Miracle-dz/UniFAR-FTUs huggingface dataset:
Exposure to 56Fe-Particle Radiation Accelerates Electrophysiological Alterations in the Hippocampus of APP23 Transgenic Mice

Abstract An unavoidable complication of space travel is exposure to high-charge, high-energy (HZE) particles. In animal studies, exposure of the CNS to HZE-particle radiation leads to neurological alterations similar to those seen in aging or Alzheimer's disease. In this study we examined whether HZE-particle radiation accelerated the age-related neuronal dysfunction that was previously described in transgenic mice overexpressing human amyloid precursor protein (APP). These APP23 transgenic mice exhibit age-related behavioral abnormalities and deficits in synaptic transmission. We exposed 7-week-old APP23 transgenic males to brain-only 56Fe-particle radiation (600 MeV/nucleon; 1, 2, 4 Gy) and recorded synaptic transmission in hippocampal slices at 2, 6, 9, 14 and 18–24 months. We stimulated Schaeffer collaterals and recorded field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in CA1 neurons. Radiation accelerated the onset of age-related fEPSP decrements recorded at the PS threshold from 14 months of age to 9 months and reduced synaptic efficacy. At 9 months, radiation also reduced PS amplitudes. At 6 months, we observed a temporary deficit in paired-pulse inhibition of the PS at 2 Gy. Radiation did not significantly affect survival of APP23 transgenic mice. We conclude that irradiation of the brain with HZE particles accelerates Alzheimer's disease-related neurological deficits.
Accumulation of cortical hyperphosphorylated neurofilaments as a marker of neurodegeneration in multiple sclerosis

Background: Axonal loss and grey matter neuronal injury are pathological processes that contribute to disease progression in multiple sclerosis (MS). Axon damage has been associated with changes in the phosphorylation state of neurofilaments and the presence of axonal spheroids. Perikaryal accumulation of abnormally phosphorylated neurofilament proteins has been reported in some neurodegenerative diseases. Objectives: The objective of this article is to determine whether abnormally phosphorylated neurofilament accumulates in neuronal perikarya in demyelinated MS cortex. Methods: We used an antibody to hyperphosphorylated neurofilament-H (SMI-34) to assess the level and distribution of this antigen in paraffin sections of cerebral cortex from cases of neuropathologically confirmed MS and controls. We also examined the relationship of neurofilament phosphorylation to cortical demyelination. Results: The number of SMI-34-positive neuronal somata was significantly higher in the MS cortex than the control cortex. As a proportion of the total number of neurons present (i.e. taking account of neuronal loss), the proportion of SMI-34-positive neurons was also significantly higher in the demyelinated and non-demyelinated MS cortex than the control cortex. Conclusions: MS is associated with the widespread accumulation of hyperphosphorylated neurofilament protein in neuronal somata, with the most marked accumulation in regions of cortical demyelination. This aberrant localisation of hyperphosphorylated neurofilament protein may contribute to neuronal dysfunction and degeneration in MS patients.
Morphological aspects and expression of estrogen and progesterone receptors in the interdigital sinus in cyclic ewes

Many species that belong to Artiodactyls order show an interdigital sinus (IS), as it occurs in sheep, in all four extremities. These are considered to be scent glands responsible for sexual communication having strong attractiveness to mature males at the peak of the breeding season. The aim of this study was to evaluate, in IS in cyclic ewes, the microscopic and ultrastructure (scanning and transmission electron microscopy) anatomy, secretion composition, and mRNA and protein expression of estrogen receptors α and β and progesterone receptors. Glandular sebaceous structures occupy a superficial area of the pouch. The other glands present in the IS show a coiled tubular structure and tall and polyhedral secretory cells with irregular luminal surface resulting from the secretory process. Protein and mRNA gene transcription studies were performed to determine the presence of ER (α and β) and P4r in IS. At the follicular phase, IS cell populations analyzed using flow cytometry expressed higher levels of ERβ compared with ERα (P < 0.05), whereas no difference was observed between them in the luteal phase. The IS amount of secretion was the highest in the follicular phase compared with luteal phase (P < 0.05) or pregnancy (P < 0.001). To the best of our knowledge, for the first time, the presence of ER (α and β) within the IS was demonstrated. As estrogen action is mediated by specific receptors in target cells, the presence of these receptors in IS might be needed to trigger signaling pathways involved in conspecific chemical (sexual) communication attributed to this area. Microsc. Res. Tech. 77:313–325, 2014. © 2014 The Authors Microscopy Research and Technique Published by Wiley Periodicals, Inc.
Increased Cell Surface Expression of Receptors for Transforming Growth Factor-β on Osteoblasts from Patients with Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder usually characterized by either a reduction in the production of normal collagen I or the synthesis of abnormal collagen. The variability in the clinical phenotype is not in each case sufficiently explained by the underlying mutation in the collagen I genes. Also, biochemical differences between mutant collagen from different tissues suggest additional regulatory mechanisms possibly involved in matrix deposition and maturation, two processes in which transforming growth factor-β (TGF-β) plays an important role. We, therefore, studied the cell surface expression and functional properties of TGF-β receptors I, II and III on osteoblasts from a group of OI patients compared to healthy controls. Receptor number and affinity were determined by Scatchard analysis of binding data and TGF-β receptor II gene expression was assessed by RT-PCR. Ligand-induced downregulation of TGF-β receptors was analyzed to demonstrate the dynamic response to exogenous stimuli. All experiments were performed in parallel in human osteoblastic cells from OI patients and from age-matched controls. TGF-β receptors I, II and III (betaglycan) were present on osteoblasts from both healthy donors and OI patients. The receptor numbers were significantly higher (29,000 per cell) on OI osteoblasts than on age-matched control osteoblasts (12,000 per cell) in spite of similar steady state levels for TGF-β receptor II mRNA in OI and control cells. Furthermore, receptor affinity was not significantly different in OI osteoblasts (181 vs. 177 nM–1), and the receptor number did not depend on the culture substrate. With respect to dynamic adaption, ligand-induced downregulation of TGF-β receptors was reduced in OI osteoblasts. In conclusion, the human osteoblastic cells from patients with OI investigated all have an elevated number of cell surface receptors for TGF-β, without any evidence for a transcriptional regulation of TGF-β receptor II. On the functional level, there is some evidence for an impaired adaptive behavior of receptor presentation, whereas receptor affinity is unchanged.
The K469E polymorphism of the ICAM-1 gene is a risk factor for peripheral arterial occlusive disease

Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in lymphocyte migration and activation, and is considered important in the pathogenesis of atherosclerosis. K469E is a common polymorphism of the ICAM-1 gene with potential functional significance. The aim of the present case–control study was to evaluate the association between this polymorphism and peripheral arterial occlusive disease (PAOD). ICAM-1 gene polymorphism was examined by polymerase chain reaction and restriction enzyme analysis in 75 Italian subjects affected by PAOD and 227 controls. The distribution of ICAM-1 genotypes in patients affected by PAOD was 32.1% EE, 50.6% EK, and 17.3% KK. The distribution of ICAM-1 genotypes in control subjects was 17.2% EE, 55.1% EK, and 27.7% KK. The EE genotype was significantly more common in patients than controls (P = 0.006). Logistic regression analysis indicated that the presence of the EE genotype significantly increases the risk of PAOD (odds ratio, 3.5; 95% confidence interval, 1.5–8.4;P = 0.004). This is the first study documenting a role of the ICAM-1 gene polymorphism in the pathogenesis of a cardiovascular disease, such as PAOD. Our data support the hypothesis that inflammatory mechanisms are important in the pathophysiology of vascular diseases with an atherosclerotic basis.
Hypercortisolism in septic shock is not suppressible by dexamethasone infusion

ObjectiveTo explore the feedback regulation of glucocorticoids on corticotropin secretion in patients with septic and nonseptic circulatory shock. DesignProspective study. SettingAn intensive care unit of a general hospital. PatientsTwo groups of patients with septic shock (n = 11) or nonseptic shock (n = 7). A control group (n = 20) was also studied. InterventionsIntravenous dexamethasone (1 mg/hr for 4 hrs) suppression test. MeasurementsPlasma concentrations of corticotropin-releasing factor, β-lipotropin, and corticosteroid-binding globulin measured by radioimmunoassays, and plasma cortisol measured by radiocompetition assay; the ratio of cortisol to corticosteroid-binding globulin calculated as the free cortisol index. Main ResultsIn both groups of patients, the concentrations of plasma cortisol and β-lipotropin, and the ratio of cortisol to corticosteroid-binding globulin, were higher than normal subjects (p < .001) and were not different between septic and nonseptic shock patients, whereas the plasma corticosteroid-binding globulin concentration was significantly (p < .001) lower in septic shock patients than in normal subjects (444 ± 154 vs. 696 ± 56 nmol/L [22.0 ± 7.6 vs. 34.5 ± 2.8 mg/L]), but not significantly lower in nonseptic shock patients (607 ± 157 nmol/L [30.0 ± 7.8 mg/L]). In contrast to the complete suppressive effect of dexamethasone infusion on cortisol and β-lipotropin concentrations in normal subjects, dexamethasone did not suppress cortisol or lipotropin in either septic or nonseptic shock patients. ConclusionsDuring circulatory shock, hypercortisolism is associated with high concentrations of lipotropin, and is not suppressible by intravenous dexamethasone infusion. (Crit Care Med 1993; 21:396–401)
Open Gastrostomy for Noninvasive Ventilation Users with Neuromuscular Disease

Bach JR, Gonzalez M, Sharma A, Swan K, Patel A: Open gastrostomy for noninvasive ventilation users with neuromuscular disease. Objective:To report open gastrostomy for ventilator-assisted or -supported patients with altered nutritional status as a result of severe dysphagia and without tracheostomy, translaryngeal intubation, or general anesthesia. Avoiding intubation and general anesthesia decreases the risk of respiratory complications and can prolong noninvasive respiratory management. Design:The procedure was performed for 62 noninvasive intermittent positive-pressure ventilation users: 44 with amyotrophic lateral sclerosis, 10 with muscular dystrophy including 6 with Duchenne muscular dystrophy, and 8 with other conditions. All had vital capacities <40% of predicted normal. Noninvasive intermittent positive-pressure ventilation was provided in ambient air before, during, and after the procedure. Oxyhemoglobin saturation was maintained at 95% or greater and end-tidal CO2 <40 cm H2O by noninvasive intermittent positive-pressure ventilation and mechanically assisted coughing. Results:There were no complications of the procedure. All patients gained weight subsequently. Mean postgastrostomy survival was 38.8 ± 6.2 mos with 26 of the patients still alive. Eighteen of the 62 patients had no ventilator-free breathing ability before, during, or after the gastrostomy. Fifty-one patients eventually lost all ventilator-free breathing abilities without tracheostomy. Conclusions:Open gastrostomy can be performed safely without airway intubation or general anesthesia for patients with little or no autonomous breathing ability. It permitted continued survival without tracheostomy despite loss of all ventilator-free breathing abilities for 51 patients.
Clinical experience with expanded use of the Ross procedure: a paradigm shift?

BACKGROUND AND AIM OF THE STUDY The study aim was to evaluate the short-term survival and functional outcome after the Ross procedure, with expanded inclusion criteria. METHODS A total of 91 patients (21 females, 70 males; mean age 57.3 +/- 13.1 years; range: 0.1-74 years) underwent aortic valve replacement (AVR) with a Ross procedure at the authors' institution during the year 2007. The underlying valve diseases were stenosis in 60 patients, regurgitation in 17, and a mixed lesion in 14. Seven patients suffered from acute infective endocarditis, and in five patients the Ross operation was a reoperative procedure. Forty-four patients (48%) underwent surgery in association with concomitant procedures, which included predominantly coronary artery bypass surgery, mitral valve repair or replacement, or procedures of the ascending aorta. RESULTS The mean cardiopulmonary bypass and aortic cross-clamp times were 147 +/- 31 min (range: 87-246 min) and 124 +/- 26 min (range: 73-195 min), respectively. Hospital mortality was 2.2%. No patient died during the follow up period. The aortic gradient was decreased from 5.1 +/- 2 mmHg at discharge, to 3.2 +/- 1 mmHg during follow up (p < 0.05); at the same times, the mean gradient of the decellularized tissue-engineered pulmonary valve was 2.8 +/- 1 mmHg and 2.7 +/- 1 mmHg, respectively. An echocardiographic examination of neo-aortic valve competence at 12 months revealed no or trivial aortic valve regurgitation in 80 patients, and mild (grade 1+) regurgitation in nine patients. No patient required reoperation of the autograft during follow up. Two patients underwent reconstruction of the right ventricular outflow tract. At 12 months' follow up, all patients enjoyed normal social interactions, were in NYHA functional class I or II, and free from complications. CONCLUSION The Ross procedure can be offered as an alternative to standard prosthetic AVR with an excellent short-term outcome. The former inclusion/exclusion criteria for this procedure should be re-evaluated.
Role of Glucose, Insulin, and Glucagon in Glycogen Mobilization in Human Hepatocytes

This study investigated the role of glucose, insulin, and glucagon in the activation of glycogen catabolism in cultured human hepatocytes. Basal glycogenolysis in unstimulated human hepatocytes was low (only 19% of initial glycogen content was degraded in a 4-h incubation) and insensitive to changes in external glucose concentration (from 10 to 0 mM). Both glycogenolysis and glucose output could be significantly stimulated by 35 ng/L glucagon or 105 pM dibutyryl cAMP; half-maximal effect was found with 28 × 102 ng/L glucagon and 4 × 105 pM dibutyryl cAMP. After a 3-h exposure to 35 × 103 ng/L glucagon, >90% of glycogen content of human hepatocytes was mobilized. This caused a 4.6-fold increase in the rate of glucose output to the medium compared with nonstimulated cells. About 85% of degraded glycogen rendered glucose to the medium. Insulin (104 pM) was able to totally suppress basal glycogenolysis; insulin was also essential to reverse the action of glucagon in hepatocytes incubated with glucagon, whereas glucose alone, even at postprandial concentration, was unable to reverse glucagon action. In summary, these experiments show that the mobilization of glycogen stores of human hepatocytes, as it occurs during the postabsorptive periods in humans, is largely dependent on the presence of glucagon and is not simply due to a decrease of external glucose. Insulin, on the other hand, was essential to suppress both basal and glucagon-activated glycogenolysis.
Regulated expression of differentiation-associated keratins in cultured epidermal cells detected by monospecific antibodies to unique peptides of mouse epidermal keratins.

Monospecific antibodies to mouse epidermal keratins were generated in rabbits and guinea pigs by injecting synthetic peptides of unique keratin sequences. The sequences were deduced from nucleotide sequences of cDNA clones representing basal (K14) and suprabasal (K1 and K10) cell-specific and hyperproliferative (K6) keratins of both the type-I and type-II subclasses. By applying single-and double-label immunofluorescence analysis, the expression of keratin peptides was analyzed in cultured keratinocytes maintained in the basal or suprabasal cell phenotypes. These cell types were selected by growth in medium containing 0.05 mM Ca2+ (basal cell) or 1.4 mM Ca2+ (suprabasal cell). The cultured basal cells expressed K6 and K14, but less than 1% expressed K1 and K10. Within a few hours after being placed in 1.4 mM Ca2+, K1 expression was observed, and by 24 h, 10%-17% of the cells expressed K1. K10 expression appeared to lag behind K1 expression, with only 5%-10% of cells in 1.4 mM Ca2+ exhibiting K10 immunoreactivity. Double-labeling studies indicated that virtually all K10-positive cells also expressed K1, while only about one-half of the K1-positive cells expressed K10. The treatment of basal cells with retinoic acid at pharmacological concentrations prevented the expression of K1 and K10 when cells were challenged by 1.4 mM Ca2+. Similarly, the introduction of the v-rasH oncogene into basal cells by a defective retroviral vector prevented the expression of suprabasal keratins in 1.4 mM Ca2+ medium. (ABSTRACT TRUNCATED AT 250 WORDS)
Geographical Differences in Myocardial Infarction Incidence in Eight Swedish Counties, 1976–1981

Considerable regional variation in coronary heart disease mortality has been observed in Sweden. This variation is of public health concern and is also a point of departure for etiologic studies. The central aim of the present study was to investigate whether there are also regional differences in myocardial infarction incidence and to evaluate whether these are likely to be explained by regional differences in smoking, blood pressure, and serum cholesterol. The study base consisted of subjects age 30–64 living in eight Swedish counties during 1976–1981. Cases of myocardial infarction were identified using both hospital discharge and death records. A 30–40% increased incidence of myocardial infarction was found in the two northernmost counties compared with Stockholm county. The regional differences in myocardial infarction incidence were not related to differences in smoking but might be due in part to differences in serum cholesterol and blood pressure, and to socioeconomic factors as well. (Epidemiology 1992;3:348–355)
Rasch analysis of SF‐Qualiveen in multiple sclerosis

A 30‐item Qualiveen questionnaire was developed to measure the impact of urinary problems on everyday living in spinal cord injury, and subsequently an 8‐item SF‐Qualiveen was developed for those with multiple sclerosis (MS). The validity of this short form has not been previously examined using modern psychometric techniques, such as the Rasch measurement model.
Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases

Background: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH.
Sexual minority status and psychotic symptoms: findings from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS)

Background Ethnic minority position is associated with increased risk for psychotic outcomes, which may be mediated by experiences of social exclusion, defeat and discrimination. Sexual minorities are subject to similar stressors. The aim of this study is to examine whether sexual minorities are at increased risk for psychotic symptoms and to explore mediating pathways. Method A cross-sectional survey was performed assessing cumulative incidence of psychotic symptoms with the Composite International Diagnostic Interview in two separate random general population samples (NEMESIS-1 and NEMESIS-2). Participants were sexually active and aged 18–64 years (n = 5927, n = 5308). Being lesbian, gay or bisexual (LGB) was defined as having sexual relations with at least one same-sex partner during the past year. Lifetime experience of any psychotic symptom was analysed using logistic regression, adjusted for gender, educational level, urbanicity, foreign-born parents, living without a partner, cannabis use and other drug use. Results The rate of any psychotic symptom was elevated in the LGB population as compared with the heterosexual population both in NEMESIS-1 [odds ratio (OR) 2.56, 95% confidence interval (CI) 1.71–3.84] and NEMESIS-2 (OR 2.30, 95% CI 1.42–3.71). Childhood trauma, bullying and experience of discrimination partly mediated the association. Conclusions The finding that LGB orientation is associated with psychotic symptoms adds to the growing body of literature linking minority status with psychosis and other mental health problems, and suggests that exposure to minority stress represents an important mechanism.
The ABC model and its applicability to basal angiosperms.

BACKGROUND Although the flower is the central feature of the angiosperms, little is known of its origin and subsequent diversification. The ABC model has long been the unifying paradigm for floral developmental genetics, but it is based on phylogenetically derived eudicot models. Synergistic research involving phylogenetics, classical developmental studies, genomics and developmental genetics has afforded valuable new insights into floral evolution in general, and the early flower in particular. SCOPE AND CONCLUSIONS Genomic studies indicate that basal angiosperms, and by inference the earliest angiosperms, had a rich tool kit of floral genes. Homologues of the ABCE floral organ identity genes are also present in basal angiosperm lineages; however, C-, E- and particularly B-function genes are more broadly expressed in basal lineages. There is no single model of floral organ identity that applies to all angiosperms; there are multiple models that apply depending on the phylogenetic position and floral structure of the group in question. The classic ABC (or ABCE) model may work well for most eudicots. However, modifications are needed for basal eudicots and, the focus of this paper, basal angiosperms. We offer 'fading borders' as a testable hypothesis for the basal-most angiosperms and, by inference, perhaps some of the earliest (now extinct) angiosperms.