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PubMedDate not supplied

Branch migration and the international dispersal of families.

This paper discusses the dispersal of facilities where family members migrate to different destination countries. Terminology for internationally dispersed families is proposed, and the term branch migration is suggested for the migration of related people from the same source country to different destination countries. Data from two 1993 surveys of senior secondary students show that 22% of Sydney students and 20% of Hong Kong students have relatives in two or more other countries. The data suggest that many Asian migrant families have branched between the US, Canada, Australia and other migrant-receiving nations. The causes and implications of the international dispersal of families are discussed.

Asia↗
PubMed2002

Cognitive rehabilitation for spatial neglect following stroke.

BACKGROUND: Unilateral spatial neglect is a failure to attend to one side of space. Various strategies have been used to treat these problems but evidence of their benefit has been lacking. OBJECTIVES: To determine the effects of cognitive rehabilitation for spatial neglect following stroke as measured on impairment and disability level assessments, and destination on discharge from hospital. To determine whether any effects persist at follow-up assessment. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched February 2001), MEDLINE (1966-December 2000), EMBASE (1980-February 2001), CINAHL (1983-January 2001), PSYCLIT and CLINPSYCH (1974-February 2001). We handsearched relevant journals, screened reference lists from relevant articles and tracked citations using SCISEARCH. SELECTION CRITERIA: Controlled trials of cognitive rehabilitation for spatial neglect in stroke. Studies with mixed patient groups were excluded unless more than 75% of their sample were stroke patients or separate stroke data were available for stroke patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials, extracted data, and assessed trial quality. MAIN RESULTS: We included 15 studies with 400 participants. A large number of different outcome measures were reported. Only six studies included a measure of disability and only four (111 participants) investigated persisting effects on any outcome. There was evidence that cognitive rehabilitation resulted in significant and persisting improvements in performance on impairment level assessments, although this varied depending on the test used. There was insufficient evidence to confirm or exclude an effect of cognitive rehabilitation at the level of disability or on destination following discharge from hospital. REVIEWER'S CONCLUSIONS: There is some evidence that cognitive rehabilitation for spatial neglect improves performance on some impairment level tests but its effect on disability is unclear. Further well-designed RCTs are warranted as well as basic research to develop valid outcome measures.

Cognitive Behavioral Therapy↗
PubMed1993

Regulative ability of the prospective cardiogenic and vasculogenic areas of the primitive streak during avian gastrulation.

Four types of microsurgical experiments were conducted to analyze heart and blood vessel development during gastrula stages of avian embryos, stages during which prospective cardiogenic and vasculogenic cells reside within the primitive streak. Experiments addressed whether cells not normally destined to form heart could form heart when given the opportunity to do so and vice versa; cells destined to form rostral levels of the heart (or, alternatively, head blood vessels) could form caudal levels of the heart (or, alternatively, trunk blood vessels) and vice versa; the early endoderm imparts rostrocaudal organization to the heart and associated blood vessels; and ingression of cells from the primitive streak and their subsequent migration into the mesodermal mantle is a cell-autonomous event for migrating cells. Our results demonstrate the lability of prospective cardiogenic and vasculogenic cells of the primitive streak, both in terms of the type of mesodermal structures they are capable of forming (or of being formed from) and in terms of the rostrocaudal patterning of the cardiovascular system. In addition, our results show that cell ingression and migration is directed by environmental cues and is not a cell-autonomous process for migrating cells. Finally, our results suggest that patterning of the cardiovascular system occurs after cells enter the mesodermal mantle, presumably through cell-cell inductive interactions. However, the early endoderm is not the primary source of the patterning influence. What is the source remains to be established.

Animals↗
PubMed1983

Mechanism of canine cyclic hematopoiesis: the role of prostaglandin E in feedback regulation.

Prostaglandin E inhibits granulocyte-macrophage colony formation in vitro in man and mouse, suggesting that it plays a role in feedback regulation of granulocyte production in vivo. Therefore, we examined the role of PGE in normal canine hematopoiesis and its potential role in the pathogenesis of cyclic hematopoiesis in grey collie dogs. The prostaglandin synthesis inhibitors indomethacin and ibuprofen (10(-5) M) increased CFU-C growth to 194 and 160% of control, respectively, while PGE2 addition caused a dose-dependent inhibition of bone marrow CFU-C growth in both normal and grey collie dogs. These concentrations of indomethacin and ibuprofen decreased bone marrow cell elaboration of PGE measured by radioimmunoassay to less than 5% of control values. The levels of PGE in leukocyte conditioned medium prepared from grey collies correlated with the number of monocytes in the conditioning cell suspension (r = 0.78, n = 10, p less than 0.05) so that PGE production per monocyte was no different in normal and grey collie dogs. The effect of PGE2 upon CFU-C was to inhibit formation of macrophage, but not neutrophil colony subtypes. These findings make aberrant PGE-mediated inhibition of precursor cells an unlikely mechanism to cause cyclic hematopoiesis, and show that PGE produced by monocytes acts as a feedback inhibitor for precursor cells destined to produce monocytes but not for those destined to form neutrophils.

Animals↗
PubMed2001

Intracellular freezing, viability, and composition of fat body cells from freeze-intolerant larvae of Sarcophaga crassipalpis.

Although it is often assumed that survival of freezing requires that ice formation must be restricted to extracellular compartments, fat body cells from freeze-tolerant larvae of the gall fly, Eurosta solidaginis (Diptera, Tephritidae) survive intracellular freezing. Furthermore, these cells are highly susceptible to inoculative freezing by external ice, undergo extensive lipid coalescence upon thawing, and survive freezing better when glycerol is added to the suspension medium. To determine whether these traits are required for intracellular freeze tolerance or whether they are incidental and possessed by fat body cells in general, we investigated the capacity of fat body cells from nondiapause-destined and diapause-destined (i.e., cold-hardy) larvae of the freeze-intolerant flesh fly Sarcophaga crassipalpis (Diptera, Sarcophagidae) to survive intracellular freezing. Fat body cells from both types of larvae were highly susceptible to inoculative freezing; all cells froze between -3.7 to -6.2 degrees C. The highest rates for survival of intracellular freezing occurred at -5 degrees C. The addition of glycerol to the media markedly increased survival rates. Upon thawing, the fat body cells showed little or no lipid coalescence. Fat body cells from E. solidaginis had a water content of only 35% compared to cells from S. crassipalpis larvae that had 52-55%; cells with less water may be less likely to be damaged by mechanical forces during intracellular freezing.

Animals↗
PubMed2005

Gap-junction communication between subtypes of direction-selective ganglion cells in the developing retina.

The On-Off direction-selective ganglion cells (DSGCs) in the rabbit retina comprise four distinct subtypes that respond preferentially to image motion in four orthogonal directions; each subtype forms a regular territorial array, which is overlapped by the other three arrays. In this study, ganglion cells in the developing retina were injected with Neurobiotin, a gap-junction-permeable tracer, and the DSGCs were identified by their characteristic type 1 bistratified (BiS1) morphology. The complex patterns of tracer coupling shown by the BiS1 ganglion cells changed systematically during the course of postnatal development. BiS1 cells appear to be coupled together around the time of birth, but, over the next 10 days, BiS1 cells decouple from each other, leading to the mature pattern in which only one subtype is coupled. At about postnatal day 5, before the ganglion cells become visually responsive, each of the BiS1 cells commonly showed tracer coupling both to a regular array of neighboring BiS1 cells, presumably destined to be DSGCs of the same subtype, and to a regular array of overlapping BiS1 cells, presumably destined to be DSGCs of a different subtype. The gap-junction intercellular communication between subtypes of DSGCs with different preferred directions may play an important role in the differentiation of their synaptic connectivity, with respect to either the inputs that DSGCs receive from retinal interneurons or the outputs that DSGCs make to geniculate neurons.

Animals↗
PubMed1975

The origin of efferent pathways from the primary visual cortex, area 17, of the macaque monkey as shown by retrograde transport of horseradish peroxidase.

The retrograde transport of horseradish peroxidase has been used to identify efferent cells in area 17 of the macaque. Cells projecting to the lateral geniculate nucleus are small to medium sized pyramidal neurons with somata in lamina 6 and the adjacent white matter. The projection to the parvocellular division arises preferentially from the upper half of lamina 6, while that to the magnocellular division arises preferentially from the lower part of the lamina. The projection to both superior colliculus and inferior pulvinar arises from all sizes of pyramidal neurons lying in lamina 58 (Lund and Boothe, '75); at least pyramidal neurons of lamina 5B send collateral axon branches to both destinations. Injections with extensive spread of horseradish peroxidase show that many cells of lamina 4B and the large pyramidal neurons of upper lamina 6 also project extrinsically but their terminal sites have not been identified. Other studies have indicated that cells of laminae 2 and 3 project to areas 18 and 19. Therefore every lamina of the visual cortex, with the exception of those receiving a direct thalamic input, contains cells projecting extrinsically. Further, each lamina projects to a different destination and from Golgi studies can be shown to contain cells with specific patterns of dendritic branching which relate to the distribution of thalamic afferents and to the patterns of intracortical connections. These findings emphasise the significance of the horizontal organisation of the cortex with relation to the flow of information through it and contrast with the current concept of columnar organisation shown in physiological studies.

Animals↗
PubMed1981

Neurogenesis of the sexually dimorphic nucleus of the preoptic area in the rat.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) of Sprague-Dawley rats is larger in volume in the male and hormone-dependent early in postnatal life. In the present study, we compared for each sex the time course of neuroblast proliferation which study, we compared for each sex the time course of neuroblast proliferation which forms SDN-POA or adjacent medial preoptic area (MPOA) neurons. Additionally, we investigated whether there is a temporal gradient of production of neurons in relation to their final position within the SDN-POA. On day 15, 15, 16, 17, or 18 postfertilization (pf) pregnant rats were given a single injection of 3H-thymidine (thy). At 30 postnatally days of age the pups were sacrificed and brain sections were prepared and processed for autoradiography. Three sections of the SDN-POA and an adjacent area just lateral to it in the MPOA were also analyzed. In the MPOA and the SDN-POA the percentage (%) of labeled neurons decreases as the day of injection of thy approaches the end of gestation, but the time period in which neuroblast divisions occurred is markedly different for the SDN-POA as compared to that for the MPOA. DNA synthesis occurs as late as day 18pf for neurons which form the SDN-POA but ceases on day 16pf for those destined for the MPOA. There is a sex difference in neuronal production on both day 14 and 17pf for neurons destined for the SDN-POA. After injection on day 14pf the % labeled neurons is larger in the female than in the male but after injection on day 17pf this is reversed. There are also significant sex differences as well as a temporal gradient associated with the % labeled neurons in the SDN-POA in relation to their final anterior-posterior position. In addition, this study confirms our previous results which justify labeling the SDN-POA a nucleus, since neuronal density in this region in the male and female is significantly greater that that in the surrounding MPOA. These data illustrate that the specific neurons which comprise the SDN-POA in both the male and female are being produced as late as day 18pf, whereas neurons located in the MPOA but not in the SDN-POA have all been born by day 16pf. Neuroblast division which produces the neurons of the SDN-POA may begin earlier and terminate sooner in the female than in the male. These differences in neuronal production may partially account for the sexual dimorphism seen in the volume and neuronal number of the SDN-POA of the adult rat.

Animals↗
PubMed1983

Extrinsic and intrinsic fiber connections of the telencephalon in a teleost, Sebastiscus marmoratus.

Extrinsic and intrinsic fiber connections of the telencephalic subdivisions of Nieuwenhuys ('62) in a teleost, Sebastiscus marmoratus, were studied by means of horseradish peroxidase (HRP) and Fink-Heimer methods. The olfactory bulb projects bilaterally to area dorsalis pars posterior, area ventralis pars ventralis, pars lateralis, pars posterior, pars intermedia, and the nucleus posterior tuberis of Peter et al. ('75) and receives fibers from ipsilateral area dorsalis pars centralis, pars posterior, area ventralis pars dorsalis, and pars supracommissuralis. Area dorsalis pars posterior sends numerous fibers to the ipsilateral ventral region of area dorsalis pars medialis, from which fibers of the medial forebrain bundle arise and terminate in the inferior lobe and nucleus posterior tuberis. Area dorsalis pars lateralis, pars dorsalis, and the dorsal region of pars medialis are the main targets of extratelencephalic ascending afferents. Area dorsalis pars lateralis receives fibers from the ipsilateral nucleus prethalamicus of Meader ('34), where tectal projections terminate massively. Area dorsalis pars dorsalis and the dorsal region of pars medialis receive afferents from the ipsilateral nucleus preglomerulosus of Schnitzlein ('62), nucleus posterior tuberis, area preoptica pars medialis of Crosby and Showers ('69), and nucleus entopeduncularis of Sheldon ('12). Raphe nuclei and locus ceruleus project bilaterally to area dorsalis pars centralis, pars dorsalis, pars lateralis, and the dorsal region of pars medialis. Area dorsalis pars centralis, pars dorsalis, and the dorsal region of pars medialis are important sources of extratelencephalic efferents. These subdivisions give rise to the lateral forebrain bundle and project to the ipsilateral nucleus prethalamicus, nucleus preglomerulosus, inferior lobe, nucleus paracommissuralis of Ito et al. ('82), optic tectum, torus semicircularis, and the bilateral mesencephalic tegmentum. Within the telencephalon, most of the ventral subdivisions project to ipsilateral area dorsalis pars centralis, pars dorsalis, pars lateralis, and the dorsal region of pars medialis. Area dorsalis pars centralis has reciprocal connections with ipsilateral area dorsalis pars lateralis, pars dorsalis, pars posterior, and the dorsal region of pars medialis. A dorsal part of the anterior commissure is composed of axons of the ventral region of area dorsalis pars medialis destined to the contralateral ventral region of area dorsalis pars medialis. A ventral part of the anterior commissure contains axons of area dorsalis pars centralis destined to contralateral area dorsalis pars lateralis.

Animals↗
PubMed1986

The growth of muscle nerves in relation to the formation of primary myotubes in the developing chick forelimb.

A study has been made of the development of muscle nerves to primary myotube clusters destined to become the flexor carpi ulnaris (fcu) and flexor digitorum profundus (fdp) muscles in the avian forelimb. Myotubes and nerves were identified by immunofluorescent techniques using antibodies to the heavy and light subunits of myosin and neurofilament, respectively. At stage 24 the main ventral nerve trunk (the brachialis longus inferior nerve; bli n) had entered the limb before the appearance of myotubes in the limb. At stage 25/26 the bli n within the ventral compartment of the forearm had given rise to the interosseus nerve (in n) and the medial-ulnar nerve (m-u n) at the junction of the stylopodium and zeugopodium. The first few myotubes of the fdp and fcu muscles were observed at this level within the ventral premuscle cell mass; however, no nerves projected toward these myotubes from either the in n or the m-u n at this time. At stage 26/27 the fcu and the fdp muscles each consisted of clusters of 20-40 myotubes; each cluster was clearly delineated within the ventral premuscle cell mass. By this time small groups of axons had left the in n and the m-u n to grow into the fdp and fcu myotube clusters, respectively; these axons formed the muscle nerves. At stage 28/29 the number of primary myotubes in the clusters composing the fdp and fcu muscles had greatly increased, as did the size of the muscle nerves; each muscle was still clearly identifiable within the ventral muscle mass. By stage 32 the fdp and fcu muscles had clearly separated and the muscle nerves had divided into several well-spaced branches within each muscle. The present observations show that the main nerve trunks grow into the limb before the formation of myotubes expressing myosin isozymes. When myotubes do form they appear in small clusters at specific sites within the premuscle mass, before muscle nerves appear; a distinct muscle is destined to form from each of these clusters. Muscle nerves first branch from the main limb nerves when the myotube cluster contains more than about ten myotubes.

Animals↗
PubMed1989

Compartmental and topographical distributions of axons in nerves to the amphibian (Bufo marinus) glutaeus muscle.

The present work seeks to determine if axons to an amphibian muscle are segregated in nerve trunks between the spinal cord and muscle according to their primary nerve destination or their topographical projection in the muscle. The distribution of axons to different compartments and subcompartments of the amphibian (Bufo marinus) glutaeus muscle has been determined in transverse sections of spinal and limb nerves after retrogradely labelling the axons with horseradish peroxidase. Glutaeus axons were dispersed widely through spinal nerves 8 and 9 but loosely gathered together in one quadrant of the sciatic nerve after passing through the lumbar plexus. Glutaeus axons became tightly clustered to the exclusion of other axons along the length of the triceps femoris nerve after it divides from the sciatic nerve. Furthermore, axons destined for one of the two glutaeus primary nerve branches segregate from those of the other branch at the level of the triceps femoris nerve before the glutaeus nerve forms. On the other hand, motoneurones that subserve a primary branch are not segregated, but are found throughout the rostrocaudal extent of the glutaeus motoneurone pool. Injection of horseradish peroxidase under the epimysium of either the ventral or the dorsal surfaces of the glutaeus muscle labelled motoneurones preferentially in either the rostral or caudal part of the motoneurone pool, respectively. This confirms studies that have shown a topographical projection from the spinal motoneurone pool onto the glutaeus muscle. However, there was no segregation of dorsally projecting axons in the glutaeus and primary nerve branches. Thus, glutaeus axons segregate according to their muscle compartmental projections well before entering the muscle, but they show no organization in nerves with respect to their topographical projections within a compartment.

Animals↗
PubMed1990

Organization and postnatal development of zebrin II antigenic compartmentation in the cerebellar vermis of the grey opossum, Monodelphis domestica.

The mammalian cerebellar cortex consists of a number of parasagittal Purkinje cell compartments that can be demonstrated cytochemically. The afferent inputs to the cerebellum are also compartmentalized, and a complex but reproducible relationship exists between the afferents and the intrinsic maps. Developmental studies in the rat have shown that many of the main features of compartmentation are already established at birth, and are therefore not easily manipulated experimentally. The compartmentation antigen zebrin II is expressed selectively by Purkinje cell subsets in a range of species, including fish and primates. In this study, zebrin II immunoreactivity has been studied in the grey opossum, Monodelphis domestica, in order to develop a marsupial model of compartment formation in which the early developmental events are more readily accessible. A monoclonal antibody to zebrin II from the weakly electric fish Apteronotus recognizes a 36 kD polypeptide in homogenates of Monodelphis cerebellum that appears to be identical to the antigen in the rat. Immunocytochemistry reveals that zebrin II in adult Monodelphis is confined exclusively to the cerebellum, where it is expressed by a subset of Purkinje cells. All regions of the cell, except the nucleus, are stained. The zebrin II+ Purkinje cells are arranged in a set of parasagittal compartments interposed by similar zebrin II- compartments. In each hemicerebellum there is one zebrin II+ band abutting the midline (P1+), and two others laterally in the vermis (P2+, P3+). A fourth zebrin II+ compartment straddles the paravermian region (P4+). Three other compartments have been identified in the hemisphere (P5+, P6+, P7+). This arrangement is very similar to that found in the rat. During postnatal development, zebrin II is first expressed between P14 and P21 in Purkinje cells of the posterior lobe vermis, and spreads throughout the cerebellar cortex by P28. As in rat, there is a stage at which all Purkinje cells are zebrin II+, including those destined to be zebrin II- in the adult. The mature pattern of expression emerges after P35 as immunoreactivity gradually disappears from the cells destined to become zebrin II-. The adult appearance is attained only after P56. The developmental timetable is therefore similar to that in rat, but is rather more protracted. Monodelphis should prove to be a valuable experimental model in which to study the early events leading to the formation of cerebellar compartments.

Animals↗
PubMed1990

Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale.

In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22. Concordant with this is the observation that the hippocampal intermediate zone, which contains the sojourning young pyramidal cells, greatly enlarges between days E16 and E20, then suddenly diminishes and disappears by day E22. The other factor that may contribute to the prolonged sojourn of pyramidal cells, specifically those destined to settle in the CA1 region, is the pattern of alveolar channel development. This transient extracellular matrix begins to form several days after the onset of pyramidal cell neurogenesis, grows in a direction opposite to the settling of pyramidal cells in the stratum pyramidale, and does not reach the subicular end of Ammon's horn until day E21.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Buried alive: how osteoblasts become osteocytes.

During osteogenesis, osteoblasts lay down osteoid and transform into osteocytes embedded in mineralized bone matrix. Despite the fact that osteocytes are the most abundant cellular component of bone, little is known about the process of osteoblast-to-osteocyte transformation. What is known is that osteoblasts undergo a number of changes during this transformation, yet retain their connections to preosteoblasts and osteocytes. This review explores the osteoblast-to-osteocyte transformation during intramembranous ossification from both morphological and molecular perspectives. We investigate how these data support five schemes that describe how an osteoblast could become entrapped in the bone matrix (in mammals) and suggest one of the five scenarios that best fits as a model. Those osteoblasts on the bone surface that are destined for burial and destined to become osteocytes slow down matrix production compared to neighbouring osteoblasts, which continue to produce bone matrix. That is, cells that continue to produce matrix actively bury cells producing less or no new bone matrix (passive burial). We summarize which morphological and molecular changes could be used as characters (or markers) to follow the transformation process.

Animals↗
PubMed2004

A randomized controlled trial of a behavior advisory service for hospitalized older patients with confusion.

OBJECTIVE: To determine whether individualized advice on non-pharmacological strategies for hospitalized older patients with confusion and behavioral problems can improve levels of agitation and reduce the use of psychotropic medication. METHOD: Pragmatic randomized controlled trial in two metropolitan teaching hospitals in South Australia. Seventy-one older patients with confusion and a behavioral disturbance were randomly allocated to receive either an assessment and ongoing individualized advice from an extended practice nurse on non-pharmacological strategies or usual care. Usual care included an assessment by a geriatrician. MEASUREMENTS: Primary outcomes were levels of agitation (Pittsburgh Agitation Scale), appropriateness of psychotropic medication prescribing (Medication Appropriateness Index) and levels of psychotropics administered (chlorpromazine and diazepam dose equivalents). Secondary outcomes were length of stay, discharge destination, number of falls, restraint use and satisfaction from nursing staff and next of kin. RESULTS: Levels of agitation were modest at baseline with mean PAS intervention group 3.4 (SD = 0.5) and control group 4.0 (SD = 0.4) and both groups improved over time to 1.7 (SD = 0.4) for the intervention group and 1.8 (SD = 0.3) for the control group on the final day of data collection. Median length of follow-up was nine days. There was no effect of the intervention on levels of agitation, amount and appropriateness of psychotropic medication prescribed and administered, falls, length of stay, discharge destination, restraint use and nursing and next of kin satisfaction. CONCLUSION: A nursing consultation service providing individualized non-pharmacological advice does not improve patient agitation or use of psychotropic medication for older patients with confusion and behavioral problems in an acute hospital.

Aged↗
PubMed1995

Elevated antibody titers to Epstein-Barr virus prior to the diagnosis of Epstein-Barr-virus-associated gastric adenocarcinoma.

Epstein-Barr virus (EBV) has recently been identified in the tumor cells of patients with gastric carcinoma. We tested pre-morbid serum samples from a carefully monitored cohort of Japanese men in order to investigate the possibility that patients with EBV-associated gastric cancer represent a sub-set of individuals with long-standing difficulties in appropriately managing EBV infection. From a serum bank, we obtained 108 samples derived from 54 patients destined to develop gastric adenocarcinoma and 54 controls. Samples were tested under code for antibodies to EBV-capsid antigen, early antigen and nuclear antigen. Individuals who were positive for IgA antibodies against EBV viral-capsid antigen (VCA) and IgG antibodies against the R component of EBV early antigen were at a 3.9-fold and 1.9-fold excess risk of disease, respectively. Antibody titers to EBV VCA were significantly higher in those destined to get EBV-associated gastric cancer than those subsequently developing non-EBV-associated gastric cancer or age-and-gender-matched controls. These findings suggest that the inability to control EBV infection on a long-term basis exists many years prior to the development of EBV-associated gastric cancer, and that EBV may play an etiologic role in this sub-set of malignancies.

Adenocarcinoma↗
PubMed1984

Acidification of endocytic compartments and the intracellular pathways of ligands and receptors.

Several hormones, serum proteins, toxins, and viruses are brought into the cell by receptor-mediated endocytosis. Initially, many of these molecules and particles are internalized into a common endocytic compartment via the clathrin-coated pit pathway. Subsequently, the ligands and receptors are routed to several destinations, including lysosomes, the cytosol, or the plasma membrane. We have examined the mechanism by which sorting of internalized molecules occurs. A key step in the process is the rapid acidification of endocytic vesicles to a pH of 5.0-5.5 This acidification allows dissociation of several ligands from their receptors, the release of iron from transferrin, and the penetration of diphtheria toxin and some viral nucleocapsids into the cytoplasm. Transferrin, a ligand that cycles through the cell with its receptor, has been used as a marker for the recycling receptor pathway. We have found that in Chinese hamster ovary (CHO) cells transferrin is rapidly segregated from other ligands and is routed to a complex of small vesicles and/or tubules near the Golgi apparatus. The pH of the transferrin-containing compartment is approximately 6.4, indicating that it is not in continuity with the more acidic endocytic vesicles which contain ligands destined to be degraded in lysosomes.

Animals↗
PubMed2005

GABAB receptor intracellular trafficking after internalization in Paramecium.

The number of neurotransmitter receptors on the plasma membrane is regulated by the traffic of intracellular vesicles. Golgi-derived vesicles provide newly synthesized receptors to the cell surface, whereas clathrin-coated vesicles are the initial vehicles for sequestration of surface receptors, which are ultimately degraded or recycled. We have previously shown that GABAB receptors display a punctuate vesicular pattern dispersed on the cell surface and throughout the cytoplasm and are internalized via clathrin-dependent and -independent endocytosis. Here we have studied constitutive GABAB receptor trafficking after internalization in Paramecium primaurelia by confocal laser scanning microscopy and multiple immunofluorescence analysis. After internalization, receptors are targeted to the early endosomes characterized by the molecular markers EEA1 and rab5. Some of these receptors, destined for recycling back to the plasma membrane, traffic from the early endosomes to the endosomal recycling compartment that is characterized by the presence of rab4-immunoreactivity (IR). Receptors that are destined for degradation exit the endosomal pathway at the early endosomes and traffic to the late endosome-lysosome pathway. In fact, some of the GABAB-positive compartments were identified as lysosomal structures by double staining with the lysosomal marker LAMP-1. GABAB vesicle structures also colocalize with TGN38-IR and rab11-IR. TGN38 and rab11 are proteins found in association with post-Golgi and recycling endosomes, respectively.

Animals↗