Publications by authors named "Jeffrey Lake"

15 Publications

  • Page 1 of 1

Effects of housing density in five inbred strains of mice.

PLoS One 2014 21;9(3):e90012. Epub 2014 Mar 21.

The Jackson Laboratory, Bar Harbor, Maine, United States of America.

To evaluate the effect of increased mouse density in a cage, mice were housed at the density recommended by the 1996 Guide for the Care and Use of Laboratory Animals and at densities that were approximately 2, 2.6, and 3 times greater. Five strains of mice (129S1/SvImJ, A/J, BALB/cByJ, C57BL/6J, and DBA/2J) were evaluated throughout 3- and 8-month timeframes for health and well-being, including mortality, cardiac measures, plasma cholesterol, body weight, bone mineral density, organ weights, hematology, behavioral observations, and open field and light-dark tests. For 22 of the 27 traits measured, increased housing density had no significant effect. Kidney weight, adrenal weight, and heart rate decreased as mice were housed more densely, and some of the decreases were statistically significant. Reduced kidney weight, adrenal weight, and heart rate are not considered to be negative outcomes and may even indicate reduced stress. However, all measurements of these three traits were within normal physiological ranges. Percent fat increased slightly in strains 129S1/SvImJ, A/J, and DBA/2J, but did not increase in strains BALB/cByJ, and C57BL/6J. These results indicate that mice can be housed at higher densities than those currently recommended.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962340PMC
January 2015

The public health leadership certificate: a public health and primary care interprofessional training opportunity.

Health Promot Pract 2014 Mar;15(1 Suppl):64S-70S

1Eastern Virginia Medical School, Norfolk, VA, USA.

This article describes a public health leadership certificate curriculum developed by the Commonwealth Public Health Training Center for employees in public health and medical trainees in primary care to share didactic and experiential learning. As part of the program, trainees are involved in improving the health of their communities and thus gain a blended perspective on the effectiveness of interprofessional teams in improving population health. The certificate curriculum includes eight one-credit-hour didactic courses offered through an MPH program and a two-credit-hour, community-based participatory research project conducted by teams of trainees under the mentorship of health district directors. Fiscal sustainability is achieved by sharing didactic courses with MPH degree students, thereby enabling trainees to take advantage of a reduced, continuing education tuition rate. Public health employee and primary care trainees jointly learn knowledge and skills required for community health improvement in interprofessional teams and gain an integrated perspective through opportunities to question assumptions and broaden disciplinary approaches. At the same time, the required community projects have benefited public health in Virginia.
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http://dx.doi.org/10.1177/1524839913509275DOI Listing
March 2014

A qualitative investigation of the motivations, experiences and views of female sunbed users under the age of 18 in England.

J Public Health (Oxf) 2014 Mar 30;36(1):56-64. Epub 2013 Jan 30.

NHS North Central London, London, UK.

Objective: To explore the motivations, experiences and views of female regular sunbed users aged 15-17 and consider the implications of legislation seeking to restrict sunbed use among the under-18s. Design Qualitative study of 12 focus groups.

Method: Participants were recruited opportunistically through community and social networks, around tanning salons, leisure and educational facilities in six English towns and cities. Interviews were transcribed, a thematic framework generated and a validation exercise conducted. Setting Urban communities in England. Participants Sixty-nine female regular sunbed users aged 15-18.

Results: Respondents consistently valued tanning and attached considerable personal and social importance to it. They showed an awareness of the risks of sunbed use that they accepted, downplayed and/or ignored. While experiences and responses to supervision varied, respondents were resistant to any measures that restricted their use and expressed willingness to find ways around such restrictions.

Conclusions: The sunbed users interviewed in this study attached considerable significance to tanning, rationalized the risks of sunbed use and expressed their determination to continue using them. The impact of legislation to limit sunbed access may be weakened without requirements to ensure supervision of salons.
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http://dx.doi.org/10.1093/pubmed/fds107DOI Listing
March 2014

Mouse gestation length is genetically determined.

PLoS One 2010 Aug 25;5(8):e12418. Epub 2010 Aug 25.

The Jackson Laboratory, Bar Harbor, Maine, United States of America.

Background: Preterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined.

Methodology/principal Findings: To further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#(A/J)/NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length.

Conclusions/significance: Together, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928290PMC
August 2010

Comment on "Functional traits and niche-based tree community assembly in an Amazonian forest".

Science 2009 May;324(5930):1015; author reply 1015

Department of Ecology and Evolutionary Biology, University of Michigan, Kraus Natural Sciences Building, 830 North University, Ann Arbor, MI 48109, USA.

Kraft et al. (Reports, 24 October 2008, p. 580) used a variety of metrics describing the distribution of functional traits within a tropical forest community to demonstrate simultaneous environmental filtering and niche differentiation. We discuss how these results could have arisen from sampling design and statistical assumptions, suggesting alternative approaches that could better resolve these questions.
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http://dx.doi.org/10.1126/science.1169721DOI Listing
May 2009

Ovalbumin serves as a neo-transplantation antigen in retinal pigment epithelial cells.

Mol Vis 2007 Oct 5;13:1902-11. Epub 2007 Oct 5.

Department of Ophthalmology, Emory University, Atlanta, GA, USA.

Purpose: Our long-term goal is to determine the optimal methods for inducing allograft tolerance to facilitate transplantation of retinal pigment epithelial cells or stem cells for the treatment of retinal degenerative diseases. These goals have been hampered by the extreme complexity of allograft rejection and the heterogeneity of responding T cells. The current studies were undertaken to develop a simplified transplant model for studying rejection and tolerance in the unique environment of the eye.

Methods: To provide a defined transplantation antigen, transgenic C57BL/6 (B6) mice were produced, which express the exogenous chicken egg ovalbumin (OVA) gene under the regulation of the mouse tyrosinase related protein-1 (TRP-1) promoter that is transcriptionally active in retinal pigmented epithelial (RPE) cells. To determine whether the transgene was expressed as a neo-transplantation antigen, RPE from TRP-1-OVA mice were injected into the subretinal space of B6 mice or B6 mice expressing the OVA-specific (OT1) TCR transgenes and examined for inflammatory cell infiltration.

Results: The TRP-1-OVA transgenic mice expressed OVA mRNA in the brain and eye but not the heart or kidney. RPE cells from TRP-1-OVA transgenic mice expressed mRNA and protein encoded by the OVA gene and RPE expressing TRP-1-OVA induced an inflammatory response within the subretinal space of OT1 mice but not in B6 mice.

Conclusions: OVA serves as a defined, neo-transplantation antigen in RPE that is recognized by mice whose CD8+ T cells recognize OVA peptide. These observations provide new tools for future studies of the mechanisms of rejection and prolongation of RPE transplants in the eye.
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October 2007

Molecular predictors of lymph node metastasis in colon cancer: increased risk with decreased thymidylate synthase expression.

J Gastrointest Surg 2005 Dec;9(9):1216-21; discussion 1221

Department of Colorectal Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

TNM staging in colon cancer has several limitations. Prognostic molecular markers are now being developed to address these limitations. The aim of this study was to identify a combination of genes and markers whose expression is predictive of nodal status and outcome in colon cancer. The expression of 12 genetic markers were examined in 66 node-positive and 65 node-negative T3 colon cancers. Gene expression was quantified using real-time polymerase chain reaction. Microsatellite instability status was available through the registry. Association with lymph node status was examined using univariate and multivariate logistic regression. Thymidylate synthase expression was statistically significantly associated with lymph node status (odds ratio 0.36; 95% confidence interval: 0.16-0.81). Microsatellite instability and the other genes were not associated with nodal status. Multiple logistic regression did not identify a significant multivariate predictive model. Decreased expression of thymidylate synthase is associated with a higher risk of lymph node metastasis in patients with T3 colon cancers. Microsatellite instability and the expression of other genes are not predictive of nodal status in this population. Thymidylate synthase gene expression may help identify patients at greater risk for progression of disease.
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http://dx.doi.org/10.1016/j.gassur.2005.06.028DOI Listing
December 2005

The management of complicated diverticulitis and the role of computed tomography.

Am J Gastroenterol 2005 Apr;100(4):910-7

Department of Colorectal Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

Purpose: Acute diverticulitis is a disease with a wide clinical spectrum, ranging from a phlegmon (stage Ia), to localized abscesses (stages Ib and II), to free perforation with purulent (stage III) or feculent peritonitis (stage IV). While there is little debate about the best treatment for mild episodes and/or very severe episodes, uncertainty persists about the optimal management for intermediate stages (Ib and II). The aim of our study was therefore to define the role of computed tomography (CT) and to analyze its impact on the management of acute diverticulitis.

Methods: We retrospectively analyzed 511 patients (296 males, 215 females) admitted for acute diverticulitis between January 1994 and December 2003. Excluded were patients with stoma reversal only, "diverticulitis" mimicked by cancer, or significantly deficient patient records. Patients were analyzed either as a whole or subgrouped according to age (<40 yr, >40 yr). A modified Hinchey classification was used to stage the severity of acute diverticulitis.

Results: In 99 patients (19.4%), an abscess was found (74 pericolic, 25 pelvic, median diameter: 4.0 cm). CT-guided drainage was performed in 16 patients, one failure requiring a two-stage operation. Whereas conservative treatment failed in 6.8% in patients without abscess or perforation, 22.2% of patients with an abscess required an urgent resection (68.2%, one-stage, 31.8%, two-stage). Recurrence rates were 13% for mild cases, as compared to 41.2% in patients with a pelvic abscess (stage II) treated conservatively with/without CT-guided drainage. Of all surgical cases, resection/primary anastomosis was achieved in 73.6% with perioperative mortality of 1.1% and leak rate was 2.1%.

Conclusions: CT evidence of a diverticular abscess has a prognostic impact as it correlates with a high risk of failure from nonoperative management regardless of the patient's age. After treatment of diverticulitis with CT evidence of an abscess, physicians should strongly consider elective surgery in order to prevent recurrent diverticulitis.
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http://dx.doi.org/10.1111/j.1572-0241.2005.41154.xDOI Listing
April 2005

Management of retained colorectal foreign bodies: predictors of operative intervention.

Dis Colon Rectum 2004 Oct;47(10):1694-8

Department of Colorectal Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

Purpose: This study was designed to review experience at our hospital with retained colorectal foreign bodies.

Methods: We reviewed the consultation records at Los Angeles County + University of Southern California General Hospital from October 1993 through October 2002. Ninety-three cases of transanally introduced, retained foreign bodies were identified in 87 patients. Data collected included patient demographics, extraction method, location, size and type of foreign body, and postextraction course.

Results: Of 93 cases reviewed, there were 87 individuals who presented with first-time episodes of having a retained colorectal foreign body. For these patients, bedside extraction was successful in 74 percent. Ultimately, 23 patients were taken to the operating room for removal of their foreign body. In total, 17 examinations under anesthesia and 8 laparotomies were performed (2 patients initially underwent an anesthetized examination before laparotomy). In the eight patients who underwent exploratory laparotomy, only one had successful delivery of the foreign object into the rectum for transanal extraction. The remainder required repair of perforated bowel or retrieval of the foreign body via a colotomy. In our review, a majority of cases had objects retained within the rectum; the rest were located in the sigmoid colon. Fifty-five percent of patients (6/11) presenting with a foreign body in the sigmoid colon required operative intervention vs. 24 percent of patients (17/70) with objects in their rectum (P = 0.04).

Conclusions: This is the largest single institution series of retained colorectal foreign bodies. Although foreign objects located in the sigmoid colon can be retrieved at the bedside, these cases are more likely to require operative intervention.
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http://dx.doi.org/10.1007/s10350-004-0676-4DOI Listing
October 2004

Patterns of Internet use: bariatric versus colorectal patients in a private institution.

J Am Coll Surg 2004 Aug;199(2):223-8

Department of Surgery, University of Southern California, Los Angeles, CA, USA.

Background: The frequency of Internet use for self-directed medical care in different patient populations is increasing. We evaluated Internet use by patients presenting for bariatric surgery.

Study Design: Surveys were completed by 136 patients (109 women, 22 men) presenting to a private academic clinic for bariatric surgery. Data collected included age, gender, education level, household income, and pattern of Internet use. Comparisons were made with a group of 135 patients who visited a colorectal surgery clinic in the same institution.

Results: Bariatric patients who used the Internet were more likely than colorectal patients to inform themselves about their medical problem (76% versus 49%, p < 0.001) and tended to use the Internet more overall (85% versus 78%, p = ns). Use of the Internet to research bariatric surgery was associated with education level (p = 0.002) and household income (p = 0.01), but not with age or gender. Bariatric patients were more likely than colorectal patients to search our institution's Web site (40% versus 17%, p < 0.001) and to use the Internet to find out about their surgeon (47% versus 31%, p = 0.01). Only 9% of bariatric patients used a chat room. Ninety-six percent of bariatric patients found the information on the Internet easy to understand and 58% described it as very helpful.

Conclusions: Bariatric patients are especially likely to use the Internet to gain information about their medical condition, possibly reflecting their limited mobility. This represents an educational opportunity for the surgical community.
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http://dx.doi.org/10.1016/j.jamcollsurg.2004.03.009DOI Listing
August 2004

Effect of high-dose steroids on anastomotic complications after proctocolectomy with ileal pouch-anal anastomosis.

J Gastrointest Surg 2004 Jul-Aug;8(5):547-51

Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

This review was designed to determine whether "high-dose" steroid therapy (> or =20 mg prednisone/day) increases the likelihood of anastomotic complications after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The hospital records of 100 patients undergoing proctocolectomy with IPAA were reviewed. Patient characteristics were analyzed to determine what factors were associated with higher rates of anastomosis-related complications. Seventy-one of our patients were given diverting ileostomies, whereas the remaining 29 underwent a single-stage procedure. Fifty-four percent of the patients in our review were taking steroids preoperatively, 39 of whom were on high-dose therapy. The overall anastomosis-related complication rate was 14%. There was no significant difference in complication rates with respect to age, steroid use, steroid dose, use of a diverting ileostomy, type of anastomosis, duration of disease, or presence of backwash ileitis. A trend toward higher leakage rates was found in patients undergoing single-stage procedures (10.3% vs. 2.8%, P=0.14) as well as in patients undergoing single-stage procedures on high-dose steroids (22% vs. 5.0, P=0.22). Nevertheless, neither of these trends was found to be statistically significant, which was likely influenced by the small sample size. Our data suggest that there may be an increase in anastomotic leakage rates in patients on high-dose steroids undergoing a single-stage proctocolectomy with IPAA. Nevertheless, our rate was not as high as the rates seen by other investigators and did not reach statistical significance. During preoperative counseling, patients on high-dose steroids should be informed of this uncertain but real risk of anastomotic leakage.
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http://dx.doi.org/10.1016/j.gassur.2004.01.002DOI Listing
January 2005

Internet use by colorectal surgery patients: a surgeon's tool for education and marketing.

Am Surg 2004 Jun;70(6):553-8

Department of Colorectal Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

The goal of this study is to understand the role of the Internet in the education and recruitment of patients within colorectal surgery practices. Surveys of Internet use were completed by 298 patients visiting five outpatient colorectal surgery clinics affiliated with the University of Southern California. Data collected included the patient's age, gender, level of education, zip code at home, type of clinic visited, and information on the respondent's Internet use. Overall, 20 per cent of the respondent patients visiting our clinics had used the Internet to research the medical condition that prompted their visit. Highest grade level completed (P < 0.001), age (P < 0.01), type of clinic (P < 0.001), and household income (P < 0.001) were all found to be associated with any prior use of the Internet whereas gender was not (P = 0.58). Among Internet users, only household income and frequent use of the Internet were associated with searching the Internet for medical information (P < 0.001). Ultimately, all of the Internet-using patients surveyed felt the medical information they found was "some what" or "very helpful." Understanding which patients "go online" to search for medical information is essential for surgeons who wish to use the Internet for marketing their practices and educating their patients.
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June 2004

Three new Drosophila markers of intracellular membranes.

Biotechniques 2004 May;36(5):784-8, 790

University of North Carolina Greensboro, Department of Biology, 231 Eberhart Bldg., Greensboro, NC 27402, USA.

The need for cellular markers that permit a quick and accurate evaluation of a protein's subcellular localization has increased with the surge of new data generated by the Drosophila genome project. In this report, we present three ubiquitously expressed Drosophila transgenes that expressed a green fluorescent protein variant (enhanced yellow fluorescent protein) that has been targeted to different intracellular membrane targets: the Golgi apparatus, mitochondria, and endoplasmic reticulum. These markers serve as an internal standard for characterizing a protein's subcellular localization or as a means of tracking the dynamics of intracellular organelles during normal or abnormal cellular or developmental processes. We have also examined fixation artifacts using these constructs to illustrate the effects that fixation and permeabilization have on intracellular membrane organization.
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http://dx.doi.org/10.2144/04365ST01DOI Listing
May 2004

gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo.

Immunology 2004 Feb;111(2):155-64

Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Oral administration of antigen induces a state of tolerance that is associated with activation of CD8+ T cells that can transfer unresponsiveness to naïve syngeneic hosts. These T cells are not lytic, but they inhibit development of antibody, CD4+ T helper cell, and CD8+ cytotoxic T lymphocyte (CTL) responses upon adoptive transfer into naïve, syngeneic mice. In addition, we have shown that depletion of gammadelta T cells by injection of the anti-delta chain antibody (GL3) down modulates the expression of gammadelta T-cell receptor (TCR) and inhibits the induction of oral tolerance to ovalbumin. Oral administration of antigen also fails to induce tolerance in TCR delta-chain knockout mice suggesting that gammadelta T cells play a critical, active role in tolerance induced by orally administered antigen. To further study the contribution of gammadelta T cells to tolerance, murine gammadelta T cells were isolated from intraepithelial lymphocytes (IEL) of the small intestine by stimulation with splenic filler cells, concanavalin A and growth factors. gammadelta IEL lines demonstrated lytic activity in a redirected lysis assay. gammadelta T-cell clones express different gammadelta TCR genes and secrete large amounts of interleukin (IL)-10, but little or no IL-2, IL-4, or interferon-gamma. gammadelta IEL clones expressed transforming growth factor-beta1 and macrophage migration inhibitory factor, as well as IL-10, mRNA. Moreover, gammadelta T-cell clones potently inhibited the generation of CTL responses by secreted molecules rather than by direct cell-to-cell contact.
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http://dx.doi.org/10.1111/j.0019-2805.2003.01793.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782403PMC
February 2004

An alternative structure for improving the public's health.

J Public Health Manag Pract 2002 Jan;8(1):75-82

Virginia Department of Health, Richmond, USA.

The emergence of public health institutes outside government is one of many innovative approaches to promote community health improvement. This article describes the state of Virginia's current model of government public health and provides a context for Virginia's approach to the Turning Point initiative. The article explores the reasons why Virginia chose to establish its public health institute outside government and demonstrates how development of the institute is changing community health improvement in the state. The article also describes a new initiative to create a national network of public health institutes.
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http://dx.doi.org/10.1097/00124784-200201000-00015DOI Listing
January 2002