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Biomedical subjects

R Kiefer

Publications and source records attributed to R Kiefer.

At least 55 records · Page 3Linked to original sources
PubMed1993

Transforming growth factor beta expression in reactive spinal cord microglia and meningeal inflammatory cells during experimental allergic neuritis.

Experimental allergic neuritis (EAN), an inflammatory demyelinating disorder of the peripheral nervous system, is preceded and accompanied by a massive microglial reaction in the spinal cord which occurs in the absence of inflammatory cells infiltrating the cord parenchyma. Since transforming growth factor beta (TGF-beta) has been shown to play a beneficial role in experimental autoimmune disease and might be involved in the regulation of glial activity, we have investigated the expression of TGF-beta in EAN spinal cord and nerve root tissue. Adoptive transfer EAN was induced by the injection of neurotogenic T-cells specific for the P2 myelin protein. In normal spinal cord tissue, both TGF-beta 1 and TGF-beta 3 mRNA were constitutively expressed at low levels. Already 3 days following injection of P2-specific T-cells, TGF-beta 1 mRNA levels began to increase, peaked at day 6 at levels about tenfold above normal, and thereafter declined. TGF-beta 3 was induced even earlier with a sharp rise at day 3 and a peak fourfold above normal at day 4. In situ hybridization for TGF-beta 1 performed on spinal cord sections 6 days after injection of cells localized TGF-beta 1 mRNA to many nonneuronal cells with the typical morphology of microglia. In addition, TGF-beta 1 mRNA was observed in the meninges, and massive accumulation of signal was seen over inflammatory cells infiltrating the nerve roots. Our data indicate that TGF-beta 1 and -beta 3 are involved in regulating the glial response in EAN and that activated microglial cells might control their own activity state by expressing TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interleukin-6 and transforming growth factor-beta 1 mRNAs are induced in rat facial nucleus following motoneuron axotomy.

Transection of the rat facial nerve leads to a rapid activation of both astrocytes and microglia around axotomized motoneurons. The factors involved in glial activation in vivo are poorly defined but cytokines have been implicated as major regulators of glial activity in vitro. In the present study we have investigated the expression of cytokine mRNAs in the axotomized facial nucleus that might be involved in glial activation. Eight hours after axotomy unilateral transection of the facial nerve had already induced a rapid accumulation of interleukin (IL)-6-mRNA, with a peak at 24 hours. No IL-6 mRNA was detected on the unoperated control side. Transforming growth factor (TGF)-beta 1 mRNA was detected at low levels in the normal facial nucleus, increasing to three times the normal level 2 days after axotomy. After day 7 TGF-beta 1 mRNA levels gradually declined, with a second minor peak 21 days after axotomy. In situ hybridization experiments, 4 and 21 days after axotomy, localized TGF-beta 1 mRNA to activated microglial cells around regenerating motoneurons, as well as probably some astrocytes. Motoneurons did not express TGF-beta 1 mRNA. TGF-beta 3 was found to be normally expressed in the facial nucleus but was not regulated by axotomy. No mRNA for IL-1, tumour necrosis factor-alpha or interferon-gamma was found in the regenerating facial nucleus at any point in time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation.

Transforming growth factor-beta 1 (TGF-beta 1) has been shown to up-regulate the synthesis of nerve growth factor (NGF) in cultured rat astrocytes and in neonatal brain in vivo (Lindholm, D., B. Hengerer, F. Zafra, and H. Thoenen. 1990. NeuroReport. 1:9-12). Here we show that mRNA encoding TGF-beta 1 increased in rat cerebral cortex after a penetrating brain injury. The level of NGF mRNA is also transiently increased after the brain trauma, whereas that of brain-derived neurotrophic factor remained unchanged. In situ hybridization experiments showed a strong expression of TGF-beta 1 4 d after the lesion in cells within and in the vicinity of the wound. Staining of adjacent sections with OX-42 antibodies, specific for macrophages and microglia/brain macrophages, revealed a similar pattern of positive cells, suggesting that invading macrophages, and perhaps reactive microglia, are the source of TGF-beta 1 in injured brain. Both astrocytes and microglia express TGF-beta 1 in culture, and TGF-beta 1 mRNA levels in astrocytes are increased by various growth factors, including FGF, EGF, and TGF-beta itself. TGF-beta 1 is a strong inhibitor of astrocyte proliferation and suppresses the mitotic effects of FGF and EGF on astrocytes. The present results indicate that TGF-beta 1 expressed in the lesioned brain plays a role in nerve regeneration by stimulating NGF production and by controlling the extent of astrocyte proliferation and scar formation.

Animals↗
PubMed1991

Effects of dexamethasone on microglial activation in vivo: selective downregulation of major histocompatibility complex class II expression in regenerating facial nucleus.

Following axotomy of the facial nerve microglial cells in the facial nucleus become activated, proliferate, and newly express class I and class II major histocompatibility complex (MHC) antigens. Dexamethasone treatment, starting 2 days prior to axotomy at 1 mg/kg/day, selectively inhibited axotomy-induced MHC class II expression on microglial and perivascular cells. In contrast, MHC class I expression was not significantly affected, nor was the expression of other microglial activation markers and the light microscopic morphology of activated microglia. A recently suggested inducer of MHC expression in rat nervous tissue, neuronal gamma interferon-like immunoreactive material, was also unaffected, as was glial fibrillary acidic protein immunoreactivity as a marker for concomitant astroglial activation. The differential effects of the drug suggest the presence of distinct regulatory pathways for different aspects of microglial activation. Inhibition of class II expression on activated microglia might be one mechanism how glucocorticoids act in the suppression of neuroinflammatory disease.

Animals↗
PubMed1991

Gamma interferon-like immunoreactive material in rat neurons: evidence against a close relationship to gamma interferon.

Gamma interferon is a potent immunoregulatory peptide produced by activated lymphocytes. Recently, a gamma interferon-like immunoreactive molecule has been demonstrated immunohistochemically in subpopulations of rat neurons. We have now further characterized this molecule. Western blot analysis of spinal ganglia homogenates revealed a single 60,000 mol. wt band that was immunoreactive with monoclonal antibody DB1 directed against rat gamma interferon. A polyclonal antiserum and the monoclonal antibodies DB10 and DB12 failed to detect this band although all antibodies were able to label the major 18,000 mol. wt band of recombinant gamma interferon on the same blots. The 60,000 mol. wt band was selectively present in homogenates from primary sensory and sympathetic ganglia but was absent from the central nervous system and other peripheral organs, corresponding to the reported immunocytochemical distribution of gamma interferon-like immunoreactivity. The 60,000 mol. wt protein does not appear to be glycosylated. It could not be solubilized by detergents such as Triton X-100 and it co-purified with cytoskeleton-enriched preparations. At the nucleic acid level, Northern blot analysis using probes specific for rat gamma interferon mRNA failed to detect specific mRNA in rat spinal ganglia, whereas a strong 1.2 kb signal was detected in activated spleen cells. Functionally, gamma interferon-like immunoreactive material is strongly induced in superior cervical ganglion neurons after preganglionic axotomy of the sympathetic chain, but remains constant or slightly decreases in L5 spinal ganglion neurons after sciatic nerve transection. In contrast, major histocompatibility complex antigens are strongly induced on non-neuronal cells in both systems. We conclude that the neuronal gamma interferon-like immunoreactive material is clearly distinct from lymphocyte-derived gamma interferon and might not be involved in the control of major histocompatibility complex expression on glial cells.

Animals↗
PubMed1990

New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury.

The results of the present study demonstrate that following lethal motor neuron injury microglia and perivascular cells, as well as brain macrophages derived from the latter two cell types, newly express antigens of the myelomonocytic lineage as recognized by the monoclonal antibodies ED1 and ED3. It is suggested that differences in the immunophenotype of resident brain macrophage precursor cells, i.e. microglia and perivascular cells, and macrophages occurring outside the central nervous system (CNS) may be explained by differences in local macrophage antigen expression rather than by a different embryological lineage. The new appearance of antigens common to peripheral macrophages on neural phagocytes in CNS lesions may therefore not necessarily imply that most or all of these cells are of recent blood origin.

Animals↗
PubMed1990

Gamma interferon-like immunoreactivity in the rat nervous system.

The presence of gamma interferon-like immunoreactivity in the peripheral nervous system and in some central nervous system neurons is described. The immunohistochemical evidence is based upon labeling of neurons with five different monoclonal antibodies against rat gamma interferon and one polyclonal antiserum. Immunoreactive material was abundantly present in the peripheral nervous system including small primary sensory neurons in dorsal root ganglia and postsynaptic neurons of the sympathetic and parasympathetic nervous system. Large neurons in dorsal root ganglia were not stained. Neurites stained with DB1 antibody against rat gamma interferon were found in most organs examined such as the gastrointestinal tract, heart, lungs, kidney, sexual organs and skin. In contrast, staining was weak in the central nervous system and restricted to a few neurons in the hypothalamus and in the midbrain. It is speculated that this newly discovered system containing a gamma interferon-like neuropeptide could be involved in the neuronal control of immunological processes in its target organs.

Adrenal Glands↗
PubMed1989

Cerebellar injury due to phenytoin. Identification and evolution of Purkinje cell axonal swellings in deep cerebellar nuclei of mice.

The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytoin. Thirty male C57Bl/6J mice received phenytoin orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion.

Animals↗
PubMed1989

The management of dermal necrosis after acute Neisseria infection.

Although the occurrence of dermal necrosis following Neisseria meningitidis is rare, it portends a grave prognosis with a high mortality rate. A child having this complication is described who sustained a loss of over 30% of the body skin surface. She was successfully treated with aggressive nutritional support, meshed split-thickness skin grafting, and early rehabilitation. The pathophysiology of this complication is discussed, along with principles that are important in the day-to-day management of the patient.

Child, Preschool↗
PubMed1977

Genetic factors in childhood epilepsy with focal sharp waves. I. Clinical data and familial morbidity for seizures.

203 epileptic children (127 boys, 76 girls), who had demonstrated at least once focal sharp waves in the EEG during the course were investigated regarding clinical and historical data as well as familial morbidity for seizures. Expectedly, the seizure symptomatology was multiform: focal seizures of different type, especially secondarily generalized, grand mal, psychomotor fits, infantile spasms etc. Organic brain lesions play an important role. In 23% of cases a familial seizure affliction can be registered. The morbidity (close family) is significantly lower than in families of patients with spike wave absences (2.5 and 4.4% resp., Doose et al. 1973). Like in spike wave absence epilepsies mothers and mothers' siblings are more often affected than fathers and fathers' siblings. Among the affected relatives grand mal epilepsies predominate. The increase of febrile convulsions and spike wave absences observed in the families of absence epileptics is not present. In probands with onset of epilepsy during early childhood a significantly increased familial affliction can be observed. A more extensive discussion of the results will follow in a second paper deeling with EEG findings in probands and siblings.

Child↗
PubMed1977

Genetic factors in childhood epilepsy with focal sharp waves. II. EEG findings in patients and siblings.

Electroencephalographical investigations were performed in 203 epileptic children exhibiting focal sharp waves in the EEG and in 312 siblings. As controls served 685 brain-healthy children (Gerken 1971) as well as 252 children with spike wave absences and their 242 siblings (Doose et al. 1973). According to the EEG findings in probands so-called "centrencephalic" EEG-criteria (theta rhythms, spikes and waves, photosensitivity) as a symptom of a genetically determined seizure susceptibility can be expected in at least 60% of the probands. 18% of the siblings showed at least once one definite "centrencephalic" EEG pattern. These results must be regarded as minimal values, since in siblings only one electro-encephalographic study could be performed. The results make it evident, that in the pathogenesis of epilepsy with focal sharp waves a genetically determined seizure susceptibility plays a very important role. After comparison with the results of genetic investigations in patients with spike wave absences (Doose et al. 1973) the difference as for the genetic basis between "centrencephalic" and focal epilepsies apparently is only due to a different gene density.

Brain Damage, Chronic↗
PubMed1976

[Value of clinical history, skin testing and nasal allergen challenge in the diagnose of perennial rhinopathia].

In 64 out-patients suffering from perennial and partly from additional saisonal rhinopathia correlations between clinical history, skin testing (prick test) and nasal provocation tests were investigated. Most patients showed several positive skin tests to common allergens particular to grass pollen, house dust and mites (Dermatophagoides pteronyssimus). 123 nasal provocation tests were done. The correlation between history and skin test or nasal challenge was very strong for grass pollen (agreement in 78%), but very unsatisfctory for house dust and mites. Even in patients with positive skin tests to house dust and mites the history was only positive in 50-60%. Therefore the diagnose of perennial rhinopathia due to house dust and/or mites is only relevant if the nasal provocation gives a positive result. But if skin test are negative, nasal allergen challenge seldom showed positive reactions. For practical purpose nasal provocation is unneccessary if the skin test is negative. But the nasal provocation test don't give an absolutely right diagnose, because neither the environmental concentration nor the nasal threshold generally are known. Therefore, it is difficult to decide in many cases, if a reaction is positive because of testing a relevant allergen or because a latent allergen was overdosed. Finally the investigations show that simple and reproducible methods like the nasal forced expiratory volume in one second are sufficient to detect a positive nasal reaction.

Adolescent↗