Miracle-dz/UniFAR-FTUs huggingface dataset:
The Anti-Apoptotic Activity of Albumin for Endothelium Is Mediated by a Partially Cryptic Protein Domain and Reduced by Inhibitors of G-Coupled Protein and PI-3 Kinase, but Is Independent of Radical Scavenging or Bound Lipid

Increased vascular disease occurs with low albumin (human serum albumin, HSA), possibly reflecting specific inhibition of endothelial apoptosis reported for tissue culture. Despite the reported specificity for endothelial protection by HSA, the high but physiological concentrations needed appear more consistent with non-specific low-affinity interactions. We reconcile this contradiction by demonstrating protection is mediated by a partially cryptic HSA protein domain, which becomes more exposed and active following cyanogen bromide fragmentation (p < 0.001). Also, although others reported HSA radical scavenging and bound lipids as important for inhibiting apoptosis in non-endothelial cell types, we demonstrate the protective effect for endothelium is unaffected when HSA radical scavenging is blocked by alkylation, or following delipidation. Further probing the mechanism responsible, we found that the G-coupled protein inhibitors pertussis toxin and suramin reduced protection of endothelium by HSA (p < 0.005), while the tyrosine kinase inhibitor genistein had no effect. Consistent with a role for phosphoinositide 3 kinase (PI3K) was inhibition by both wortmannin and LY294002 (p < 0.05), as well as phosphorylation of Akt, while MAP kinase inhibitors had no effect. We conclude the active site in HSA inhibiting endothelial apoptosis is partially cryptic, and acts via a G-coupled protein PI3K-dependent mechanism.
Androgenetic Embryonic Stem Cells Form Neural Progenitor Cells In Vivo and In Vitro

Uniparental zygotes with two paternal (androgenetic [AG]) or two maternal (gynogenetic [GG]; parthenogenetic [PG]) genomes are not able to develop into viable offspring but can form blastocysts from which embryonic stem cells (ESCs) can be derived. Although some aspects of the in vitro and in vivo differentiation potential of PG and GG ESCs of several species have been studied, the developmental capacity of AG ESCs is much less clear. Here, we investigate the potential of murine AG ESCs to undergo neural differentiation. We observed that AG ESCs differentiate in vitro into pan‐neural progenitor cells (pnPCs) that further give rise to cells that express neuronal‐ and astroglial‐specific markers. Neural progeny of in vitro‐differentiated AG ESCs exhibited fidelity of expression of six imprinted genes analyzed, with the exception of Ube3a. Bisulfite sequencing for two imprinting control regions suggested that pnPCs predominantly maintained their methylation pattern. Following blastocyst injection of AG and biparental (normal fertilized [N]) ESCs, we found widespread and evenly distributed contribution of ESC‐derived cells in both AG and N chimeric early fetal brains. AG and N ESC‐derived cells isolated from chimeric fetal brains by fluorescence‐activated cell sorting exhibited similar neurosphere‐initiating cell frequencies and neural multilineage differentiation potential. Our results indicate that AG ESC‐derived neural progenitor/stem cells do not differ from N neural progenitor/stem cells in their self‐renewal and neural multilineage differentiation potential.
[Analysis of a series of 55 patients with biopsy proven giant cell temporal arteritis].

INTRODUCTION Our main aim with this study is to establish the epidemiologic and clinical features, treatment response and complications of a group composed of 55 patients with biopsy proven temporal arteritis in a local hospital. MATERIAL AND METHODS Retrospective study based on clinical records revision of patients diagnosed of giant cell arteritis (GCA) made by temporal artery biopsy between 1989 and 2001. RESULTS The approximated annual incidence of GCA in our area is 4.1 cases per 100,000 persons over the age of 50. The mean age at diagnostic was 74 years and the 78,2% were women. The most common symptom at diagnostic was headache (81.5%) followed by systemic manifestations (74.1%) and later we found jaw claudication (32,7%), visual impairment (30.2%), isquemic manifestations (17%). Polymyalgia rheumatica was associated to GCA in 49.1% of cases. The temporal artery explorations was abnormal in the 76.9% of patients. The mean initial dose of corticoids was 69 mg prednisone per day, with a half dose reduction time of . 5 months. In spite of that, 24,1% of patients relapsed during the first year. The 38% of patients did some complications during the corticosteroid treatment. The ESR was lower 50 mm in 12.7% of patients; it was anaemia in the 37.7% and thrombocytosis in 32,1%. In these last patients we detected a relation between thrombocytosis and specific visual impairment. CONCLUSIONS The incidence of GCA in our area is low. The results of our series aren't different from others publicated before in clinical manifestations, there is a prevalence of female sex and there is a relation between specific visual impairment and the presence of thrombocytosis.
Megamitochondria formation in hepatocytes of patient with chronic hepatitis C – a case report

Although chronic hepatitis C virus (HCV) infection affect 185 million people world-wide, pathomechanism of liver damage is still unclear. Electron microscopy can reveal liver injury in very early stage and help understanding the mechanisms that is crucial in the pathogenesis of chronic hepatitis C. We present the morphological changes in the liver of HCV infected 24-year-old female patient, using light and transmission electron microscopy. Examination by TEM revealed wide range of specific subcellular abnormalities in hepatocellular ultrastructure. The most common observed changes were ring-shaped nuclei with intranuclear inclusion, megamitochondria, and “membranous web” structures – the hallmark of RNA-viruses infection.
The Toxicology of Interleukin-12: A Review

Recombinant murine interleukin (IL)-12 (rmIL-12) exhibits antitumor, antiviral, and antimicrobial activities and can modify allergic inflammatory reactions in animal models. Recombinant human IL-12 (rhIL-12) is currently in clinical trials for treatment of cancer, asthma, and viral hepatitis. Principally a phagocyte-derived cytokine, IL-12 targets natural killer cells and T lymphocytes, stimulating their activity and the secretion of interferon (IFN)-γ. An understanding of the toxicology of IL-12, due in part to effects mediated by IFN-γ, has emerged from preclinical safety and mechanistic studies and initial clinical trials. Target organs common to several animal species and humans include the lymphohematopoietic system, intestines, liver, and lung.
In vivo detection of acinar microstructural changes in early emphysema with (3)He lung morphometry.

PURPOSE To quantitatively characterize early emphysematous changes in the lung microstructure of current and former smokers with noninvasive helium 3 ((3)He) lung morphometry and to compare these results with the clinical standards, pulmonary function testing (PFT) and low-dose computed tomography (CT). MATERIALS AND METHODS This study was approved by the local institutional review board, and all subjects provided informed consent. Thirty current and former smokers, each with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT, underwent (3)He lung morphometry. This technique is based on diffusion MR imaging with hyperpolarized (3)He gas and yields quantitative localized in vivo measurements of acinar airway geometric parameters, such as airway radii, alveolar depth, and number of alveoli per unit lung volume. These measurements enable calculation of standard morphometric characteristics, such as mean linear intercept and surface-to-volume ratio. RESULTS Noninvasive (3)He lung morphometry was used to detect alterations in acinar structure in smokers with normal PFT findings. When compared with smokers with the largest forced expiratory volume in 1 second (FEV(1)) to forced vital capacity (FVC) ratio, those with chronic obstructive pulmonary disease had significantly reduced alveolar depth (0.07 mm vs 0.13 mm) and enlarged acinar ducts (0.36 mm vs 0.3 mm). The mean alveolar geometry measurements in the healthiest subjects were in excellent quantitative agreement with literature values obtained by using invasive techniques (acinar duct radius, 0.3 mm; alveolar depth, 0.14 mm at 1 L above functional residual capacity). (3)He lung morphometry depicted greater abnormalities than did PFT and CT. No adverse events were associated with inhalation of (3)He gas. CONCLUSION (3)He lung morphometry yields valuable noninvasive insight into early emphysematous changes in alveolar geometry with increased sensitivity compared with conventional techniques.
Evaluating the Effectiveness of the Massachusetts Workforce Development System Using No-Shows as a Nonexperimental Comparison Group

This article examines the effect of the Massachusetts workforce development system on the earnings of disadvantaged adults using nonexperimental data from the late 1990s. The authors construct a comparison sample for program participants using individuals who apply for and are offered services yet do not participate in a training program. They present a series of difference-in-difference estimates that make several alternative efforts to correct for selectivity bias, including econometric models that regression adjust for observable characteristics and fixed-effect models that adjust for time-invariant person effects. They also employ probabilistic matching techniques to more finely align the treatment and comparison samples. On average, program participants experienced 20% increases in annual earnings 1 year postintervention and 25% increases after 2 years. The authors uncover considerable heterogeneity in these effects, suggesting that the most difficult to serve and the most job ready benefit the least.
Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome.

BACKGROUND Treatment of adults with steroid-dependent minimal change nephrotic syndrome (SD-MCNS) can be a significant challenge. Cyclophosphamide (CYC) and cyclosporin (CYA) are often effective steroid-sparing agents. Tacrolimus (TAC) may be another treatment option. METHODS This open, prospective cohort study enrolled Chinese adults with SD-MCNS. At the start of the study, we administered TAC or intravenous CYC together with prednisone (0.5 mg/kg/day), the dose of which was tapered off throughout the study. The TAC cohort received oral TAC (target trough blood level of 4-8 ng/ml) for 24 weeks and the CYC cohort received intravenous CYC (750 mg/m(2) body surface) once every 4 weeks for 24 weeks. RESULTS Twenty-six patients met the criteria for enrollment (14 patients in the CYC group and 12 patients in the TAC group). One patient from each group discontinued treatment because of a drug-related side effect. Complete remission (CR) after the 24-week therapeutic period was 76.9% (10/13) in the CYC group and 90.9% (10/11) in the TAC group. The mean time required for CR in the TAC group was significantly less than in the CYC group (P = 0.031). Eight of 13 (61.5%) patients in the CYC group and 8 of 11 (72.7%) patients in the TAC group successfully stopped steroids and changed their status from steroid dependence. Sixty percent (6/10) of the CYC patients and 50% (5/10) of the TAC patients who achieved CR maintained remission during the follow-up period of 23.0 +/- 10.1 months. Four (40%) CYC patients and five (50%) TAC patients experienced relapses, and two CYC patients experienced frequent relapses. CONCLUSION A 24-week course of TAC is a favorable steroid-sparing agent for treatment of Chinese adults with SD-MCNS. Therapy with TAC accompanied by a tapering dose of prednisolone appears to yield quicker remission than treatment with CYC together with prednisone.
WWOX hypomorphic mice display a higher incidence of B‐cell lymphomas and develop testicular atrophy

WWOX is a putative tumor suppressor gene encoded within common chromosomal fragile site region FRA16D, in chromosome band 16q23. Multiple studies have demonstrated that WWOX expression is often reduced or lost in various tumor types. WWOX tumor suppressor activity was suggested by re‐expressing WWOX in breast, ovarian, and lung tumor cell lines leading to tumor growth inhibition in vivo. To determine whether loss of Wwox gene expression has a role in tumorigenesis, we generated a mouse strain containing a Wwox gene mutated by a gene‐trap vector. Homozygous Wwox gene‐trap mice (Wwoxgt/gt) had no detectable Wwox protein in most tissues examined, although, a low level could be detected in a minority of tissues. Because of these observations, we concluded that these mice are Wwox hypomorphs. Remarkably, Wwox hypomorphic mice are viable in contrast to the recently reported postnatal lethality of Wwox knockout mice. Testes from Wwoxgt/gt males had high numbers of atrophic seminiferous tubules and reduced fertility when compared with wild‐type counterparts. We observed that the Wwoxgt/gt mice had a significantly shorter lifespan, and female hypomorphs had a higher incidence of spontaneous B‐cell lymphomas. In conclusion, we describe a novel Wwox hypomorphic mouse model that overcomes postnatal lethality that was recently observed in Wwox knockout mice. Therefore, tumorigenesis studies using this model more closely recapitulates the loss of WWOX expression observed in human cancers. Importantly, our observation that Wwox hypomorphs had an increased incidence of B‐cell lymphomas supports a role of Wwox as a tumor suppressor. © 2007 Wiley‐Liss, Inc.
Small changes in lymphocyte development and activation in mice through tissue‐specific alteration of heparan sulphate

We have examined the role of heparan sulphate in lymphocyte development and activation in mice by conditionally deleting the genes encoding the heparan sulphate biosynthetic enzymes N‐deacetylase/N‐sulphotransferase‐1 and ‐2 (Ndst1 and Ndst2) and glucuronic acid/N‐acetylglucosamine co‐polymerase‐1 (Ext1) in T cells and B cells, respectively. Ndst1 and Ndst2 are the only Ndst isoforms in T cells. In T‐cell Ndst‐deficient mice there were normal ratios of CD4+/CD8+ cells in the blood, spleen and thymus, indicating no dramatic effect on development. However, Ndst‐deficient T cells were hyperresponsive to low‐level activation, suggesting that cell surface heparan sulphate plays a role in T‐cell proliferation. The hyperresponsive state correlated with a decrease in cell surface heparan sulphate that occurs in response to activation in wild‐type cells. There was a slight change in the number of developing B cells in B‐cell Ext1‐deficient mice, but the alteration did not cause a change in antibody production. These findings demonstrate that cell surface heparan sulphate may not play a crucial role in lymphocyte development, but can modulate the sensitivity of T cells to activation.
Structural and dynamic changes in the elastic arteries due to arterial hypertension and hypercholesterolemia

Five groups of 20 patients each were studied to analyze the vascular dynamics and structure of the elastic arteries. Group I consisted of healthy young individuals (27±4 years); Group II of healthy adults (46±9 years); Group III of normotensive hypercholesterolemic adults (45±12 years and serum cholesterol >239 mg/dl); Group IV of hypertensive normocholesterolemic adults (56±13 years); and Group V of hypertensive hypercholesterolemic adults (56±9 years). The differential arterial pressure was estimated and divided by the volume change (delta P/delta V) of the aorta and the carotid and brachial arteries. The volume change was calculated using the “cylinder formula,” measuring the radius from the ultrasonographic vessel image and assigning the cylinder a height of 1 cm. The A/E index of the Doppler transmitral spectrum and the maximum velocity flow using Doppler in the above arteries were calculated. The presence of carotid atherosclerosis was observed and given an arbitrary scoring grade of 0, 1, or 2. A higher arterial and ventricular stiffness was found in the hypertensive patients regardless of the presence of hypercholesterolemia. A higher fall in Doppler velocity and an increase in atherosclerosis lesions were found in Group V. Based on the results of this study, it was concluded that vascular and left ventricular stiffness have a close relationship with arterial hypertension but not with hypercholesterolemia. The hypercholesterolemic patients had a higher prevalence of carotid atherosclerosis and a higher scoring grade of severity.
Increased incidence of bronchopulmonary dysplasia in preterm infants exposed to preeclampsia

Objective: The aims of the study were to determine the effect of preeclampsia on bronchopulmonary dysplasia (BPD) development in preterm infants and to investigate the possible association between BPD severity and preeclampsia. Methods: The study group involved preterm infants (≤32 gestational week) born to a preeclamptic mother with no co-existing medical condition, whereas the comparison group involved preterm infants born to a normotensive mother. BPD was defined as requirement for supplemental oxygen for the first 28 days of life and classified as mild, moderate and severe. Results: There were a total of 117 and 215 premature infants that were born to a preeclamptic mother and a normotensive mother, respectively. The incidence of BPD in preterm infants born to preeclamptic mothers (38.5%) was significantly higher than those born to normotensive mothers (19.5%). Frequencies of moderate and severe BPD were significantly higher in the infants born to preeclamptic mothers. Moderate and severe BPD was also significantly higher in infants born to a mother with severe preeclampsia compared with a mother with mild preeclampsia. In logistic regression model, preeclampsia was found to be predictive of BPD. Conclusions: Preeclampsia was found to be an important risk factor for BPD development in preterm infants. The incidence of both moderate and severe BPD was significantly higher in infants born to preeclamptic mothers. These findings might be associated with altered angiogenesis in the preeclamptic mother which might be shared by the fetus.
Stromelysin‐1: Three‐dimensional structure of the inhibited catalytic domain and of the C‐truncated proenzyme

The proteolytic enzyme stromelysin‐1 is a member of the family of matrix metalloproteinases and is believed to play a role in pathological conditions such as arthritis and tumor invasion. Stromelysin‐1 is synthesized as a proenzyme that is activated by removal of an N‐terminal prodomain. The active enzyme contains a catalytic domain and a C‐terminal hemopexin domain believed to participate in macromolecular substrate recognition. We have determined the three‐dimensional structures of both a C‐truncated form of the proenzyme and an inhibited complex of the catalytic domain by X‐ray diffraction analysis. The catalytic core is very similar in the two forms and is similar to the homologous domain in fibroblast and neutrophil collagenases, as well as to the stromelysin structure determined by NMR. The prodomain is a separate folding unit containing three α‐helices and an extended peptide that lies in the active site of the enzyme. Surprisingly, the amino‐to‐carboxyl direction of this peptide chain is opposite to that adopted by the inhibitor and by previously reported inhibitors of collagenase. Comparison of the active site of stromelysin with that of thermolysin reveals that most of the residues proposed to play significant roles in the enzymatic mechanism of thermolysin have equivalents in stromelysin, but that three residues implicated in the catalytic mechanism of thermolysin are not represented in stromelysin.
Involvement of the external anal sphincter in amyotrophick lateral sclerosis

In amyotrophic lateral sclerosis the striated pelvic floor sphincter muscles are functionally uninvolved, and pathological studies have confirmed the relative resistance of the Onuf nucleus motor neurons. We have evaluated the external anal sphincter (EAS) muscle in 16 patients with ALS using single fiber EMG, and compared the results with the findings in the semimembranosus‐semitendinosus (SM‐ST) muscles that have innervation from the L‐5, S‐1, and S‐2 segments. The results were compared with a group of controls matched for age and sex. None of the patients or controls had symptomatic sphincter involvement and none of the 4 women studied were parous. Eight patients with ALS showed an increased fiber density in the EAS; 6 had an abnormal neuromuscular jitter. In 1 there was fibrillation in the EAS. In the SM‐ST muscle 11 patients showed an increased fiber denstiy, and 7 had an abnormal neuromuscular jitter. In 3 patients with ALS in whom there were abnormal findings in the EAS the bulbocavernosus reflex and pudendal nerve evoked potentials were normal. Neurogenic change was more marked in the SM‐ST than in the EAS muscle. These findings show that the EAS is not normal in ALS. However, the relative resistance of the EAS to ALS is sufficient to prevent incontinence, even in the longer‐surviving older patients. © 1995 John Wiley & Sons, Inc.
State and phase transition behaviors of quercus rubra seed axes and cotyledonary tissues: relevance to the desiccation sensitivity and cryopreservation of recalcitrant seeds

Freezing and melting transitions of cellular water in embryonic axes and cotyledonary tissues of recalcitrant Quercus rubra (red oak) seeds were compared under slow and rapid cooling conditions. The relevance of desiccation sensitivity (critical water content) and state/phase transition behaviors to cryopreservation was examined. Under a slow to intermediate cooling condition (</=10 degrees C min(-1)), unfrozen water content in the tissues decreased to less than the critical water content, resulting in a dehydration damage. Under a rapid cooling condition (>100 degrees C min(-1)) using liquid nitrogen (LN(2)), freeze-induced dehydration damage could be avoided if the initial water content was >0.50 g g(-1) dry wt. However, at water content >0.50 g g(-1) dry wt, the vitrified cellular matrix was highly unstable upon warming at 10 degrees C min(-1). These results offered a theoretical explanation on the difficulty for successful cryopreservation of recalcitrant red oak embryonic axes. A complete state/phase transition diagram for red oak axes was constructed, and a vitrification-based cryopreservation protocol that employed predehydration and rapid cooling was examined. State/phase transition behaviors of cellular water are important parameters for cryopreservation; however, vitrification alone was not sufficient for seed tissues to survive the cryopreservation condition. Copyright 1999 Academic Press.
Poor results after augmenting autograft with xenograft (Surgibone) in hip revision surgery

Background Surgibone Unilab is prepared from bovine bone and contains hydroxyapatite and protein. It is supposed to be immunogenically inert but the protein could be antigenic in man. Patients and methods We followed 27 patients for an average of 2.5 (1–5) years, all of whom had received Surgibone mixed with autograft to fill in defects in the acetabulum and the proximal femur in revision hip surgery. Results In 17 patients, there was apparently complete incorporation of the bone graft within 6 months. In 3 of these patients, the graft was incorporated after 3 months. In 3 patients, however, there was no incorporation of the graft as late as 3 years after the operation. 3 other patients appeared to have a type of graft rejection (pseudoinfection). 1 other patient suffered MRSA deep infection of the prosthesis which resulted in removal of the implants 1 month postoperatively. Interpretation Use of Surgibone xenograft in revision hip surgery, even in combination with autograft, resulted in failure and the need for rerevision in at least one quarter of the cases studied.