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1.
Dis Aquat Organ ; 119(1): 75-83, 2016 Apr 12.
Article in English | MEDLINE | ID: mdl-27068505

ABSTRACT

We investigated interactions between the corallivorous gastropod Coralliophila violacea and its preferred hosts Porites spp. Our objectives were to experimentally determine whether tissue loss could progress in Porites during or after Coralliophila predation on corals with and without tissue loss and to histologically document snail predation. In 64% of feeding scars, tissue regenerated within 3 wk, leaving no trace of predation. However, in roughly 28% of scars, lesions progressed to subacute tissue loss resembling white syndrome. In feeding experiments, scars from snails previously fed diseased tissue developed progressive tissue loss twice as frequently as scars from snails previously fed healthy tissue. Scars from previously healthy-fed snails were 3 times as likely to heal as those from previously diseased-fed snails. Histology revealed marked differences in host responses to snails; P. cylindrica manifested a robust inflammatory response with fewer secondary colonizing organisms such as algae, sponges, and helminths, whereas P. rus showed no evident inflammation and more secondary colonization. We conclude that lesion progression associated with Coralliophila may be associated with secondary colonization of coral tissues damaged by predator-induced trauma and necrosis. Importantly, variation at the cellular level should be considered when explaining interspecific differences in host responses in corals impacted by phenomena such as predation.


Subject(s)
Anthozoa/physiology , Feeding Behavior/physiology , Gastropoda/physiology , Animals
2.
Vet Comp Oncol ; 14(4): 361-370, 2016 Dec.
Article in English | MEDLINE | ID: mdl-25223579

ABSTRACT

This retrospective case series evaluates survival outcome of 94 dogs with high metastatic risk mast cell tumours (MCT). Patients were treated with a cytotoxic chemotherapy protocol or the tyrosine kinase inhibitor masitinib, in the presence of gross disease or as an adjunct to surgical resection of the primary tumour. In patients presenting with metastatic disease, surgical resection of the primary tumour with adjunctive therapy with any chemotherapy incurred a significant survival advantage [median survival time (MST): 278 days] compared to patients receiving chemotherapy without surgical excision of the primary tumour (MST: 91 days, P < 0.0001). Patients with a surgically excised Patnaik grade II tumour and high Ki-67 in the absence of metastatic disease treated with vinblastine and prednisolone showed a significantly longer survival (MST: 1946 days) than those treated with masitinib (MST: 369 days, P = 0.0037). Further prospective case-controlled clinical trials of high-risk MCTs are required to make precise evidence-based treatment decisions for individual patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Dog Diseases/drug therapy , Mastocytoma/veterinary , Animals , Benzamides , Chemotherapy, Adjuvant/veterinary , Dog Diseases/mortality , Dog Diseases/surgery , Dogs , Mastocytoma/drug therapy , Mastocytoma/mortality , Mastocytoma/surgery , Neoplasm Grading , Piperidines , Protein Kinase Inhibitors/therapeutic use , Pyridines , Retrospective Studies , Risk Factors , Survival Analysis , Thiazoles/therapeutic use , Treatment Outcome
3.
Neuroscience ; 218: 110-25, 2012 Aug 30.
Article in English | MEDLINE | ID: mdl-22641087

ABSTRACT

The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. Second, the in situ hybridization method combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+ parabrachial neurons, indicating these neurons use glutamate as a transmitter. Third, conscious rats were maintained in a hypotensive or hypertensive state for 2h, and then, their brainstems were prepared by the standard c-Fos method which is a measure of neuronal activity. Both hypotension and hypertension resulted in c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostral-most part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo- and hypertension, and the PBcl signaling only hypotensive changes.


Subject(s)
Hypertension/metabolism , Hypotension/metabolism , Neurons/cytology , Neurons/metabolism , Pons/cytology , Pons/metabolism , Animals , Cardiovascular Physiological Phenomena , Consciousness , Evoked Potentials , Forkhead Transcription Factors/metabolism , LIM-Homeodomain Proteins/metabolism , Male , Microscopy, Confocal , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors/metabolism
4.
Allergy ; 67(7): 904-10, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22583153

ABSTRACT

BACKGROUND: Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T-helper genes in third-generation mice (F2). METHODS: Female BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 µg, or saline) and re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A. fumigatus (62.5 µg) at 9 weeks. IgE, IgG(1) , and IgG(2a) levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon (IFN)-γ and interleukin (IL)-4 promoters. RESULTS: Grandoffspring of mothers dosed with 1250 µg early during pregnancy developed increased airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed early had lower methylation at IL-4 CpG(-408) and CpG(-393) compared to late dosed mice (P < 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE. CONCLUSION: Prenatal exposure to A. fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A. fumigatus was associated with changes in CpG methylation in the IFN-γ and IL-4 promoters that did not correlate consistently with indicators of allergic sensitization.


Subject(s)
Allergens/immunology , DNA Methylation , Hypersensitivity/immunology , Prenatal Exposure Delayed Effects , Allergens/administration & dosage , Animals , Antigens, Fungal/administration & dosage , Antigens, Fungal/immunology , Aspergillus fumigatus/immunology , Eosinophils/immunology , Female , Immunoglobulin E/blood , Immunoglobulin E/immunology , Inflammation/immunology , Inflammation/pathology , Interferon-gamma/genetics , Interleukin-4/genetics , Lung/immunology , Lung/pathology , Mice , Mice, Inbred BALB C , Pregnancy , Promoter Regions, Genetic
5.
Neuroscience ; 193: 229-40, 2011 Oct 13.
Article in English | MEDLINE | ID: mdl-21784133

ABSTRACT

The present study demonstrates that serotonin (5-hydroxytryptamine, 5-HT)-containing axons project to two sets of neurons in the dorsolateral pons that have been implicated in salt appetite regulation. These two neuronal groups are the pre-locus coeruleus (pre-LC) and a region in the parabrachial nucleus termed the external lateral-inner subdivision (PBel-inner). Neurons in both regions constitutively express the transcription factor Forkhead protein2 (FoxP2), and become c-Fos activated after prolonged sodium depletion. They send extensive projections to the midbrain and forebrain, including a strong projection to the ventral tegmental area (VTA)-a reward processing site. The retrograde neuronal tracer cholera toxin ß-subunit (CTb) was injected into the VTA region; this was done to label the cell bodies of the pre-LC and PBel-inner neurons. After 1 week, the rats were killed and their brainstems processed by a triple-color immunofluorescence procedure. The purpose was to determine whether the CTb-labeled pre-LC and PBel-inner neurons, which also had FoxP2 immunoreactive nuclei, received close contacts from 5-HT axons. Neurons with these properties were found in both sites. Since the origin of this 5-HT input was unknown, a second set of experiments was carried out in which CTb was injected into the pre-LC or lateral PB. One week later, the rats were perfused and the brainstems from these animals were analyzed for the presence of neurons that co-contained CTb and tryptophan hydroxylase (synthetic enzyme for 5-HT) immunoreactivity. Co-labeled neurons were found mainly in the area postrema and to a lesser degree, in the dorsal raphe nucleus. We propose that the 5-HT inputs to the pre-LC and PBel-inner may modulate the salt appetite-related functions that influence the reward system.


Subject(s)
Area Postrema/cytology , Forkhead Transcription Factors/metabolism , Locus Coeruleus/cytology , Serotonergic Neurons/physiology , Serotonin/metabolism , Ventral Tegmental Area/physiology , Animals , Cholera Toxin/metabolism , Female , Male , Neural Pathways/physiology , Rats , Rats, Sprague-Dawley
6.
Indoor Air ; 21(6): 512-20, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21658130

ABSTRACT

UNLABELLED: We designed and tested a sampling and analysis system for quantitative measurement of airborne cockroach allergen with sufficient sensitivity for residential exposure assessment. Integrated 1-week airborne particle samples were collected at 10-15 LPM in 19 New York City apartments in which an asthmatic child who was allergic to cockroach allergen resided. Four simultaneous air samples were collected in each home: at heights of 0.3 and 1 m in the child's bedroom and in the kitchen. Extracts of air samples were analyzed by ELISA for the cockroach allergen Bla g2, modified by amplifying the colorimetric signal generated via use of AMPLI-Q detection system (DAKO Corporation, Carpinteria, CA, USA). Settled dust samples were quantified by conventional ELISA. Of the homes where cockroach allergen was detected in settled dust, Bla g2 also was detected in 87% and 93% of air samples in the bedroom and kitchen, respectively. Airborne Bla g2 levels were highly correlated within and between the bedroom and kitchen locations (P < 0.001). Expressed as picogram per cubic meter, the room average geometric mean for Bla g2 concentrations was 1.9 pg/m³ (95% CI 0.63, 4.57) and 3.8 pg/m³ (95% CI 1.35, 9.25) in bedrooms and kitchens, respectively. This method offers an attractive supplement to settled dust sampling for cockroach allergen exposure health studies. PRACTICAL IMPLICATIONS: Until now, cockroach allergen exposures have usually been assessed by collection and analysis of settled dust, on the assumption that airborne cockroach allergen cannot be reliably measured. In this study, a sensitive and quantitative method for measuring indoor airborne exposures to cockroach allergens involving a 7-day integrated total suspended particulate (TSP) sample collected at approximately 10-15 l/min was developed. Investigators are now empowered with an alternative exposure assessment method to supplement their studies and the understanding of allergen aerodynamics in the homes of children with asthma. We report airborne cockroach allergen in apartments, suggesting an ongoing burden of inhalation exposure.


Subject(s)
Air Pollution, Indoor/analysis , Allergens/analysis , Asthma/etiology , Cockroaches/immunology , Allergens/immunology , Animals , Asthma/epidemiology , Asthma/immunology , Child , Child, Preschool , Dust/analysis , Dust/immunology , Housing , Humans , Infant , New York City/epidemiology , Risk Assessment , Time Factors
7.
Clin Exp Allergy ; 40(11): 1602-10, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20718778

ABSTRACT

Significant strides in the understanding of the role of epigenetic regulation in asthma and allergy using both epidemiological approaches as well as experimental ones have been made. This review focuses on new research within the last 2 years. These include advances in determining how environmental agents implicated in airway disease can induce epigenetic changes, how epigenetic regulation can influence T helper cell differentiation and T regulatory cell production, and new discoveries of epigenetic regulation associated with clinical outcomes.


Subject(s)
Environment , Epigenesis, Genetic , Hypersensitivity/genetics , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Asthma/genetics , Epigenesis, Genetic/drug effects , Evidence-Based Medicine/trends , Female , Genetic Predisposition to Disease , Humans , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Phenotype , Pregnancy , Prenatal Exposure Delayed Effects , Risk Assessment , Risk Factors
8.
J Agric Saf Health ; 15(1): 37-47, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19266883

ABSTRACT

This comprehensive study was conducted primarily to identify the common causes of agricultural injuries on active Virginia farms and to identify hazardous agricultural operations, exposure duration, and injuries associated with each hazardous operation. In addition, the influences of factors such as general health status of farmers, age, weight, and alcohol and tobacco use on injury were examined. This information will be used for the development of educational programs that will improve the safety of agricultural operations. The sample selected for the study included farms of 28 ha or more, operating on a full- or part-time basis. This stipulation was to ensure that all farms in the sample are active and that participants generated a major portion of their income from the farm. Of the 26,000 farms meeting this requirement, 1,650 were selected to participate in the study. A survey instrument was mailed to the farmers selected to collect the information needed for meeting the established objectives of the study. Approximately 19% of the surveys were returned. In terms of percentage injuries, livestock handling was the primary cause. This was followed by working in elevated locations, operating and repairing agricultural machinery, and heavy lifting. The activities carried out most frequently by the participants were: operating farm tractors, operating trucks/automobiles, using hand and power tools, and working with agricultural chemicals. The overall injury rate was 5.6 injuries per 100,000 h. The exposure to agricultural hazards appeared to have minimal or no effect on the health status of Virginia farmers. Farm workers in the 45 to 64 age group sustained the most injuries. Older, more experienced farmers reported fewer injuries because of limited exposure to hazards and work experience. The average age of Virginia farmers surveyed was 60. This is expected to rise because most respondents reported no plans to retire during the next five years. Based on the results, educational programs for improving the agricultural safety in Virginia should focus on aging farmers, hazardous agricultural activities, and weight control.


Subject(s)
Accidents, Occupational/statistics & numerical data , Agriculture , Animal Husbandry/statistics & numerical data , Health Status , Wounds and Injuries/epidemiology , Adult , Age Distribution , Animals , Female , Health Surveys , Humans , Incidence , Injury Severity Score , Male , Middle Aged , Population Surveillance , Risk Factors , Surveys and Questionnaires , Virginia/epidemiology
9.
J Agric Saf Health ; 14(3): 273-82, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18788330

ABSTRACT

Geographic disbursement, unsecured environments, and the concentration and commingling of agricultural products make agriculture a vulnerable target for a terrorist attack. To counter an act of agroterrorism, efforts are needed at the organism level, the farm level, the agricultural sector level, and the national level. Producers and the measures they take are essential in countering an attack at the farm level. However, producers may question the need for security measures, especially if they feel that their farm or ranch is an unlikely target. The attitudes and perceptions of Utah agricultural producers towards agroterrorism were examined in a mixed methods study using a QUAN-QUAL model. Twenty-five producers were purposefully selected to provide a cross-section of Utah agriculture. All participants filled out a questionnaire followed by a face-to-face interview in which they were asked to rate their level of concern about an act of agroterrorism at the farm, state, and national level. They were also asked about any security measures that they had taken and why, the identification of highly transmissible diseases, and their willingness to implement security measures. Producers were most concerned about an act of agroterrorism at the national level and least concerned about an act of agroterrorism occurring on their farm or ranch. Although many of the producers had implemented some security measures within the last year, most actions were in response to vandalism. More efforts are needed to educate Utah producers regarding highly transmissible diseases and their symptoms.


Subject(s)
Agriculture/standards , Bioterrorism , Consumer Product Safety , Food Contamination/prevention & control , Security Measures/organization & administration , Animals , Attitude , Disaster Planning , Female , Food Supply/standards , Humans , Interviews as Topic , Male , Middle Aged , Perception , Risk Assessment , Surveys and Questionnaires , Utah
10.
Br J Dermatol ; 157(6): 1132-47, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17944981

ABSTRACT

BACKGROUND: The molecular events leading to actinic keratosis (AK) are not well understood. OBJECTIVE: To identify and compare gene expression changes in AK lesions and in sun-exposed nonlesional skin and to determine the effect of imiquimod 5% cream on these changes. METHOD: A double-blind, vehicle-controlled, randomized study was conducted to evaluate the molecular changes in AK treated with imiquimod. Seventeen male subjects with >/= 5 AK lesions on the scalp applied vehicle or imiquimod three times a week for 4 weeks. Gene expression analysis using Affymetrix oligonucleotide arrays was performed on shave biopsies of lesions taken before and after treatment. Confocal microscopy was performed on the study area as an adjunctive diagnostic procedure. RESULTS: We identified gene expression changes which occur in sun-exposed, nonlesional skin as well as in AK lesions. These changes include, but are not limited to, the overexpression of oncogenic and proliferative genes and diminished expression of tumour suppressor genes. The gene expression changes observed in AK lesions and in sun-exposed, nonlesional skin were consistent with the confocal microscopy observations, which showed abnormalities in the sun-exposed, nonlesional skin, similar in nature but less pronounced than abnormalities seen in AK. Imiquimod partially or totally reversed the aberrant expression of some of the genes observed in AK, consistent with clearing of lesions and normalization of confocal cellular images. CONCLUSIONS: The data show that profound gene expression changes occur in sun-exposed, nonlesional skin which progress further in AK lesions. The data also suggest that imiquimod may play a role in normalizing gene expression and cellular morphology in sun-damaged skin.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Aminoquinolines/therapeutic use , Gene Expression/drug effects , Keratosis/genetics , Photosensitivity Disorders/genetics , Scalp Dermatoses/genetics , Toll-Like Receptor 7/agonists , Administration, Topical , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Double-Blind Method , Follow-Up Studies , Humans , Imiquimod , Keratosis/drug therapy , Male , Middle Aged , Oligonucleotide Array Sequence Analysis/methods , Photosensitivity Disorders/drug therapy , Scalp Dermatoses/drug therapy , Treatment Outcome
11.
Arch Dis Child Fetal Neonatal Ed ; 92(1): F68-73, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17185433

ABSTRACT

Atopic diseases are complex entities influenced by an array of risk factors, including genetic predisposition, environmental allergens, antenatal exposures, infections and psychosocial factors. One proposed mechanism by which these risk factors contribute to the development of atopic disease is through changes in the production of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) cytokines. The objectives of this review are to discuss antenatal exposures that are associated with paediatric atopic diseases, to discuss the influence of the intrauterine environment on neonatal immune responses, to provide an overview of the Th1 and Th2 pathways and how they relate to atopic disease, and to summarise our current understanding of the association between cytokine responses in cord blood and the development of atopic disease in early childhood.


Subject(s)
Cytokines/immunology , Hypersensitivity/immunology , Child, Preschool , Epitopes/immunology , Female , Fetal Blood/immunology , Humans , Models, Immunological , Pregnancy , Prenatal Exposure Delayed Effects/immunology , Risk Factors , Th1 Cells/immunology , Th2 Cells/immunology
12.
Clin Exp Allergy ; 36(7): 892-8, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16839404

ABSTRACT

BACKGROUND: Asthma is the most common medical condition during pregnancy. While increased production of T helper cytokines has been reported to occur in both asthma and pregnancy, the effect of T-helper type 2 (Th2) polarization on asthma symptoms during pregnancy has not been well-characterized. OBJECTIVE: We hypothesized that systemic Th2 cytokine and chemokine polarization occurs among asthmatics to a greater extent during their pregnancy, and is associated with more severe asthma and increased Th2 polarization in the newborn. METHODS: Fifty-six pregnant asthmatics were recruited from prenatal clinics affiliated with New York Presbyterian Hospital. Systemic production of interleukin-4, interferon-gamma, eotaxin and IP10 were measured by intracytoplasmic staining or ELISA at recruitment, peripartum and post-partum, and in the cord blood. The frequency of asthma symptoms was measured by questionnaires and compared with Th biomarkers. RESULTS: The chemokine ratio (IP10/eotaxin) declined over the course of pregnancy (from 3.3 +/- 1.3 to 1.4 +/- 0.2, P = 0.016), but IP10 and eotaxin increased post-partum. The decrease in the chemokine ratio was associated with more frequent asthma symptoms. A non-significant trend towards decreased interferon-gamma and increased interleukin-4 production was detected. Cord blood eotaxin levels correlated with maternal levels (r = 0.35, P = 0.03). Other peripartum biomarkers were not associated with Th2 polarization nor with subsequent respiratory symptoms in the newborn. CONCLUSION: IP10/eotaxin declined over the course of pregnancy and was associated with worse asthma symptoms. Alterations of Th1/Th2 chemokine balance during pregnancy may identify women prone to more severe asthma during pregnancy.


Subject(s)
Asthma/immunology , Infant, Newborn/immunology , Pregnancy Complications/immunology , Th2 Cells/immunology , Adult , Biomarkers/blood , Chemokine CCL11 , Chemokines/biosynthesis , Chemokines, CC/biosynthesis , Cohort Studies , Cytokines/biosynthesis , Female , Fetal Blood/immunology , Humans , Influenza Vaccines/immunology , Postpartum Period/immunology , Pregnancy , Respiration/immunology , Severity of Illness Index
13.
Proc Natl Acad Sci U S A ; 103(4): 837-42, 2006 Jan 24.
Article in English | MEDLINE | ID: mdl-16415159

ABSTRACT

Isotope, aerosol, and methane records document an abrupt cooling event across the Northern Hemisphere at 8.2 kiloyears before present (kyr), while separate geologic lines of evidence document the catastrophic drainage of the glacial Lakes Agassiz and Ojibway into the Hudson Bay at approximately the same time. This melt water pulse may have been the catalyst for a decrease in North Atlantic Deep Water formation and subsequent cooling around the Northern Hemisphere. However, lack of direct evidence for ocean cooling has lead to speculation that this abrupt event was purely local to Greenland and called into question this proposed mechanism. We simulate the response to this melt water pulse using a coupled general circulation model that explicitly tracks water isotopes and with atmosphere-only experiments that calculate changes in atmospheric aerosol deposition (specifically (10)Be and dust) and wetland methane emissions. The simulations produce a short period of significantly diminished North Atlantic Deep Water and are able to quantitatively match paleoclimate observations, including the lack of isotopic signal in the North Atlantic. This direct comparison with multiple proxy records provides compelling evidence that changes in ocean circulation played a major role in this abrupt climate change event.


Subject(s)
Climate , Atlantic Ocean , Cold Climate , Computer Simulation , Earth, Planet , Environment , Evolution, Planetary , Greenhouse Effect , Greenland , Methane/chemistry , Temperature , Water , Water Movements
14.
Leukemia ; 20(2): 286-95, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16341037

ABSTRACT

Weak immunogenicity of chronic lymphocytic leukemia (CLL) cells may contribute to disease progression and inhibit effective immunotherapy. Accordingly, agents that enhance the immunogenicity of CLL cells may be useful in immunotherapeutic approaches to this disease. Since Toll-like receptors (TLRs) are major regulators of innate immunity and initiation of adaptive immunity, we studied the effects of viral pathogen associated molecular pattern agonists (that are recognized by TLRs) on the costimulatory phenotype and function of CLL cells. CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors. Additional activation of protein kinase C pathways increased the ability to stimulate T-cell proliferation, blocked phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT)3, and resulted in the acquisition of a dendritic cell surface phenotype by TLR7-activated CLL cells. Normal B cells also responded to TLR7 activation by increasing costimulatory molecule expression and cytokine production. These findings suggest a potential role for TLR7 agonists in CLL immunotherapy.


Subject(s)
Imidazoles/pharmacology , Immunologic Factors/pharmacology , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Phorbol Esters/pharmacology , Quinolines/pharmacology , Toll-Like Receptor 7/metabolism , Adult , Aged , Aged, 80 and over , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Chemokines/biosynthesis , Cytokines/biosynthesis , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Male , Middle Aged , STAT3 Transcription Factor/drug effects , STAT3 Transcription Factor/metabolism , Sensitivity and Specificity , Toll-Like Receptor 7/drug effects , Tumor Cells, Cultured
15.
J Agric Saf Health ; 10(4): 287-95, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15603227

ABSTRACT

The purposes of this study were to identify the source and frequency of agricultural injuries in Utah, and determine an injury rate for common agricultural activities. Previous studies conducted in Utah examined injury rates by utilizing emergency room logs. This study collected data directly from the source, farmers and ranchers in Utah, and included all modes of treatment. A random sample of Utah Farm Bureau members were mailed questionnaires to assess the number of injuries occurring during the past three years, the mode of treatment for the most recent injury, and the percentage of time spent in hazardous activities. The rate of injuries requiring medical treatment (19.9%) observed in this survey-based study was higher than reported in previous studies at the state and national level. Nearly half (48.7%) of the injuries reported were treated at home or by a family member. As in the previous Utah studies, working with horses was found to be the single most dangerous activity for agriculturalists in Utah in terms of injuries per unit time of exposure, followed by servicing agricultural machinery.


Subject(s)
Accidents, Occupational/statistics & numerical data , Agricultural Workers' Diseases/epidemiology , Adult , Aged , Aged, 80 and over , Agricultural Workers' Diseases/etiology , Agricultural Workers' Diseases/pathology , Female , Humans , Injury Severity Score , Male , Middle Aged , Utah/epidemiology
16.
Int Immunopharmacol ; 2(4): 443-51, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11962724

ABSTRACT

In this review, we discuss the ongoing development of a new treatment option for genital herpes (GH), the disease caused by herpes simplex virus (HSV) types I and II. Following infection, the virus establishes a latent infection in peripheral neurons, which periodically activates to cause recurrent skin lesions or asymptomatic shedding in the anogenital area. A new class of drugs, the immune response modifiers (IRMs), modulates the immune system against viral infection. This approach is currently being tested as a treatment for GH. We first review the effectiveness of treatment of other viral diseases with imiquimod, the first IRM to be licensed (Aldara, imiquimod 5% cream), and one used for the treatment of external anogenital warts. We then focus on resiquimod, an analog of imiquimod, which shows early promise as a new treatment option for GH. The evidence from in vitro and in vivo studies, in particular the guinea pig model of GH, describing the effectiveness and mode of action of this novel immunopharmacological agent is presented. Resiquimod stimulates specific cells of the innate immune system (including monocytes/macrophages, dendritic cells (DC) and B lymphocytes) to produce cytokines (in particular IFN-alpha, IL-12, TNF-alpha and IFN-gamma) that initiate and drive the development of the Th1 acquired immune response against HSV-infected cells. Recent results from clinical trials and in vivo studies in animal models are consistent with the hypothesis that the development of HSV-specific cell-mediated immunity may prove to be the key in providing a long-lasting protection against GH recurrences.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Herpes Genitalis/drug therapy , Herpes Genitalis/immunology , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Aminoquinolines/chemistry , Aminoquinolines/pharmacology , Aminoquinolines/therapeutic use , Animals , Herpes Genitalis/pathology , Herpes Genitalis/virology , Herpesvirus 1, Human/drug effects , Herpesvirus 2, Human/drug effects , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Imidazoles/therapeutic use , Imiquimod , Recurrence
17.
BMC Dev Biol ; 1: 14, 2001.
Article in English | MEDLINE | ID: mdl-11701088

ABSTRACT

BACKGROUND: In vitro maturation of mammalian oocytes is an area of great interest due to its potential application in the treatment of infertility. The morphological and physiological changes that occur during oocyte development are poorly understood, and further studies are needed investigating the physiological changes associated with oocyte maturation. In this study we evaluated the membrane potential and the sodium/potassium permeability ratio of oocytes acutely isolated, and cumulus-oocyte complexes in metaphase II and preantral follicle stages. RESULTS: Intracellular electrical recordings revealed that cumulus-enclosed oocytes have a membrane potential significantly more negative at the preantral follicle stage than at metaphase II stage (-38.4 versus -19.7 mV, p < 0.0005). The membrane potential of the cumulus-free oocytes was not different between the preantral and metaphase II stages. The membrane potential of the cumulus cells forming preantral stage follicles was shown to be significantly different from that of the oocyte within the follicle (-28.6 versus -38.4 mV, p < 0.05). The sodium/potassium permeability measured in cumulus-enclosed oocytes at the preantral stage equaled a mean value of 0.33. The ratio was significantly lower when measured in oocytes denuded of cumulus cells or cumulus-enclosed metaphase II oocytes, 0.76, 0.79, 0.77 respectively (p < 0.001). CONCLUSIONS: These data show a change in the membrane potential and Na+/K+ permeability ratio during ooycte development from the preantral stage oocyte to the metaphase II stage. We have also demonstrated a change in the preantral oocyte membrane potential when surrounding cumulus cells are removed; either due to membrane changes or loss of cumulus cells.


Subject(s)
Cell Membrane Permeability/physiology , Membrane Potentials/physiology , Oocytes/growth & development , Oocytes/physiology , Ovarian Follicle/embryology , Ovarian Follicle/metabolism , Potassium/metabolism , Sodium/metabolism , Animals , Cricetinae , Female , Mesocricetus
18.
Am J Respir Crit Care Med ; 164(6): 995-1001, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11587985

ABSTRACT

Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 upregulation.


Subject(s)
Allergens/immunology , Asthma/etiology , Fetus/immunology , Hypersensitivity/etiology , Pregnancy Complications , Adult , Animals , Cells, Cultured , Cockroaches/immunology , Cohort Studies , Cytokines/immunology , Data Interpretation, Statistical , Dust , Female , Fetal Blood/immunology , Humans , Hypersensitivity/diagnosis , Immunoglobulin E/analysis , Infant, Newborn , Lymphocytes/immunology , Mice , Mites/immunology , New York City/ethnology , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/etiology , Risk Factors , T-Lymphocytes/cytology , T-Lymphocytes/immunology
19.
Focus ; 16(10): 1-4, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11668967
20.
Am J Community Psychol ; 29(4): 621-47, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11554155

ABSTRACT

A multiple case study design was used to explore the organizational characteristics of community-based organizations that provide HIV prevention programs and the criteria these organizations employ when judging the merits of externally-developed HIV prevention programs. In-depth interviews were conducted with organizational representatives of 38 randomly-selected HIV prevention providers throughout Illinois. Results indicated that there were three main types of adopting organizations: adopters of entire programs, adopters of program components and practices, and adopters of common ideas. These three types of organizations were distinguished by their level of organizational commitment to HIV prevention, organizational resources, and level of organizational maturity. Narrative data from the interviews are used to describe the dimensions that underlie the organizations' program adoption criteria. The criteria of merit used by these organizations to evaluate prevention programs provide partial empirical support for existing theories of technology transfer. Implications for designing and disseminating HIV prevention programs are discussed.


Subject(s)
Community Health Services/organization & administration , Diffusion of Innovation , HIV Infections/prevention & control , Health Promotion/organization & administration , Adolescent , Adult , Anecdotes as Topic , Female , Humans , Illinois , Interviews as Topic , Male , Marketing of Health Services , Organizational Case Studies , Organizational Innovation , Organizations, Nonprofit , Persuasive Communication , Program Evaluation
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