Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo differentiation of rat liver oval cells into hepatocytes.

The Solt-Farber protocol, in the absence of an initiating agent, was used to examine the precursor-product relationship between oval cells and hepatocytes in rat liver. The animals were administered 2-acetylaminofluorene (AAF) by gavage for 2 wk combined with partial hepatectomy 1 wk after administering AAF Two dose levels of AAF were used: 9- and 21-mg total dose for animals in Groups I and II, respectively. [3H]Thymidine was administered i.p. to one-half of the animals at Day 6 post-partial hepatectomy. Animals were sacrificed 7, 9, 11, and 13 days after surgery. Only oval cells became labeled on Day 7 in both groups. On Day 9 both labeled oval cells and labeled basophilic hepatocytes were present in Group I, whereas in Group II only oval cells remained labeled. On Days 11 and 13 both oval cells and basophilic hepatocytes were labeled in both groups. The total amount of radioactivity in Group II livers remained the same on Day 9 when only labeled oval cells were present and on Days 11 and 13 when both labeled oval cells and labeled basophilic hepatocytes were present. The calculated half-life for basophilic hepatocytes was about 50 h. The differentiation of oval cells into basophilic hepatocytes was delayed in Group II as compared to Group I, and the higher dose of AAF also induced the formation of both intestinal metaplasia and bile duct formation. In situ hybridization with an alpha-fetoprotein probe showed a strong expression in groups of typical oval cells and in cells arranged in duct-like structures. In addition a transient expression of AFP was also observed in the areas of basophilic hepatocytes 9 to 11 days after partial hepatectomy. Administration of AAF decreased the level of albumin mRNA in preexisting hepatocytes and caused a significant decrease of serum albumin. In contrast, oval cells showed a strong albumin expression, and basophilic hepatocytes formed islands of albumin-expressing cells. Oval cells and the foci of early basophilic hepatocytes lacked glucose-6-phosphatase activity. At Day 13 significant numbers of basophilic hepatocytes were positive for glucose-6-phosphatase. Oval cells were strongly gamma-glutamyltranspeptidase positive, whereas the foci of basophilic hepatocytes were negative for gamma-glutamyltranspeptidase. Only occasionally were transiently gamma-glutamyltranspeptidase-positive hepatocytes observed in basophilic foci. In summary our data indicate that oval cells can differentiate to hepatocytes and may have an important physiological function as a source of major serum proteins when hepatocytes are unable to synthesize these proteins.
Differential Phospholipase D Activation by Bradykinin and Sphingosine 1-Phosphate in NIH 3T3 Fibroblasts Overexpressing Gelsolin*

Gelsolin, an actin-binding protein, shows a strong ability to bind to phosphatidylinositol 4,5-bisphosphate (PIP2). Here we showed in in vitroexperiments that gelsolin inhibited recombinant phospholipase D1 (PLD1) and PLD2 activities but not the oleate-dependent PLD and that this inhibition was not reversed by increasing PIP2concentration. To investigate the role of gelsolin in agonist-mediated PLD activation, we used NIH 3T3 fibroblasts stably transfected with the cDNA for human cytosolic gelsolin. Gelsolin overexpression suppressed bradykinin-induced activation of phospholipase C (PLC) and PLD. On the other hand, sphingosine 1-phosphate (S1P)-induced PLD activation could not be modified by gelsolin overexpression, whereas PLC activation was suppressed. PLD activation by phorbol myristate acetate or Ca2+ ionophore A23187 was not affected by gelsolin overexpression. Stimulation of control cells with either bradykinin or S1P caused translocation of protein kinase C (PKC) to the membranes. Translocation of PKC-α and PKC-β1 but not PKC-ε was reduced in gelsolin-overexpressed cells, whereas phosphorylation of mitogen-activated protein kinase was not changed. S1P-induced PLC activation and mitogen-activated protein kinase phosphorylation were sensitive to pertussis toxin, but PLD response was insensitive to such treatment, suggesting that S1P induced PLD activation via certain G protein distinct from Gi for PLC and mitogen-activated protein kinase pathway. Our results suggest that gelsolin modulates bradykinin-mediated PLD activation via suppression of PLC and PKC activities but did not affect S1P-mediated PLD activation.
Quality of Life Indicators in Long Term Care: Opinions of Elderly Residents and Their Families

Background. There are very few studies that have integrated the opinions of nursing home residents and their families into the process of developing valid outcome measures for the quality of life in long-term care facilities. Purpose. The objective of this study was to identify the interpersonal and environmental characteristics for the best substitute living environment, as perceived by recently (< 6 months) and not as recently (> 6 months of residency) admitted residents and their families. Methods. A qualitative research approach was used with 27 elderly residents and families from five nursing homes. Results. Of the 11 quality of life indicators identified by the participants, the three most important ones were being treated with respect, sympathetic involvement in relationships, and perceived competency through technical (nursing) acts and attitudes. Practice Implications. As nursing home residents age, substitute homes have to adapt if they are to continue offering opportunities for self-actualization and a continuing sense of identity. Opinions of elderly residents and their families are very helpful for occupational therapists particularly when designing programs in long-term care facilities.
TNF-alpha promoter polymorphisms and primary open-angle glaucoma.

PURPOSE Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-alpha(TNF-alpha) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-alpha-308G>A and -238G>A gene polymorphisms and the presence of POAG in a Caucasian population. METHODS The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-alpha-308G>A and -238G>A polymorphisms was performed using polymerase chain reaction. RESULTS Allelic frequencies and genotype distributions of both the TNF-alpha-308G>A and -238G>A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-alpha-308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-alpha-238A-allele. CONCLUSION Our data suggest that none of the investigated TNF-alphagene polymorphisms is a major risk factor among Caucasian patients with POAG.
The chemokine CXCL12 and the HIV‐1 envelope protein gp120 regulate spontaneous activity of Cajal–Retzius cells in opposite directions

• The CXC chemokine ligand 12 (CXCL12) modulates spontaneous firing of Cajal–Retzius cells via the CXC chemokine receptor 4 (CXCR4). However, the underlying mechanism(s) are poorly understood. CXCR4 also binds the human immunodeficiency virus type 1 (HIV‐1) envelope glycoprotein 120 (gp120), but the functional effects of this interaction on Cajal–Retzius cell excitability remain unknown. • We show that CXCL12 reduces spontaneous firing in Cajal–Retzius cells by opening a BK‐type calcium‐activated potassium conductance, whereas gp120 increases their excitability via a calcium‐ and chloride‐dependent mechanism. • Our data suggest that, depending on the use of CXCL12 or gp120 as ligands, partial agonism at the CXCR4 receptor generates calcium responses of different strengths, which lead to the recruitment of either calcium‐activated potassium or chloride channels. • We propose that HIV infection disrupts a signalling pathway important for the regulation of the excitability of Cajal–Retzius cells, and alters their functions.
Major contribution of vasospasm-induced coronary blood flow reduction to anaphylactic ventricular dysfunction assessed in isolated blood-perfused rat heart.

BACKGROUND Cardiac anaphylaxis is accompanied by coronary spasm and decreased left ventricular (LV) contractility. However, it has not been determined experimentally whether LV dysfunction during anaphylaxis is induced mainly by reduced coronary blood flow (CBF) or direct negative inotropic actions of chemical mediators. To demonstrate the major role of CBF reduction in anaphylactic LV dysfunction, we determined LV contractility during anaphylaxis and forcible CBF reduction maneuver to reproduce the anaphylaxis-induced CBF reduction in isolated blood-perfused rat hearts. METHODS Isolated hearts from Wistar rats in the ovalbumin-sensitized anaphylaxis, non-sensitized flow reduction, and non-sensitized time control group were subjected to coronary perfusion with blood at a constant pressure and measurements of CBF and LV pressure. Cardiac anaphylaxis was induced by intracoronary injections of ovalbumin antigen. RESULTS In response to antigen administrations, sensitized anaphylaxis group rat hearts showed decreases in CBF and the maximum increasing rate of systolic LV pressure (dP/dtmax) with an increased coronary vascular resistance as evidence of coronary spasm. The non-sensitized flow reduction group rat hearts whose CBF was forcibly reduced as in anaphylaxis showed the same degree of dP/dtmax reduction. CONCLUSIONS The contractile failure during cardiac anaphylaxis is caused mainly by decreased CBF due to coronary spasm.
COUNTERACTING SELECTIVE REGIMES AND HOST PREFERENCE EVOLUTION IN ECOTYPES OF TWO SPECIES OF WALKING‐STICKS

Abstract The evolution of ecological specialization has been a central topic in ecology because specialized adaptations to divergent environments can result in reproductive isolation and facilitate speciation. However, the order in which different aspects of habitat adaptation and habitat preference evolve is unclear. Timema walking‐stick insects feed and mate on the host plants on which they rest. Previous studies of T. cristinae ecotypes have documented divergent, host‐specific selection from visual predators and the evolution of divergent host and mate preferences between populations using different host‐plant species (Ceanothus or Adenostoma). Here we present new data that show that T. podura, a nonsister species of T. cristinae, has also formed ecotypes on these host genera and that in both species these ecotypes exhibit adaptive divergence in color‐pattern and host preference. Color‐pattern morphs exhibit survival trade‐offs on different hosts due to differential predation. In contrast, fecundity trade‐offs on different hosts do not occur in either species. Thus, host preference in both species has evolved before divergent physiological adaptation but in concert with morphological adaptations. Our results shed light onto which traits are involved in the initial stages of ecological specialization and ecological based reproductive isolation.
Effects of prior moderate exercise on exogenous and endogenous lipid metabolism and plasma factor VII activity.

Moderate exercise reduces postprandial triacylglycerol concentrations, which are a risk marker for coronary heart disease. The present study sought to determine the qualitative nature of exercise-induced changes in lipid metabolism and their association (if any) with changes in factor VII activation. Eleven normotriglyceridaemic men, aged 51.7+/-6.1 years (mean+/-S.D.), participated in two oral fat tolerance tests after different pre-conditions: control (no exercise), and exercise (90 min of brisk walking the day before). Venous blood samples were obtained in the fasted state and for 8 h after ingestion of a high-fat meal (1.32 g of fat, 1.36 g of carbohydrate, 0.30 g of protein and 10 mg of [1,1,1-(13)C] tripalmitin x kg(-1) body mass). Prior exercise reduced postprandial plasma triacylglycerol concentrations by 25+/-3% (mean+/-S.E.M.), with lower concentrations in the Svedberg flotation rate (Sf) 20--400 (very-low-density lipoprotein) fraction accounting for 79+/-10% of this reduction. There was no effect on plasma factor VII coagulant activity or on the concentration of the active form of factor VIIa. Prior exercise increased postprandial serum 3-hydroxybutyrate and plasma fatty acid concentrations, decreased serum postprandial insulin concentrations and increased exogenous (8 h (13)C breath excretion of 15.1+/-0.9% of ingested dose compared with 11.9+/-0.8%; P=0.00001) and endogenous postprandial fat oxidation. These data raise the possibility that reduced hepatic secretion of very-low-density lipoprotein plays a role in the attenuation of plasma triacylglycerol concentrations seen after exercise, although it is possible that increased triacylglycerol clearance also contributes to this effect.
Simvastatin Prevents Angiotensin II–Induced Cardiac Alteration and Oxidative Stress

The influence of the HMG-CoA reductase inhibitor simvastatin was assessed on the cardiovascular alterations and production of free radicals associated with chronic angiotensin II (Ang II) infusion. Simvastatin (60 mg/kg per day PO) or placebo were given concomitantly for 10 days in Sprague-Dawley rats infused with Ang II (200 ng/kg per minute SC, osmotic pump). In addition, simvastatin or placebo was also given in vehicle-infused rats. Tail-cuff pressure and albuminuria were measured before and at the end of the treatment period. Cardiac weight, carotid structure, production of reactive oxygen species (ROS, by chemiluminescence) by polymorphonuclear leukocytes and aortic wall as well as protein and lipid oxidation products were determined at the end of the study. Ang II increased tail-cuff pressure by 56±12 mm Hg and simvastatin blunted the development of hypertension by ≈70% (19±5 mm Hg). Increases in heart weight index and carotid cross-sectional area induced by Ang II were obliterated by simvastatin (3.18±0.09 versus 3.46±0.11 mg/g body wt and 0.125±0.010 versus 0.177±0.010 mm2, respectively). The Ang II–induced increases in leukocyte and aortic production of ROS as well as protein and lipid oxidation products were prevented by simvastatin. No effect of simvastatin was detected in non–Ang II–infused rats. These results indicate that simvastatin prevented the development of hypertension and cardiovascular hypertrophy together with inhibition of the induced angiotensin II production of ROS. Therefore, inhibition of HMG CoA reductase by statins may have a beneficial effect on cardiovascular alterations through its antioxidant action in experimental Ang II–dependent hypertension.
The E1B 19-kilodalton protein is not essential for transformation of rodent cells in vitro by adenovirus type 5

The newly constructed adenovirus type 5 mutant in1 carries a single AT base pair insertion immediately after nucleotide position 1715 in the E1B gene sequence which destroys the proximal AUG normally present in E1B messages and prevents production of intact E1B 19-kDa protein in infected cells. We have used in1, variants of in1 containing mutant alleles of viral genes known to enhance transformation frequency, and adenovirus type 5 mutant dl337 (S. Pilder, J. Logan, and T. Shenk, J. Virol. 52:664-671, 1984), in which the sequence between nucleotides 1770 and 1916 within the 19-kDa reading frame is deleted, to test the generally accepted hypothesis that this E1B protein is essential for the transformation of rodent cells and maintenance of the transformed phenotype. We find that these mutants transform rat embryo cells, rat kidney and mouse kidney primary cells, and cells of the 3Y1 rat line with decreased frequencies only when virus is added to these various cells at high input multiplicities of infection. In contrast, when lower doses of virus are used, the mutants transform with wild-type frequencies. Cells infected with higher doses of mutant virus show increased levels of DNA degradation and cell killing compared with those of cells infected with the same levels of wild-type virus, and these effects most likely contribute to the decreased transformation frequencies observed. On the basis of these results and the results of phenotypic analyses of numerous transformants, we propose that the E1B 19-kDa protein is not required for induction and/or maintenance of transformed-cell characteristics in rodent cells infected with adenovirus type 5.
Applying diagnostic criteria for type 1 von Willebrand disease to a pediatric population

Definitive diagnosis of type 1 von Willebrand disease (VWD) remains elusive in clinical practice. Both the International Society on Thrombosis and Haemostasis (ISTH) and the Hospital for Sick Children (HSC) have proposed diagnostic criteria for type 1 VWD, which include abnormal laboratory values, significant mucocutaneous bleeding history, and/or positive family history. The objective of this study was to apply ISTH and HSC criteria to a large pediatric population previously diagnosed with type 1 VWD. We hypothesized that a substantial number of patients would not meet these diagnostic criteria.
Defective actin dynamics in dendritic spines: cause or consequence of age-induced cognitive decline?

Abstract Ageing is a complex deteriorating process that coincides with changes in metabolism, replicative senescence, increased resistance to apoptosis, as well as progressive mitochondria dysfunction that lead to an increase production and accumulation of reactive oxygen species (ROS). Although controversy on the paradigm of the oxidative damage theory of ageing exists, persuasive studies in Caenorhabditis elegans and yeast have demonstrated that manipulation of ROS can modify the process of ageing and influences the damage of proteins, lipids and DNA. In neurons, ageing impacts on the intrinsic neuronal excitability, it decreases the size of neuronal soma and induces the loss of dendrites and dendritic spines. The actin cytoskeleton is an abundant and broadly expressed system that plays critical functions in many cellular processes ranging from cell motility to controlling cell shape and polarity. It is thus hardly surprising that the expression and the function of actin in neurons is crucial for the morphological changes that occur in the brain throughout life. We propose that alterations in actin filament dynamics in dendritic spines may be one of the key events contributing to the initial phases of ageing in the brain.
Postoperative improvement in visual function in patients with tuberculum sellae meningiomas: results of the extended transsphenoidal and transcranial approaches.

OBJECT Recently, extended transsphenoidal surgery (ETSS) has become an alternative to transcranial surgery (TCS) for suprasellar meningiomas, although the relative benefits of ETSS have yet to be established. To evaluate the effectiveness of ETSS, the authors analyzed surgical outcomes of TCS and ETSS. METHODS During a 12-year period, 28 patients with meningiomas arising from the tuberculum sellae underwent tumor removal at Kinki University Hospital. The first 12 patients underwent TCS, and the remaining 16 underwent ETSS. In the TCS group, the optic canal on the approach side was unroofed in all cases. In the ETSS group bilateral optic canals were opened, and the dural and bone defects of the skull base were repaired using abdominal fascia and hydroxyapatite cement. In half of the cases, lumbar drainage of cerebrospinal fluid (CSF) was also performed. RESULTS In a retrospective analysis of this consecutive series of patients, improvement in visual acuity and intraoperative blood loss were significantly better in the ETSS group (p = 0.010 and p = 0.011, respectively), whereas improvement in visual field defects, operative times, and the tumor removal rate were not significantly different between the two groups. Nonvisual surgical complications such as CSF leakage (one patient) and infarction of a perforating artery (three patients) were observed in the TCS group. In the ETSS group, CSF leakage (two patients), anosmia (two patients), and infarction of a perforating artery (two patients) were observed. CONCLUSIONS Given the encouraging results in improvement in visual acuity, ETSS may be acceptable for the treatment of tuberculum sellae meningiomas.
Altered levels of circulating GABAergic 5α/β-reduced pregnane and androstane steroids in schizophrenic men

Abstract The role of GABAergic pathways in the pathophysiology of schizophrenia is generally accepted. Therefore, the information concerning alterations of the steroid metabolome associated with the disease and/or its treatment is of interest with regard to the pathophysiology of the disease. Hence, we assessed 18 serum steroids and steroid polar conjugates in a group of drug-naive patients (13 adult men) and after 6-months therapy by atypical antipsychotics and age-matched controls (19 men) using gas chromatography-mass spectrometry analysis. This study, for the first time, demonstrates the altered circulating GABAergic steroids in schizophrenic men as well as the effect of the therapy with two types of atypical antipsychotics. The GABAergic androsterone (3α5α) and etiocholanolone (3α5β) are reduced in schizophrenic men but the therapy with atypical antipsychotics reinstates their levels. This reinstatement could be of importance when considering that the GABAergic substances generally improve the well-being of patients. In addition to the unconjugated androsterone, being the most abundant GABAergic steroid in men, most of the other GABAergic steroids also tended to decrease in the patients. By contrast, the conjugated 5β-pregnanolone isomers were elevated in the patients. In conclusion, although schizophrenia status in adult men is associated with unfavorable alterations in neuroactive steroids, the treatment with antipsychotics could at least partly reinstate their circulating levels.
Birth defects in Norway by levels of external and food-based exposure to radiation from Chernobyl.

In Norway, external doses of radiation resulting from fallout from the Chernobyl nuclear accident were estimated from detailed measurements, including soil deposition patterns. Internal doses were estimated from measurements of radioactive cesium in meat and milk supplies. The doses were calculated as average monthly doses for each of 454 municipalities during 36 consecutive months after the accident in spring 1986. Prospectively collected data on all newborns listed in the Medical Birth Registry of Norway who were conceived in the period May 1983-April 1989 were used to assess possible dose-response relations between estimated external and food-based exposures and congenital malformations and some other conditions. A positive association was observed between total radiation dose (external plus food-based) and hydrocephaly, while a negative association was observed for Down's syndrome. However, an important conclusion of the study was that no associations were found for conditions previously reported to be associated with radiation, i.e., small head circumference, congenital cataracts, anencephaly, spina bifida, and low birth weight. Potential sources of bias, including exposure misclassification and incomplete ascertainment of cases, are discussed.