[What to do with a sleepy patient treated with CPAP].
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Biomedical subjects
Publications and source records attributed to J Krieger.
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Four recombinant odorant-binding proteins of Bombyx mori, pheromone-binding protein (PBP), general odorant-binding protein 1 (GOBP1), general odorant-binding protein 2 (GOBP2) and antennal binding protein X (ABPX), were expressed in E. coli and used to raise polyclonal antisera. Immunoblots of antennal homogenates showed that these antisera were specific. In Western blot analysis and immunocytochemical labelling experiments, the sera against recombinant PBP and GOBP2 of B. mori gave identical results as sera against native PBP and GOBP2 of Antheraea polyphemus, respectively, thus confirming earlier results obtained with the latter. Labelling consecutive cross sections of various sensillum types with all four antisera revealed different labelling patterns in male and female sensilla (s.) trichodea and s. basiconica. Long s. trichodea in males and females represented uniform labelling types, whereas for short s. trichodea, s. intermedia, and s. basiconica a great variety of labelling patterns was observed, some being more common than others. Long s. trichodea, which in males are uniformly tuned to the pheromone components bombykol and bombykal, all strongly expressed PBP; labelling with antisera against the other three odorant-binding proteins hardly was above background, only in some hairs GOBP1 was expressed somewhat more strongly. Long s. trichodea of females, which respond specifically to linalool and benzoic acid, showed a different labelling pattern. Here, we observed strong labelling with antibodies against GOBP2 and medium labelling with anti-GOBP1, sometimes with anti-ABPX. S. basiconica in both sexes most commonly co-expressed GOBP1 and GOBP2, but other patterns were occasionally found, with some of them showing PBP expression, also in females. The great variety of labelling types in short s. trichodea, s. intermedia, and s. basiconica suggests a similar variety of functional subtypes as observed in plant odour-sensitive sensilla of other moth species.
The remarkable responsiveness of male moths to female released pheromones is based on the extremely sensitive and selective reaction of highly specialized sensory cells in the male antennae. These cells are supposed to be equipped with male-specific receptors for pheromonal compounds, however, the nature of these receptors is still elusive. By using a combination of genomic sequence analysis and cDNA-library screening, we have cloned various cDNAs of the tobacco budworm Heliothis virescens encoding candidate olfactory receptors. A comparison of all identified receptor types not only highlighted their overall high degree of sequence diversity but also led to the identification of a small group of receptors sharing >40% identity. In RT-PCR analysis it was found that distinct members of this group were expressed exclusively in the antennae of male moths. In situ hybridization experiments revealed that the male-specific expression of these receptor types was confined to antennal cells located beneath sensillar hair structures (sensilla triochoidea), which have been shown to contain pheromone-sensitive neurons. Moreover, two-color double in situ-hybridization approaches uncovered that cells expressing one of these receptor types were surrounded by cells expressing pheromone-binding proteins, as expected for a pheromone-sensitive sensillum. These findings suggest that receptors like Heliothis receptor 14-16 (HR14-HR16) may render antennal cells responsive to pheromones.
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Candidate olfactory receptors of the moth Heliothis virescens were found to be extremely diverse from receptors of the fruitfly Drosophila melanogaster and the mosquito Anopheles gambiae, but there is one exception. The moth receptor type HR2 shares a rather high degree of sequence identity with one olfactory receptor type both from Drosophila (Dor83b) and from Anopheles (AgamGPRor7); moreover, in contrast to all other receptors, this unique receptor type is expressed in numerous antennal neurons. Here we describe the identification of HR2 homologues in two further lepidopteran species, the moths Antheraea pernyi and Bombyx mori, which share 86-88% of their amino acids. In addition, based on RT-PCR experiments HR2 homologues were discovered in antennal cDNA of the honey bee (Apis mellifera; Hymenoptera), the blowfly (Calliphora erythrocephala; Diptera) and the mealworm (Tenebrio molitor; Coleoptera). Comparison of all HR2-related receptors revealed a high degree of sequence conservation across insect orders. In situ hybridization of antennal sections from the bee and the blowfly support the notion that HR2-related receptors are generally expressed in a very large number of antennal cells. This, together with the high degree of conservation suggests that this unique receptor subtype may fulfill a special function in chemosensory neurons of insects.
OBJECTIVE AND DESIGN: We have explored the in vitro immunomodulatory effects of pure ruthenium red and a series of pyridine and imidazole substituted ruthenium complexes (RCs). MATERIAL: Human peripheral blood lymphocytes and purified T cells were used in these studies along with various cell lines. METHODS: Cells were treated with dilutions of RCs and assessed in various assays of immune function, cytotoxicity and cell cycle progression. RESULTS: RCs efficiently blocked T cell receptor (TCR)-mediated stimulation (IC(50)'s in the low nM range) of human peripheral blood lymphocytes (hPBL) by various agents, including tetanus toxoid, alloantigens, superantigens, and receptor-specific antibodies. RCs are not cytotoxic to T cells. Antiproliferative activity was also observed for B cells. Some non-lymphoid cell lines or primary cultures showed sensitivity to the RCs, but only at higher concentrations. The inhibitory effect on human T cells was assessed and demonstrated at the level of proliferation (DNA synthesis), IL-2 secretion, and IL-2 receptor (CD25) upregulation. RCs also inhibited IL-2-mediated proliferation of antigen-induced T-cell blasts and the IL-2-dependent T cell line Kit-225. Cell cycle analysis indicates that RCs inhibit the progression of activated T cells from G(0)/G(1) to S phase. CONCLUSIONS: Since the mechanism of T cell inhibition by RCs appears to be different than that of rapamycin (RAP) or cyclosporin A (CsA), they may provide a new tool to investigate intracellular signaling in T cells, and may present novel opportunities for immunosuppression
The respiratory disorders expressed by obstructive hypopneas and apneas during sleep, as well as the sequences of crescendo in respiratory effort without hypopneas or apneas which define the upper airway resistance syndrome, terminate with (thanks to) an arousal, defined by EEG changes. In some cases, the activation of the central nervous system is restricted to a sympathetic activation, which has been mainly studied in the cardiovascular area, and is not always accompanied by a cortical arousal. Various approaches (heart rate, blood pressure, pulse transit time, peripheral arterial tonometry) make the identification of sympathetic activation possible. Sympathetic activation seems to be more sensitive than cortical arousal to the stimulations generated by the respiratory system via an activation of mechanoreceptors stimulated by the increased respiratory effort in response to total or partial occlusion of the upper airway. The mechanisms of the cortical or autonomic arousal are not fully understood, but their detection could be a diagnostic tool for the identification of such disorders. Such tools are currently under validation.
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UNLABELLED: We investigated the effect of adapted management of sleep on the duration and quality of sleep in shift workers working the night shift. Twenty-nine shift workers suffering from insomnia were included and treated with zopiclone (7.5mg/day) or placebo according to a random double-blind protocol. Patients completed a sleep diary and a wrist actigraph was used to evaluate episodes of rest/activity. A self-administered subjective sleep questionnaire was filled out just after awakening. Zopicone was found to increase the duration of sleep significantly (p<0.05) over the baseline duration after the first and second night on duty. Subjective estimation of sleep was better in patients taking zopiclone who exhibited a smaller number of shorter awakening episodes. IN CONCLUSION: zopiclone improves the quality and duration of sleep in shift workers suffering from insomnia.
Analyzing the chemosensory organs of the moth Heliothis virescens, three proteins belonging to the family of insect chemosensory proteins (CSPs) have been cloned; they are called HvirCSP1, HvirCSP2 and HvirCSP3. The HvirCSPs show about 50% identity between each other and 30-76% identity to CSPs from other species. Overall, they are rather hydrophilic proteins but include a conserved hydrophobic motif. Tissue distribution and temporal expression pattern during the last pupal stages were assessed by Northern blots. HvirCSP mRNAs were detected in various parts of the adult body with a particular high expression level in legs. The expression of HvirCSP1 in legs started early during adult development, in parallel with the appearance of the cuticle. HvirCSP1 mRNA was detectable five days before eclosion (day E-5), increased dramatically on day E-3 and remained at high level into adult life. The tissue distribution and the time course of appearance of HvirCSPs are in agreement with a possible role in contact chemosensation.
Myelin oligodendrocyte glycoprotein (MOG) has attracted considerable attention due to its possible role in multiple sclerosis (MS). Previous studies have shown that MOG-reactive T cells are more commonly detected in MS patients than controls. In this report, we studied human MOG-reactive T cell clones generated from healthy individuals as well as MS patients. Our results indicate that immunoaffinity-purified MOG, which was routinely used in prior studies, is contaminated by anti-MOG antibody (mouse IgG), despite the inability to detect IgG by Western blotting. Here, we used continuous SDS-PAGE, which enabled us to isolate highly purified MOG devoid of contaminating mouse IgG.
Stable associations of more than one species of symbiont within a single host cell or tissue are assumed to be rare in metazoans because competition for space and resources between symbionts can be detrimental to the host. In animals with multiple endosymbionts, such as mussels from deep-sea hydrothermal vents and reef-building corals, the costs of competition between the symbionts are outweighed by the ecological and physiological flexibility gained by the hosts. A further option for the coexistence of multiple symbionts within a host is if these benefit directly from one another, but such symbioses have not been previously described. Here we show that in the gutless marine oligochaete Olavius algarvensis, endosymbiotic sulphate-reducing bacteria produce sulphide that can serve as an energy source for sulphide-oxidizing symbionts of the host. Thus, these symbionts do not compete for resources but rather share a mutalistic relationship with each other in an endosymbiotic sulphur cycle, in addition to their symbiotic relationship with the oligochaete host.
Immunologic data supporting immediate antiretroviral therapy in primary human immunodeficiency virus type 1 (HIV-1) infection are emerging; however, clinical benefit has not been demonstrated. The clinical and virologic course of 47 patients who were enrolled from September 1993 through June 1996 and who were not initially treated with potent therapy was compared with the course of 20 patients who immediately began therapy with zidovudine, lamivudine, and indinavir. Demographic and baseline laboratory data were comparable. During 78 weeks of follow-up, the early-treatment cohort showed a reduced frequency of opportunistic infections (5% vs. 21.3%; relative risk, 0.11; P=.02), less frequent progression to AIDS (13% vs. 0%), and significantly less frequent nonopportunistic mucocutaneous disorders and respiratory infections (P<.01). Plasma HIV-1 RNA levels were <50 copies/mL in all patients who continued therapy; however, after 9--12 months, HIV-1 remained detectable in latently infected CD4(+) T cells and in lymph node mononuclear cells. Combination antiretroviral therapy during primary HIV-1 infection demonstrated a decreased frequency of minor opportunistic infections, mucocutaneous disorders, and respiratory infections and reduced progression to AIDS.
Pheromone-binding proteins (PBPs), located in the sensillum lymph of pheromone-responsive antennal hairs, are thought to transport the hydrophobic pheromones to the chemosensory membranes of olfactory neurons. It is currently unclear what role PBPs may play in the recognition and discrimination of species-specific pheromones. We have investigated the binding properties and specificity of PBPs from Mamestra brassicae (MbraPBP1), Antheraea polyphemus (ApolPBP1), Bombyx mori (BmorPBP), and a hexa-mutant of MbraPBP1 (Mbra1-M6), mutated at residues of the internal cavity to mimic that of BmorPBP, using the fluorescence probe 1-aminoanthracene (AMA). AMA binds to MbraPBP1 and ApolPBP1, however, no binding was observed with either BmorPBP or Mbra1-M6. The latter result indicates that relatively limited modifications to the PBP cavity actually interfere with AMA binding, suggesting that AMA binds in the internal cavity. Several pheromones are able to displace AMA from the MbraPBP1- and ApolPBP1-binding sites, without, however, any evidence of specificity for their physiologically relevant pheromones. Moreover, some fatty acids are also able to compete with AMA binding. These findings bring into doubt the currently held belief that all PBPs are specifically tuned to distinct pheromonal compounds.
Current models suggest that during human immunodeficiency virus type 1 (HIV-1) transmission virions are selected that use the CCR5 chemokine receptor on macrophages and/or dendritic cells. A gradual evolution to CXCR4 chemokine receptor use causes a shift in the proportion of productively infected cells to the CD4 cell population. Productively infected cells during acute and early infection in lymphoid tissue were assessed, as well as the impact of productive infection on the T cell population in 21 persons who had biopsies performed on days 2-280 after symptoms of acute HIV-1 seroconversion. Even in the earliest stages of infection, most productively infected cells were T lymphocytes. There were sufficient infected cells in lymphoid tissue (LT) to account for virus production and virus load in plasma. Despite the relatively high frequency of productively infected cells in LT, the impact on the size of the T cell population in LT at this stage was minor.
BACKGROUND: We conducted a cost-effectiveness analysis as part of a randomized, controlled trial of a community-based outreach initiative to promote the pneumococcal and influenza vaccines for people aged 65 years or older. METHODS: The analysis was based on primary data from the trial on the increase in vaccination rates and cost of the intervention, and published estimates of the effectiveness of the vaccines and cost of treatment. We performed partial stochastic analyses based on the confidence intervals (CIs) of the effectiveness of the intervention and of the vaccines. RESULTS: The cost-effectiveness ratio of the combined-outreach initiative as implemented was $35 486 per quality-adjusted life-year (QALY), whereas it was $53 547 per QALY for the pneumococcal vaccine and $130 908 per QALY for the influenza vaccine. In partial stochastic analyses, the quasi-CI of the combined-outreach initiative ranged from $15 145 to $152 311 per QALY. The cost-effectiveness ratio of the intervention targeted to people who had never received the pneumococcal vaccine or who had not received the influenza vaccine in the previous year was $11 771 per QALY, with a quasi-CI of $3330 to $46 095 per QALY. With the use of the projected cost of replicating the intervention, the cost-effectiveness ratio was $26 512 per QALY for the initiative as implemented and $7843 per QALY for a targeted initiative. CONCLUSIONS: The community-based outreach initiative to promote the pneumococcal and influenza vaccines was reasonably cost-effective. Further improvements in cost-effectiveness could be made by targeting the initiative or through lessons learned during the first year that would reduce the cost of the initiative in subsequent years.
SNMP1-Apol is an antennal-specific protein of the wild silk moth Antheraea polyphemus; the protein is abundantly expressed and localized to the receptor membranes of sex-pheromone specific olfactory sensory neurons (OSNs). SNMP1-Apol is thought to function in odor detection based on its olfactory-specific expression, localization within OSNs, developmental time of expression, and apparent homology to the CD36 family of membrane-bound receptor proteins. In the current study, SNMP1-Apol homologues were identified from the moths Bombyx mori, Heliothis virescens, and Manduca sexta. These species posses antennal mRNAs encoding proteins with amino acid sequence identities ranging from 75-80%; these proteins are collectively designated SNMP1. A second M. sexta SNMP homologue, previously identified and partially sequenced [Robertson et al.: Insect Mol Biol 8:501-518, 1999] was fully sequenced and characterized. The encoded protein shares only 26-27% sequence identity with the SNMP1 proteins, and is thus designated SNMP2-Msex. The SNMP sequences were used to identify 14 and four possible homologues in Drosophila melanogaster and Caenorhabditis elegans genome databases, respectively; thus, greatly expanding CD36 family membership among the invertebrate lineages. Despite their sequence difference, SNMP1-Msex and SNMP2-Msex expression is localized to OSNs and occurs simultaneously with the onset of olfactory function. These findings suggest that SNMPs play a central role in odor detection in insects, and that the CD36 gene family is widely represented among animal phyla. The SNMPs are the only identified neuronal members of the CD36 family, and as such expand the activities of this gene family into roles influencing brain function and behavioral action.
Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.