J Handy

Publications (6)30.17 Total impact

• Article: Obesity is associated with impaired immune response to influenza vaccination in humans.

  P A Sheridan, H A Paich, J Handy, E A Karlsson, M G Hudgens, A B Sammon, L A Holland, S Weir, T L Noah, M A Beck
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  ABSTRACT: Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250,000-500,000 people worldwide each year. More than one in ten of the world's adult population is obese and more than two-thirds of the US adult population is overweight or obese. No studies have compared humoral or cellular immune responses to influenza vaccination in healthy weight, overweight and obese populations despite clear public health importance. The study employed a convenience sample to determine the antibody response to the 2009-2010 inactivated trivalent influenza vaccine (TIV) in healthy weight, overweight and obese participants at 1 and 12 months post vaccination. In addition, activation of CD8⁺ T cells and expression of interferon-γ and granzyme B were measured in influenza-stimulated peripheral blood mononuclear cell (PBMC) cultures. Body mass index (BMI) correlated positively with higher initial fold increase in IgG antibodies detected by enzyme-linked immunosorbent assay to TIV, confirmed by HAI antibody in a subset study. However, 12 months post vaccination, higher BMI was associated with a greater decline in influenza antibody titers. PBMCs challenged ex vivo with vaccine strain virus, demonstrated that obese individuals had decreased CD8⁺ T-cell activation and decreased expression of functional proteins compared with healthy weight individuals. These results suggest obesity may impair the ability to mount a protective immune response to influenza virus.
  International journal of obesity (2005) 10/2011; 36(8):1072-7. · 4.34 Impact Factor
• Article: The role of oxidative stress in viral infections.

  M A Beck, J Handy, O A Levander
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  ABSTRACT: 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.
  Annals of the New York Academy of Sciences 02/2000; 917:906-12. · 3.15 Impact Factor
• Article: Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient.

  R M Aris, D M Maia, I P Neuringer, K Gott, S Kiley, K Gertis, J Handy
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  ABSTRACT: Post-transplantation lymphoproliferative disorder (PTLD) is a widely recognized and often catastrophic complication of organ transplantation. The incidence of PTLD after lung transplantation ranges from 6.2 to 9.4% and is two-fold higher than that seen after organ transplantation of other organs. Primary Epstein-Barr virus (EBV) infection is a major risk factor for PTLD, but the incidence of PTLD in EBV seronegative (EBV-) patients seems to vary with type of organ transplant. The goal of this study was to quantify the risk of PLTD based on pre-lung transplantation EBV serostatus in lung transplant patients. Pre- and post-lung transplant serostatus was defined in 80 patients, and our six cases of PTLD occurred in this group. Six of 94 lung transplant patients (6.4%) who survived > 1 mo developed PTLD. All cases of PTLD involved thoracic structures at presentation and occurred in the first post-operative year. Patients who were EBV- before lung transplant were much more likely to develop PTLD than those who were seropositive (EBV+) (five of 15 [33%] versus one of 60 [< 2%], p < 0.001). Consistent with the prevailing adult (donor) EBV+ rate (85%), two of our EBV-patients remained EBV-after lung transplant. Therefore, the rate of PTLD was 42% in those with primary EBV infection. As compared with EBV-patients that remained tumor-free, those who developed PLTD had similar levels of immunosuppressants and doses of anti-viral therapy. We conclude that PLTD occurs predominantly in EBV-naïve patients (risk approximately 1/3). EBV-patients should be monitored more closely after lung transplantation and, possibly, managed with lower immunosuppression. Our data also suggest that anti-viral therapy alone does not decrease the incidence of PTLD in high risk patients, PTLD can be successfully treated in most cases, and EBV-naïve patients should not be excluded from lung transplant because their risk of death from PTLD is < 15%.
  American Journal of Respiratory and Critical Care Medicine 12/1996; 154(6 Pt 1):1712-7. · 11.08 Impact Factor
• Article: Nasal cytokine production in viral acute upper respiratory infection of childhood.

  T L Noah, F W Henderson, I A Wortman, R B Devlin, J Handy, H S Koren, S Becker
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  ABSTRACT: Children in a day care center underwent serial nasal lavages in order to assess nasal cytokine expression during acute upper respiratory infections (URI). Interleukin (IL)-1 beta, IL-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were markedly elevated in nasal lavage fluid during acute URI compared to baseline, and all except TNF-alpha decreased significantly by 2-4 weeks later. Cytokine patterns in respiratory syncytial virus-positive and -negative illnesses did not differ significantly. A subgroup of children also underwent superficial mucosal biopsy under the inferior nasal turbinate. During acute URI, biopsy cells (90%-95% epithelial) showed increased transcripts for IL-1 beta, IL-8, and IL-6 in 7 of 9 subjects, suggesting that epithelial cells may be one source of cytokines during acute URI. The results show that inflammatory cytokines are elevated in nasal secretions during acute URI in preschool children. Thus, cytokines are likely to participate in regulation of respiratory virus-induced inflammation.
  The Journal of Infectious Diseases 04/1995; 171(3):584-92. · 6.41 Impact Factor
• Article: A strong association between mefloquine and halofantrine resistance and amplification, overexpression, and mutation in the P-glycoprotein gene homolog (pfmdr) of Plasmodium falciparum in vitro.

  S A Peel, P Bright, B Yount, J Handy, R S Baric
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  ABSTRACT: Stepwise selection for increased mefloquine resistance in a line of Plasmodium falciparum in vitro resulted in increased resistance to halofantrine and quinine, increased sensitivity to chloroquine, and amplification and overexpression of the P-glycoprotein gene homolog (pfmdr1). A point mutation (tyrosine to phenylalanine) noted at amino acid 86 in pfmdr1 in the mefloquine-resistant line W2mef was amplified in more resistant lines derived from it by in vitro selection pressure with mefloquine. Conversely, lines selected for increased chloroquine resistance exhibited a revertant phenotype that was sensitive to mefloquine and halofantrine. These lines also demonstrated increased sensitivity to quinine, loss of amplification of pfmdr1, loss of the mefloquine/halofantrine phenylalanine-86 mutation, and selection for a tyrosine-86 mutation previously associated with chloroquine resistance. These findings provide strong evidence for pfmdr1 mediating cross-resistance to halofantrine and mefloquine in P. falciparum in vitro.
  The American journal of tropical medicine and hygiene 12/1994; 51(5):648-58. · 2.59 Impact Factor
• Article: Derivation of highly mefloquine-resistant lines from Plasmodium falciparum in vitro.

  S A Peel, S C Merritt, J Handy, R S Baric
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  ABSTRACT: Serial passage of a multidrug-resistant clone of Plasmodium falciparum in concentrations of mefloquine hydrochloride ranging from 30 to 2,400 ng/ml resulted in the derivation of increasingly resistant parasite lines in vitro. Parasite lines isolated in mefloquine concentrations greater than 300 ng/ml demonstrated increased vacuolization, enhanced pigment production, and increased growth rates as compared with the progenitor clone, W2-mef. Although microdilution incorporation assays demonstrated that the 50% inhibitory concentration (IC50) of mefloquine were similar for all lines, the IC90, IC95, and IC99 levels were significantly increased. Growth rate assays performed in 5% hematocrit suspensions demonstrated different levels of mefloquine resistance among these lines. Under these conditions the most resistant line, Mef 2.4, grew efficiently in approximately 10-fold higher concentrations of mefloquine than the progenitor clone W2-mef. Analysis of drug susceptibility profiles to mefloquine hydrochloride, chloroquine diphosphate, quinine sulfate, and halofantrine hydrochloride indicated that selection for high levels of mefloquine resistance had resulted in significant increases in resistance to halofantrine and increased sensitivity to chloroquine. The phenotypic changes demonstrated in the most resistant line, Mef 2.4, reflect a multidrug resistant-like phenotype, and appear to mimic changes recently reported in drug susceptibility profiles of recrudescent isolates following mefloquine treatment failures in Thailand.
  The American journal of tropical medicine and hygiene 04/1993; 48(3):385-97. · 2.59 Impact Factor