Miracle-dz/UniFAR-FTUs huggingface dataset:
A role for natural antibody in the pathogenesis of leprosy: antibody in nonimmune serum mediates C3 fixation to the Mycobacterium leprae surface and hence phagocytosis by human mononuclear phagocytes

We have previously determined that complement receptors on human mononuclear phagocytes and complement component C3 in nonimmune serum mediate phagocytosis of the intracellular bacterial pathogen Mycobacterium leprae, the agent of leprosy. We have also determined that C3 fixes selectively to the major surface glycolipid of M. leprae, phenolic glycolipid 1 (PGL-1). In this study, we have explored the role of natural antibody in nonimmune serum in C3 fixation and C1q binding to M. leprae and PGL-1. At serum concentrations within the range at which phagocytosis of M. leprae is maximal, C3 fixation was mediated by both the classical and the alternative complement pathways. At the low end of this serum concentration range (2.5%), C3 fixation was mediated predominantly by the classical pathway. Consistent with a role for both pathways, C3 fixation to M. leprae was enhanced by the addition of either pure C1q to C1q-depleted serum or pure factor B to factor B-depleted serum. C3 fixation to M. leprae was strictly antibody dependent regardless of the serum concentration used. C3 fixation to M. leprae occurred in nonimmune serum but not in agammaglobulinemic serum unless heat-inactivated nonimmune serum or small amounts of pure immunoglobulin G (IgG) or IgM were added. C3 fixation by both the alternative and the classical complement pathways was mediated by antibody, and the antigen-binding portion of the antibody molecule was required. C3, IgG, IgM, and C1q were readily detected on the surface of M. leprae. Consistent with the previously demonstrated exclusive role of the classical complement pathway in C3 fixation to PGL-1, C1q bound to PGL-1 in a dose-dependent fashion; C1q binding was evident in > 1.25% nonimmune serum. C1q binding to PGL-1 was strictly antibody dependent. When PGL-1 was incubated with pure C1q, little or no C1q bound to PGL-1 unless heat-inactivated nonimmune serum or pure IgG or IgM was added. When PGL-1 was incubated in nonimmune serum, C3 bound directly to PGL-1 and not to anti-PGL-1 antibody, since the amount of C3 bound to PGL-1 was not reduced by acid elution of the antibody. However, the amount of C3 bound to PGL-1 was markedly reduced by hydroxylamine treatment, providing evidence for C3 fixation via a covalent ester bond. Nonimmune serum contained antibody to all four major M. leprae surface carbohydrates. Relative to PGL-1, nonimmune serum contained more antibody to the other surface carbohydrates. (ABSTRACT TRUNCATED AT 400 WORDS)
The microbial association of Greek taverna sausage stored at 4 and 10 °C in air, vacuum or 100% carbon dioxide, and its spoilage potential

J. SAMELIS and K.G. GEORGIADOU.2000. Strains of the Lactobacillus sakei/curvatus group, mainly non‐slime‐producing Lact. sakei, dominated the microbial flora of industrially manufactured taverna sausage, a traditional Greek cooked meat, stored at 4 °C and 10 °C in air, vacuum and 100% CO2. Atypical, arginine‐positive and melibiose‐negative strains of this group were isolated. The isolation frequency of Lact. sakei/curvatus from sausages stored anaerobically was as high as 92–96%, while other meat spoilage organisms were practically absent. Conversely, in air‐stored sausages, leuconostocs, mainly Leuconostoc mesenteroides ssp. mesenteroides, had a considerable presence (14–21%), whereas Brochothrix thermosphacta, pseudomonads and Micrococcaceae grew, but failed to increase above 105 cfu g−1 in all samples during storage. Only yeasts were able to compete against LAB and reached almost 107 cfu g−1 after 30 d of aerobic storage at 10 °C. The great dominance (> 108 cfu g−1) of LAB caused a progressive decrease of pH and an increase of the concentration of l‐lactate, d‐lactate and acetate in all sausage packs. The growth of LAB and its associated chemical changes were more pronounced at 10 °C than 4 °C. At both storage temperatures, l‐lactate and acetate increased more rapidly and to a higher concentration aerobically, unlike d‐lactate, which formed in higher amounts anaerobically. Storage in air was the worst packaging method, resulting in greening and unpleasant off‐odours associated with the high acetate content of the sausages. Carbon dioxide had no significant effect on extending shelf‐life. The factors affecting the natural selection of Lact. sakei/curvatus in taverna sausage are discussed. Moreover, it was attempted to correlate the metabolic activity of this group with the physicochemical changes and the spoilage phenomena occurring in taverna sausage under the different storage conditions.
Health risk assessment of cadmium via dietary intake by adults in China.

BACKGROUND Cadmium in the human diet constitutes a potential chronic hazard to health. The objective of this study was to make a health risk assessment of dietary cadmium intake by adults in the 31 provinces (excluding Hong Kong, Taiwan and Macau) of China. RESULTS The cadmium levels in a total of 2629 individual food samples ranged from not detected (below the limit of detection) to 17.32 mg kg⁻¹, with the highest concentration being found in an offal sample. The food group 'meat' showed the highest mean level of 0.129 mg kg⁻¹, while the lowest concentration of 8.0×10⁻⁴ mg kg⁻¹ was measured in the food group 'fruit'. The mean cadmium intakes, hazard quotients and annual excess lifetime cancer risks for national, northern and southern adult populations in China were 3.67 μg kg⁻¹ body weight (BW) week⁻¹, 0.52 and 4.56×10⁻⁵ a⁻¹, 2.63 μg kg⁻¹ BW week⁻¹, 0.38 and 3.27×10⁻⁵ a⁻¹ and 4.56 μg kg⁻¹ BW week⁻¹, 0.65 and 5.67×10⁻⁵ a⁻¹ respectively. CONCLUSION The results of risk characterization for the national adult population were lower than safety risk levels of hazard quotient and annual excess lifetime cancer risk (5×10⁻⁵ a⁻¹). The mean annual excess lifetime cancer risk for the southern adult population was higher than the safety risk level. Therefore the carcinogenic risk for the southern population is of concern.
Seeing is believing: How the MIP-luc mouse can advance the field of islet transplantation and β-cell regeneration

In the last five years, bioluminescence has emerged as a vital tool in the non-invasive quantification of beta-cell mass following islet transplantation in murine models. The successes achieved in bioluminescence imaging in islet transplantation has prompted its use in the discipline of beta-cell regeneration. Employing bioluminescence permits quantifying changes in β-cell mass in an individual mouse over time, which can provide valuable insights into the kinetics of beta-cell regeneration.
Oxidant regulated inter-subunit disulfide bond formation between ASIC1a subunits

The acid-sensing ion channel-1a (ASIC1a) is composed of 3 subunits and is activated by a decrease in extracellular pH. It plays an important role in diseases associated with a reduced pH and production of oxidants. Previous work showed that oxidants reduce ASIC1a currents. However, the effects on channel structure and composition are unknown. We found that ASIC1a formed inter-subunit disulfide bonds and the oxidant H2O2 increased this link between subunits. Cys-495 in the ASIC1a C terminus was particularly important for inter-subunit disulfide bond formation, although other C-terminal cysteines contributed. Inter-subunit disulfide bonds also produced some ASIC1a complexes larger than trimers. Inter-subunit disulfide bond formation reduced the proportion of ASIC1a located on the cell surface and contributed to the H2O2-induced decrease in H+-gated current. These results indicate that channel function is controlled by disulfide bond formation between intracellular residues on distinct ASIC1a subunits. They also suggest a mechanism by which the redox state can dynamically regulate membrane protein activity by forming intracellular bridges.
Identification and Characterization of the Hemophore-Dependent Heme Acquisition System of Yersinia pestis

ABSTRACT Yersinia pestis possesses a heme-protein acquisition system (Hmu) that allows it to utilize heme and heme-protein complexes as the sole sources of iron. Analysis of the Y. pestisCO92 genomic sequence revealed a second heme-protein acquisition gene cluster that shares homology with the hemophore-dependent heme acquisition system (Has system) of Serratia marcescens. This locus consisted of thehasRyp receptor gene, thehasAyp hemophore gene, and genes encoding components of the HasAyp dedicated ABC transporter factor (hasDEyp), as well as atonB homologue (hasByp). By using a reconstituted secretion system in Escherichia coli, we showed that HasAyp is a secreted heme-binding protein and that expression of HasAyp is iron regulated in E. coli. The use of a transcriptional reporter fusion showed that the hasRADEB promoter is Fur regulated and has increased activity at 37°C. Hemoglobin utilization via the Hasyp system was studied with both E. coli and Y. pestis, for which hasand has hmu mutant strains were used. No contribution of the Has system to heme utilization was observed in either E. coli or Y. pestis under the conditions we tested. Previously it was shown that a deletion of the Hmu system had no effect on the virulence of Y. pestis in a mouse model of bubonic plague. An Hmu− Has− double mutant also retained full virulence in this model of infection. This report constitutes the first attempt to investigate the contribution of the hemophore-dependent heme acquisition system in bacterial pathogenicity.
Strategic Responses to Used Goods Markets: Airbus and Boeing

This paper examines the relationship between innovation, production, and used-good markets, then evaluates government subsidies to Airbus and Boeing, which have recently been ruled illegal by the WTO. This research sheds new light on the crucial role of innovation as a competitive tool against used-good markets. Moreover, this paper shows that a production or RD in the aircraft manufacturing industry, a production subsidy reduction has a bigger negative impact on innovation than subsidy reduction in research and development. Finally, this paper nds that, though it reduces innovation and production, the cut in the government subsidies has a minor eect on consumer welfare due to the presence of active used-goods markets.
Novel therapies for the prevention of stroke

The health and economic burden of stroke to society is enormous. Pharmacological therapies remain the primary stroke prevention strategy for the vast majority. Several existing and newer pharmacological agents aimed at the treatment of hypertension and lowering cholesterol are proving to be effective. For example, the antiplatelet agent clopidogrel has reduced end points in the secondary prevention of stroke, as have combinations of aspirin with traditional therapies, including dipyramidole. The direct oral thrombin inhibitor ximelagatran is a novel oral anticoagulant that has shown significant potential as a possible replacement to warfarin therapy, for the prevention of stroke for patients with non-valvular atrial fibrillation. Additional novel agents with hypothetical, although not yet proven, benefits in stroke prevention include fish oils, homocysteine-lowering therapy and anti-inflammatory agents. Finally, a controversial novel polypill, which would include fixed combinations of several pharmacological agents, may yet become a realistic and promising stroke prevention option.
Reliability and Predictive Validity of the Ohio State University TBI Identification Method With Prisoners

ObjectivesEvaluate the psychometric properties of indices of lifetime exposure to traumatic brain injury (TBI) among prisoners. ParticipantsConvenience samples recruited from male (N = 105) and female (N = 105) state prison facilities. DesignAssess test/retest reliability and criterion-related validity. Primary MeasuresSummary indices of the number, severity, timing, and effects of lifetime exposure to TBI calculated from data elicited via a structured interview. ResultsTest/retest reliability ranged from acceptable to high. Factor analysis showed that indices of lifetime exposure could be characterized by (1) age of onset (especially childhood onset), (2) combinations of number and likely severity of injuries, and (3) number of symptoms and functional effects. Age at injury, number of TBIs with loss of consciousness, and symptoms persisting contributed independently to the prediction of common cognitive and behavioral consequences of TBI. ConclusionThese results provide further support for the reliability and validity of summary indices of lifetime exposure to TBI when elicited via a structured interview.
Prognostic significance of bone marrow micrometastases in patients with gastric cancer.

BACKGROUND Monoclonal antibodies (mabs) against components of the cytoskeleton such as cytokeratins allow single disseminated epithelial carcinoma cells to be detected in the bone marrow. The aim of this study was to examine the prognostic relevance of these cells in patients with gastric cancer and to evaluate by multivariate analysis their predictive value compared with conventional risk factors. PATIENTS AND METHODS A total of 1 x 10(6) cells from bone marrow aspirates were screened immunoctochemically for the presence and absolute number of disseminated tumor cells using mab CK2 to cytokeratin component no. 18. Patients were monitored prospectively for 30.6 +/- 15.2 months. RESULTS Between one and 122 CK2-positive cells per 1 million mononuclear bone marrow cells were present in 95 of 180 patients (53%). A similar prevalence of 51% was found in curatively operated patients (55 of 109). Comparison with conventional prognostic risk factors showed a correlation of cell dissemination with pathohistologic tumor (pT) stage (P = .07) and Bormann classification (P = .022). Tumor-cell content in the bone marrow predicted disease-free and overall survival in curatively resected patients (P = .007 and P = .049, respectively). Multivariate analysis, which included established risk factors, showed that extent of tumor-cell dissemination was an independent prognostic parameter for disease-free survival in T1/2 tumors (P = .014; relative risk [RR], 1.84; 95% confidence interval [CI], 1.35 to 2.52), in intestinal type carcinomas according to Laurén (P = .008; RR, 1.62; 95% CI, 1.23 to 2.12), and in patients without lymph node involvement (P = .004; RR, 2.43; 95% CI, 1.22 to 4.82). CONCLUSION Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.
Rapid induction of neutrophil apoptosis by sulfasalazine: implications of reactive oxygen species in the apoptotic process

Accumulating evidence indicates that neutrophils are crucially involved in the pathogenesis of inflammatory bowel diseases and rheumatoid arthritis. We therefore investigated the effect of sulfasalazine (SSZ), which is widely used in the treatment of these diseases, on neutrophil apoptosis in vitro. The apoptosis of neutrophils was determined by morphology, a DNA histogram of propidium iodide‐stained nuclei, and DNA fragmentation. SSZ rapidly accelerated the rate of spontaneous neutrophil apoptosis within clinically relevant concentrations. This effect is unique to neutrophils because other types of leukocytes and a number of leukocyte cell lines are resistant to SSZ. Neutrophil apoptosis caused by SSZ was abrogated by a tyrosine kinase inhibitor, a protein kinase A inhibitor, and antioxidants. The subsequent results provided pharmacological evidence that the phosphorylation of tyrosine kinase and protein kinase A and generation of reactive oxygen species are involved in SSZ‐mediated neutrophil apoptosis. These data suggest that SSZ‐induced neutrophil apoptosis may account, in part, for the clinical benefits of SSZ on inflammatory bowel diseases and rheumatoid arthritis. J. Leukoc. Biol. 62: 817–826; 1997.
Psychological function changes among maintenance house painters exposed to low levels of organic solvent mixtures

The adverse psychological effects of long‐term exposure to organic solvent mixtures were studied among 219 maintenance house painters. Their mean age was 42 years and the duration of exposure 22 years. 229 reinforcement workers of the same mean age served as a nonexposed reference group. The groups were also matched according to pre‐exposure intellectual level. The painters average exposure to white spirit was estimated to be 40 ppm. The maintenance house painters were characterized by defects in short‐term visual memory and prolonged simple reaction times. Some slight relationships were found between low test performances and various individual indices of long‐term exposure to solvents. The results implied that adverse psychological effects existed even though the exposure level was much lower than the hygienic standard applied for white spirit in many countries.
Different roles of the Mre11 complex in the DNA damage response in Aspergillus nidulans

The Mre11‐Rad50‐Nbs1 protein complex has emerged as a central player in the cellular DNA damage response. Mutations in scaANBS1, which encodes the apparent homologue of human Nbs1 in Aspergillus nidulans, inhibit growth in the presence of the anti‐topoisomerase I drug camptothecin. We have used the scaANBS1 cDNA as a bait in a yeast two‐hybrid screening and report the identification of the A. nidulans Mre11 homologue (mreA). The inactivated mreA strain was more sensitive to several DNA damaging and oxidative stress agents. Septation in A. nidulans is dependent not only on the uvsBATR gene, but also on the mre11 complex. scaANBS1 and mreA genes are both involved in the DNA replication checkpoint whereas mreA is specifically involved in the intra‐S‐phase checkpoint. ScaANBS1 also participates in G2‐M checkpoint control upon DNA damage caused by MMS. In addition, the scaANBS1 gene is also important for ascospore viability, whereas mreA is required for successful meiosis in A. nidulans. Consistent with this view, the Mre11 complex and the uvsCRAD51 gene are highly expressed at the mRNA level during the sexual development.
‘It's okay, it helps me to breathe’: the experience of home ventilation from a child's perspective

There are few studies that focus on children's subjective responses to home ventilation and how this in turn affects their daily lives. This multiple case study explored the experience of home ventilation from the children's perspective. Data were collected from five children through observation and audiotaped interviews. Children expressed their physical and emotional relationship with the ventilator, stating: ‘It's okay. It helps me to breathe’–a theme that had a number of distinct dimensions. Other themes included the medicalization of childhood, being a child and hopes for the future. Unlike other study findings to date, the children in this study concluded that the technology was only one small part of their lives. Nurses must ensure that these children have an opportunity to communicate their perspectives, in order to provide care that is clinically effective and childcentered.
MALE‐BIASED FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN DROSOPHILA MELANOGASTER

In populations with males and females, sexual selection may often represent a major component of overall selection. Sexual selection could act to eliminate deleterious alleles in concert with other forms of selection, thereby improving the fitness of sexual populations. Alternatively, the divergent reproductive strategies of the sexes could promote the maintenance of sexually antagonistic variation, causing sexual populations to be less fit. The net impact of sexual selection on fitness is not well understood, due in part to limited data on the sex‐specific effects of spontaneous mutations on total fitness. Using a set of mutation accumulation lines of Drosophila melanogaster, we found that mutations were deleterious in both sexes and had larger effects on fitness in males than in females. This pattern is expected to reduce the mutation load of sexual females and promote the maintenance of sexual reproduction.
Habituation of the psycho-galvanic reflex in patients with anxiety states and in normal subjects

Anxiety is a term which has had many meanings. It may refer to a commonly experienced emotion, to a personality variable, to a symptom accompanying physical or mental illness, or it may be a symptom occurring in relative isolation. Patients who complain primarily of feelings of fear or anxiety, occurring either continually or in attacks, without organic basis or any other marked psychiatric symptoms, may be referred to as suffering from anxiety states. In these patients, symptoms referable to the autonomic nervous system, such as palpitations and cold, clammy hands, are common. It has been postulated (Malmo, 1957, 1959) that patients with anxiety states are chronically 'overaroused'. The term 'level of arousal' is widely used by psychologists to refer to a hypothetical continuum ranging from sleep through normal waking to terror and anger. Much earlier, the similar term 'level of vigilance' was introduced by Sir Henry Head (1923) based on physiological observations. Head regarded the level of vigilance of any part of the central nervous system as reflecting its high-grade 'physiological efficiency', which could be lowered by sleep or chloroform thus lessening its efficiency of responsiveness. One of the most extensively used indices of the level of vigilance in man is the electrical resistance of the palmar skin which is dependent on sweat-gland activity (Lader and Montagu, 1962). Three aspects of the skin resistance are commonly studied: first, the background level, which is a measure of normal continuing sweat-gland activity; secondly, variations in the rate of sympathetic, sudomotor discharge result in 'spontaneous fluctuations' which can be counted; and thirdly, responses to specific external stimuli can be measured. Such responses are termed psycho-galvanic reflexes or galvanic skin responses. If identical, discrete stimuli are repeated, the psycho-galvanic reflex tends to diminish in size or 'habituate'. Also, the background levels may alter during a series of stimuli. Such a change in the direction of those levels obtaining before the stimuli started will be termed 'adaptation'. The purpose of the experiments to be described was to use a relatively simple stimulus situation to detect differences between patients with anxiety states and normal control subjects with respect to the various aspects of palmar resistance. We were especially interested in any differences in the mean rates of habituation between the two groups, as this relatively simple property of the central nervous system has not been extensively studied.