Showing papers by "University of Bern published in 1997"
TL;DR: Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1.
Abstract: Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago. Today, more than 30 human chemokines are known. They are often upregulated in inflammation and act mainly on leukocytes inducing migration and release responses. The present review deals largely with the new developments of the last three years. Several structural studies have shown that most chemokines form dimers. The dimers, however, dissociate upon dilution, and the monomers constitute the biologically active form. Chemokine activities are mediated by seven-transmembrane-domain, G protein coupled receptors, five of which were discovered in the past three years. The primary receptor-binding domain of all chemokines is near the NH2 terminus, and antagonists can be obtained by truncation or substitutions in this region. Major progress has been made in the understanding of chemokine actions on T lymphocytes that respond to several CC chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract ...
2,249 citations
TL;DR: Results indicate that this gene is responsible for the pathogenesis of APECED, a autosomal-recessive disorder that maps to human chromosome 21q22.3 and should facilitate the genetic diagnosis and potential treatment of the disease and enhance the general understanding of the mechanisms underlying autoimmune diseases.
Abstract: Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C-->T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A-->G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.
1,295 citations
TL;DR: A quasi-conservative tracer N*, defined as a linear combination of nitrate and phosphate, is proposed to investigate the distribution of nitrogen fixation and denitrification in the world oceans.
Abstract: A new quasi-conservative tracer N*, defined as a linear combination of nitrate and phosphate, is proposed to investigate the distribution of nitrogen fixation and denitrification in the world oceans. Spatial patterns of N* are determined in the different ocean basins using data from the Geochemical Ocean Sections Study (GEOSECS) cruises (1972–1978) and from eight additional cruises in the Atlantic Ocean. N* is low ( 2.0 µmol kg−1) indicative of prevailing nitrogen fixation are found in the thermocline of the tropical and subtropical North Atlantic and in the Mediterranean. This suggests that on a global scale these basins are acting as sources of fixed nitrogen, while the Indian Ocean and parts of the Pacific Ocean are acting as sinks. Nitrogen fixation is estimated in the North Atlantic Ocean (10°N–50°N) using the N* distribution along isopycnal surfaces and information about the water age. We calculate a fixation rate of 28 Tg N yr−1 which is about 3 times larger than the most recent global estimate. Our result is in line, however, with some recent suggestions that pelagic nitrogen fixation may be seriously underestimated. The implied flux of 0.072 mol N m−2 yr−1 is sufficient to meet all the nitrogen requirement of the estimated net community production in the mixed layer during summer at the Bermuda Atlantic Time-series Study (BATS) site in the northwestern Sargasso Sea. Extrapolation of our North Atlantic estimate to the global ocean suggests that the present-day budget of nitrogen in the ocean may be in approximate balance.
1,236 citations
TL;DR: It can be concluded that non-submerged ITI implants maintain success rates well above 90% in different clinical centers for observation periods up to 8 years indicating that the applied life table analysis is a reliable statistical method to evaluate the long-term prognosis of dental implants.
Abstract: In the present multi-center study. non-submerged ITI implants were prospectively followed to evaluate their long-term prognosis in fully and partially edentulous patients. In a total of 1003 patients, 2359 implants were consecutively inserted. Following a healing period of 3–6 months, the successfully integrated implants were restored with 393 removable and 758 fixed restorations. Subsequently, all consecutive implants were documented annually up to 8 years. At each examination, the clinical status of all implants was evaluated according to predefined criteria of success. Therefore, the data base allowed the evaluation of 8-year cumulative survival and success rates for 2359 implants. In addition, cumulative success rates were calculated for implant subgroups divided per implant type, implant length. and implant location. Furthermore, the actual 5-year survival and success rates could be determined for 488 implants. During the healing period, 13 implants did not successfully integrate, whereas 2346 implants fulfilled the predefined criteria of success. This corresponds with an early failure rate of 0.55%. During follow-up, 19 implants were classified as failures due to several reasons. In addition, 17 implants (= 0.8%) demonstrated at the last annual examination a suppurative periimplant infection. Including 127 drop out implants (= 5.4% drop out rate) into the calculation, the 8-year cumulative survival and success rates resulted in 96.7% and 93.3%, respectively. The analysis of implant subgroups showed slightly more favorable cumulative success rates for screw type implants (> 95%) compared to hollow-cylinder implants (91.3%). and clearly better success rates for mandibular implants (= 95%) when compared to maxillary implants (= 87%). The actual 5-year survival and success rates of 488 implants with 98.2% and 97.3%. respectively, were slightly better than the estimated 5-year cumulative survival and success rates of 2359 implants indicating that the applied life table analysis is a reliable statistical method to evaluate the long-term prognosis of dental implants. It can be concluded that non-submerged ITI implants maintain success rates well above 90% in different clinical centers for observation periods up to 8 years.
1,206 citations
TL;DR: English language bias may be introduced in reviews and meta-analyses if they include only trials reported in English if authors are more likely to report trials with statistically significant results in English than in German.
956 citations
TL;DR: The three‐dimensional structure of stromal cell‐derived factor‐1 was determined by NMR spectroscopy and the RFFESH formed a receptor binding site, which is proposed to be an important initial docking site of SDF‐1 with its receptor.
Abstract: The three‐dimensional structure of stromal cell‐derived factor‐1 (SDF‐1) was determined by NMR spectroscopy. SDF‐1 is a monomer with a disordered N‐terminal region (residues 1–8), and differs from other chemokines in the packing of the hydrophobic core and surface charge distribution. Results with analogs showed that the N‐terminal eight residues formed an important receptor binding site; however, only Lys‐1 and Pro‐2 were directly involved in receptor activation. Modification to Lys‐1 and/or Pro‐2 resulted in loss of activity, but generated potent SDF‐1 antagonists. Residues 12–17 of the loop region, which we term the RFFESH motif, unlike the N‐terminal region, were well defined in the SDF‐1 structure. The RFFESH formed a receptor binding site, which we propose to be an important initial docking site of SDF‐1 with its receptor. The ability of the SDF‐1 analogs to block HIV‐1 entry via CXCR4, which is a HIV‐1 coreceptor for the virus in addition to being the receptor for SDF‐1, correlated with their affinity for CXCR4. Activation of the receptor is not required for HIV‐1 inhibition.
753 citations
TL;DR: Inequalities in health favoured the higher income groups and were statistically significant in all countries, and were particularly high in the United States and the United Kingdom.
702 citations
TL;DR: In this article, a set of environmental variables relating to the physical limnology, geography, catchment characteristics, climate, and water chemistry were recorded or measured for each lake and the explanatory power of each of these predictor variables for the different biological data-sets was estimated by a series of canonical correspondence analyses (CCA) and the statistical significance of each model was assessed by Monte Carlo permutation tests.
Abstract: Diatom, chrysophyte cyst, benthic cladocera, planktonic cladocera, and chironomid assemblages were studied in the surface sediments of 68 small lakes along an altitudinal gradient from 300 to 2350 m in Switzerland. In addition, 43 environmental variables relating to the physical limnology, geography, catchment characteristics, climate, and water chemistry were recorded or measured for each lake. The explanatory power of each of these predictor variables for the different biological data-sets was estimated by a series of canonical correspondence analyses (CCA) and the statistical significance of each model was assessed by Monte Carlo permutation tests. A minimal set of environmental variables was found for each biological data-set by a forward-selection procedure within CCA. The unique, independent explanatory power of each set of environmental variables was estimated by a series of CCAs and partial CCAs. Inference models or transfer functions for mean summer (June, July, August) air temperature were developed for each biological data-set using weighted-averaging partial least squares or partial least squares. The final transfer functions, after data screening, have root mean squared errors of prediction, as assessed by leave-one-out cross-validation, of 1.37 °C (chironomids), 1.60 °C (benthic cladocera), 1.62 °C (diatoms), 1.77 °C (planktonic cladocera), and 2.23 °C (chrysophyte cysts).
640 citations
TL;DR: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality in Switzerland.
Abstract: OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.
634 citations
TL;DR: These findings, as evaluated by non-decalcified histology under unloaded conditions, demonstrate that crestal bone changes occur during the early phase of healing after implant placement, and are dependent on the surface characteristics of the implant and the presence/absence of an interface.
Abstract: Background: Today, implants are placed using both non-submerged and submerged approaches, and in 1- and 2-piece configurations. Previous work has demonstrated that peri-implant crestal bone reactions differ radiographically under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of the interface (microgap) between the implant and abutment/restoration in 2-piece configurations. The purpose of this investigation was to examine histometrically crestal bone changes around unloaded non-submerged and submerged 1- and 2-piece titanium implants in a side-by-side comparison. Methods: A total of 59 titanium implants were randomly placed in edentulous mandibular areas of 5 foxhounds, forming 6 different implant subgroups (types A-F). In general, all implants had a relatively smooth, machined coronal portion as well as a rough, sandblasted and acid-etched (SLA) apical portion. Implant types A-C were placed in a non-submerged approach, while types D-F were inser...
620 citations
TL;DR: The Cosmic Ray on Micro-Electronics (CREME) as mentioned in this paper is a suite of programs for creating numerical models of the ionizing-radiation environment in near-Earth orbits and for evaluating radiation effects in spacecraft.
Abstract: CREME96 is an update of the Cosmic Ray on Micro-Electronics code, a widely-used suite of programs for creating numerical models of the ionizing-radiation environment in near-Earth orbits and for evaluating radiation effects in spacecraft. CREME96, which is now available over the World-Wide Web (WWW) at http://crsp3.nrl.navy.mil/creme96/, has many significant features, including: (1) improved models of the galactic cosmic ray, anomalous cosmic ray, and solar energetic particle ("flare") components of the near-Earth environment; (2) improved geomagnetic transmission calculations; (3) improved nuclear transport routines; (4) improved single-event upset (SEU) calculation techniques, for both proton-induced and direct-ionization-induced SEUs; and (5) an easy-to-use graphical interface, with extensive on-line tutorial information. In this paper we document some of these improvements.
TL;DR: In this paper, the authors examine the relation between managers' financial interests and firm performance and find no evidence that larger stockholdings lead to better performance, however, it may not be necessary for top executives to own stock to be residual claimants.
TL;DR: In this paper a particular cost function for graph edit distance is introduced, and it is shown that under this cost functiongraph edit distance computation is equivalent to the maximum common subgraph problem.
TL;DR: In this paper, a simple coupled atmosphere-ocean climate model is used to show that the Atlantic thermohaline circulation is not only sensitive to the final atmospheric CO2 concentration attained, but also depends on the rate of change in the atmosphere.
Abstract: Present estimates of the future oceanic uptake of anthropogenic CO2 and calculations of CO2-emission scenarios1 are based on the assumption that the natural carbon cycle is in steady state. But it iswell known from palaeoclimate records2,3,4,5 and modelling studies6,7,8,9 that the climate system has more than one equilibrium state, and that perturbations can trigger transitions between them. Anticipated future changes in today's climate system due to human activities have the potential to weaken the thermohaline circulation of the North Atlantic Ocean10,11,12, which would greatly modify estimates of future oceanic CO2 uptake13. Here we use a simple coupled atmosphere–ocean climate model to show that the Atlantic thermohaline circulation is not only sensitive to the final atmospheric CO2 concentration attained, but also depends on the rate of change of the CO2 concentration in the atmosphere. A modelled increase to 750 parts per million by volume (p.p.m.v.) CO2 within 100 years (corresponding approximately to a continuation of today's growth rate) leads to a permanent shut-down of the thermohaline circulation. If the final atmospheric concentration of 750 p.p.m.v. CO2 is attained more slowly, the thermohaline circulation simply slows down. The reason for this rate-sensitive response of the climate system lies with the transfer of buoyancy in the form of heat and fresh water from the uppermost layers of the ocean into the deep waters below. This sensitivity of the simulated thermohaline circulation to the rate ofchange of atmospheric CO2 concentration has potentially important implications for the choice of future CO2-emission scenarios1.
TL;DR: Recent studies that have identified amino acid residues that are thought to form the binding pocket for these compounds imply pseudosymmetry of channel agonist and channel modulatory sites, which may be a general principle realized in other pseudos asymmetric protein complexes.
TL;DR: Two highly similar, PtdIns(4,5)P2-selective, G beta gamma-activated PI3Ks were purified from pig neutrophil cytosol and bound tightly to one another, both in vivo and in vitro, and in so doing, p101 amplified the effect of G beta gammas on thePI3K activity of p120 from less than 2-fold to greater than 100-fold.
TL;DR: It is shown that the evolution of eusociality is associated with a 100-fold increase in insect lifespan, predicted by evolutionary theories because termite, bee and ant queens live in colonies that are sheltered and heavily defended against predators.
Abstract: Senescence presents not only a medical problem, but also an evolutionary paradox because it should be opposed by natural selection. Evolutionary hypotheses propose that ageing evolves as the necessary cost of processes increasing early reproductive success1,2, or because of weaker selection against late-acting mutations3. A prediction of these hypotheses is that the rate of ageing should increase and the average lifespan decrease as therate of extrinsic mortality increases1,2,3,4,5,6,7. Alternatively, non-adaptive, purely mechanistic hypotheses invoke damage to DNA, cells, tissues and organs as being the unique cause of senescence and ineluctable death of organisms8. Here we show that the evolution of eusociality is associated with a 100-fold increase in insect lifespan. Such an increase is predicted by evolutionary theories because termite, bee and ant queens live in colonies that are sheltered and heavily defended against predators. Moreover, a comparison of ants with contrasting life histories also reveals an association between lifespan and extrinsic rate of mortality. Theseresults provide strong support for evolutionary theories of ageing, as purely mechanistic hypotheses of senescence do not propose any association between the rate of extrinsic mortality and lifespans.
TL;DR: The data suggest that a biologic width exists around unloaded and loaded nonsubmerged one-part titanium implants and that this is a physiologically formed and stable dimension as is found around teeth.
Abstract: The use of endosseous dental implants as transmucosal devices necessitates the successful integration of three different tissues: bone, connective tissue, and epithelium. So far, studies have predominantly focused on hard tissue integration. Much less is known about soft tissues. This study examined the dimensions of the implantogingival junction in relation to clinically healthy unloaded and loaded nonsubmerged implants. In total, 69 titanium plasma-sprayed (TPS) and sandblasted acid-etched (SLA) implants were placed in an alternating fashion in six foxhounds and allowed to heal for 3 months. Two dogs were sacrificed after the initial healing period. The remaining four dogs had crowns fabricated that were allowed to function for up to 12 months. These animals were sacrificed after 3 and 12 months of loading. Histometric analysis of undecalcified histologic sections included the evaluation of the sulcus depth (SD), the dimensions of the junctional epithelium (JE), and the connective tissue contact (CTC). ...
TL;DR: It is suggested that basophils and eosinophils, which are the characteristic effector cells of allergic inflammation, depend largely on CCR3 for migration towards different chemokines into inflamed tissues.
Abstract: Eosinophil leukocytes express high numbers of the chemo- kine receptor CCR3 which binds eotaxin, monocyte chemo- tactic protein (MCP)-4, and some other CC chemokines. In this paper we show that CCR3 is also highly expressed on human blood basophils, as indicated by Northern blotting and flow cytometry, and mediates mainly chemotaxis. Eo- taxin and MCP-4 elicited basophil migration in vitro with similar efficacy as regulated upon activation normal T cells expressed and secreted (RANTES) and MCP-3. They also in- duced the release of histamine and leukotrienes in IL-3-primed basophils, but their efficacy was lower than that of MCP-1 and MCP-3, which were the most potent stimuli of exocyto- sis. Pretreatment of the basophils with a CCR3-blocking an- tibody abrogated the migration induced by eotaxin, RANTES, and by low to optimal concentrations of MCP-4, but de- creased only minimally the response to MCP-3. The CCR3- blocking antibody also affected exocytosis: it abrogated his- tamine and leukotriene release induced by eotaxin, and partially inhibited the response to RANTES and MCP-4. In contrast, the antibody did not affect the responses induced by MCP-1, MCP-3, and macrophage inflammatory protein- 1 a , which may depend on CCR1 and CCR2, two additional receptors detected by Northern blotting with basophil RNA. This study demonstrates that CCR3 is the major receptor for eotaxin, RANTES, and MCP-4 in human basophils, and suggests that basophils and eosinophils, which are the char- acteristic effector cells of allergic inflammation, depend largely on CCR3 for migration towards different chemo- kines into inflamed tissues. ( J. Clin. Invest. 1997. 100:1137- 1143.) Key words: allergyinflammationchemotaxis
TL;DR: No significant effect was found when tests were tested for an influence of the MHC on odour preferences after the degree of similarity between T–shirt–wearer and smeller was statistically controlled for, which suggests that in study populations the M HC influences body Odour preferences mainly, if not exclusively, by thedegree of similarity or dissimilarity.
Abstract: The major histocompatibility complex (MHC) is an immunologically important group of genes that appears to be under natural as well as sexual selection. Several hypotheses suggest that certain MHC-allele combinations (usually heterozygous ones) are superior under selective pressure by pathogens. This could influence mate choice in a way that preferences function to create MHC-heterozygous offspring, or that they function to create specific allele combinations that are beneficial under the current environmental conditions through their complementary or epistatic effects. To test these hypotheses, we asked 121 men and women to score the odours of six T-shirts, worn by two women and four men. Their scorings of pleasantness correlated negatively with the degree of MHC similarity between smeller and T-shirt-wearer in men and women who were not using the contraceptive pill (but not in Pill-users). Depending on the T-shirt-wearer, the amount of variance in the scorings of odour pleasantness that was explained by the degree of MHC similarity (r2) varied between nearly 0 and 23%. There was no apparent effect of gender in this correlation: the highest r2 was actually reached with one of the male odours sniffed by male smellers. Men and women who were reminded of their own mate/ex-mate when sniffing a T-shirt had significantly fewer MHC-alleles in common with this T-shirt-wearer than expected by chance. This suggests that the MHC or linked genes influence human mate choice. We found no significant effect when we tested for an influence of the MHC on odour preferences after the degree of similarity between T-shirt-wearer and smeller was statistically controlled for. This suggests that in our study populations the MHC influences body odour preferences mainly, if not exclusively, by the degree of similarity or dissimilarity. The observed preferences would increase heterozygosity in the progeny. They do not seem to aim for more specific MHC combinations.
TL;DR: This work used resistance to EMB as a tool to identify genes participating in the biosynthesis of the mycobacterial cell wall and led to the identification of the embCAB gene cluster, recently proposed to encode for myc Cobacterium tuberculosis arabinosyl transferases.
Abstract: Ethambutol (EMB), a frontline antituberculous drug, targets the mycobacterial cell wall, a unique structure among prokaryotes which consists of an outer layer of mycolic acids covalently bound to peptidoglycan via the arabinogalactan. EMB inhibits the polymerization of cell wall arabinan, and results in the accumulation of the lipid carrier decaprenol phosphoarabinose1,2, which suggests that the drug interferes with the transfer of arabinose to the cell wall acceptor. Unfortunately, resistance to EMB has been described in up to 4% of clinical isolates of Mycobacterium tuberculosis and is prevalent among isolates from patients with multidrug-resistant tuberculosis3. We used resistance to EMB as a tool to identify genes participating in the biosynthesis of the mycobacterial cell wall. This approach led to the identification of the embCAB gene cluster, recently proposed to encode for mycobacterial arabinosyl transferases4. Resistance to EMB results from an accumulation of genetic events determining overexpression of the Emb protein(s), structural mutation in EmbB, or both. Further characterization of these proteins might provide information on targets for new chemotherapeutic agents and might help development of diagnostic strategies for the detection of resistant M. tuberculosis.
TL;DR: Inter‐individual and intra‐individual reproducibility studies indicate that the error of the method is about 6% and that IMCL levels differ significantly between identical muscles in different subjects, as well as intra‐individually when measured at 1 week intervals.
Abstract: Intra-myocellular lipids (IMCL) are stored in droplets in the cytoplasm of muscle cells and are an energy storage form readily accessed during long-term exercise. 1H-MR spectroscopy methods are presented for noninvasive determination of IMCL in human muscle. This is based on (a) the separation of two resonances in the lipid-CH2-region, with the one assigned to IMCL being independent of muscle orientation relative to the magnetic field and (b) the fact that IMCL resonances scale along with signal amplitudes of metabolites in the muscle cell (e.g., creatine) when voxel size is increased, while lipid signals of bulk fat show a disproportionate growth. Inter-individual and intra-individual reproducibility studies indicate that the error of the method is about 6% and that IMCL levels differ significantly between identical muscles in different subjects, as well as intra-individually when measured at 1 week intervals. IMCL determinations in a single subject before and after strenuous exercise indicate that lipid stores recover with a t1/2 of about 1 day.
TL;DR: A novel human CC chemokine consisting of 78 amino acids and having a molecular mass of 8,778.3 daltons was isolated together with three minor COOH-terminally truncated variants with 73, 75, and 76 residues, which is functionally very similar to eotaxin and induced chemotaxis of eosinophils as well as basophils with typically bimodal concentration dependence.
Abstract: A novel human CC chemokine consisting of 78 amino acids and having a molecular mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCLKAGVIFT TKKGQQ SCGD PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated together with three minor COOH-terminally truncated variants with 73, 75, and 76 residues. The new chemokine was termed eotaxin-2 because it is functionally very similar to eotaxin. In terms of structure, however, eotaxin and eotaxin-2 are rather distant, they share only 39% identical amino acids and differ almost completely in the NH2-terminal region. Eotaxin-2 induced chemotaxis of eosinophils as well as basophils, with a typically bimodal concentration dependence, and the release of histamine and leukotriene C4 from basophils that had been primed with IL-3. In all assays, eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent. The migration and the release responses were abrogated in the presence of a monoclonal antibody that selectively blocks the eotaxin receptor, CCR3, indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor usage was also studied in desensitization experiments by measuring [Ca2+]i changes in eosinophils. Complete cross-desensitization was observed between eotaxin-2, eotaxin and MCP-4 confirming activation via CCR3. No Ca2+ mobilization was obtained in neutrophils, monocytes and lymphocytes, in agreement with the lack of chemotactic responsiveness. Intradermal injection of eotaxin-2 in a rhesus monkey (100 or 1,000 pmol per site) induced a marked local infiltration of eosinophils, which was most pronounced in the vicinity of postcapillary venules and was comparable to the effect of eotaxin.
TL;DR: Beads loaded with purified expansin induced bulging on the leaf-generating organ of tomato plants, resulting in a reversal of the direction of phyllotaxis, suggesting a role for biophysical forces in the regulation of plant development.
Abstract: Expansins are extracellular proteins that increase plant cell wall extensibility in vitro. Beads loaded with purified expansin induced bulging on the leaf-generating organ, the apical meristem, of tomato plants. Some of these bulges underwent morphogenesis to produce leaflike structures, resulting in a reversal of the direction of phyllotaxis. Thus, expansin can induce tissue expansion in vivo, and localized control of tissue expansion may be sufficient to induce leaf formation. These results suggest a role for biophysical forces in the regulation of plant development.
TL;DR: It is shown that young, otherwise healthy people can survive accidental deep hypothermia with no or minimal cerebral impairment, even with prolonged circulatory arrest, and cardiopulmonary bypass appears to be an efficacious rewarming technique.
Abstract: Background Cardiopulmonary bypass has been used to rewarm victims of accidental deep hypothermia. Unlike other rewarming techniques, it restores organ perfusion immediately in patients with inadequate circulation. This study evaluated the long-term outcome of survivors of accidental deep hypothermia with circulatory arrest who had been rewarmed with cardiopulmonary bypass. Methods Deep hypothermia (core temperature, <28°C) with circulatory arrest was found in 46 of 234 patients with accidental hypothermia. In 32 of the 46 patients, rewarming with cardiopulmonary bypass was attempted, resulting in 15 long-term survivors. In most of these patients, deep hypothermia developed after mountaineering accidents or suicide attempts. After an average (±SD) of 6.7±4.0 years of follow-up, we obtained the patients' medical histories and performed neurologic and neuropsychological examinations, neurovascular ultrasound studies, electroencephalography, and magnetic resonance imaging of the brain. Results The average age...
TL;DR: The purified mouse protein (mXRN1p), isolated from mouse demonstrated to encode a 5′–3′ exoribonuclease, exhibited a novel substrate preference for G4 RNA tetraplex–containing substrates demonstrated in binding and hydrolysis experiments, and is the first RNA turnover function that has been localized in the cytoplasm of mammalian cells.
Abstract: Exoribonucleases are important enzymes for the turnover of cellular RNA species. We have isolated the first mammalian cDNA from mouse demonstrated to encode a 5′–3′ exoribonuclease. The structural conservation of the predicted protein and complementation data in Saccharomyces cerevisiae suggest a role in cytoplasmic mRNA turnover and pre-rRNA processing similar to that of the major cytoplasmic exoribonuclease Xrn1p in yeast. Therefore, a key component of the mRNA decay system in S. cerevisiae has been conserved in evolution from yeasts to mammals. The purified mouse protein (mXRN1p) exhibited a novel substrate preference for G4 RNA tetraplex–containing substrates demonstrated in binding and hydrolysis experiments. mXRN1p is the first RNA turnover function that has been localized in the cytoplasm of mammalian cells. mXRN1p was distributed in small granules and was highly enriched in discrete, prominent foci. The specificity of mXRN1p suggests that RNAs containing G4 tetraplex structures may occur in vivo and may have a role in RNA turnover.
TL;DR: In this paper, a combined solution for the two major terrestrial lead paradoxes has been sought, namely, the future paradox (upper crustal and upper mantle Pb isotope compositions plot in the future field in 207pb/204Pb vs. 206Pb/ 204Pb space) and the Th/U mantle paradox (The Th /U ratio of the upper mantle is ca. 2.6, whereas Pb values indicate a value of 3.8).
TL;DR: An optical method for the visualization of boundaries of cylindrical bovine humeral head articular cartilage disks, immersed in physiological solution, and compressed in unconfined geometry revealed that the lateral expansion, especially during the initial phase of relaxation, was inhomogeneous through the tissue depth.
Journal Article•
TL;DR: Gastrin mRNA measured by in situ hybridization was present in most CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representing the molecular basis of a possible autocrine growth regulation of these tumors.
Abstract: Cholecystokinin (CCK)-A and CCK-B/gastrin receptors were evaluated with in vitro receptor autoradiography in 406 human tumors of various origins using a sulfated 125I-labeled CCK decapeptide analogue 125I-(D-Tyr-Gly, Nle28,3l)-CCK 26-33 and 125I-labeled Leu15-gastrin as radioligands. CCK-B/gastrin receptors were found frequently in medullary thyroid carcinomas (92%), in small cell lung cancers (57%), in astrocytomas (65%), and in stromal ovarian cancers (100%). They were found occasionally in gastroenteropancreatic tumors, breast, endometrial, and ovarian adenocarcinomas. They were either not expressed or rarely expressed in colorectal cancers, differentiated thyroid cancers, non-small cell lung cancers, meningiomas, neuroblastomas, schwannomas, glioblastomas, lymphomas, renal cell cancers, prostate carcinomas, and the remaining neuroendocrine tumors (i.e., pituitary adenomas, pheochromocytomas, paragangliomas, and parathyroid adenomas). CCK-A receptors were expressed rarely in tumors except in gastroenteropancreatic tumors (38%), meningiomas (30%), and some neuroblastomas (19%). The identified CCK-A and CCK-B receptors were specific and of high affinity in the subnanomolar range. The rank order of potency of various CCK analogues was: sulfated CCK-8 = L-364,718 >> nonsulfated CCK-8 = L-365,260 > or = gastrin for CCK-A receptors and sulfated CCK-8 > gastrin = nonsulfated CCK-8 > L-365,260 > L-364,718 for CCK-B receptors. CCK-B receptors could also be selectively and specifically labeled with a newly designed nonsulfated 125I-(D-Tyr-Gly, Nle28,31)-CCK 26-33. Gastrin mRNA measured by in situ hybridization was present in most CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representing the molecular basis of a possible autocrine growth regulation of these tumors. Gastrin and CCK mRNAs were lacking in medullary thyroid cancers. Thus, these results may have pathogenic, diagnostic, differential diagnostic, and therapeutic implications.
TL;DR: Molecular detection of resistance to the two main antituberculous drugs, INH and RMP, can be accomplished accurately by using a strategy which limits analysis to four genetic regions, which may allow the expedient analysis of drug resistance by reference laboratories.
Abstract: Progress in understanding the basis of resistance to isoniazid (INH) and rifampin (RMP) has allowed molecular tests for the detection of drug-resistant tuberculosis to be developed. Consecutive isolates (n = 95) of Mycobacterium tuberculosis, from a Spanish reference laboratory investigating outbreaks of multidrug-resistant tuberculosis, were coded and sent to two external laboratories for genotypic analysis of INH and RMP resistance by PCR-single-strand conformation polymorphism (SSCP) analysis of specific regions of four genes: part of the coding sequence of katG and the promoter regions of inhA and ahpC for INH and the RMP resistance region of rpoB. After correction for the presence of outbreak strains and multiple isolates from single patients, RMP resistance was detected successfully by PCR-SSCP in > 96% of the RMP-resistant strains. PCR-SSCP had a sensitivity of 87% for INH resistance detection, and mutations in katG, inhA, katG-inhA, ahpC, and katG-ahpC were identified in 36.8, 31.6, 2.6, 13.2, and 2.6%, respectively, of the unique strains. Specificity was 100%. Molecular detection of resistance to the two main antituberculous drugs, INH and RMP, can be accomplished accurately by using a strategy which limits analysis to four genetic regions. This may allow the expedient analysis of drug resistance by reference laboratories.