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Biomedical subjects

M A Beck

Publications and source records attributed to M A Beck.

At least 19 recordsLinked to original sources
PubMed2004

Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents.

BACKGROUND: Recent evidence suggests that atopic disease may in part be mediated by fetal growth, as well as exposure to infectious disease early in life. Few studies have been able to evaluate these associations simultaneously, or to investigate prospectively the long-term effects of early environments while adequately controlling for potentially confounding variables. OBJECTIVE: To examine how prenatal growth and infectious disease in infancy are related to total IgE production in adolescence. METHODS: Ninety-nine adolescents (aged 14-15 years) were selected from a larger cohort study according to the following criteria: full-term birth, currently healthy, and small-for-gestational age (N=53) or appropriate-for-gestational age (N=46). Plasma total IgE was measured with ELISA, and analysed in relation to anthropometric, nutritional, and environmental quality data collected prospectively beginning in the third trimester prior to birth. RESULTS: Each episode of infectious morbidity recorded at bimonthly intervals in the first 6 months of life was associated with a 0.12 log IU/mL reduction in total IgE in adolescence (P=0.004). Prenatal undernutrition was associated with increased adolescent IgE, but only under conditions of an unsanitary household environment (P=0.002). Each additional kilogram gained per month in the first 6 months of life was associated with an increase in adolescent IgE of 0.74 log IU/mL (P=0.03). Each quartile increase in weekly household income at the time of blood sampling was associated with a 0.10 log IU/mL reduction in total IgE (P=0.02). CONCLUSION: Infectious disease in infancy, as well as interactions between prenatal and postnatal environments, appear to have long-term effects on adolescent total IgE production. Future research should investigate the mechanisms behind these effects, and their implications for symptoms of atopic disease.

Adolescent↗
PubMed2001

Antioxidants and viral infections: host immune response and viral pathogenicity.

Malnutrition has long been associated with increased susceptibility to infectious disease. The increase in severity from and susceptibility to infectious disease in malnourished hosts is thought to be the result of an impaired immune response. For example, malnutrition could influence the immune response by inducing a less effective ability to manage the challenge of an infectious disease. Work in our laboratory has demonstrated that not only is the host affected by the nutritional deficiency, but the invading pathogen is as well. Using a deficiency in selenium (Se) as a model system, mice deficient in Se were more susceptible to infection with coxsackievirus, as well as with influenza virus. Se-deficient mice develop myocarditis when infected with a normally benign strain of coxsackievirus. They also develop severe pneumonitis when infected with a mild strain of influenza virus. The immune system was altered in the Se-deficient animals, as was the viral pathogen itself. Sequencing of viral isolates recovered from Se-deficient mice demonstrated mutations in the viral genome of both coxsackievirus and influenza virus. These changes in the viral genome are associated with the increased pathogenesis of the virus. The antioxidant selenoenzyme, glutathione peroxidase-1, was found to be critically important, as glutathione peroxidase knockout mice developed myocarditis, similar to the Se-deficient mice, when infected with the benign strain of myocarditis. This work points to the importance of host nutrition in not only optimizing the host immune response, but also in preventing viral mutations which could increase the viral pathogenicity.

Animals↗
PubMed2001

Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence.

BACKGROUND: Recently, researchers have considered the fetal and infant origins of several adult cardiovascular and metabolic diseases, but the implications of early events for immune function and infectious disease are unclear. OBJECTIVE: We investigated the association between prenatal undernutrition and immunocompetence in adolescence and hypothesized that intrauterine growth retardation is associated with a lower likelihood of mounting an adequate antibody response later in life. DESIGN: A subsample of one hundred three 14-15-y-olds was recruited from an ongoing longitudinal study in which data collection began while participants were in utero. A typhoid vaccine was given, and anti-typhoid antibodies were measured 2 wk and 3 mo later as a functional marker of immunocompetence. The likelihood of mounting an adequate antibody response was compared for adolescents who were small for gestational age or appropriate for gestational age at birth while controlling for a range of postnatal exposures. RESULTS: The predicted probability of mounting a positive antibody response for adolescents who were prenatally and currently undernourished was 0.32, compared with probabilities of 0.49-0.70 for adequately nourished adolescents (P = 0.023). Diarrhea in the first year of life (P = 0.009) and fast weight gain during the first 6 mo (P = 0.003) were also associated with a higher probability of response. CONCLUSIONS: These findings extend the concept of fetal and early infant programming of adult diseases to the immune system and suggest that early environments may have long-term implications for immunocompetence and infectious disease risk, particularly in developing countries.

Adolescent↗
PubMed2001

Prenatal undernutrition and postnatal growth are associated with adolescent thymic function.

The fetal and early infant origins of a number of adult cardiovascular and metabolic diseases have received considerable attention, but the long-term consequences of early environments for human immune function have not been reported. We investigated the effects of pre- and postnatal environments on thymic hormone production in adolescents participating in an ongoing longitudinal study in the Philippines. Prospective data collected at birth, during y 1 of life, in childhood and in adolescence were used to predict plasma thymopoietin concentration in 14- to 15-y-old adolescents (n = 103). Thymopoietin concentration was compared for small-for-gestational-age and appropriate-for-gestational-age individuals while controlling for a range of postnatal exposures. Prenatal undernutrition was significantly associated with reduced thymopoietin production in interaction with the duration of exclusive breast-feeding (P = 0.006). Growth in length during y 1 of life was positively associated with adolescent thymopoietin production (P = 0.002). These associations remained significant after adjusting for a range of potentially confounding variables. These findings provide support for the importance of fetal and early infant programming of thymic function, and suggest that early environments may have long-term implications for immunocompetence and adult disease risk.

Adolescent↗
PubMed2000

Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus.

The immune response to influenza A virus is characterized by an influx of both macrophages and T lymphocytes into the lungs of the infected host, accompanied by induced expression of a number of CC chemokines. CC chemokine receptors CCR5 and CCR2 are both expressed on activated macrophages and T cells. We examined how the absence of these chemokine receptors would affect pulmonary chemokine expression and induced leukocyte recruitment by infecting CCR5-deficient mice and CCR2-deficient mice with a mouse-adapted strain of influenza A virus. CCR5(-/-) mice displayed increased mortality rates associated with acute, severe pneumonitis, whereas CCR2(-/-) mice were protected from the early pathological manifestations of influenza because of defective macrophage recruitment. This delay in macrophage accumulation in CCR2(-/-) mice caused a subsequent delay in T cell migration, which correlated with high pulmonary viral titers at early time points. Infected CCR5(-/-) mice and CCR2(-/-) mice both exhibited increased expression of the gene for MCP-1, the major ligand for CCR2(-/-) and a key regulator of induced macrophage migration. These studies illustrate the very different roles that CCR5 and CCR2 play in the macrophage response to influenza infection and demonstrate how defects in macrophage recruitment affect the normal development of the cell-mediated immune response.

Animals↗
PubMed2000

Micronutrients and host resistance to viral infection.

Previous work in our laboratory demonstrated that a virus could undergo rapid mutation in a host deficient in Se, leading to a normally avirulent virus acquiring virulence due to genome changes. Once these mutations occur, even a host with adequate Se-nutriture is susceptible to the newly virulent virus. What influence does the deficiency in Se have on the immune response of the host? Infection with myocarditic strains of coxsackievirus induces an inflammatory response in the cardiac tissue. It is this immune response that induces the heart damage, rather than direct viral effects on the heart tissue. Chemokines are chemo-attractant molecules that are secreted during an infection in order to attract immune cells to the site of the injury, and have been found to be important for the development of coxsackievirus-induced myocarditis. We found that a deficiency in Se influences the expression of mRNA for the chemokine monocyte chemo-attractant protein-1, which may have implications for the development of myocarditis in the Se-deficient host. Expression of mRNA for interferon-gamma was also greatly decreased in the Se-deficient animal. Thus, a deficiency in Se can have profound effects on the host as well as on the virus itself. How the alteration of the immune response of the Se-deficient animal affects the development of the virulent genotype remains to be answered.

Animals↗
PubMed2000

Host nutritional status and its effect on a viral pathogen.

The nutritional status of the host has long been associated with both severity and susceptibility to infectious disease. The accepted model system proposes that inadequate nutrition impairs the functioning of the immune system, thus resulting in increased susceptibility to infection. However, current work suggests that not only can the nutritional status of the host affect the immune response, but it can also affect the viral pathogen. In a mouse model, a benign strain of coxsackievirus B3 became virulent and caused myocarditis in selenium- and vitamin E-deficient mice. This change in pathogenicity was due to mutations in the viral genome, which changed an avirulent virus into a virulent one. Once these mutations occurred, even mice with normal nutriture developed disease from the mutated virus. These results suggest that the oxidative stress status of the host can have a profound influence on a viral pathogen.

Animals↗
PubMed2000

Nutritionally induced oxidative stress: effect on viral disease.

It has long been known that the nutritional status of the host can influence both susceptibility to infectious disease and the severity of the disease if contracted. In studies of coxsackievirus infection and selenium deficiency in mice, we found that mice fed a selenium-deficient diet developed myocarditis, but mice fed a diet adequate in selenium did not. Similarly, mice fed a diet deficient in vitamin E developed myocarditis, but mice fed a diet with adequate vitamin E did not. The epidemic of optic and peripheral neuropathy that occurred in Cuba in the early 1990s provides another example of how the nutritional status of the host may affect the impact of a virus. Patients who developed neuropathy had lower blood concentrations of riboflavin, vitamin E, selenium, alpha- and beta-carotenes, and the carotenoid lycopene, which suggests that the disease was associated with an impairment of protective antioxidant pathways. After supplementation of the population with these nutrients, the disease began to subside. The nutritional status of the host can have a profound influence on a virus, so that a normally avirulent virus becomes virulent because of changes in the viral genome. Our studies suggest that outbreaks of disease attributed to a nutritional deficiency may actually result from infection by a virus that has become pathogenic by replicating in a nutritionally deficient host.

Animals↗
PubMed2000

The role of oxidative stress in viral infections.

Oxidative stress is implicated as a pathogenic factor in a number of viral infections. Our work has shown that nutritionally induced oxidative stress exacerbates the pathogenesis of coxsackievirus B3 (CVB3) infection in mice. Of particular note, mice fed on a diet deficient in antioxidants developed myocarditis when infected with a normally benign strain of CVB3. This change in virulence was found to be due to changes in the viral genome. Immune functions of the oxidatively stressed mice were also altered. Another example of the effect of oxidative stress on a viral pathogen took place in Cuba in the 1990s. An epidemic of optic and peripheral neuropathy in the population occurred that was associated with a lack of dietary antioxidants and with smoking (a pro-oxidant). A coxsackie-like virus was isolated from the cerebrospinal fluid from 84% of patients cultured. Thus, oxidative stress can have profound effects, not only on the host, but on the pathogen as well.

Animals↗
PubMed1999

Flavonol glycosides from Eschscholtzia californica.

The aqueous EtOH extract of aerial parts of Eschscholtzia californica Cham. yielded six flavonol 3-O-glycosides including two new compounds: quercetin 3-O-[alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)-beta- glucopyranoside] and isorhamnetin 3-O-[alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)-beta- glucopyranoside]. Their structures were established on the basis of spectroscopic studies.

Flavonoids↗
PubMed1999

Selenium and host defence towards viruses.

The association between viral disease and nutrition has long been thought to be due to effects on the host immune system. This theory suggests that when a host is malnourished, the immune system is compromised, and thus increased susceptibility to viral infection will occur. However, the virus itself may also be affected by the nutritional status of the host. We have demonstrated that a normally-benign strain of coxsackievirus B3 (CVB3/0) becomes virulent in either Se-deficient or vitamin E-deficient mice. Although the deficient animals are immunosuppressed, the virus itself is also altered. Six nucleotide changes were found in the virus that replicated in the deficient mice, and once these mutations occurred, even mice with normal nutrition became susceptible to disease. Thus, the nutritional status of the host was able to transform an avirulent virus into a virulent one due to genomic changes in the virus. We believe that a common mechanism of oxidative stress is the underlying cause of the genetic changes. Both vitamin E and Se act as antioxidants, and benign virus inoculated into GSH peroxidase (EC 1.11.1.9)-knockout mice will also convert to virulence due to genomic changes. Our work points to the importance of host nutrition during a viral disease, not only from the perspective of the host, but from the perspective of the viral pathogen as well.

Animals↗
PubMed1999

Selenium and viral virulence.

A mouse model of coxsackievirus-induced myocarditis is being used to investigate nutritional determinants of viral virulence. This approach was suggested by research carried out in China which showed that mice fed diets composed of low selenium ingredients from a Keshan disease area suffered more extensive heart damage when infected with a coxsackie B4 virus than infected mice fed the same diet but supplemented with selenium by esophageal intubation. Selenium deficiency in our mice increased the virulence of an already virulent strain of coxsackievirus B3 (CVB3/20) and also allowed conversion of a non-virulent strain (CVB3/0) to virulence. Such conversion of CVB3/0 was accompanied by a change in the viral genome to more closely match that of the virulent virus, CVB3/20. As far as the authors are aware, this is the first report of host nutrition influencing the genetic make-up of an invading pathogen. Nutritionists may need to consider this mechanism of increased viral virulence in order to gain a better understanding of diet/infection relationships.

Animals↗
PubMed1998

Glutathione peroxidase protects mice from viral-induced myocarditis.

Glutathione peroxidase 1 (GPX-1) is a selenium-dependent enzyme with antioxidant properties. Previous investigations determined that mice deficient in selenium developed myocarditis when infected with a benign strain of coxsackievirus B3 (CVB3/0). To determine whether this effect was mediated by GPX-1, mice with a disrupted Gpx1 gene (Gpx1-/-) were infected with CVB3/0. Gpx1-/- mice developed myocarditis after CVB3/0 infection, whereas infected wild-type mice (Gpx1+/+) were resistant. Sequencing of viruses recovered from Gpx1(-/-)-infected mice demonstrated seven nucleotide changes in the viral genome, of which three occurred at the G residue, the most easily oxidized base. No changes were found in virus isolated from Gpx1+/+ mice. These results demonstrate that GPX-1 provides protection against viral-induced damage in vivo due to mutations in the viral genome of a benign virus.

Animals↗
PubMed1998

Dietary oxidative stress and the potentiation of viral infection.

Oxidative stress is implicated in the pathogenesis of several viral infections, including hepatitis, influenza, and AIDS. Dietary oxidative stress due to either selenium or vitamin E deficiency increases cardiac damage in mice infected with a myocarditic strain of coxsackievirus B3. Such dietary oxidative stress also allows a normally benign (i.e., amyocarditic) coxsackievirus B3 to convert to virulence and cause heart damage. This conversion to virulence is due to a nucleotide sequence change in the genome of the benign virus, which then resembles more closely the nucleotide sequence of virulent strains. Although it has been known for many years that poor nutrition can affect host response to infection, this is the first report of host nutrition affecting the genetic sequence of a pathogen. Further research is needed to determine whether poor host nutrition plays any role in the emergence of new viral diseases via alterations in he genotype of an infectious agent.

Animals↗
PubMed1997

Contribution to the quantitative and enantioselective determination of kavapyrones by high-performance liquid chromatography on ChiraSpher NT material.

A simultaneous HPLC separation of the enantiomers of kavain, dihydrokavain, methysticin and dihydromethysticin, as well as the achiral dienolides yangonin and desmethoxyyangonin was carried out on a ChiraSpher NT column. For quantitative determinations, calibration curves with correlation coefficients between 0.9982 and 0.9996 were established for the genuine kavapyrones. Detection limits between 0.25 microg and 0.5 microg per injection were measured at 240 nm. The defined scopes of work corresponded with the different kavapyrone amounts, depending on growth factors of distinct plant locations. The precision of the method was verified by analysing a phytopharmacon with a nominal value of 40 mg kavapyrones per tablet. The evaluation revealed 39.62 mg per tablet by the sum of single calculated kavapyrones. Relative standard deviations between 1.06% and 2.39% were found for the compounds under investigation. The accuracy of the method was proved by a recovery of 99.7%. To simplify the determination of the total kavapyrone amount, response factors and correlation factors for (+)-dihydrokavain, (+)-methysticin, (+)-dihydromethysticin, yangonin and desmethoxyyangonin were calculated relative to (+)-kavain.

Anti-Anxiety Agents↗