Miracle-dz/UniFAR-FTUs huggingface dataset:
Leptin: A Potential Marker of Placental Insufficiency

To investigate placental leptin production in placental insufficiency, placental leptin production was measured in women with severe preeclampsia (group 1) and in normotensive pregnancies associated with intrauterine growth restriction (group 2), compared to controls (group 3). Placental leptin content was increased 3-fold in group 1 compared to group 2 (192.5.1 ± 39.5 vs. 67.8 ± 10.6 ng/g) and 8-fold in group 1 compared to group 3 (192.5.1 ± 39.5 vs. 25.4 ± 6.9 ng/g). Placental leptin content was positively correlated with maternal leptin/BMI ratio (r = 0.62) and the resistance index of the umbilical artery (r = 0.60). These data demonstrate that placental insufficiency is associated with a dramatic increase in placental leptin production. This results in a rise in maternal leptinemia that may be taken as an early index of placental dysfunction.
CGA gene (coding for the alpha subunit of glycoprotein hormones) overexpression in ER alpha-positive prostate tumors.

OBJECTIVE The precise role of estrogen, estrogen receptor (ER) and ER-responsive genes in prostate carcinogenesis is unclear. Paradoxically, estrogens and antiestrogens are used in the treatment of advanced metastatic prostate cancers. Recently, we identified CGA gene coding for the alpha subunit of glycoprotein hormones as a new ER alpha-responsive gene in human breast cancer cells. The aim of this study was to explore the role of CGA in the second major hormone-related cancer, i.e. prostate cancer. PATIENTS AND METHODS We quantified CGA mRNA in nine cases of benign prostatic hyperplasia (BPH) and 23 sporadic prostate tumors (TP) by using a real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. RESULTS CGA overexpression (> 10 S.D. above the mean in normal prostate tissues (NP)) was observed in 39% of the TP (ranging from 4.4 to 174.5 times the level in NP) and in none of the BPH samples. CGA overexpression was not accompanied by overexpression of the CGB, LHB, TSHB or FSHB genes to produce ectopic glycoprotein hormones. CGA gene overexpression correlated with ER alpha normal expression (P = 0.016), but not with ER beta or androgen receptor (AR) expression status. CONCLUSION These results point to CGA gene as a member of a novel dysregulated pathway in prostate cancer. CGA should therefore be considered for investigation as possible novel molecular marker in clinical applications and as possible new potential therapeutic target.
Prevalence of visual field loss following exposure to vigabatrin therapy: A systematic review

Purpose: Vigabatrin is an efficacious antiepileptic drug licensed as add‐on therapy in refractory epilepsy and used in infantile spasms. Eight years after licensing, there emerged a strong and possibly causative association with bilateral visual field loss. We report a systematic review ascertaining the magnitude of risk of vigabatrin associated visual field loss (VAVFL) and any clinical predictors of risk.
Dealing with risk: a practical approach

Most software projects take place in a volatile environment in which many dangers exist that may affect the successful outcome of the project. After completion of the project an evaluation may show that many of the problems encountered during the project could have been foreseen before they actually occurred. Risk management is an approach that is aimed at predicting the occurrence of this type of problem and at taking counter measures to either prevent them from affecting the project or to soften their impact. In this paper the basic activities related to risk management are described. Furthermore a concrete method aimed at supporting risk management is presented. This method has been used successfully in practice. Some of the results obtained by using it are presented on the basis of five cases. Some conclusions are that:(1) the use of a short and structured checklist will ease identification of and discussions about risks,(2) a risk management method in which explicit use is made of a group related approach, involving all parties, will increase reliability and acceptance of the results, and(3) involvement of a neutral process risk advisor will further both the successful use of the method and the acceptance of the results.
Advances in Brief Therapeutic Tumor Immunity Induced by Polyimmunization with Melanoma Antigens gp 100 and TRP-2

To improve the immunogenicity of melanoma self-antigens, we used a novel strategy of nonviral genetic vaccination coupled with muscle electroporation. Electroporation-enhanced immunization with plasmids encoding either human gp100 or mouse TRP-2 antigens induced only partial rejection of B16 melanoma challenge. However, immunization with a combination of these two antigens caused tumor rejection in 100% of the immunized mice. Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2. Immune cell depletion experiments identified CD8 T lymphocytes as the primary effectors of antitumor immunity. Most importantly, polyimmunization led to the generation of a therapeutic immune response that significantly improved the mean survival time of mice bearing established lung metastases. These results validated the usefulness of electroporation-enhanced, nonviral genetic immunization for the active immunotherapy of cancer and indicated that using a combination of different tumor antigens may be a decisive strategy for a successful therapeutic
An 83 kDa O-GlcNAc-glycoprotein is found in the axoplasm and nucleus of Aplysia neurons

Glycoproteins containing O-linked N-acetylglucosamine (O-GlcNAc) are present in axons of Aplysia neurons (Gabel et al., 1989) and among transcription factors and other proteins in the nucleus of eukaryotic cells (Jackson and Tjian, 1988). A recently discovered pathway in neurons transports proteins through the axon and then into the nucleus (Ambron et al., 1992). If any of the axonal O-GlcNAc glycoproteins use this pathway, then the axon and the nucleus will have these glycoproteins in common. We addressed this issue by using galactosyltransferase and UDP-3H-galactose to label and identify the glycoproteins in three regions of Aplysia neurons: axoplasm, extruded from nerves; nuclei, isolated by manual dissection of single neurons; and cytoplasm, obtained after removal of nuclei. At least 21 glycoproteins were labeled by this procedure; several, at 200, 180, 83, 76, and 66 kDa, from the nucleus and axoplasm comigrated after SDS- PAGE. Radiolabeled galactosyl-N-acetylglucosaminitol was released from the glycoproteins by base/borohydride, thereby verifying the presence of O-GlcNAc. Comparison of the 83 kDa glycoprotein from the nucleus and axoplasm revealed that both were soluble, had multiple O-GlcNAcs, and were bound to WGA. Thus, the 83 kDa constituent is a good candidate to use the axonal transport/nuclear import pathway.
Cardiopulmonary Bypass Is Associated With Hemolysis and Acute Kidney Injury in Neonates, Infants, and Children*

Objectives: This pilot study assesses the degree of hemolysis induced by cardiopulmonary bypass and determines its association with acute kidney injury in pediatric patients. Further, it evaluates the degree to which the use of urinary biomarkers neutrophil gelatinase–associated lipocalin and cystatin C correlate with the presence of acute kidney injury and hemolysis following cardiopulmonary bypass. Design: Prospective observational study. Setting: A 13-bed pediatric cardiac ICU in a university hospital. Patients: Children undergoing cardiac surgery with the use of cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Blood and urine samples were obtained at multiple time points before and after cardiopulmonary bypass. Hemolysis was assessed by measuring levels of plasma hemoglobin and haptoglobin. Acute kidney injury was defined as a doubling in serum creatinine from preoperative baseline and by using the pediatric-modified RIFLE criteria. Urinary neutrophil gelatinase–associated lipocalin and cystatin C levels were measured. A total of 40 patients (range, 3 d to 4.8 yr) were enrolled. Plasma hemoglobin levels increased markedly on separation from cardiopulmonary bypass with a concurrent decrease in haptoglobin. This was associated with an increase in protein oxidation in the plasma. Hemolysis was more evident in younger patients with a longer duration of bypass and in those requiring a blood-primed circuit. Forty percent of patients had a doubling in serum creatinine and acute kidney injury was developed in 88% of patients when defined by the pediatric-modified RIFLE criteria. Controlling for cardiopulmonary bypass time, persistently elevated levels of plasma hemoglobin were associated with a five-fold increase in acute kidney injury. Further, urinary neutrophil gelatinase–associated lipocalin measured 2 hours after separation from cardiopulmonary bypass was associated with acute kidney injury and with elevations in plasma hemoglobin. Conclusions: Cardiopulmonary bypass in pediatric patients results in significant hemolysis, which is associated with the development of acute kidney injury. The biomarker neutrophil gelatinase–associated lipocalin correlates with both acute kidney injury and hemolysis in this population.
The innovation of the potter's wheel: a comparative perspective between Mesopotamia and the southern Levant

The southern Levant and northern Mesopotamia are two areas in which the potter's wheel seems to have appeared independently. New data enable us to undertake a comparison between both regions. As a result, it appears that in both regions the context of production of the first wheel-made vessels was very similar. Wheel-coiled bowls were made by craft specialists attached to some kind of elite and responding to the demand of this same elite for fine vessels. Thus the potter's wheel was not adopted to improve productivity, but to produce to strong vessels with status value. As a consequence, this technology was not transferred to more utilitarian categories of vessels, and in both regions its development followed the same distinctive saw-tooth evolutionary trajectory.
Sugar tests detect celiac disease among first-degree relatives

OBJECTIVES:First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients.METHODS:We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy.RESULTS:Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific.CONCLUSIONS:Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.
The role of claudin-1 and claudin-7 in cervical tumorigenesis.

BACKGROUND/AIM The claudin family of proteins are key constituents of tight junctions and the aberrant expression of these proteins can contribute to de-stabilisation of tight junctions and thus to loss of cell polarity and cohesion. Increased expression of claudin-1 and claudin-7 has been observed in pre-invasive cervical lesions and cervical carcinomas. The present study attempted to assess the effect of claudin-1 and claudin-7 overexpression on the HeLa cervical carcinoma cell line, in terms of cell proliferation/viability, permeability, invasion and migration. MATERIALS AND METHODS HeLa cells were stably transfected with expression vectors containing the claudin-1 and claudin-7 genes to produce two separate stable cell lines expressing claudin-1 and claudin-7, respectively. The stable cell lines were examined with regard to their invasion and migration abilities, cell permeability and cell proliferation/viability and compared to non-claudin-1 or -7 transfected HeLa. RESULTS The present study found that claudin-1 and claudin-7 affected the migratory ability of HeLa cells, reducing their ability to migrate in a gap closure assay compared to non-claudin-transfected HeLa cells. Monolayers of claudin-1 and claudin-7 transfected cells also displayed an increased transepithelial electrical resistance indicating decreased permeability compared to non-claudin-transfected HeLa. The study found that claudin-1 or claudin-7 expression had no effect on the proliferation or viability of HeLa cells. Claudin-1 or -7 expression also did not affect the invasive ability of HeLa cells with both stable cells lines and non-claudin-transfected HeLa cells all showing low invasive ability. CONCLUSION The results of the present study indicate that claudin-1 and claudin-7 overexpression alone does not contribute to increased tumorigenesis in cervical carcinoma, instead claudin-1 and - 7 expression in HeLa cells contribute to reducing the migratory ability of cells and decrease their permeability.
Deletion of TnAbaR23 Results in both Expected and Unexpected Antibiogram Changes in a Multidrug-Resistant Acinetobacter baumannii Strain

ABSTRACT Since the 2006 discovery of the Acinetobacter baumannii strain AYE AbaR1 resistance island, similar elements have been reported in numerous members of this species. As AbaR1 is distantly related to Tn7, we have renamed it TnAbaR1. TnAbaR transposons are known to carry multiple antibiotic resistance- and efflux-associated genes, although none have been experimentally studied en bloc. We deleted the TnAbaR transposon in A. baumannii A424, which we have designated TnAbaR23, and characterized independent deletion mutants DCO163 and DCO174. The NotI pulsed-field gel electrophoresis (PFGE) profile of strain DCO174 was consistent with targeted deletion of TnAbaR23 alone, but strain DCO163 apparently harbored a second large genomic deletion. Nevertheless, “subtractive amplification” targeting 52 TnAbaR and/or resistance-associated loci yielded identical results for both mutants and highlighted genes lost relative to strain A424. PCR mapping and genome sequencing revealed the entire 48.3-kb sequence of TnAbaR23. Consistent with TnAbaR23 carrying two copies of sul1, both mutants exhibited markedly increased susceptibility to sulfamethoxazole. In contrast, loss of tetAR(A) resulted in only a minor and variable increase in tetracycline susceptibility. Despite not exhibiting a growth handicap, strain DCO163 was more susceptible than strain DCO174 to 9 of 10 antibiotics associated with mutant-to-mutant variation in susceptibility, suggesting impairment of an undefined resistance-associated function. Remarkably, despite all three strains sharing identical gyrA and parC sequences, the ciprofloxacin MIC of DCO174 was >8-fold that of DCO163 and A424, suggesting a possible paradoxical role for TnAbaR23 in promoting sensitivity to ciprofloxacin. This study highlights the importance of experimental scrutiny and challenges the assumption that resistance phenotypes can reliably be predicted from genotypes alone.
Specific Effect of 5-Fluorouracil on α-Fetoprotein Gene Expression During the In Vitro Mouse Embryonic Stem Cell Differentiation

Embryonic stem (ES) cells are considered an important alternative to develop in vitro screening methods for embryotoxicity. Mouse ES cells can be cultured as cell suspension aggregates termed “embryoid bodies” (EBs) in which cells start to differentiate. We have studied the expression of several genes in the presence of a wide range of concentrations of 5-fluorouracil (5-FU). This well-established embryotoxic compound completely inhibited cell viability at 200 nmol/L in monolayer cultures. At lower concentrations, 5-FU led to decrease in the expression of the α-fetoprotein gene, a marker of the visceral endoderm, in the EBs. However, the expression of several mesodermal gene markers was not significantly affected at these concentrations. These results suggest a high sensitivity of the visceral endoderm differentiation to 5-FU. Therefore, the quantification of the α-fetoprotein gene after exposure to potential embryotoxicants should be considered an additional end point in future embryotoxicity assays in vitro with ES cells.
Audit of patients with mesothelioma treated with pemetrexed in a single institution in Western Australia

Malignant pleural mesothelioma (MPM) is a devastating malignancy that until recently has had no effective treatment. Pemetrexed in combination with cisplatin entered routine clinical practice following reports of efficacy in 2003. We performed a retrospective analysis of all patients with malignant mesothelioma at a single institution treated with pemetrexed in any combination or as monotherapy between 2004 and 2007. During this period, 62 patients received pemetrexed‐based chemotherapy for MPM, most of whom were male (87%), treated in the palliative setting (84%) and received pemetrexed in combination with a platinum agent (95%). Pemetrexed was found to be well tolerated and produced clinical benefit and response rates similar to other published studies for its use in MPM in the phase IV or community practice settings. Patients with progressive disease as their best radiological response had very poor outcomes, while patients with stable disease had similar outcomes to those with responses. We confirmed that survival after commencement of pemetrexed‐based chemotherapy remains under one year in this group of patients, somewhat less than the survival reported in phase III trials that currently inform clinical decision making. Further research is required to identify those patients who might benefit from pemetrexed based on molecular predictive markers.
SESAME OIL ATTENUATES CISPLATIN-INDUCED HEPATIC AND RENAL INJURIES BY INHIBITING NITRIC OXIDE-ASSOCIATED LIPID PEROXIDATION IN MICE

Although cisplatin (cis-diamminedichloroplatinum) is an effective drug for the treatment of several solid tumors and has been used therapeutically for decades, several cisplatin-induced side effects have limited its therapeutic dosage in clinical studies. Our aim was to examine the effect of sesame oil on cisplatin-induced hepatic and renal injuries in mice (8-week-old female SPF C57BL/6) given subcutaneous cisplatin (0, 5, 10, or 20 mg/kg). Hepatic and renal functions, lipid peroxidation (LPO) levels, and reactive oxygen free radicals were evaluated 3 days after cisplatin administration, and tumor volumes were recorded 0, 3, 6, and 9 days after cisplatin administration. Sesame oil (i) potently attenuated cisplatin-associated hepatic and renal injuries; (ii) decreased cisplatin-initiated LPO as well as the production of hydroxyl radical, peroxynitrite, and nitrite in blood and tissue; and (iii) did not affect the antitumor capacity exerted by cisplatin in mice with melanoma. We suggest that sesame oil attenuates cisplatin-induced hepatic and renal damage by at least partially inhibiting nitric oxide-associated LPO in mice. Sesame oil might be a new approach for preventing cisplatin-induced multiple organ injury during the treatment of tumors.
Hidrozoos de Galicia

Se han estudiado los hidrozoos del litoral gallego, efectuandose para ello un total de 180 muestreos, repartidos en 144 localidades distribuidas a lo largo de toda la costa gallega. Los hidrozoos recolectados y determinados en este estudio comprenden un total de 71 especies, una variedad, y dos formas identificadas a nivel generico, de las cuales cinco constituyen primeras citas para las costas de la peninsula iberica, una para el litoral espanol, y dos para la vertiente atlantica de la peninsula iberica. 20 especies y una variedad se citan por primera vez para el litoral gallego, y se confirma ademas la presencia de otras dos especies en aguas de la peninsula iberica. Asimismo, se realizan precisiones morfologico-sistematicas en varias especies, y en aquellos casos en los que se considera necesario se discute la posicion sistematica de algunas de ellas, y la validez o la prioridad de los nombres genericos o especificos empleados por los distintos autores. Finalmente se aportan datos concernientes a la auto ecologia (habitat) de la practica totalidad de las especies recolectadas, observaciones relativas a la biologia (periodos de reproduccion) de 44 de ellas, y se revisa, para cada especie, su distribucion geografica establecida actualmente.
Combined Carotid and Transcranial Ultrasound Findings Compared with Clinical Classification and Stroke Severity in Acute Ischemic Stroke

Background: The aim of this study was to assess the association between cerebral hemodynamics and the clinical picture as defined by the Oxfordshire Community Stroke Project (OCSP) classification, as well as the clinical severity as defined by the National Institute of Health Stroke Scale (NIHSS) within the first 6 h of an acute middle cerebral artery (MCA) stroke onset. Methods: 70 unselected patients were grouped according to the OCSP classification and NIHSS. All patients immediately had extracranial and transcranial Doppler (TCD) ultrasound examinations. Results: In the study population as a whole, there was a significant association between intracranial vascular pathology and the OCSP classification (p < 0.001) as well as the NIHSS score (p < 0.001). In patients with severe stroke, however, TCD demonstrated the hypothesized proximal MCA1 occlusion in only 34% of patients with an OCSP-defined total anterior circulation syndrome and in 42% of patients with an NIHSS score of ≧15. In moderate stroke, the OCSP classification was misleading in almost half of the patients with a partial anterior circulation syndrome, i.e. a hypothesized distal MCA2 occlusion suitable for thrombolysis. Conclusions: Neither the OCSP classification nor the NIHSS grading provided reliable information about the site or presence of intracranial arterial occlusion in acute stroke within the first 6 h after stroke onset in the individual patient. The results of this study strongly suggest that selection of acute ischemic stroke patients for thrombolysis should also include an assessment of cerebral hemodynamics.