Miracle-dz/UniFAR-FTUs huggingface dataset:
Effector molecules of the host defence mechanism against Mycobacterium avium complex: the evidence showing that reactive oxygen intermediates, reactive nitrogen intermediates, and free fatty acids each alone are not decisive in expression of macrophage antimicrobial activity against the parasites

In this study, we evaluated the roles of reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and free fatty acids (FFA) as effectors of the macrophage‐mediated host defence mechanism against Mycobacterium avium complex (MAC). First, M. avium (three strains) and M. intracellulare (two strains) were treated with the H2O2‐Fe2+‐mediated halogenation system, acidified NaNO2‐derived RNI, or FFA (linolenic acid) in sodium acetate buffer pH 5.5, and then counted for the number of residual colony‐forming units (CFU) of organisms. Although these effectors exerted strong bactericidal activity against the MAC, the susceptibility of test organisms markedly varied from strain to strain. There was no significant relationship between the degree of resistance of a given MAC strain to these effectors and its virulence in mice, indicating that ROI, RNI, and FFA each alone are not decisive as the effector components of the host defence mechanism against the MAC. Second, the increase in ROI‐producing ability in murine peritoneal macrophages due to tumour necrosis factor‐alpha (TNF‐α) treatment was not accompanied by parallel potentiation of anti‐MAC activity of the same macrophage population. This excludes the possibility that ROI play a central role in macrophage‐mediated killing and inhibition of MAC organisms. Third, anti‐MAC activity of BAM3 macrophage cell line was not significantly attenuated by NG‐monomethyl‐l‐arginine (NO synthase‐inhibitor causing reduction of RNI production) or by quinacrine (phospholipase A2‐inhibitor causing reduction of FFA release), indicating that RNI and FFA each alone do not play crucial roles in the expression of macrophage antimicrobial activity against the MAC. The present findings suggest important roles of collaborating actions of various antimicrobial effectors and/or the participation of other kinds of effectors in macrophage‐mediated killing and inhibition of MAC organisms.
[Frequency of Helicobacter pylori infection in patients with chronic urticaria of Puebla University Hospital].

BACKGROUND Chronic urticaria may be continuous or recurrent according to its form of appearance. Within the diseases associated to chronic urticaria there are mycosis, parasitism and bacterial infections where Helicobacter pylori stands out. This has been related to the allergic diseases promoting a Th2 response. OBJECTIVE To determine the frequency of infection caused by Helicobacter pylori in patients with chronic urticaria of the allergic and clinical immunology service of the Puebla University Hospital. PATIENTS AND METHODS A descriptive, cross-sectional, prolective and observational study was made in adult patients, between 18 and 60 years old, with diagnosis of chronic urticaria. Inhalated and food skin prick test were made to all the patients. The infection by Helicobacter pylori was documented by serology, fecal antigen, endoscopy with fast test of urease and histological study. Descriptive statistics was implemented such as frequency, percentage, central tendency and dispersion measures. RESULTS 30 patients were included; 83.3% were women. The average age was 37.8 years (SD 13.2). The most frequent type of chronic urticaria was the persistent one, representing 56.7%. The frequency of positivism of IgG antibodies against Helicobacter pylori represented the 60.0%, for IgM 33.3% and for fecal antigen 60.0%, the combined IgG, IgM, fecal antigen, fast test of ureasa and histological study was of 83%. CONCLUSION The high frequency of infection caused by Helicobacter pylori in the patient with chronic urticaria suggests a possible role in its etiopathogeny, extending the therapeutic possibilities.
The importance of SRS-1 residues in catalytic specificity of human cytochrome P450 3A4.

The structural basis for the regioselective hydroxylation of Delta-4-3-ketosteroids by human CYP3A4 was investigated. Prior studies had suggested that the chemical reactivity of the allylic 6beta-position might have a greater influence than steric constraints by the enzyme. Six highly conserved CYP3A residues from substrate recognition site 1 were examined by site-directed mutagenesis. F102A and A117L showed no spectrally detectable P450. V101G and T103A exhibited a wild-type progesterone metabolite profile. Of five mutants at residue N104, only N104D yielded holoenzyme and exhibited the same steroid metabolite profile as wild-type. Of four mutants at position S119 (A, L, T, V), the three hydrophobic ones produced 2beta-OH rather than 6beta-OH progesterone or testosterone as the major metabolite. Kinetic analysis showed S(50) values similar to wild-type for S119A (progesterone) and S119V (testosterone), whereas the V(max) values for 2beta-hydroxysteroid formation were increased in both cases. All four mutants exhibited an altered product profile for 7-hexoxycoumarin side-chain hydroxylation, whereas the stimulation of steroid hydroxylation by alpha-naphthoflavone was similar to the wild-type. The results indicate that the highly conserved residue S119 is a key determinant of CYP3A4 specificity and reveal an important role of the active site topology in steroid 6beta-hydroxylation.
Cholinergic input from the ventral nucleus of the trapezoid body to cochlear root neurons in rats

Brain stem pathways are essential for the modulation of the acoustic startle reflex by sounds; nevertheless, the neural circuits that convey fast auditory information to the primary acoustic startle circuit are still unclear. In the rat, cochlear root neurons (CRNs) comprise the first component of the primary acoustic startle circuit and are critical in the initiation and full expression of the acoustic startle reflex. To determine whether CRNs receive auditory descending inputs, we developed tract‐tracing studies combined with immunohistochemistry, electron microscopy, morphometry, and confocal microscopy. Either FluoroGold or biotinylated dextran amine (BDA) injections in CRNs showed retrogradely labeled neurons in the ventral nucleus of the trapezoid body (VNTB). We verified the projection to CRNs by injecting BDA into the VNTB. Our results showed that neurons from VNTB project bilaterally and directly to CRNs, giving off numerous endings onto cell bodies and preferentially dendrites of CRNs. Electron microscopy analysis of labeled VNTB terminals demonstrated that they made multiple symmetric synapses and contained small round vesicles. Colocalization of the vesicular acetylcholine transporter and fluorescein dextran after injection in the VNTB indicated that these terminals use acetylcholine as neurotransmitter. We also revealed that the inferior colliculus, an important nucleus mediating the auditory prepulse inhibition, projects to VNTB neurons that innervate CRNs. Our data show a novel and short descending auditory pathway from the VNTB to the first nucleus of the primary acoustic startle circuit that might play an important role in the auditory prepulse inhibition of the startle reflex elicited by sounds. J. Comp. Neurol. 505:452–468, 2008. © 2007 Wiley‐Liss, Inc.
Redox imbalance provokes deactivation of macrophages in sepsis

Sepsis accounts for the majority of deaths in critically ill patients. Symptoms of septic disease are often associated with monocyte/macrophage desensitization. In the current study, impaired macrophage function was determined in a sepsis mouse model with decreased cytokine release and weak phagocytosis, coinciding with ectopic elevation of serum‐ROS levels. Furthermore, in the experimental cell model, RAW264.7 macrophages displayed a “deactivated” phenotype, characterized by impaired inflammatory and phagocytosis function. Cellular anti‐oxidative proteins were further investigated; lipopolysaccharide (LPS)‐ and H2O2‐treated cells exhibited lower ratio of reductive‐to‐oxidized glutathione as compared with LPS‐treated cells only, without inducing cell death. 2‐DE and MALTI‐TOF/TOF were employed to illustrate protein expression differentiation patterns. A total of 33 proteins were found to be differently expressed. Among them, 33% of proteins were associated with oxidative stress. We further investigated the role of the ROS/LPS/Toll‐like receptor 4 (TLR4) axis in modulating the immunosuppression during sepsis. LPS‐ and H2O2‐treated macrophages demonstrated decreased cytokine release, whereas TLR4 expression was up‐regulated. Western blot analysis showed decreased levels of phosphorylation of MAP kinases and IκB. Electrophoretic mobility shift assay analysis demonstrated attenuated DNA‐binding activities of AP‐1 and NF‐κB, as compared with those of their control. Collectively, these findings indicate that ROS mediates critical aspects of innate immunity that result in an immunocompromised state through an imbalance of cellular oxidation/reduction during sepsis.
Effects of n‐alcohols on junctional coupling and amylase secretion of pancreatic acinar cells

We have tested the effects of alcohols differing by their alkyl chain length on the membrane channels and amylase secretion of rat pancreatic acinar cells. In intact acini, alcohols with a chain of seven, eight, or nine carbons (C‐7, C‐8, and C‐9) induced dye uncoupling and increased basal amylase release. These effects were readily reversible after alcohol removal. By contrast, an alcohol with a chain of 15 carbons (C‐15) and several alcohols with chains of fewer than six carbons (C‐2, C‐4, and C‐6) did not uncouple acinar cells and had no effects on amylase secretion. Neither did alkanes and oxidized derivatives of C‐7 and C‐8 alcohols did not affect dye coupling. Double patch‐clamp experiments on pairs of acinar cells, under conditions of strong cytosolic Ca2+ and pH buffering, showed that C‐7, C‐8, and C‐9 alcohols blocked completely and reversibly the electrical conductance of junctional channels. Furthermore, studies of single voltage‐clamped acinar cells revealed that the uncoupling alcohols did not affect the resting nonjunctional membrane conductances. Thus the alcohols that did not affect acinar cell coupling did not affect amylase secretion, whereas the alcohols that caused uncoupling increased secretion. The latter effect was not mediated by changes in the conductance of nonjunctional membrane, cytosolic Ca2+, and pH and, as revealed by an immunological hemolytic plaque assay for amylase, had a time course consistent with the rapid (within 1 min) inhibition of coupling. These data provide new support for the view that the regulation of cell‐to‐cell communications is correlated with that of digestive enzyme secretion.
An autopsied case of Creutzfeldt‐Jakob disease with the lateral geniculate body lesion showing antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses

We reported an necropsy finding of a patient with Creutzfeldt‐Jakob disease (CJD) who showed photo‐stimulated giant spikes that simultaneously suppressed periodic synchronous discharges (PSD) and the loss of pupillary light reflex during the course of the illness. The necropsy revealed extensive gray and white matter lesions, and both the lateral geniculate body (LGB) and pregeniculate body were primarily affected. The superior colliculus, optic nerve and tracts were not affected. The cerebral cortices particularly of the occipital lobe were severely damaged. The Gennari line, however, was spared from lesion. The primary involvement of the LGB has been reported infrequently in CJD, however, it appears to be associated with the unusual electroencephlograph (EEG) feature of the present case. The pregeniculate lesion contributed to the loss of pupillary reflex. This finding indicates that the visual pathway may be involved in the mechanism of the generation of PSD in CJD.
Predictors of stunting and thinness in post-menarcheal adolescent girls in rural Bangladesh

Abstract Objective To assess the nutritional status and risk factors of undernutrition in post-menarcheal girls in rural northern Bangladesh. Design Cross-sectional data on anthropometric measurements, dietary intake, work activity, morbidity and socio-economic status were collected from 12- to 19-year-old primigravidae (n 209) and never-pregnant adolescents (n 456) matched on age and time since menarche. Multiple regression analyses were conducted to determine predictors of stunting, thinness, upper-arm muscle (UAMZ) and fat area Z-scores (UAFZ) among the adolescent girls. Results A large proportion of adolescents (49 %) were stunted (height-for-age Z-score <−2) and underweight (40 %; weight-for-age Z-score <−2), but not thin (BMI-for-age <5th percentile; ∼10 %). The mean (sd) UAMZ and UAFZ of the adolescent girls was −0·3 (0·64) and −0·9 (0·40), respectively. Lean mass increased whereas fat mass declined with age. Both stunting and thinness were positively associated with age and time since menarche (P < 0·05). Young age (12–14 years) and literacy were protective against stunting among pregnant adolescents (OR = 0·29, 95 % CI 0·09, 0·88 and OR = 0·50, 95 % CI 0·26, 0·96, respectively). Having symptoms of diarrhoea or dysentery (OR = 7·40, 95 % CI 1·43, 38·29) predicted thinness and was associated with lower UAMZ and UAFZ among never-pregnant girls (both P < 0·05). Performing light-to-moderate activities was protective against thinness among never-pregnant girls (OR = 0·43, 95 % CI 0·22, 0·82), whereas pregnant adolescents who performed high levels of strenuous activities had greater UAMZ (P < 0·05). Conclusion Undernutrition was widespread among this post-menarcheal adolescent population. Younger and literate adolescents were less likely to be stunted, whereas thinness and body composition were associated with morbidity and work activity.
Histone sumoylation is associated with transcriptional repression

Histone proteins are subject to modifications, such as acetylation, methylation, phosphorylation, ubiquitination, glycosylation, and ADP ribosylation, some of which are known to play important roles in the regulation of chromatin structure and function. Here we report that histone H4 is modified by small ubiquitin-related modifier (SUMO) family proteins both in vivo and in vitro. H4 binds to the SUMO-conjugating enzyme (E2), UBC9, and can be sumoylated in an E1 (SUMO-activating enzyme)- and E2-dependent manner. We present evidence suggesting that histone sumoylation mediates gene silencing through recruitment of histone deacetylase and heterochromatin protein 1.
Functional Expression of a Recombinant Unitary Glutamate Receptor from Xenopus, Which Contains N-Methyl-D-aspartate (NMDA) and Non-NMDA Receptor Subunits*

A cDNA encoding a 100-kDa subunit (XenNR1) of the N-methyl-D-aspartate (NMDA) glutamate receptor type has been cloned from Xenopus central nervous system. When XenNR1 is coexpressed in a mammalian cell line with a recently cloned 51-kDa non-NMDA receptor subunit (XenU1), also from Xenopus, it forms a functional unitary receptor exhibiting the pharmacological properties characteristic of both NMDA and non-NMDA receptors. Firstly, XenU1 can replace NR2 subunits, in complementing XenNR1 to introduce the ligand binding properties of a complete NMDA receptor. Second, responses to both NMDA and non-NMDA receptor agonists and antagonists were obtained in patch-clamp recordings from the cotransfected cells, but no significant responses were recorded when the cells were singly transfected. Third, from solubilized cell membranes from the cotransfected cells, an antibody to the NR1 subunit coprecipitated the binding sites of the non-NMDA receptor subunit. The unitary glutamate receptor has a unique set of properties that denote intersubunit interaction, including a glycine requirement for the responses to non-NMDA as well as to NMDA receptor agonists and voltage-dependent block by Mg2+ of the non-NMDA agonist responses.
Episodic Memories and Their Relevance for Psychoactive Drug Use and Addiction

The majority of adult people in western societies regularly consume psychoactive drugs. While this consumption is integrated in everyday life activities and controlled in most consumers, it may escalate and result in drug addiction. Non-addicted drug use requires the systematic establishment of highly organized behaviors, such as drug-seeking and -taking. While a significant role for classical and instrumental learning processes is well established in drug use and abuse, declarative drug memories have largely been neglected in research. Episodic memories are an important part of the declarative memories. Here a role of episodic drug memories in the establishment of non-addicted drug use and its transition to addiction is suggested. In relation to psychoactive drug consumption, episodic drug memories are formed when a person prepares for consumption, when the drug is consumed and, most important, when acute effects, withdrawal, craving, and relapse are experienced. Episodic drug memories are one-trial memories with emotional components that can be much stronger than “normal” episodic memories. Their establishment coincides with drug-induced neuronal activation and plasticity. These memories may be highly extinction resistant and influence psychoactive drug consumption, in particular during initial establishment and at the transition to “drug instrumentalization. ” In that, understanding how addictive drugs interact with episodic memory circuits in the brain may provide crucial information for how drug use and addiction are established.
Study V: Children's Interview for Psychiatric Syndromes (ChIPS): psychometrics in two community samples.

OBJECTIVE To determine sensitivity and specificity of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) revised Children's Interview for Psychiatric Syndromes (ChIPS) in nonclinical samples. METHOD Participants were 40 children 6 to 18 years of age from a community sample (n = 22) or a bereaved sample 1 to 2 years following the death of a parent (n = 18). ChIPS and the Diagnostic Interview for Children and Adolescents (DICA-R-C) were administered in a Latin Square design. A consensus conference (CC) of child psychopathology experts determined presence or absence of syndromes or symptoms after reviewing assessment materials not including ChIPS. RESULTS Sensitivity is commensurate with epidemiologic base rates (17.5% of participants endorsed at least one syndrome). Low base rate kappas and percentage agreement were calculated to determine agreement on symptom or syndrome endorsement for 20 disorders. For syndrome analyses, over half the kappas could not be calculated due to 100% agreement on absence. For symptom analyses, 3 of 20 kappas could not be calculated (100% agreement on absence). Eleven of ChIPS/DICA-R-C symptom kappas were significant (p < 0.04), 2 of 17 had 95% agreement (kappas, p < 0.08), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). Thirteen of 17 ChIPS/CC symptom kappas were significant (p < 0.04), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). CONCLUSION ChIPS' psychometrics in nonclinical samples compares favorably with that of other structured interviews.
Clinical and Financial Benefits of Rapid Detection of Respiratory Viruses: an Outcomes Study

ABSTRACT To assess the expected benefits of rapid reporting of respiratory viruses, we compared patients whose samples were processed using standard techniques such as enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to patients whose samples were processed with the same standard techniques in addition to immunofluorescent testing (FA) directly on cytocentrifuged samples (year 2). The cytospin FA screened for influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO Diagnostics Ltd.). The specificity of the cytospin FA for all viruses was 100%. The sensitivities for influenza A virus and RSV were 90 and 98%, respectively, but the sensitivities for influenza B virus and adenovirus were unacceptable (14.3 and 0%, respectively). However, since the former viruses account for >85% of our isolates from clinical specimens, the cytospin FA is an excellent screening test since the positive result was available within hours. The mean turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in year 2 (P = 0.001). This rapid reporting resulted in physicians having access to information sooner, enabling more appropriate treatment. The mean length of stay in the hospital for inpatients with respiratory viral isolates was 10.6 days for year 1 versus 5.3 days for year 2. Mean variable costs for these patients was $7,893 in year 1 and $2,177 in year 2. After subtracting reagent costs and technological time, the savings in variable costs was $144,332/year. Summarizing, the cytospin FA markedly decreased turnaround time and was associated with decreased mortality, length of stay, and costs and with better antibiotic stewardship.
Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells

Significance Dendritic cells (DCs) are pivotal for immune responses as they present antigens to T cells. Different DC subsets have different functions and are associated with different diseases. For example, plasmacytoid DCs (pDCs) produce type 1 interferons and are associated with the autoimmune disease, systemic lupus erythematosus. Understanding control of survival/apoptosis in different DC subsets may not only provide a molecular basis for their homeostasis but also guide therapeutic intervention of immunopathology. We revealed that two major DC subsets (pDCs and conventional DCs) express distinct BCL-2 family proteins at different levels and this correlated with their survival requirements. Accordingly, clinically applicable antagonist drugs killed the appropriate DC subsets, informing on the future use of these compounds for treating immune-mediated damage. Dendritic cells (DCs) are heterogeneous, comprising subsets with functional specializations that play distinct roles in immunity as well as immunopathology. We investigated the molecular control of cell survival of two main DC subsets: plasmacytoid DCs (pDCs) and conventional DCs (cDCs) and their dependence on individual antiapoptotic BCL-2 family members. Compared with cDCs, pDCs had higher expression of BCL-2, lower A1, and similar levels of MCL-1 and BCL-XL. Transgenic overexpression of BCL-2 increased the pDC pool size in vivo with only minor impact on cDCs. With a view to immune intervention, we tested BCL-2 inhibitors and found that ABT-199 (the BCL-2 specific inhibitor) selectively killed pDCs but not cDCs. Conversely, genetic knockdown of A1 profoundly reduced the proportion of cDCs but not pDCs. We also found that conditional ablation of MCL-1 significantly reduced the size of both DC populations in mice and impeded DC-mediated immune responses. Thus, we revealed that the two DC types have different cell survival requirements. The molecular basis of survival of different DC subsets thus advocates the antagonism of selective BCL-2 family members for treating diseases pertaining to distinct DC subsets.