Miracle-dz/UniFAR-FTUs huggingface dataset:
Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross‐over comparison

Abstract. In a randomized cross‐over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run‐in period, patients were fed two equi‐caloric, equi‐nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+ 0.2 (SD 1.4) g vs. — 1.7 (2.4): P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.
Polymerization of actin modified with fluorescein isothiocyanate.

Solution properties of skeletal muscle actin, modified at lysine-61 with fluorescein isothiocyanate (FITC) [Burtnick, L.D. (1984) Biochim. Biophys. Acta 791, 57-62], were re-examined in this work by light scattering, analytical ultracentrifugation, fluorescence, electron microscopy and myosin ATPase activity measurements. Fluorescence measurements using trace amounts of actin labeled with N-(1-pyrenyl)iodoacetamide showed that the FITC modification inhibited but did not block completely the polymerization of actin by KCl and MgCl2. Sedimentation velocity runs of FITC-actin, incubated with 100 mM KCl and 2 mM MgCl2, revealed the presence in these solutions of polymeric, oligomeric and monomeric species. The critical concentration for FITC-actin polymerization under these conditions was 12 microM. As judged by electron microscopy, FITC-actin polymers were similar to but generally shorter than standard F-actin filaments. Light scattering measurements indicated that FITC modification inhibited also the polymerization of actin by myosin subfragment 1 (S1) but the resulting complexes were indistinguishable from standard, decorated actin filaments. MgATPase measurements showed that FITC-actin, polymerized by preincubation with S1, activated the MgATPase activity of S1 while the monomeric labeled protein did not. Thus, in analogy to native actin, the activating function of FITC-actin depended on the formation of actin filaments. Results presented in this study suggest that the region around lysine-61 of actin plays an important role in actin-actin contact and is less crucial to actomyosin interaction.
Sleep, circadian rhythm and body weight: parallel developments

Circadian alignment is crucial for body-weight management, and for metabolic health. In this context, circadian alignment consists of alignment of sleep, meal patterns and physical activity. During puberty a significant reduction in sleep duration occurs, and pubertal status is inversely associated with sleep duration. A consistent inverse association between habitual sleep duration and body-weight development occurs, independent of possible confounders. Research on misalignment reveals that circadian misalignment affects sleep-architecture and subsequently disturbs glucose–insulin metabolism, substrate oxidation, leptin- and ghrelin concentrations, appetite, food reward, hypothalamic–pituitary–adrenal-axis activity and gut-peptide concentrations enhancing positive energy balance and metabolic disturbance. Not only aligning meals and sleep in a circadian way is crucial, also regular physical activity during the day strongly promotes the stability and amplitude of circadian rhythm, and thus may serve as an instrument to restore poor circadian rhythms. Endogenicity may play a role in interaction of these environmental variables with a genetic predisposition. In conclusion, notwithstanding the separate favourable effects of sufficient daily physical activity, regular meal patterns, sufficient sleep duration and quality sleep on energy balance, the overall effect of the amplitude and stability of the circadian rhythm, perhaps including genetic predisposition, may integrate the separate effects in an additive way.
Phosphatase inhibition prevents the activity‐dependent trafficking of GABAA receptors during status epilepticus in the young animal

To determine if the activity‐dependent trafficking of γ2 subunit–containing γ‐aminobutyric acid type A receptors (GABAARs) that has been observed in older animals and posited to contribute to benzodiazepine pharmacoresistance during status epilepticus (SE) is age‐dependent, and to evaluate whether blockade of protein phosphatases can inhibit or reverse the activity‐dependent plasticity of these receptors.
Role of helicobacter pylori infection in autoimmune diseases

Purpose of reviewThe etiology of most autoimmune diseases remains elusive. Prevailing evidence suggests an environmental trigger in a genetically susceptible individual. Helicobacter pylori (H. pylori) have managed to survive in a hostile environment in their host for long period and have evaded eradication by the immune system. Its chronic interaction with the immune system and the ubiquitous presence worldwide makes H. pylori an ideal candidate to study as a trigger of autoimmune phenomena. In this review, we would present data regarding the interplay between H. pylori and various components of the immune system and its association with various autoimmune diseases. Recent findingsStrong associations of H. pylori with some autoimmune diseases such as immune thrombocytopenia have been found; but most other autoimmune disease studies have revealed conflicting data. The chronic survival of H. pylori in humans is possible because of an overall downregulation of the body's immune response. In addition to this overall effect on the immune system, there are clinical and epidemiological data suggestive of H. pylori infection having a protective role in some autoimmune diseases. SummaryBased on our review H. pylori status should be checked and treated only in certain autoimmune diseases such as ITP. For the majority of the autoimmune diseases, the role of H. pylori remains controversial signifying need for further research.
A liquid chromatography tandem mass spectrometry assay for plasma renin activity using online solid-phase extraction

Background The plasma renin activity (PRA) assay measures the ability of renin to generate angiotensin I (AngI) from angiotensinogen. It is used to monitor mineralocorticoid therapy and to screen hypertensive individuals for primary aldosteronism (PA). Methods Samples were incubated in the presence of protease inhibitors for 6.5 and 24 h. The reaction was stopped by the addition of 2% ammonium hydroxide. AngI was then quantified by liquid chromatography tandem mass spectrometry using online solid-phase extraction (XLC-MS/MS). Results This method requires a sample volume of 50 μL and has an inter-assay precision <14% across the working range. A 6.5-h incubation gave a lower limit of quantification (LLOQ) of 0.3 nmol/L/h and this can be reduced to 0.08 nmol/L/h using a 24-h incubation. Comparison to a radioimmunoassay revealed excellent correlation (r 2 = 0.98), but a 37% negative bias. We also found that renin is stable in whole blood for up to 24 h at room temperature. In contrast, storage at 4°C should be avoided as prorenin cryoactivation can affect the PRA result in some patient groups. Conclusions We have developed and fully validated a semi-automated XLC-MS/MS method for the measurement of PRA. In addition, a reference range specific to this assay has been defined. We have also demonstrated that renin is stable for up to 24 h at room temperature. This will enable this assay to be extended to samples taken in primary care, potentially increasing the number of hypertensive patients who can be screened for PA.
The role of amino acid transporters in nutrition

Purpose of reviewWe consider recent advances in epithelial amino acid transport physiology and our understanding of the functioning of amino acid transporters as sensors, as well as carriers, of tissue nutrient supplies. Recent findingsGut hormones (e.g. leptin) may regulate intestinal amino acid transporter activity by a variety of mechanisms, although the overall functional significance of such regulation is not yet fully understood. Important functional interactions between amino acid transporters and nutrient-signalling pathways which regulate metabolism [e.g. the mammalian target of rapamycin (mTOR)C1 pathway which promotes cell growth] have been revealed in recent studies. Amino acid transporters on endosomal (e.g. lysosomal) membranes may be of unexpected significance as intracellular nutrient sensors. It is also now evident that certain amino acid transporters may have dual receptor–transporter functions and act as ‘transceptors’ to sense amino acid availability upstream of signal pathways. SummaryIncreased knowledge on the timescale of the amino acid sensor-signal-effector process(es) should help in the optimization of protein-feeding regimes to gain maximum anabolic effect. New opportunities for nutritional therapy include targeting of amino acid transceptors to promote protein-anabolic signals and mechanisms up-regulating amino acid transporter expression to improve absorptive capacity for nutrients.
Isolation, Structural Characterization, and Bioactivity of a Novel Neuromedin U Analog from the Defensive Skin Secretion of the Australasian Tree Frog, Litoria caerulea * 210

We report the isolation of a novel bioactive peptide, neuromedin U-23 (NmU-23), from the defensive skin secretion of the Australasian tree frog, Litoria caerulea. The primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy and site-directed antiserum immunoreactivity as SDEEVQVPGGVISNGYFLFRPRN-amide (Mr 2580.6). A synthetic replicate of frog NmU-23 displaced monoradioiodinated rat NmU-23 from uterine membranes in a dose-dependent fashion indistinguishable from nonisotopically labeled rat NmU-23. In a rat uterine smooth muscle strip preparation, synthetic frog NmU-23 produced dose-dependent contractions identical to porcine NmU-25. However, in a preparation of human urinary bladder muscle strip, the synthetic frog peptide was more potent than porcine NmU-25 in eliciting contraction and produced desensitization of the preparation to the latter peptide. This report demonstrates that the defensive skin secretion of a frog contains a novel peptide exhibiting a high degree of primary structural similarity to the endogenous vertebrate peptide, NmU, and that this frog skin analog displays biological activity in mammalian tissues.
Abortion and the risk of breast cancer: A case‐control study in greece

We have examined the association between induced or spontaneous abortion and breast cancer risk in Greece. In a hospital‐based case‐control study in Athens, 820 patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to cases by age and interviewer. Logistic regression was used to analyze the data, controlling for demographic, reproductive and nutritional variables. Odds ratio (OR) patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not increased for women who had a history of abortion, compared to nulliparous women with no history of abortion. Thus ORs and 95% confidence intervals were for nulliparous women with spontaneous abortion, 1.17 (0.64–2.13); for nulliparous women with induced abortion, 0.98 (0.56–1.73); for parous women with no abortion, 0.56 (0.31–1.01); for parous women with spontaneous abortion, 0.61 (0.33–1.14) and for parous women with induced abortion, 0.99 (0.56–1.74). When the analysis was restricted to parous women, using parous women with no history of abortion as the baseline, ORs and 95% confidence intervals were for induced abortion before first full‐term pregnancy, 2.06 (1.45–2.90); for induced abortion after first full‐term pregnancy, 1.59 (1.24–2.04) and for spontaneous abortion, 1.10 (0.82–1.40). Our findings suggest that an interrupted pregnancy does not impart the long‐term protective effect of a full‐term pregnancy attributable to terminal differentiation. © 1995 Wiley‐Liss, Inc.
CD8+ effector cells responding to residual class I antigens, with help from CD4+ cells stimulated indirectly, cause rejection of "major histocompatibility complex-deficient" skin grafts.

BACKGROUND Skin grafts from mice that are deficient in the expression of both class I and class II major histocompatibility complex (MHC) antigens are rejected rapidly by normal recipients. METHODS To determine the mechanism of this rejection, MHC-deficient skin grafts were placed on recipients with different degrees of antigenic disparity and on recipients depleted of selected T cell subpopulations. In addition, the recipient's T cells were examined in vitro for their responses before and after graft rejection. RESULTS The results indicate that (1) CD4+ cells provide help for this rejection by recognizing donor antigens presented by recipient class II antigens, and (2) CD8+ cells can participate as effector cells, recognizing residual class I antigens expressed by the MHC-deficient grafts. CONCLUSIONS The primary conclusion from these studies is that the supposedly MHC-deficient mice actually do have sufficient class I antigen expression to cause skin graft rejection. This finding prevents the use of these mice to answer definitively the question of whether grafts entirely lacking MHC antigens would be rejected. However, these studies do illustrate two important (although previously recognized) features of allogeneic skin graft rejection: (1) that rejection can be initiated by help provided entirely through the indirect pathway, and (2) that help provided through the indirect pathway is available for effector T cells sensitized directly by donor cells. However, the results from these and other studies suggest that indirect effector mechanisms would probably be able to destroy truly MHC-deficient grafts under some circumstances.
Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi's sarcoma.

BACKGROUND Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. PURPOSE The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. METHODS Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3-6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. RESULTS The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3-27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. CONCLUSION Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. IMPLICATION Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted.
The Krüppel-like Factor Epiprofin Is Expressed by Epithelium of Developing Teeth, Hair Follicles, and Limb Buds and Promotes Cell Proliferation*

We identified a cDNA clone for epiprofin, which is preferentially expressed in teeth, by differential hybridization using DNA microarrays from an embryonic day 19.5 mouse molar cDNA library. Sequence analysis revealed that this cDNA encodes a member of the Krüppel-like factor family containing three characteristic C2H2-type zinc finger motifs. The full-length cDNA was obtained by the 5′ Cap capture method. Except for its 5′-terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of Krüppel-like factor 14/Sp6 (specificity protein 6), which was previously identified in expressed sequence tag data bases and GenBank™ by an Sp1 zinc finger DNA-binding domain search (Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P. L., Van Vooren, P., Riviere, M., Szpirer, J., and Szpirer, C. (2000) Genomics 70, 93-101). This sequence difference is due to differences in the assignment of the location of exon 1. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating dental epithelium, differentiated odontoblast, and also hair follicle matrix epithelium. In addition, whole mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge in developing limbs and the posterior neuropore. Transfection of an epiprofin expression vector revealed that this molecule is localized in the nucleus and promotes cell proliferation. Thus, epiprofin is a highly cell- and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of teeth, hair follicles, and limbs that may function in the development of these tissues by regulating cell growth.
Evaluation of Erythropoietic Activity on the Basis of the Red Cell and Reticulocyte Distribution Widths during Epoetin Beta Therapy in Patients Undergoing Cardiac Surgery

The changes in the red cell and reticulocyte distribution widths during preoperative treatment with recombinant human erythropoietin (rhEPO) were evaluated in a double-blind, placebo-controlled trial in cardiac surgery patients. The increases in the reticulocyte count, in the hemoglobin and in all distribution widths are the expression of the marked preoperative stimulation of erythropoiesis in the patients treated with rhEPO. Only placebo patients with a hemoglobin ≤7.5 mmol/l or a transferrin >4.0 g/l at baseline showed an increase in the red cell distribution width or in the reticulocyte hemoglobin distribution width on oral iron therapy alone. While the reticulocyte count and the distribution widths of red cells in the rhEPO patients decreased postoperatively, only the increases in the distribution widths of reticulocytes after the second postoperative day indicate that stimulation of erythropoiesis had taken place. In patients with a low hemoglobin or a high transferrin the rhEPO therapy should be preceded by iron therapy in order to raise the hemoglobin level and reduce the cost of treatment.
High‐frequency stimulation of the subthalamic nucleus modulates the activity of pedunculopontine neurons through direct activation of excitatory fibres as well as through indirect activation of inhibitory pallidal fibres in the rat

Recent data suggest a potential role of pedunculopontine nucleus (PPN) electrical stimulation in improving gait and posture in Parkinson's disease. Because the PPN receives fibres from the subthalamic nucleus (STN), we investigated the effects of STN‐high‐frequency stimulation (HFS) on PPN neuronal activity in intact rats and in rats bearing either an ibotenate lesion of the entopeduncular nucleus (EP) or a lesion of the substantia nigra (SN). The main response of PPN neurons to STN single‐shock stimulations in the three experimental groups was a short latency (4.5 ± 2.1 ms) and brief (15.3 ± 6.5 ms) excitation. This response was maintained during 1–5 s of STN‐HFS (130 Hz, 60 µs, 100–1000 µA). In EP‐lesioned rats the percentage (75.0%) of PPN neurons showing a modulation of activity following STN‐HFS was significantly higher compared with that observed in intact (39.7%) and in SN‐lesioned rats (35.4%). Furthermore, in EP‐lesioned rats the most frequent response of PPN neurons following STN‐HFS was a 5–20 s excitation, which was present in 76.6% of responsive neurons in comparison to 15.4% and 9.1% of neurons responsive in intact and in 6‐hydroxydopamine‐lesioned rats, respectively. Neurons responsive to STN‐HFS in the three experimental groups showed either a sharp positively skewed distribution of interspike intervals or multisecond oscillations in autocorrelograms. The results support that STN‐HFS modulates the PPN through a balance of excitatory and inhibitory influences, which may be independent from the dopaminergic nigral neurons. In the absence of inhibitory EP fibres, the direct excitatory influence exerted by the STN on the PPN appears to predominate.