 2.4 ulcers/person) were included in this study. A biopsy specimen from a representative ulcer was taken from each patient. Hematoxylin-eosin, periodic acid-Schiff, cytomegalovirus, and herpes simplex virus immunocytochemical stains were performed on tissue sections. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). Mean ulcer size was 1.8 cm with a mean duration of 5.6 weeks. The ulcerogenic viral agents were cytomegalovirus alone in 53% of cases, cytomegalovirus and herpes simplex virus coinfection in 28% of cases, and herpes simplex virus alone in 19% of cases. Treatment response to ganciclovir with or without topical steroids resulted in lesion resolution in the cytomegalovirus and cytomegalovirus/herpes simplex virus groups; however, recurrence/resistance was relatively high (23%). Herpes simplex virus/cytomegalovirus ulcers responded to oral acyclovir in combination with systemic ganciclovir. Increasing the oral acyclovir dosage resulted in resolution of herpes simplex virus-only ulcers in all but one case. Cytomegalovirus and herpes simplex virus are associated with persistent mucocutaneous ulcers in AIDS. These lesions responded to systemic antiviral therapy but are difficult to differentiate from other ulcerogenic diseases such as aphthous major, necrotizing stomatitis, and ulcerations not otherwise specified without biopsy and histopathologic examination.
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PMID:Herpesviridae-associated persistent mucocutaneous ulcers in acquired immunodeficiency syndrome. A clinicopathologic study. 870 89

The authors review the literature on aetiopathogenesis and therapeutic management of recurrent aphthous stomatitis. The data regarding the role of genetic, nutritional and microbiological factors in the genesis of recurrent aphthous stomatitis has been particularly examined. Despite significant associations with some antigens HLA have been reported in Southern Europe, there is no clear genetic predisposition in recurrent aphthous stomatitis. Several studies have analyzed the importance of iron, folic acid and vitamin B12 deficiencies, gluten intolerance and sensitivity to certain foods in the triggering of recurrent aphthous stomatitis however the results have been controversial. Recently, it has been suggested that recurrent aphthous stomatitis could be caused by reactivation of varicella-zoster virus and/or cytomegalovirus but these viruses may be reactivated by the immunodysregulation known to underlie recurrent aphthous stomatitis. Moreover, antiviral drugs appear to have only an equivocal effect on recurrent aphthous stomatitis. Recurrent aphthous stomatitis is probably determined by immunological mechanisms although there actually no unifying hypothesis which attempt to integrate the results of the many immunologic studies on recurrent aphotous stomatitis. Moreover, the target antigen and the cause of recurrences of recurrent aphthous stomatitis are still unknown. As far as the management of this disease it is important to recognize recurrent aphthous stomatitis secondary to systemic diseases like Behcet's syndrome, gluten enteropathy and haematinics deficiencies. Subsequently, the symptoms can be reduced with several drugs (mainly topical corticosteroids) but there are no effective therapies preventing recurrences.
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PMID:[Recurrent aphthous stomatitis: current etiopathogenetic and therapeutic concepts]. 872 Dec 6

The synthesis of some new aminoadamantane derivatives is described. The new compounds were evaluated against a wide range of viruses [influenza A H1N1, influenza A H2N2, influenza A H3N2, influenza B, parainfluenza 3, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), thymidine kinase-deficient (TK-) HSV-1, vaccinia, vesicular stomatitis, polio 1, Coxsackie B4, Sindbis, Semliki forest, Reo 1, varicella-zoster virus (VZV), TK- VZV, human cytomegalovirus (HCMV), and human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)]. Some of them proved markedly active against the influenza A H2N2 (compounds 4a,b, 5a, 6a, and 7a), H3N2 (compounds 5a, 6a, and 7a), and H1N1 (compounds 4b,c and 6d). Since compounds 5a, 6a, and 7a, amantadine, and rimantadine showed the same comparative pattern of potency against influenza strains H2N2, H3N2, and B, it may postulated that they act according to a similar mechanism, with regard to their "amine" effect, on the M2 ion channel of influenza A (H1N1, H2N2, or H3N2). In general, no significant activity was noted with any of the new compounds against any of the other viruses tested, making their activity against influenza virus more specific and striking. Borderline activity was noted with some of the compounds (4b,c, 5a-c, and 8a) against HIV-1.
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PMID:Synthesis and antiviral activity evaluation of some new aminoadamantane derivatives. 2. 876 14


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