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1.
Aging Ment Health ; 26(3): 486-492, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33291990

ABSTRACT

BACKGROUND: Few studies have measured the impact of dementia-related fear on daily functioning, despite its clinical relevance. Our aim was to determine the relationship between fear-avoidance of memory loss, perceived memory failures and self-reported quality of life in a community based sample of older adults using a novel fear of memory loss (FAM) scale. METHODS: Sixty-seven older adults (59-81 years) completed a 23-item self-report scale designed to capture multi-faceted components of fear of memory loss, known as the FAM scale. Perceived memory failures were measured using the Memory Failures Scale (MFS) and quality of life was assessed using the Older Person's Quality of Life scale (OPQOL-35). Participants also completed the Wechsler Memory Scale (WMS-IV) as a measure of objective memory performance and the Depression, Anxiety and Stress Scales (DASS) and the Geriatric Anxiety Inventory (GAI) as measures of general anxiety. RESULTS: The FAM scale demonstrated strong internal consistency (Cronbach's α = .82) and concurrent validity with the GAI (r = .47). Three latent factors were observed: (1) fear-avoidance, (2) problematic beliefs and (3) affective resilience. After adjusting for objective memory performance and general anxiety, higher fear-avoidance significantly predicted increased perceived memory failures (p = .014) and reduced quality of life (p = .033). CONCLUSIONS: Fear of memory loss predicts increased perceived memory failures and lower self-reported quality of life in a community sample of older adults. Based on these findings, we propose a preliminary fear-avoidance model that explains the development and maintenance of dementia-related functional disability in terms of psychological processes.


Subject(s)
Dementia , Quality of Life , Aged , Amnesia , Anxiety/psychology , Fear/psychology , Humans , Memory Disorders , Reproducibility of Results , Surveys and Questionnaires
2.
J Urol ; 204(4): 754-759, 2020 10.
Article in English | MEDLINE | ID: mdl-32294397

ABSTRACT

PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.


Subject(s)
Cystitis, Interstitial , Prostatitis , Quality of Life , Biomedical Research , Correlation of Data , Female , Humans , Male , Prospective Studies , Time Factors
3.
Vet Pathol ; 54(1): 178-187, 2017 01.
Article in English | MEDLINE | ID: mdl-27507806

ABSTRACT

Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelin+/alpha-smooth muscle actin (α-SMA)+/vimentin- smooth muscle cells and fewer smoothelin-/α-SMA+/vimentin+ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.


Subject(s)
Lung/pathology , Rabbits/physiology , Aging/pathology , Animals , Female , Male , Pneumonia/pathology , Pneumonia/veterinary , Pulmonary Artery/pathology , Rabbits/anatomy & histology , Retrospective Studies
4.
Spinal Cord ; 52(11): 821-5, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25023861

ABSTRACT

STUDY DESIGN: Comparison of diagnostic tests; methodological validation. OBJECTIVES: Primary: to investigate the precision and reliability of a knee bone mineral density (BMD) assessment protocol that uses an existing dual energy X-ray absorptiometry (DXA) forearm acquisition algorithm in individuals with spinal cord injury (SCI). Secondary: to correlate DXA-based knee areal BMD with volumetric BMD assessments derived from quantitative computed tomography (QCT). SETTING: Academic medical center, Chicago, IL, USA. PARTICIPANTS: a convenience sample of 12 individuals with acute SCI recruited for an observational study of bone loss and 34 individuals with chronic SCI who were screened for a longitudinal study evaluating interventions to increase BMD. MAIN OUTCOME MEASURES: Root-mean-square standard deviation (RMS-SD) and intra/inter-rater reliability of areal BMD acquired at three knee regions using an existing DXA forearm acquisition algorithm; correlation of DXA-based areal BMD with QCT-derived volumetric BMD. RESULTS: The RMS-SD of areal BMD at the distal femoral epiphysis, distal femoral metaphysis and proximal tibial epiphysis averaged 0.021, 0.012 and 0.016 g cm(-2), respectively, in acute SCI and 0.018, 0.02 and 0.016 g cm(-2) in chronic SCI. All estimates of intra/inter-rater reliability exceeded 97% and DXA-based areal BMD was significantly correlated with QCT-derived volumetric BMD at all knee regions analyzed. CONCLUSIONS: Existing DXA forearm acquisition algorithms are sufficiently precise and reliable for short-term assessments of knee BMD in individuals with SCI. Future work is necessary to quantify the reliability of this approach in longitudinal investigations and to determine its ability to predict fractures and recovery potential. SPONSORSHIP: This work was funded by the Department of Defense, grant number DOD W81XWH-10-1-0951, with partial support from Merck & Co, Inc.


Subject(s)
Absorptiometry, Photon , Bone Diseases/etiology , Knee/diagnostic imaging , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Tomography Scanners, X-Ray Computed , Adolescent , Adult , Bone Diseases/diagnosis , Cohort Studies , Female , Forearm/diagnostic imaging , Forearm/pathology , Humans , Male , Middle Aged , Reproducibility of Results , Young Adult
5.
Psychol Med ; 40(7): 1125-36, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19903363

ABSTRACT

BACKGROUND: Several theories have posited a common internalizing factor to help account for the relationship between mood and anxiety disorders. These disorders are often co-morbid and strongly covary. Other theories and data suggest that personality traits may account, at least in part, for co-morbidity between depression and anxiety. The present study examined the relationship between neuroticism and an internalizing dimension common to mood and anxiety disorders. METHOD: A sample of ethnically diverse adolescents (n=621) completed self-report and peer-report measures of neuroticism. Participants also completed the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Structural equation modeling showed that a single internalizing factor was common to lifetime diagnosis of mood and anxiety disorders, and this internalizing factor was strongly correlated with neuroticism. Neuroticism had a stronger correlation with an internalizing factor (r=0.98) than with a substance use factor (r=0.29). Therefore, neuroticism showed both convergent and discriminant validity. CONCLUSIONS: These results provide further evidence that neuroticism is a necessary factor in structural theories of mood and anxiety disorders. In this study, the correlation between internalizing psychopathology and neuroticism approached 1.0, suggesting that neuroticism may be the core of internalizing psychopathology. Future studies are needed to examine this possibility in other populations, and to replicate our findings.


Subject(s)
Neurotic Disorders/diagnosis , Adolescent , Anxiety Disorders/diagnosis , Anxiety Disorders/psychology , Diagnosis, Differential , Diagnostic and Statistical Manual of Mental Disorders , Ethnicity/statistics & numerical data , Female , Humans , Male , Mood Disorders/diagnosis , Mood Disorders/psychology , Neurotic Disorders/psychology , Surveys and Questionnaires
6.
Genes Brain Behav ; 8(7): 714-27, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19671078

ABSTRACT

A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F(2) mice from a C57BL/6J x DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions approximately 1 month apart (average age at test 150, 450 and 750 days, approximately 400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F(2) analysis. There was a significant phenotypic correlation between Hbact and Hbrear (approximately 0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for approximately 15% of the phenotypic variance (sex approximately 3%), and there were genotype by age interactions at approximately 25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.


Subject(s)
Aging/genetics , Behavior, Animal/physiology , Gene Expression Regulation, Developmental/genetics , Motor Skills/physiology , Quantitative Trait Loci/genetics , Age Factors , Animals , Chromosome Mapping , Chromosomes, Mammalian , Crosses, Genetic , DNA Mutational Analysis , Epistasis, Genetic , Female , Genetic Variation/genetics , Genotype , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Inbred Strains , Penetrance , Phenotype , Sex Factors , Species Specificity , Time Factors
7.
Cancer Lett ; 171(2): 193-200, 2001 Oct 10.
Article in English | MEDLINE | ID: mdl-11520603

ABSTRACT

Transgenic rabbits carrying the EJras oncogene have been established in our laboratory (Am. J. Pathol. 155 (1999) 315). The expression of the ras gene is targeted to the epidermal keratinocytes using the upstream regulatory region (URR) of the cottontail rabbit papillomavirus (CRPV). All of the transgenic rabbits develop keratoacanthomas at multiple sites in the skin at 2-3 days after birth, and the tumors spontaneously regress in 1.5-2 months. With regression of the keratoacanthomas, the rabbits appear normal and EJras expression is undetectable in their skin. To determine if CRPV infection would reinitiate the expression of the EJras transgene and make the rabbits more sensitive to tumorigenesis, the rabbits were infected with CRPV at 2 months of age when the keratoacanthomas had regressed. This study shows that CRPV infection of the transgenic rabbit skin could shorten the latency required for CRPV papilloma initiation, and significantly increase the tumor growth and persistence rate compared with non-transgenic rabbits. Furthermore, EJras expression became detectable in the CRPV induced papillomas in transgenic rabbits, but not in the papillomas of non-transgenic rabbits. These results indicate that CRPV infection is able to reinitiate the expression of the CRPV URR controlled EJras oncogene carried by the transgenic rabbits and that the expression of EJras can enhance the tumorigenesis of CRPV infection.


Subject(s)
Cottontail rabbit papillomavirus , Epidermis/physiology , Oncogene Proteins/genetics , Papillomavirus Infections/genetics , Skin Neoplasms/genetics , Skin Neoplasms/virology , Animals , Animals, Genetically Modified , Cocarcinogenesis , Female , Gene Expression Regulation, Viral/genetics , Genes, ras/genetics , Genetic Predisposition to Disease , Keratoacanthoma/genetics , Keratoacanthoma/virology , Oncogene Proteins/biosynthesis , Papillomavirus Infections/virology , Rabbits
8.
Mol Biol Cell ; 11(12): 4117-30, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11102512

ABSTRACT

Cyclin-dependent kinases (Cdk) are essential for promoting the initiation of DNA replication, presumably by phosphorylating key regulatory proteins that are involved in triggering the G1/S transition. Human Cdc6 (HsCdc6), a protein required for initiation of DNA replication, is phosphorylated by Cdk in vitro and in vivo. Here we report that HsCdc6 with mutations at potential Cdk phosphorylation sites was poorly phosphorylated in vitro by Cdk, but retained all other biochemical activities of the wild-type protein tested. Microinjection of mutant HsCdc6 proteins into human cells blocked initiation of DNA replication or slowed S phase progression. The inhibitory effect of mutant HsCdc6 was lost at the G1/S transition, indicating that phosphorylation of HsCdc6 by Cdk is critical for a late step in initiation of DNA replication in human cells.


Subject(s)
Cell Cycle Proteins/genetics , Cell Cycle Proteins/physiology , Cyclin-Dependent Kinases/metabolism , DNA Replication , Nuclear Proteins/genetics , Nuclear Proteins/physiology , Amino Acid Substitution , Cell Cycle , Cell Cycle Proteins/metabolism , Chromosomes , HeLa Cells , Humans , Mutation , Nuclear Proteins/metabolism , Phosphorylation
9.
Contemp Top Lab Anim Sci ; 39(4): 43-6, 2000 Jul.
Article in English | MEDLINE | ID: mdl-11487230

ABSTRACT

A female Dorset-cross sheep developed labored respirations and was anorexic, weak, ataxic and febrile (42.0 degrees C) 15 days after implantation of a cardiac device. Clinical pathologic evaluation identified a mild leukocytosis (11,800 cells/microl), neutrophilia (8,969 cells/microl), and hypokalemia (2.9 mmol/L). Despite intensive therapy, the animal was euthanized 7 days later. Necropsy of the sheep revealed meningitis and vegetative endocarditis associated with the cardiac device. Blood cultures collected antemortem and tissue cultures collected at necropsy yielded Streptococcus suis. Histopathology confirmed the diagnosis of bacterial valvular endocarditis and meningoencephalitis. A variety of environmental and host factors are proposed as contributing to the infection, and the zoonotic potential of S. suis is discussed.


Subject(s)
Endocarditis, Bacterial/veterinary , Heart Valve Prosthesis Implantation/veterinary , Heart Valve Prosthesis/adverse effects , Meningitis, Bacterial/veterinary , Sheep Diseases/microbiology , Streptococcal Infections/veterinary , Streptococcus suis/pathogenicity , Animals , Endocarditis, Bacterial/etiology , Endocarditis, Bacterial/pathology , Female , Heart Valve Prosthesis/microbiology , Heart Valve Prosthesis Implantation/adverse effects , Meningitis, Bacterial/etiology , Meningitis, Bacterial/pathology , Sheep , Sheep Diseases/etiology , Sheep Diseases/pathology , Streptococcal Infections/etiology , Streptococcal Infections/pathology , Streptococcus suis/isolation & purification
10.
Cardiology ; 91(2): 96-101, 1999.
Article in English | MEDLINE | ID: mdl-10449880

ABSTRACT

BACKGROUND: Conventional cineradiology has been used clinically to detect partially broken outlet struts (single leg separations, SLSs) in normally functioning Björk-Shiley convexo-concave (C/C) heart valves. The value of radiographic screening has, however, been debated in the medical literature. This study uses the same radiographic technique in sheep implanted with known-status C/C valves in combination with a newly developed geometric image magnification radiography system. This study was designed to test whether sensitivity and specificity of radiographic screening of C/C valves in detecting SLSs could be improved through the combination of readers and imaging modalities. METHODS: Twenty-one sheep with mitral C/C valves were studied on both systems. Five were used for extensive scanning training. When operators were expert on both systems, 16 blinded study valves (4 intact and 12 with outlet strut SLSs) were scanned twice on both systems, first on a modified conventional and then a prototype geometric image magnification (Feinfocus(TM)) cineradiographic system by two expert physicians working together. RESULTS: Among the 32 scanned valves, the two combined expert physicians were required to evaluate 40 intact legs and 24 with an SLS. For all SLS valves, the conventional and Feinfocus systems separately detected 50 (12/24) and 54% (13/24), respectively. When the two systems were combined, the final consensus score was correct in 67% (16/24) of all SLS valves. CONCLUSIONS: Combined modality, paired expert physicians detected 67% of all SLSs. The Feinfocus system might be best reserved for those patients in whom the Siemens screening study demonstrates in minimally suspicious (grade 2) or suspicious (grade 3) appearance of a C/C valve outlet strut leg.


Subject(s)
Cineradiography , Heart Valve Prosthesis , Mitral Valve/diagnostic imaging , Animals , Disease Models, Animal , Mitral Valve/surgery , Monitoring, Physiologic/methods , Prosthesis Design , Prosthesis Failure , Sensitivity and Specificity , Sheep
11.
Ann Thorac Surg ; 68(1): 67-74, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10421117

ABSTRACT

BACKGROUND: In isolated hearts, the potassium-channel opener pinacidil is an effective cardioplegic agent. This study tested the hypothesis that pinacidil is superior to St. Thomas' solution in the more clinically relevant intact animal. METHODS: Sixteen pigs were placed on full cardiopulmonary bypass. Hearts underwent 2 hours of global ischemia (10 degrees to 15 degrees C). Either St. Thomas' or 100 micromol/L pinacidil was administered every 20 minutes (10 mL/kg). Preischemic and postreperfusion slopes of the preload-recruitable stroke work relationship were determined. Changes in myocardial adenine nucleotide levels and cellular ultrastructure were analyzed. RESULTS: Pinacidil cardioplegia resulted in an insignificant change in the slope of the preload-recruitable stroke work relationship (40.6+/-2.1 mm Hg/mm before ischemia and 36.5+/-3.7 mm Hg/mm after ischemia; p = 0.466). In contrast, St. Thomas' solution resulted in a significant decrease in the slope after reperfusion (34.3+/-5.5 mm Hg/mm and 13.5+/-2.3 mm Hg/mm; p = 0.003). Adenine nucleotide levels, myocardial tissue water, and ultrastructural changes were similar between groups. CONCLUSIONS: Pinacidil ameliorated myocardial stunning associated with traditional hyperkalemic cardioplegia without causing significant differences in cellular metabolism.


Subject(s)
Cardioplegic Solutions , Pinacidil , Potassium Channels/drug effects , Adenine Nucleotides/metabolism , Animals , Bicarbonates , Calcium Chloride , Cardiopulmonary Bypass , Magnesium , Myocardial Contraction , Myocardial Reperfusion , Myocardial Stunning/metabolism , Myocardial Stunning/pathology , Myocardium/metabolism , Myocardium/ultrastructure , Potassium Chloride , Sodium Chloride , Stroke Volume , Swine
12.
Am J Pathol ; 155(1): 315-24, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10393863

ABSTRACT

Activated ras genes have been frequently identified in both benign and malignant human tumors, including keratoacanthoma and squamous cell carcinoma. In this study, we developed two lines of transgenic rabbits in which the expression of EJras has been specifically targeted to the rabbit epidermal keratinocytes, using the upstream regulatory region of cottontail rabbit papillomavirus. All of the F1 transgenic progenies developed multiple keratoacanthomas at about 3 days after birth. The rabbits developed an average of 20 tumors, which usually reached the size of approximately 1 cm in diameter and then spontaneously regressed in about 2 months, similar to keratoacanthoma regression in humans. In addition, up to 18% of the rabbits then developed squamous cell carcinoma at about 5 months of age. The expression of EJras was detectable in all of the keratoacanthomas and squamous cell carcinomas. These results strongly support the involvement of the ras oncogene in both the initiation and regression of keratoacanthoma, and in the development of squamous cell carcinomas. These novel transgenic rabbits, with their consistent tumorigenic phenotype at an early age, high similarity to the human lesions, and easy accessibility for examination, manipulation, biopsy, and treatment, should provide a unique model system for studying ras activation-related tumor initiation, regression, and progression, and for evaluating antitumor therapies.


Subject(s)
Carcinoma, Squamous Cell/genetics , Epidermis/physiology , Gene Expression/physiology , Keratoacanthoma/genetics , Oncogene Proteins/genetics , Skin Neoplasms/genetics , Animals , Animals, Genetically Modified/genetics , Carcinoma, Squamous Cell/pathology , Keratoacanthoma/pathology , Male , Rabbits , Skin Neoplasms/pathology , Transgenes/genetics
13.
Cancer Lett ; 128(1): 65-70, 1998 Jun 05.
Article in English | MEDLINE | ID: mdl-9652794

ABSTRACT

To determine whether alteration of PKC alpha expression would affect the metastatic potential of human melanoma cells, replicate cultures of C8161 cells were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161 cultures were treated with a scrambled sequence ODN, cationic liposomes or were left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75% when ISIS-3521-treated cells were injected intravenously into athymic mice. These results show that PKC alpha expression is important in the regulation of human melanoma metastasis.


Subject(s)
Isoenzymes/metabolism , Melanoma/enzymology , Oligonucleotides, Antisense/pharmacology , Protein Kinase C/metabolism , Animals , Humans , Isoenzymes/genetics , Lung Neoplasms/secondary , Mice , Mice, Nude , Neoplasm Metastasis , Protein Kinase C/genetics , Protein Kinase C-alpha , RNA/analysis , Thionucleotides , Tumor Cells, Cultured
14.
J Virol ; 72(6): 5239-44, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9573297

ABSTRACT

Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus which naturally infects oral mucosal sites of domestic rabbits. In this study, we tested the hypothesis that rabbit genital mucosa is also susceptible to ROPV infection by using the athymic mouse xenograft system and adult immunocompetent rabbits. Subrenal xenografts of ROPV-infected rabbit vulvar and penile sheath tissues were strongly positive for ROPV infection by histologic, in situ hybridization, and Southern analyses. Direct inoculation of adult rabbit penises with infectious ROPV produced small raised lesions of approximately 1 by 1 by 1 mm that were ROPV positive by both in situ hybridization and Southern analyses and were also viral capsid antigen positive by immunohistological staining. Infection of rabbit genital tissues with ROPV may be a useful animal model for the study of genital tissue-targeting papillomaviruses.


Subject(s)
Cottontail rabbit papillomavirus , Genitalia, Male/virology , Mouth Mucosa/virology , Papillomavirus Infections , Tumor Virus Infections , Animals , Cottontail rabbit papillomavirus/pathogenicity , Disease Models, Animal , Male , Mice , Rabbits
15.
J Thorac Cardiovasc Surg ; 115(3): 582-90, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9535446

ABSTRACT

OBJECTIVE: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies. CONCLUSIONS: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.


Subject(s)
Cineradiography/methods , Heart Valve Prosthesis , Radiographic Image Interpretation, Computer-Assisted , Animals , Evaluation Studies as Topic , Odds Ratio , Prosthesis Design , Prosthesis Failure , ROC Curve , Random Allocation , Sensitivity and Specificity , Sheep
16.
Lab Anim Sci ; 48(4): 340-3, 1998 Aug.
Article in English | MEDLINE | ID: mdl-10090039

ABSTRACT

During a 5-year period, 16 freshwater turtles (Trachemys scripta elegans and Chrysemys picta) that were purchased for research purposes died spontaneously. Clinical signs of disease included lethargy, constant swimming, swimming sideways, hemiplegia, and ulcerative lesions on the carapace. At necropsy, subcutaneous edema, hepatic necrosis, pancreatic necrosis, splenic necrosis, and intestinal parasites were identified. Histologically, trematode eggs were seen within the liver, brain, spleen, kidney, myocardium, lung, pancreas, testes, and bladder, and were associated with granulomatous reactions. The size and distribution of the eggs were consistent with Spirorchis sp. infection, although adults could not be found to confirm the species. Spirorchid flukes are 1 to 2 mm long and inhabit the heart and blood vessels where they produce eggs. Spirorchis parvus are capable of invading various tissues, including pancreas and the central nervous system. The pathogenicity of the flukes seems to be related to widespread deposition of the eggs, which may block small blood vessels within the intestines, causing necrosis and bacteremia. Antemortem diagnosis is made by direct examination of fecal smears for eggs. Postmortem diagnosis is accomplished by examination of tissues for adult parasites and microgranulomas associated with the fluke eggs. The parasite requires a snail intermediate host to complete its life cycle. Intramuscular or oral administration of praziquantel is reported to be an effective treatment.


Subject(s)
Animals, Laboratory , Trematode Infections/veterinary , Turtles , Animals , Feces/parasitology , Liver/pathology , Necrosis , Pancreas/pathology , Parasite Egg Count , Spleen/pathology , Trematoda/isolation & purification , Trematode Infections/diagnosis , Trematode Infections/pathology
18.
J Virol ; 71(11): 8157-66, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9343166

ABSTRACT

The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation.


Subject(s)
Antigens, Polyomavirus Transforming/physiology , Carcinoma, Acinar Cell/virology , Pancreatic Neoplasms/virology , Animals , Carcinoma, Acinar Cell/pathology , Genes, p53 , Mice , Mice, Inbred C57BL , Mice, Transgenic , Pancreatic Elastase/genetics , Pancreatic Neoplasms/pathology , Promoter Regions, Genetic
19.
Pharmacology ; 54(5): 241-55, 1997 May.
Article in English | MEDLINE | ID: mdl-9380770

ABSTRACT

This study was designed to determine whether pyrazinoylguanidine (PZG) can attenuate diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced within 1 week after a single intraperitoneal dose of STZ (45 mg/kg in 0.05 mol/l sodium citrate buffer). Diabetic rats were divided into five groups. Each group received by gavage for 24 weeks one of the following: vehicle (saline 10 ml/kg, b.i.d.), PZG (35 mg/kg, b.i.d.), captopril (15 mg/kg, b.i.d.), or hydrochlorothiazide (HCTZ, 20 mg/kg, b.i.d.). Insulin (NPH 7.5 U/day) was given subcutaneously. PZG treatment for 24 weeks reduced mortality and attenuated diabetic nephropathy, as indicated by reduced urinary excretion of total protein (79% of control), low-molecular-weight protein (12% of control), and albumin (60% of control). PZG also preserved renal structure and function. Compared to HCTZ or vehicle-treated rats, STZ-diabetic rats receiving either captopril or insulin exhibited decreased excretion of total protein, low-molecular-weight protein, and albumin, as well as amelioration of renal pathology. Collectively, these results indicate that PZG, as well as captopril and insulin, improved longevity and several indices of diabetic nephropathy in STZ-diabetic rats.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Guanidines/therapeutic use , Hypoglycemic Agents/therapeutic use , Pyrazines/therapeutic use , Analysis of Variance , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Captopril/administration & dosage , Captopril/pharmacology , Captopril/therapeutic use , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/mortality , Disease Models, Animal , Guanidines/administration & dosage , Guanidines/pharmacology , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/pharmacology , Hydrochlorothiazide/therapeutic use , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Injections, Subcutaneous , Insulin/administration & dosage , Insulin/pharmacology , Insulin/therapeutic use , Kidney/drug effects , Kidney/pathology , Kidney/physiology , Kidney Function Tests , Male , Molecular Weight , Pyrazines/administration & dosage , Pyrazines/pharmacology , Rats , Rats, Sprague-Dawley , Serum Albumin/metabolism , Streptozocin
20.
J Vasc Interv Radiol ; 8(1 Pt 1): 113-8, 1997.
Article in English | MEDLINE | ID: mdl-9025049

ABSTRACT

PURPOSE: Investigation of a technique for nonsurgical female sterilization. MATERIALS AND METHODS: A custom designed platinum microcoil with Dacron fibers was placed unilaterally into a fallopian tube and uterine horn of 10 rabbits after transcervical selective tubal catheterization with use of fluoroscopic guidance. The contralateral uterus and fallopian tube served as controls. After the rabbits were bred, pregnancy was determined by palpation and confirmed at autopsy. Postmortem histopathologic evaluation of uteri and fallopian tubes was performed. RESULTS: Nine of the 10 rabbits became pregnant. None of the animals had embryos on the microcoil side. Nine rabbits had a total of 45 embryos on the control side. One animal failed to become pregnant on either side. The microcoil remained in good position in all 10 rabbits. There was a microcoil-associated, mild inflammatory tissue response in the uteri and fallopian tubes. CONCLUSION: A platinum occlusion microcoil placed in a utero-tubal location has potential as a means for nonsurgical female sterilization.


PIP: At Milton S. Hershey Medical Center in Hershey, Pennsylvania, researchers used fluoroscopy to guide transcervical selective tubal catheterization in order to correctly insert a custom-designed platinum microcoil with Dacron fibers 1.5-6 cm into a fallopian tube and 1.5-5.5 cm into a uterine horn of 10 rabbits. The fallopian tube and uterine horn on the opposite side were the controls. The researchers sacrificed the rabbits to conduct histopathologic examination of the uteri and fallopian tubes in order to determine the presence or absence of embryos. One rabbit had no embryos on either side, even after 4 breeding attempts. Among the remaining 9 rabbits, there were no embryos on the microcoil side and 45 embryos on the control side. The position of the microcoil did not change in any rabbit. The microcoil caused a mild inflammatory tissue response in the uteri and fallopian tubes. Longer-term studies in more animals are necessary to confirm the efficacy and safety of this sterilization method as well as to determine the potential for retrievability of the microcoil and reversibility of the sterilization effect. In conclusion, a uterotubal coil may someday be a safe, effective, minimally invasive means of female sterilization.


Subject(s)
Cervix Uteri , Intrauterine Devices , Sterilization, Tubal/methods , Animals , Cell Division , Equipment Design , Fallopian Tubes/pathology , Female , Follow-Up Studies , Hysterosalpingography , Male , Platinum , Polyethylene Terephthalates , Pregnancy , Rabbits , Sterilization, Tubal/instrumentation , Uterus/pathology
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