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PubMed2000

VIP and peptides related to activity-dependent neurotrophic factor protect PC12 cells against oxidative stress.

Oxidative stress is a common associative mechanism that is part of the pathogenesis of many neurodegenerative diseases. Vasoactive intestinal peptide (VIP) is a principal neuropeptide associated with normal development and aging. We have previously reported that VIP induced the secretion of proteins from glial cells, including the novel survival-promoter: activity-dependent neurotrophic factor (ADNF). ADNF-9, a nine amino acid peptide derived from ADNF, protects neurons from death caused by various toxins. In the present study, we examined the neuroprotective effect of VIP against oxidative stress in a pheochromocytoma cell line (PC12). In addition, a lipophilic derivative of VIP, Stearyl-Nle17-VIP (SNV), and two femtomolar-acting peptides: ADNF-9 and a 70% homologous peptide to ADNF-9, NAP were tested as well. PC12 cells were treated with 100 microM H2O2 for 24 h resulting in a reduction in cell survival to 35-50% as compared to controls. Addition of VIP or SNV prior and during the exposure to100 microM H2O2 increased cell survival to 80-90% of control values. Culture treatment with ADNF-9 or NAP in the presence of 100 microM H2O2 increased cell survival to 75-80% of control values. Messenger RNA expression analysis revealed that incubation with VIP resulted in a twofold increase in VIP mRNA, whereas NAP treatment did not cause any change in VIP expression, implicating different mechanisms of action. Furthermore, addition of an ADNF-9 antibody prevented the ability of VIP to protect against oxidative stress, suggesting that VIP protection is partially mediated via an ADNF-like protein.

Animals↗

PubMedDate not supplied

Hantavirus infection in children in Argentina.

Clinical hantavirus infection was diagnosed in five Argentine children ages 5 to 11 years by immunoglobulin M (IgM)- capture enzyme-linked immunosorbent assay using Sin Nombre virus (SNV) antigens. Death in three of the children was associated with absence of detectable IgG to SNV antigens. An additional two cases in healthy children were studied: one, a breast-fed 15-month-old whose mother died of suspected hantavirus pulmonary syndrome (HPS) 8 months previously, had hantavirus IgG (> 1:6400); a second, whose mother survived HPS during month three of pregnancy, apparently had maternal antibodies no longer detectable 1 year after birth.

Antibodies, Viral↗

PubMed1996

Cocirculation of multiple hantaviruses in Texas, with characterization of the small (S) genome of a previously undescribed virus of cotton rats (Sigmodon hispidus).

An environmental and laboratory investigation was conducted after a fatal childhood case of hantavirus pulmonary syndrome occurred in Deaf Smith County, Texas in May 1995. A trapping campaign was conducted to identify possible rodent carriers. Six species of murid and heteromyid rodents were collected, and at least one hantavirus-seropositive specimen was found in each of the five murid species. Tissues from a selection of 11 seropositive specimens were examined by the polymerase chain reaction (PCR) and sequencing of viral genetic material. The predominant hantavirus was El Moro Canyon virus (ELMCV), which occurred in three of three harvest mice (Reithrodontomys megalotis) and in three of four deer mice (Peromyscus maniculatus) examined. Sin Nombre virus (SNV) was found in one deer mouse and one white-footed mouse (P. leucopus). A seropositive house mouse (Mus musculus) was negative by PCR. Two cotton rats (Sigmodon hispidus) were infected by a virus of novel genotype (Muleshoe virus [MULEV]) that bears closet resemblance to Bayou hantavirus. The sequence of the complete small genomic segment was determined for one MULEV, and high-level expression of its nucleocapsid protein was induced in Escherichia coli. Serologic studies indicated that the most likely etiologic agent in the human infection was SNV.

Adolescent↗

PubMed1998

Small mammal survival and trapability in mark-recapture monitoring programs for hantavirus.

Following the 1993 hantavirus pulmonary syndrome (HPS) epidemic in the south-western United States, mammalogists and epidemiologists instituted long-term studies to monitor population density and prevalence of infection in rodents which constitute the reservoir for Sin Nombre virus (SNV). In this study, field techniques used in sampling small mammals for SNV infection were evaluated to determine if trapping and handling protocols were having significant effects on future trapability or mortality of animals. We compared rodent mark-recapture control plots, on which all rodents were simply measured, marked, and released on site, with experimental plots on which all animals were anesthetized with methoxyflurane, sampled for blood and saliva, measured, marked, and released. Blood samples were obtained from anesthetized animals on the experimental plots via a retro-orbital sinus puncture using a heparinized capillary tube. Dacron tipped oral swabs were used to collect buccal cells and saliva from the rodent's oral cavity. Field data were collected monthly from August 1994 to August 1996 at two sites in New Mexico (USA). Analyses were based on 3,661 captures of 1,513 individuals representing 21 species from three rodent families (Rodentia: Muridae, Heteromyidae, Sciuridae) and two species of rabbits (Lagomorpha: Leporidae). Overall, for most murid rodents (including five Peromyscus spp., Neotoma albigula, and Onychomys leucogaster) and one rabbit species (Sylvilagus floridanus), the handling/bleeding procedures had no significant effects on recapture rates or mortality. In contrast, several species of heteromyids (Dipodomys ordii and Perognathus flavus), one murid (Reithrodontomys megalotis) and one leporid (S. auduboni) suffered higher mortality rates, and heteromyid kangaroo rats (D. ordii and D. merriami) exhibited lower trapability as a result of the anesthesia and sampling procedures. In view of the overall non-significant influence of the sampling procedures on murid rodents, the anesthesia and blood/saliva sampling protocols described herein appear to be appropriate for hantavirus research, and may serve as a model for environmental monitoring of other zoonotic agents and their reservoirs.

Animal Welfare↗

PubMed2001

Serologic evidence of hantavirus infection in sigmodontine rodents in Mexico.

Antibodies to hantaviruses in two species of sigmodontine rodents (Peromyscus maniculatus and Reithrodontomys sumichrasti) collected in central Mexico are reported. Peromyscus maniculatus, a common species throughout much of Mexico, is the reservoir of Sin Nombre virus (SNV), the etiologic agent of the great majority of cases of hantavirus pulmonary syndrome (HPS) in North America. Although the identity of the virus detected in P. maniculatus in Mexico could not be determined by these serologic results, our findings suggest that SNV may occur throughout the range of P. maniculatus in North America. If true, the failure to identify HPS in Mexico is not due to the absence of pathogenic hantaviruses in Mexico.

Animals↗

PubMed2003

Rapid and simple method for screening wild rodents for antibodies to Sin Nombre hantavirus.

Sin Nombre hantavirus (SNV) is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in the United States and Canada. Hantavirus cardiopulmonary syndrome is a zoonotic disease. The most common reservoir is the deer mouse (Peromyscus maniculatus), although numerous other species of wild rodent can carry the viruses that cause HCPS throughout the Americas. Infected rodents show no signs of clinical disease but they develop persistent infection. Sin Nombre virus can be contracted by exposure to feces, urine, or saliva of its rodent reservoirs. Detection of infection in rodents is most often based upon detection of specific antibodies; many laboratories use enzyme linked immunosorbent assays (ELISAs), which require a specialized electrical ELISA reader. Enzyme linked immunosorbent assay readers are not readily amenable to field usage. We describe a portable test, the strip immunoblot assay (SIA), which we have utilized in field diagnosis. The test can be conducted in approximately 6 hr during the day or can be conducted overnight. The test can be used to detect rodents positive for SNV antibody while they are in traps. We show that results with the SIA have excellent concordance with western blot and reverse transcriptase polymerase chain reaction tests.

Animals↗

PubMed2000

[The partial nucleotide sequence of L segment of Hantavirus strain].

OBJECTIVE: To study the nucleotide sequence of L segment of Hantavirus strain A9. METHODS: The partial L segment cDNA of A9 strain was amplified by PCR, the PCR product was sequenced. RESULTS: The nucleotide sequence of partial L segment of A9 strain was provided, the sequence was A, T rich, similar to other Hantaviruses, and similar to both M, S segments. Compared with nucleotide sequences from other Hantaviruses, it revealed a higher homology to HTN virus strain 76-118,83.5% at nucleotide level and 96.7% at deduced amino level. SNV, PUU and Tula viruses shared the lower homology. A9 and 76-118 were at same cluster in phylogenetic analysis, close to SEO virus but not to PUU, SNV, Tula viruses. Comparing of partial nucleotide sequence of strain A9 with 76-118, some conserved regions were found, but also some regions of A9 were more conserved to other viruses not 76-118. It suggested that when design the primers for L segments amplification, more than one type of Hantavirus sequence should he concerned. Like the homology from M and S segments of Hantaviruses, the viruses isolated from same host animal showed high homology. CONCLUSIONS: Nucleotide sequence of L segment of Hantavirus strain A9 revealed homology between 85.2% -70.8% to different types of Hantavirus and shared a higher homology of 85.2% to strain 76-118.

Animals↗

PubMed2005

A longitudinal study of Bayou virus, hosts, and habitat.

What is currently known about the ecology of North American hantaviruses has come largely from studies on Sin Nombre virus (SNV). We conducted a longitudinal study of Bayou virus (BAYV), the second-leading agent of hantavirus pulmonary syndrome in the United States. Antibodies to hantavirus were detected from Oryzomys palustris (most commonly infected species), Sigmodon hispidus, Peromyscus leucopus, Reithrodontomys fulvescens, and Baiomys taylori. However, only O. palustris had viral RNA in tissues and excreta, suggesting that antibodies detected in other species may have resulted from spill-over infection. Seroprevalence rates averaged around 16% for O. palustris and varied seasonally. The heaviest males exhibited the highest levels of seroprevalence. Seroprevalence was higher in coastal prairie (20.0%) than old-fields (10.5%) and was associated with host abundance. These patterns are similar to those of SNV and can be used in identification of potentially at-risk areas.

Animals↗

PubMedDate not supplied

Latent hepatitis B virus (HBV) infection in systemic necrotizing vasculitis.

We have investigated hepatitis B virus (HBV) infection in systemic necrotizing vasculitis (SNV). Our approach included the detection of the viral surface antigen (HBsAg) with a radioimmunoassay employing monoclonal anti-HBs (m-RIA); in addition, HBV DNA was looked for in serum and peripheral mononuclear blood cells. Among 28 subjects with SNV, 12 were found to be positive for HBsAg with the conventional test (p-RIA) and 7 additional subjects had anti-HBc and/or anti-HBs. From the 16 HBsAg negative individuals, 9 had HBsAg epitopes identified in serum with the m-RIA test and 1 had a low amount of circulating viral DNA. In contrast, only 1 among 6 subjects with other systemic vasculitis showed a positive test for m-RIA and HBV DNA assays; this individual had acquired HIV infection through transfusions which were also probably the source of his HBV infection. HBV DNA sequences were identified in peripheral mononuclear blood cells of 9 from the 37 tested, including 2 individuals who were HBsAg positive only with m-RIA. Therefore, our study indicates a much higher rate of HBV infection in patients with polyarteritis nodosa than previously suspected.

Antibodies, Monoclonal↗

PubMed2006

[First serological evidence of Hantavirus infection in rodents in Colombia].

OBJECTIVE: Determining Hantavirus infection prevalence in rodents in the C6rdoba department, Colombia. METHODS: Rodents were captured using Sherman live-capture traps (8 x 9 x 23 cm; Sherman Traps, Inc., Tallahassee, FL) in peridomestic areas of Córdoba. Hantavirus IgG antibodies were detected by ELISA using Sin Nombre virus (SNV) recombinant nucleocapsid antigen (CDC, Atlanta, Georgia, USA). RESULTS: 336 rodents were captured in 11 townships in the Córdoba department (Murinae: 249; Sigmodontinae: 68; Heteromyidae: 17; Echimyidae: 2; 8.5% overall trap success) during 79 nights of trapping between January 2003 and November 2004. Hantavirus antibody seroprevalence was 2.1% (7 out of 336 captures). Prevalence by genus varied between 5.9% (1 out of 17 Heteromys) to 50% (1 out of 2 Proechimys). CONCLUSIONS: SNV-reactive antibody prevalence in rodents in Córdoba, Colombia, indicated that at least one hantavirus is endemic in rodents in northern Colombia and is frequently transmitted to rural residents.

Animals↗

PubMed2006

Use of IgG avidity to indirectly monitor epizootic transmission of sin nombre virus in deer mice (Peromyscus maniculatus).

An IgG avidity assay was developed to differentiate deer mice that had recently acquired Sin Nombre virus (SNV) from those that were infected in the distant past. Using this procedure, low avidity antibodies were predominantly detected in experimentally infected deer mice (89.5%) within the first 30 days post-inoculation. The assay was then applied to sera from naturally infected deer mice collected during a field investigation associated with a cluster of hantavirus pulmonary syndrome cases. A higher proportion of seropositive mice collected during the outbreak had serum with low avidity antibodies (16.7%) when compared with mice trapped four months later (5.7%). Sin Nombre virus RNA was detectable in blood in a similar fraction of low- (45%) and high- (38.7%) avidity groups. Non-adult mice were more likely to contain low-avidity antibodies (44.4%) than were adults (9.6%). Our results indicate that the IgG avidity assay shows promise as a tool to better characterize epizootic intensity and to identify factors involved in SNV transmission.

Animals↗

PubMed1988

The lung in systemic vasculitis.

Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible.

Churg-Strauss Syndrome↗

PubMed1980

Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature.

Typical Cogan syndrome (CS) is a disease of young adults consisting of flares of interstitial keratitis (IK) and sudden onset of Ménière-like attacks. The prognosis of typical CS is excellent with life-threatening aortic insufficiency (AI) developing in only 10% of reported cases. Serious systemic necrotizing vasculitis (SNV) rarely, if ever, complicates typical CS. Atypical S (vestibuloauditory dysfunction with types of inflammatory eye disease other than IK) frequently overlaps other defined rheumatologic syndromes, is associated with vasculitis in 21% of cases, and carries a less favorable prognosis than typical CS. Topical ocular corticosteroids can usually control IK, and a short trial of systemic corticosteroids is warranted as soon as possible after the onset of hearing loss. SNV should be treated initially with prednisone and may also require the administration of cytotoxic agents, while aortitis and AI can be controlled with the administration of prednisone and surgical replacement of the aortic valve.

Adolescent↗

PubMed2026

SeqQC-former: A sequence-quality fusion framework for QC-aware review prioritization of candidate somatic SNVs in cancer genomics.

The accurate prioritization of candidate somatic single-nucleotide variants (SNVs) remains a challenge due to the substantial variability in sequencing quality across genomic loci. SeqQC-Former is a sequence-quality fusion framework that integrates the local nucleotide context with read-level quality-control (QC) covariates derived from matched tumor-normal sequencing data. This integration generates QC-aware prioritization scores for the downstream review of candidate variants. Unlike conventional variant callers, SeqQC-Former is designed not to infer biological truth but to support post-calling review and prioritization under heterogeneous sequencing conditions. The framework was trained and evaluated on a SEQC2-derived dataset comprising 89,447 candidate loci, including 1378 positive and 88,069 negative loci. In chromosome-held-out validation, which aims to reduce potential genomic-position leakage, SeqQC-Former demonstrated strong discrimination (AUROC = 0.9479; AUPRC = 0.9448), indicating good generalization to previously unseen chromosomes. Given that the SEQC2-derived labels contain QC-associated information; these results should be interpreted as an evaluation of QC-aware prioritization capability rather than an independent validation of biological variant correctness. Ablation analyses revealed that structured QC covariates provided the dominant predictive signal under the current SEQC2-derived labeling regime. SeqQC-Former achieved a significantly higher AUROC than classical machine-learning baselines, as determined by DeLong's test (p < 0.01). Application to 53,164 glioblastoma variants demonstrated that external predictions were sensitive to QC scaling and threshold selection, underscoring that model outputs should be interpreted as QC-dependent prioritization scores rather than calibrated probabilities or definitive biological classifications. Overall, SeqQC-Former offers a reproducible post-calling QC-aware prioritization framework for large-scale somatic SNV review and underscores the importance of explicitly modeling sequencing-quality information when interpreting structured cancer genomics datasets.

Humans↗

PubMed1992

Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus. III: Polyclonal origin of adjacent ventricular myocytes.

Replication-incompetent variants of the avian spleen necrosis virus (SNV) encoding cytoplasmic or nuclear-directed beta-galactosidase (beta-gal) have been used to trace the clonal growth of myocytes during left ventricular free-wall formation. Tubular-stage hearts were infected with a mixed suspension of both retroviruses and, after hatching, the progeny of marked cells in the ventricular wall were examined by X-gal histochemistry. When a small number of virions was introduced individual blue patches contained myocytes with only one label type (cytoplasmic or nuclear). These results confirmed our previous conclusion that each cluster or patch represents a single clone (Mikawa et al., 1992, Dev. Dynamics, 193:11-23). Each of these clones formed a clone-shaped patch which often extended through the entire thickness of the ventricular myocardium, but typically each patch was heterogeneous, containing a mixture of labeled and unlabeled cells. We then asked whether the two populations of myocytes in each patch were clonally related or generated from more than one progenitor. When hearts were infected with high titer viral suspensions many patches were observed in which cytoplasmic-tagged myocytes were intermingled with nuclear-tagged myocytes. Thus, the cone-shaped myocyte patches in the ventricular wall are polyclones derived from separate progenitors in the precardiac mesoderm. This finding led us to examine the separation of clonally related ventricular myocytes in the developing hearts. Embryos were infected with retroviral suspensions at varying stages of development and the resulting colonies examined after hatching.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

Fluorescence spectroscopy as a tool for monitoring solubility and aggregation behavior of beta-lactoglobulin after heat treatment.

Denaturation and aggregation of whey proteins are of interest to the food and pharmaceutical industry due to the importance of final structure in functionality, impact on food texture, and the chemical stability of the final product. In this study, we demonstrate the potential of fluorescence spectrometry combined with multivariate chemometric methods for quantifying solubility and aggregation behavior of beta-lactoglobulin (beta-LG); a major whey protein and a frequent food ingredient. Heat-induced aggregation of beta-LG was studied under different conditions including pH, temperature and heating durations. Results showed very good agreement between the fluorescence-based predictions and measurements obtained by HPLC and gravimetric analysis regardless of the conditions. Standard normal variate (SNV), a signal preprocessing and filtering tool, was found to enhance the predictive accuracy and robustness of the fluorescence-based model.

Chromatography, High Pressure Liquid↗

PubMed1982

Isolation and characterization of retrovirus-like elements from normal human fetuses.

Retrovirus-like particles have been isolated from normal fetal human plasma and from different embryonic organs collected from late first-trimester fetuses. The majority of the virus-like particles banded at a density region of of 1.19-1.22 g/ml, although lighter particles having a density of 1.15-1.17 g/ml were observed in some fetal tissues. The particles appeared similar to retroviruses when viewed electron-microscopically. They contained reverse transcriptase (RT) which accepted oligo (dG)-poly(C) in Mn+2 over other synthetic template-primers and transcribed heteropolymeric RNAs primed with oligo (dT). The enzyme was partially (40%) inhibited by the antiserum against RT of feline endogenous virus (RD114) and not at all by the antisera against RT of avian myeloblastosis virus (AMV), spleen necrosis virus (SNV) and gibbon ape leukemia virus (GALV). The simultaneous detection test in the presence of actinomycin D revealed that the particles contained high mol. wt. (70 S and 35 S) RNAs. The single-stranded DNA complementary to RNA of the human fetal particle hybridized to DNA obtained from different tissues of human adults, showing that the nucleic acids of the virus-like particles were endogenous. The particles could be isolated only from the embryonic organs during differentiation. This suggests that the retroviral gene expression is correlated with embryonic differentiation. These particles could not be induced and as yet infectivity has not been demonstrated, therefore, they are at present described as retroviral elements, not as retroviruses.

Cell Differentiation↗

PubMed2025

Enrichment of G-to-U Substitution in SARS-CoV-2 Functional Regions and Its Compensation via Concurrent Mutations.

We surveyed single nucleotide variant (SNV) patterns from 5 903 647 complete SARS-CoV-2 genomes. Among 10 012 SNVs, APOBEC-mediated C-to-U (C > U) deamination was the most prevalent, followed by G > U and other RNA editing-related substitutions including (A > G, U > C, G > A). However, C > U mutations were less frequent in functional regions, for example, S protein, intrinsic disordered regions, and nonsynonymous mutations, where G > U were over-represented. Notably, G-loss substitutions rarely appeared together. Instead, G-gain mutations tended to more frequently co-occur with others, with a marked preference in the S protein, suggesting a compensatory mechanism for G loss in G > U mutations. The temporal patterns revealed C > U frequency declined until late 2021 then resurged in early 2022. Conversely, G > U steadily decreased, with a pronounced drop in January 2022, coinciding with reduced COVID-19 severity. Vaccinated individuals exhibited a slightly but significantly higher C > U frequency and a notably lower G > U frequency compared to the unvaccinated group. Additionally, cancer patients had higher G > U frequency than general patients during the same period. Interestingly, none of the C > U SNVs were uniquely identified in 2724 environmental samples. These findings suggest novel functional roles of G > U in COVID-19 symptoms, potentially linked to oxidative stress and reactive oxygen species, while C > U remains the dominant substitution, likely driven by host immune-mediated RNA editing.

SARS-CoV-2↗