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Biomedical subjects

J J Vanderhaeghen

Publications and source records attributed to J J Vanderhaeghen.

At least 19 recordsLinked to original sources
PubMed1998

Effect of sensory deafferentation on the GABAergic circuitry of the adult cat visual system.

The effect of bilateral central retinal lesions on the GAD67 and GAD65 messenger RNA levels in the dorsal lateral geniculate nucleus, the perigeniculate nucleus and the visual cortex of the adult cat was investigated by in situ hybridization. Three days post-lesion, a decrease in the number of GAD67-expressing cells was apparent in the deafferented dorsal lateral geniculate nucleus. This decrease persisted until 7.5 months post-lesion and was more pronounced with longer survival times. The decrease in GAD67 mRNA was mirrored by a decrease in glutamate decarboxylase-immunoreactive cells. GAD65 messenger RNA expression levels were low in the dorsal lateral geniculate nucleus of both control and retinally-lesioned cats. In the perigeniculate nucleus the messenger RNA levels of both glutamate decarboxylase isoforms were clearly decreased over a restricted region. In the lesion-affected visual cortex, no changes at the messenger RNA level were observed for either GAD67 or GAD65 although changes in glutamate decarboxylase immunoreactivity have been previously described. Hence, in the dorsal lateral geniculate nucleus, the perigeniculate nuclcus and the visual cortex, different intracellular mechanisms seem to lead to decreased GABAergic inhibition in response to sensory deafferentation.

Animals↗
PubMed1997

Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor.

Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors. The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR-/-) mice were viable and bred normally. Their exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety tests, and male mice were much more aggressive towards intruders. The response of A2aR-/- mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested.

Adenosine↗
PubMed1996

Interstitial cells of Cajal in human colon and in Hirschsprung's disease.

BACKGROUND & AIMS: Subpopulations of interstitial cells of Cajal are regarded as the source of spontaneous slow waves of the gut musculature (pacemaker cells). Their ontogeny remains unclear, but a role of the tyrosine kinase receptor c-kit in their development has recently been recognized. This study examined the interstitial cells in the human colon and in Hirschsprung's disease (aganglionosis). METHODS: The distribution of the c-kit receptor was studied using specific antibodies in 5 normal patients, 10 patients with Hirschsprung's disease, and 3 patients with diversion loop enterostomies. c-kit immunohistochemistry was also combined with reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry or with c-kit ligand (stem cell factor) immunohistochemistry. Transmission electron microscopy was performed in 1 patient with Hirschsprung's disease. RESULTS: c-kit immunoreactivity labeled a network of interstitial cells at the outer edge of the submucosa, in the muscular layers, and around the myenteric plexus. In aganglionic segments, interstitial cells were scarce and its network appeared disrupted. Interstitial cells of Cajal were identified in aganglionic regions by electron microscopy. Interstitial cells of Cajal are identifiable in newborns and exhibit similar distribution in diversion loops independent of contact with luminal nutrients. CONCLUSIONS: Our morphological data may explain the abnormal spontaneous electrical activity in aganglionic segments of Hirschsprung's disease and may give new insight into the ontogeny of interstitial cells.

Child, Preschool↗
PubMed1996

The pathology of infantile hypertrophic pyloric stenosis after healing.

INTRODUCTION: Infantile hypertrophic pyloric stenosis (IHPS) is a common surgical affection of unknown etiology. The muscular hypertrophy is known to resolve within a few months after pyloromyotomy (PM). The pathology of IHPS has been studied extensively at the time of PM, but the fate of the pylorus after healing remains unknown. MATERIALS AND METHODS: We had the rare opportunity to study two pyloric biopsy specimens obtained 4 months and 2 years (respectively) after an uncomplicated PM for IHPS. They were compared with the initial specimen in one case, with 26 other specimens of IHPS, and with five normal controls. Immunohistochemistry using the avidin-biotin complex (ABC) system was performed for S-100 and nerve growth factor receptor, as markers for the enteric nervous system, and for the tyrosine kinase receptor c-kit, as a marker for the interstitial cells of Cajal (pacemaker cells). NADPH-diaphorase histochemistry was performed as a marker for the neuronal enzyme nitric oxide synthase, which produces the inhibitory neurotransmitter nitric oxide. RESULTS: In both cases of IHPS, after healing, the circular musculature was not hypertrophic. For all markers studied, the distribution appeared similar to that in the normal pylorus. In contrast, all specimens obtained at the time of PM displayed a severe reduction of the different markers in the hypertrophic musculature. DISCUSSION: The pathological features observed in the circular layer in IHPS appear to resolve within a few months after PM. This suggests that the involvement of the enteric nervous system in IHPS might be milder than generally assumed. The etiology remains obscure, but our occasional observations may provide new insight into the pathophysiology of IHPS, and are in agreement with the excellent longterm clinical outcome for IHPS.

Biomarkers↗
PubMed1996

Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis.

BACKGROUND & AIMS: The interstitial cells of Cajal form a network in close association with the smooth muscle of the gut. They are regarded as pacemaker cells and might be involved in motility disorders. Their distribution was studied in a common disorder with a dysfunction of the pyloric sphincter called infantile hypertrophic pyloric stenosis. METHODS: Specimens from 27 infants with pyloric stenosis and 12 controls were processed for immunohistochemistry using a specific antiserum raised against c-kit, a tyrosine kinase receptor expressed by interstitial cells. RESULTS: In the normal pylorus, numerous interstitial cells were labeled throughout the tissue. In pyloric stenosis, c-kit immunoreactivity was absent in the major part of the tissue. Interstitial cells were observed only in the inner part of the musculature, near the submucosal edge, and in the antrum, at the proximal end of the biopsy specimens. CONCLUSIONS: The lack of interstitial cells in the pylorus possibly contributes to the motility disturbance of infantile pyloric stenosis.

Female↗
PubMed1995

Decrease of zif-268 and c-fos and increase of c-jun mRNA in the cat areas 17, 18 and 19 following complete visual deafferentation.

We used in situ hybridization to investigate the effect of complete visual deafferentation on immediate early gene expression in adult cat visual cortex. Deafferentation was obtained by unilateral section of the optic tract and sections of both the corpus callosum and anterior commissure. In this model, one hemisphere served as control for the other within the same animal. A decrease in zinc finger protein (zif)-268 and c-fos mRNA was observed in the superficial and deep layers of areas 17 and 18, and all layers of area 19 in the deafferented hemisphere. This decrease, present 3 days after surgery, was maximal after 30 days. An increase of c-jun mRNA was observed in the deep layers of areas 17, 18 and 19 in the deafferented hemisphere 3, 10 and 30 days after surgery. These results suggest that visual input activates zif-268 and c-fos expression and tonically depresses c-jun expression in the primary visual complex yielding similar levels of c-jun and c-fos expression in normal conditions.

Animals↗
PubMed1995

Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction.

A cortical infarct of 2 mm diameter was obtained in the parietal cortex after a craniotomy, disruption of the dura mater and topical application of 3 M KCl. It has been shown previously that the presence of a small cortical infarct induces an increase in immediate early gene messenger RNA expression followed by an increase in neuropeptide and glutamic acid decarboxylase messenger RNA expression. Glutamate, acting at N-methyl-D-aspartate receptors, is held responsible for these changes, since they are blocked by pretreatment with dizocilpine. In the present study, we have analysed the consequences of the dramatic changes in messenger RNA expression on the level of immediate early gene products c-fos and zif 268, and on that of neuropeptides by using immunohistochemistry. After just 1 h, an increase in c-fos- and zif 268-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct, and is no longer detected after 6 h. An increase in cholecystokinin octapeptide-, substance P-, neuropeptide Y- and somatostatin-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after 30 days. To investigate if these dramatic increases in neuropeptide immunoreactivities may have functional consequences, we studied the level of cholecystokinin receptors by autoradiographic binding using [125I]cholecystokinin-8S and in situ hybridization for the detection of cholecystokinin-b receptor messenger RNA. A decrease in cholecystokinin binding sites and cholecystokinin-b receptor messenger RNA is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after nine days. This study shows that a topical stimulation has diffuse effects, reaching regions far from the site of the lesion, and some of them are still strongly present after nine days. The increase in neuropeptide messenger RNAs is followed by an increase in the protein products of these genes, which may modify the neurotransmission. As a corollary to this, a decrease in cholecystokinin binding sites occurs. This may have further consequences on signal transduction pathways. This decrease in cholecystokinin binding sites is associated with a decrease in the cholecystokinin-b receptor messenger RNA, and this is the first example of a decrease in messenger RNA levels in this experimental model.

Animals↗
PubMed1995

Localization of the two protein kinase C beta-mRNA subtypes in cat visual system.

Protein kinase C (PKC) consists of a family of different subtypes encoded by different PKC genes. We investigated the distribution of PKC beta 1 and PKC beta 2 in the visual system of the adult cat by in situ hybridization using oligonucleotide probes complementary to the PKC beta 1 and PKC beta 2 mRNAs, two splicing variants of the same gene transcript. In the primary visual cortex PKC beta 1 and PKC beta 2 were both present. The laminar distribution patterns found for the two PKC subtypes were identical. A remarkable finding was the difference between the laminar distribution of the PKC beta s in areas 17 and 18 when compared with area 19. In all three areas the highest expression levels were found in layer VI, moderately high levels were found in layers II, III and V, while layer I was devoid of signal. In area 17 and 18 layer IV stood out by its low PKC beta signal. In sharp contrast, layer IV of area 19 was indiscernible from the superficial layers because of an evenly high signal. In the dLGN of the adult cat PKC beta 1 and PKC beta 2 mRNAs were distributed rather homogeneously over the different layers, but the expression levels for PKC beta 1 were clearly higher than those for PKC beta 2.

Animals↗
PubMed1995

Prostate capsule: computerized morphometric analysis of its components.

OBJECTIVES: There is little objective information on what is designated as being the prostate capsule. We have quantified objectively with computerized image analysis the percentage of smooth muscle fibers (SMFs) surrounding the surgical specimens of radical prostatectomies. METHODS: Ten radical prostatectomy specimens were used. Six different parts from prostate lobe were analyzed. Thirty different fields were examined from each tissue section. For tissue sections, different stains were used: hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining with antiactin for SMFs. RESULTS: The mean thickness of the prostate capsule was 0.5 to 2 mm. The mean percentages of SMFs in the different regions of the prostate capsule was 30.6%. No difference was noted between the percentage of SMFs in the prostatic capsule compared with that in the prostate parenchyma itself (30.7%). CONCLUSIONS: This study provides objective evidence to demonstrate that the prostate does not have a true capsule. This capsule represents a fibromuscular band that probably should be considered as the extension of the internal parenchyma.

Humans↗
PubMed1995

In memory of Amico Bignami (1930-1994).

Amico Bignami, neuropathologist and neuroscientist, professor of Neuropathology at Harvard Medical School, died on August 5, 1994. He is best known for his pioneering work on spongiform encephalopathies and intermediate filaments, in particular glial fibrillary acidic protein (GFAP).

Creutzfeldt-Jakob Syndrome↗
PubMed1995

Cavernous oxygen tension and smooth muscle fibers: relation and function.

PURPOSE: We studied the effect of intracavernous oxygen tension on the alteration of cavernous smooth muscle fibers in potent and impotent men. MATERIALS AND METHODS: Intracavernous oxygen tension (mm. Hg) was measured during flaccidity and 10 minutes after intracavernous prostaglandin E1 injection in psychogenic control patients, and those with venous leakage and arterial lesions. Cavernous biopsies were performed and the percent of smooth muscle fibers was analyzed objectively using immunohistochemical actin anti-actin staining. Simultaneously brachial oxygen tension (mm. Hg) was measured and the cavernous brachial oxygen tension index was then determined. RESULTS: At flaccidity no significant difference was noted in oxygen tension values among the 3 groups of patients. After prostaglandin E1 injection cavernous oxygen tension and the cavernous brachial oxygen tension index in the control group were significantly different (p < 0.01) from those of the venogenic and arteriogenic groups (p < 0.01). The mean percent of cavernous smooth muscle fibers in the control group was significantly different from those of the venous leakage and arterial lesion groups (p < 0.01). There was a good correlation between the percent of cavernous muscle fibers and the value of oxygen tension before (p < 0.05) and after prostaglandin E1 injection (p < 0.01). A similar correlation was noted between cavernous muscle fibers and cavernous brachial oxygen tension index in the different groups of patients (p < 0.01). CONCLUSIONS: Reduction of the intracavernous smooth muscle fibers in impotent patients could be explained by low intracavernous oxygen tension.

Adult↗
PubMed1994

Distribution of immediate early gene zif-268, c-fos, c-jun and jun-D mRNAs in the adult cat with special references to brain region related to vision.

The distribution of immediate early gene zif-268, c-fos, c-jun and jun-D mRNAs was investigated in the visual cortex, dorsal lateral geniculate nucleus and hippocampus of the adult cat brain with in situ hybridization. In area 17, zif-268, c-jun and jun-D were found predominantly in layers II-III and VI, while c-fos mRNA was abundant in layer VI. In area 18, the zif-268, c-fos and c-jun labelling pattern was identical to that of area 17, this was not true for jun-D. In area 19, only c-jun retained the lamination pattern of areas 17 and 18, while zif-268, c-fos and jun-D were homogeneously distributed. In the dorsal lateral geniculate nucleus, only c-fos and jun-D resulted in labelling. In the pyramidal layer of hippocampus, zif-268 was found in CA1-4, c-jun in CA1-3, and jun-D in CA2-4. In the dentate gyrus, c-jun was abundant, jun-D moderate and zif-268 faint. C-fos labelling was absent in the hippocampal formation.

Animals↗
PubMed1994

delta-9-Tetrahydrocannabinol regulates gene expression of the growth factor pleiotrophin in the forebrain.

delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We here studied, by quantitative in situ hybridization at the macroscopic level, the possible modulatory effects of acute THC (5 mg/kg/i.p.) on gene expression of the growth factor pleiotrophin (PTN) in the adult rat forebrain. We found, 30 min after a single injection of THC, a significant increase of PTN mRNA concentrations in the cingulate cortex (38%), fronto-parietal cortex (31%) and caudate-putamen (27%). In conclusion, this is the first report on THC regulation of growth factor gene expression in the brain.

Animals↗
PubMed1994

Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain.

delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We have recently localized a receptor for THC in the forebrain and found in the caudate-putamen that its gene expression is modulated by glucocorticoids, dopamine and glutamate. Here, we report for the first time, using quantitative in situ hybridization, that acute THC (5 mg kg-1, i.p.) regulates the mRNA levels of multiple immediate early genes in the adult rat forebrain. Twenty minutes after a single THC injection, significant increases in concentration of the mRNAs for C-FOS, C-JUN and ZIF-268 were observed in the cingulate cortex (75, 45 and 37%) and for C-FOS and ZIF-268 in the fronto-parietal cortex (60 and 64%) and caudate-putamen (81 and 32%) while JUN-D mRNA levels were not changed. These transcription factor genes might mediate putative THC modulation of neurotransmitter gene expression.

Animals↗
PubMed1994

delta-9-Tetrahydrocannabinol regulates substance P and enkephalin mRNAs levels in the caudate-putamen.

We have recently localized delta-9-tetrahydrocannabinol (THC) receptor in the projecting neurons of the striatum which are known to express the neuropeptides substance P and enkephalin. We now report for the first time, by quantitative in situ hybridization, that a 3-week treatment with THC significantly increases in the adult rat caudate-putamen the messenger RNAs levels for substance P and enkephalin. These data indicate that THC may regulate gene expression of neuropeptides in the brain.

Animals↗
PubMed1994

Glutamatergic regulation of cannabinoid receptor gene expression in the caudate-putamen.

Glutamatergic regulation of delta-9-tetrahydrocannabinol (THC) receptor gene expression in the adult rat dorsal striatum following a 2 week unilateral cerebral decortication or pharmacological treatment with MK-801 was investigated by quantitative in situ hybridization. The caudate-putamen on the side of the cerebral decortication contains about 30% significantly lower mRNA levels than the control. In addition, we observed a 52% significant decrease in THC receptor mRNA levels in intact dorsal striatum after treatment with MK-801. Together these results suggest that in vivo, through the NMDA receptor subtype, glutamate up-regulates THC receptor gene expression in the rat caudate-putamen.

Animals↗