Protective cellular immunity against influenza virus induced by plasmid inoculation of newborn mice

The mercury-binding capacity of seleno-DL-methionine and selenium dioxide was assessed in male Wistar rats. Mercury was supplied as fish loaves made of northern pike or rainbow trout. We used a selenium concentration of 3.4 mg/kg fish, about sixfold compared to the equivalent quantity of mercury. Seleno-DL-methionine had a tendency to increase both methyl mercury and total mercury in blood, although it also seemed to reduce the proportion of methyl mercury of total mercury. Selenium dioxide lowered mercury levels by 24-29% both in the blood and in the liver of rats that were fed with northern pike.     

Comparison of selected canine vaccines for their ability to induce protective immunity against canine parvovirus infection

BACKGROUND AND AIMS: The ingestion of a corrosive agent including strong alkaline material causes serious caustic damage to the upper gastrointestinal tract. We describe four cases in patients who had ingested alkaline substances. MATERIAL AND METHODS: During the years 1992-1996, four patients who had ingested strong alkali were treated in the Oulu University Hospital. The patients were reviewed retrospectively. RESULTS: In one case a third-degree, in two cases a second-degree and in one case a first-degree injury developed in the oesophagus. The patient with first-degree injury was treated with repeated endoscopic dilatations and he refused any more aggressive surgical therapy. The patients with more severe injuries were operated, on all with good end results. CONCLUSION: Aggressive surgical treatment of severe corrosive injuries involving the upper gastrointestinal tract is recommended.     

Neonatal DNA immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge

Conventional vaccines are remarkably effective in adults but are much less successful in the very young, who are less able to initiate a mature immune response and who may carry maternal antibodies which inactivate standard vaccines. We set out to determine whether DNA immunization might circumvent these problems. We have previously shown that intramuscular injection of plasmid DNA encoding the nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) is capable of inducing immune responses and protecting 50% of adult mice against lethal and sublethal challenge with LCMV. Here we demonstrate that mouse pups injected with the same plasmid hours or days after birth produce major histocompatibility complex-restricted, NP-specific cytotoxic T lymphocytes (CTL) that persist into adulthood; 48% of vaccinated pups responded to subsequent sublethal viral challenge by the accelerated production of anti-NP LCMV-specific CTL, indicating that these animals had been successfully immunized by the plasmid DNA. In addition, these mice showed a >95% reduction in splenic viral titers 4 days postinfection compared to control mice, demonstrating a more rapid control of infection in vivo. Furthermore, pups born of and suckled on LCMV-immune dams (and therefore containing passively acquired anti-LCMV antibodies at the time of DNA inoculation) responded to the DNA vaccine in a similar manner, showing that maternally derived anti-LCMV antibodies do not significantly inhibit the generation of protective immune responses following DNA vaccination. These findings suggest that, at least in this model system, DNA immunization circumvents many of the problems associated with neonatal immunization.     

Strategies to protect crop plants against viruses: pathogen-derived resistance blossoms

Since 1986, the ability to confer resistance against an otherwise devastating virus by introducing a single pathogen-derived or virus-targeted sequence into the DNA of a potential host plant has had a marked influence on much of the research effort, focus, and short-term objectives of plant virologists throughout the world. The vast literature on coat protein-mediated protection, for example, attests to our fascination for unraveling fundamental molecular mechanism(s), our (vain) search for a unifying hypothesis, our pragmatic interest in commercially exploitable opportunities for crop protection, and our ingenuity in manipulating transgene constructions to broaden their utility and reduce real or perceived environmental risk issues. Other single dominant, pathogen-derived plant resistance genes have recently been discovered from a wide variety of viruses and are operative in an ever-increasing range of plant species. Additional candidates seem limited only by the effort invested in experimentation and by our ingenuity and imagination. This review attempts to consider, in a critical way, the current state of the art, some exceptions, and some proposed rules. The final impression, from all the case evidence considered, is that normal virus replication requires a subtle blend of host- and virus-coded proteins, present in critical relative concentrations and at specific times and places. Any unregulated superimposition of interfering protein or nucleic acid species can, therefore, result in an apparently virus-resistant plant phenotype.     

Stress exacerbates age-related decrements in the immune response to an experimental influenza viral infection

To test the hypothesis that stress exacerbates immune decrements associated with aging, the impact of restraint stress on immunosenescence was assessed using an experimental model of influenza A/Puerto Rico/8/34 viral infection. Beginning one day prior to infection, male C57BL/6 mice, 3 and 22 months of age, were subjected nightly to 12 hours of restraint stress. In both age groups, restraint induced a comparable increase in serum corticosterone levels. However, in contrast to the 3-month-old controls, serum corticosterone levels in 22-month-old mice returned to baseline slower after removal of the stressor. The characteristic influenza-driven increase in cellularity of the lung and draining lymph node was decreased by age and further suppressed by stress. Natural killer cell activity and virus-specific T helper cell function were also blunted by age and almost completely abrogated by stress. Furthermore, due to the weak immune response to viral infection, aged animals subjected to stress had a lower survival rate than age-matched controls.     

Present status of the use of cytokines as adjuvants with vaccines to protect against infectious diseases

Vaccine adjuvants are expected to play an important role in enhancing the immunogenicity of existing and new-generation vaccines against infectious diseases. In particular, adjuvants should direct the immune response in the most appropriate manner--furthering, for example, an expanded B-cell response, a cytotoxic T-cell response, or a T-helper 1 or 2 subset response. While some noncytokine adjuvants have exerted potent effects, their modes of action are most likely mediated by cytokines. Several cytokines have already been shown to be efficient adjuvants in animal models and/or in clinical trials. The mechanisms of cytokine function must be better understood and the techniques for the use of cytokines improved if the full potential of these substances as vaccine adjuvants is to be realized. When used to best advantage, such adjuvants enhance the immunity induced by viral, bacterial, and parasitic vaccines and thereby promote efficient protection or even cure.     

Does the Ukrain preparation protect mice against lethal doses of bacteria?

Ukrain, a semi-synthetic preparation obtained from Chelidonium majus L, is used in the treatment of cancer diseases. It has been observed to exert a protective influence in mice infected by influenza viruses. Recently, the influence of the preparation on the survival of mice infected by lethal doses of E. coli and S. aureus has been estimated. This preparation was administered to Balb/c mice subcutaneously in doses of 0.04, 0.4 and 4.0 mg/kg of body weight. Ukrain was given every second day during 20 days, or a short-term before-and-after method at 48, 24 and 2 h before the infection and or 2, 24 and 48 h after the infection of mice. The mice were infected intraperitoneally with E. coli or S. aureus in doses equivalent to 2LD50. Increased survival of mice, depending on the dose of the preparation and the kind of infecting bacterium was observed. The highest survival (50%) occurred in mice infected with E. coli and receiving the amount of the preparation corresponding to 0.4 mg/kg. The lowest survival was observed in mice infected by S. aureus and receiving the preparation in the amount of 4.0 mg/kg. Higher protective effectiveness of the Ukrain preparation was observed in mice when the preparation had been administered during 20 days as compared to the short-term before-and-after regime.     

Saccharides that protect yeast against hydrostatic pressure stress correlated to the mean number of equatorial OH groups

Several saccharides were found to be significantly effective in providing protection against hydrostatic pressure and high temperature damage in the yeast Saccharomyces cerevisiae. The extent of barotolerance and thermotolerance with seven different sugars showed a linear relationship to their mean number of equatorial OH groups. The same linear relationship is seen when sugars protect protein molecules against elevated temperatures in vitro. Some sugars were more effective in providing protection against hydrostatic pressure nearly a hundred times than high temperature. Pre-heat shock treatment on yeast cells induce various stress tolerances. In this report, pre-heat shocked cells showed potent protection against elevated temperature, but these cells showed faint protection against elevated pressure. These results suggest that sugars may protect cells against hydrostatic pressure and high temperature in a similar manner, probably by stabilizing the macromolecule(s), and such type of protection may be suited for pressure stress.     

Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice

A case-control study was conducted between 1992 and 1996 in six Italian areas. It included 537 women with colon cancer, 291 women with rectal cancer and 2081 control women in hospital for acute conditions, unrelated to hormonal or gynaecological diseases. A higher age at menopause was associated with increased colon cancer risk (odds ratio (OR) for > or = 53 years compared with < 50 years = 1.39, 95% confidence interval (CI) 1.04-1.87). Among parous women, a significant trend of decreasing colon cancer risk with increasing number of births was seen for colon (OR for > or = 4 births compared with 1 birth = 0.62, 95% CI 0.42-0.90), but not for rectal cancer. Nulliparous women, however, were at lower risk than women with a single birth, and age at first birth was directly associated with risk. While oral contraceptive use showed no significant influence, ever users of hormone replacement therapy had a reduced risk of rectal cancer (OR = 0.56, 95% CI 0.31-1.01). Thus, the association of colorectal cancer with reproductive and menstrual factors is neither strong nor consistent.     

Failure of maternal antibodies to protect young turkey poults against challenge with turkey rhinotracheitis virus

Groups of turkey poults with high levels of maternal antibodies (MA+) to turkey rhinotracheitis virus (TRTV) were challenged with virulent TRTV at 1, 5, and 10 days of age. A maternal antibody-free group (MA-) was also challenged at 1 day of age. Before each challenge, levels of maternal antibodies to TRTV were measured by enzyme-linked immunosorbent assay. Clinical signs were scored for each group. Unchallenged poults showed no signs. Respiratory signs in poults infected at 10 days of age resembled those seen in MA- birds infected at 1 day of age but both were more severe than in MA+ birds infected at 1 day of age, when the maternal antibodies were highest. However, overall, the presence of high levels of maternal antibodies did not prevent the development of clinical disease.     

Transient post-renal obstruction may protect the kidney against nephrotoxic damage--a case report

In critically ill patients, acute renal failure is mostly multifactorial in origin. In general, the simultaneous presence of several deleterious factors tends to aggravate the renal damage. The present case report describes a patient with multifactorial acute renal failure, in whom one of the factors contributing to the renal failure, i.e. transient unilateral post-renal obstruction, apparently protected the obstructed kidney against damage from other causes.     

Attempts to protect rabbits against challenge with virulent, cell-associated, malignant catarrhal fever virus

Rabbits hyperimmunized with inactivated malignant catarrhal fever virus (MCFV) infected rabbit lymph node cells did not develop specific antibodies to the virus and succumbed to challenge with live MCFV-infected lymphoid cells. Rabbits hyperimmunized with either inactivated or live, cultured bovine kidney cells infected with MCFV developed antibodies to the virus, but also succumbed to challenge with live MCFV-infected rabbit lymphoid cells. Rabbits hyperimmunized with live cultured rabbit kidney cells infected with MCFV developed antibodies to the virus and resisted challenge with live MCFV-infected rabbit lymphoid tissues 47 weeks later. However, rechallenge of this group at 90 weeks post immunization resulted in the death of 2/4 rabbits suggesting a waning immunity.     

Analysis of viral and cellular parameters which affect the fusion process of influenza viruses

In the present investigation we studied the fusogenic process developed by influenza A, B and C viruses on cell surfaces and different factors associated with virus and cell membrane structures. The biological activity of purified virus strains was evaluated in hemagglutination, sialidase and fusion assays. Hemolysis by influenza A, B and C viruses ranging from 77.4 to 97.2%, from 20.0 to 65.0% from 0.2 to 93.7% and from 9.0 to 76.1% was observed when human, chicken, rabbit and monkey erythrocytes, respectively, were tested at pH 5.5. At this pH, low hemolysis indexes for influenza A, B and C viruses were observed if horse erythrocytes were used as target cells for the fusion process, which could be explained by an inefficient receptor binding activity of influenza on N-glycolyl sialic acids. Differences in hemagglutinin receptor binding activity due to its specificity to N-acetyl or N-glycolyl cell surface oligosaccharides, density of these cellular receptors and level of negative charges on the cell surface may possibly explain these results, showing influence on the sialidase activity and the fusogenic process. Comparative analysis showed a lack of dependence between the sialidase and fusion activities developed by influenza B viruses. Influenza A viruses at low sialidase titers (< 2) also exhibited clearly low hemolysis at pH 5.5 (15.8%), while influenza B viruses with similarly low sialidase titers showed highly variable hemolysis indexes (0.2 to 78.0%). These results support the idea that different virus and cell-associated factors such as those presented above have a significant effect on the multifactorial fusion process.     

Reducing effort to protect perceived ability: "They'd do it but I wouldn't."

Researchers have proposed that when students expect a failure that will indicate their incompetence, they intentionally reduce effort so that failure can be attributed to low effort, rather than low ability. Impaired performance has been found when students anticipate feedback that would indicate incompetence, but there is not clear evidence that the impairment results from a calculated reduction in effort. It was hypothesized that this self-protective mechanism makes better sense to observers than to people in a position to use it. In three experiments, college students (Ns?=?123, 70, 60) were asked how they or a hypothetical student would behave in a situation where they anticipated demonstrating low ability. They rejected the notion that they might not work hard but expected others to reduce effort. Thus, if students reduce effort when their perceived ability is threatened, it may not reflect an intentional strategy designed to maintain perceived ability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CCK(B) antagonists protect against some aspects of the ethanol withdrawal syndrome

The relative contribution to development of hepatocellular carcinoma of the mouse equivalent to the human p53ser249 mutation, found in human hepatocellular carcinoma associated with aflatoxin (AFB1) exposure, is compared with other major risk factors in a transgenic mouse model. Transgenic p53ser246 mice, expressing the mutant protein gene under the control of a truncated albumin promoter, were bred to mice lacking p53 (p53-/-) and to transgenic mice expressing hepatitis B surface antigen (HBsAg). AFB1 hepatocarcinogenesis was then determined in offspring with single or multiple risk factors by determination of the numbers of high-grade hepatic tumors at 13 months of age. In AFB1-treated male mice, expression of the p53ser246 mutation increases the incidence of high-grade tumors from 0% to 14% in HBsAg-negative, p53+/+ (wild-type homozygous) control mice; from 14% to 71% in HBsAg-negative, p53+/- (wild-type heterozygous) mice; and from 62% to 100% in HBsAg-positive, p53+/+ mice. Thus, whereas HBsAg expression and AFB1 together are strongly cocarcinogenic, the presence of the p53ser246 mutant not only significantly enhances this cocarcinogenic effect, it also increases tumorigenesis in AFB1-treated p53 heterozygous and homozygous mice not expressing HBsAg. The possibility that the p53ser246 mutant protein may act as a promoting agent for AFB1 hepatocarcinogenesis is discussed.     

Intraspinal injection of adenosine agonists protect against L-NAME induced neuronal loss in the rat

Intraspinal injection of the nonspecific inhibitor of nitric oxide synthase N-nitro-L-arginine methyl ester (L-NAME) results in a dose-dependent loss of neurons in the rat spinal cord. This effect is thought to result from a reduction in basal levels of nitric oxide (NO), thereby producing an ischemic reaction secondary to vasoconstriction and reduced spinal cord blood flow (SCBF). An important component of this ischemic reaction is the release of excitatory amino acids and the initiation of an excitotoxic cascade. In the present study, microinjections of adenosine A1 and A2 receptor agonists were made in the spinal cord to evaluate the neuroprotective effects of these drugs against neuronal loss produced by L-NAME. Animals were divided into six groups based on the composition of injected solutions: (a) L-NAME; (b) L-NAME + N6-cyclopentyladenosine (CPA, A1 agonist); (c) L-NAME + 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, A2 agonist); (d) L-NAME + CPA + CPCA; (e) N-methyl D-aspartate (NMDA); and (f) NMDA + CPA. Injections of L-NAME or NMDA produced a unilateral loss of spinal neurons, a local inflammatory response, and darkly stained pyknotic nuclei surrounding the area of neuronal loss. CPA and CPCA significantly reduced the area of L-NAME-induced neuronal loss, and a synergistic effect was observed when ineffective doses of these agonists were co-injected with L-NAME. The excitotoxic effects of NMDA were not affected by CPA. The results have shown that A1 and A2 receptor agonists provide significant neuroprotection against L-NAME induced neuronal loss, presumably by inhibiting ischemia induced release of excitatory amino acids (A1 agonist), or by restoring SCBF secondary to vasodilation (A2 agonist). It is suggested by these results that the intraspinal injection of L-NAME is an effective model to study the pathological consequences of vasoconstriction, reduced SCBF, and ischemia secondary to decreased NO production in the rat spinal cord. Finally, the results provide support for the continued investigation of specific adenosine agonists as therapeutic agents directed against the ischemic and excitotoxic components of spinal injury.     

Application of the duty to protect to HIV-positive patients.

The spread of acquired immune deficiency syndrome (AIDS) has led to new questions regarding the limits of confidentiality in the psychotherapeutic relationship. We describe the duty-to-protect doctrine that has arisen out of Tarasoff and subsequent court decisions and apply it to situations in which human immunodeficiency virus (HIV)-positive patients may pose a health threat to others. No courts have as yet applied the duty to protect to cases of HIV infection. We conclude that although parallels exist between Tarasoff and HIV-infected patients, following good clinical practices can significantly reduce instances in which a duty to warn might arise. We recommend statutory solutions that would permit but not require warning potential victims of the HIV infection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Production of uninfectious human immunodeficiency virus type 1 containing viral protein R fused to a single-chain antibody against viral integrase

A single-chain antibody (scAb) against human immunodeficiency virus type 1 (HIV-1) integrase was expressed as a fusion protein of scAb and HIV-1 viral protein R (Vpr), together with the HIV-1 genome, in human 293T cells. The expression did not affect virion production much but markedly reduced the infectivity of progeny virions. The fusion protein was found to be incorporated into the virions. The incorporation appears to account for the reduced infectivity.     

Time-resolved fluorescence studies of tomaymycin bonding to synthetic DNAs

Tomaymycin reacts covalently with guanine in the DNA minor groove, exhibiting considerable specificity for the flanking bases. The sequence dependence of tomaymycin bonding to DNA was investigated in synthetic DNA oligomers and polymers. The maximum extent of bonding to DNA is greater for homopurine and natural DNA sequences than for alternating purine-pyrimidine sequences. Saturation of DNA with tomaymycin has little effect on the melting temperature in the absence of unbound drug. Fluorescence lifetimes were measured for DNA adducts at seven of the ten unique trinucleotide bonding sites. Most of the adducts had two fluorescence lifetimes, representing two of the four possible binding modes. The lifetimes cluster around 2-3 ns and 5-7 ns; the longer lifetime is the major component for most bonding sites. The two lifetime classes were assigned to R and S diastereomeric adducts by comparison with previous NMR results for oligomer adducts. The lifetime difference between binding modes is interpreted in terms of an anomeric effect on the excited-state proton transfer reaction that quenches tomaymycin fluorescence. Bonding kinetics of polymer adducts were monitored by fluorescence lifetime measurements. Rates of adduct formation vary by two orders of magnitude with poly(dA-dG).poly(dC-dT), reacting the fastest at 4 x 10(-2) M-1 s-1. The sequence specificity of tomaymycin is discussed in light of these findings and other reports in the literature.