Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of propofol on CB 1 receptor expression in spinal cord of rats with intrathecal morphine-induced pruritus

Backgrounds: It has been demonstrated that cannabinoid-1 (CB1) receptors in anterior cingulate cortex (ACC) may play a key role in propofol-mediated relief of the intrathecal morphine-induced pruritus in rats. Objective: To explore the effect of propofol on the CB1 receptor expression of rat spinal cord with intrathecal morphine-induced pruritus. Materials and methods: A total of 108 rats were randomly divided into 6 groups: control, normal saline, propofol, intralipid, SR141716A + propofol and Tween 80 + propofol groups. Rats were intrathecally injected with 10 μl normal saline or 40 μg/kg morphine. 10 min after the intrathecal administration, 80 μl/kg normal saline, 80 μl/ kg normal saline, 0.8 mg/kg propofol and 80 μl/kg intralipid were administered via the jugular vein to rats in control, normal saline, propofol, and intralipid groups, respectively; while in the SR141716A + propofol and Tween 80 + propofol groups, rats were administered with SR141716A (1 mg/kg) or Tween 80 (Tween 80/isotonic saline = 1/9) 1 mg/kg by the jugular vein respectively, followed by venous injection of 0.8 mg/kg propofol to both groups. Results: The scratching response was significantly attenuated in propofol and Tween 80 + propofol groups while significantly increased in SR141716A + propofol group (P < 0.001). The expression of CB1 receptor in spinal cord of propofol and Tween 80 + propofol groups were significant increased at 8 min after the administration and remarkably lower in SR141716A + propofol group at 16 min after the administration. Conclusion: Increased expression of CB1 receptors in spinal cord may contribute to the propofol reversal of intrathecal morphine-induced scratching.
Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart.

OBJECTIVE The aim was to study the contribution of ATP sensitive potassium channels (KATP channels) in the coronary vasodilatation produced by prostaglandins I2, E2, and D2 in rats. METHODS Isolated Langendorff rat hearts, perfused under constant flow conditions, and rat aortic rings were used. Dose-response curves to PGE2, PGD2, and iloprost, a PGI2 analogue, were performed before and during KATP channel blockade with glibenclamide. Arachidonic acid was used to increase the formation of endogenous PGI2. RESULTS Infusions of PGE2, PGD2, and iloprost in isolated hearts induced marked vasodilatation, as reflected by the reduction in coronary perfusion pressure of 27(SEM 7), 30(6), and 43(6)%, for 0.1 microM PGE2, PGD2, and iloprost, respectively. Infusion of glibenclamide (0.3 microM) was accompanied by a 23(3)% increase in coronary perfusion pressure. The vasodilatation induced by levcromakalim (0.1 microM) was completely inhibited in the presence of glibenclamide, whereas that of papaverine (30 microM) was unaffected. Glibenclamide significantly reduced the vasodilatation induced by iloprost (at 3 to 100 nM), PGE2 (30 and 100 nM), and PGD2 (30 and 100 nM), at all concentrations studied. In contrast, glibenclamide (1 microM) had no effect on iloprost induced relaxation of aortic rings. Arachidonic acid infusion (from 0.1 to 3 microM) in isolated hearts induced a pronounced vasodilatation and a significant release of 6-keto-PGF1 alpha into the coronary effluent in a dose dependent fashion. Both responses to arachidonic acid were significantly reduced in the presence of the cyclo-oxygenase inhibitor diclofenac (1 microM). In an additional experimental series, the vasodilatation induced by arachidonic acid infusions was found to be significantly reduced in the presence of glibenclamide. CONCLUSIONS Glibenclamide is a potent inhibitor of the coronary dilator action of prostaglandins I2, E2, and D2. This observation suggests that these prostaglandins may cause vasodilatation by opening KATP channels.
Adverse Health Effects for Individuals Who Move Between HIV Care Centers

Background:Studies on patient mobility have focused on patients who become lost-to-follow-up (LTFU). Much less is known about patients who move with a planned transfer of care from one HIV center to another. We assess disease progression in patients who moved and then returned to our care compared with patients remaining or were LTFU. Methods:We identified which patients left our HIV care program between January 01,2000, to January 01,2008, defined how they left (either moved or LTFU), and then determined the health status of returning patients. We examined the impact of the move on their health by comparing clinical measurements (eg, CD4, new AIDS) at their departure and on return. Results:Forty-four percent of all patients left care; 38% of these returned. In contrast to those remaining in local care whose CD4 counts climbed, “moved” patients exhibited deterioration in both CD4 counts and incident AIDS comparable to LFTU patients. Only 1 in 3 patients who moved had our medical records requested by a new HIV center. Conclusions:We suspect that despite forward planning, a move may result in potential serious interruptions and/or disengagements of care. The potential harmful health effects can in some be equivalent becoming LTFU. Recognizing and addressing the potential disruption in care from a planned move may be of value in improving outcomes.
Recurrence of sleep apnea without concomitant weight increase 7.5 years after weight reduction surgery.

In this study we report on a long-term follow-up of 14 morbidly obese sleep apneic patients, 11 of whom were male and 3 female. The mean age was 46 +/- 8.5 years. These patients had undergone weight reduction surgery. Before surgery, body mass index (BMI) and apnea index (AI) were 45 +/- 7.2 kg/m2 and 40 +/- 28.8 (SD) h-1, respectively. Four and a half months after surgery (range, 2 to 7 months), both BMI and AI significantly decreased to 33 +/- 7.5 kg/m2 and 11 +/- 16.4 h-1, respectively. Seven and half years after surgery (range, 5 to 10 years), BMI increased only slightly to 35 +/- 6.0 kg/m2 (p > 0.2), while AI increased significantly to 24 +/- 23 h-1 (p < 0.05). There were poor and insignificant correlations between changes in BMI and AI prior to 4.5 months after operation (r = 0.23; p > 0.4). and 4.5 months to 7.5 years after operation (r = 0.41; p > 0.1). We conclude that morbid obesity is not the only causative factor in the sleep apnea syndrome for these patients. Weight reduction surgery alone does not "cure" their sleep apnea, and they are still at risk.
Transcriptional repression by PRC 1 in the absence of H 2 A monoubiquitylation

Histone H2A monoubiquitylation (H2Aub) is considered to be a key effector in transcriptional repression by Polycomb-repressive complex 1 (PRC1). We analyzed Drosophila with a point mutation in the PRC1 subunit Sce that abolishes its H2A ubiquitylase activity or with point mutations in the H2A and H2Av residues ubiquitylated by PRC1. H2Aub is essential for viability and required for efficient histone H3 Lys27 trimethylation by PRC2 early in embryogenesis. However, H2Aub-deficient animals fully maintain repression of PRC1 target genes and do not show phenotypes characteristic of Polycomb group mutants. PRC1 thus represses canonical target genes independently of H2Aub.
Neonatal nephrocalcinosis: long term follow up

Aims: To assess the spontaneous resolution of neonatal nephrocalcinosis and its long term effects on renal function. Methods: Fourteen very low birthweight preterm babies with nephrocalcinosis were followed up at 5–7 years of age; 14 controls were matched for sex, gestation, and birth weight. Height, weight, blood pressure, and renal symptomatology were recorded, and a renal ultrasound scan was performed. Early morning urine osmolality and creatinine ratios of albumin, phosphate, calcium, oxalate and β microglobulin were determined. Urea and electrolytes in the study group were determined, and glomerular filtration rate (GFR) and TmP/GFR (tubular reabsorption of phosphate per GFR) were calculated. Statistical analysis was performed on a group basis using the Mann-Whitney confidence interval. Results: Mean age was 6.9 years (range 5.81–7.68). An early morning urine osmolality >700 mOsm/kg was achieved in all cases. In two cases and four controls, the calcium/creatinine ratio was >0.7 mmol/mmol. In all cases, the GFR was normal (median 132.6 ml/min/1.73 m2 (range 104.1–173.1)). Median TmP/GFR was 1.22 mmol/l (0.73–1.61), with two having levels below the normal range. These did not have persisting nephrocalcinosis. Nephrocalcinosis was found in three of the 12 cases scanned and one control. There were no significant differences in urine biochemistry. Conclusions: Resolution of nephrocalcinosis occurred in 75% of cases. No evidence was found to suggest that nephrocalcinosis is associated with renal dysfunction in the long term. There was evidence of hypercalciuria in the cases and controls, suggesting that prematurity may be a risk factor.
Peripheral arterial vascular function at altitude: sea-level natives versus Himalayan high-altitude natives

Objectives Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5050 m. Methods We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance. Results Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 ± 2.5 versus 3.8 ± 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high-altitude than in the sea-level natives at low frequencies (28 ± 12 versus 6.4 ± 20% at 2 Hz, P < 0.01). Conclusions Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function.
Higher productivity in importing German manufacturing firms: self-selection, learning from importing, or both?

This paper uses a newly available comprehensive panel data set for manufacturing enterprises from 2001 to 2005 to document the first empirical results on the relationship between imports and productivity for Germany, a leading actor on the world market for goods. Furthermore, for the first time the direction of causality in this relationship is investigated systematically by testing for self-selection of more productive firms into importing, and for productivity-enhancing effects of imports (‘learning-by-importing’). We find a positive link between importing and productivity. From an empirical model with fixed enterprise effects that controls for firm size, industry, and unobservable firm heterogeneity we see that the premia for trading internationally are about the same in West and East Germany. Compared to firms that do not trade at all two-way traders do have the highest premia, followed by firms that only export, while firms that only import have the smallest estimated premia. We find evidence for a positive impact of productivity on importing, pointing to self-selection of more productive enterprises into imports, but no clear evidence for the effect of importing on productivity due to learning-by-importing.
Role of SAP97 in the Regulation of 5-HT2AR Endocytosis and Signaling

Serotonin (5-HT) interacts with a wide variety of 5-HT receptors (5-HTR) of which 5-HT2AR plays an important target for antidepressant and atypical antipsychotic drugs. The carboxyl-terminal tail of 5-HT2AR encodes a motif that mediates interactions with PSD-95/disc large/zona occludens (PDZ) domain–containing proteins. In the present study, we found that 5-HT2AR interacts with synapse-associated protein 97 (SAP97; also known as DLG1) by coimmunoprecipitation in human embryonic 293 (HEK 293) cells and cortical brain lysates. We found that 5-HT2AR expression results in the recruitment of SAP97 from the cytosol to the plasma membrane and that this recruitment is dependent on an intact 5-HT2AR PDZ binding motif. We also show that 5-HT2AR interacts with SAP97 using bioluminescence energy transfer and that overexpression of SAP97 retards 5-HT2AR endocytosis, while single hairpin RNA knockdown facilitates 5-HT2AR internalization. The knockdown of SAP97 in HEK 293 cells results in a reduction in the maximum efficacy for 5-HT2AR-stimulated inositol phosphate formation and that the deletion of the 5-HT2AR PDZ motif also impairs 5-HT2AR signaling. Similarly to what has been observed for the corticotropin-releasing factor receptor 1 (CRFR1), SAP97 expression is essential for 5-HT2AR-stimulated extracellular-regulated protein kinase 1/2 (ERK1/2) phosphorylation by a PDZ interaction-independent mechanism. Moreover, we find that SAP97 is not responsible for CRFR1-mediated sensitization of 5-HT2AR signaling. Taken together, our studies show that SAP97 plays a conserved role in regulating 5-HT2AR endocytosis and ERK1/2 signaling, but plays a novel role in regulating 5-HT2AR G protein coupling.
Neuropilins

It is now well established that neuropilins (NRP1 and NRP2), first described as mediators of neuronal guidance, are also mediators of angiogenesis and tumor progression. NRPs are receptors for the class-3 semaphorin (SEMA) family of axon guidance molecules and also for the vascular endothelial growth factor (VEGF) family of angiogenic factors. VEGF-NRP interactions promote developmental angiogenesis as shown in mouse knockout and zebrafish knockdown studies. There is also evidence that NRPs mediate tumor progression. For example, overexpression of NRP1 enhances tumor growth whereas NRP1 antagonists, such as soluble NRP1 and anti-NRP1 antibodies, inhibit tumor growth. Furthermore, some class-3 SEMAs acting via NRPs inhibit tumor angiogenesis, progression and metastasis. Clinical data suggest that high NRP levels correlate with poor prognosis and survival in a variety of cancer types. Taken together, these results suggest that NRPs are potentially valuable targets for new anti-cancer therapies. We analyze here the current knowledge on NRPs and their role in angiogenesis and tumor progression and enumerate strategies for targeting these receptors.
Chronic pure thrombocytopenia in elderly patients. An aspect of the myelodysplastic syndrome

From a group of 276 elderly patients studied in the last 12 years in a department of nuclear medicine for investigating a chronic thrombocytopenia, 36 patients have an acquired disorder, with normal platelet life span, a normal megakaryocytic bone marrow count, and absence of any evident cause at the time of clinical evaluation. During the 2 to 10 subsequent years, 16 patients developed symptoms of the myelodysplastic syndrome, i.e., chronic aregenerative anemia, granulocytopenia, dysmyelopoiesis, and appearance of circulating blast cells; three of them died from acute myeloblastic leukemia. So a pure thrombocytopenia due to a platelet production defect, without any demonstrated functional platelet defect or morphologic dysmegakaryocytosis, may be a preleukemic syndrome. In the other 20 patients, with the same pure chronic thrombocytopenia, no malignant evolution has been seen with long follow‐up delays, which is often also the case in pure refractory anemias. In the absence of objective criteria of a possible premalignant disorder, the classification of these cases is difficult, which it is also the case for the so‐called refractory anemias. We suggest to individualize, in the classification of the myelodysplastic syndromes, a group of pure refractory thrombocytopenias. From a practical point of view such a diagnosis may be useful, at least to avoid inefficient and possibly harmful treatments. Cancer 64:2506–2510, 1989.
Thermogenesis in muscle.

Skeletal muscles are most often examined at the cellular level in relationship to their primary role in force generation. Throughout the animal kingdom, regardless of phylogeny, muscle generates heat. Exercise, shivering, and nonshivering thermogenesis provide excess heat in muscle that affords adaptive significance to a wide variety of organisms. Although there is reasonable concordance on the mechanisms involved in muscle as a force­ generating cell, the physiological mechanisms for thermogenesis, biological significance, and evolutionary role of muscle as a heat-producing cell are not as clearly defined. Heat liberation resulting from contractile activity is well understood, actively studied, and has been carefully measured by muscle energeticists. Heat production during periods of nonshivering thermogenesis (NST) is not as well defined, and its existence is controversial in many species, despite compelling evidence for NST from fish, birds, and mam­ mals . Investigators interested in the role of heat production in skeletal muscle primarily focus on the relationship between heat liberation during the contraction-relaxation cycle ( 1 , 77, 90, 1 10, 1 28). Discussions of heat production independent of contractile activity usually focus on mammals where extensive reviews exist (44, 46, 47 , 83, 86, 95) . Despite major efforts to understand how muscle contributes to basal metabolic rate (BMR) and to cold-induced thermogenesis in endotherms, the mechanistic basis of such activity remains poorly defined. The fundamental mechanisms for heat generation without contractile activity have not been elucidated. This review examines skeletal muscle in light of its secondary role as a furnace and
Ambulatory Blood Pressure Monitoring in Secondary Arterial Hypertension Due to Adrenal Diseases

The aim of this study was to evaluate ambulatory blood pressure monitoring in patients with essential hypertension and hypertension caused by adrenal pathology. Sixty‐six patients with primary aldosteronism, 37 with pheochromocytomas, and 45 with adrenal incidentalomas were included. These patients were compared with 152 essential hypertensive patients and 64 normotensive subjects. Ambulatory blood pressure monitoring evaluated daytime and nighttime systolic and diastolic blood pressure and heart rate. The authors found that the “nondipper” phenomenon was present in 51.5% of patients with primary aldosteronism, 43.2% with pheochromocytomas, 42.2% with incidentalomas, 34.2% with hypertension, and 15% of subjects who were normotensive. In 58% of primary aldosteronism patients with idiopathic adrenal hyperplasia, there was an absence of the physiologic blood pressure nocturnal fall (nondipper), which was statistically significant (P<.001) compared with nondipper primary aldosteronism patients with adrenocortical adenoma (38%). In conclusion, the prevalence of the nondipping pattern was higher in patients with adrenal hypertension compared with patients with essential hypertension, suggesting an independent cardiovascular risk factor.
The HU–DNA binding interaction probed with UV resonance Raman spectroscopy: Structural elements of specificity

The Escherichia coli protein HU functions as an architectural DNA‐binding protein by facilitating DNA looping or bending to form multiprotein complexes. Although HU does not recognize a specific DNA sequence, site‐specific binding to a number of discontinuous, looped, or bent DNA substrates has been observed. In this study UV resonance Raman (UVRR) spectroscopy is used to identify structural elements associated with low‐ and high‐affinity binding by examining three different HU–DNA complexes. UVRR spectra obtained with an excitation wavelength of 210 nm, which preferentially enhances protein backbone amide vibrations, indicate that HU secondary structure content increases and the protein structure becomes more rigid upon binding to DNA. The increase in α‐helical content is attributed to the C‐terminal helix, which interacts with the DNA and may play a role in binding affinity and specificity. UVRR spectra obtained with a 215 nm excitation wavelength demonstrate that Pro mode intensity at 1455 cm−1 decreases upon complex formation. This intensity decrease is attributed to the intercalation of Pro residues between DNA base pairs to induce a bend in the DNA, as has been observed previously in the IHF–DNA and HU–DNA cocrystal structures. DNA vibrational modes are also indicative of significant base unstacking and opening of the minor groove upon protein binding, consistent with bending and distortion of the DNA. In all three complexes, A‐DNA conformational features are indicated by deoxyribose‐phosphate backbone modes. These and other results suggest that protein‐induced bending plays an important role in HU site‐specific binding and supports a model of a mutually induced fit.
A survey of adult recreational drug use via the World Wide Web: the DRUGNET study.

DRUGNET was a cross-sectional survey of adult recreational drug users (i.e., not abusers) via the World Wide Web of the Internet. The purpose of this survey was to provide a unique, broad description of nondeviant adult recreational drug users. The survey instrument had four divisions: demographic and lifestyle indices, drug use history, legal history and attitudes about drug issues, and the General Well-being Schedule (GWBS). Responses were received from 1,473 self-identified drug users. Of these, 567 completed only the first section, leaving 906 respondents who completed the entire survey. The typical respondent was a White male who was well educated, employed full-time, a participant in recreational and community activities, and who described his physical health status as good. Their mental health, as measured by the GWBS, was similar to the general adult U.S. population. Their drug-taking behavior appeared to be well-controlled, at mild to moderate levels in both frequency of use and degree of intoxication. These findings have major implications for drug policy and indicate the need for further research on the majority of drug users, who may be expected to resemble this sample more than they do clinical populations of drug abusers.
Dual brain stem projection from the cortical masticatory area in guinea‐pig

THE cortical masticatory area (CMA) in the guinea pig is subdivided into the anterior and posterior parts (A-CMA and P-CMA), based on the pattern of the CMA-induced rhythmical digastric EMG burst and the cytoarchitec-ture. The anterograde tracing of horseradish peroxidase from the A-CMA and P-CMA revealed, in addition to a common projection to the region around the trigeminal motor nucleus and the parvicellular reticular formation bilaterally, a massive projection to the ipsilateral superior colliculus (SC) from the A-CMA but not from the P-CMA. The results suggest a dual brain stem projection system from the CMA: the direct pyramidal route from the P-CMA and the SC-mediated indirect route from the A-CMA.