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D Fellmann

Publications and source records attributed to D Fellmann.

At least 19 recordsLinked to original sources
PubMed2004

Expression of the secreted FAD-dependent sulfydryl oxidase (QSOX) in the guinea pig central nervous system.

cpQSOx1 is a member of the QSOx family of proteins, expressed in the guinea pig (Cavia porcellus) and ortholog of the rat rQSOx1. In this study, in vitro experiments were conducted and showed that, as other member of this family, cpQSOx1 has a sulfydryl oxidase activity, and is a secreted protein. Then, the expression of this enzyme was researched in the guinea pig brain, as very little information exists yet on the expression of QSOx family members in the central nervous system. By immunohistochemistry, RT-PCR and in situ hybridization, cpQSOx1 is synthesized by neurons throughout the whole guinea pig central nervous system. Reticular structures as the basal forebrain, reticular thalamic nucleus and reticular nuclei of the brainstem contained the densest labeling. These results are discussed in terms of putative roles of this protein in synaptic strengthening and in redox activities.

Animals↗
PubMed2004

QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens.

The expression of the rat quiescin sulfhydryl oxidase (rQSOX) and its putative regulation by estrogens were investigated in the adenohypophysis. Immunohistochemical observations revealed that rQSOX protein is abundantly expressed throughout the anterior lobe of the pituitary, and can be found in almost all the different cell populations. However, as shown by double immunohisto-chemistry, the cells displaying the strongest rQSOX labeling belong to a subset of gonadotrophs. Immunoelectron microscopy showed that, in adenohypophyseal cells, the protein is linked to the membranes of the rough endoplasmic reticulum, the Golgi apparatus and to dense-core secretory granules. These results are consistent with the secretion of the protein and its presumed role in the extracellular matrix. According to its sulfhydryl oxidase function, rQSOX could also participate in the intracellular folding of secreted proteins or hormones like LH and FSH and act as an endogenous redox modulator of hormonal secretion. A semiquantitative RT-PCR analysis of rQSOX level across the estrous cycle and the fact that chronic administration of 17 beta-estradiol to ovariectomized rats led to a sustained up-regulation of rQSOX in the pituitary suggest that rQSOX expression is controlled by sex hormone levels. Further investigations are needed in order to elucidate its precise roles in that gland and the mechanisms of its regulation.

Animals↗
PubMed2003

Evidence of melanin-concentrating hormone-containing neurons supplying both cortical and neuroendocrine projections.

In the rat, melanin-concentrating hormone-containing projections are detected in the median eminence and in the neural lobe of the pituitary. After vascular injections of the retrograde tracers fluorogold or fastblue, melanin-concentrating hormone neurons are retrogradely labeled in the rostromedial zona incerta and adjacent perifornical region. These neurons may be the source of the melanin-concentrating hormone projections toward the median eminence and posterior pituitary, and may release their secretory products into the bloodstream. After fastblue injections in the cerebral cortex and vascular fluorogold injections, some melaninconcentrating hormone neurons contain both tracers, indicating that they send collaterals in the cerebral cortex and in the median eminence/posterior pituitary. No such collaterals have been described for the classical neuroendocrine systems. The melanin-concentrating hormone system is thought to play a role in arousal in correlation with specific goal oriented behaviors such as feeding or reproduction. Some MCH neurons may be involved in such functions by modulating directly cortical activity as well as being neuroendocrine.

Afferent Pathways↗
PubMed2003

Diencephalic neurons producing melanin-concentrating hormone are influenced by local and multiple extra-hypothalamic tachykininergic projections through the neurokinin 3 receptor.

As melanin-concentrating hormone (MCH) neurons express the neurokinin 3 receptor (NK3) in the rat diencephalon, their innervation by tachykininergic fibers, the origin of this innervation and the effect of a NK3 agonist on MCH mRNA expression were researched. The obtained results show that the tachykininergic system develops complex relationships with MCH neurons. Overall, MCH cell bodies appeared targeted by both NKB- and SP-inputs. These afferents have multiple hypothalamic and extra-hypothalamic origins, but a local (intra-lateral hypothalamic area) origin from small interneurons was suspected as well. MCH cell bodies do not express NK1, but around 2.7% of the MCH neurons contained SP after colchicine injection. Senktide, a NK3 agonist, produced an increase of the MCH mRNA expression in cultured hypothalamic slices. This effect was reversed by two NK3 antagonists. Tachykinins enhance MCH mRNA expression, and, thus, may modulate the effect of MCH in functions such as feeding and reproductive behaviors in which this peptide has been experimentally involved.

Animals↗
PubMed2003

Sensitivity of galanin- and melanin-concentrating hormone-containing neurones to nutritional status: an immunohistochemical study in the ovariectomized ewe.

The sensitivities of galanin and melanin-concentrating hormone (MCH) neuronal systems to nutrition are poorly understood in sheep compared to rodents. The aim of this study was to describe the changes in the numbers of galanin and MCH neurones in ovariectomized ewes submitted to different nutritional levels. In the first experiment, ewes were fed ad libitum or food deprived for 24 h. In the second experiment, two groups of ewes were fed at maintenance level (group 100) or undernourished (group 40) for 167 days, after which one-half of each group was killed or refed ad libitum (group 100R and 40R) for 4 days. The MCH neuronal population located in the lateral hypothalamic area was not affected by these nutritional changes. Long-term undernutrition enhanced the number of galanin neurones located in the infundibular nucleus and the dorsal hypothalamic area (DHA), refeeding resulted in an increase of neurones in the DHA and preoptic area, but short-term starvation had no effect on any galanin subpopulations. Our data suggest that the sensitivity of MCH neuronal populations to nutrition in sheep differs from that of rodents. Various populations of galanin-containing neurones differ in sensitivity in ewes subjected to long undernutrition and refeeding but not to short starvation.

Animals↗
PubMed2002

Early and transient ontogenetic expression of the cocaine- and amphetamine-regulated transcript peptide in the rat mesencephalon: correlation with tyrosine hydroxylase expression.

The ontogeny of cocaine- and amphetamine-regulated transcript (CART) expression has been analyzed by immunohistochemistry in the mesencephalon of the rat central nervous system, and compared to the pattern of tyrosine hydroxylase- (TH-) expression. CART-producing neurons were first detected on the embryonic day 11 (E11) in the ventral mesencephalic vesicle. These neurons are among the first cells of the mantle layer to differentiate. From E13, a complementary pattern of distribution was observed, dividing the mantle layer into an external TH zone and an internal CART zone. Many TH-positive neurons were found to migrate from the neuroepithelium through the area containing the CART-immunoreactive neurons to settle more laterally. These TH cells exhibited prominent leading and trailing dendrites in the immediate vicinity of CART perikarya. On E16, the number of CART neurons appeared to diminish, and they were confined near the ventricle and around the fasciculus retroflexus. On E18 and E20, only the Edinger-Westphal nucleus exhibited a strong CART staining as described in the adult brain. Thus, the very early detection of CART during prenatal ontogeny led us to speculate that this peptide might have a role in the development of specific regions of the rat brain. In particular, our observations suggest that CART-expressing neurons might help the migration of the dopaminergic neurons of the substantia nigra.

Animals↗
PubMed2002

Time of genesis determines projection and neurokinin-3 expression patterns of diencephalic neurons containing melanin-concentrating hormone.

Anatomical and functional evidence suggests that the diencephalic melanin-concentrating hormone- (MCH-) containing neurons do not form a homogeneous population. In this work, the expression of the neurokinin-3 receptor (NK3) has been researched in MCH neurons which have been retrogradely labelled following fast blue injections into either the spinal cord or the cerebral cortex. The birth-date of these cortically and spinally projecting cells has been determined using the bromodeoxyuridine method. The results obtained show that neurons projecting to the spinal cord are born early (E11) and most of them (78,7%) do not express NK3, but neurons that send axons to the cerebral cortex are born later (E12-E13) and most of them (84,8%) express NK3. Both neuronal types are largely intermingled in the lateral hypothalamic area proper. These results are discussed in terms of the functional organization of the MCH neuronal population.

Animals↗
PubMed2001

Down regulation of melanin concentrating hormone in virally induced obesity.

Obesity is a complex disease involving genetic components and environmental factors and probably associated with the dysregulation of central homeostasis normally maintained by the hypothalamic neuroendocrine/neurotransmitter network. We previously reported that canine distemper virus (CDV), which is closely related to human measles virus, can target hypothalamic nuclei, and lead to obesity syndrome in the late stages of infection. Here, using differential display PCR, we demonstrate specific down-regulation of melanin-concentrating hormone precursor mRNA (ppMCH) in infected-obese mice. Although ppMCH was down-regulated in all infected mice during the acute stage of infection, this was only seen during the late stage of infection in infected-obese mice. In addition, ppMCH mRNA and protein expression in the lateral hypothalamus was decreased in the absence of neuronal death. These results show the importance of ppMCH in the establishment and maintenance of obesity and the involvement of a virus as an environmental factor.

Acute Disease↗
PubMed2001

Ontogenetic development of the diencephalic MCH neurons: a hypothalamic 'MCH area' hypothesis.

The ontogeny of rat diencephalic melanin-concentrating hormone (MCH) neurons has been analysed, using the bromodeoxyuridine method to determine the period of birth of these neurons, and using in situ hybridization and immunohistochemistry to study their chemical differentiation. The spatiotemporal pattern of MCH neuron generation is complex, although it is broadly lateromedial with a peak between embryonic days (E) 12 and E13. The first expression of the MCH gene has been detected on E13 in neurons in the presumptive lateral hypothalamic area. But the adult-like pattern was observed from E18. Medial-most MCH neurons express the peptide CART (cocaine-amphetamine-regulated transcript) from E18, and the receptor neurokinin 3 (NK3) from between postnatal day (P) 0 and P5. These results are discussed and compared with data from the literature to better understand the organization of the 'MCH-containing area'.

Animals↗
PubMed2000

Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area.

Following an i.p. injection of 2-deoxyglucose (2DG), a nonmetabolizable analogue of glucose known to induce intracellular glucopenia, a progressive decrease in the level of hypocretin (Hcrt)/orexin mRNA was observed in the rat lateral hypothalamus while the melanin-concentrating hormone (MCH) expression in neighbouring neurons remained unaffected. This result together with the previously reported stimulation of Hcrt expression by insulin confirms that Hcrt neurons, but not MCH neurons, are sensitive to glucose availability and suggests that they respond through different mechanisms and/or different pathways to intracellular glucopenia and hypoglycemic conditions.

Animals↗
PubMed2000

An in vitro model for the study of human bone marrow angiogenesis: role of hematopoietic cytokines.

This study describes a human bone marrow endothelial cell culture in which endothelial cells are organized into capillary tubes. These endothelial cells were positive for von Willebrand Factor, expressed CD34, CD31, and L-fucose residues, took up acetylated low-density lipoproteins, contained Weibel-Palade bodies, and were ensheathed in a basal lamina (which included laminin beta1, EDa+ and EDb+ fibronectin, and collagen type iv). Pericytes expressing alpha-smooth muscle (alpha-SM) actin were spatially associated with the capillary tubes and there was a highly significant correlation between the number of capillary tubes and pericytes. In this model, basal angiogenesis was found to be vascular endothelial growth factor (VEGF)-dependent, because neutralization of endogenous VEGF induced a dramatic regression in the number of tubes. However, the presence of alpha-SM actin-expressing pericytes in the linings of endothelial tubes partially prevented the VEGF-neutralized tube regression. We also observed that nitric oxide production contributed to basal angiogenesis and that upregulation of nitric oxide increased the number of tubes. Tube numbers also decreased when antibodies neutralizing the integrin alphavbeta5 were applied to the cultures. Moreover, addition of any of the hematopoietic cytokines, erythropoietin, stem cell factor, granulocytic colony stimulating factor, or granulomonocytic colony stimulating factor induced a highly significant increase in tube formation. When erythropoietin and granulocytic colony stimulating factor were added, this increase was larger than the maximum increase observed with VEGF. Thus, we have described an in vitro model for human bone marrow angiogenesis in which pericytes and basal lamina matrix were associated with endothelial cells and formed fully organized capillary tubes. In this model, cytokines known to regulate hematopoiesis also seemed to be mediators of angiogenesis. This culture system may therefore prove to be a valuable tool for the study of hematopoietic cytokines on angiogenesis.

Bone Marrow↗
PubMed2000

[Solid cell nests and thyroid pathologies. Retrospective study of 1,390 thyroids].

Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants or as squamous metaplasia of follicular epithelium. In a retrospective study of 1 390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2) : p <0, 01). The number of SCN rises with increasing number of sections examined. No statistical differences were found with age or thyroid disorders and presence of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases, neuroendocrine cells (calcitonin and/or calcitonin gene related peptide, chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The different cell types of SCN fitted with the ultimobranchial remnant theory. Thus, some rare carcinomas (like mixed medullary and vesicular carcinoma or mucoepidermoid carcinoma) might originate from SCN.

Adenoma↗
PubMed1999

Melanin-concentrating hormone-producing neurons in birds.

The peptidergic melanin-concentrating hormone (MCH) system was investigated by immunocytochemistry in several birds. MCH perikarya were found in the periventricular hypothalamic nucleus near the paraventricular organ and in the lateral hypothalamic areas. Immunoreactive fibers were very abundant in the ventral pallidum, in the nucleus of the stria terminalis, and in the septum/diagonal band complex, where immunoreactive pericellular nets were prominent. Many fibers innervated the whole preoptic area, the lateral hypothalamic area, and the infundibular region. Some fibers also reached the dorsal thalamus and the epithalamus. The median eminence contained only sparse projections, and the posterior pituitary was not labeled. Thus, in birds, a neurohormonal role for MCH is not likely. Immunoreactive fibers were observed in other regions, such as the intercollicular nucleus, stratum griseum periventriculare (mesencephalic tectum), central gray, nigral complex (especially the ventral tegmental area), reticular areas, and raphe nuclei. Although no physiological investigation concerning the role of MCH has been performed in birds, the distribution patterns of the immunoreactive perikarya and fibers observed suggest that MCH may be involved in functions similar to those described in rats. In particular, the projections to parts of the limbic system (ventropallidal ganglia, septal complex, hypothalamus, dorsal thalamus, and epithalamus) and to structures concerned with visceral and other sensory information integration suggest that MCH acts as a neuromodulator involved in a wide variety of physiological and behavioral adaptations (arousal) with regard to feeding, drinking, and reproduction.

Animals↗
PubMed1999

Melanin-concentrating hormone expression in slice cultures of rat hypothalamus is not affected by 2-deoxyglucose.

In rats, melanin-concentrating hormone (MCH) neurons are mainly located within the lateral hypothalamic area (LHA). This area is known to be involved in the control of feeding and to contain glucose-sensitive cells. As a role for MCH in the regulation of food intake has been reported, we investigated the effects of 2-deoxyglucose (2DG) on MCH expression in cultured LHA slices, to verify if MCH neurons are sensitive to local glucoprivation through a modulation of MCH synthesis. After a 2-10 h 2DG incubation, competitive reverse transcription-polymerase chain reaction (RT-PCR) did not show any variation of MCH mRNA; no change was also observed in MCH immunocytochemical labeling. A slight decrease of MCH mRNA (5-15%) after a 17 h 2DG treatment might be due to a general degradation of neurons induced by long-term glucoprivation. In conclusion, we suggest that MCH neurons are not the glucose-sensitive cells previously described in the LHA and that the signals inducing their previously reported response to glycemia variations do not arise from the LHA itself.

Animals↗
PubMed1999

Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area.

The recent identification of two peptides named hypocretins (Hcrt), and expressed in neurons of the rat tuberal lateral hypothalamus (LHA) previously detected by an ovine prolactin antiserum, led us to revisit some experimental procedures intented to understand the physiological roles of these neurons. In the present study, rats received intraperitoneal injections of insulin and/or glucose. Immunocytochemical observations and quantitation of in situ hybridization signals pointed out a clear stimulation of Hcrt neurons following the sole injection of insulin in hypoglycemic but not in hyperglycemic conditions. This result, together with the robust appetite boosting effect of Hcrt reported elsewhere, suggests the involvement of Hcrt neurons in the control of food intake.

Animals↗
PubMed1999

Preprohypocretin (orexin) and prolactin-like immunoreactivity are coexpressed by neurons of the rat lateral hypothalamic area.

Recently, two new neuropeptides named hypocretins I and II (Hcrt) have been described in the rat lateral hypothalamus. The distribution of the neurons expressing these new peptides is similar to that of neurons described in the literature as prolactin (PRL) immunoreactive neurons and specifically labeled by an antiserum (AS) raised against ovine prolactin (oPRL). In this study, we report that every neuron labeled by immunohistochemistry or in situ hybridization for Hcrt is also labeled by the oPRL-AS, and conversely. Furthermore, the labeling of the oPRL-AS is inhibited when this AS is pre-incubated with the 104-109 fragment of the preproHcrt, thus indicating that the oPRL-AS is recognizing an epitope carried by this particular fragment of the preproHcrt. Our previous experimental work on these neurons showed that they may be involved in energy metabolism and water balance, which is in agreement with the current literature about Hcrt functions.

Animals↗
PubMed1999

Prevalence and clinical significance of antiphospholipid antibodies in renal transplant recipients.

BACKGROUND: The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients. METHODS: To further define the prevalence and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed. RESULTS: Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and hemodialysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3% [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients with posttransplant ACAs had ACAs in the pretransplant period (85%). Pretransplant ACAs were associated with a posttransplant history of venous thrombosis (P<0.001). CONCLUSIONS: Our study demonstrates a high prevalence of APAs in non-SLE renal transplant recipients. Most of them have been acquired in the pretransplant period. Both pretransplant ACAs and posttransplant APAs are associated with posttransplant episodes of thrombosis. Further studies are required to determine the interest of prophylactic measures.

Adult↗