An extended core nanocoax pillar architecture for enhanced molecular detection.

Biosensors that incorporate nanomaterials and nanofabrication techniques enable molecular detection of chemical and biological macromolecules with a high degree of specificity and ultrasensitivity. Here, we present a novel fabrication process that yields a nanostructure capable of detecting biological macromolecules. The extended core nanocoax (ECC) structure builds on a previously reported nanocoaxial-based sensor. The fabrication of the device incorporates an extended inner pillar, with controllable extension above the annulus and into the surrounding solution. This new design eliminates structural constraints inherent in the original nanocoax architecture. We also provide results demonstrating improvement in biosensing capability. Specifically, we show the capability of the new architecture to detect the B subunit of the Vibrio cholerae toxin at improved sensitivity (100 pg/ml) in comparison to optical enzyme-linked immunosorbant assay (1 ng/ml) and previously reported coaxial nanostructures (2 ng/ml).

Evaluation of two-dimensional ultrasonography and computed tomography in the mapping and measuring of canine urinary bladder tumors.

Determining the dimensions of transitional cell carcinomas (TCCs) of the urinary bladder in dogs is important in assessing tumor progression and the response to treatment. The primary aim of this study was to evaluate the reliability of a standardized two-dimensional (2-D) ultrasound (US) protocol performed by a single experienced operator. Secondary aims were to compare World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and to compare measurements by two operators following these guidelines. These were evaluated by inter-operator and intra-operator reliability using the concordance correlation coefficient (CCC) and Cohen's κ statistics, which demonstrated substantial to better agreement by an experienced operator using either set of guidelines. It was demonstrated that 2-D US provides a reliable means to determine the dimensions of urinary bladder TCC when an experienced operator used a standardized protocol. In a subset of dogs, urinary bladder distension was varied, which resulted in differences in measurement with 2-D US and computed tomography.

Origin of anomalous magnetite properties in crystallographic matched heterostructures: Fe3O4(111)/MgAl2O4(111).

Magnetite films grown on crystallographically matched substrates such as MgAl2O4 are not expected to show anomalous properties such as negative magnetoresistance and high saturation fields. By atomic resolution imaging using scanning transmission electron microscopy we show direct evidence of anti-phase domain boundaries (APB) present in these heterostructures. Experimentally identified 1/4<101> shifts determine the atomic structure of the observed APBs. The dominant non-bulk superexchange interactions are between 180° octahedral-Fe/O/octahedral-Fe sites which provide strong antiferromagnetic coupling across the defect interface resulting in non-bulk magnetic and magnetotransport properties.

Canine intracranial gliomas: relationship between magnetic resonance imaging criteria and tumor type and grade.

Limited information is available to assist in the ante-mortem prediction of tumor type and grade for dogs with primary brain tumors. The objective of the current study was to identify magnetic resonance imaging (MRI) criteria related to the histopathological type and grade of gliomas in dogs. A convenience sample utilizing client-owned dogs (n=31) with gliomas was used. Medical records of dogs with intracranial lesions admitted to two veterinary referral hospitals were reviewed and cases with a complete brain MRI and definitive histopathological diagnosis were retrieved for analysis. Each MRI was independently interpreted by five investigators who were provided with standardized grading instructions and remained blinded to the histopathological diagnosis. Mild to no contrast enhancement, an absence of cystic structures (single or multiple), and a tumor location other than the thalamo-capsular region were independently associated with grade II tumors compared to higher grade tumors. In comparison to oligodendrogliomas, astrocytomas were independently associated with the presence of moderate to extensive peri-tumoral edema, a lack of ventricular distortion, and an isointense or hyper-intense T1W-signal. When clinical and MRI features indicate that a glioma is most likely, certain MRI criteria can be used to inform the level of suspicion for low tumor grade, particularly poor contrast enhancement. Information obtained from the MRI of such dogs can also assist in predicting an astrocytoma or an oligodendroglioma, but no single imaging characteristic allows for a particular tumor type to be ruled out.

Contrast magnetic resonance imaging for measurement of cartilage glycosaminoglycan content in dogs: a pilot study.

OBJECTIVE: To assess the ability of a contrast-enhanced magnetic resonance imaging (MRI) technique to quantitatively determine glycosaminoglycan content in canine articular cartilage. METHODS: Fifty-four full-thickness cartilage discs were collected from the femorotibial and scapulohumeral joints of three adult dogs immediately following euthanasia. One set of discs from each dog was analysed for glycosaminoglycan content using a colourimetric laboratory assay. The remaining position-matched set of discs from contralateral limbs underwent pre- and post-contrast gadolinium-enhanced MRI, using repeated saturation recovery pulse sequences which were used to generate calculated T1 maps of the cartilage discs. Linear regression analysis was then performed relating delayed gadolinium-enhanced MRI T1 calculated signal intensity to the cartilage glycosaminoglycan content normalized to DNA content. Repeatability of triplicate measurements was estimated by calculating the coefficient of variation. RESULTS: Mean coefficient of variation estimates for the gadolinium-enhanced MRI T1 signal intensity values for nine sampling sites from three dogs ranged from 5.9% to 7.5%. Gadolinium-enhanced MRI T1 signal intensity was significantly correlated (p <0.05) with normalized glycosaminoglycan content in two dogs (r = 0.79, p = 0.011; r = 0.78, p = 0.048), but not in the third dog (r = 0.53, p = 0.071). CLINICAL SIGNIFICANCE: Gadolinium-enhanced MRI assessment of cartilage may be predictive of glycosaminoglycan content and therefore offer an in vivo assessment of changes in cartilage characteristics over time. Additional studies appear indicated to determine the reliability and clinical applicability of gadolinium-enhanced MRI in detecting changes in cartilage over time.

Uterine myometrium as a cell patch as an alternative graft for transplantation to infarcted cardiac myocardium: a preliminary study.

PURPOSE: Currently, only a small fraction of patients are able to receive reperfusion therapy for myocardial infarctions. We hypothesize that myometrial cell patch transplantation could be an alternative approach for the treatment of myocardial infarction. DESIGN: We performed a preliminary study to determine the feasibility of this novel therapeutic approach in a rabbit model. PROCEDURES: Six adult female New Zealand rabbits were used. Myocardial infarction was induced by left anterior descending artery ligation. A segment of uterus was removed via a laparotomy incision, and this uterine segment was transplanted as an autologous graft over the infarcted myocardium, which was then reinforced by greater omentum. Statistical methods and outcome measures: Hemodynamic measurements and histological studies. MAIN FINDINGS: All uterine myometrial patches survived in the test animals. Fluoroscopic hemodynamic measurements were made for ejection fractions at 8 weeks after the application of the uterine patch. Histological study demonstrated well-healed myometrial-myocardium junctions with minimum scar tissue. Angiogenesis occurred in the transplanted myometrium. Connexin 43 expression was demonstrated in the transplanted patches. CONCLUSION: Our noncontrolled preliminary rabbit experiments indicate that patches of uterine myometrium reinforced by greater omentum can be used as autologous transplant therapy for infracted myocardium. This is an innovative technique that could lead to future treatment for individuals who may suffer from an infarcted myocardium and may not be eligible for traditional reperfusion therapy.

Studies on cell-cycle synchronization in the asexual erythrocytic stages of Plasmodium falciparum.

Multiplication of Plasmodium parasites within human erythrocytes is essential to malarial disease. The cell-division cycle of this organism, however, is still poorly understood. In other eukaryotes, various techniques for (apparent) cell-cycle synchronization have been used to shed light on the mechanisms involved in cell division and its control. Thus far there is no technique for cell-cycle synchronization (as opposed to selection of parasites of a limited age-range) in Plasmodium. We therefore investigated the possibility that inhibitors of DNA synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin-dependent kinases) could be used to synchronize P. falciparum cultures to a particular cell-cycle phase. Surprisingly, most of these compounds did not cause a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L-mimosine, did block development at the trophozoite-schizont transition (S or G2 phase). The block caused by the latter 2 inhibitors was reversible, suggesting that they might be used as synchronizing agents. However, a consideration of the perturbing effects of inhibitors and problems with 'batch' synchronization techniques in general lead us to believe that any results obtained using roscovitine- or L-mimosine-treated parasites may not be reflective of the normal cell cycle.

Correlates of compliance in a randomized exercise trial in myocardial infarction patients.

PURPOSE: Exercise-based rehabilitation programs have been associated with decreased morbidity and mortality after myocardial infarction. Unfortunately, attendance is often poor, and information is limited regarding predictors of long-term compliance to such programs. This study examined factors associated with exercise session compliance over 3 yr in male myocardial infarction (MI) survivors. METHODS: Subjects were participants in the National Exercise and Heart Disease Project, a 3-yr (1976-1979) multicenter, randomized clinical trial (N = 651); 308 men, 30-64 yr of age, were randomized to the exercise treatment group, that met three times/week throughout the study. Compliance was defined as the number of sessions attended/number of sessions conducted. Patient characteristics at enrollment were considered as possible predictors of compliance. RESULTS: Compliance decreased as time since enrollment increased with the largest decrease observed after the first 8 wk. Compliance correlated positively with exercise test measures [last completed stage (r = 0.17, P < 0.01), peak heart rate (r = 0.11, P = 0.06)], high density lipoprotein (HDL) cholesterol (r = 0.15, P = 0.10), age (r = 0.11, P = 0.07), and inversely with body mass index (r = -0.19, P = 0.001), sum of three skinfolds (r = -0.15, P < 0.01), total cholesterol (r = -0.18, P < 0.01), triglycerides (r = -0.16, P < 0.01), and depression (r = -0.09, P < 0.11). Current smokers were less compliant than former and nonsmokers (r = -0.21, P < 0.001). The correlations with last completed stage, BMI, skinfolds, total cholesterol, and smoking status were statistically significant. The model explained 22.2% of the variance in compliance (r2 = 0.222). Baseline work capacity was among the most consistent predictors of early and late compliance. CONCLUSION: Compliance decreased over time. Men already at high risk for repeat events due to elevated risk factors were less compliant. These findings have important clinical implications regarding screening, intervention, and participation in potential cardiac rehabilitation program dropouts.

Prognostic value of peak exercise systolic blood pressure on long-term survival after myocardial infarction.

This study examined the association between peak exercise systolic blood pressure and other exercise test parameters and the long-term (19-year) survival of 625 patients with myocardial infarction who were original participants of the National Exercise and Heart Disease Project, a 3-year (1976 to 1979) multicenter randomized exercise clinical trial. Results show that low peak exercise systolic blood pressure (< or =140 mm Hg) was associated with increased mortality throughout the 19 years of follow-up, and men with this finding obtained no survival benefit from participating in an exercise program.

TVB receptors for cytopathic and noncytopathic subgroups of avian leukosis viruses are functional death receptors.

The identification of TVB(S3), a cellular receptor for the cytopathic subgroups B and D of avian leukosis virus (ALV-B and ALV-D), as a tumor necrosis factor receptor-related death receptor with a cytoplasmic death domain, provides a compelling argument that viral Env-receptor interactions are linked to cell death (4). However, other TVB proteins have been described that appear to have similar death domains but are cellular receptors for the noncytopathic subgroup E of ALV (ALV-E): TVB(T), a turkey subgroup E-specific ALV receptor, and TVB(S1), a chicken receptor for subgroups B, D, and E ALV. To begin to understand the role of TVB receptors in the cytopathic effects associated with infection by specific ALV subgroups, we asked whether binding of a soluble ALV-E surface envelope protein (SU) to its receptor can lead to cell death. Here we report that ALV-E SU-receptor interactions can induce apoptosis in quail or turkey cells. We also show directly that TVB(S1) and TVB(T) are functional death receptors that can trigger cell death by apoptosis via a mechanism involving their cytoplasmic death domains and activation of the caspase pathway. These data demonstrate that ALV-B and ALV-E use functional death receptors to enter cells, and it remains to be determined why only subgroups B and D viral infections lead specifically to cell death.

Maximal exercise systolic pressure, exercise training, and mortality in myocardial infarction patients.

The relation of maximal exercise systolic pressure to physical conditioning and to mortality was determined in 641 men with > or =1 myocardial infarctions. Each performed a standardized multistage exercise test before randomized assignment either to an exercise group or a control group and at scheduled periodic intervals over 3 years. This study compares 123 men with maximal exercise systolic pressures (MESP) of < or =140 mm Hg with 518 men whose maximal exercise systolic pressure was > or =140 mm Hg. At baseline, the 2 groups were comparable for age, entry time since the occurrence of the qualifying cardiac event, and reported use of antihypertensive medications. Men with low MESP used more beta blockers, had lower systolic pressure measurements at rest and by definition at maximal exercise, and lower work capacity than men with higher levels of MESP. Men with low MESP experienced: (1) no reduction in mortality with exercise conditioning (p<0.86), and (2) a significantly higher mortality rate over 3 years (p<0.003) compared with men with higher levels of MESP. The relation of a low MESP to mortality persisted: (1) whether MESP or work capacity increased from the baseline exercise test to the last performed exercise test, and (2) whether it was measured at low (<6 METs) or high (> or =6 METs) levels of work capacity. We conclude that low maximal exercise systolic blood pressure is a predictor of mortality and is associated with an ineffective training response in men with myocardial infarction.

Results of a multicenter randomized clinical trial of exercise and long-term survival in myocardial infarction patients: the National Exercise and Heart Disease Project (NEHDP).

BACKGROUND: This study examined whether a supervised exercise program improved 19-year survival in 30- to 64-year-old male myocardial infarction patients. METHODS AND RESULTS: The men (n=651) were participants in the National Exercise and Heart Disease Project, a 3-year multicenter randomized clinical trial conducted in the United States (1976-1979). The treatment group (n=315) exercised for 8 weeks in a laboratory. Thereafter, they jogged, cycled, or swam in a gymnasium/pool setting guided by an individualized target heart rate. Participants in the control group (n=319) were to maintain normal routines but not participate in any regular exercise program. Participants were followed up until their death or December 31, 1995. Cox proportional hazards analysis revealed the all-cause mortality risk estimates (95% CIs) in the exercise group compared with controls to be 0.69 (0.39 to 1.25) after an average follow-up of 3 years, 0.84 (0.55 to 1.28) after 5 years, 0.95 (0.71 to 1.29) after 10 years, 1.02 (0.79 to 1.32) after 15 years, and 1.09 (0.87 to 1. 36) after 19 years. Cardiovascular disease (CVD) mortality risk estimates (95% CI) for the same follow-up periods were 0.73 (0.37 to 1.43), 0.98 (0.60 to 1.61), 1.21 (0.79 to 1.60), 1.14 (0.84 to 1.54), and 1.16 (0.88 to 1.52). However, each 1-MET increase in work capacity from baseline to the end of the original trial resulted in consistent reductions in all-cause and CVD mortality risk at each follow-up period, regardless of initial work-capacity level. CONCLUSIONS: These findings indicate exercise-program participation resulted in nonsignificantly reduced mortality risks early in the follow-up period. Benefits diminished as time since participation increased, which suggests that the protective mechanisms associated with the program may be short term. Contamination between groups over time could also explain the diminished effects, because increased work capacity provided survival benefits up to 19 years.

Work and leisure time physical activity and mortality in men and women from a general population sample.

PURPOSE: The purpose of this study was to examine the long-term relationships between total physical activity and mortality from all causes and coronary heart disease (CHD) in the general population. METHODS: A prospective design was used, following participants for 29 years, beginning in 1960. The study population consisted of a randomly selected sample of white male (n = 698) and female (n = 763) residents of Buffalo, New York with a 79.0% participation rate and follow-up rates of 96.0% and 90.2% in males and females, respectively. At baseline, comprehensive information was obtained regarding participants' usual physical activity at work and during leisure time. RESULTS: As of December 31, 1989, three hundred and two (43.3%) men and 276 (41.0%) women died, 109 (15.6%) and 81 (10.6%) from CHD, respectively. In men, a significant interaction was found between activity and body mass index (BMI) for both outcomes. In women, a significant activity by age interaction was observed. In non-obese men (BMI<27.02), activity was inversely associated with all-cause [relative risk (RR) = 0.59; 95% confidence interval (CI), 0.39-0.89] and CHD mortality (RR = 0.39; 95% CI, 0.18-0.83), independent from the effects of age and education. No such associations were found in obese men and increased risks could not be ruled out. Among women, younger participants (age <60 years) had a significantly reduced risk of CHD death with increased activity (RR = 0.26; 95% CI, 0.07-0.99). No other significant associations were observed. CONCLUSIONS: Physical activity favorably influences mortality risks in non-obese men and younger women. Gender-specific factors should be considered for potential effect modification.

The CAR1 gene encoding a cellular receptor specific for subgroup B and D avian leukosis viruses maps to the chicken tvb locus.

Host susceptibility to subgroup B, D, and E avian leukosis viruses (ALV) is determined by specific alleles of the chicken tvb locus. Recently, a chicken gene that encodes a cellular receptor, designated CAR1, specific for subgroups B and D ALV was cloned, and it was proposed that this gene was the s3 allele of tvb (J. Brojatsch, J. Naughton, M. M. Rolls, K. Zingler, and J. A. T. Young, Cell 87:845-855, 1996). We now report that in a backcross derived from an F1 (Jungle Fowl x White Leghorn [WL]) male mated with inbred WL females, the cloned ALV receptor gene cosegregated with two markers linked to tvb. The two markers used were a tvb(s1)-specific antigen recognized by the chicken R2 alloantiserum and restriction fragment length polymorphisms associated with the expressed sequence tag com152e. With all three markers, no crossovers were observed among 52 backcross progeny tested and LOD linkage scores of 15.7 were obtained. These data demonstrate that CAR1 is the subgroup B and D ALV susceptibility gene located at tvb(s3).

Allospecific vocal learning by Grey parrots (Psittacus erithacus): A failure of videotaped instruction under certain conditions.

Grey parrots (Psittacus erithacus) do not acquire referential English labels when tutored with videotapes in social isolation (Pepperberg, I.M., 1994. Auk 111, 300-313) possibly because of (1) lack of social interaction to direct their attention appropriately or (2) absence of reward for an attempt at a targeted label. To test the first premise, two parrots watched videotapes with trainers who directed the birds' attention to the video monitor. Vocal praise rewarded attempts at a targeted label. To test the second premise, subjects watched videotapes in social isolation with a reward system that, in the absence of social interaction, could furnish the appropriate item after an attempt at the label. Subjects also received live interactive tutoring on a different set of object labels. Birds learned referential labels from live interactive tutors but not from videotapes. Specific aspects of live tutoring appear critical for the acquisition of referential English labels.

Identification of a cellular receptor for subgroup E avian leukosis virus.

Genetic studies in chickens and receptor interference experiments have indicated that avian leukosis virus (ALV)-E may utilize a cellular receptor related to the receptor for ALV-B and ALV-D. Recently, we cloned CAR1, a tumor necrosis factor receptor (TNFR)-related protein, that serves as a cellular receptor for ALV-B and ALV-D. To determine whether the cellular receptor for ALV-E is a CAR1-like protein, a cDNA library was made from turkey embryo fibroblasts (TEFs), which are susceptible to ALV-E infection, but not to infection by ALV-B and ALV-D. The cDNA library was screened with a radioactively labeled CAR1 cDNA probe, and clones that hybridized with the probe were isolated. A 2.3-kb cDNA clone was identified that conferred susceptibility to ALV-E infection, but not to ALV-B infection, when expressed in transfected human 293 cells. The functional cDNA clone is predicted to encode a 368 amino acid protein with significant amino acid similarity to CAR1. Like CAR1, the TEF protein is predicted to have two extracellular TNFR-like cysteine-rich domains and a putative death domain similar to those of TNFR I and Fas. Flow cytometric analysis and immunoprecipitation experiments demonstrated specific binding between the TEF CAR1-related protein and an immunoadhesin composed of the surface (SU) envelope protein of subgroup E (RAV-0) virus fused to the constant region of a rabbit immunoglobulin. These two activities of the TEF CAR1-related protein, specific binding to ALV-E SU and permitting entry only of ALV-E, have unambiguously identified this protein as a cellular receptor specific for subgroup E ALV.

A consortium, graduate medical education, and Buffalo: defining a common ground.

Regional graduate medical education (GME) consortia are a strategy to align public support for GME with societal goals. One such consortium was established in Buffalo, NY, to pool financial resources, facilitate processing of Accreditation Council for Graduate Medical Education requirements, guarantee quality education, and more appropriately use community resources. Cooperation has attracted external funding from state and federal governments and private foundations, fostering community-wide undergraduate medical education, as well as GME. The American Association of Medical Colleges has identified 36 GME consortia in the United States. New York may lead the nation on a strategy to use consortia for the distribution of all state-appropriated GME support. The relationships fostered by consortial interactions have benefitted family medicine and provided opportunities for leading regional medical education into a primary care-specialty balanced future.

CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis.

Viral envelope (Env)-receptor interactions have been implicated in the cell death associated with infection by subgroups B and D avian leukosis-sarcoma viruses (ALVs). A chicken protein, CAR1, was identified that permitted infection of mammalian cells by these viral subgroups. CAR1 bound to a viral Env fusion protein, comprising an ALV-B surface Env protein and the Fc region of an immunoglobulin, indicating that it is a specific viral receptor. CAR1 contains two extracellular cysteine-rich domains characteristic of the TNFR family and a cytoplasmic region strikingly similar to the death domain of TNFR1 and Fas, implicating this receptor in cell killing. Chicken embryo fibroblasts susceptible to ALV-B infection and transfected quail QT6 cells expressing CAR1 underwent apoptosis in response to the Env-Ig fusion protein, demonstrating that this cytopathic ALV receptor can mediate cell death.

The academic health center and the healthy community.

US medical care reflects the priorities and influence of academic health centers. This paper describes the leadership role assumed by one academic health center, the State University at Buffalo's School of Medicine and Biomedical Sciences and its eight affiliated hospitals, to serve its region by promoting shared governance in educating graduate physicians and in influencing the cost and quality of patient care. Cooperation among hospitals, health insurance payers, the business community, state government, and physicians helped establish priorities to meet community needs and reduce duplication of resources and services; to train more primary care physicians; to introduce shared governance into rural health care delivery; to develop a regional management information system; and to implement health policy. This approach, spearheaded by an academic health center without walls, may serve as a model for other academic health centers as they adapt to health care reform.