Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Fas Ligand in Metastatic Prostatic Carcinoma: Suggestive of Possible Clonal Expansion of Subpopulation With Metastatic Potential

Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases. Analysis of the FasL gene and its mRNA by polymerase chain reaction and reverse transcriptase–polymerase chain reaction, respectively, suggested that the expression of immunohistochemically detectable FasL in metastatic tumor cells was not due to mutation in the FasL gene with resulting overexpression. Further, FasL expression was detectable in the acinar epithelial cells of prostates with morphologic atrophic changes, suggesting that FasL also plays a role in the physiologic apoptosis process of noncancerous prostate. The current data suggest that a subpopulation of prostate carcinoma cells clonally expresses FasL, and this subpopulation may have metastatic potential. Evaluation of FasL expression in the primary tumor thus may provide a useful parameter for predicting metastatic potential of the tumor.
Dominant-Negative α-Subunit of Farnesyl- and Geranyltransferase Inhibits Glucose-Stimulated, but Not KCl-Stimulated, Insulin Secretion in INS 832/13 Cells

The majority of small G-proteins undergo posttranslational modifications (e.g., isoprenylation) at their C-terminal cysteine residues. Such modifications increase their hydrophobicity, culminating in translocation of the modified proteins to their relevant membranous sites for interaction with their respective effectors. Previously, we reported glucose-dependent activation and membrane association of Rac1 in INS 832/13 cells. We also demonstrated modulatory roles for Rac1/GDP dissociation inhibitor in glucose-stimulated insulin secretion (GSIS) in INS 832/13 cells, further affirming roles for Rac1 in GSIS. Herein, we demonstrate that geranylgeranyltransferase inhibitor-2147 (GGTI-2147), an inhibitor of protein prenylation, markedly increased cytosolic accumulation of Rac1 and elicited significant inhibition of GSIS from INS 832/13 cells. In the current study, we also examined the localization of protein prenyltransferases (PPTases) and regulation of GSIS by PPTases in INS 832/13 cells. Western blot analyses indicated that the regulatory α-subunit and the structural β-subunit of PPTase holoenzyme are predominantly cytosolic in their distribution. Overexpression of an inactive mutant of the regulatory α-subunit of PPTase markedly attenuated glucose- but not KCl-induced insulin secretion from INS 832/13 cells. Together, our findings provide the first evidence for the regulation of GSIS by PPTase in INS 832/13 cells. Furthermore, they support our original hypothesis that prenylation of specific G-proteins may be necessary for GSIS.
Aberrant patterns of cellular communication in diabetes-induced embryopathy I. Membrane signalling

Objective: Our purpose was to investigate the role of membrane signalling in the mechanism of diabetes-induced embryopathy. Methods: Three groups of 70-90-day-old Sprague-Dawley rats were employed in our study: group 1 was normal control rats receiving a normal diet; group 2 represented experimentally induced diabetic rats with malformed offspring (intravenous injection of 65 mg/kg streptozotocin on pregnancy day 6) and group 3 included streptozotocin-induced diabetic rats with normal offspring. Embryos were examined on day 12 under light microscopy, categorized as morphologically normal or defective, and yolk sac cells were harvested from each group. Activities of ERK1 and 2, Raf-1, JNK 1 and 2 in yolk sac cells were analyzed by Western blot with primary antibodies specific to the phosphorylated kinases, respectively. Results: A strong link between hyperglycemia and congenital malformations was confirmed. Key mitogen-activated protein kinases serve as syllabic intermediates: increased activities of Jun-amino-terminal kinase (JNK1 and 2) and decreased activities of extracellular signal-regulated kinase (ERK1 and 2) were observed during hyperglycemia-induced embryopathy. Conclusions: Poorly controlled maternal diabetes results in embryopathy which is mediated via a pattern of aberrant cellular communication manifested by both macroscopic and microscopic membrane injury.
Changes and Prognostic Impact of Apoptotic and Inflammatory Cytokines in Patients Treated with Cardiac Resynchronization Therapy

Objectives: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-β cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. Methods: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-α, TNF-receptor 1, TGF-β1 and interleukin (IL)-6 were measured using ELISA. Results: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-α and TGF-β1 decreased significantly. In nonresponders, the concentration of TGF-β1 even increased significantly. In multivariate analysis, the concentration of TGF-β1 was a significant predictor of death during follow-up. Conclusions: The response to CRT implantation was associated with a decrease of TGF-β1, IL-6 and TNF-α. Higher pre-implant concentrations of TGF-1β were independently associated with a poor prognosis in CRT patients.
Palliative care in adolescents and young adults with cancer

Adolescents and young adults (AYA) with advanced or terminal cancer have distinctive medical and psychosocial needs that may not have been adequately provided by either pediatric or adult palliative care services. A discussion group, as part of a larger workshop on AYA with cancer, was held in Toronto on March 11‐13, 2010;117:–. Recommendations were as follows: Develop a specific AYA screening tool designed to detect increased anxiety or new symptoms and to initiate discussion about palliative or symptom care; Set Canadian standards for palliative care in AYA patients. These standards should be included in hospital accreditation; Involve the palliative/symptom care team early in the disease trajectory to help manage clinically important symptoms that may not be associated with imminent death; Establish specific AYA multidisciplinary palliative care teams throughout Canada that are flexible and can work in both pediatric and adult facilities, and are able to work in a “virtual” environment to support patients being cared for at home; Improve physical facilities in hospices and hospitals to meet the distinctive needs of terminally ill AYA patients; Enhance support for palliative care at home by: changing legislation to improve Compassionate Care Benefits and developing “virtual palliative care support teams”. Adequate provision of AYA palliative care and symptom management services will likely confer notable benefits to AYA patients and their families, and is likely to be cost saving to the tax payer by avoiding prolonged hospitalization and promoting easier return to work for the families and caregivers. Cancer 2011;117(10 suppl):2323–8. © 2011 American Cancer Society.
Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

STUDY OBJECTIVE Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. DESIGN We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. MEASUREMENTS AND RESULTS Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. CONCLUSIONS We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.
One-year follow-up results of a randomized controlled clinical trial on internet-based cognitive behavioural therapy for subthreshold depression in people over 50 years

Background Internet-based cognitive behaviour therapy (CBT) is a promising new approach for the treatment of depressive symptoms. The current study had two aims: (1) to determine whether, after 1 year, an internet-based CBT intervention was more effective than a waiting-list control group; and (2) to determine whether the effect of the internet-based CBT differed from the group CBT intervention, 1 year after the start of treatment. Method A total of 191 women and 110 men (mean age=55 years, s.d.=4.6) with subthreshold depression were randomized into internet-based treatment, group CBT (Lewinsohn's Coping with Depression Course), or a waiting-list control condition. The main outcome measure was treatment response after 1 year, defined as the difference in pretreatment and follow-up scores on the Beck Depression Inventory (BDI). Missing data were imputed using the multiple imputation procedure of data augmentation. Analyses were performed using multiple imputation inference. Results In the waiting-list control group, we found a pretreatment to follow-up improvement effect size of 0.69, which was 0.62 in the group CBT condition and 1.22 with the internet-based treatment condition. Simple contrasts showed a significant difference between the waiting-list condition and internet-based treatment (p=0.03) and no difference between both treatment conditions (p=0.08). Conclusions People aged over 50 years with subthreshold depression can still benefit from internet-based CBT 1 year after the start of treatment.
Evaluation of lipid parameters and bioindices in patients with different stages of chronic renal failure.

BACKGROUND/AIM Cardiovascular morbidity and mortality are markedly increased in chronic renal failure (CRF). The aim of this study was to evaluate lipid parameters and bioindices in patients with different stages of CRF. METHODS In 46 hemodialysed (HD), 50 CRF patients with II, III and IV stage of CRF (non-HD) and 48 control subjects triglycerides (TG), total cholesterol (C), HDL-C, urea, creatinine, creatinuria (standard biochemical methods), apolipoprotein (apo) AI, apo B, lipoprotein(a), cystatin C (immunoturbidimetric method) were evaluated, and LDL-C, non-HDL-C, LDLC/HDL-C, non-HDL-/HDL-C, TG/HDL-C, and new bioindices, LTI (lipid tetrad index), logLTI, LPI (lipid pentad index), logLPI, AIP (atherogenic index of plasma), and creatinine clearance were calculated. RESULTS There were significant differences in the levels of TG, HDL-C, LDL-C, non-HDL-C, total C and apo A-I between the HD and non-HD patients, and the HD patients and the controls. LTI and LPI were significantly higher in the HD and non-HD patients compared to the controls (p < 0.05), without a good separation by the Box-Whisker plots. The values of TG/HDL-C ratio and AIP were significantly higher in the HD and nonHD-patients compared to the controls (p < 0.05), and significantly higher in the HD compared to non-HD patients (p < 0.05). AIP > 0.11 was found in 71.7% of the HD, 56% of non-HD and 31.3% of the controls. CONCLUSION Among lipid parameters and indices, AIP and TG/HDL-C ratio are most suitable for evaluation of lipid disturbances in different stages of CRF. In addition to, non-HDL-/HDL-C, and apoB/A-I ratios, apo A-I, HDL-C and TG are important markers in HD patients. Non-HDL-C is not a suitable marker. LTI and LPI need to be further investigated.
Gait changes with balance-based torso-weighting in people with multiple sclerosis.

BACKGROUND AND PURPOSE People with multiple sclerosis (PwMS) commonly have mobility impairments that may lead to falls and limitations in activities. Physiotherapy interventions that might improve mobility typically take several weeks. Balance-based torso-weighting (BBTW), a system of strategically placing light weights to improve response to balance perturbations, has resulted in immediate small improvements in clinical measures in PwMS, but changes in spatiotemporal gait parameters are unknown. The purpose was to investigate the effects of BBTW on gait parameters in PwMS and healthy controls. METHODS DESIGN This study is a non-randomized controlled experiment. PARTICIPANTS This study included 20 PwMS and 20 matched healthy controls PROCEDURES People with multiple sclerosis walked on an instrumented mat at their fastest speed for three trials each in two conditions: without BBTW then with BBTW. Healthy controls walked in both conditions at two speeds: their fastest speed and at velocities equivalent to their matched PwMS. RESULTS Averaged gait trials showed that, with BBTW, PwMS had significantly increased velocity (p = 0.002), cadence (p = 0.007) and time spent in single-limb support (p = 0.014), with decreased time in double-limb support (p = 0.004). Healthy controls increased velocity (p = 0.012) and cadence (p = 0.015) and decreased support base (p = 0.014) in fast trials with BBTW; at matched velocities, step length (p = 0.028) and support base (p = 0.006) were significantly different from PwMS. All gait variables in healthy controls at fast speeds were significantly different from PwMS walking at their fastest speeds. DISCUSSION All participants showed increases in gait velocity and cadence during fast walk with BBTW. Improvements in time spent in single-limb and double-limb support by PwMS with BBTW may reflect greater stability in gait. Future research might ascertain if these immediate improvements could enhance effectiveness of longer-term physiotherapy on functional mobility in PwMS.
CADAVERIC RENAL ALLOGRAFT AT THE TIME OF IMPLANTATION HAS THE SIMILAR IMMUNOLOGICAL FEATURES WITH THE REJECTING ALLOGRAFT1

Background. Compared to living donations, cadaveric transplants have a poorer outcome, and the immunologic status of renal tissues at the time of transplantation might influence the final outcome of the renal allograft. Patients and Methods. We used quantitative RT-PCR to evaluate the differential expression of cytokine genes from 37 implantation tissues [18 cadaveric tissues (CI), 19 specimens from living donors (LI)]. We compared them with 17 acutely rejecting allograft (AR). Results. Acute rejection within 6 months after transplantation occurred 8 times in patients with cadaveric allograft, but the living-donor recipients experienced 4 episodes (P <0.05). Proinflammatory cytokines were co-expressed more frequently in CI than in LI. The levels of IFN-&ggr;, TNF-&agr; and IL-10 mRNA were also higher in CI. We compared the profiles of several cytokine expressions of CI with those of AR. The messages for IL-6 were more abundant in the CI, IFN-&ggr; was more expressed in AR, and the other cytokine expression levels were similar in both types. However, when comparing LI and AR, all the cytokine messages except IL-6 were up-regulated in AR than in LI. In CI, the levels of cytokine gene expressions were similar despite various cold ischemic time except IL-10 that were elevated for those cases where the operation was done within 4 hr of nephrectomy. Conclusions. The numbers and levels of gene transcription of inflammatory cytokines were higher in the tissues from a cadaver, and were not different from those of AR. This immunologic hostility at the time of implantation would contribute to the poorer outcome of cadaveric allograft.
Tissue-specific Distribution and Modulatory Role of the γ Subunit of the Na,K-ATPase

The Na,K-ATPase comprises a catalytic α subunit and a glycosylated β subunit. Another membrane polypeptide, γ, first described by Forbush et al.(Forbush, B., III, Kaplan, J. H., and Hoffman, J. F. (1978)Biochemistry 17, 3667–3676) associates with α and β in purified kidney enzyme preparations. In this study, we have used a polyclonal anti-γ antiserum to define the tissue specificity and topology of γ and to address the question of whether γ has a functional role. The trypsin sensitivity of the amino terminus of the γ subunit in intact right-side-out pig kidney microsomes has confirmed that it is a type I membrane protein with an extracellular amino terminus. Western blot analysis shows that γ subunit protein is present only in membranes from kidney tubules (rat, dog, pig) and not those from axolemma, heart, red blood cells, kidney glomeruli, cultured glomerular cells, α1-transfected HeLa cells, all derived from the same (rat) species, nor from three cultured cell lines derived from tubules of the kidney, namely NRK-52E (rat), LLC-PK (pig), or MDCK (dog). To gain insight into γ function, the effects of the anti-γ serum on the kinetic behavior of rat kidney sodium pumps was examined. The following evidence suggests that γ stabilizes E1conformation(s) of the enzyme and that anti-γ counteracts this effect: (i) anti-γ inhibits Na,K-ATPase, and the inhibition increases at acidic pH under which condition the E2(K) → E1 phase of the reaction sequence becomes more rate-limiting, (ii) the oligomycin-stimulated increase in the level of phosphoenzyme was greater in the presence of anti-γ indicating that the antibody shifts the E1 ↔ ↔ E2P equilibria toward E2P, and (iii) when the Na+-ATPase reaction is assayed with the Na+concentration reduced to levels (≤2 mm) which limit the rate of the E1 → → E2P transition, anti-γ is stimulatory. These observations taken together with evidence that the pig γ subunit, which migrates as a doublet on polyacrylamide gels, is sensitive to digestion by trypsin, and that Rb+ions partially protect it against this effect, indicate that the γ subunit is a tissue-specific regulator which shifts the steady-state equilibria toward E1. Accordingly, binding of anti-γ disrupts αβ-γ interactions and counteracts these modulatory effects of the γ subunit.
Mutations in the B Subunit of Escherichia coli DNA Gyrase That Affect ATP-dependent Reactions (*)

We have previously reported specific labeling of Escherichia coli DNA gyrase by the ATP affinity analog pyridoxal 5′-diphospho-5′adenosine (PLP-AMP), which resulted in inhibition of ATP-dependent reactions. The analog was found to be covalently bound at Lys and Lys on the gyrase B subunit (Tamura, J. K., and Gellert, M.(1990) J. Biol. Chem. 265, 21342-21349). In this study, the importance of these two lysine residues is examined by site-directed mutagenesis. Substitutions of Lys result in the loss of ATP-dependent functions. These mutants are unable to supercoil DNA, to hydrolyze ATP, or to bind a nonhydrolysable ATP analog, 5′-adenylyl-β,-imidodiphosphate (ADPNP). The ATP-independent functions of gyrase, such as relaxation of negatively supercoiled DNA and oxolinic acid-induced cleavage of double-stranded DNA, are unaffected by these mutations, suggesting that the mutant B subunits are assembling correctly with the A subunits. Gyrase with substitutions of Lys retains all activities. However, the affinity of ATP is decreased. The DNA supercoiling activity of gyrase AB tetramers reconstituted with varying ratios of inactive mutant and wild-type gyrase B subunits is consistent with a mechanism of DNA supercoiling that requires the interdependent activity of both B subunits in ATP binding and hydrolysis.
Alteration of HGF and TSP‐1 expression in ovarian carcinoma associated with clinical features

Aim: The aim of this study was to investigate the expression levels of hepatocyte growth factor (HGF) and thrombospondin‐1 (TSP‐1) with the clinical pathological factors in ovarian cancer, and the correlation between HGF and TSP‐1 expression at the protein level.
Retinotopic mapping of the peripheral visual field to human visual cortex by functional magnetic resonance imaging

Retinotopic mapping is a key property of organization in the human occipital cortex. The retinotopic organization of the central visual field of visual areas V1, V2, and V3 has been well established. We used fMRI to measure the retinotopic map of the peripheral visual field (eccentricity up to 60°). We estimated the sizes of the visual areas between 0° and 60° and obtained results consistent with anatomical studies. We also estimated the cortical distances and magnification factors for reconstruction of the retinotopic map using the peripheral wedge dipole model. By comparing the retinotopic map with the flattened surface, we analyzed the datasets used to reconstruct the map. We found that: (1) the percentage of the striate cortex devoted to peripheral vision in humans is significantly larger than that in the macaque, (2) the estimate of the scaling factor in linear magnification is larger than that found in previous studies focusing on central vision, and (3) the estimate of the peripheral factor in the dipolar model is too large to make the curve direction of the dipolar map in the periphery equivalent to that in the center. On the basis of our results, we revised the dipolar map to fit our conditions. The revised map in humans has a similar elliptical shape to that of macaques, and the central parts of the two species are the same. The different parts of the map are the peripheral regions, for which the peripheral wedge dipole model in humans is reversed compared to that of macaques. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.