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PubMed1985

Changes in motility after jejunal and ileal resection: electromyographic study in rats.

The aim of this work was to compare the effects of massive jejunal and ileal resections on intestinal motility using an electromyographic technique. Male Wistar rats were used: in the first group a massive jejunal resection was performed, conserving a 7-cm segment after the ligament of Treitz; the rats of the second group underwent an ileal resection, preserving 7 cm of the terminal ileum. Motility was studied at the 10th and 30th postoperative days by means of electrodes implanted throughout the remaining bowel and was expressed by the pattern of recurrence of the migrating myoelectric complex (MMC). In a fasting state, in both transected and resected animals at the 10th postoperative day, the gradient in the duration of MMC along the intestine still existed. However, on the 30th postoperative day, in animals with jejunal resection only, there was an adaptive process: the duration of MMC in the remaining jejunum was significantly increased to the duration in the ileum. After the end of the postprandial inhibition of the appearance of the MMC, on the 10th postoperative day there was a significant decrease in the duration of MMC in the ileum in both types of resection, compared to the controls. However, on the 30th postoperative day, the duration of MMC returned to its control value. In conclusion, jejunal resection seems to induce more important adaptive processes in intestinal motility than does ileal resection. The different results are discussed.

Animals↗
PubMed1998

Cellular and molecular mechanisms of radiation inhibition of restenosis. Part I: role of the macrophage and platelet-derived growth factor.

PURPOSE: The major radiobiological issue in determining the rationale for the use of radiation to inhibit vascular restenosis is the identification of the target cell(s) and/or cytokine(s) responsible for neointimal hyperplasia and vascular remodeling. The central hypothesis of this report is that the macrophage/monocyte and PDGF are key elements in the process of neointimal hyperplasia seen following angioplasty, similar to their role in lesion formation and progression found in atherosclerotic thickening. Specific immunohistochemical and cytochemical stains were applied to a rat carotid model in a temporal series after balloon angioplasty to determine macrophage activity vs. smooth muscle cell proliferation, the latter being classically thought to be the cell responsible for restenosis. METHODS AND MATERIALS: Neointimal hyperplasia was created in an established rat carotid artery model by a balloon catheter technique. Immediately following injury, treatment groups received irradiation via high dose rate (HDR) brachytherapy, the 192Ir source being placed externally to the vessel. Radiation was delivered to a length of 2 cm of the injured vessel at doses of 5, 10, and 15 Gy, and the animals were sacrificed at various time points following treatment (24 h to 6 months). Serial sections of tissue were stained immunohistochemically with the primary antibodies CD11b, mac-1, anti-PDGF, and alpha-smooth muscle actin. RESULTS: Immediately (24 h) postinjury, there is an apparent migration of macrophages seen in the adventitia; after 1 week, proliferation and migration of macrophages could be seen clearly within all the vessel layers, especially in the intima; by 3 weeks, when there was evidence of neointimal hyperplasia, macrophages could still be seen, mainly in the intima scattered among the smooth muscle cells and myofibroblasts, and to a lesser degree at 6 months. There was corresponding expression of PDGF, whenever and wherever there were zones of activation/neointimal hyperplasia. Alpha-smooth muscle actin staining identified the smooth muscle cells distinct from the macrophages, and these SMCs exhibited activation in the neointimal hyperplasia zones at all later time points. Furthermore, we showed that radiation significantly reduced the macrophage population, while the onset of neointimal hyperplasia was accompanied by a return of the macrophage population. CONCLUSION: Our results suggest that the activated adventitial macrophage/monocyte are the key cells responsible for initiating the arterial neointimal hyperplasia and vascular remodeling developing postangioplasty as they are in the initiation and perpetuation of atheromatous thickening. Irradiation delivered immediately postinjury is, therefore, highly effective, because the macrophage population is exquisitely radiosensitive.

Animals↗
PubMed1996

Heparan sulfate proteoglycans function in the binding and degradation of vitronectin by fibroblast monolayers.

Vitronectin, a 75-kDa plasma protein is also found in the extracellular matrix, where it is believed to promote cell adhesion and migration. In addition to its role in adhesion, matrix vitronectin is also believed to function as an opsonin promoting the clearance of thrombin-serpin complexes from the matrix. Vitronectin is cleared from the matrix by receptor-mediated endocytosis followed by lysosomal degradation, suggesting that cells can regulate the levels of vitronectin present in the matrix. However, the mechanism by which plasma vitronectin associates with the extracellular matrix remains unclear. Studies were conducted to define the binding site(s) for vitronectin in fibroblast cell layers. Sodium chlorate, a competitive inhibitor of proteoglycan sulfation, produced a dose-dependent decrease in both binding and degradation of vitronectin. This inhibition was reversible in that removal of chlorate returned both binding and degradation of vitronectin to near control levels within 24 h. The binding of vitronectin to cell layers was not dependent on cells because vitronectin bound directly to isolated matrix. Isolated matrices prepared from cell layers treated with sodium chlorate also exhibited a dose-dependent decrease in vitronectin binding, consistent with the binding site for vitronectin in the matrix being sulfated proteoglycans. Binding and degradation of vitronectin were also sensitive to the addition of exogenous heparin, suggesting that the heparin binding domain of vitronectin was mediating binding to the matrix. Incubating fibroblast monolayers with heparinase III resulted in a 40% decrease in binding and degradation of vitronectin. Taken together, the above findings suggest that vitronectin's binding to the matrix and its subsequent degradation are dependent on heparan sulfate proteoglycans.

Binding Sites↗
PubMed2004

Is there a future for neural transplantation?

Traditionally neural transplantation has had as its central tenet the replacement of missing neurons that have been lost because of neurodegenerative processes, as exemplified by diseases such as Parkinson disease (PD). However, the effectiveness and widespread application of this approach clinically has been limited, primarily because of the poor donor supply of human fetal neural tissue and the incomplete neurobiological understanding of the circuit reconstruction required to normalize function in these diseases. So, in PD the progress from promising neural transplantation in animal models to proof-of-principle, open-labeled clinical transplants, to randomized, placebo-controlled studies of neural transplantation has not been straightforward. The emergence of previously undescribed adverse effects and lack of significant functional advantage in recent clinical studies has been disappointing and has served to cast a new, and perhaps more realistic, perspective on this treatment approach. In fact, there have been calls by some involved in neural transplantation to return to the drawing board before pressing on with further clinical trials, and the return to basic experimentation. This therefore precipitates the question - is there a future for neural transplantation? It is important to remember that there are a number of possible explanations for the disappointing results from the recent clinical trials in PD, ranging from the mode of transplantation to patient selection. Nevertheless, almost irrespective of these reasons for the current trial results, there have always been significant practical and ethical problems with using human fetal tissue, and so a number of alternative cell sources have been investigated. These alternative sources include stem cells, which are attractive for cell-based therapies because of their potential ease of isolation, propagation and manipulation, and their ability in some cases to migrate to areas of pathology and differentiate into specific and appropriate cell types. Furthermore, the availability of stem cells derived from non-embryonic sources (e.g. adult stem cells derived from the sub-ventricular zone) has removed some of the ethical limitations associated with the use of embryonic human tissue. These potentially beneficial aspects of stem cells means that there is a future for neural transplantation as a means of treating patients with a range of neurological disorders, although whether this will ever translate into a truly effective, widely available therapy remains unknown.

Animals↗
PubMed1989

Lymphocyte migration in the spleen: the effect of macrophage elimination.

To study the influence of macrophages on the migration and distribution of lymphocytes in the spleen, macrophages were eliminated from the spleen of mice by injection of liposomes in which DMDP was encapsulated. This leads to an elimination of macrophages in both the red pulp and marginal zone of the spleen within 1-2 days. In these animals the distribution of lymphocytes was determined by transfer of either syngeneic fluoresceinated or Ly 5 congeneic cells. It was found that after elimination of the macrophages the number of lymphocytes immigrating into the spleen had decreased, although a comparable mode of compartimentalization was found with an initial localization in the marginal zone and a subsequent distribution into the white pulp. After this elimination spleen macrophage subsets return with different kinetics, and in this way the influence of the red pulp macrophages, the marginal zone macrophages and the marginal metallophilic macrophages on lymphocyte immigration and redistribution could be investigated. A quantitative decrease of immigration was still found when red pulp and marginal metallophilic macrophages had repopulated their compartments, but was only fully restored when the last population to repopulate the spleen after treatment with DMDP-liposomes, the marginal zone macrophages, had returned. Experiments with isolated T and B cells showed that the elimination of macrophages had a profound effect on the localization of B cells in the white pulp, whereas it hardly affected T cells.

Animals↗
PubMed2006

A longitudinal study of PTSD in a sample of adult mass-evacuated Kosovars, some of whom returned to their home country.

PTSD among a sample of mass-evacuated adults from Kosovo was studied using a prospective design with a baseline study and follow-ups at 3 and 6 months in Sweden, and with an additional follow-up after 1.5 years in both Sweden and Kosovo. Trauma events and PTSD-related symptoms were measured by the Harvard Trauma Questionnaire (HTQ). At the additional follow-up after 1.5 years the same measure (HTQ) was used as well as clinical diagnostic interviews with the SCID instrument and measurement of saliva cortisol levels. Thirty-seven percent had PTSD-related symptoms at baseline. Morbidity increased at the three follow-ups. About 80% of the participants had PTSD at the additional follow-up after 1.5 years. The HTQ results were confirmed by clinical diagnoses and the participants diagnosed with PTSD also had low saliva cortisol levels. The results are discussed in terms of trauma, time needed to develop PTSD, post-migration stress and selection mechanisms.

Adolescent↗
PubMed2006

A beta1,4-galactosyltransferase is required for convergent extension movements in zebrafish.

Our understanding of how complex carbohydrates function during embryonic development is still very limited, primarily due to the large number of glycosyltransferases now known to be involved in their synthesis. To overcome these limitations, we have taken advantage of the zebrafish system to analyze the function of complex carbohydrates during development by down-regulating the expression of specific glycosyltransferases. Herein, we report the identification of the zebrafish ortholog of mammalian beta1,4-galactosyltransferase I, beta4GalT1, and its requirement for proper convergent extension movements during gastrulation. beta4GalT1 is expressed in the oocyte and throughout the embryo during the first 24 h of development. Knockdown of zebrafish beta4GalT1 by two independent morpholino oligonucleotides results in embryos with a truncated anterior-posterior axis, as well as elongated somites and moderate defects in the patterning of the head mesenchyme. Co-injection of zebrafish beta4GalT1 mRNA returns galactosyltransferase activity to control levels and rescues the defects produced by morpholino oligonucleotides. In situ hybridizations of various molecular markers reveal that the axial mesoderm of epiboly stage embryos is abnormally widened in beta4GalT1 morphants, indicative of abnormal convergent extension. Consistent with this, the rate of anterior-posterior axis elongation is reduced relative to control-injected embryos, similar to that seen in known convergent extension mutants. Among the many potential substrates for beta4GalT1 is laminin, a principle component of the extracellular matrix that supports cell movements such as those that occur during convergent extension. Previous in vitro studies have shown that the galactosylation status of laminin directly influences its ability to support cell spreading and migration. In this regard, laminin isolated from beta4GalT1 morphant embryos is poorly galactosylated, which may contribute to defective cell migration during convergent extension movements. This work demonstrates that zebrafish can be used to identify critical developmental roles for specific glycosyltransferases that would not be obvious otherwise, such as an absolute requirement for beta4GalT1 during convergent extension movements.

Amino Acid Sequence↗
PubMed1984

Morphogenesis of the cranial segments and distribution of neural crest in the embryos of the snapping turtle, Chelydra serpentina.

Recent studies of the heads of vertebrates have shown a primitive pattern of segmentation in the mesoderm and neural plate not previously recognized. The role of this pattern in the subsequent distribution of cranial crest and the development of branchial arches and cranial nerves, may resolve century-old arguments about the evolution of vertebrate segmentation. In this study, we examine the early embryonic development of the cranium of a primitive amniote, the snapping turtle, with the SEM. We show that the paraxial mesoderm cranial to the first-formed somites is segmented and that this pattern is based on somitomeres, similar to those described in the embryos of chick and mouse. Seven contiguous pairs of somitomeres comprise the "head mesoderm"; the first pair of somites actually arise from the eighth pair of somitomeres added to the axis. Cranial somitomeres are associated with specific brain regions, in that the first pair lie adjacent to prosencephalon, the second and third pair are adjacent to the mesencephalon, and the fourth, fifth, sixth, and seventh pair of somitomeres lie adjacent to individual neuromeres of the rhombencephalon. Prior to the closure of the anterior neuropore, cranial neural crest cells first emerge from the mesencephalon and migrate onto the second and third somitomeres. Shortly thereafter, neural crest cells emerge at more caudal levels of the rhombencephalon, beginning at the juncture of the fifth and sixth somitomeres. Eventually, neural crest originating from the mesencephalon spreads caudally as far as the fourth somitomere, leaving a gap in crest emigration adjacent to the fifth somitomere. The otic placode develops from the surface ectoderm covering the sixth and seventh somitomeres, and the adjacent rhombencephalic neural crest moves around the cranial and caudal edge of the placode. At more caudal levels, rhombencephalic crest cells merge with cervical crest populations to form a continuous sheet over the somites. By the time the anterior neuropore closes, some of the mesencephalic crest cells return from the paraxial mesoderm to spread onto the rostral wall of the optic vesicle and future telencephalon. The segmentation of the mesoderm and patterned distribution of cranial neural crest seen in snapping turtle embryos, further strengthens the argument that the heads of amniotes are derived from a common metameric pattern established early during gastrulation.

Animals↗
PubMed1985

A simplified method for the preparation of rat thyroxine-binding prealbumin. Factors influencing its circulating level.

Rat thyroxine-binding prealbumin (TBPA) was isolated in three simple steps by means of a serum precipitation by a 5% phenol solution and two consecutive semi-preparative polyacrylamide gel electrophoreses. The overall yield was 15% and the TBPA preparation contained less than 1% impurities. In addition a monospecific antiserum was raised in the rabbit. In polyacrylamide gel, rat TBPA, as with its human counterpart, migrated anodally to albumin while in agarose gel, its electrophoretic mobility was similar to that of albumin. Serum TBPA measured in adult male Wistar rats did not exhibit a circadian rhythm. However, a significant 13% decrease was observed between 9 and 15 h, followed by the restoration of the initial value by 21 h. TBPA concentration was measured in 1-, 15- and 28-day-old male and female pups as well as in adult rats. The level of this protein increased from 1 to 28 days of age and did not display any sexual difference. Yet, while TBPA concentrations in adult males were similar to those recorded in the 28-day-old pups, for adult females, they returned to the levels measured in the 1-day-old pups.

Age Factors↗
PubMed1995

[Contribution of a mathematical model in the control of a parasitosis: the case of human African trypanosomiasis due to Trypanosoma brucei gambiense].

Trypanosoma brucei gambiense sleeping sickness transmitted by tsetse flies (Glossina spp.) is lethal if not treated adequately. The endemicity was generally well under control in the sixties. However, since the seventies the disease is returning in most of its old foci, with alarming endemic levels in several areas. Mathematical modelling provides a rational basis for finding the optimal strategies to control these recrudescences. We present a deterministic model of the basic transmission of trypanosomiasis between human and vector hosts in natural situations. The parameters were quantified on the basis of available evidence from the literature. The model predicts a stable equilibrium state with very high prevalences: approximately 95% of humans and 27% of flies being infected. The model further shows that the build-up of an epidemic is initially very slow, and it takes several months before the equilibrium state is reached. Consequently communities have enough time to avoid catastrophic situations by migrating to safer areas. If is therefore unlikely that such high equilibrium situations will occur in practice. The expression of the basic reproductive rate R0, the number of new infections during the lifetime of an infected subject with high values of R0 implies that efforts to diminish transmission to levels where the disease cannot maintain itself in the population, have to be substantial. The necessary reduction of fly numbers in order to enable eradication, has been calculated. In almost all situations a reduction of at least 90% is necessary, which is in accordance with the field experiences of vector control programmes. The present model can be considered as a starting point in the further development of a complete simulation model, which could be applied in supporting decision making in trypanosomiasis control.

Animals↗
PubMed1994

Kainic acid induced alterations in antibody recognition of connexin43 and loss of astrocytic gap junctions in rat brain.

Intracerebral administration of kainic acid (KA) in rats was previously shown to abolish immunohistochemical labelling for the astrocytic gap junction protein connexin43 (Cx43) at sites depleted of neurons (Vukelic et al: Neurosci Lett 130:120-124, 1991). This response of Cx43 has now been further investigated with a number of different sequence-specific anti-Cx43 antibodies. At lesion sites in the thalamus, striatum, and hippocampus examined immunohistochemically with an antibody against amino acids (aa's) 346-363 in the Cx43 sequence, the antibody used in the earlier study, Cx43-immunoreactivity was increased 5 h after KA injections, absent by 24 h and for up to 2 weeks post-injection, and began to return to less than normal levels by 2 to 3 weeks post-injection. Analyses of KA lesion sites with antibodies against other sequences of Cx43 (amino acids 283-298, 253-270, 241-260, 113-123, and 49-61) revealed not only the presence but in some cases an increased density of Cx43 immunoreactivity after a survival time of 1 week. Immunolabelling patterns at these sites consisted of relatively large, coarse profiles rather the fine punctate labelling typically seen in sections of normal brain. In homogenates of KA-injected striatum analyzed by Western blots, Cx43 was detected at near normal or slightly increased levels at various survival times examined. The 43 kDa phosphorylated form of Cx43 and its faster migrating 41 kDa dephosphorylated form which is generated post-mortem by a brain phosphatase were both present after standard methods of tissue preparation for Western blot analysis, while only the 43 kDa form was present in normal and KA-injected striatum after inactivation of brain metabolism by focused cranial microwave irradiation. Ultrastructural investigations of lesions sites within the thalamus revealed a virtual absence of astrocytic gap junctions. These results demonstrate that Cx43 levels initially increase after intracerebral KA treatment, that its molecular organization in resident astrocytes is altered such that epitopes that are normally accessible to antibody are hidden while those that may be hidden or relatively inaccessible are exposed, and that this molecular alteration in Cx43 is associated with loss of astrocytic gap junctions.

Animals↗
PubMed1997

The regulation of p42/p44 mitogen-activated protein kinases in the injured rat carotid artery.

UNLABELLED: Arterial smooth muscle cell (SMC) proliferation is an important factor in the development of atherosclerotic plaques and restenotic lesions following arterial reconstruction. Basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and thrombin are known to induce SMC proliferation and migration in vitro and in vivo. In cultured cells the proliferative responses to these mitogens depend on the activation of the p42/p44 mitogen-activated protein kinases (MAPKs), whereas the role of these kinases in vivo has yet to be established. We tested whether MAPK activity is induced following vessel injury and whether activity is dependent on the release of bFGF, PDGF, and thrombin. Following balloon injury of the left carotid of male Sprague-Dawley rats, arteries were removed and analyzed with respect to MAPK activity, BrdU-labeled nuclei, and/or luminal, medial, and intimal areas. MAPK activity is induced in the rat carotid artery following balloon-catheter injury with a maximum activation at 30 min with a return to just above baseline at 11 hr after injury. Intravenous administration of heparin or neutralizing antibodies to bFGF or PDGF prior to injury reduced SMC proliferation and neointimal lesional formation but did not affect the early induction of MAPK activity. Administration of a tissue factor inhibitor or thrombin inhibitor also did not affect MAPK activity, although it impaired the initiation of the coagulation cascade. IN CONCLUSION: (1) MAPK is activated in a time-dependent manner in response to injury; (2) the antiproliferative effect of heparin in vivo is not mediated through the inhibition of MAPK activity induced 30 min after injury; (3) the activation of MAPK after 30 min is not dependent on PDGF, bFGF, or thrombin following vessel injury in the rat.

Animals↗
PubMed2000

PDGF regulates gap junction communication and connexin43 phosphorylation by PI 3-kinase in mesangial cells.

BACKGROUND: Gap junctional intercellular communication (GJIC) plays an important role in the regulation of cell growth, migration, and differentiation. Ultrastructural and histochemical studies indicate the existence of a high density of gap junctions among mesangial cells (MCs), but little is known about their regulation. Because of the close link between growth and GJIC, we examined how platelet-derived growth factor (PDGF) may affect GJIC in cultured MCs. METHODS: MCs were exposed to PDGF in the presence or absence of phosphatidylinositol 3' kinase (PI3K) inhibitors, and GJIC was evaluated by the transfer of Lucifer yellow. The gap junction protein connexin43 (Cx43) was examined by immunohistochemistry, immunoprecipitation, and Western blot. RESULTS: The addition of PDGF into MC culture caused a rapid and transient inhibition of GJIC, with maximal inhibition (80%) occurring 15 minutes after PDGF exposure and returning to control levels after 90 minutes. This action of PDGF could be largely prevented by pretreatment of MCs with the PI3K inhibitor LY294002. Immunochemical staining showed that PDGF did not alter the localization and distribution of Cx43. Immunoprecipitation studies demonstrated that PDGF induced a rapid and transient increase of tyrosine phosphorylation of Cx43 protein, which was dose dependent and in accordance with the time course of the disruption of GJIC. PDGF also elicited activation of extracellular signal-regulated kinase (ERK). Using two structurally unrelated PI3K inhibitors, wortmanin and LY294002, both tyrosine phosphorylation of Cx43 and activation of ERK stimulated by PDGF were largely blocked. CONCLUSION: These results suggest that PDGF abrogates GJIC function in MCs via the PI3K-dependent signaling pathway. Disruption of GJIC by PDGF could be one mechanism by which PDGF modulates MC behavior. Participation of PI3K in the regulation of GJIC demonstrates the complex coordination of molecular events that accompany MC mitogenesis.

Animals↗
PubMed1997

Cardiovascular malformations in Smith-Lemli-Opitz syndrome.

We reviewed 215 patients (59 new, 156 from the literature) with Smith-Lemli-Opitz syndrome (SLOS), and found that 95 (44%) had a cardiovascular malformation (CVM). Classifying CVMs by disordered embryonic mechanisms, there were 5 (5.3%) class 1 (ectomesenchymal tissue migration abnormalities), 56 (58.9%) class II (abnormal intracardiac blood flow), 25 (26.3%) class IV (abnormal extracellular matrix), and 5 (5.3%) class V (abnormal targeted growth). Comparing the frequencies of individual CVMs in this series with a control group (the Baltimore-Washington Infant Study), there were 6 individual CVMs which showed a significant difference from expected values. When frequencies of CVMs in SLOS were analyzed by mechanistic class, classes IV and V were significantly more frequent, and class I significantly less frequent, than the control group. Although CVMs in SLOS display mechanistic heterogeneity, with an overall predominance of class II CVMs, the developmental error appears to favor alteration of the cardiovascular developmental mechanisms underlying atrioventricular canal and anomalous pulmonary venous return. This information should assist the clinical geneticist evaluating a patient with possible SLOS, and should suggest research direction for the mechanisms responsible for the SLOS phenotype.

Female↗
PubMed1998

The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7.

Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a novel CC chemokine with selectivity for T lymphocytes and preferential expression in lymphoid tissues. We have studied its production, receptor usage and biological activities. High levels of SLC mRNA were detected in lymph nodes, the gastrointestinal tract and several gland tissues, but no expression was found by Northern blot analysis in freshly isolated or stimulated blood monocytes and lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed constitutive expression of SLC in the T cell areas and the marginal zone of follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B cell areas or sinuses. Comparison with immunocytochemical staining showed similarity between the in situ expression of SLC and the distribution of interdigitating dendritic cells but not with sinus-lining dendritic cells, macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its activity increased considerably when the cells were conditioned with IL-2 or phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also induced Ca2+ mobilization in these cells. Similar responses were obtained with EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7. This was confirmed using murine pre-B cells stably transfected with CCR7 which bound SLC with high affinity and showed chemotaxis and Ca2+ mobilization in response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A maximum was reached in 2-3 days and expression returned to initial levels within 8-10 days. The present study shows that SLC is constitutively produced within the T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.

Animals↗
PubMed1997

Thyrotropin regulates the levels of free ubiquitin and ubiquitin-protein conjugates in the male mouse thyroid.

The conjugation of ubiquitin to proteins can be a signal for their degradation, but can also be involved in regulatory processes not directly involved in protein degradation. Because thyrotropin (TSH) is the major physiological regulator of the thyroid, we have investigated whether changes in the circulating level of TSH influence the level of immunoreactive ubiquitin in the thyroid, as assessed by dot-blot assays. Putting male Balb/c mice on a low iodine diet with methimazole (MMI) in their drinking water for 14 days raised the level of ubiquitin by 425 % (p < 0.001) per microgram nonthyroglobulin protein (the mean thyroglobulin level dropped by 35% (p < 0.05)). Western blots similarly indicated that immunoreactivity migrating in the region of monoubiquitin, ubiquitin oligomers, and ubiquitinated thyroid proteins increased on the low iodine/MMI diet. Injecting 1 microg triiodothyronine (T3) 6 hours prior to sacrifice appeared to reduce the ubiquitin levels by 31% when compared with mice only on the low iodine/MMI (p < 0.07), but injection of T3 had no effect on ubiquitin levels in mice on the control diet. Injecting male ICR mice with a large dose of TSH (200 mU) increased immunoreactive ubiquitin levels by 50% (p < 0.05) 2 hours later. After a second dose of TSH was injected 12 hours later, the level of immunoreactive thyroglobulin fell by 17% (p < 0.05). With further 12 hourly injections, thyroglobulin levels then began to reaccumulate, and they had returned to the level of saline-injected controls after 50 hours (five TSH injections), while ubiquitin levels fell, but remained significantly elevated above the saline-injected controls (36%, p < 0.01). When ICR mice were given perchlorate in their drinking water to block the iodide pump, thus preserving thyroidal responsiveness to repeated TSH injections, the responses to the initial two TSH injections were similar to mice who received ordinary tap water. However, with further TSH injections, the reaccumulation of thyroglobulin did not occur: at 50 hours, thyroglobulin levels remained suppressed by 28% (p < 0.05), and ubiquitin levels actually rose slightly, and were significantly higher (57%, p < 0.01) than the saline-injected controls. These in vivo responses of free ubiquitin, oligoubiquitin, and ubiquitinated protein to changes in the level of circulating TSH suggest that ubiquitin-mediated mechanisms are involved in some of the thyroid's metabolic responses.

Animals↗
PubMed1988

Inhibition by colchicine of phospholipid secretion induced by lung distension.

The effect of colchicine, a microtubule disruptor, on phospholipid secretion stimulated by distension of fetal rabbit lungs was investigated. After colchicine injection and breathing for 45 min, pups were killed and their lungs were lavaged with colchicine. Controls were injected and lavaged with saline. All lungs were given static air inflation and a final lavage, and the returns were analyzed for phospholipid DNA, and lactate dehydrogenase. The first lavage after breathing yielded 33% less phospholipid with colchicine, 3.83 compared with 5.72 mg/g dry lung wt (P less than 0.05). The postinflation phospholipid yield was also significantly reduced with colchicine from 1.04 to 0.70 mg/g dry lung wt (P less than 0.05). The postinflation DNA was significantly reduced with colchicine, from 1.26 to 0.44 micrograms (P less than 0.01), suggesting reduced alveolar macrophages. Colchicine did not change the recovery by lavage of exogenous radioactive phospholipid. As reflected by ATP and lactate levels, tissue metabolism was well maintained. The results are interpreted to mean that colchicine reduced simultaneously lavage-associated phospholipid secretion, inflation-produced phospholipid secretion, and macrophage migration.

Adenosine Triphosphate↗
PubMed1988

A neuronal protein (NP185) associated with clathrin-coated vesicles. Characterization of NP185 with monoclonal antibodies.

Two monoclonal antibodies (S-8G8 and S-6G7) are characterized that react with an abundant neuronal protein associated with brain clathrin-coated vesicles (CCVs). This 185-kDa polypeptide (NP185) is not a transmembrane cargo molecule and is distinguishable from clathrin by several criteria including neuronal specificity, chymotryptic sensitivity, migration during two-dimensional gel electrophoresis, lack of cross-reactivity of S-8G8 or S-6G7 with purified clathrin, and lack of associated clathrin light chains. When 0.9 M NaCl extracts of CCVs were diluted and immunoprecipitated by either S-8G8 or S-6G7, NP185 precipitated as a complex with a fraction of the CCV assembly polypeptides. Immunofluorescence microscopy of PC12 cells cultured in nerve growth factor (NGF) revealed that NP185 was distributed in a punctate manner throughout the mature neurites. Immunoblot analysis of PC12 cell extracts, taken at various times during NGF-induced differentiation, revealed that steady-state accumulation of NP185 reaches significant levels 3 days after the addition of NGF and returns to undetectable levels when NGF is removed from the cultures. Significantly, the quantity of NP185 detected in differentiated PC12 cells exceeded the quantity of clathrin. These data indicate that while NP185 may be a specialized component of neuronal CCVs, its function in neuronal cells cannot be associated exclusively with these organelles.

Adaptor Proteins, Vesicular Transport↗