PubMed Health⌕ Search

Biomedical subjects

Thomas Henry

Publications and source records attributed to Thomas Henry.

10 recordsLinked to original sources
PubMed2006

The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche.

The facultative intracellular pathogen Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. Inside epithelial cells, Salmonella replicates in vacuoles, which localize in the perinuclear area in close proximity to the Golgi apparatus. Among the effector proteins translocated by the Salmonella pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of Salmonella vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts functionally and physically with SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that the intracellular positioning of Salmonella vacuoles is a complex phenomenon resulting from the combined action of several effector proteins.

Animals↗
PubMed2006

The Salmonella effector protein PipB2 is a linker for kinesin-1.

Understanding the mechanisms of Salmonella virulence is an important challenge. The capacity of this intracellular bacterial pathogen to cause diseases depends on the expression of virulence factors including the second type III secretion system (TTSS-2), which is used to translocate into the eukaryotic cytosol a set of effector proteins that divert the biology of the host cell and shape the bacterial replicative niche. Yet little is known about the eukaryotic functions affected by individual Salmonella effectors. Here we report that the TTSS-2 effector PipB2 interacts with the kinesin light chain, a subunit of the kinesin-1 motor complex that drives anterograde transport along microtubules. Translocation of PipB2 is both necessary and sufficient for the recruitment of kinesin-1 to the membrane of the Salmonella-containing vacuole. In vivo, PipB2 contributes to the attenuation of Salmonella mutant strains in mice. Taken together, our data indicate that the TTSS-2-mediated fine-tuning of kinesin-1 activity associated with the bacterial vacuole is crucial for the virulence of Salmonella.

Animals↗
PubMed2006

Molecular motors hijacking by intracellular pathogens.

Cargoes are transported intracellularly along cytoskeletal tracks composed of actin or tubulin. Their movement involves the action of molecular motor proteins that generate directed movement along microtubules or actin filaments. The three classes of molecular motors--kinesins, dyneins and myosins--are involved in a multiplicity of biological movements such as mitosis, positioning of organelles, intracellular transports and also vesicular sorting through membrane tubulation and fission and delivery to their target compartment. Intracellular pathogens use this molecular machinery to reach their site of replication, to leave their host or to control the dynamics of membrane exchanges with their replication compartment.

Actins↗
PubMed2005

The complexity of treatments for persons with epilepsy.

The purpose of this study was to describe the types of antiepileptic medication regimens and the types of actions required to take medications for a group of patients with epilepsy. The Epilepsy Medication and Treatment Complexity Index (EMTCI) was used to gather information about medications and treatments. The sample of 314 reported on 585 epilepsy medications. The majority (56%) were on more than one treatment. On average, an individual took 1.86 medications per day (range, 1-6) and 7.98 pills per day (range, 1-36 pills). Most medications (54%) were taken twice a day. The most common special instruction was taking different doses on the same day. Taking more than one tablet per dose was the most common administrative action. Data presented here raise interesting areas for further research as well as important clinical implications.

Adult↗
PubMed2005

The intracellular fate of Salmonella depends on the recruitment of kinesin.

Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. The success of this pathogen depends on its capacity to proliferate within host cells in a membrane-bound compartment. We found that the Salmonella-containing vacuole recruited the plus-end-directed motor kinesin. Bacterial effector proteins translocated into the host cell by a type III secretion system antagonistically regulated this event. Among these effectors, SifA targeted SKIP, a host protein that down-regulated the recruitment of kinesin on the bacterial vacuole and, in turn, controlled vacuolar membrane dynamics.

Adaptor Proteins, Signal Transducing↗
PubMed2003

The association of stigma with self-management and perceptions of health care among adults with epilepsy.

OBJECTIVE: The purpose of this study was to examine the perception of stigma among adults with epilepsy including its association with epilepsy self-management and perceptions of health care. METHODS: Participants for the study were recruited from two epilepsy centers and a neurology clinic. Individuals agreeing to participate in the study were asked to complete three assessments each 3 months apart. Data were collected from 320 adult men and women with epilepsy; 314 provided responses on stigma and were included in this analysis. RESULTS: Participants ranged in age from 19 to 75 years (mean=43). Fifty percent of the sample was female, and 80% was white. The mean age of seizure onset was 22 years, and 76% of participants reported having had a seizure within the past year. Analysis suggests levels of perceived stigma are similar for men and women and across ethnic and age groups. However, participants who were not married or living with a partner, were not working for pay, and had limited income reported higher levels of stigma than did married participants, those working for pay, and those in higher income brackets. Participants reporting higher levels of stigma included those who had their first seizure before the age of 50 and a seizure in the last year. Participants whose seizures interfered more with activities, who rated their seizures as under less control, and who were not legally able to drive also reported higher levels of stigma. Tests of association between stigma and health-related variables revealed that participants reporting higher levels of perceived stigma also reported lower levels of self-efficacy to manage epilepsy; more negative outcome expectancies related to treatment and seizures; and lower levels of medication management, medication adherence, and patient satisfaction. However, they also reported greater management of information related to seizures. In regression analysis, income, age at first seizure, seizures during the past year, lower self-efficacy, negative outcome expectancies for seizures, and less patient satisfaction explained 54% of the variance in perceived stigma. CONCLUSIONS: The results of the study suggest that perceived stigma is significant for people with epilepsy and is associated with factors that are known to be important in the management of epilepsy. Understanding who is at greatest risk for feeling stigmatized could lead to the development of preventive measures.

Adolescent↗
PubMed2003

The epilepsy medication and treatment complexity index: reliability and validity testing.

Medications are the most common treatment for epilepsy. Regimens vary from once per day dosing to several pills several times per day. More complex regimens have been associated with lower adherence rates. To date, medication complexity has been measured by the number of pills and the number of times per day the pills are taken. However, complexity also includes special instructions (e.g., take at a separate time than other medications) and the specific administration actions (e.g., take 1/2 pill). This article describes the development of an instrument designed to measure the complexity associated with epilepsy treatment regimens. The medication complexity tool (MCI) was modified to create the Epilepsy Medication and Treatment Complexity Index (EMTCI). The EMTCI comprises four sections: (a) general medication information, (b) frequency of administration, (c) special instructions, and (d) administration actions. Points are given for dosing schedules, special instructions, and administration actions. A total complexity score is calculated by adding points for each section. One form is completed for each medication prescribed for each person. The initial development of the EMTCI included revising the MCI to make it applicable to epilepsy medication. Interrater and intrarater reliability assessments were conducted. The EMTCI was administered to adults with epilepsy as part of a larger study of self-management in people with epilepsy. Data from that study were used for further assessments of the EMTCI including test-retest reliability, criterion validity, and construct validity. The EMTCI shows evidence of both reliability and validity. Information from the tool can be used to describe the medication complexity of epilepsy medication regimens in much greater detail than has been done previously for this population. This information is useful in describing the treatment and adherence issues for persons with epilepsy.

Adult↗
PubMed2002

Induction of protective antiviral cytotoxic T cells by a tubular structure capable of carrying large foreign sequences.

Bluetongue virus (BTV) produces large numbers of tubules during infection which are formed by a single virus coded non-structural protein, NS1. The NS1 protein has been fused with full length green fluorescent protein (GFP) and was shown to retain the capacity to form tubules when expressed in heterologous expression systems. Moreover, recombinant purified chimeric tubules were demonstrated to be internalized by macrophages and dendritic cells. The ability of such chimeric tubules to induce protective cytotoxic T lymphocytes (CTL) responses has been assessed by generating chimeric tubules carrying a single CD8(+) T cell epitope from the lymphocytic choriomeningitis virus (LCMV) nucleoprotein. These chimeric tubules were recognized by MHC class I restricted T cell hybridoma in vitro and induced in vivo strong CD8(+) class I-restricted CTL responses in immunized mice. Further, the immunized mice were protected when challenged with a lethal dose of LCMV. This is the first study that demonstrates that the virus derived tubules synthesized by a recombinant non-structural protein carrying a single viral CTL epitope could induce protective immunity against a lethal viral challenge. Since recombinant tubules carrying large inserts can be purified at a large quantity from insect cells, they have potential to develop as safe multi-CTL vaccine delivery systems.

Animals↗
PubMedDate not supplied

Improved methods for producing outer membrane vesicles in Gram-negative bacteria.

Outer membrane vesicle formation occurs during Gram-negative bacterial growth. However, natural production of large amounts of outer membrane vesicles has only been described in a few bacterial genera. The purified vesicles of some bacterial pathogens have shown potential applications in vaccinology and in antibiotic therapy. This study focused on the development of a gene expression system able to induce production of large amounts of outer membrane vesicles. The Tol-Pal system of Escherichia coli, required to maintain outer membrane integrity, is composed of five cell envelope proteins, TolA, TolB, TolQ, TolR and Pal. Tol proteins are parasitized by filamentous bacteriophages and by colicins. The phage infection process and colicin import require, respectively, the N-terminal domain of the minor coat g3p protein and the translocation domain of colicins, with both domains interacting with Tol proteins. In this study, we show that the periplasmic production of either Tol, g3p or colicin domains was able to specifically destabilize the E. coli or Shigella flexneri cell envelope and to induce production of high amounts of vesicles. This technique was further found to work efficiently in Salmonella enterica serovar Typhimurium.

Bacterial Outer Membrane Proteins↗