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Biomedical subjects

M Gumpel

Publications and source records attributed to M Gumpel.

At least 37 records · Page 2Linked to original sources
PubMed1991

Oligodendrocytes of the jimpy phenotype can be partially restored by environmental factors in vivo.

Cross-transplantations of neural tissue between jimpy (jp) shiverer (shi) and normal mice have been performed under heterochronic conditions. In all series, fragments of E14-E15 embryonic neural tissue from the different donors have been transplanted into newborn host brain in order to study environmental influences by differentiated tissue on transplanted embryonic cell lines. Large patches of proteolipid protein (PLP)-positive myelin have been observed in the jp brain after transplantation of shi or normal embryonic tissue into the newborn jp brain, suggesting that the jp parenchyma did not inhibit the differentiation of other oligodendrocytes (ODCs). Jp embryonic tissue had the same mitotic potential as normal tissue, as demonstrated by the larger size of myelin patches observed when jp embryonic tissue was used instead of newborn jp tissue. By contrast, whatever the conditions, jp myelin patches were always obviously smaller than normal or shi myelin patches, suggesting that the myelinating capacity of jp ODCs was not enhanced by environmental factors. Finally, comparison of the ratio of successful outcomes observed following embryonic vs. newborn jp donor tissue, strongly suggests a partial or total normalization of jp embryonic ODCs survival by a more mature shi environment.

Animals↗
PubMed1991

Acidic fibroblast growth factor (aFGF) is expressed in the neuronal and glial spinal cord cells of adult mice.

Fibroblast growth factors (FGFs) are known to be synthesized in the central nervous system (CNS) and to act on CNS cells in vitro, but less is known about their synthesis, expression, and role in vivo. In this work, using specific anti-acidic fibroblast growth factor (aFGF) antibodies, we have shown for the first time, by immunohistochemistry, that aFGF is expressed in spinal cord cells of young adult normal mice. This expression is predominant in the cell nucleus. Using immunohistochemical double staining procedures, we identified the cell type expressing aFGF as neurons, astrocytes, and oligodendrocytes, but for each type, cells were not all positively immunostained.

Animals↗
PubMed1991

A nuclear marker for mammalian cells and its use with intracerebral transplants.

The Hoechst dye staining method has been successfully applied to the central nervous system in mammals and its use has been demonstrated in intracerebral transplantation. The technique is rapid, simple and based on intrinsic nuclear properties. It was found to be permanent and valid whatever the animal strains or ages, allowing the distinction of rat cells from those of mouse, studied either separately or in a cross-transplantation model. It permitted the detection of grafted cells in the area of transplantation and the observation of early dispersion around the implantation site. Moreover, it can be combined with immunohistochemistry as demonstrated by a myelin marker in a relevant model. Immunodetection can thus help to directly observe grafted cells, at distance from the locus of transplantation, confirming their presence in the graft-type myelin patches. Because of its rapid performance, this technique can be used systematically after transplantation to check for the presence of grafted cells in the host.

Animals↗
PubMed1990

Patchy myelination pattern in the jimpy mouse brain: immunohistochemical study.

The jimpy (jp) mutation of the mouse leads to a dramatic decrease of myelination in the hemizygous mutant central nervous system (CNS). Several descriptions based on classical histology, immunohistochemistry, and electron microscopy (EM) have demonstrated the scarcity of myelin formation in the different parts of the CNS. The immunohistochemical study presented here showed a very singular patchy pattern of myelin distribution in the different areas of the whole mutant brain. The myelin patches are randomly dispersed without bilateral symmetry, and their density and location vary from one animal to another. No reproducible pattern of myelination could be found among the population observed. This distribution has been compared with observations on young heterozygotes and wild-type homozygotes from the same strain. A similar patchy and random distribution of myelin could be observed in heterozygotes, which present an intermediate level of myelination. This strongly suggests that a migration of precursors or immature oligodendrocytes (ODCs) from the periventricular zone followed by local multiplication of colonies of ODCs before myelination is a general feature in normal as well as pathological conditions.

Animals↗
PubMed1990

Immunohistochemical studies on cross-transplantations between jimpy, shiverer, and normal newborn mice.

Cross-transplantations of neural tissue have been performed between jimpy (jp), shiverer (shi), and normal mice. Taking advantage of the absence of immunodetectable myelin basic protein (MBP) in the shi brain, jp myelin has been identified in the shi recipient by using an anti-MBP antiserum. By contrast, shi as well as normal myelin have been identified in the jp brain by using an anti-C-terminal hexapeptide of the proteolipid protein (PLP) (this PLP hexapeptide being absent in the jp PLP). When transplanted under homochronic conditions (newborn into newborn), jp oligodendrocytes (ODC) express their usual phenotype in a normal or a shi environment, suggesting that at birth the jp ODCs phenotype is strictly established and cannot be modified by environmental conditions. The reverse transplantations (newborn shi or normal into newborn jp brain) demonstrate that the jp environment does not modify the phenotype of normal or shi ODCs. Finally, these experiments demonstrated a normal timing of differentiation of jp axons and of jp ODCs.

Animals↗
PubMed1990

Endogenous cerebellar soluble lectin and its ligands in central nervous system myelin of quaking and jimpy mutant mice.

The presence of an endogenous 'cerebellar soluble lectin' (CSL) involved in myelin compaction and myelination was analyzed in the dysmyelinating mutant mice quaking and jimpy. The primary defect in these mutations with severe hypomyelination is still unknown in the quaking mutant but results from a single mutation in the proteolipid protein gene in the jimpy mutant. Both immunocytochemical and immunoblotting techniques showed that CSL was not considerably reduced in its expression in the myelin fraction purified from adult quaking mutants. Furthermore, the myelin-associated glycoprotein and an axonal glycoprotein with a relative molecular weight (Mr) of 31 kilodaltons (kDa) were not decreased in quaking mice. This contrasted with several glycoproteins of Mr 23, 18, 16 and 12 kDa which were absent from the purified quaking myelin. In myelin preparations obtained from the jimpy mutant the CSL level was considerably reduced. This defect did not result from a deficient synthesis of CSL. However, as in the quaking mutation low-Mr glycoproteins were lacking. The nature of the low-Mr glycoproteins absent in quaking and jimpy mice is discussed in relation to previous reports on myelin glycoproteins. In the various mutants, due to different primary mutations, a similar absence of myelin compaction was observed, which could be associated with a deficient level of low-Mr glycoproteins. It is thus postulated that these molecules are essential for ensuring myelin compaction as ligands for the endogenous CSL.

Animals↗
PubMed1990

Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat.

The expression of peripherin, an intermediate filament protein, had been shown by biochemical methods to be localized in the neurons of the PNS. Using immunohistochemical methods, we analyzed this expression more extensively during the development of the rat and compared it with that of the low-molecular-mass neurofilament protein (NF-L), which is expressed in every neuron of the CNS and PNS. The immunoreactivity of NF-L is first apparent at the 25-somite stage (about 11 d) in the ventral horn of the spinal medulla and in the posterior part of the rhombencephalon. The immunoreactivity of peripherin appears subsequently, first colocalized with that of NF-L. Both immunoreactivities then spread out along rostral and caudal directions, but whereas the immunoreactivity of NF-L finally becomes noticeable in every part of the nervous system, that of peripherin remains localized to (1) the motoneurons of the ventral horn of the spinal medulla; (2) the autonomic ganglionic and preganglionic neurons; and (3) the sensory neurons. These results demonstrate that, in the neurons that originate from migrating neural crest cells, the immunoreactivities of peripherin and of NF-L become apparent only when they have reached their destination. The results also show that peripherin is expressed more widely than has been previously observed and that this protein occurs in neuronal populations from different lineages (neural tube, neural crest, placodes) with different functions (motoneurons, sensory and autonomic neurons). The common point of these neurons is that they all have axons lying, at least partly, at the outside of the axis constituted by the encephalon and the spinal medulla; this suggests that peripherin might play a role in the recognition of the axonal pathway through the intermediary of membrane proteins.

Animals↗
PubMed1990

Acute medical admissions: changes following a sudden reduction in bed numbers at Northwick Park Hospital.

The aim of this study was to gather information on the consequences of hospital bed closures on acute admission patterns. Each November during 1986-1988 we carried out a survey of requests and referrals for acute medical admission to Northwick Park Hospital (NPH). Between the first study in 1986 and the second study in 1987, 15 acute medical and 16 surgical beds were closed. In 1986 the hospital was 'full' and closed overnight to admissions from general practitioners (GPs) on 3/25 days. In 1987 this had increased to 16/27 days and in 1988 it was closed overnight on 20/31 days. Because GPs found it unreasonably difficult to admit patients to NPH, the number of patients referred by them fell from 55.8% of all admissions to 49.8% and 44.3%, while the number of self-referred patients rose from 27.1% to 34.5% and 39.1%. An increasing proportion of elderly patients had to be admitted to acute medical beds: those over 75 years of age represented 24.8% of admissions in 1986, 43.7% in 1987, and 43.8% in 1988. These changes have had important effects on our medical practice, and we suggest that audits of this type are necessary to quantify these changes. We make suggestions for improving such medical audits in the future.

Bed Occupancy↗
PubMed1989

Presence of Schwann cells in neurodegenerative lesions of the central nervous system.

Ultrastructural analysis of neurodegenerative CNS lesions produced by an excitotoxic substance revealed that the majority of cells ensheathing axons were not oligodendrocytes. By their morphology and the presence of both a basal lamina and collagen fibers they were identified as Schwann cells. The presence of Schwann cells, whose growth-promoting role in the peripheral nervous system has been largely documented, may account for the development of regenerating growth cones which have been observed in the excitotoxically lesioned central nervous system. Further support for this hypothesis came from the analysis of fetal neural transplants implanted into the lesioned area. Schwann cells ensheathing axons were indeed numerous in the neuron-depleted area surrounding the transplants, where neurite outgrowth of graft origin occurred.

Animals↗
PubMed1989

Myelination and remyelination in the central nervous system by transplanted oligodendrocytes using the shiverer model. Discussion on the remyelinating cell population in adult mammals.

In the early sixties, remyelination was first observed in animal models of demyelination and described a few years later in multiple sclerosis. The spontaneous remyelination process is now well documented. Remyelination by transplantation of myelin-forming cells has been attempted. Transplanted Schwann cells can myelinate a central nervous system lesion but the remyelination is limited to the area of implantation. Oligodendrocytes or precursor cells are much more invasive and have been shown to migrate from the implantation site to the lesion at a distance of several millimeters. Thus, remyelination by transplantation of myelin-forming cells is possible at least in animal models, the oligodendrocytes being more efficient.

Animals↗
PubMed1988

Remyelination by transplanted oligodendrocytes of a demyelinated lesion in the spinal cord of the adult shiverer mouse.

Fragments of normal newborn mouse central nervous system (CNS) were transplanted into the spinal cord of adult shiverer mice at distance of 1, 2 or 3 intervertebral spaces from a lysolecithin-induced demyelinating lesion. Remyelination by grafted oligodendrocytes was observed by electron microscopy (EM). This result showed the capability of grafted oligodendrocytes or precursor cells to migrate to a demyelinated lesion and to remyelinate naked axons in an adult host, even in presence of host spontaneous remyelination.

Animals↗
PubMed1988

Myelination by oligodendrocytes isolated from 4-6-week-old rat central nervous system and transplanted into newborn shiverer brain.

Oligodendrocytes isolated from 4-6-week-old rat brains were transplanted into newborn shiverer brains. Cells were identified as mature oligodendrocytes both by immunocytological and ultrastructural criteria. Normal myelin was detected using immunolocalisation (with an anti-MBP antiserum) and electron microscopy (presence of the major dense line). Patches of normal myelin (made by transplanted oligodendrocytes), widely spread throughout the host brains, were detected between 20 and 130 days after grafting. No sign of acute rejection was observed, but the graft became progressively delimited by astrocytic processes forming a continuous basal lamina.

Animals↗
PubMed1988

[Comparative expression of 2 intermediate filament proteins, peripherin and the 68 kDa neurofilament protein, during embryonal development of the rat].

Peripherin, an intermediate filament protein, was originally detected by biochemical methods in the neurons of the peripheral nervous system. We now studied its expression and cellular localization by immunocytochemical methods in the developing rat embryo, and compared them with the expression and localization of the 68 kDa neurofilament protein. It appears that peripherin is expressed not only in the neurons of the peripheral nervous system, but also in some well defined neuronal populations of the central nervous system. These results focus on the questions of the phylogenetic origin and of the function of peripherin.

Animals↗
PubMed1987

Transplantation of oligodendrocytes in the newborn mouse brain: extension of myelination by transplanted cells. Anatomical study.

The shiverer model allows for the immunocytochemical staining of the patches of myelin formed by transplanted oligodendrocytes from a normal newborn mouse. Fragments of the olfactory bulb were transplanted into various parts of the brain to place the myelinating cells in different anatomical conditions. Whole brains were horizontally sectioned in order to study the full pattern of migration and myelination of the grafted oligodendrocytes. Transplanted oligodendrocytes were capable of short and long distance migration before their differentiation. Long distance migration occurred in the caudal as well as in the rostral direction and into the contralateral part of the brain through the commissures. The patches of immunoreactive myelin were mainly found in the large myelinated bundles: corpus callosum, internal capsule, fimbria-fornix, medial lemniscus, cerebellar peduncles and spinal cord funiculi. Some sites of migration indicate that oligodendrocytes followed at least two different axonal pathways successively. The thalamic area which contained numerous patches could be a place where oligodendrocytes switch from one fasciculus to another.

Animals↗
PubMed1987

Anaemia in juvenile chronic arthritis: serum inhibition of normal erythropoiesis in vitro.

Serum from patients with juvenile chronic arthritis (JCA) was shown to inhibit colony formation by normal erythropoietic progenitor cells cultured in vitro. The inhibition was proportional to the degree of anaemia and to certain indices of activity of the arthritis and systemic disease. It occurred in a dose dependent manner with increasing serum concentration and was independent of previous blood transfusion or administered drugs. Erythropoietic progenitor cells from the bone marrows of anaemic patients with JCA showed normal requirements for accessory cells (T lymphocytes and macrophages) in culture, and autologous accessory cells were not deficient in providing normal growth requirements.

Adolescent↗
PubMed1987

[Intracerebral transplantation of oligodendrocytes in mice].

We describe in this paper experiments in which oligodendrocytes (from newborn mouse, human embryonic brain, or isolated from adult rat brain) have been transplanted into the brain of the newborn mouse. Experimental conditions (Shiverer model) allowed the detection of myelin formed by transplanted oligodendrocytes into the Shiverer brain. The transplanted oligodendrocytes have been shown to survive, migrate over long distances and myelinate host axons. The maturation of transplanted oligodendrocytes depends upon the age of the brain tissue in which they differentiate.

Animals↗