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)

The nonsegmented negative strand (NNS) RNA viruses include some of the mosr problematic human, animal and plant pathogens extant: for example, rabies virus, Ebola virus, respiratory syncytial virus, the parainfluenza viruses, measles and infectious hemapoietic necrosis virus. The key feature of transcriptional control in the NNS RNA viruses is polymerase entry at a single 3' proximal site followed by obligatory sequential transcription of the linear array of genes. The levels of gene expression are primarily regulated by their position on the genome. The promoter proximal gene is transcribed in greatest abundance and each successive downstream gene is synthesized in progressively lower amounts due to attenuation of transcription at each successive gene junction. In addition, NNS RNA virus gene expression is regulated by cis-acting sequences that reside at the beginning and end of each gene and the intergenic junctions. Using vesicular stomatitis virus (VSV), the prototypic NNS, many of these control elements have been identified.The signals for transcription initiation and 5' end modification and for 3' end polyadenylation and termination have been elucidated. The sequences that determine the ability of the polymerase to slip on the template to generate polyadenylate have been identified and polyadenylation has been shown to be template dependent and integral to the termination process. Transcriptional termination is a key element in control of gene expression of the negative strand RNA viruses and a means by which expression of individual genes may be silenced or regulated within the framework of a single transcriptional promoter. In addition, the fundamental question of the site of entry of the polymerase during transcription has been reexamined and our understanding of the process altered and updated. The ability to engineer changes into infectious viruses has confirmed the action of these elements and as a consequence, it has been shown that transcriptional control is key to controlling the outcome of a viral infection. Finally, the principles of transcriptional regulation have been utilized to develop a new paradigm for systematic attenuation of virulence to develop live attenuated viral vaccines.
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PMID:Transcriptional control of the RNA-dependent RNA polymerase of vesicular stomatitis virus. 1221 62

Interferon (IFN)-gamma, is not only a marker of T(H)1 CD4, CD8 and natural killer (NK) cells, it is also a critical antiviral mediator which is central to the elimination of viruses from the CNS. In this review, we describe IFN-gamma, its receptor, signal transduction from receptor engagement, and antiviral downstream mediators. We demonstrate that although neurons are post-mitotic and non-renewing, they respond to IFN-gamma in a fashion similar to peripheral fibroblasts or lymphocytes. We have illustrated this review with details about studies on the role(s) of IFN-gamma in the pathogenesis of measles virus (MV), herpes simplex virus (HSV) type 1, and vesicular stomatitis virus (VSV) infections of the CNS. For VSV infection, IFN-gamma signals through Jaks 1 and 2 and STAT1 to activate (interferon regulatory factor) IRF-1; although viral protein synthesis is inhibited, PKR is not a critical mediator in the antiviral response to VSV in murine neurons. In contrast, induction of nitric oxide synthase (NOS) type 1 and its production of nitric oxide is essential in the elimination of viruses from neurons.
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PMID:The role of IFN-gamma in immune responses to viral infections of the central nervous system. 1240 79

Spirulina has been used in a variety of practical applications in biotechnology and medical sciences. This paper presents the antiviral activity found in a hot water extract (HWE) of a commercial preparation of Spirulina maxima, studied by a microplate inhibition assay, using several viruses. The HWE inhibited the infection for: herpes simplex virus type 2 (HSV-2), pseudorabies virus (PRV), human cytomegalovirus (HCMV), and HSV-1, and the 50% effective inhibition doses (ED(50)) were 0.069, 0.103, 0.142, and 0.333 mg/ml for each virus, respectively. For adenovirus the inhibition was less than 20%, and no inhibition was found for measles virus, subacute sclerosing panencephalitis virus (SSPE), vesicular stomatitis virus (VSV), poliovirus 1 and rotavirus SA-11, at concentrations of 2 mg/ml of the HWE. The highest antiviral activity was for HSV-2, with a selectivity index of 128. The antiviral activity was not due to a virucidal effect. Herpesvirus infection was inhibited at the initial events (adsorption and penetration) of the viral cycle. To initiate the isolation and identification of the compound that exhibits the antiviral activity of S. maxima, some extracts made by using several solvents with different polarity were evaluated by microplate inhibition assay using HSV-2. The highest antiviral activity was detected in the methanol-water 3:1, which suggests that the antiviral activity is probably due to highly polar compounds.
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PMID:Antiviral activity of Spirulina maxima against herpes simplex virus type 2. 1240 11

RNA viruses are rapidly emerging as extraordinarily promising agents for oncolytic virotherapy. Integral to the lifecycles of all RNA viruses is the formation of double-stranded RNA, which activates a spectrum of cellular defense mechanisms including the activation of PKR and the release of interferon. Tumors are frequently defective in their PKR signaling and interferon response pathways, and therefore provide a relatively permissive substrate for the propagation of RNA viruses. For most of the oncolytic RNA viruses currently under study, tumor specificity is either a natural characteristic of the virus, or a serendipitous consequence of adapting the virus to propagate in human tumor cell lines. Further refinement and optimization of these oncolytic agents can be achieved through virus engineering. This article provides a summary of the current status of oncolytic virotherapy efforts for seven different RNA viruses, namely, mumps, Newcastle disease virus, measles virus, vesicular stomatitis virus, influenza, reovirus, and poliovirus.
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PMID:RNA viruses as virotherapy agents. 1252 35

The biological therapy of tumors using live viruses was first proposed a century ago but was abandoned due to potential virulence of wild-type strains. Thanks to advances in recombinant technology, replication-restricted strains have been genetically engineered, which replicate selectively within tumor cells. Examples include replication-competent mutants of herpes simplex virus (HSV), adenovirus, vesicular stomatitis virus, reovirus and measles virus. Replication-restricted oncolytic viruses are able to propagate selectively within solid tumor nodules exerting direct antitumor activity by killing infected tumor cells at the completion of a replicative cycle. In the process, they generate an intratumoral inflammatory response, which under the appropriate circumstances, may trigger the activation of an adaptive antitumor immune response, a process that has been named in situ tumor vaccination. Recombinant HSV may offer distinct advantages in oncolytic therapy of epithelial tumors. HSV is highly infectious to tumors of epithelial origin, resulting in high efficacy, there is considerable redundancy in HSV receptors, which makes the loss of HSV receptors by tumors due to mutations less likely and potent anti-herpetic drugs are commercially available, which may be used clinically to control undesired side effects. Herewith we describe the use of oncolytic viral therapy against intraperitoneal malignancies with special emphasis on oncolytic herpes simplex virus. We review the preclinical evidence on the efficacy and safety of intraperitoneal applications of HSV and discuss the rationale for its use for oncolytic therapy and in situ tumor vaccination of intraperitoneal tumors.
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PMID:Intraperitoneal oncolytic and tumor vaccination therapy with replication-competent recombinant virus: the herpes paradigm. 1265 5

Noma (necrotizing ulcerative stomatitis, stomatitis gangrenosa, or cancrum oris) is a devastating orofacial gangrene that occurs mainly among children. The disease has a global yearly incidence of 140,000 cases and a mortality rate of approximately 90 percent. Patients who survive noma generally suffer from its sequelae, including serious facial disfigurement, trismus, oral incontinence, and speech problems. The medical history of noma indicates that the disease was already known in classical and medieval civilizations in Europe. In the sixteenth and seventeenth centuries, Dutch chirurgeons clearly described noma as a clinical entity and realized that the popular name "water canker" was not sufficient, because this quickly spreading ulceration in the faces of children was different from "cancer." In the eighteenth century, awareness that noma is related to poverty, malnutrition, and preceding diseases such as measles increased in northwestern Europe. In the first half of the nineteenth century, extensive surgical procedures were described for the treatment of the sequelae of noma. At the end of that century, noma gradually disappeared in the Western world because of economic progress, which gave the poorest in society the opportunity to feed their children sufficiently. Only in the twentieth century were effective drugs (sulfonamides and penicillin) against noma developed, as well as adequate surgical treatment for the sequelae of noma. These modes of treatment remain inaccessible for the many present-day victims of noma because of their extreme poverty. The only truly effective approach to the problem of noma throughout the world is prevention, namely, combating the extreme poverty with measures that lead to economic progress. In the meantime, medical doctors in the Western world should not forget their own history and ignore this global health problem; rather, they should face "the face of poverty" with the eyes of mercy and concern suited to their profession.
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PMID:A history of noma, the "Face of Poverty". 1265 18

Noma (cancrum oris, stomatitis gangrenosa) is a quickly spreading orofacial gangrene in children, caused by a combination of malnutrition, debilitation because of concomitant diseases (measles) and intraoral infections. The global incidence of noma in the world is uncertain. By comparing large numbers of noma patients and cleft lip patients in a large referral hospital for these disorders in Sokoto, Nigeria, we calculated the incidence of noma in north-west Nigeria as 6.4 per 1000 children. Extrapolation of this incidence to the developing countries bordering the Sahara Desert (the noma belt of the world) gives an incidence of 25,600 for that region and a global incidence of 30,000-40,000. Noma is a good biological parameter of extreme poverty, and hence a global monitoring system for noma can be justified. Though economic progress is the most effective preventive measure against noma, medical prevention by vaccination programmes against measles should be enhanced as well.
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PMID:An estimation of the incidence of noma in north-west Nigeria. 1275 33

The vaccine or Vero cell-adapted strains of measles virus (MV) have been reported to use CD46 as a cell entry receptor, while lymphotropic MVs preferentially use the signalling lymphocyte activation molecule (SLAM or CD150). In contrast to the virus obtained from patients with acute measles, little is known about the receptor that is used by defective variants of MV isolated from patients with subacute sclerosing panencephalitis (SSPE). The receptor-binding properties of SSPE strains of MV were analysed using vesicular stomatitis virus pseudotypes expressing the envelope glycoproteins of SSPE strains of MV. Such pseudotype viruses could use SLAM but not CD46 for entry. The pseudotype viruses with SSPE envelope glycoproteins could enter Vero cells, which do not express SLAM. In addition, their entry was not blocked by the monoclonal antibody to CD46, pointing to another entry receptor for SSPE strains on Vero cells. Furthermore, the unknown receptor(s), distinct from SLAM and CD46, may be present on cell lines derived from lymphoid and neural cells. Biochemical characterization of the receptor present on Vero cells and SK-N-SH neuroblastoma cells was consistent with a glycoprotein. Identification of additional entry receptors for MV will provide new insights into the mechanism of spread of MV in the central nervous system and possible reasons for differences between MVs isolated from patients with acute measles and SSPE.
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PMID:Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis. 1286 45

After passive transfer of measles virus (MV)-specific antibodies, vaccine-induced seroconversion and subsequent protection is inhibited in cotton rats (Sigmodon hispidus). In this system, an attenuated, recombinant vesicular stomatitis virus expressing the MV haemagglutinin (VSV-H) was found previously to induce neutralizing antibodies and protection against MV challenge after intranasal (i.n.) immunization. Here it is demonstrated that, after i.n. immunization, VSV-H is found in both lung and brain tissue in the absence of clinical signs. Intratracheal inoculation, which does not lead to infection of the brain, proved that immunization via the lung mucosa is sufficient to protect. To reduce or eliminate infection of the brain after i.n. inoculation, stepwise-attenuated VSV-H mutants with truncated cytoplasmic tails of the G protein were tested in cotton rats. A mutant with 9 aa in the G cytoplasmic tail was found at much lower levels in the brain and was protective in the absence or presence of MV-specific antibodies. A more attenuated mutant containing only 1 aa in its tail was not found in brain tissue after inoculation, but it still induced protective antibody to measles in the absence of MV-specific antibody. However, its ability to induce MV-neutralizing antibodies in the presence of passively transferred MV-specific antibodies and its protective capacity was abolished unless higher-dose immunizations were used. This study demonstrates that a lower degree of attenuation is required to be able to immunize in the presence of MV-specific antibodies.
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PMID:Successful mucosal immunization of cotton rats in the presence of measles virus-specific antibodies depends on degree of attenuation of vaccine vector and virus dose. 1286 46

Signalling lymphocyte activation molecule (SLAM, also known as CD150), a membrane glycoprotein involved in lymphocyte activation, has two extracellular immunoglobulin superfamily domains, V and C2. It has been shown previously that human SLAM is a cellular receptor for measles virus (MV) and that its V domain is necessary and sufficient for receptor function. Although mouse SLAM has functional and structural similarity to human SLAM, it hardly acts as a receptor for MV. By producing human/mouse chimeric molecules and assessing their receptor function with a vesicular stomatitis virus pseudotype assay, the region at amino acid positions 58-67 was found to be critically responsible for the difference in MV receptor function between human and mouse SLAMs. Exchange of this region allowed mouse SLAM to act as a receptor for MV, almost comparable to human SLAM. Among three amino acid differences (positions 60, 61 and 63) in this region, histidine 61 present in human SLAM was most significant, but combined substitutions with this residue and one or both of isoleucine 60 and valine 63 increased further the receptor activity of mouse SLAM. On the other hand, converse substitution at position 61 compromised receptor function of human SLAM. Thus, histidine 61 and its adjacent residues at positions 60 and 63 are critical for SLAM to act as a receptor for MV. Notably, the pseudotype assay indicated that residues at these three positions are also critical for the function of SLAM as a receptor for canine distemper virus.
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PMID:Histidine at position 61 and its adjacent amino acid residues are critical for the ability of SLAM (CD150) to act as a cellular receptor for measles virus. 1291 59


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