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Arbuscular mycorrhizal (AM) fungi associate with the roots of many plant species, enhancing their hosts access to soil nutrients whilst obtaining their carbon supply directly as photosynthates. AM fungi often face competition for plant carbon from other organisms. The mechanisms by which plants prioritise carbon allocation to mutualistic AM fungi over parasitic symbionts remain poorly understood. Here, we show that host potato plants (Solanum tuberosum cv. Désirée) selectively allocate carbon resources to tissues interacting with AM fungi rather than those interacting with phytophagous parasites (the nematode Globodera pallida). We found that plants reduce the supply of hexoses but maintain the flow of plant-derived fatty acids to AM fungi when concurrently interacting with parasites. Transcriptomic analysis suggest that plants prioritise carbon transfer to AM fungi by maintaining expression of fatty acid biosynthesis and transportation pathways, whilst decreasing the expression of mycorrhizal-induced hexose transporters. We also report similar findings from a different plant host species (Medicago truncatula) and phytophagous pest (the aphid Myzus persicae). These findings suggest a general mechanism of plant-driven resource allocation in scenarios involving multiple symbionts. Plant antagonists may disrupt the allocation of carbon resources from plants to mutualistic microorganisms. Here, the authors report how plants attacked by cyst nematodes and aphids maintain carbon transfer to arbuscular mycorrhizal fungi through fatty acid transfer whilst the limiting the loss of sugars. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88-1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78-1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort ( p = 0.0089). Fever within 24 h ( p = 0.0092) and early skin and soft tissue infections ( p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients. [ABSTRACT FROM AUTHOR]

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research. [ABSTRACT FROM AUTHOR]

Scanning superconducting quantum interference device (SQUID) measurements recently revealed enhanced channels of conductivity at the conducting LaAlO/SrTiO (LAO/STO) interface (Kalisky et al. Nat. Mater. 12, 1091 2013). The orientation of the channels and their thermal behavior suggest that they originate as a consequence of the STO tetragonal domain formation which sets in below ∼105 K. In this work, we use polarized light microscopy to acquire images of the tetragonal domains in the same group of LAO/STO samples. We looked at the configuration of the domains (orientation and spacing) and followed their behavior as a function of temperature and back-gate voltage. The optical data agrees with the electrical behavior mapped magnetically. This direct and independent study of the domain structure confirms that the channel-like conductivity in LAO/STO is due to the STO tetragonal domain structure and emphasizes the importance of STO physics to the interfacial properties. These results demonstrate how small structural changes in perovskite crystals strongly influence the electronic characteristics of heterostructures. [ABSTRACT FROM AUTHOR]

Consistent with theories of modern racism, we argue that white, non-Hispanic Americans have adopted a 'coded,' race-neutral means of expressing prejudice toward Hispanic immigrants by citing specific behaviors that are deemed inappropriate-either because they are illegal or threatening in an economic or cultural manner. We present data from a series of nationally representative, survey-embedded experiments to tease out the distinct role that anti-Hispanic prejudice plays in shaping public opinion on immigration. Our results show that white Americans take significantly greater offense to transgressions such as being in the country illegally, 'working under the table,' and rejecting symbols of American identity, when the perpetrating immigrant is Hispanic rather than White (or unspecified). In addition, we demonstrate that these ethnicity-based group differences in public reactions shape support for restrictive immigration policies. The findings from this article belie the claim of non-prejudice and race-neutrality avowed by many opponents of immigration. [ABSTRACT FROM AUTHOR]

Iron oxide and cobalt ferrite magnetic nanoparticles (MNPs) of 5-15 nm range have been synthesized by the co-precipitation method, and the magnetic MNPs are functionalized by 3-aminopropyl triethoxy silane and citric acid. The crystalline quality of the MNPs was confirmed using X-ray diffraction, verifying the spinel structure. Spectroscopy study confirmed the presence of the corresponding functional groups on MNP surfaces and thermogravimetric analysis further confirmed functionalization. Coercivity and saturation magnetization exhibited superior superparamagnetic properties. Toxicity studies compared the dose dependent toxicity of both pure iron oxide and cobalt ferrite samples. The toxicity of surface functionalized MNPs showed the potential for use in biomedicine. [ABSTRACT FROM AUTHOR]

Extracellular enzymes produced by heterotrophic microbial communities are major drivers of carbon and nutrient cycling in terrestrial, freshwater, and marine environments. Although carbon and nutrient cycles are coupled on global scales, studies of extracellular enzymes associated with terrestrial, freshwater, and marine microbial communities are not often compared across ecosystems. In part, this disconnect arises because the environmental parameters that control enzyme activities in terrestrial and freshwater systems, such as temperature, pH, and moisture content, have little explanatory power for patterns of enzyme activities in marine systems. Instead, factors such as the functional diversity of microbial communities may explain varying patterns of enzyme activities observed in the ocean to date. In any case, many studies across systems focus on similar issues that highlight the commonalities of microbial community organization. Examples include the effective lifetime of enzymes released into the environment; the extent to which microbial communities coordinate enzyme expression to decompose complex organic substrates; and the influence of microbial community composition on enzyme activities and kinetics. Here we review the often-disparate research foci in terrestrial, freshwater, and marine environments. We consider the extent to which environmental factors may regulate extracellular enzyme activities within each ecosystem, and highlight commonalities and current methodological challenges to identify research questions that may aid in integrating cross-system perspectives in the future. [ABSTRACT FROM AUTHOR]

A number of recent transport and magnetization studies have shown signs of ferromagnetism in the LaAlO3/SrTiO3 heterostructure, an unexpected property with no bulk analogue in the constituent materials. However, no experiment thus far has provided direct information on the host of the magnetism. Here we report spectroscopic investigations of the magnetism using element-specific techniques, including X-ray magnetic circular dichroism and X-ray absorption spectroscopy, along with corresponding model calculations. We find direct evidence for in-plane ferromagnetic order at the interface, with Ti3+ character in the dxy orbital of the anisotropic t2g band. These findings establish a striking example of emergent phenomena at oxide interfaces. [ABSTRACT FROM AUTHOR]

The effect of the exchange energy variation in weakly ferromagnetic alloys on the superconducting resistive transition of superconductor/ferromagnet/superconductor (S/F/S) trilayers is studied. Critical temperature, T, and resistive transitions versus the F-layer thickness, d, have been analyzed in Nb/CuNi/Nb and Nb/PdNi/Nb trilayers. We show that T( d) dependence is sensitive to magnetic inhomogeneities in the F-layer for values of d corresponding to thickness range where the π-superconducting state is established. [ABSTRACT FROM AUTHOR]

PurposeTo assess the effectiveness of anti-tuberculous treatment in patients with chronic uveitis and either active systemic or latent tuberculosis (TB) in a non-endemic community.MethodsRetrospective study of patients with chronic uveitis, non-ocular evidence of latent or active TB and no other identified cause of uveitis who underwent a 6-month course of standard anti-tuberculous chemotherapy. Response to treatment was assessed at 6 and 12 months after initiation of treatment.ResultsA total of 27 patients were included of whom 59% were female. In all, 19 were Asian, 4 Caucasian, and 4 Black. More than half of patients had a history of contact with another person treated for TB. Inflammation resolved after chemotherapy in 70.3% of patients, 18.5% had a change in the nature of their inflammation and 11.1% had no benefit.ConclusionsThere were no uveitis features characteristic of TB uveitis and a wide range of manifestations was seen ranging from non-granulomatous anterior uveitis to occlusive retinal vasculitis. TB is not endemic in the United Kingdom, therefore consideration of ethnicity, immigration, and history of TB contact remain important to direct investigations. In a patient with uveitis and latent TB, a full 6-month course of anti-tuberculous chemotherapy is recommended although it may not be curative of the uveitis. [ABSTRACT FROM AUTHOR]

Semiconductor heterostructures provide an ideal platform for studying high-mobility, low-density electrons in reduced dimensions. The realization of superconductivity in heavily doped diamond, silicon, silicon carbide and germanium suggests that Cooper pairs eventually may be directly incorporated in semiconductor heterostructures, but these newly discovered superconductors are currently limited by their extremely large electronic disorder. Similarly, the electron mean free path in low-dimensional superconducting thin films is usually limited by interface scattering, in single-crystal or polycrystalline samples, or atomic-scale disorder, in amorphous materials, confining these examples to the extreme ‘dirty limit’. Here we report the fabrication of a high-quality superconducting layer within a thin-film heterostructure based on SrTiO3 (the first known superconducting semiconductor). By selectively doping a narrow region of SrTiO3 with the electron-donor niobium, we form a superconductor that is two-dimensional, as probed by the anisotropy of the upper critical magnetic field. Unlike in previous examples, however, the electron mobility is high enough that the normal-state resistance exhibits Shubnikov–de Haas oscillations that scale with the perpendicular field, indicating two-dimensional states. These results suggest that delta-doped SrTiO3 provides a model system in which to explore the quantum transport and interplay of both superconducting and normal electrons. They also demonstrate that high-quality complex oxide heterostructures can maintain electron coherence on the macroscopic scales probed by transport, as well as on the microscopic scales demonstrated previously. [ABSTRACT FROM AUTHOR]

We describe the prototype to product development process of a low cost, socio-culturally relevant, easily implemented Internet-based depression prevention intervention for adolescents in primary care. The intervention named 'Project CATCH-IT' (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training) includes an initial motivational interview in primary care to engage the adolescent, fourteen Web-based modules based on behavioral activation, cognitive behavioral and interpersonal psychotherapy which target known risk factors, and a follow-up motivational interview in primary care. This was successfully fielded in a pilot study with 25 adolescents. We know of no other similar interventions developed for the prevention of depression in youth that is potentially universally available at low cost and that utilizes existing systems of healthcare providers. [ABSTRACT FROM AUTHOR]

In the search for new physical properties of S/F structures, we have found that the superconductor critical current can be controlled by the domain state of the neighboring ferromagnet. The superconductor is a thin wire of thickness ds ≈2ξS. Nb/Co and Nb/Py (Permalloy Ni80Fe20) bilayer structures were grown with a significant magnetic anisotropy. Critical current measurements of Nb/Co structures with ferromagnet thickness dF > 30 nm show sudden drops in two very defined steps when the measurements are made along the hard axes direction (i.e. current track parallel to hard anisotropy axes direction). These drops disappear when they are made along the easy axis direction or when the ferromagnet thickness is below 30 nm. The drops are accompanied by vortex flux flow. In addition magnetorestistance measurements close to TC show a sharp increase near saturation fields of the ferromagnet. Similar results are reproduced in Nb/Py bilayer structure with the ferromagnet thickness dF ~ 50 nm along the easy anisotropy axes. These results are explained as being due to spontaneous vortex formation and flow induced by Bloch domain walls of the ferromagnet underneath. We argue these Bloch domain walls produce a 2D vortex-antivortex lattice structure. [ABSTRACT FROM AUTHOR]

In vivo bioluminescence imaging of reporter enzymes has proven to be a uniquely powerful tool that allows the study of the biology of viral and nonviral gene transfer agents. Cost-effective, noninvasive, longitudinal gene transfer studies in individual animals yield important information, which can influence the design of subsequent preclinical studies. The broad and expanding use of luciferase transgenes, specifically firefly luciferase, has prompted the study of luciferase-specific T-cell activation following in vivo gene transfer. Herein, we report the mapping of the dominant T cell epitope in C57BL/6 mice (LMYRFEEEL) and the mapping of the dominant and minor T-cell epitopes in BALB/c mice (GFQSMYTFV and VPFHHGFGM, VALPHRTAC, respectively). These CD8 T-cell epitopes can be used to monitor cellular responses in vivo as well as be important tools in studies designed to suppress transgene-specific T cells.Gene Therapy (2009) 16, 441–447; doi:10.1038/gt.2008.177; published online 8 January 2009 [ABSTRACT FROM AUTHOR]

The superconducting phase transition in Nb/Cu0.41Ni0.59/Nb trilayers, with superconducting (S) Nb and ferromagnetic (F) Cu0.41Ni0.59, has been experimentally studied as a function of the F-layer thickness by measuring the temperature dependence of the electrical resistance R( T). It is shown that the shape and the width of the R( T) curves depends on the Cu0.41Ni0.59 thickness, in particular in the regime where π is the coupling between the S layers, which can be expected. To explain the data, we developed a qualitative model which makes the interconnection between the superconducting phase transition and the 0 to π transition in SFS structures are more evident. [ABSTRACT FROM AUTHOR]

The aim of the present work was to investigate whether nestin, a member of the intermediate filament family, is immunohistochemically expressed in the non-tumoral human hypophysis and pituitary neoplasms. Twenty-three normal pituitaries and 125 pituitary neoplasms were included. The tissues were formalin-fixed and paraffin embedded. The neoplasms were identified on hematoxylin–eosin stained sections and were classified by immunohistochemistry as well as electron microscopy. For immunohistochemistry, the streptavidin–biotin–peroxidase complex method was applied using appropriate controls. Several corticotrophs in the autopsy obtained pituitaries showed cytoplasmic nestin immunopositivity. No nestin immunoreactivity was found in other cell types in non-tumorous adenohypophyses and in the cells of various pituitary adenomas. Nestin was, however, expressed in a small proportion of endothelial cells in both anterior and posterior lobes. Staining was also noted in several pituicytes, neurohypophysial nerve fibers, and Herring bodies. In contrast to CD-34 and Factor-8 immunostaining which demonstrated immunopositivity in practically all endothelial cells of every capillary, nestin expression was only focally seen suggesting that the functional status of the immunoreactive and non-staining endothelial cells was not the same. No statistically significant correlation was apparent between nestin immunoreactivity and patient age, gender, tumor size, mitotic index, Ki-67, labeling nuclear index, hormonal immunoprofile, and tumor type. In conclusion, nestin expression in adenomas cannot be viewed as a biologically relevant marker of cell proliferation and as a prognostic indicator. The patchy expression of nestin in endothelial cells remains unexplained and its significance requires further studies. [ABSTRACT FROM AUTHOR]

Chronic aerobic exercise lowers blood pressure (BP), peripheral resistance and cardiac work, and is used widely in antihypertensive and cardiac rehabilitation programmes. In this study, we tested the hypothesis that the cardiovascular benefits of training would occur progressively over several weeks and would diminish over a similar time course on termination of training. In all, 17 young, healthy men undertook a 4-week programme of cycle ergometry (30 min at 60% VO2peak 3–4 times/week) and 13 subjects matched for age, body mass index and fitness acted as controls. Resting BP and rate-pressure product (RPP) had fallen significantly after only 1 week's training and reached a nadir after 2 weeks training. At this time, BP had fallen from 121±7/66±6 to 110±5/57±7 mmHg and resting RPP had fallen from 85±10 to 71±9 (mmHg (beats min−1))−2 (P<0.001 each). In parallel, resting forearm conductance had risen from 0.026±0.010 to 0.052±0.029 (ml min−1) 100 ml−1 mmHg−1 and peak reactive hyperaemia following 3 min brachial artery occlusion was increased from 0.105±0.031 to 0.209±0.041 (ml min−1) 100 ml−1 mmHg−1 (P<0.001 each). No significant further circulatory changes occurred over weeks 3–4 of training. On cessation of training, all values returned to pretraining levels within between 1 (SBP, RPP, vascular conductance) and 2 (DBP, MAP, heart rate, reactive hyperaemia) weeks. The results indicate that the optimal cardiovascular benefits of moderate exercise occur rapidly. At least with short training programmes, the benefits regress once training stops just as quickly as they appeared.Journal of Human Hypertension (2006) 20, 193–200. doi:10.1038/sj.jhh.1001970; published online 5 January 2006 [ABSTRACT FROM AUTHOR]

Using various immunohistochemical markers, the objective of our study was to assess whether correlation exists between growth potential of paraganglioma (pheochromocytoma) cells and formation of metastasis. The patient was a 28-yr-old man who presented with intermittent episodes of gross hematuria due to a mass in the urinary bladder. He had no constitutional symptoms to suggest paraganglioma. Histologic, immunohistochemical, and electron microscopic investigation of the surgically removed tissue proved that the tumor was a malignant paraganglioma with metastases in the regional lymph nodes. The immunohistochemical tests were not supportive of high cell proliferation index, indicating that metastases can develop in the absence of rapid multiplication of the tumor cells. Abnormalities in vascular architecture and marked expression of VEGF in the tumor cells may be regarded as prognostic signs to predict the formation of metastases. [ABSTRACT FROM AUTHOR]

MAP-2, a well characterized member of the microtubule associated protein (MAP) family, binds to and stabilizes microtubules and is involved in cell proliferation as well as neuronal differentiation. The aim of the present work was to study MAP-2 expression in human adenohypophyses and pituitary adenomas. To our knowledge, data regarding MAP-2 expression in human pituitaries has not been reported to date. For immunohistochemistry, the streptavidin-biotin-peroxidase complex method was used. Nine non-tumorous adenohypophyses and 77 adenomas (GH-, PRL-, ACTH-, TSH-, FSH/LH- and/or alpha subunit- producing or immunonegative tumors) were investigated. The results show that MAP-2 is expressed in the cytoplasm of non-tumorous adenohypophysial cells as well as of various pituitary adenoma types. No significant correlation was found between MAP-2 expression and gender, patient age, mitotic activity, MIB-1 labelling indices, hormone immunoprofile, and endocrine status, ie. hormonal activity or lack thereof. Thus MAP-2 expression cannot be used to estimate cell proliferation rate, growth potential, endocrine activity or biologic behaviour of an adenoma. Immunopositivity appeared to be stronger in the cytoplasm of adenoma cells than in that of non-tumorous adenohypophysial cells, implying that the adenoma cells contain larger quantities of MAP-2. It can be concluded that the functional activity of MAP-2 is not associated with the manufacture of any specific adenohypophysial hormone(s) and is not limited to one specific cell type. [ABSTRACT FROM AUTHOR]

We investigated cyclooxygenase expression in parathyroid glands from patients with various pathological conditions in order to coordinate levels of immunoreactivity with histology, with preoperative serum levels of calcium, phosphate, and intact parathyroid hormone, and with clinical diagnoses. Surgical specimens were obtained from 38 patients diagnosed with adenoma and primary, secondary, and tertiary hyperplasias. Incidentally removed parathyroids served as controls. After routine histological processing, approximations of total area and area of oncocytic nodules were calculated for each section of gland. Immunohistochemical reactivities for Cox-1, Cox-2, and values for integrated Cox-2 reactivity were quantified and compared with the clinical diagnoses and preoperative serum biochemistry. For the pooled cases, serum phosphate and PTH were directly related to each other, to total glandular area, and to integrated oncocytic area. Serum calcium was inversely related to serum phosphate and PTH levels as well as to total gland size. Within the adenoma group, the pure chief cell adenoma patients were younger and their tumors showed greater proliferative activity than those in the oncocytic adenoma group. For secondary and tertiary hyperplasias, the number of oncocytic nodules was significantly higher than in the adenomas and primary hyperplasias. In our study, the oncocytic cells are the only demonstrable site of Cox activity. It is suggested that the oncocytic cells play a role in prostaglandin metabolism within the parathyroids and may have a role in the regulation of PTH secretion. [ABSTRACT FROM AUTHOR]

BACKGROUND:: ß-Adrenergic receptor sympathetic nervous system (ß-AR SNS) support of resting metabolic rate (RMR) is attenuated with older age, female sex, and a sedentary lifestyle. Total and abdominal adiposity and/or body fat pattern modulate some SNS-mediated physiological functions. OBJECTIVE:: To determine if total and abdominal adiposity and/or body fat distribution are independently related to SNS support of RMR. DESIGN:: Cross-sectional comparison of ß-AR SNS support of RMR. SUBJECTS:: A total of 54 healthy male and female subjects aged 18-75?y. MEASUREMENTS:: RMR (ventilated hood, indirect calorimetry) before (baseline) and during complete ß-AR blockade; body composition by dual energy X-ray absorptiometry. RESULTS:: Forward stepwise multiple regression analysis using sex, exercise status, age group, %body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity as variables revealed sex to be the strongest predictor, explaining 21% of the variability in ß-AR SNS support of RMR (P=0.0006). Age group explained an additional 4% and exercise status a further 4% (both P=0.10). %Body fat, total adiposity, abdominal adiposity, and the ratio of abdominal adiposity to hip adiposity did not enter the equation. CONCLUSION:: Total and abdominal adiposity and body fat pattern are not independent physiological determinants of ß-AR SNS support of RMR among healthy men and women. Moreover, further support is provided for our previous finding of attenuated ß-AR SNS support of RMR with age, female sex, and sedentary lifestyle.International Journal of Obesity (2003) 27, 1315-1318. doi:10.1038/sj.ijo.0802413 [ABSTRACT FROM AUTHOR]

A government target of a maximum 2-week wait for women referred urgently with suspected breast cancer was introduced in April 1999. We have assessed changes in the distributions of waiting times and the proportions of cases meeting proposed targets before and after this date, using clinical audit data on 5750 women attending 19 hospitals in southeast England during the period July 1997-December 2000, who were subsequently found to have breast cancer. The proportion of cases being seen within 2 weeks of referral rose from 66.0 to 75.2%, and the median wait to first appointment fell from 13.6 to 12.3 days, following the introduction of the government target. The proportion of cases waiting 5 weeks or less between first hospital appointment and treatment fell from 83.8 to 80.3%, and median waits for treatment increased from 21.4 to 24.1 days. We also examined the effects on waiting times of various sociodemographic and care related factors. A total of 85.7% of screening cases vs 67.9% of symptomatic cases were seen within 2 weeks, and 95.0% of cases treated with tamoxifen received treatment within 5 weeks, as opposed to 77.6% of cases treated with surgery, 81.2% of chemotherapy cases and 52.8% of radiotherapy cases. While waiting times from GP referral to first hospital appointment have improved since the introduction of the government target, times from first appointment to treatment have increased, and consequently total waiting times have changed little. [ABSTRACT FROM AUTHOR]

There has been much recent investigation of the cyclooxygenase (Cox) enzymes in tumor biology, but, to our knowledge, no study has yet been published describing Cox activity in medullary carcinoma of the thyroid (MTC). Nine cases of MTC from the past 10 yr were retrieved from our hospital archives. Slides cut from formalin-fixed paraffin-embedded tumor tissue from these cases were assessed for the activities of Cox-1 and Cox-2 enzymes by immunohistochemistry as well as by a battery of immunohistochemical stains for intermediate filaments, peptide hormone, and proliferation and promoter antigens. The staining reactions were semiquantitatively assessed and scored for comparison with each other as well as with each patient’s clinical presentation and course. Staining for Cox-1 and Cox-2 enzymes was present only in tumorous tissue, not in nontumorous thyroid tissue or C-cells. Cox-2 staining was not consistently increased over Cox-1 staining; however, Cox-2 staining bore statistically significant correlations with the expression of low molecular weight keratin, thyroid-transforming factor-1, topoisomerase, and MIB1. Hyperplastic C-cells from patients with diverse physiologic conditions and from three patients with C-cell hyperplasia accompanying medullary carcinoma or multiple endocrine neoplasia type IIa showed no reactivity for the Cox antibodies. It appears that Cox enzyme immunoreactivity is present only in the neoplastic C-cells of medullary carcinoma, but with variable expression. A practical application of the preceding finding might involve the use of Cox staining to distinguish invasive medullary carcinoma cells from hyperplastic C-cells. [ABSTRACT FROM AUTHOR]

We report on a 37-yr-old woman with known antemortem ingestion of minocyclin who died suddenly from a ruptured cerebral aneurysm. At autopsy, her thyroid gland, although not enlarged, was diffusely black, caused by the deposition of a melanin-like pigment that stained positive with Schmorl’s reagent. The pigment could be bleached with permanganate, and on examination by electron microscopy, it appeared to be deposited within the thyrocyte lysosomes. Additional immunostaining with many antibodies revealed an increase in vimentin staining in the follicular epithelium compared with normal control thyroid glands. Staining for cytoplasmic thyroglobulin was markedly reduced, despite normal thyroid indices performed on stored antemortem blood. Stainable ubiquitin in the follicular epithelium appeared reduced compared with control thyroid tissues. These immunohistochemical findings may reflect disruptions of lysosomal transport and function associated with the abnormal accumulation of pigment. This appears to be the only case of minocyclin-associated “black thyroid” in which extensive immunohistochemical investigations have been performed. [ABSTRACT FROM AUTHOR]

Background: Devices that record from the finger have potential practical advantages for home monitoring of blood pressure. However, digital arterial pressure may vary substantially from that in the brachial artery, due to the influence of peripheral wave reflection. Aims: (1) To compare digital arterial pressure, as measured with the Omron F3 device, with brachial arterial pressure and (2) to determine the effect on digital pressure of changing local vascular resistance. Method: The subjects were normotensive young adult non-smokers (12 males, 14 females). Pressures were recorded simultaneously from arm (using an Omron HEM-705CP) and finger with subjects seated and both recording sites at the level of the xiphisternum. Measurements were made at ambient temperatures of 193C and 303C; at rest, during brief contralateral hand cooling and after hand rewarming. Results: In many cases, resting finger values differed substantially from arm values; sometimes by 20 mm Hg or more. The extent of individual variations was not correlated with gender or temperature. However, group pressure differences between the sites were greater in females at ovulation than at menstruation and greater at 30°C than at 19°C. For all groups, pressure differences between sites were attenuated during hand cooling and restored by rewarming. Conclusions: Finger blood pressure, as measured with the Omron F3, misestimates brachial blood pressure in a high proportion of normal subjects. This error is increased under circumstances associated with cutaneous vasodilation. The Omron F3 does not appear to be suitable for unsupervised home monitoring of blood pressure. [ABSTRACT FROM AUTHOR]

Paget's disease of bone (PDB) is a common disorder characterized by focal areas of increased and disorganized osteoclastic bone resorption, leading to bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. Genetic factors play an important role in the pathogenesis of Paget's disease. In some families, the disease has been found to be linked to a susceptibility locus on chromosome 18q21-22, which also contains the gene responsible for familial expansile osteolysis (FEO)--a rare bone dysplasia with many similarities to Paget's disease. Insertion mutations of the TNFRSF11A gene encoding Receptor Activator of NF kappa B (RANK) have recently been found to be responsible for FEO and rare cases of early onset familial Paget's disease. Loss of heterozygosity (LOH) affecting the PDB/FEO critical region has also been described in osteosarcomas suggesting that TNFRSF11A might also be involved in the development of osteosarcoma. In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines. No specific abnormalities of the TNFRSF11A gene were identified in a Pagetic osteosarcoma, the osteosarcoma cell lines, DNA extracted from Pagetic bone lesions, or DNA extracted from peripheral blood in patients with familial or sporadic Paget's disease including several individuals with early onset Paget's disease. These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma. [ABSTRACT FROM AUTHOR]

Among women in the Thames Cancer Registry database with a first breast cancer diagnosed between 1961-1995 observed numbers of subsequent cancers were compared with expected numbers and standardized incidence ratios were calculated. The occurrence of breast cancers subsequent to cancers at other sites was also examined. Women diagnosed with breast cancer before age 50 had significantly elevated risks for 9 cancer sites namely, oesophagus, stomach, lung, bone, connective tissue, breast, corpus uteri, ovary and myeloid leukaemia compared with 2 sites (corpus uteri and myeloid leukaemia) in women diagnosed at age 50 and above. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes, shared environmental factors, or therapy. [ABSTRACT FROM AUTHOR]

Abstract Rationale: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. Objectives: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. Methods: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients' own homes, using the Oxford Medilog system. Results: At 12 weeks, 7/12 patients had responded (HAM-D decreased by >50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed nonsignificant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the... [ABSTRACT FROM AUTHOR]

We have examined how the electric organ discharge (EOD) of a mormyrid ( Gnathonemus petersii) is affected by changes in resistive load (Figs. 3, 4, 5). We have also shown how this load depends on resistivity and distance to non-conducting boundaries (Figs. 10, 11). When resistive load was varied, voltage and current were related in a linear, battery-like manner for the initial, head positive phase of the EOD (Figs. 4, 5). This linear relation made it possible to estimate first phase e.m.f. and source resistance. For the second, head negative phase, however, voltage rose to a peak and then fell as resistance increased. Furthermore, the waveform of the second but not the first phase was strongly affected by load changes. These second phase features were shown to reflect a dependence of second phase e.m.f. on first phase current. A linear and battery-like relation between second phase voltage and current was seen when first phase load was held constant while varying second phase load (Fig. 6). These results on the behavior of the whole electric organ can be understood in terms of the underlying properties of the cellular generators, the electrocytes. [ABSTRACT FROM AUTHOR]

In order to clarify further the neural control of digestive tract function, we have compared the neuronal localization of tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC) in rat small intestine. Immunoreactivity for TH was found in numerous varicose axons associated with neurons of the enteric plexuses and in axons within the circular muscular coat and the mucosal villi. Axons with AADC immunoreactivity had a similar distribution, but were sparser in the enteric plexuses and musculature than those containing TH. Chronic extrinsic denervation of a segment of intestine removed all TH-positive nerves from that region. By contrast, the intensity of AADC immunoreactivity was enhanced and more AADC-positive axons were visible than in adjacent intact areas of intestine. The AADC-positive axons appear to represent the intrinsic 'amine-handling' neurons rather than intrinsic tryptaminergic neurons or extrinsic dopaminergic neurons, and the effect on AADC activity of removing the extrinsic nerve supply suggests that this normally exerts some restraining influence on the metabolism of the 'amine-handling' population. [ABSTRACT FROM AUTHOR]

The ability of the kidney to excrete sodium appears to depend on release of dopamine from intrarenal sources. In the present study, we have used immunohistochemistry to examine the possibility that renal dopaminergic nerves constitute one of these sources. We found that the sympathetic axons supplying cortical structures in human kidney contain tyrosine hydroxylase-like immunoreactivity but lack DOPA decarboxylase-like immunoreactivity. By contrast, the vasa recta arterioles of the renal medulla are supplied by varicose tyrosine hydroxylase-positive nerve fibres, some of which also contain DOPA decarboxylase. As DOPA decarboxylase has been demonstrated in other situations to be a selective marker for dopaminergic terminal axons, our results suggest the innervation of renal medullary blood vessels in man by both noradrenergic and dopaminergic sympathetic nerves. [ABSTRACT FROM AUTHOR]

This note contains a characterization of exponential distributions based on the properties of linear transformations of order statistics. This is a certain converse of a well known theorem of Rényi about the distribution of linear combinations of order statistics from exponential distributions. Some statistical applications of the result are indicated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a bedside clinical prediction rule for detecting moderate or severe aortic stenosis.Design: Cross-sectional study with independent comparison to a diagnostic reference standard, doppler echocardiography.Setting: Urban university hospital.Participants: Consecutive hospital inpatients (n = 124) who had been referred for echocardiography.Measurements and Main Results: Participants were examined by a third-year general internal medicine resident and a staff general internist. We hypothesized in advance that absence of a murmur over the right clavicle would rule out aortic stenosis, while the presence of three or four associated findings (slow carotid artery upstroke, reduced carotid artery volume, maximal murmur intensity at the second right intercostal space, and reduced intensity of the second heart sound) would rule in aortic stenosis. Study physicians were unaware of echocardiographic findings. The outcome was echocardiographic moderate or severe aortic stenosis, defined as a valve area of 1.2 cm2 or less, or a peak instantaneous gradient of 25 mm Hg or greater. Absence of a murmur over the right clavicle ruled out aortic stenosis (likelihood ratio [LR] 0.10; 95% confidence interval [CI] 0.01, 0.44). The presence of three or four associated findings ruled in aortic stenosis (LR 40; 95% CI 6.6, 240). If a murmur was present over the right clavicle, but no more than two associated findings were present, then the examination was indeterminate (LR 1.8; 95% CI 0.93, 2.9).Conclusion: A clinical prediction rule, using simple bedside maneuvers, accurately ruled in and ruled out aortic stenosis. [ABSTRACT FROM AUTHOR]