Hydarthrosis of the ankle in a patient with a longitudinal stress fracture of the tibia.
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Ankle Joint↗
Biomedical subjects
M Landry
Publications and source records attributed to M Landry.
Regulation of expression of galanin and galanin receptors in dorsal root ganglia and spinal cord after axotomy and inflammation.
Galanin can normally be detected only in a few dorsal root ganglion (DRG) neurons, but it is dramatically upregulated after peripheral nerve injury in both rat and monkey. Galanin is stored in large dense core vesicles, which after axotomy are often found close to the membrane of afferent nerve endings in the dorsal horn. In the monkey there is an increase in galanin in many nerve terminals in the superficial dorsal horn after axotomy, but such an increase is more difficult to detect in the rat. Galanin is also present in local dorsal horn neurons, where it is upregulated by peripheral inflammation. Both galanin-R1 and galanin-R2 receptor mRNAs are expressed in rat DRGs, mainly in, respectively, large and small DRG neurons. Galanin-R1 receptor mRNA is downregulated in DRG neurons after axotomy, and a small decrease in galanin-R2 receptor mRNA levels can also be seen. After peripheral tissue inflammation galanin-R1 receptor mRNA levels decrease and galanin-R2 receptor mRNA levels increase. The present results show that galanin and galanin receptors are present in sensory and local dorsal horn neurons and are regulated by nerve injury and inflammation. Galanin may therefore be involved in processing of pain information, primarily exerting analgesic effects. Whereas local dorsal horn neurons represent a defense system against inflammatory pain, we have proposed that a second defense system, against neuropathic pain, is intrinsic to DRG neurons.
Animals↗
Galanin-R1 receptor in anterior and mid-hypothalamus: distribution and regulation.
The distribution and regulation of galanin-R1 receptor (GAL-R1-R) mRNA has been studied in the anterior and mid-diencephalon by using in situ hybridization. Moreover, possible colocalization of GAL-R1-R mRNA and prepro-galanin or vasopressin mRNAs has been analyzed at the cellular level using double in situ hybridization methodology. Many nuclei in the hypothalamus expressed GAL-R1-R mRNA, including the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). Strong expression was also seen in the same sections in various areas outside of the diencephalon. The distribution patterns are similar to those described in earlier studies. Double labeling experiments showed GAL-R1-R mRNA in vasopressin neurons in the PVN and SON. Moreover, GAL-R1-R mRNA and prepro-galanin mRNA were colocalized in several hypothalamic nuclei. GAL-R1-R mRNA levels showed a high degree of plasticity. Thus, salt loading resulted in a marked increase in GAL-R1-R mRNA levels in the PVN and SON and a moderate decrease was seen during lactation. In contrast, hypophysectomy caused a decrease in GAL-R1-R mRNA levels. Differential effects of colchicine were recorded with a decrease of GAL-R1-R mRNA in the magnocellular hypothalamic neurons. After salt loading or during lactation, GAL-R1-R mRNA and prepro-galanin mRNA were regulated in parallel, whereas their levels changed in opposite directions after hypophysectomy and colchicine injection. In conclusion, GAL-R1-Rs are present in several hypothalamic nuclei, partly in neurons synthesizing galanin. The receptors are regulated in a specific fashion in the various nuclei, depending on the stimulus applied. The results suggest that the effect of galanin in the hypothalamus partly depends on the state of receptor expression.
Animals↗
Computed tomographic imaging of subcutaneous gouty tophi.
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Adult↗
Altered frequency of a promoter polymorphic allele of the kinin B1 receptor gene in inflammatory bowel disease.
BACKGROUND & AIMS: Evidence of kinin-mediated inflammation in the gastrointestinal tract is accumulating. The genes and some polymorphic sites have been characterized for both kinin B1 and B2 receptors. These candidate genes were studied for their possible association with inflammatory bowel disease (IBD). METHODS: In a retrospective study, the prevalence of allele pairs for four polymorphic sites of the two kinin receptor genes was determined in 53 patients with IBD and in 110 healthy volunteers similar in age, body weight, and gender proportions, using polymerase chain reaction and other techniques. RESULTS: Only the B1 receptor promoter polymorphism (G-699-->C) exhibited a significantly different allele frequency between the two groups (prevalence of the C allele of 5.7% in patients with IBD compared with 33.6% in controls; P = 0.0002) or between the controls and either etiologic subgroup (ulcerative colitis and Crohn's disease). Allelic polymorphisms affecting exon 3 of the B1 receptor gene (A1098-->G) or exon 2 (C181-->T) or 1 (a 9-base pair deletion) of the B2 receptor gene were found to be neutral. CONCLUSIONS: The gene corresponding to the B1 receptor for kinins may be a nonetiologic marker of symptomatic IBD, as suggested by the altered prevalence of a polymorphism presumably affecting its regulation.
Adult↗
Neuropeptide Y: some viewpoints on a multifaceted peptide in the normal and diseased nervous system.
Using immunohistochemical and in situ hybridization methodologies the localization of neuropeptide tyrosine (NPY) and two of its receptors, the Y1- and the Y2-receptor (R), has been analysed in various tissues in normal animals and animals subjected to different experimental procedures as well as animals with a genetic and an acquired disease. (1) Dorsal root ganglion (DRG) neurons are discussed with special focus on the effect of peripheral nerve injury. In normal DRG neurons NPY cannot be detected, whereas Y1-R mRNA and Y1-R-like immunoreactivity (LI) are strongly expressed. The Y1-Rs decorate the membrane of the cell soma and are not transported peripherally into the axonal branches. Y2-R mRNA levels are low. After axotomy there is a marked increase in NPY, a decrease in Y1-Rs and an increase in Y2-Rs. The Y2-R is transported centrifugally. These findings suggest that NPY-ergic mechanisms participate in the adaptive changes of sensory neurons in response to injury. (2) Using specific antibodies the cellular and subcellular localization of the Y1-R protein have been analysed in cerebral blood vessels. The results demonstrate high concentrations of receptors in smooth muscle cells around pial arterioles with lower numbers in large vessels on the basal surface of the brain. In many regions the receptors 'disappear' after the arterioles have entered the brain tissue. At the ultrastructural level the receptors are found both on the endothelial and peripheral side of the muscle cells as well as laterally, where muscle cells oppose each other. The receptor protein is often associated with small vesicles. No NPY-positive nerve fibers were found around the Y1-R-rich arterioles, but they were only seen around the arteries with low Y1-R levels. The Y1-R-rich arterioles were, however, seen close to numerous NPY-positive fibers originating from central interneurons. These findings raise the possibility that centrally originating NPY can influence cerebral blood flow, possibly by stimulating NPY-Rs on the peripheral side of the muscle cells. However, also blood borne NPY, released under special conditions, such as stress from sympathetic nerves and the adrenal medulla and transported with blood, may stimulate receptors on the endothelial side of the smooth muscle cells. (3) In the arcuate nucleus Y1- and Y2-Rs are found, whereby the Y1-Rs are located in its ventro-medial portion and co-localized with POMC peptides, and the Y2-R in its ventromedial part, partly co-localized with NPY. NPY nerve endings makes synaptic contact with the POMC/Y1-R-positive neurons. In a mouse model for genetic anorexia very high levels of NPY were observed in arcuate neurons as compared to control mice. However, NPY mRNA levels were not different between the two groups. Taken together these findings are in good agreement with the view that NPY in the arcuate nucleus plays an important role in regulating feeding behaviour. (4) After intracerebral prion inoculation in mice an upregulation of NPY mRNA levels was observed in CA3 pyramidal neurons, and this effect was seen at a time point just before the first behavioural symptoms were manifested. At approximately the same time there was a dramatic decrease in Y2-R binding in strata oriens and radiatum of the CA1 region of the hippocampus, whereas in other regions no changes or much smaller changes were observed. Also, there was only a very slight decrease in Y2-R mRNA levels in CA3 neurons. It thus appears as if the prion disease prevents ligand binding to the Y2-R, perhaps by influencing traffic of receptor proteins, possibly at the level of cell membrane-associated caveolae, which have been implicated in the conversion of normal protein to scrapie protein. It is possible that these changes in NPY-ergic mechanisms may underlie some of the central symptoms associated with the prion disease. (ABSTRACT TRUNCATED)
Animals↗
Subcellular localization of preprogalanin messenger RNA in perikarya and axons of hypothalamo-posthypophyseal magnocellular neurons: an in situ hybridization study.
The subcellular compartmentalization and axonal transport of oxytocin and vasopressin messenger RNAs have recently been reported in the rat hypothalamo-posthypophyseal system using in situ hybridization. So far, no data are available concerning the intracellular distribution of co-localized peptide transcripts, for example of galanin, which is synthesized in the vasopressinergic magnocellular neurons of the rat and which is up-regulated in these neurons under different conditions, including salt loading and colchicine injection. In the present study, using non-radioactive in situ hybridization and immunohistochemistry at the light and electron microscope levels, preprogalanin messenger RNA and galanin-like immunoreactivity were localized in the hypothalamo-posthypophyseal system. After salt loading, preprogalanin transcripts were found throughout the perikaryal cytoplasm, especially in the peripheral cytoplasm and in the perinuclear area. Since immunohistochemistry also showed galanin-like immunoreactivity preferentially in the perinuclear area of control rats, galanin synthesis may occur mainly in this cytoplasmic domain. Preprogalanin messenger RNA was also clustered in dendrites containing rough endoplasmic reticulum. The use of a new in situ hybridization method involving tyramide signal amplification, based on catalysed reporter deposition, allowed visualization of preprogalanin messenger RNA in axonal projections running through the internal layer of the median eminence after salt loading, but not in control or in colchicine-injected animals. The negative results obtained after colchicine injection indicate that the mechanism of messenger RNA transport may require an intact cytoskeleton. The labelling was found in non-dilated axon segments as well as in a subset of axonal swellings in the rostral aspect of the median eminence, but was restricted to a few swellings in its caudal part, with no labelling in the posterior pituitary. Thus, preprogalanin messenger RNA was segregated in the axons. The functional significance of messenger RNAs' exportation into axons is not known, but our results suggest that this phenomenon may not be limited to the two principal magnocellular hormone messenger RNAs, but may also involve co-existing peptide messenger RNAs.
Animals↗
Characterization of two polymorphic sites in the human kinin B1 receptor gene: altered frequency of an allele in patients with a history of end-stage renal failure.
On the basis of the genomic structure of the human B1 receptor (B1R) for kinins, the presence of possible allelic polymorphisms of this gene was investigated using restriction fragment-length polymorphism and single-strand conformation polymorphism. The frequencies of the found alleles were determined in healthy volunteers and in patients with a history of end-stage renal failure, because there is evidence for a nephroprotective action of the kallikrein-kinin system. An A1098-->G polymorphism has been identified in exon 3 in a minority of volunteer blood donors, and is located 35 nucleotides downstream from the stop codon and 14 nucleotides upstream from the polyadenylation signal. The frequency of the G allele is 4.4% in the control sample and not significantly altered in patients with a history of end-stage renal failure. A second and more frequent polymorphism (18.1% of the alleles in the control group, prevalence of 33.3%) consists of a single base substitution (G-699-->C) in the putative promoter region. This polymorphism is significantly less frequent in the population of renal failure patients (prevalence of 20.6%) and determines an increased activity of the promoter function in constructions involving a reporter gene. The altered prevalence of this allele was also found in some etiologic subgroups of uremic patients. This study confirms the mapping of the B1R gene to 14q32. Other investigators have mapped the bradykinin B2 receptor (B2R) gene to a close site on human chromosome 14. A previously described B2R polymorphism (exon 2, C181-->T) had an allele frequency of 9.7% in the control sample and appears to be clinically neutral. The polymorphism of the B1R promoter may be a marker of prognostic significance for the preservation of renal function in diseased individuals.
Adult↗
A 3-year study of prevention of postmenopausal bone loss: conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone.
The aim of this study was to investigate the effects of tibolone in the prevention of postmenopausal bone loss over 3 years, and to compare these with the effects of sequential hormone replacement therapy. Forty early postmenopausal women were randomized to a 21-day regimen of conjugated equine estrogens (CEE, Premarin) plus sequential medroxyprogesterone acetate (MPA, Prodafem), or tibolone (Livial) daily. In total, 36 women completed 12 months and were considered for the intent-to-treat analysis, 34 completed 24 months and 23 completed 36 months. Main drop-out reasons were: lost to follow-up (n = 9) and minor side-effects (n = 4). Bone mineral density was measured at baseline and after 6, 12, 24 and 36 months, using dual-energy X-ray absorptiometry at the lumbar spine and the upper femur (neck, trochanter, total hip). In both groups, bone loss was prevented. Treatment with tibolone demonstrated significant increases in bone density at the spine (+4.6%; p < 0.01), at the total hip (+3.2%; p < 0.01) and at the trochanter (+4.5%; p < 0.01), whereas the CEE/MPA group showed a non-significant increase of bone mineral density at the lumbar spine (+2.6%) but no increases at the hip. Between-group differences in bone mineral density changes were significant (p < 0.05) for the total hip and the trochanter at 36 months. This increase of bone mineral density was not accompanied by changes in insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP-3) in either group. Osteocalcin, alkaline phosphatase and urinary ratios of hydroxyproline/creatinine and calcium/creatinine significantly decreased in both groups. In conclusion, sequential CEE/MPA prevented cortical and trabecular bone loss, with a transient increase of bone mineral density only during the first 6 months. Tibolone not only prevented cortical and trabecular bone loss, but further increased bone mineral density at the lumbar spine and at the hip throughout the 3 years of treatment, suggesting a sustained positive effect on bone mass.
Absorptiometry, Photon↗
[Radiological aspects of venous problems in the legs].
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Chronic Disease↗
The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia.
Peripheral nerve injury causes a marked change in expression of the neuropeptide galanin in dorsal root ganglion (DRG) neurons. We have used DRG cell cultures to study whether growth factors, especially nerve growth factor (NGF), play a role in this regulation. Adult rat DRG cultures seem to represent a suitable model for this study, since the neurons are axotomized during culture preparation and are known to survive independently of added neurotrophic factors. The effect of NGF, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) was studied on the expression of galanin and galanin message-associated peptide (GMAP)-like immunoreactivities using immunohistochemistry, as well as of prepro-galanin (ppGAL) mRNA levels using radioactive and non-radioactive in situ hybridization. The results show that 100, but not 20 or 50 ng/ml NGF, as well as 10 ng/ml BDNF cause a 40% decrease in the number of GMAP expressing neurons in 72 h cell cultures. A 50% decrease was observed after treatment with 10 ng/ml bFGF. The high dose needed and the modest effect suggest that NGF is not a major factor involved in galanin regulation, whereas BDNF and bFGF may have a role. Moreover, the strong upregulation of galanin/GMAP and ppGAL mRNA levels in the untreated cultures indicates that DRG neurons in vitro have a phenotype similar to DRG neurons after axotomy, i.e. a phenotype distinctly different from normal DRG neurons.
Animals↗
Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia.
The Y2 subtype of neuropeptide tyrosine (NPY) receptors (Y2R) and some neuropeptides have been studied with in situ hybridization in sensory and autonomic neurons of rat and monkey. Between 10% and 20% of the lumbar dorsal root ganglion (DRG) neuron profiles (NPs) contain Y2R mRNA in the rat and monkey. In rat DRGs Y2R mRNA is expressed in calcitonin gene-related peptide (CGRP)-positive, medium-sized, and large neurons, that is in a complementary fashion to the Y1R that is located in small CGRP neurons. In monkey DRGs Y2R mRNA is expressed mainly in small neurons. Peripheral axotomy up-regulates the Y2R in small and large DRG neurons in both species. Y2R and NPY mRNAs are colocalized in many large neurons in axotomized rat DRGs. Y2R mRNA is expressed in 50% of the NPs in the nodose ganglion with a modest increase after axotomy. Y2R mRNA is detected in a few NPs in normal rat superior cervical ganglia, with a marked increase after transection of the carotid nerves. No Y2R mRNA-positive, but many (approximately 30%) weakly Y1R mRNA-positive NPs were found in the sphenopalatine ganglion. Finally, Y2R mRNA levels increase in rat spinal motoneurons after axotomy. Thus, under normal circumstances NPY may act on Y1 and Y2Rs expressed, respectively, in small and large CGRP-positive DRG neurons in the rat. Y2R may be an important receptor in the viscero-sensory neurons. Y2Rs may be particularly important after axotomy serving as presynaptic and/or autoreceptors on rat DRG, superior cervical ganglion, and nodose ganglion neurons and as presynaptic receptors in monkey DRG neurons.
Animals↗
Developmental expression of nitric oxide synthase in the rat diencephalon with special reference to the thalamic paratenial nucleus.
Using immunohistochemistry and in situ hybridization the distribution of nitric oxide synthase (NOS) was investigated in the rat brain during pre- and postnatal development. At E15 weak NOS-like immunoreactivity (NOS-LI) could be seen in the differentiation field of the anterior hypothalamus. At E17 strong NOS-LI was observed in the developing neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus, anterodorsal nucleus and lateral hypothalamic areas. In the thalamic paratenial nucleus a strong NOS-LI was observed in these neurons at E17, E18 and P1 with a weaker intensity at P3, P7, P9 and P15, whereas at P30 and in adult rats no NOS-positive neurons could be detected. NOS expression at E17 and P3 was verified by in situ hybridization. These results suggest that NO may have a developmental role at least in one of the regions studied, the thalamic paratenial nucleus.
Aging↗
Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus.
The arcuate nucleus of the hypothalamus houses a number of neurochemically different cell populations. Among these, a dense cluster of small neuropeptide-Y (NPY)-expressing neurons is located in its ventromedial subdivision and a pro-opiomelanocortin (POMC)-expressing neuron population in its ventrolateral part. Furthermore, both neuropeptide Y Y1 and Y2 receptors (Y1-Rs and Y2-Rs) are expressed in the arcuate nucleus. Here we analyse the co-expression of NPY and POMC/adrenocorticotropic hormone with the Y1-R and Y2-R in arcuate neurons using immunohistochemistry and in situ hybridization. Many, but not all, POMC neurons expressed Y1-R mRNA and protein. Conversely, several Y1-R-positive, POMC-negative neurons were found. NPY-positive nerve terminals were found in close apposition to Y1-R-like immunoreactivity localized close to the dendritic and somatic cell membranes. Y2-R mRNA was found in almost all NPY mRNA-expressing neurons, but also in a group of NPY mRNA-negative cells. These results show that the POMC neurons are targets for NPY, which is presumably present in, and released from, fibres originating in the ventromedial arcuate nucleus and which may play a role in NPY-induced feeding. Release of NPY, and possible coexisting messengers, may be controlled by presynaptic Y2-R expressed in NPY neurons. Taken together, the findings support the division of Y1-Rs and Y2-Rs into post- and presynaptic receptors, respectively.
Adrenocorticotropic Hormone↗
Expression of galanin in hypothalamic magnocellular neurones of lactating rats: co-existence with vasopressin and oxytocin.
Lactation is a physiological condition known to upregulate the expression of the hypothalamic neurohormones, oxytocin and vasopressin, in the rat supraoptic and paraventricular nuclei. Other neuropeptides such as galanin are co-localized in the same magnocellular neurones and their expression has been demonstrated to be regulated by different experimental and physiological conditions. In the present study, we investigated the possible changes in galanin expression during lactation, using in situ hybridization and immunohistochemistry separately or in combination. Galanin messenger RNA concentrations decreased on day 3 of lactation in both the supraoptic and paraventricular nuclei and remained low on day 7 of lactation, but no differences were observed between control and 14-day lactating rats. In parallel, immunopositive cell bodies were almost undetectable on day 7 of lactation and immunoreactivity remained weak after 14 days of lactation, whereas galanin immunoreactive profiles in the supraoptic nucleus were more numerous than in the control group. Moreover, the subcellular distribution of immunostaining changed on day 14 of lactation. Galanin immunoreactivity was confined around the nucleus in the control females, but it became weaker and more homogenously distributed throughout the cytoplasm in the lactating rats. Electron microscopy using a pre-embedding technique confirmed that galanin immunoreactivity was no longer restricted to the Golgi complex, but was apparent throughout in the cytoplasm. Multiple labellings showed galanin and galanin messenger RNA to be co-localized with oxytocin messenger RNA in neurones of the dorsomedial part of the supraoptic nucleus during lactation. Some of those doubly labelled cells also expressed vasopressin messenger RNA in the same conditions as revealed by a triple-labelling procedure. As these co-localizations have not been observed in female control rats, lactation provided an example of a physiological condition inducing oxytocin and galanin co-synthesis in a subpopulation of magnocellular neurones. In conclusion, we have demonstrated plasticity of galanin expression during lactation in the hypothalamic magnocellular neurones. This plasticity could be caused by changes in galanin expression or in galanin processing in magnocellular neurones.
Animals↗
Pantopaque droplets: another cause of hyperintensity on unenhanced T1-weighted MR images of the brain.
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Aged↗
The impact of a treatment process for substance users as a function of their degree of exposure to treatment.
The objective of this research is to evaluate the outcomes of a treatment for addicts. 248 subjects were tested before and 5 months after treatment with the Addiction Severity Index (ASI). Exposure to treatment was based on the number of clients' contact hours with a therapist. The sample was divided into three groups according to number of hours spent in treatment. The data were analyzed using MANOVA on the seven scales of the ASI for the three groups and the two time periods. Results showed that the severity of addiction problems decreased after treatment, and decreased more for subjects who underwent treatment for a longer period of time.
Adolescent↗
Evidence for galanin receptors in primary sensory neurones and effect of axotomy and inflammation.
Using in situ hybridization, mRNA coding for the galanin R1 receptor (GAL-R1) was demonstrated in > 20% of all lumbar 4 and 5 dorsal root ganglion neurone profiles, mainly constituting small and medium sized neurones. Almost all of these neurones expressed CGRP mRNA as revealed by analysis of adjacent sections and of the same section using a double-labelling technique. GAL-R1 mRNA levels were down-regulated transiently by inflammation, and more strongly by peripheral nerve injury. These results suggest that DRG neurones are sensitive to galanin and that GAL-R1 receptors are involved in sensory processing.
Animals↗