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1.
J Cancer Educ ; 38(2): 467-475, 2023 04.
Article in English | MEDLINE | ID: mdl-35112296

ABSTRACT

Ideal efforts for cancer prevention would include lifestyle modifications along with routine, age-eligible cancer screening. Employing an asset-based approach within vulnerable populations already engaging in at least one healthy behavior (i.e., physical activity) may be an ideal way to further reduce cancer risk across peer groups with low cancer screening rates. Guided by the theory of planned behavior (TPB), the aim of this study was to identify constructs associated with cancer screening intentions among young to middle aged adults for influencing educational and behavioral interventions designed to promote cancer prevention. A cross-sectional, web-based survey was utilized to assess attitudes, subjective norms, perceived behavioral control, and intention to screen for cancer among physically active adults aged 18-49 years. Descriptive and bivariate analyses were conducted to characterize the sample, and hierarchical linear regression analyses were conducted to assess the influence of sociodemographic variables and TPB constructs on cancer screening intentions. Age, female sex, reporting a routine doctor's visit, reported knowledge of physical activity as a lifestyle behavior to reduce cancer risk, and an increased number of motivating factors for engaging in physical activity were significantly associated with higher cancer screening intention (P < 0.001). With the addition of TPB constructs (i.e., subjective norms and perceived behavioral control), the final analytic model accounted for 31% of the variance in intention to screen for cancer. Findings suggest that the TPB could be used to tailor or design asset-based, cancer education interventions to effectively promote age-eligible cancer screenings among physically active adults. Educational content to increase social support for cancer screening and enhance perceived behavioral control to complete screening is essential in this population.


Subject(s)
Intention , Neoplasms , Middle Aged , Adult , Humans , Female , Early Detection of Cancer , Cross-Sectional Studies , Surveys and Questionnaires , Neoplasms/diagnosis , Neoplasms/prevention & control
2.
Prev Med Rep ; 30: 101978, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36157713

ABSTRACT

To achieve the lowest risk level for various cancers, individuals would engage in several healthy lifestyle behaviors and age-eligible cancer screenings as recommended. Nonetheless, research has largely omitted exploration of concurrent primary and secondary prevention behaviors. This study was designed to explore influences of cervical cancer screening among physically active women who reported participation in recreational sports. U.S. based women between the ages of 21-49, who had never been diagnosed with cancer, were eligible to complete a web-based survey. Logistic regression analyses were conducted using SAS 9.4. On average, women were 31 years of age (N = 394) and self-identified as Black (51.3 %). Although low overall (30.7 %), higher odds of cervical cancer screening were associated with age (OR = 1.06, 95 % CI = 1.03-1.10), employment (OR = 2.43, 95 % CI = 1.14-5.18), knowledge of cancer-related risk behaviors (OR = 4.04, 95 % CI = 1.33-12.28), routine doctor's visit (OR = 4.25, 95 % CI = 1.56-11.54), and team-based vs individual-based sport participation (OR = 1.95, 95 % CI = 1.13-3.34). Our study provides insight into the health profile of physically active women, ages 21-49, as it relates to risks for cervical cancer. Screening uptake among this diverse sample was much lower than the general population and national goals set by Healthy People 2030. Interventions should be tailored to increase knowledge of cancer-related risk behaviors, access to healthcare, and recommended cervical cancer screenings among even assumed-to-be healthy populations.

3.
JAMA Otolaryngol Head Neck Surg ; 145(6): 536-541, 2019 06 01.
Article in English | MEDLINE | ID: mdl-30946454

ABSTRACT

Importance: Erich arch bars, 4-point fixation, and bone-supported arch bars are currently used in maxillomandibular fixation, although to what extent they differ in terms of overall charges and clinical outcomes has yet to be reported. Objective: To determine the association of Erich arch bars, 4-point fixation, and bone-supported arch bars in maxillomandibular fixation with hospital charges and clinical outcomes. Design, Setting, and Participants: This historical cohort included 93 patients with mandible fracture who underwent maxillomandibular fixation from January 1, 2005, to June 30, 2015, at a tertiary care center. Statistical analysis was conducted from October 4, 2015, to September 8, 2017. Main Outcomes and Measures: Charge analysis from an institutional perspective, operative time, necessity for a secondary procedure, and postoperative complications. Results: Of the 93 patients in the study (18 women and 75 men; median age, 28.0 years [interquartile range, 23.0-40.0 years]), 27 (29%) received Erich arch bars, 51 (55%) received 4-point fixation, and 15 (16%) received bone-supported arch bars. The mean operative time for Erich arch bars (98.7 minutes; 95% CI, 89.2-108.2 minutes) was significantly longer than for 4-point fixation (48.8 minutes; 95% CI, 41.8-55.7 minutes) and bone-supported arch bars (55.9 minutes; 95% CI, 43.1-68.6 minutes). A total of 17 patients who received Erich arch bars (63%), 37 patients who received 4-point fixation (72%), and 1 patient who received bone-supported arch bars (7%) needed to return to the operating room for hardware removal. Patients who received Erich arch bars and those who received 4-point fixation had significantly higher odds of requiring a secondary procedure than did patients who received bone-supported arch bars (Erich arch bars: odds ratio, 27.1; 95% CI, 2.7-274.6; and 4-point fixation: odds ratio, 42.8; 95% CI, 4.4-420.7). Mean total operative charges for application of the hardware alone were significantly less for 4-point fixation ($5290; 95% CI, $4846-$5733) and bone-supported arch bars ($6751; 95% CI, $5936-$7566) than for Erich arch bars ($7919; 95% CI, $7311-$8527). When secondary procedure charges were included, the mean total charge for Erich arch bars ($9585; 95% CI, $8927-$10 243) remained significantly more expensive than the mean total for 4-point fixation ($7204; 95% CI, $6724-$7684) and bone-supported arch bars ($6924; 95% CI, $6042-$7807). No clinically meaningful difference in complications between groups was found (Erich arch bars, 3 [11%]; 4-point fixation, 5 [10%]; and bone-supported arch bars, 2 [13%]). Conclusions and Relevance: Bone-supported arch bars have comparable complication outcomes, operative time for placement, and overall charges when compared with Erich arch bars and 4-point fixation, and have a lower likelihood of requiring removal in an operative setting.


Subject(s)
Fracture Fixation, Internal , Jaw Fixation Techniques/instrumentation , Mandibular Fractures/surgery , Adult , Bone Plates , Bone Screws , Cost-Benefit Analysis , Female , Fracture Fixation, Internal/economics , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Humans , Jaw Fixation Techniques/economics , Male , Middle Aged , Multivariate Analysis , Operative Time , Young Adult
4.
East Afr Med J ; 91(5): 152-60, 2014 May.
Article in English | MEDLINE | ID: mdl-26866115

ABSTRACT

BACKGROUND: Primary School Action for Better Health (PSABH) became the national HIV prevention curriculum of Kenya in 2005. OBJECTIVE: To examined implementation of PSABH and student risk behaviour s. SETTING: Muhuru, a rural division of Nyanza Province. SUBJECTS: One thousand one hundred and forty six students aged 9-21 years from six primary schools in Muhuru. OUTCOME MEASURES: Anonymous surveys were administered to assess students'exposure to PSABH curriculum components, sexual activity, condom use, and self-efficacy related to engaging in lower risk behaviours. RESULTS: The six schools implementing PSABH were not implementing the full curriculum. Fifty-five percent of males and 44% of females reported a history of sexual activity. For females, condom self-efficacy was related to lower risk behaviour, while HIV education during pastoral instruction was associated with higher risk. Boys who reported higher self-efficacy and learning about abstinence strategies engaged in lower risk behaviour , while exposure to HIV education in assemblies and communication with relatives about HIV was associated with higher risk. CONCLUSION: Previous studies documented benefits of PSABH. However, it is unclear how effective the curriculum is after national scale-up. In this community, PSABH was implemented at a low level, with some curriculum components associated with higher risk behaviour, calling into question how PSABH is being delivered. Future studies should examine effective strategies for ongoing support, monitoring, and evaluation. Successfully disseminating evidence-based prevention strategies could reduce HIV incidence and the burden on healthcare providers struggling to care for people living with HIV/AIDS.


Subject(s)
Curriculum , HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , School Health Services , Adolescent , Child , Female , Humans , Kenya , Male , Sexual Behavior , Young Adult
5.
Arthritis Rheum ; 65(9): 2279-89, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23740612

ABSTRACT

OBJECTIVE: The ability to noninvasively monitor the development of inflammatory arthritis longitudinally has become increasingly important in experimental rheumatology. Magnetic resonance imaging (MRI) allows for detailed examination of anatomic structures, as well as the assessment of joint and soft tissue inflammation. The aim of this study was to extend the use of MRI to include quantitative measurements of bone destruction in murine ankle joints. METHODS: Joint disease was measured serially using clinical, histologic, in vivo imaging system (IVIS), micro-computed tomography (micro-CT), and MRI techniques in mouse ankle joints, using the K/BxN serum transfer-induced acute arthritis and K/BxA(g7) chronic arthritis models. Ankle joint MRI was performed using a gradient-echo pulse sequence to evaluate bone destruction and a spin-echo sequence to evaluate inflammation (long T2 signal). RESULTS: Arthritic mice, as compared to control mice, demonstrated increased disease severity according to clinical, histologic, IVIS, and MRI measures. Following induction of arthritis, the majority of volume expansion of the long T2 signal occurred in a juxtaarticular, rather than intrarticular, manner within the ankle joints. Bone destruction in K/BxA(g7) mouse ankle joints was readily detectible by MRI. Linear regression analyses demonstrated significant correlations between the clinical score and joint radiance intensity assessed by IVIS, between the ankle joint width and increased long T2 signal on MRI, and between the bone volume obtained by micro-CT and bone volume obtained by MRI. CONCLUSION: MRI is an optimal technology for anatomic localization of articular and soft tissue changes during the development and progression of inflammatory arthritis. Future studies may combine MRI with in vivo labeling agents to investigate joint disease in a cell type-specific manner.


Subject(s)
Ankle Joint/pathology , Arthritis, Experimental/pathology , Bone Resorption/pathology , Inflammation/pathology , Animals , Ankle Joint/diagnostic imaging , Arthritis, Experimental/diagnostic imaging , Bone Resorption/diagnostic imaging , Disease Progression , Inflammation/diagnostic imaging , Magnetic Resonance Imaging , Mice , Radiography
6.
Neurobiol Dis ; 33(3): 315-30, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19027857

ABSTRACT

With spontaneous elongation of the CAG repeat in the R6/2 transgene to > or =335, resulting in a transgene protein too large for passive entry into nuclei via the nuclear pore, we observed an abrupt increase in lifespan to >20 weeks, compared to the 12 weeks common in R6/2 mice with 150 repeats. In the > or =335 CAG mice, large ubiquitinated aggregates of mutant protein were common in neuronal dendrites and perikaryal cytoplasm, but intranuclear aggregates were small and infrequent. Message and protein for the > or =335 CAG transgene were reduced to one-third that in 150 CAG R6/2 mice. Neurological and neurochemical abnormalities were delayed in onset and less severe than in 150 CAG R6/2 mice. These findings suggest that polyQ length and pathogenicity in Huntington's disease may not be linearly related, and pathogenicity may be less severe with extreme repeats. Both diminished mutant protein and reduced nuclear entry may contribute to phenotype attenuation.


Subject(s)
Huntington Disease/genetics , Longevity/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Trinucleotide Repeat Expansion , Aging , Animals , Base Sequence , Brain/metabolism , Brain/pathology , DNA Mutational Analysis , Disease Models, Animal , Gene Expression , Huntingtin Protein , Huntington Disease/mortality , Mice , Mice, Transgenic , Molecular Sequence Data , Neurons/metabolism , Neurons/ultrastructure , Peptides/physiology , Phenotype , RNA, Messenger/metabolism , Survival Rate
7.
Ecol Appl ; 18(3): 735-47, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18488631

ABSTRACT

Entomopathogenic nematodes (EPN) are currently marketed worldwide for use in inundative biological control, where the applied natural enemy population (rather than its offspring) is expected to reduce insect numbers. Unlike classical biological control, in inundative control natural enemy establishment is not crucial in order to achieve pest suppression. Field trials in Irish forestry provided the opportunity to test predictions regarding the establishment of two exotic (Steinernema carpocapsae and Heterorhabditis megidis) and two indigenous (Steinernema feltiae and Heterorhabditis downesi) species. Nematodes were inundatively applied to pine stumps to control populations of pine weevil, Hylobius abietis, on three clearcut sites, and their persistence and spread monitored for up to five years. All species were recovered three years after application but only S. feltiae was recovered in years 4 and 5. Limited horizontal dispersal to 20 cm (but not 100 cm) was observed, but the majority of nematodes were recovered close to the area of application. Steinernema feltiae was also recovered from nearby stumps to which it had not been applied, indicating possible phoretic dispersal by weevils or other stump-associated fauna. EPN were not recovered from stumps outside the treated area, suggesting that such dispersal is quite localized. Two strains of S. feltiae (Irish and exotic) were applied. Amplified fragment length polymorphism (AFLP) analysis on 11 populations isolated from soil four years later showed that all had a much closer affinity to the applied Irish strain, suggesting persistence of this genotype and extinction of the exotic one. Some strains were clustered close together, and this is interpreted in the light of possible population genetic scenarios. The findings from the field study confirm predictions based on background knowledge of the species and demonstrate the importance of medium-term studies, as a 3-year study would have overestimated the risk of establishment of exotic species. Short-term persistence and spread of S. carpocapsae, S. feltiae, and H. downesi was also studied in pine forest mesocosms. Similar trends to field results, such as limited horizontal dispersal, even vertical distribution, and more abundant recovery of S. feltiae than of other species, point to the utility of mesocosm studies as a predictive tool.


Subject(s)
Ecosystem , Insecta/parasitology , Nematoda/physiology , Trees , Animals , Host-Parasite Interactions , Ireland , Pest Control, Biological , Time Factors
8.
Neurobiol Dis ; 20(3): 907-17, 2005 Dec.
Article in English | MEDLINE | ID: mdl-15990326

ABSTRACT

Striatal degeneration in Huntington's disease (HD) is associated with increases in perikaryal calbindin immunolabeling in yet-surviving striatal projection neurons. Since similar increases have also been observed in surviving striatal projection neurons after intrastriatal injection of the excitotoxin quinolinic acid, the increased calbindin in HD striatum has been interpreted to suggest an excitotoxic process in HD. We used immunolabeling to assess if calbindin is elevated in striatal projection neurons of R6/2 HD transgenic mice. These mice bear exon 1 of the human huntingtin gene with 144 CAG repeats and show some of the neuropathological signs (e.g., neuronal intranuclear inclusions) and clinical traits (e.g., wasting prior to early death) of HD. We found an increased frequency of calbindin-immunoreactive neuronal perikarya in the striatum of 6- and 12-week-old R6/2 mice compared to wild-type controls. This increase was most notable in the normally calbindin-poor dorsolateral striatum. We found no significant changes in the total area of striatum occupied by the calbindin-negative striosomes and no consistent changes in striatal calbindin mRNA. The increase in calbindin in R6/2 striatal neurons was thus limited to the matrix compartment, and it may be triggered by increased Ca2+ entry due to the demonstrated heightened NMDA sensitivity of these neurons. The data further support the similarity of R6/2 mice to HD, and are consistent with the occurrence of an excitotoxic process in striatum in both.


Subject(s)
Huntington Disease/metabolism , Neostriatum/metabolism , Neurons/metabolism , S100 Calcium Binding Protein G/metabolism , Animals , Calbindin 1 , Calbindins , Calcium Signaling/genetics , Disease Models, Animal , Excitatory Amino Acid Agonists/metabolism , Female , Glutamic Acid/metabolism , Humans , Huntingtin Protein , Huntington Disease/genetics , Huntington Disease/physiopathology , Immunohistochemistry , Male , Mice , Mice, Transgenic , Mutation/genetics , Neostriatum/pathology , Neostriatum/physiopathology , Nerve Degeneration/genetics , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Nerve Tissue Proteins/genetics , Neurons/pathology , Neurotoxins/metabolism , Nuclear Proteins/genetics , RNA, Messenger/metabolism , S100 Calcium Binding Protein G/genetics , Trinucleotide Repeat Expansion/genetics , Up-Regulation/physiology
9.
Ann Trop Med Parasitol ; 97(4): 351-66, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12831521

ABSTRACT

Genomic DNA fragments encoding nine, novel, P-type ATPases in trypanosomatid organisms were amplified in PCR, using degenerate oligonucleotide primers that recognize the ATP-binding and -phosphorylation sites present in all P-type ATPases. Subsequent phylogenetic analysis, based on the presence of conserved motifs in predicted peptide sequences for six Trypanosoma brucei, T. cruzi or Leishmania donovani PCR fragments, identified calcium-, proton- and phospholipid-translocating ATPases. DNA fragments that predict proteins homologous to the fungal, type-IID, P-type, ATPase pumps that transport Na(+) or K(+) ions were also present in T. brucei (TBCA1; 1022 nucleotides representing 340 amino acids), T. cruzi (TCNA1; 1022 nucleotides representing 340 amino acids) and L. donovani (LDCA1; 1031 nucleotides representing 343 amino acids). Southern blots showed that the Na(+)-ATPases were each present as a single-copy gene. The LDCA1 fragment was used to clone the complete LDCA1 gene from an L. donovani genomic-DNA library. The LDCA1 gene encodes a protein, of 1047 amino acids, with a predicted molecular mass of 115,501 Da. The results of analyses based on northern blots and the rapid amplification of cDNA ends (RACE) indicated that LDCA1 was expressed in promastigotes and amastigotes from axenic cultures and in animal-derived amastigotes. TBCA1 was expressed, as a 5.0-kb transcript, in procyclic culture stages and bloodstream trypomastigotes, with the 5.0-kb message up-regulated six-fold in the trypomastigote stage. Western blots probed with an antibody to the partial TBCA1 peptide identified a 150-kDa protein that was detected, by immunofluorescence, on the surface membrane of procyclic T. brucei.


Subject(s)
Adenosine Triphosphatases/analysis , Leishmania donovani/enzymology , Trypanosoma brucei brucei/enzymology , Trypanosoma cruzi/enzymology , Adenosine Triphosphatases/genetics , Animals , DNA, Protozoan/genetics , Fluorescent Antibody Technique , Gene Expression/genetics , Genes, Protozoan/genetics , Immunoblotting/methods , Leishmania donovani/genetics , Mice , Mice, Inbred BALB C , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sodium-Potassium-Exchanging ATPase/analysis , Sodium-Potassium-Exchanging ATPase/genetics , Transcription, Genetic/genetics , Translocation, Genetic/genetics , Trypanosoma brucei brucei/genetics , Trypanosoma cruzi/genetics
10.
Urol Nurs ; 22(5): 324-5, 328-30, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12432718

ABSTRACT

Urologic and continence nursing advanced significantly during the 1990s. Today's health care environment emphasizes careful rationalizing of hospital-based resources. This trend is more or less responsible for the demise of medically managed suprapubic catheter (SPC) change. The results of this study indicate that first change of SPC, performed in the patient's home or outpatient clinic by appropriately skilled registered nurses, is a cost-effective practice with no increased risk of complication to the patient.


Subject(s)
Urinary Catheterization/adverse effects , Urinary Catheterization/economics , Cost-Benefit Analysis , Female , Humans , Male , Statistics, Nonparametric , Urinary Catheterization/nursing
11.
AIDS Care ; 14(3): 309-18, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12042076

ABSTRACT

Highly active antiretroviral therapy (HAART) has been a major breakthrough for the treatment of patients with HIV; however, adherence to treatment remains a formidable barrier. This paper evaluates the current state-of-the-science in adherence to HAART. Barriers to treatment success, determinants of adherence and interventions to improve adherence are reviewed. Overall, multifaceted interventions appear most promising. We conclude with recommendations to enhance clinical practice and improve treatment outcomes for patients with HIV. Despite substantial attention to adherence in recent years, much more remains to be done to understand and promote adherence to HAART.


Subject(s)
Antiretroviral Therapy, Highly Active/statistics & numerical data , HIV Infections/drug therapy , Patient Compliance/statistics & numerical data , Antiretroviral Therapy, Highly Active/psychology , Humans , Patient Compliance/psychology , Risk Factors
12.
J Prosthodont ; 11(1): 4-10, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11935504

ABSTRACT

Maxillary cuspids are commonly included in ablative block resections in maxillectomy patients. Although the remaining incisors are poor abutments for interim or definitive obturators, they must be used if adequate retention and support is to be achieved. Orthodontic biomechanical concepts for removable appliances offer solutions for the treatment of these patients. The proper application of these concepts can improve retention, support, and force distribution to the anterior teeth and is particularly useful in younger patients when long-term maintenance of teeth is critical. The purpose of this article is to describe the rationale for this approach and its application to interim and definitive Aramany Class I and II obturators.


Subject(s)
Orthodontics, Corrective , Palatal Obturators , Prosthesis Design , Biomechanical Phenomena , Bite Force , Dental Abutments , Dental Clasps , Humans , Incisor/physiology , Maxilla/surgery , Pliability , Rotation , Stress, Mechanical , Surface Properties
13.
Neurobiol Dis ; 11(3): 369-85, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12586547

ABSTRACT

In early adult-onset Huntington's disease (HD), enkephalinergic striatopallidal projection neurons show preferential loss, reduced preproenkephalin (PPE) expression in surviving striatopallidal neurons, and loss of fibers in their projection target area. We examined PPE and PPT (preprotachykinin) gene expression in striatal projection neurons and in striatal projection fibers immunoreactive for the PPE product enkephalin (ENK) and the PPT product substance P (SP) in a transgenic HD model, the R6/2 mouse, to see if changes occur in these neuron types similar to those seen in early adult-onset HD. The results show that PPE mRNA level, the number of striatal neurons expressing PPE, and the staining intensity of fibers immunoreactive for ENK in the pallidum were all decreased. By contrast, the SP-containing striatal projection systems to the pallidum and substantia nigra were relatively normal in R6/2 mice. The selective reduction in striatal PPE in R6/2 mice is reminiscent of adult-onset HD, but the preservation of the striatonigral projection system is not. Thus, R6/2 mice do not strictly mimic adult-onset HD in their striatal pathology.


Subject(s)
Corpus Striatum/metabolism , Enkephalins/metabolism , Huntington Disease/metabolism , Neurons/metabolism , Protein Precursors/metabolism , Substance P/metabolism , Tachykinins/metabolism , Age Factors , Animals , Autoradiography , Disease Models, Animal , Gene Expression , Genotype , Globus Pallidus/metabolism , Immunohistochemistry , In Situ Hybridization , Mice , Mice, Transgenic , Neural Pathways/metabolism , Nucleus Accumbens/metabolism , RNA, Messenger/metabolism , Substantia Nigra/metabolism
14.
J Neurosci ; 21(19): 7608-19, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11567051

ABSTRACT

To determine whether neurons lacking huntingtin can participate in development and survive in postnatal brain, we used two approaches in an effort to create mice consisting of wild-type cells and cells without huntingtin. In one approach, chimeras were created by aggregating the 4-8 cell embryos from matings of Hdh (+/-) mice with wild-type 4-8 cell embryos. No chimeric offspring that possessed homozygous Hdh (-/-) cells were obtained thereby, although statistical considerations suggest that such chimeras should have been created. By contrast, Hdh (-/-) ES cells injected into blastocysts yielded offspring that were born and in adulthood were found to have Hdh (-/-) neurons throughout brain. The Hdh (-/-) cells were, however, 5-10 times more common in hypothalamus, midbrain, and hindbrain than in telencephalon and thalamus. Chimeric animals tended to be smaller than wild-type littermates, and chimeric mice rich in Hdh (-/-) cells tended to show motor abnormalities. Nonetheless, no brain malformations or pathologies were evident. The apparent failure of aggregation chimeras possessing Hdh (-/-) cells to survive to birth is likely attributable to the previously demonstrated critical role of huntingtin in extraembryonic membranes. That Hdh (-/-) cells in chimeric mice created by blastocyst injection are under-represented in adult telencephalon and thalamus implies a role for huntingtin in the development of these regions, whereas the neurological dysfunction in brains enriched in Hdh (-/-) cells suggests a role for huntingtin in adult brain. Nonetheless, the lengthy survival of Hdh (-/-) cells in adult chimeric mice indicates that individual neurons in many brain regions do not require huntingtin to participate in normal brain development and to survive.


Subject(s)
Brain/pathology , Chimera/genetics , Huntington Disease/genetics , Nerve Tissue Proteins/deficiency , Neurons/metabolism , Nuclear Proteins/deficiency , Animals , Behavior, Animal , Brain/embryology , Brain/metabolism , Cell Differentiation , Cell Movement , Cell Survival , Genes, Reporter , Genotype , Huntingtin Protein , Hypothalamus/metabolism , Hypothalamus/pathology , Mesencephalon/metabolism , Mesencephalon/pathology , Mice , Motor Activity/genetics , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Nervous System Diseases/diagnosis , Nervous System Diseases/genetics , Neurons/pathology , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Organ Specificity/genetics , Rhombencephalon/metabolism , Rhombencephalon/pathology , Stem Cells , Survival Rate , Telencephalon/metabolism , Telencephalon/pathology , Thalamus/metabolism , Thalamus/pathology
15.
Life Sci ; 69(11): 1225-40, 2001 Aug 03.
Article in English | MEDLINE | ID: mdl-11521747

ABSTRACT

Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A2b or A3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE/antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.


Subject(s)
Adenosine-5'-(N-ethylcarboxamide)/administration & dosage , Asthma/physiopathology , Bronchial Spasm/physiopathology , Vasodilator Agents/administration & dosage , Administration, Inhalation , Animals , Bronchoconstriction/drug effects , Bronchoconstriction/physiology , Disease Models, Animal , Eosinophilia/physiopathology , Humans , In Vitro Techniques , Mast Cells/physiology , Rats , Rats, Inbred Strains , Receptors, Purinergic P1/classification , Receptors, Purinergic P1/physiology
16.
J Pharmacol Exp Ther ; 297(1): 458-66, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11259574

ABSTRACT

BIIL 284 is a new LTB(4) receptor antagonist. It is a prodrug and has negligible binding to the LTB(4) receptor. However, ubiquitous esterases metabolize BIIL 284 to the active metabolites BIIL 260 and BIIL 315, the glucuronidated form of BIIL 260. Both metabolites have high affinity to the LTB(4) receptor on isolated human neutrophil cell membranes with K(i) values of 1.7 and 1.9 nM, respectively. On vital human neutrophilic granulocytes K(i) was around 1 nM. BIIL 260 and BIIL 315 interact with the LTB(4) receptor in a saturable, reversible, and competitive manner. BIIL 260 and its glucuronide BIIL 315 also potently inhibited LTB(4)-induced intracellular Ca(2+) release in human neutrophils (IC(50) values of 0.82 and 0.75 nM, respectively) as measured with Fura-2. High efficacy of BIIL 284 has been demonstrated in various in vivo models. BIIL 284 inhibited LTB(4)-induced mouse ear inflammation with ED(50) = 0.008 mg/kg p.o., LTB(4)-induced transdermal chemotaxis in guinea pigs with ED(50) = 0.03 mg/kg p.o., LTB(4)-induced neutropenia in various species (monkey: ED(50) = 0.004 mg/kg p.o.), and LTB(4)-induced Mac1-expression in monkeys (ED(50) = 0.05 mg/kg p.o. in Tylose). Full blockade of LTB(4) receptors over 24 h was achieved by 0.3 mg/kg BIIL 284 after single oral dose as measured by LTB(4)-induced neutropenia or Mac1-expression in the monkey model. BIIL 284 is an unusually potent and long-acting orally active LTB(4) antagonist, and is therefore under clinical development as a novel anti-inflammatory principle.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Receptors, Leukotriene B4/antagonists & inhibitors , Amidines/pharmacology , Animals , Benzoates/pharmacology , Calcium/metabolism , Carbamates/pharmacology , Cell Line , Chemotaxis, Leukocyte/drug effects , Guinea Pigs , Humans , Leukotriene B4/metabolism , Leukotriene B4/pharmacology , Macrophage-1 Antigen/biosynthesis , Neutrophils/drug effects , Neutrophils/metabolism , Rabbits , Rats , Species Specificity , Succinates/pharmacology
17.
Hum Mol Genet ; 10(2): 145-52, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11152662

ABSTRACT

In an effort to characterize the basis of abnormalities in body weight regulation (i.e. wasting) in Huntington's disease (HD), we examined adipocytes in a transgenic model of HD, the R6/2 mouse. These mice typically show severe wasting beginning at approximately 12 weeks of age and die between 12 and 15 weeks. Despite an overall growth retardation compared with wild-type littermates, we observed an enhanced accumulation of body fat at 8-9 weeks of age in R6/2 mice fed laboratory chow or a synthetic high fat, high sugar diet. The obesity was not accompanied by symptoms associated with diabetes, as there were no abnormalities in serum glucose, serum insulin or the ability of insulin to stimulate glucose metabolism in epididymal adipose tissue. As expected, the obesity in the high fat, high sugar-fed R6/2 mice was accompanied by increased serum leptin. The ability of insulin to stimulate leptin release from isolated epididymal adipose tissue was also enhanced in R6/2 mice. In contrast, the ability of isoproterenol to inhibit leptin release was reduced in adipose tissue from R6/2 mice, as was the lipolytic effect of isoproterenol. These data suggest that the obesity observed at 8-9 weeks in R6/2 mice may stem from a defect in fat breakdown by adipocytes.


Subject(s)
Adipocytes/metabolism , Huntington Disease/genetics , Huntington Disease/metabolism , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Adipocytes/drug effects , Adipose Tissue/cytology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adrenergic beta-Agonists/pharmacology , Animals , Blood Glucose/analysis , Culture Techniques , Dexamethasone/pharmacology , Diabetes Mellitus, Experimental/metabolism , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Epididymis/anatomy & histology , Glucocorticoids/pharmacology , Huntingtin Protein , Insulin/pharmacology , Isoproterenol/pharmacology , Leptin/metabolism , Lipolysis/drug effects , Male , Mice , Mice, Mutant Strains , Mice, Obese , Mice, Transgenic
18.
Oncol Nurs Forum ; 28(10): 1577-84, 2001.
Article in English | MEDLINE | ID: mdl-11759305

ABSTRACT

PURPOSE/OBJECTIVES: To examine effective strategies for building community-academic partnerships for the promotion of breast cancer education and outreach among rural and Hispanic migrant and seasonal farmworker women, mostly from Mexican descent. DATA SOURCES: Published research and education articles and books, community-education models, personal experiences, and community key informant feedback. DATA SYNTHESIS: Effective community partnerships for enhanced education and outreach include a framework based on a network of partners with common goals, communication processes based on trust, and bilingual/bicultural and culturally competent staff. CONCLUSIONS: A sustainable community partnership can be achieved through systematic but flexible approaches to community planning. Involvement of community members in the development and implementation of education and screening activities helps ensure that community needs are met. Relationships based on mutual respect are key. IMPLICATIONS FOR NURSING PRACTICE: Nurses can act as catalysts through community capacity building to create community-academic partnerships to reach medically underserved populations with cancer screening, outreach, and education through the delivery of strategies that are based on common goals.


Subject(s)
Academies and Institutes/organization & administration , Breast Neoplasms/prevention & control , Cancer Care Facilities/organization & administration , Community Health Centers/organization & administration , Community-Institutional Relations , Health Education/organization & administration , Health Promotion/organization & administration , Hispanic or Latino/education , Interinstitutional Relations , Program Development/methods , Rural Health Services/organization & administration , Transients and Migrants/education , Women's Health Services/organization & administration , Breast Neoplasms/ethnology , Cooperative Behavior , Female , Florida , Humans , Mass Screening/organization & administration , Models, Organizational , Nurse's Role , Organizational Objectives , Outcome Assessment, Health Care , Program Evaluation
19.
Exp Neurol ; 166(2): 307-23, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11085896

ABSTRACT

The various types of striatal projection neurons and interneurons show a differential pattern of loss in Huntington's disease (HD). Since striatal injury has been suggested to involve similar mechanisms in transient global brain ischemia and HD, we examined the possibility that the patterns of survival for striatal neurons after transient global ischemic damage to the striatum in rats resemble that in HD. The perikarya of specific types of striatal interneurons were identified by histochemical or immunohistochemical labeling while projection neuron abundance was assessed by cresyl violet staining. Projectionneuron survival was assessed by neurotransmitter immunolabeling of their efferent fibers in striatal target areas. The relative survival of neuron types was determined quantitatively within the region of ischemic damage, and the degree of fiber loss in striatal target areas was quantified by computer-assisted image analysis. We found that NADPHd(+) and cholinergic interneurons were largely unaffected, even in the striatal area of maximal damage. Parvalbumin interneurons, however, were as vulnerable as projection neurons. Among immunolabeled striatal projection systems, striatoentopeduncular fibers survived global ischemia better than did striatopallidal or striatonigral fibers. The order of vulnerability observed in this study among the striatal projection systems, and the resistance to damage shown by NADPHd(+) and cholinergic interneurons, is similar to that reported in HD. The high vulnerability of projection neurons and parvalbumin interneurons to global ischemia also resembles that seen in HD. Our results thus indicate that global ischemic damage to striatum in rat closely mimics HD in its neuronal selectivity, which supports the notion that the mechanisms of injury may be similar in both.


Subject(s)
Corpus Striatum/pathology , Huntington Disease/pathology , Interneurons/pathology , Ischemic Attack, Transient/pathology , Animals , Cell Survival , Choline O-Acetyltransferase/analysis , Corpus Striatum/blood supply , Disease Models, Animal , Enkephalins/analysis , Image Processing, Computer-Assisted , Interneurons/chemistry , Interneurons/enzymology , Male , NADPH Dehydrogenase/analysis , Nerve Fibers/chemistry , Nerve Fibers/enzymology , Nerve Fibers/pathology , Neural Pathways , Rats , Rats, Sprague-Dawley , Rats, Wistar , Somatostatin/analysis , Substance P/analysis
20.
Eur Respir J ; 14(5): 1068-75, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10596692

ABSTRACT

Epinastine is an antihistamine drug with binding affinities at 5-hydroxytryptamine (5-HT) receptors. The current study was performed to investigate whether epinastine could modulate the cholinergic contraction in guinea pig and human airways in vitro. Isolated guinea pig and human airway preparations were suspended in organ baths containing modified Krebs-Henseleit solution. Electrical field stimulation was applied to elicit cholinergic contractions. Epinastine produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig airways and pretreatment with methysergide (5-HT1/2/7 antagonist) significantly attenuated these inhibitory effects of epinastine. Pretreatment with tropisetron (5-HT3/4 antagonist), ketanserin (5-HT2 antagonist), SDZ216-525 (5-HT1A antagonist) or phentolamine (alpha-adrenergic antagonist) had no effect. Epinastine did not displace the concentration-response curve to acetylcholine. These results suggest that epinastine inhibits the cholinergic contraction in guinea pig airways through stimulation of prejunctional 5-hydroxytryptamine receptors, located to postganglionic cholinergic nerves. Inhibitory effects of epinastine on the cholinergic contraction in human airways in vitro were also demonstrated, which suggests that a similar mechanism might be present in human airways. The pharmacological profile of epinastine, which shows binding affinity at the 5-hydroxytryptamine7 receptor but not at the 5-hydroxytryptamine1 receptor subtypes corroborates the hypothesis that the inhibitory prejunctional 5-hydroxytryptamine receptor on cholinergic nerves is of the 5-hydroxytryptamine7 subtype.


Subject(s)
Bronchi/drug effects , Dibenzazepines/pharmacology , Histamine H1 Antagonists/pharmacology , Imidazoles/pharmacology , Trachea/drug effects , Aged , Animals , Electric Stimulation , Female , Guinea Pigs , Humans , In Vitro Techniques , Male , Parasympathetic Nervous System/drug effects , Parasympathetic Nervous System/physiology , Receptors, Serotonin/drug effects
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