Faculty Bibliography

CTX-M extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolates are infrequently reported in the United States. In this study, we analyzed nonduplicate ESBL-producing K. pneumoniae and Escherichia coli clinical isolates collected during 2005-2012 at a tertiary care medical center in suburban New York City, USA, for the presence of blaCTX-M, blaSHV, blaTEM, and blaKPC genes. Despite a high prevalence of blaCTX-M genes in ESBL-producing E. coli since 2005, blaCTX-M genes were not detected in K. pneumoniae until 2009. The prevalence of CTX-M-producing K. pneumoniae increased significantly over time from 1.7% during 2005-2009 to 26.4% during 2010-2012 (p<0.0001). CTX-M-15 was the dominant CTX-M genotype. Pulsed-field gel electrophoresis and multilocus sequence typing revealed high genetic heterogeneities in CTX-M-producing K. pneumoniae isolates. This study demonstrates the recent emergence and polyclonal spread of multidrug resistant CTX-M-producing K. pneumoniae isolates among patients in a hospital setting in the United States.

A prior study in mice has shown that the timely application of topical antibiotics to the skin at the tick bite site could eradicate Borrelia burgdorferi infection. That study, however, did not evaluate antibiotic preparations that are considered suitable for use in humans. In this murine study, topical application of 2% erythromycin and 3% tetracycline preparations that are acceptable for use in humans was found to be ineffective in eliminating B. burgdorferi from the tick bite site or in preventing dissemination to other tissues. Reasons for the discrepant findings are discussed.

Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.

The inhibitor of apoptosis protein (IAP) plays an important role in tumorigenesis and may be a potential target for cancer therapy. Livin, which belongs to this family, is highly expressed in various tumors. The previous study demonstrated that silencing Livin gene promoted lung cancer cell apoptosis; however, the effects on tumor growth suppression by targeting this gene in vivo, to thereby determine the efficacy of targeting Livin for patient therapy, have not been determined. This study injected lentivirus-delivered livinshRNA into established xenograft tumors derived from the lung adenocarcinoma cell line SPC-A-1 in BALB/C nude mice, the result showed that LivinshRNA down-regulated Livin expression effectively, induced tumor cell apoptosis, reduced tumor cell proliferation, and suppressed tumor growth dramatically, with a tumor volume inhibitory rate of (58.65±4.82)% and a tumor weight inhibitory rate of (47.44±1.64)%, but with less severe adverse reaction to the mouse. This study further demonstrated that Livin gene silencing induced a G0/G1-phase cell cycle arrest and cyclin D1 downregulation, which is a key regulator of the G0/G1- to S-phase transition. These findings suggest that LivinshRNA local injection may serve as a therapeutic method for patient treatment, and that LivinshRNA may suppress tumor growth by arresting the cell cycle in the G0/G1-phase.

Superior response inhibition is an essential component of the advanced cognitive abilities of gifted children. This study investigated response inhibition in intellectually gifted children by recording event-related brain potentials (ERPs) during a Go/NoGo task. Fifteen intellectually gifted children and 15 intellectually average children participated. Our present findings showed that intellectually gifted children had shorter Go-P3 latency, indicating faster processing of Go stimuli, a finding consistent with previous studies. We focused on the two inhibition-related components, NoGo-N2 and NoGo-P3. The results showed that NoGo-P3 latency was shorter for intellectually gifted children compared to their average peers. N2 latency did not indicate the intelligence difference. These results suggested that intellectually gifted children showed faster inhibition when dealing with NoGo stimuli, and this superiority came from the later stages of inhibition, i.e., response evaluation or the success of inhibiting a response, as indexed by the shorter P3 latency.

OBJECTIVE:To describe the distribution of over weight and obesity to discover the level of exposure on risk factors of stroke among people aged 40 and over, in a community-based population. METHODS:From 2003 to 2004, people aged > or = 40 years in a community of Fengxian district in Shanghai were selected by cluster sampling. Out of 11,791 individuals who were selected, 10,565 met the inclusion criteria and responded to the investigation. By face to face interview, a cross-sectional survey was carried out, using a questionnaire for risk factors of stroke. Height, weight and blood pressures were measured and cerebrovascular hemodynamic parameters (CVHP) were checked. Age and gender distribution of over weight and obesity in the population were described. Using 60 year as cut-off point, participants were grouped into three: normal, over weight and obesity by body mass index. Level of stroke risk factor exposure between groups was compared and logistic regression model was used for multiple analyses. RESULTS:Proportions of over weight and obesity were 28.5 percent and 4.1 percent in male and 26.3 percent and 4.2 percent in female (P = 0.045). Systolic and diastolic blood pressure in over weight group were (132.5 +/- 19.4) mm Hg and (83.9 +/- 10.5) mm Hg (1 mm Hg = 0.133 kPa), which were higher than that in normal weight group and lower than that in obese group (P < 0.05). Exposure rate of heart disease, family history of stroke in < 60 year old group and diabetes in > or = 60 year group increased along with the increase of weight. Exposure rate of hypertension, abnormality of CVHP score in both age groups were also increased with the increase of weight. Data from multiple logistic regression indicated that hypertension, family history of stroke and heart disease, CVHP score below 75 points, sex and age were independent factors of over weight and obese. CONCLUSION/CONCLUSIONS:The prevalence of over weight or obesity in a community-based population among aged 40 years or over was around 30 percent. The overall exposure rate of stroke risk factors were increasing along with the increase of weight, especially for those in the middle age.

Lyme disease pathogenesis results from a complex interaction between Borrelia burgdorferi and the host immune system. The intensity and nature of the inflammatory response of host immune cells to B. burgdorferi may be a determining factor in disease progression. Gene array analysis was used to examine the expression of genes encoding cytokines, chemokines, and related factors in the joint tissue of infected C3H/HeJ mice and in a murine macrophage-like cell line in response to a disseminating or attenuated clinical isolate of B. burgdorferi. Both isolates elicited a robust proinflammatory response in RAW264.7 cells characterized by an increase in transcript levels of genes encoding CC and CXC chemokines, proinflammatory cytokines, and TNF superfamily members. Transcription of genes encoding IL-1beta, IL-6, MCP-1, MIP-1alpha, CXCR4, and TLR2 induced in RAW264.7 cells by either live or heat-killed spirochetes did not differ significantly at any time point over a 24-h period, nor was there a difference in the protein levels of IL-10, TNF-alpha, IL-6, and IL-12p70 in culture supernatants. Thus, induction of host macrophage expression of proinflammatory mediators by host macrophages does not contribute to the differential pathogenicity of different B. burgdorferi strains.