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PubMed1997

Travel advice: a study among Swiss and German general practitioners.

Travelling to tropical and subtropical destinations is common among European citizens. Many of them consult their general practitioners (GPs) for pre-travel advice. Little is known about the knowledge, the sources of information and the needs of physicians. One hundred and fifty Swiss and I50 German GPs giving travel advice were interviewed using pretested telephone interviews and questionnaires to assess their knowledge about travel advice to be given for 2 frequent holiday destinations (Kenya and Thailand), and to ask which information sources were available to them. Ninety-six per cent and 89%, respectively, of GPs in 2 neighbouring areas of Switzerland and Germany gave travel advice to their clients. In telephone interviews, standard recommendations on malaria medication, as approved by the national travel advice committees, were stated by 45 and 25% of Swiss GPs, and 22 and 9% of German GPs for Kenya and Thailand. The figures for correct advice on vaccination requirements were 23 and 47% for the Swiss GPs, and 2 and 25% for the German GPs. Half of the GPs wanted to consult their documents before giving advice. The main source of information used by Swiss GPs was the monthly updated Bulletin of the Federal Office of Public Health (BFOPH). A variety of different sources was recorded among German practitioners. Regular, concise information on travel advice tops the list of requested information material in both countries. The extent of correct pre-travel advice is unsatisfactory in both study groups. Use of standardized, regularly updated and readily available sources of information on travel advice for the GP could avoid uncertainties of both the provider and the recipient of advice.

Family Practice↗
PubMed1997

Compliance with malaria chemoprophylaxis and preventative measures against mosquito bites among Dutch travellers.

Self-reported compliance with a malaria chemoprophylaxis regimen of proguanil (PG) plus chloroquine (CQ) was assessed in a cohort of 547 Dutch travellers who visited a single travel clinic when travelling to various areas endemic for falciparum malaria. 503 (92%) had taken PG/CQ prophylaxis, but only 326 (60%) reported regular and uninterrupted use throughout the journey and 4 weeks afterwards. Compliance differed by travel destination and was 45% in South America, 52% in West Africa, 53% in South-east Asia, 60% in the Indian Subcontinent and 78% in East Africa. Parasitologically confirmed falciparum malaria occurred in 5 travellers (0.9%), including 3 of 24 non-compliant travellers to West Africa (12.5%). Apart from destination, independent risk factors for non-compliance were young age, extensive travel experience and adventurous travel. Compliance with protection against mosquito bites was 80% for wearing long-sleeved shirts and long-legged trousers after sunset, 73% for use of repellents, 56% for sleeping under bed nets and 37% for keeping the sleeping quarters free of mosquitoes. Although 440 travellers (80%) reported to have taken two or more of these measures at least once, only 88 (16%) had done so on a daily basis. Daily use of bed nets was reported more frequently among subjects who were non-compliant with chemoprophylaxis. Compliance regarding malaria chemoprophylaxis should be improved, particularly in high-risk areas such as Sub-saharan Africa, with extra attention to young, adventurous travellers. More emphasis should be placed on prevention of Anopheles bites.

Adult↗
PubMed2001

Predicted impact on Victoria's ambulance services of a new major trauma system.

BACKGROUND: In 1999, a new major trauma system was proposed for the state of Victoria, Australia. The guidelines for the new system were aimed at delivering major trauma cases to definitive trauma care in the least time possible. The aim of the present study was to analyse the potential effect of this system on Victoria's ambulance services. METHODS: The present study modelled the workload of major trauma cases in Victoria's ambulance service for one year pre- and post-introduction of the guidelines. Cases were analysed regarding whether their first hospital destination would change under the proposed guidelines, and, subsequently, whether they would require interhospital transport to a higher level trauma service. The impact on the ambulance services was modelled as annual changes in distances travelled due to predicted changes in hospital destinations. RESULTS: Analysis of the predicted changes indicated that, in general, Victoria's metropolitan and rural road ambulance crews would not be greatly affected. However, some metropolitan road crews may have to travel extra distances for up to 110 cases per year. The major impact was on air retrieval crews, where the annual number of interhospital transfers is predicted to increase from approximately 150 to 330. CONCLUSIONS: The present study demonstrated that most of the impact of a new trauma system on Victoria's ambulance services could be readily absorbed into the current workload. However, it also highlighted areas affected disproportionately within the ambulance services; in particular, air retrieval. Such studies are important to enable the effective implementation of new trauma systems.

Aged↗
PubMed2002

Differential post-transcriptional regulation of p21WAF1/Cip1 levels in the developing nervous system following gamma-irradiation.

Radiation-induced death in the developing brain is p53-dependent. However, genetic studies indicate that the signalling pathways that couple irradiation to p53 expression can vary between different developing neural populations [Herzog et al. (1998) Science, 280, 1089-1091]. Here we establish that signalling downstream of p53 also exhibits brain region-specific differences that are associated with the relative vulnerability of some cell populations to radiation-induced killing in the mouse. Following gamma-irradiation, p53 and p21WAF1/cip1, but not Bax, protein levels increased in the developing cerebellum. In contrast, neither p21WAF1/cip1 nor Bax protein levels were elevated in the retina following irradiation, despite increased p53 expression. In the retina, p53 expression was associated with cells destined to die, whereas in the cerebellum, p53 was expressed in both radiation-sensitive and radiation-resistant neuroblasts of the external granule cell layer. Although p21WAF1/cip1 mRNA was expressed in all p53-positive neuroblasts after irradiation, p21WAF1/cip1 protein was only detected in radiation-resistant neuroblasts of the cerebellum. Thus, p21WAF1/cip1 was subject to post-transcriptional regulation with p21WAF1/cip1 protein only accumulating in cells destined to survive irradiation. Nevertheless, p21WAF1/cip1 function was not essential for radiation resistance, as postmitotic neuroblasts in the external granule cell layer were spared in p21WAF1/cip1 knockout mice.

Animals↗
PubMed1995

Natural history of trisomy 21 fetuses with increased nuchal translucency thickness.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation can identify 80% of trisomy 21 pregnancies. However, a potential disadvantage of screening in the first trimester of pregnancy is that earlier screening preferentially identifies those chromosomally abnormal pregnancies that are destined to miscarry. In this study, we report on the outcome of six fetuses with increased nuchal translucency thickness and trisomy 21 whose parents chose to continue with the pregnancy. During the second trimester, the nuchal translucency resolved in five of the cases and in one it evolved into nuchal edema. Therefore, resolution of translucency with advancing gestation is not indicative of a normal karyotype. All pregnancies resulted in live births, suggesting that increased nuchal translucency does not necessarily identify those trisomic fetuses that are destined to die in utero.

Adult↗
PubMedDate not supplied

Future devices and directions.

This article summarizes the status of left ventricular assist devices currently in the stages of bench testing, animal experiments, and pilot clinical trials. The major design features and estimate of costs for 17 devices are described under 3 major categories of indications for use: destination therapy, bridge to transplant, and bridge to recovery. A sleeved piston pump located in the aorta and a unique, magnetically suspended centrifugal pump are described in the destination therapy section. Eight centrifugal and 4 axial flow devices are listed in the bridge to transplant category, and an external cup and a very low-cost centrifugal pump with a left atrium-to-aorta circuit are described in the bridge to recovery section. The key design features of the future, which will be required for success in both the clinical and marketplace arenas, will be simplicity, safety, low-power requirements, and low cost.

Animals↗
PubMed2006

[Travel medicine and vaccination as a task of infection prevention--data of the special consultation hours of the public health department Frankfurt on the Main, Germany, 2002-2004].

UNLABELLED: Infection prevention is one of the main tasks of the Public Health authorities. Because of hundreds of travel associated infections imported by travellers every year and considering increasing travel activities to tropical countries, travel medicine and consultation on the correct prevention measures including vaccination is becoming more and more important. Hence the data of the special consultation hours of the public health department of Frankfurt am Main are reported and discussed with regard to possible improvements. MATERIAL AND METHODS: The public health department of Frankfurt am Main has been offering special consultation hours for travel medicine for many years. Here, data derived from the anamneses of the clients from 2002 - 2004 are reported: personal data such as age, sex, travel destination as well as medical data such as vaccination and malaria prevention. RESULTS: 2002 - 2004, more than 14,000 persons were seen in the consultation hours, more than 66% of them asked for travel health advice, about 25% of them asked for standard vaccination (such as influenza), some others asked for attestation or certification. More than 20,000 doses of vaccines were given, the most important vaccination against hepatitis A (n = 5791), hepatitis B (n = 4064), typhoid fever (n = 2718) and yellow fever (n = 2473). 2814 were informed with regard to malaria prevention, including recipes. 7814 persons with complete data on their reason for travel were subjected to more detailed analysis: 75% of them were holiday tourists, 18% travelled as "hikers", 7% were business travellers and less than 1% of them planned a round-the-world tour. The most frequent travel destinations were: Asian or African countries about 33% each, 25% Middle or South America. Thailand, South Africa with Namibia, Brazil and India were the most important countries. The time from health consultation to the beginning of the journey was too short for full vaccine protection against typhoid fever and meningococcal disease in 10% and against rabies in 44% of the consultants. There were no significant differences between holiday tourists, business and "hikers" travellers. CONCLUSION: According to many studies, only one-third of the travellers going abroad, especially to developing countries, obtain travel health information. Hence, the clients of our consultation hours are a positive selection. Nevertheless, great need for improvement could be seen as well. In many of the clients the time from getting health information and vaccination was too short for obtaining complete vaccination protection. People travelling to countries where most hepatitis A infections are obtained and re-imported home, such as Turkey and Tunisia and other Mediterranean countries almost never came for health advice and vaccination. Therefore, public health authorities should improve and increase their publicity campaigns for travel health and vaccination in order to prevent travel-associated infections and re-importation of such diseases.

Communicable Disease Control↗
PubMed1993

[Asymmetric multizone lenses--a new concept in multifocal intraocular lenses].

BACKGROUND: Asymmetrical multifocal lenses (MIOLs) represent a new concept for binocular implantation of MIOLs: one asymmetrical IOL--destined for implantation in the dominant eye--is favouring distance vision by assuring that 60-70% of the light rays coming from an object will pass through the distance part of the optic. The other IOL--destined for implantation in the second eye--is favouring near vision, enabling that 60-70% of the light energy will be focused by the near zone(s) of the IOL. METHODS: Modulation transfer function (MTF), Strehl-Ratio (SR) and resolution efficiency (RE) were determined in both foci by in vitro measurement. Defocus curves were performed after clinical implantation as well as after "optical implantation" by means of an optical device developed by Reiner. RESULTS: In vitro measurements showed superior results of SR and RE in the favoured focus of the MIOL. Defocus curves after clinical and "optical" implantation yielded higher peaks for visual acuity and contrast in the favoured focus. CONCLUSION: First theoretical and clinical results do confirm the new concept of asymmetrical multifocal IOLs.

Contrast Sensitivity↗
PubMed2006

Spectrum of disease and relation to place of exposure among ill returned travelers.

BACKGROUND: Approximately 8 percent of travelers to the developing world require medical care during or after travel. Current understanding of morbidity profiles among ill returned travelers is based on limited data from the 1980s. METHODS: Thirty GeoSentinel sites, which are specialized travel or tropical-medicine clinics on six continents, contributed clinician-based sentinel surveillance data for 17,353 ill returned travelers. We compared the frequency of occurrence of each diagnosis among travelers returning from six developing regions of the world. RESULTS: Significant regional differences in proportionate morbidity were detected in 16 of 21 broad syndromic categories. Among travelers presenting to GeoSentinel sites, systemic febrile illness without localizing findings occurred disproportionately among those returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatologic problems among those returning from the Caribbean or Central or South America. With respect to specific diagnoses, malaria was one of the three most frequent causes of systemic febrile illness among travelers from every region, although travelers from every region except sub-Saharan Africa and Central America had confirmed or probable dengue more frequently than malaria. Among travelers returning from sub-Saharan Africa, rickettsial infection, primarily tick-borne spotted fever, occurred more frequently than typhoid or dengue. Travelers from all regions except Southeast Asia presented with parasite-induced diarrhea more often than with bacterial diarrhea. CONCLUSIONS: When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases. Diagnostic approaches and empiric therapies can be guided by these destination-specific differences.

Adult↗
PubMed2006

Intermolecular potentials of the methane dimer calculated with Møller-Plesset perturbation theory and density functional theory.

We have calculated the intermolecular interaction potentials of the methane dimer at the minimum-energy D(3d) conformation using the Hartree-Fock (HF) self-consistent theory, the correlation-corrected second-order Møller-Plesset (MP2) perturbation theory, and the density functional theory (DFT) with the Perdew-Wang (PW91) functional as the exchange or the correlation part. The HF calculations yield unbound potentials largely due to the exchange-repulsion interaction. In the MP2 calculations, the basis set effects on the repulsion exponent, the equilibrium bond length, the binding energy, and the asymptotic behavior of the calculated intermolecular potentials have been thoroughly studied. We have employed basis sets from the Slater-type orbitals fitted with Gaussian functions (STO-nG) (n=3-6) [Quantum Theory of Molecular and Solids: The Self-Consistent Field for Molecular and Solids (McGraw-Hill, New York, 1974), Vol. 4], Pople's medium size basis sets of Krishnan et al. [J. Chem. Phys. 72, 650 (1980)] [up to 6-311++G(3df,3pd)] to Dunning's correlation consistent basis sets [J. Chem. Phys. 90, 1007 (1989)] (cc-pVXZ and aug-cc-pVXZ) (X=D, T, and Q). With increasing basis size, the repulsion exponent and the equilibrium bond length converge at the 6-31G** basis set and the 6-311++G(2d,2p) basis set, respectively, while a large basis set (aug-cc-pVTZ) is required to converge the binding energy at a chemical accuracy (approximately 0.01 kcal/mol). Up to the largest basis set used, the asymptotic dispersion coefficient has not converged to the destined C6 value from molecular polarizability calculations. The slow convergence could indicate the inefficacy of using the MP2 calculations with Gaussian-type functions to model the asymptotic behavior. Both the basis set superposition error (BSSE) corrected and uncorrected results are presented to emphasize the importance of including such corrections. Only the BSSE corrected results systematically converge to the destined potential curve with increasing basis size. The DFT calculations generate a wide range of interaction patterns, from purely unbound to strongly bound, underestimating or overestimating the binding energy. The binding energy calculated using the PW91PW91 functional and the equilibrium bond length calculated using the PW91VP86 functional are close to the MP2 results at the basis set limit.

Journal Article↗
PubMed2001

The role of thrombin in preterm parturition.

OBJECTIVE: Previous reports from our laboratory have shown that thrombin is a potent uterotonic agonist; those studies have suggested a role for thrombin during parturition, especially with regard to intrauterine bleeding. Thrombin activation can be quantified in peripheral blood by measurement of thrombin-antithrombin III (TAT) complex levels. This study sought to determine whether thrombin activation, as measured by thrombin-antithrombin III levels, is associated with premature labor. STUDY DESIGN: Thrombin-antithrombin III levels were measured in patients and control subjects with preterm labor. Quantitative TAT levels were determined by use of an enzyme-linked immunoassay with a working range from 0 to 60 ng/mL. All patients were monitored for pregnancy outcome. Receiver operating curve analysis was performed to determine the optimal TAT cutoff values. Further statistical analyses with one-way ANOVA, the chi2 test, or the Fisher exact test were performed to determine statistical significance (P <.05). RESULTS: Patients admitted with preterm labor who were subsequently delivered within 3 weeks had significantly higher mean TAT levels (7.80 +/- 2.86 ng/mL; P <.05) than control subjects (5.77 +/- 1.43 mL) or patients with preterm labor who were not delivered within 3 weeks of presentation with preterm labor (5.57 +/- 1.69 ng/mL; P <.05). Given a diagnosis of preterm labor, a TAT level of 8.0 ng/mL had a positive predictive value of 80% for delivery within 3 weeks of enrollment. CONCLUSIONS: This study showed that TAT levels are elevated in patients with preterm labor who are destined to deliver before term. These results suggest that preterm labor resulting in premature delivery is associated with the activation of thrombin. Future studies will further elucidate the role of thrombin in preterm parturition and confirm whether tests for thrombin activation can accurately identify those patients destined for preterm delivery.

Adult↗
PubMed1984

Why the islands move.

Micronesian navigators routinely make voyages across large expanses of open ocean. To do this, a navigator must judge both the direction in which he is sailing and the distance he has travelled. The rising and setting points of the stars (and other cues) provide instantaneous information about direction, but distance can only be judged by integrating velocity-related information over time. Micronesian navigators judge distance in a way that seems odd. When they are out of sight of land, they imagine that the canoe is stationary and that the islands move back past them. For each voyage, they 'attend' to an island off to the side of the course which is out of sight over the horizon. As they sail, they imagine the island moving back along the horizon changing in bearing until it is imagined to be under the bearing it is known to have from the destination island. Then they know they are near their destination. There is good reason for using a frame of reference whose origin is defined by the boat. We show how it finesses a perceptual paradox--the rising and setting points of the stars do not exhibit motion parallax.

Cues↗
PubMed2004

A transitional care service for elderly chronic disease patients at risk of readmission.

BACKGROUND: Multiple hospital admissions, especially those related to chronic disease, represent a particular challenge to the acute health care sector in Australia. OBJECTIVE: To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care. DESIGN: A quasi-experimental controlled trial. SETTING: A large tertiary metropolitan teaching hospital. PARTICIPANTS: 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities. INTERVENTION: Implementation of a chronic disease management model of transitional care aimed at improving patient management and reducing readmissions to acute care. MAIN OUTCOME MEASURES: Readmission rates and emergency department presentation rates at 3-and 6-month follow up. Secondary outcome measures include quality of life, discharge destination, and primary health care service utilisation. RESULTS: There was no difference in readmission rates, emergency department presentation rates, quality of life, discharge destination or primary health care service utilisation. The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors, the difficulty of influencing readmission rates, and local system issues. CONCLUSION: The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research methodologies.

Aged↗
PubMed2001

The future fertility of mankind: effects on world population growth and migration.

The world's population, currently just over 6 billion, is projected to increase to 9-10 billion by the year 2050. Most of this growth will occur in the developing countries of Asia, where there is an enormous unmet demand for contraception, while an increasing number of developed countries will have declining populations. The human immunodeficiency virus (HIV) pandemic will target developing countries, with India destined to become its new epicenter. By 2050, there may be 1 billion HIV-infected people in the world. The significant protective effect of male circumcision may spare Islamic countries, such as Pakistan, Bangladesh, Iran and Indonesia, from the worst effects of the pandemic. Australia will be increasingly threatened by the high rates of population growth of her Asian neighbours. This, coupled with political instability and sea-level rises as a consequence of global warming, will turn the present trickle of refugees from a variety of Asian countries seeking safe haven on our sparsely populated northern coastline into a veritable flood. There will come a time when we have neither the manpower, nor the means, nor even the moral right to intercept, detain or repatriate the thousands who will come in peace, in search of a better life. However, if Australia is to stabilize its future population at around 23 million, which seems highly desirable on ecological grounds, then the net immigration rate must be limited to approximately 50000 people per year. Because the final point of departure for all these refugees is Indonesia, it is essential that Australia maintains good relations with Indonesia, so that together we can attempt to manage the refugee problem. However, Indonesia's own population is destined to increase by 100 million in the next 50 years, which will only exacerbate the situation. Australia would be well advised to make a major increase in its paltry financial assistance to Indonesia's excellent family planning programmes, which are currently starved of funds. Helping Indonesia to contain its population growth is Australia's best long-term investment for its own future.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Isolation and characterization of Staufen-containing ribonucleoprotein particles from rat brain.

Localized mRNAs are thought to be transported in defined particles to their final destination. These particles represent large protein complexes that may be involved in recognizing, transporting, and anchoring localized messages. Few components of these ribonucleoparticles, however, have been identified yet. We chose the strategy to biochemically enrich native RNA-protein complexes involved in RNA transport to identify the associated RNAs and proteins. Because Staufen proteins were implicated in intracellular RNA transport, we chose mammalian Staufen proteins as markers for the purification of RNA transport particles. Here, we present evidence that Staufen proteins exist in two different complexes: (i) distinct large, ribosome- and endoplasmic reticulum-containing granules preferentially found in the membrane pellets during differential centrifugation and (ii) smaller particles in the S100 from rat brain homogenates. On gel filtration of the S100, we identified soluble 670-kDa Staufen1-containing and 440-kDa Staufen2-containing particles. They do not cofractionate with ribosomes and endoplasmic reticulum but rather coenrich with kinesin heavy chain. Furthermore, the fractions containing the Staufen1 particles show a 15-fold enrichment of mRNAs compared with control fractions. Most importantly, these fractions are highly enriched in BC1, and, to a lesser extent, in the alpha-subunit of the Ca(2+)/calmodulin-dependent kinase II, two dendritically localized RNAs. Finally, both RNAs colocalize with Staufen1-hemagglutinin in particles in dendrites of transfected hippocampal neurons. We therefore propose that these Staufen1-containing particles may represent RNA transport intermediates that are in transit to their final destination within neurons.

Animals↗
PubMed2005

Multiple modes of interaction of the deglycosylation enzyme, mouse peptide N-glycanase, with the proteasome.

Peptide N-glycanase (PNGase) is involved in the cleavage of oligosaccharide chains from misfolded glycoproteins that are destined for degradation by the proteasome. Earlier, a number of potential binding partners of mouse PNGase (mPNGase) were detected by using the yeast two-hybrid system. In the current study, an in vitro system was set up to investigate direct interactions between mPNGase and these candidate proteins. Although the yeast two-hybrid system suggested an interaction of six different proteins with mPNGase, only mHR23B and the proteasome subunit mS4 were found to interact with mPNGase. In fact, mS4 competes with mHR23B for binding to mPNGase. These results suggested two possible pathways for the interaction between mPNGase and the proteasome. In one pathway, mHR23B mediates the interaction between mPNGase and the proteasome. In an alternative pathway, mPNGase directly binds to the proteasome subunit, mS4. In either case, it is clear that PNGase is located in close proximity to the proteasome and is available for deglycosylation of glycoproteins destined for degradation. Surprisingly, mPNGase also was found to mediate binding of the cytoplasmic protein, p97, to the proteasome through the formation of a ternary complex made up of mHR23B, mPNGase, and p97. Because p97 is known to bind to the endoplasmic reticulum membrane protein AMFR (gp78), an E3 ligase, we propose a model in which p97, mPNGase, and mHR23B mediate interaction of the endoplasmic reticulum with the proteasome.

Adenosine Triphosphatases↗
PubMed2006

Prenatal exposure to ultrasound waves impacts neuronal migration in mice.

Neurons of the cerebral neocortex in mammals, including humans, are generated during fetal life in the proliferative zones and then migrate to their final destinations by following an inside-to-outside sequence. The present study examined the effect of ultrasound waves (USW) on neuronal position within the embryonic cerebral cortex in mice. We used a single BrdU injection to label neurons generated at embryonic day 16 and destined for the superficial cortical layers. Our analysis of over 335 animals reveals that, when exposed to USW for a total of 30 min or longer during the period of their migration, a small but statistically significant number of neurons fail to acquire their proper position and remain scattered within inappropriate cortical layers and/or in the subjacent white matter. The magnitude of dispersion of labeled neurons was variable but systematically increased with duration of exposure to USW. These results call for a further investigation in larger and slower-developing brains of non-human primates and continued scrutiny of unnecessarily long prenatal ultrasound exposure.

Animals↗
PubMed2003

Endosomal compartmentalization in three dimensions: implications for membrane fusion.

Endosomes are major sorting stations in the endocytic route that send proteins and lipids to multiple destinations in the cell, including the cell surface, Golgi complex, and lysosomes. They have an intricate architecture of internal membrane structures enclosed by an outer membrane. Recycling proteins remain on the outer membrane, whereas proteins that are destined for degradation in the lysosome are sorted to the interior. Recently, a retrograde pathway was discovered whereby molecules, like MHC class II of the immune system, return from the internal structures to the outer membrane, allowing their further transport to the cell surface for T cell activation. Whether this return involves back fusion of free vesicles with the outer membrane, or occurs via the continuity of the two membrane domains, is an unanswered question. By electron tomography of cryo-immobilized cells we now demonstrate that, in multivesicular endosomes of B-lymphocytes and dendritic cells, the inner membranes are free vesicles. Hence, protein transport from inner to outer membranes cannot occur laterally in the plane of the membrane, but requires fusion between the two membrane domains. This implies the existence of an intracellular machinery that mediates fusion between the exoplasmic leaflets of the membranes involved, which is opposite to regular intracellular fusion between cytoplasmic leaflets. In addition, our 3D reconstructions reveal the presence of clathrin-coated areas at the cytoplasmic face of the outer membrane, known to participate in protein sorting to the endosomal interior. Interestingly, profiles reminiscent of inward budding vesicles were often in close proximity to the coats.

Animals↗