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Biomedical subjects

N Kopp

Publications and source records attributed to N Kopp.

At least 73 records · Page 4Linked to original sources

[Abnormalities of the nervous system in sudden infant death syndrome].

Anomalies seem to be present in the brain of infants who died of sudden infant death syndrome. They imply dendritic synapses, myelinisation, some neurotransmitters, some peptides, their enzymes and receptors. More precisely, catecholaminergic systems seem to be abnormal. The changes were found mainly in brain stem, in vegetative central areas. These anomalies are probably maturational in nature. They could represent a fragility of vegetative control systems, especially cardiorespiratory and swallowing control systems. They probably do not explain, per se, the occurrence of death; they probably would need to be potentiated by additional etiological factors (environmental, viral, etc). These anomalies have to be considered as provisional and, in our opinion, need confirmation. Apart from the brain stem, other areas are under investigation, particularly cerebral structures implied in temperature control, sleep-wakefulness control and hemispheric structures.

Brain↗

Autoradiographic distribution of TRH binding sites in the human hypothalamus.

Using in vitro quantitative autoradiography and [3H]3MeTRH, a selective high affinity radioligand, we examined the rostrocaudal distribution of TRH binding sites in both the infant and the adult human hypothalamus. The saturation curve shows that the [3H]3MeTRH binds with high affinity to a single class of TRH binding sites and is saturable, the apparent constant of dissociation is in the namomolar range. TRH binding sites showed a wide distribution, principally in the anterior and mediobasal levels of the hypothalamus. TRH binding site concentration was highest within the diagonal band of Broca, the lateral preoptic area, the infundibular and the tuberal nuclei. TRH binding site concentration was moderate in the ventromedial nucleus and the medial preoptic area, whereas we observed low densities in the periventricular, paraventricular and mammillary nuclei. The distribution in the infant and the adult is generally similar. However, it is noteworthy that the infant tuberal nuclei displayed a lower binding site density when compared to the adult. On the other hand, the diagonal band of Broca is relatively more labeled in infant. The analysis of the whole hypothalamus allows us to ascertain the absence of lateral asymmetric distribution both in the infant and the adult. No significant difference is noticed when considering as parameters of variation age, sex or post mortem delay.

Adult↗

Characterization and distribution of [3H]ohmefentanyl binding sites in the human brain.

Binding properties and localization of [3H]ohmefentanyl, a new ligand for mu opioid receptors, were investigated on normal human brain sections. Binding assays performed at the level of the basal ganglia revealed: (1) a steady-state binding reached after 60 min incubation at room temperature, (2) the presence, in saturation experiments, of an apparent single class of binding sites with a Kd = 1.68 +/- 0.45 nM and a Bmax = 162 +/- 9 fmol/mg protein, (3) an order of potency to inhibit [3H]ohmefentanyl binding as follows: ohmefentanyl greater than [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) greater than ethylketocyclazocine (EKC) much greater than Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu) (BUBU) and U-50,488H. Quantitative autoradiography showed an heterogeneous distribution of [3H]ohmefentanyl binding sites with the highest densities in amygdala, medical geniculate body, thalamus, and caudate nucleus. Binding characteristics and anatomical distribution also show that [3H]ohmefentanyl may bind to a small proportion of additional sites called "DAGO-inaccessible [3H]ohmefentanyl specific binding sites." [3H]Ohmefentanyl binding to these sites can be partly inhibited by sigma ligands such as 1,3-di-o-tolylguanidine (DTG) and haloperidol. However, unlabeled DAGO inhibited more than 80% of [3H]ohmefentanyl specific binding in most of the human brain regions studied, suggesting that the major population of sites labeled by [3H]ohmefentanyl represented mu opioid receptors.

Adult↗

Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study.

Using in vitro quantitative autoradiography and [125I]Tyr0-D-Trp8SRIF 14 as radioligand, we characterized the detailed distribution of somatostatin binding sites in human hypothalamus of both infants and adults. Guanosine triphosphate pretreatment, before incubation, allowed us to detect higher [125I]Tyr0-D-Trp8SRIF 14 binding site densities in hypothalamic structures such as preoptic and anterior hypothalamic areas and ventromedial and dorsomedial nuclei. In contrast, guanosine triphosphate was without effect in the other hypothalamic regions. The regional effects of guanosine triphosphate pretreatment were not different in infant and adult hypothalamus. Scatchard analysis showed that in a guanosine triphosphate-sensitive region (preoptic area) and a guanosine triphosphate-insensitive area (infundibular nucleus), [125I]Tyr0-D-Trp8SRIF 14 bound to a single class of binding sites. Affinities were similar in both regions, not modified by guanosine triphosphate pretreatment and not different in the adult (1.5 +/- 1.2 nM vs 3.2 +/- 2.1 nM for preoptic area and infundibular nucleus, respectively) and infant (0.9 +/- 0.5 nM vs 2.4 +/- 1.7 nM for preoptic area and infundibular nucleus). [125I]Tyr0-D-Trp8SRIF 14 binding sites were widely distributed in the anterior, mediobasal and posterior hypothalamus. Somatostatin 28 was twice as potent as somatostatin 14 to displace [125I]Tyr0-D-Trp8SRIF 14 binding in the preoptic area and infundibular nucleus. However, IC50s were 30 times lower in the preoptic area as compared with the infundibular nucleus. In adult as well as in infant, high densities were found mainly in the diagonal band of Broca, preoptic area and infundibular nucleus. Intermediate densities were localized in the anterior hypothalamic area, ventromedial, dorsomedial and lateral mammillary nuclei. The dorsal hypothalamic area, the paraventricular and medial mammillary nuclei displayed low but measurable densities. The only marked difference in the distribution of [125I]Tyr0-D-Trp8SRIF 14 binding sites in adult vs infant was observed in the medial and tuberal nuclei where the concentrations were seven-fold higher in adult hypothalamus.

Adult↗

Anatomical distribution of substance P-immunoreactive neurons in human brainstem during the first postnatal year.

The localization of substance P (SP)-immunoreactive structures in the infant brainstem was investigated by immunohistochemistry using the peroxidase antiperoxidase technique. SP-immunoreactive structures are widely distributed throughout the brainstem region. SP-immunoreactive cell bodies are prominent in the superior colliculis, the central grey, the nucleus tractus solitarius and the reticular formation. A high density of SP-immunoreactive fibers is found in the nucleus tractus solitarius, the trigeminal nucleus and the dorsal horn of the spinal cord. Large SP-immunoreactive fibers are seen in the substantia nigra. In the present study, we also investigated the development of substance P-immunoreactive fibers in the infant brainstem during the first postnatal year. We note a qualitative increase in the density of SP-immunoreactivity in some brainstem regions such as colliculus superior and substantia nigra with respect to age.

Aging↗

Anatomical distribution of LHRH-immunoreactive neurons in the human infant hypothalamus and extrahypothalamic regions.

The morphological features and distribution of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cell bodies and fibers of the hypothalamic and the neighboring mesencephalic regions were studied in the normal newborn infant by immunohistochemistry. Within the hypothalamus, numerous LHRH-immunoreactive like (IL) cell bodies were found mainly in the ventral portion of the infundibular nucleus close to the median eminence and at a lower extent in the medial preoptic area. In addition, sparse immunoreactive cell bodies were displayed in the paraventricular and medial mammillary nuclei. The mesencephalon also exhibited rare immunoreactive cell bodies in the periaqueductal gray. LHRH-IL fibers, predominantly varicose, formed a continuum from the septo-preoptico level to the mesencephalon. In the hypothalamus, the median eminence exhibited the highest LHRH innervation. LHRH-IL fibers are also observed in the lamina terminalis, the medial preoptic area, the suprachiasmatic, the supraoptic, the peri- and the paraventricular nuclei. In the last two nuclei, some fibers projected to the dorsomedial and ventromedial nuclei whereas others were in close relation with the ependyma. The mesencephalon displayed low LHRH-IL fibers, present essentially in the raphe and interpeduncular nuclei and around the ependyma. When compared with data obtained in other mammals, the present findings agree well with the general distribution and morphological features of LHRH-IL neuronal structures reported elsewhere.

Brain↗

Immunohistochemical distribution of somatostatin in the infant hypothalamus.

Somatostatin (SS)-containing neurons were mapped in the normal infant hypothalamus with immunohistochemistry, using the peroxidase anti-peroxidase technique. Neurons displaying SS immunoreactivity show a widespread distribution throughout the hypothalamic region. Principal SS-immunoreactive like (SS-IL) perikarya are located in the paraventricular, infundibular and posterior nuclei and in the preoptic region. High SS innervation is also found in the ventromedial and in the lateral mammillary nuclei, and in the median eminence. In general this distribution of SS-IL agrees well with that reported for rat. Compared to the immunohistochemical distribution of SS in human adult hypothalamus, this mapping in the infant hypothalamus is grossly similar. However some differences may be underlined: the presence of a moderately dense group of SS-IL perikarya in the tuberal and posterior nuclei, and a dense innervation of the ventromedial nucleus and in the median eminence. This first detailed distribution of SS immunoreactivity in infant hypothalamus can provide basic knowledge for further studies of infant neuropathology.

Humans↗

Microangiopathy of endoneurial vessels in hypoxemic chronic obstructive pulmonary disease (COPD). A quantitative ultrastructural study.

A peripheral neuropathy has been reported in patients with chronic respiratory insufficiency due to chronic obstructive pulmonary disease (COPD). It is mainly characterized by axonal degeneration, secondary demyelination and abnormal endoneurial vessels. The pathogenesis of these lesions remains obscure. To investigate whether relationships exist between neuritic and vascular lesions, a qualitative and quantitative ultrastructural study was performed on nerve biopsies in 13 patients with chronic respiratory insufficiency due to COPD, and in 9 normal controls without pulmonary lesions. A computer-assisted multiple regression analysis taking into account clinical, electrophysiological, biological and morphometric parameters was performed. Statistically significant differences in the endoneurial structure of microvessels were: (1) thickening of the basement membrane; (2) narrowing of the lumen; (3) mural pericytic debris deposits, occurring in the COPD group. In the latter, hypercapnia correlated positively with nerve fibers lesions (P = 0.03) and endothelial area (P = 0.03). No correlations were found between age and other parameters. These findings highlight the fact that the microangiopathy in peripheral nerves in patients with COPD may be diffuse and essentially due to hypoxia and reduction in blood flow, as in diabetic neuropathy.

Aged↗

Possible increase of dopamine-beta-hydroxylase activity in the locus ceruleus of paranoid schizophrenic patients: a preliminary post-mortem study.

Five schizophrenic brains and seven control brains were compared for phenylethanolamine-N-methyl-transferase and dopamine-beta-hydroxylase activities. The two groups were comparable in age, sex, and post-mortem delay before autopsy. A radioenzymatic assay showed a statistically significant increase of dopamine-beta-hydroxylase activity in the rostral part of the locus ceruleus in the schizophrenic brains.

Adult↗

Anatomical distribution of somatostatin immunoreactivity in the infant brainstem.

The distribution of somatostatin-immunoreactive structures in the infant brainstem was investigated using the peroxidase-antiperoxidase technique. A wide distribution of somatostatin-immunoreactive cell bodies and fibers was observed throughout the brainstem. Numerous somatostatin-immunoreactive cell bodies and fibers were present in several areas of the brainstem including the substantia grisea centralis and the reticular formation. Some immunoreactive cell bodies were seen in cranial nerve nuclei such as the nucleus praepositus, the nucleus nervi hypoglossi and the vestibular nuclei. Immunoreactive fibers were seen in the nucleus cuneatus, the locus coeruleus, the nucleus tractus solitarius, the nucleus ambiguus, the nucleus tractus spinalis nervi trigemini and the dorsal horn of the spinal cord. These data were in agreement with previous works on the human adult. However, a high density of somatostatin-immunoreactive cell bodies and fibers in the interpeduncular nucleus and in the nucleus centralis superior, and a dense network of somatostatin-immunoreactive fibers in the dorsal part of the nucleus inferior olivarius, were also observed. The role of somatostatin in some brainstem nuclei and its probable implication in some specific neuropathological diseases of the infant brainstem is discussed.

Brain Stem↗

GnRH receptors in human granulosa cells: anatomical localization and characterization by autoradiographic study.

The presence of receptors for GnRH in human ovary has been investigated by quantitative autoradiography. Simultaneous visualization and characterization of specific receptors on frozen sections were obtained on six pairs of human ovaries. Among them only one exhibited a large preovulatory follicle. This dominant follicle exhibited a specific and high affinity binding capacity for 125I-GnRHa exclusively localized on the granulosa cell layer. Analysis of saturation curve indicates a Kd value of 0.22 nM and Bmax of 9.6 fmol/mg protein. In contrast LH-hCG binding sites were present in all antral follicles. These data demonstrate for the first time the presence of high affinity GnRH receptors in human granulosa cells at a late stage of follicular maturation.

Adult↗

[LHRH in the human hypothalamus. Immunohistochemical mapping in normal newborn infants or in sudden death infants].

The topographical distribution of neurons containing LHRH has been investigated in newborn hypothalamus using the peroxidase anti-peroxidase technique. In control subjects, LHRH immunoreactive (LHRH-IR) perikarya have been mainly observed essentially in the infundibular nucleus. The preoptic region displayed a moderate density of LHRH-IR cell bodies. High LHRH innervation was observed in the anterior hypothalamus in the lamina terminalis and in the mediobasal hypothalamus in the median eminence, and in the peri- and paraventricular regions. In sudden death infant syndrome, a comparable mapping was observed, except a low density in the mediobasal peri- and paraventricular areas.

Brain Mapping↗

[Amyloid pseudotumor of the sciatic nerve].

A 60 year-old man complained of numbness and pain in the right lower limb, suggesting lesions of the fifth lumbar and first sacral roots. Sixteen months later, CT showed a tumor of 3.5 cm at the emergence of the first right sacral root. Microscopic examination disclosed an infiltration of the fibers of the nerve by numerous masses of hyaline eosinophilic material which stained with Congo red and produced green birefringence under polarized light. The persistence of congophilic properties of the amyloid deposits after permanganate pretreatment suggested an immunoglobulin origin (AL). A research of amyloid deposit in others viscera: heart, kidneys, digestive tract, was negative. We believe that this is the first reported case of amyloid pseudo-tumor involving a peripheral nerve.

Amyloidosis↗

[Immunohistochemical absence of adrenergic neurons in the dorsal part of the solitary tract nucleus in sudden infant death].

The immunohistochemical distribution of TH and PNMT containing neuronal elements was investigated utilizing peroxidase anti-peroxidase methods in newborn control and sudden infant death syndrome (SIDS) brainstems. The TH immunoreactive neurons, within the medulla oblongata, displayed a similar distribution in both control and SIDS tissue. However, PNMT immunoreactive neurons seen in the dorsal part of the nucleus of tractus solitarius in control tissue were not observed in SIDS tissue. This alteration of adrenergic neurons in the dorsal part of NTS (region reported to be implicated in the control of blood pressure and respiration) could explain the cardiorespiratory disorders in SIDS.

Epinephrine↗

[Chronic peripheral neuropathies with corticosensitive heredodegenerative aspects: 2 cases].

Two cases of peripheral neuropathy beginning in childhood are reported. Both had features suggestive of HMSN with pes cavus and kyphoscoliosis. Familial history of HMSN type I was present in 9 members of the kinship in case 1. In case 2, a mild neuropathy without pes cavus was present in the father. Case 1 developed four relapses of ascending sensory-motor deficit with conduction blocks suggestive of a superimposed chronic inflammatory polyneuropathy (CIP) which improved under prednisone. In case 2, the course was progressive with a severe proximal and distal motor weakness and sensitive disturbances. CSF protein concentration was high. Nerve biopsy showed rare onion bulbs and intense demyelination. These results joint to the unspecificity of the father's neuropathy are consistent with a probable childhood. CIP which improved under prednisone. These two cases indicated that in some patients with unusual symptoms for HMSN, prednisone should be considered and that the physiopathology of these neuropathies is probably heterogeneous.

Child↗

[Peripheral neuropathies simulating amyotrophic lateral sclerosis in gammopathies].

Particular clinical pictures of ALS may occur during the course of some "benign gammapathies". We observed 12 patients (age range 57 to 74 years; 9 men-3 women) with initially benign gammapathy (9 IgG, 1 IgA, 2 IgM) associated to a clinical picture of progressive anterior horn and pyramidal tract involvement. These cases led us to recognize some particularities of gammapathy-associated ALS: Relative frequency of asymmetrical clinical manifestations, rarity of bulbar signs; Decrease of sensory nerve conduction velocities without evidence of sensory clinical symptoms (8 out 9); Increase CSF protein content including the monoclonal component, axonal degeneration and immunostaining evidence of the paraprotein fixation observed on nerve biopsies (5 out 7 cases). Association of ALS and gammapathy is not fortuitous as shown by epidemiology, experiments, pathology and effects of different immunological treatments as related in this study. Demonstration of infra-clinical neuropathy face to a clinical syndrome of ALS should prompt too careful screening for a gammapathy.

Aged↗

Benzodiazepine receptor and neurotransmitter studies in the brain of suicides.

The characteristics of benzodiazepine binding sites (affinity, number heterogeneity) were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. 3H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives (GABA, catecholamines, hydroxy-indols) were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. We observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, (7.48 +/- 1.7 to 17.24 +/- 1.7 nM, P less than 0.01), (m +/- SEM) and an increase in % of type I binding sites (30 +/- 4.2 to 42 +/- 2.5, P = 0.01). Among neurotransmitters, only norepinephrine differed significantly between controls and suicides (11.34 +/- 1.9 to 24.34 ng/g tissue, P = 0.02).

Adolescent↗

Neurotensin immunoreactive neurons in the human infant diencephalon.

Neurotensin-like immunoreactive (NT-IR) neurons are present in discrete subregions of the anterior, medial and lateral thalamic nuclear groups of the human infant brain. The pulvinar is notably rich in such cells. Smaller numbers of cells are present in the ventral group, centromedian nucleus, reticular nuclei and intralaminar nuclei. Neurotensin immunoreactive axons accumulate dorsally in the thalamus and cross the deep white matter. The cerebral cortex contains a rich network of NT-IR axons. The subthalamic nucleus is rich in NT-IR neurons. Within the hypothalamus NT-IR perikarya are present in parts of the lateral and tuberal regions and in the lateral mammillary area. NT-IR axons are widespread being particularly prominent in parts of the tuberal region and the mammillary body.

Diencephalon↗