Miracle-dz/UniFAR-FTUs huggingface dataset:
HSP27 and cell survival in neurones

Although the majority of studies on the protective effect of individual hsps have concentrated on the major inducible heat shock protein Hsp70, a variety of evidence suggests that the small heat shock protein Hsp27 may have a more potent protective effect in the nervous system. Thus, for example, in cultured neurones over-expression of Hsp70 can protect against subsequent exposure to thermal or ischaemic stress but not against exposure to some other stressful stimuli, whereas over-expression of Hsp27 protects against a variety of stresses. Similarly, although transgenic animals over-expressing Hsp70 are protected against cardiac ischaemia, more equivocal results have been obtained in terms of their protection against cerebral ischaemia and other stresses to the nervous system. In contrast, transgenic animals over-expressing Hsp27 have recently been shown to show neuroprotection as well as being protected against cardiac ischaemia. Recent findings have also implicated Hsp27 and related proteins in human disease. Thus, it has been demonstrated that mutation of either Hsp27 or the related protein hsp22 can be observed in specific families with hereditary motor neuropathy caused by premature axonal loss, possibly due to neuronal death and subsequent degeneration. Moreover, the mutations are associated with a reduced ability to promote neuronal survival compared to the wild type protein. Hence, Hsp27 appears to be a potent protective factor for neuronal cells whose mutation results in neuronal cell death and disease, whilst enhanced expression of the wild type protein may be a therapeutic option for human diseases involving excessive neuronal cell death.
The fractional excretion of soluble interleukin-2 receptor-&agr; is an excellent predictor of the interleukin-2 receptor-&agr; status after treatment with daclizumab

Background. Daclizumab is a humanized monoclonal antibody against the &agr;-chain of the interleukin (IL)-2 receptor (R). The authors previously have shown that the urinary excretion of soluble (s) IL-2R&agr; is dependent on the presence of daclizumab in serum. The authors investigated whether the IL-2R&agr; status, as assessed by flow cytometric analysis, is reflected by the concentration of sIL-2R&agr; in the urine and serum. Methods. Two hundred seventy-two measurements were performed in 46 renal transplant recipients who were treated with daclizumab in combination with tacrolimus and mycophenolate mofetil. Soluble IL-2R&agr; was measured in urine and serum with Immulite IL-2R, a solid-phase enzyme-linked immunosorbent assay. Complete blockade of the IL-2R&agr; was defined as the presence of less than 5% IL-2R&agr;+ lymphocytes in the CD3+ population. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of serum and urine sIL-2R&agr; in predicting IL-2R&agr; blockade. Results. The calculated fractional excretion of sIL-2R&agr; proved to be an excellent predictor of the blockade of IL-2R&agr; (ROC analysis area under the curve, 0.95±0.01). A calculated fractional excretion of sIL-2R&agr; lower than 0.5% had a specificity of 100% and a sensitivity of 75% for the assessment of blockade of IL-2R&agr;. Conclusions. Blockade of IL-2R&agr; after treatment with daclizumab can reliably be assessed by calculation of the fractional excretion of sIL-2R&agr;. This method is easier to use compared with flow cytometric analysis of IL-2R&agr;+ lymphocytes.
TP53 family members and human cancers

Based on gene sequence homologies, a p53 (TP53) gene family become apparent with the addition of the most recently identified p63 (TP73L; formerly TP63) and p73 (TP73) genes to the already known p53. The p53 gene encodes for a unique protein eliciting well‐known tumor suppressor gene (TSG) properties that mediate cellular response to DNA damage, e.g., cell cycle arrest or apoptosis. In contrast, both homologues specify an array of isoforms different in their N‐ and C‐terminal domains. Transactivating isoforms, such as TAp63/p73, show TSG properties similar to p53, while isoforms lacking N‐terminal transactivating domain such as ΔNp63/p73, induce a functional block against p53 as well as TAp63/p73 activities. Both p63/p73 types of isoforms are involved in development: p63 is critical for epithelial stem cell renewal and epithelial homeostasis, and p73 is involved in neurogenesis and natural immune response. These facts support interdependent functions for the p53 family members, which appear linked together in a complex and tight regulation network to fulfill cellular functions related to DNA damage and tissue homeostasis maintenance. The lack of p63/p73 mutations in human cancers rule out a typical TSG role for either of the p53 homologues. Nonetheless, p63 and p73 genes seem strongly involved in malignancy acquisition and maintenance process because of: 1) their tissue identities, and 2) their close interplay activities within the p53 family members, and primarily through the negative regulatory role played by ΔNp63/p73 isoforms for cell death control and differentiation. Hum Mutat 21:182–191, 2003. © 2003 Wiley‐Liss, Inc.
Audiological evaluation in Chinese patients with mitochondrial encephalomyopathies

Background Hearing impairment has been reported to be common in patients with mitochondrial disorders, a group of diseases characterized by pleiomorphic clinical manifestations due to defects in oxidative phosphorylation of mitochondria. This study aimed to investigate the audiological characteristics in a large cohort of patients with mitochondrial disease. Methods Comprehensive audiological evaluations, including pure tone audiometry, tympanometry, speech audiometry, otoacoustic emissions, electrocochleography and auditory brainstem evoked potentials, were performed in 73 Chinese patients with mitochondrial encephalomyopathy and with confirmed mitochondrial DNA (mtDNA) defects. Results Among the patients, 71% had hearing impairment. However, the incidence rate and severity of hearing impairment were much less in the chronic progressive external ophthalmoplegia (CPEO) subtype than in the mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF) and Kearns‐Sayre syndrome (KSS) subtypes. While most of our patients had a predominantly cochlea origin for the hearing deficit, five patients had an auditory neuropathy spectrum disorder and three patients had impairment of both cochlea and auditory cortex. Conclusions Various portions of the auditory system could be involved in patients with mitochondrial diseases, including cochlea, auditory nerve, auditory pathway and cortex. Hearing loss was more associated with multisystem involvement. Genotype, mutant load of mtDNA and other unknown factors could contribute to heterogeneity of hearing impairment in mitochondrial disease.
Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

ABSTRACT Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8+T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8+ T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8+T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8+ T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication.
A review and phylogeny of Scarabaeine dung beetle fossils (Coleoptera: Scarabaeidae: Scarabaeinae), with the description of two Canthochilum species from Dominican amber

Despite the increasing rate of systematic research on scarabaeine dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae), their fossil record has remained largely unrevised. In this paper, we review all 33 named scarabaeine fossils and describe two new species from Dominican amber (Canthochilum alleni sp.n., Canthochilum philipsivieorum sp.n.). We provide a catalogue of all fossil Scarabaeinae and evaluate their assignment to this subfamily, based primarily on the original descriptions but also, where possible, by examining the type specimens. We suggest that only 21 fossil taxa can be reliably assigned to the Scarabaeinae, while the remaining 14 should be treated as doubtful Scarabaeinae. The doubtful scarabaeines include the two oldest dung beetle fossils known from the Cretaceous and we suggest excluding them from any assessments of the minimum age of scarabaeine dung beetles. The earliest reliably described scarabaeine fossil appears to be Lobateuchus parisii, known from Oise amber (France), which shifts the minimum age of the Scarabaeinae to the Eocene (53 Ma). We scored the best-preserved fossils, namely Lobateuchus and the two Canthochilum species described herein, into the character matrix used in a recent morphology-based study of dung beetles, and then inferred their phylogenetic relationships with Bayesian and parsimony methods. All analyses yielded consistent phylogenies where the two fossil Canthochilum are placed in a clade with the extant species of Canthochilum, and Lobateuchus is recovered in a clade with the extant genera Ateuchus and Aphengium. Additionally, we evaluated the distribution of dung beetle fossils in the light of current global dung beetle phylogenetic hypotheses, geological time and biogeography. The presence of only extant genera in the late Oligocene and all later records suggests that the main present-day dung beetle lineages had already been established by the late Oligocene–mid Miocene.
Uptake of cystic fibrosis testing in primary care: supply push or demand pull?

OBJECTIVE--To determine the acceptability and feasibility of screening for carriers of cystic fibrosis in a primary care setting. DESIGN--Follow up study over 15 months of patients offered carrier testing by mouthwash. SETTING--A general practice in inner London. SUBJECTS--5529 patients aged 18-45 invited by various methods and combinations of methods (letter, booklet, personal approach) for testing. MAIN OUTCOME MEASURES--Uptake of screening, anxiety, and knowledge of test. RESULTS--957 (17%) invitees were screened over the 15 months. 28 carriers and no carrier couples were detected. Uptake rates were 12% (59/502 patients) among patients invited by letter and tested by appointment; 9% (47/496) among patients invited by letter, with leaflet, and tested by appointment; 4% (128/2953) among patients invited by letter six weeks before the end of the study and tested by appointment; 17% (81/471) among patients offered passive opportunistic testing; 70% (453/649) among patients offered active opportunistic testing; and 25% (22/88) among patients offered active opportunistic testing by appointment. A short term rise in anxiety among those given a positive test result had dissipated by three months. At three months about one fifth and one third of those given positive and negative results respectively did not understand their results correctly. CONCLUSION--These results suggest that the strongest variable in determining uptake of screening is the active approach by a health professional offering immediate testing. It remains to be resolved whether the high uptake rates achieved by active recruitment indicate a supply push for this new test rather than a demand from the population.
Differences in the thermal stability of acclimation temperature-associated types of carp myosin and its rod on differential scanning calorimetry.

Differential scanning calorimetry (DSC) was employed for studying the thermal unfolding of myosin and its rod part prepared from carp acclimated to 10 and 30 degrees C. Differences in the thermal stability reflecting structural properties were clearly demonstrated by the DSC data obtained at pH 8.0 in 0.6 M KCl for the two types of carp myosin and rod. The transition temperatures on myosin and rod given by the major peaks for the 10 degrees C-acclimated carp were 33.9 and 47.4 degrees C and 33.0 and 44.0 degrees C, respectively, assuming two endotherms for this type. Since the shape of the first peaks at 33.9 and 33.0 degrees C was not symmetrical, two peaks having similar transition temperatures overlapped in this temperature range. When the data were analyzed using three endotherms, the three transition temperatures obtained for myosin and rod were 32.8, 34.9, and 47.4 degrees C and 32.9, 33.4, and 44.1 degrees C, respectively. Thus, the position of the first peak for the 10 degrees C-acclimated carp myosin did not change even after removal of the large subfragment-1 part, but the transition of the second peak shifted to a lower temperature by about 3 degrees C. The myosin and rod from carp acclimated to 30 degrees C showed three distinct peaks at 35.9, 39.7, and 49.1 degrees C and 34.5, 39.7, and 46.7 degrees C, respectively. The position of the largest peak for myosin remained unchanged, and the shift of the peak position of the highest temperature was about 3 degrees C, as obtained for the 10 degrees C-acclimated carp. (ABSTRACT TRUNCATED AT 250 WORDS)
Experiential Learning in Kinesiology

Overview. Service learning is a form of experiential learning that pairs academic educational experiences and community organizations to promote training, civic engagement, and meaningful service by students to their community. Kinesiology programs have moved toward increasing experiential and service learning options in health promotion for their students, but few have evaluated the student perceptions of these programs. Purpose. The purpose of the current study was to conduct a qualitative evaluation of a service learning course for kinesiology majors located in a low-income urban area. Method. Ten recent graduates of a department of kinesiology were enrolled in focus groups, stratified by gender, facilitated by a graduate research assistant not affiliated with their school. Focus group discussions were audiotaped, transcribed, and analyzed for themes. Results. Nine themes were identified: (1) personal and professional experience, (2) decision to participate, (3) location decision, (4) self-efficacy, (5) perceptions of program members, (6) social interaction, (7) personal and program communication, (8) physical facilities, and (9) program outcomes. Students positively evaluated the learning experience as valuable to their personal and professional development; noted changes in their perceptions of low-income communities and increases to self-efficacy and skill acquisition from the beginning to the end of the course; and observed significant needs and improvements in physical, emotional, and social outcomes of community members. Conclusions. This study demonstrated multiple and varied benefits of a service learning program for kinesiology students. Ongoing evaluation of service learning programs in health promotion is needed to enhance student and community outcomes.
Increased prevalence of cardiovascular defects among 56,709 California twin pairs

This study compared the prevalence of cardiovascular defects in twin and singleton births and explored the influences of zygosity (monozygotic and dizygotic) and maternal age (<35 and ≥35 years of age) on concordance. Data on twin and singleton infants with (n = 628 twin pairs and n = 14,078 singletons) and without (n = 53,974 twin pairs and n = 4,858,255 singletons) cardiovascular defects were obtained from the California Birth Defects Monitoring Program and the California vital statistics birth and fetal death records during the period 1983–2003. Prevalence ratios (PR) (prevalence of twin/singleton) and approximate 95% confidence intervals were calculated for 16 congenital cardiovascular categories. Poisson regression techniques using log‐linear models were employed to assess whether the probability of concordance of defects within each cardiovascular category varied by zygosity or maternal age. An increased prevalence was observed in twins compared to singletons in all 16 cardiovascular categories. Seven of the cardiovascular categories had at least double the prevalence in twins compared to singletons. Like‐sex twins, as a proxy of monozygosity, had an increased prevalence of cardiovascular defects compared to unlike sex twins. Probabilities of concordance for flow lesions were higher among monozygotic than dizygotic twins. Our study provides evidence that twinning is associated with more cardiovascular defects than singletons. Increased concordance for flow lesions in monozygotic twins was observed, an observation that is in agreement with findings from familial recurrence studies of cardiovascular defects. © 2009 Wiley‐Liss, Inc.
Safety of synchronous hepatectomy and splenectomy for patients with hepatocellular carcinoma and hypersplenism.

BACKGROUND/AIMS To assess the surgical safety of synchronous hepatic resection and splenectomy for patients with hepatocellular carcinoma (HCC) and hypersplenism. METHODOLOGY Patients with HCC and hypersplenism who underwent surgical treatment were included in this study. According to the difference of operations, patients were divided into two groups (group A, patients who underwent hepatic resection; group B, patients who underwent synchronous hepatic resection and hypersplenism). Pre- and intra-operative parameters were statistically analyzed. Postoperative outcomes including white blood cell and platelet count changes, surgical complications and long-term survival rates were compared. RESULTS The pre- and intra-operative parameters of two groups were comparable except for preoperative white blood cell and platelet counts. The incidences of postoperative surgical complication were 53.33% for group A and 35.48% for group B (p=0.161). The 1- and 3-year survival rates of the two groups were 83%, 42% and 82%, 54%, respectively (p=0.313). CONCLUSIONS Synchronous hepatic resection and splenectomy could increase the postoperative WBC and platelet level for patients with hepatocellular carcinoma and hypersplenism without increasing surgical risks.
Gastric GI stromal tumors (GISTs): The role of surgery in the era of targeted therapy

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising in the stomach. These tumors were previously classified as smooth muscle tumors, but in recent years it has become clear that they are clinically, pathologically, and molecularly distinct from other tumors and are much more common than previously appreciated. Historically, patients with primary localized or advanced GIST have been managed surgically, as there was no proven role of other treatment modalities such as radiation or chemotherapy. However, the field of GIST was revolutionized with the 1998 discovery that the vast majority of these tumors have oncogenic gain‐of‐function mutations of the KIT receptor tyrosine kinase. Follow‐up studies have confirmed that KIT is both a useful diagnostic marker and an excellent therapeutic target. Imatinib, an inhibitor of KIT kinase activity, is now the standard front‐line therapy for patients with advanced GIST. In this review, we discuss pathological and molecular features of gastric GISTs and review the historic and current roles of surgery in the treatment of patients with primary or metastatic GIST. The importance of a multi‐disciplinary approach using both surgery and imatinib therapy is emphasized. J. Surg. Oncol. 2005;90:195–207. © 2005 Wiley‐Liss, Inc.
Who is more likely to respond to dual treatment with pegylated‐interferon and ribavirin for chronic hepatitis C? A gender‐oriented analysis

We assessed, in real‐life practice, viral, demographic, genetic and metabolic factors influencing the sustained virologic response (SVR), with a gender‐oriented analysis, in patients with chronic hepatitis C virus (HCV) treated with pegylated interferon and ribavirin. Six hundred and seventy naïve patients were treated with dual therapy and evaluated by gender and HCV genotype. Associations between baseline variables and SVR were assessed by multivariate logistic regression analysis. Among 362 genotype 1 patients, SVR was achieved in 158 patients (44%), and SVR was independently associated with age less than 50 years (OR 2.12; 95% CI 1.09–4.30; P = 0.039) and C/C genotype rs12979860 SNP (OR 2.83; 1.19–6.74; P = 0.002) in 163 females, while absence of visceral obesity (OR 2.491; 1.131–5.487; P = 0.023), HCV‐RNA lower than 400 000 IU/mL (OR 2.66; 1.273–5.558; P = 0.009) and C/C genotype rs12979860 SNP (OR 4.969; 2.401–10.283; P < 0.001) were independently associated with SVR in 199 males. Combining favourable baseline variables, the probability of obtaining SVR ranged from 27.6% to 84.2% in females, and from 14.3% to 85.7% in males. The rate of SVR was 81.1% in 175 genotype 2 patients, and 69% in 100 genotype 3 patients. Rapid virologic response was the only valid predictor of SVR regardless of other features. In conclusions, in the setting of HCV genotype 1, chronic hepatitis, combining rapid virologic response and predictive factors, which are different for females and males, allows clinicians to single out a group of patients whose likelihood of SVR exceeds 80%. For these patients, triple therapy with first‐generation protease inhibitors may be unwarranted.
Trophoblast Differentiation Modulates the Activity of Caspases in Primary Cultures of Term Human Trophoblasts

Cultured human cytotrophoblasts are more susceptible than syncytiotrophoblasts to hypoxia-induced apoptosis. Caspases are cysteine proteases that cleave cellular components to effect the apoptotic cascade. We hypothesized that cultured cytotrophoblasts exhibit a higher activity of caspases when compared with syncytiotrophoblasts. Using western analysis, we demonstrated that the pro-caspases 3, 6, 8, and 9 are expressed in cytotrophoblasts cultured for 24 h, and also, in trophoblasts cultured 72 h when syncytiotrophoblasts have formed. Importantly, we found significantly higher activity of all four caspases in trophoblasts cultured 24 h compared with cells cultured 72 h. Colchicine and DMSO, which hinder trophoblast differentiation, enhanced the activity of all four caspases in cells cultured 72 h. Conversely, caspase activity was reduced in trophoblasts cultured for 24 h in the presence of epidermal growth factor, which enhances differentiation. This effect was most pronounced on caspase 3 and was attenuated by addition of the tyrosine kinase inhibitor AG1478. We conclude that cytotrophoblasts exhibit a higher activity of caspases 3, 6, 8, and 9 when compared with the more differentiated syncytium. This may account for the higher susceptibility of cytotrophoblasts to hypoxia-induced apoptosis.