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Biomedical subjects

F Schmitz

Publications and source records attributed to F Schmitz.

At least 73 records · Page 4Linked to original sources
PubMed1997

Somatosensory evoked potentials modified by laser-induced lesions of the rat cortex.

The effect of focal application of laser energy on the modification of somatosensory evoked potentials (SEPs) was studied in sensory cortical fields of the rat. This article describes the methodological set-up for recording of SEPs and for determining location and size of the laser-induced lesion. The results show that both the size of the lesion of the somatosensory cortex, and the suppression and time of recovery of cortical SEPs varied depending on the laser energy dose. It remains to be analyzed by further experiments if the recovery of SEPs is due to a transient dysfunction of the somatosensory cortex or if it reflects cortical plasticity.

Animals↗
PubMed1997

Dystrophin in the retina.

Dystrophin is a plasma membrane-associated cytoskeletal protein of the spectrin superfamily. The dystrophin cytoskeleton has been first characterized in muscle. Muscular 427 kDa dystrophin binds to subplasmalemmal actin filaments via its amino-terminal domain. The carboxy-terminus of dystrophin binds to a plasma membrane anchor, beta-dystroglycan, which is associated on the external side with the extracellular matrix receptor, alpha-dystroglycan, that binds to the basal lamina proteins laminin-1, laminin-2, and agrin. In the muscle, the dystroglycan complex is associated with the sarcoglycan complex that consists of several glycosylated, integral membrane proteins. The absence or functional deficiency of the dystrophin cytoskeleton is the cause of several types of muscular dystrophies including the lethal Duchenne muscular dystrophy (DMD), one of the most severe and most common genetic disorders of man. The dystrophin complex is believed to stabilize the plasma membrane during cycles of contraction and relaxation. Muscular dystrophin and several types of dystrophin variants are also present in extramuscular tissues, e.g. in distinct regions of the central nervous systems including the retina. Absence of dystrophin from these sites is believed to be responsible for some extramuscular symptoms of DMD, e.g. mental retardation and disturbances in retinal electrophysiology (reduced b-wave in electroretinograms). The reduced b-wave in electroretinograms indicated a disturbance of neurotransmission between photoreceptors and ON-bipolar cells. At least two different dystrophin variants are present in photoreceptor synaptic complexes. One of these dystrophins (Dp260) is virtually exclusively expressed in the retina. In the neuroretina, dystrophin is found in significant amounts in the invaginated photoreceptor synaptic complexes. At this location dystrophin colocalizes with dystroglycan. Agrin, an extracellular ligand of alpha-dystroglycan, is also present at this location whereas the proteins of the sarcoglycan complex appear to be absent in photoreceptor synaptic complexes. Dystrophin and dystroglycan are located distal from the ribbon-containing active synaptic zones where both proteins are restricted to the photoreceptor plasma membrane bordering on the lateral sides of the synaptic invagination. In addition, some neuronal profiles of the postsynaptic complex also contain dystrophin and beta-dystroglycan. These profiles appear to belong at least in part to projections of the photoreceptor terminals into the postsynaptic dendritic complex. In view of the abnormal neurotransmission between photoreceptors and ON-bipolar cells in DMD patients the dystrophin/beta-dystroglycan-containing projections of photoreceptor presynaptic terminals into the postsynaptic dendritic plexus might somehow modify the ON-bipolar pathway. Another retinal site associated with dystrophin/beta-dystropglycan is the plasma membrane of Müller cells where dystrophin/beta-dystroglycan appear to be present at particular high concentrations. At this location the dystrophin/dystroglycan complex may play a role in the attachment of the retina to the vitreous, and, under pathological conditions, in traction-induced retinal detachment.

Animals↗
PubMed1996

Purification of synaptic ribbons, structural components of the photoreceptor active zone complex.

Synaptic ribbons are plasma membrane-associated structural elements in photoreceptor synaptic terminals. They seem to act as high capacity "docking sites" of synaptic vesicles that provide the fusion sites of the photoreceptor synapse ("active zones"), with a large supply of immobilized synaptic vesicles rapidly available for exocytosis. Synaptic ribbons are regarded as a specialized type of presynaptic densities found in virtually all synapses. The molecular composition of presynaptic densities and synaptic ribbons is unknown. The aim of this study was the isolation of synaptic ribbons from photoreceptor synapses. For this purpose, we first isolated a membrane fraction from the bovine retina that was strongly enriched in photoreceptor synapses. From this fraction, a Triton X-100-resistant subfraction was purified that consisted mainly of synaptic ribbons and their disassembly products. The high enrichment of synaptic ribbons was verified by electron microscopy and immunolabeling using an antibody that specifically binds to synaptic ribbons. SDS-PAGE analysis of this synaptic ribbon fraction displayed several major polypeptide bands migrating at approximately 240, 60, 55, 43, and 30 kDa. The purification procedure described here is a first promising step toward the identification of the yet unknown constituents of synaptic ribbons from photoreceptor synapses and possibly also of presynaptic densities from other synapses.

Animals↗
PubMed1996

Dystrophin and the dystrophin-associated glycoprotein, beta-dystroglycan, co-localize in photoreceptor synaptic complexes of the human retina.

Mutations in the gene encoding for dystrophin, a membrane-associated cytoskeletal protein of muscle and several non-muscle cells, are the cause of Duchenne muscular dystrophy and Becker muscular dystrophy. Patients suffering from Duchenne muscular dystrophy have recently been shown to display an abnormal b-wave of the electroretinogram, suggesting that dystrophin is important for normal retinal transmission. In the retina, dystrophin has been localized in the outer plexiform layer where dystrophin co-localizes with postsynaptic markers of photoreceptor synaptic complexes. In the present study we addressed the question of whether two major dystrophin-associated integral membrane proteins of the muscular plasma membrane, beta-dystroglycan and adhalin, are also present in photoreceptor synaptic complexes. By double immunostaining and immunoblotting we show here that beta-dystroglycan is expressed in the human retina where it co-localizes with dystrophin in photoreceptor synaptic complexes most likely on the postsynaptic side. Adhalin was not detected in the retina. Since beta-dystroglycan is a member of a transmembrane supramolecular complex thought to be important for differentiation of the neuromuscular junction, it is an attractive hypothesis that dystroglycan (linked to dystrophin) might also play a similar role in differentiation of the photoreceptor synapse. A further outcome of this study is that beta-dystroglycan is not only present in the neuromuscular junction but also associated with a well-defined synaptic complex of the central nervous system. These findings indicate a more general role of this dystrophin-associated membrane protein in synaptic functions.

Adult↗
PubMed1996

Insulin-like growth factor-I serum concentrations and patterns of insulin-like growth factor binding proteins in patients with chronic liver disease.

BACKGROUND/AIMS: Serum concentrations of insulin-like growth factor-I are decreased in liver cirrhosis. However, this growth factor is bound for the most part to specific binding proteins that are known to modulate biological actions. Plasma insulin-like growth factor binding proteins are predominantly synthesized in the liver. METHODS: The effect of liver disease on basal and on growth hormone-stimulated serum concentrations of total and "free" insulin-like growth factor-I and on insulin-like growth factor binding protein patterns is reported. Sera were obtained from 20 patients with non-cirrhotic chronic liver diseases and from 20 patients with cirrhosis before and 24 h after a single subcutaneous dose of growth hormone. Samples were analyzed using radioimmunoassays, gel chromatography, ligand blotting and immunoblotting. RESULTS: In cirrhosis, serum concentrations of total and "free" insulin-like growth factor-I were decreased, the binding protein pattern was changed profoundly showing a reduction in the 150 kD complex and an increase in the 30-40 kD complexes. Concentrations of binding protein-1 and -2 were increased, while that of binding protein-3 was decreased in cirrhosis. The response to growth hormone was blunted. These changes were related to the degree of liver dysfunction as assessed by the Child-Pugh classification. CONCLUSIONS: A pathogenetic link of altered bio-availability of insulin-like growth factor-I to clinical characteristics of advanced liver disease, e.g. insulin resistance or skeletal muscle wasting, may be suggested by the present data.

Adult↗
PubMed1996

Identification of cholecystokinin-B/gastrin receptor domains that confer high gastrin affinity: utilization of a novel Xenopus laevis cholecystokinin receptor.

A hallmark of the mammalian brain cholecystokinin (CCK) receptor, CCK-B/gastrin (CCK-BR), is its high affinity for two structurally related peptides, CCK and gastrin. Previous radioligand binding experiments suggested that the predominant CCK receptor from Xenopus laevis brain shares high affinity for sulfated cholecystokinin octapeptide but has > or = 1000-fold lower affinity for gastrin. To determine the molecular basis for this pharmacological divergence between mammalian and lower vertebrate receptors, we isolated a cDNA encoding the X. laevis brain CCK receptor (CCK-XLR). CCK-XLR shares approximately 50% homology at the amino acid level with both the human CCK-BR and the peripheral CCK-A receptor subtypes. The recombinant X. laevis receptor has a distinct pharmacological profile of agonist and antagonist affinities and as such offers a useful tool for structure-function studies. We used CCK-XLR to map the human CCK-BR domains that confer high affinity for gastrin. A series of chimeric CCK-BR/CCK-XLR constructs was generated and pharmacologically characterized. While maintaining wild-type affinity for sulfated cholecystokinin octapeptide, receptors with increasing amino-terminal contributions from CCK-BR demonstrated a stepwise increase in gastrin affinity. Further dissection of the amino-terminal third of the human receptor, a domain that confers a > 250-fold increase in gastrin affinity, revealed the importance of interactions among at least three subdomains. Additional structural requirements for gastrin affinity mapped to a segment spanning transmembrane domains IV and V.

Amino Acid Sequence↗
PubMed1995

Distribution of neurofilament-positive nerve fibres and sensory endings in the human anterior cruciate ligament.

The present immunocytochemical study describes the distribution of neurofilament-containing nerve fibres and corpuscular-like endings in the human anterior cruciate ligament. The entire anterior cruciate ligament of a non-injured knee joint from a child was cut into serial 15-microns-thick frozen sections, which were processed for immunofluorescence staining with a monoclonal antibody against the 68-kDa neurofilament subunit. Numerous neurofilament-positive fibres were found in bundles. These bundles were mostly located near blood vessels in the subsynovial layer and in interfascicular gaps. Only a few single nerve fibres were found independent of blood vessels in interfascicular gaps and between collagen bundles. Neurofilament-containing nerve fibres were preferentially located near the bony attachments of the anterior cruciate ligament. Two types of corpuscular-like endings were found, i.e. "spiral-like" (type I) and "spray-like" (type II) endings. Similarly to nerve fibres, both types of corpuscular-like endings were found mainly near the tibial and femoral attachment sites (15 of 17), whereas only two were found in the middle third of the ligament. Most likely, the type I and type II corpuscular-like endings serve a mechanoreceptive function involved in the sensory control of normal movements and in stress protection.

Anterior Cruciate Ligament↗
PubMed1995

Effect of insulin-like growth factor II on uptake of arylsulfatase A by cultured rat hepatocytes and Kupffer cells.

Mannose 6-phosphate/insulin-like growth factor II receptors have been characterized in hepatocytes and Kupffer cells isolated from adult rat liver. Affinity labeling with [125I]insulin-like growth factor II revealed a protein of Mr 250,000 in both cell types. Labeling was inhibited by an antiserum against the mannose 6-phosphate/insulin-like growth factor II receptor. In Kupffer cells, [125I]insulin-like growth factor II was also cross-linked to a second protein of Mr 130,000. In both cell types, insulin-like growth factor II was 10 times more potent than insulin-like growth factor I in displacing [125I]insulin-like growth factor II from its receptor. The mannose 6-phosphate-specific uptake of [125I]arylsulfatase A via the mannose 6-phosphate/insulin-like growth factor II receptor was inhibited by insulin-like growth factor II and antibodies against the receptor, but was not affected by insulin-like growth factor I, insulin or transforming growth factor beta 1. Cell surface iodination followed by immunoprecipitation of the mannose 6-phosphate/insulin-like growth factor II receptor showed that expression of the mannose 6-phosphate/insulin-like growth factor II receptors at the plasma membrane was increased two-fold by insulin-like growth factor II. These results suggest that binding of insulin-like growth factor II to the mannose 6-phosphate/insulin-like growth factor II receptor blocks the binding and uptake of mannose 6-phosphate-containing lysosomal enzymes and may be directly involved in a co-ordinate regulation of ligand uptake from plasma into hepatocytes and Kupffer cells.

Animals↗
PubMed1995

Somatosensory evoked potentials elicited by intraneural microstimulation of afferent nerve fibers.

Cortical somatosensory evoked potentials (SEPs) after intraneural microstimulation (IMS) of cutaneous and afferent muscle nerve fibers in the median nerve were recorded to study the contribution of different afferent fiber groups to the SEP. Thirty-seven cutaneous fiber bundles, 10 afferent muscle nerve fiber bundles, and 45 single mechanoreceptive afferents of FA I- (n = 12), FA II- (n = 8), SA I- (n = 13), and SA II-type (n = 12) were studied in 29 healthy subjects. IMS of cutaneous fiber bundles evoked cortical responses corresponding to the N20 component after median nerve stimulation in 86% of the fascicles studied, whereas IMS of muscle nerve fiber bundles elicited responses only in 20%. After IMS of single mechanoreceptive afferents of FA I-, FA II-, and SA I-type cortical responses were obtained in all groups in approximately 80% of the stimulated units. The latencies of the SEPs evoked by IMS were comparable to that after compound median nerve stimulation (mean difference 0.58 ms). The N20 amplitudes of SEPs after IMS of cutaneous fiber bundles were on average 28% (n = 32) and for single afferents 22% (n = 30) of that after compound nerve stimulation. It is concluded that the median nerve SEPs evoked by compound median nerve stimulation of the resting hand are dominated by cutaneous rather than muscle afferent input. Furthermore, the fact that selective stimulation of only a few cutaneous afferents produces cortical SEPs of rather high amplitude is compatible with the view that sensory information produced by selective afferent stimulation is differentially gated into the somatosensory cortex.

Adult↗
PubMed1994

[Frontal and temporal onset of brain atrophy. Clinical and instrumental findings].

We report the cases of a 70-year old man with left temporal brain atrophy and of a 39-year-old man with neuropathologically verified frontal lobe degeneration (FLD) of Non-Alzheimer type. 10 patients with FLD collected during a prospective study on degenerative dementia had more severe volumetric brain changes and less severe quantitative band power changes than a group of matched patients with clinically diagnosed Alzheimer's disease.

Adult↗
PubMed1994

Intracellular distribution of kinesin in chromaffin cells.

In this paper we examined the association of the microtubule motor protein kinesin with organelles in chromaffin cells. Approximately 15% of kinesin was associated with membranes as determined by differential and equilibrium centrifugation on sucrose gradients. Kinesin was not enriched in a particular organelle fraction but cofractionated with a variety of organelle markers including markers for early and late endosomes, smooth and rough endoplasmic reticulum (ER) and the Golgi apparatus. Surprisingly, low amounts of kinesin were present in fractions of purified chromaffin granules. The absence of kinesin from the bulk of chromaffin granules was also indicated by immunostaining of tissue sections. A polyclonal antibody that specifically recognized the 120 kDa kinesin heavy chain labeled predominantly a perinuclear region that is typical for most of the kinesin-binding organelles identified by cell fractionation (endosomes, Golgi, ER). Since these organelles are compartments with high membrane turnover, we speculate that kinesin might be involved in certain aspects of trafficking of these membrane systems.

Animals↗
PubMed1993

Li(+)-induced structural changes of synaptic ribbons are related to the phosphoinositide metabolism in photoreceptor synapses.

Synaptic ribbons are specialized cytoskeletal components of the presynaptic exocytotic machinery in photoreceptors. In cone photoreceptors, these structures are highly dynamic disappearing during darkness and reforming in the light phase. In this study we wanted to characterize the second messengers involved in the regulation of these cyclic changes. We show that synaptic ribbons in cone photoreceptors are very sensitive to both Li+ and inositol 1,4,5-trisphosphate suggesting that inositol polyphosphates might play a physiological role in the disassembly of synaptic ribbons. The presence of the phosphoinositide pathway was demonstrated in isolated photoreceptor synapses. The phosphoinositide metabolism in photoreceptor synapses was dark-activated and correlated with the disappearance of synaptic ribbons during dark-adaptation. Since Li+ and inositol 1,4,5-trisphosphate only influenced synaptic ribbons in cones but not in rods the dark-activated phosphoinositide metabolism should be largely ascribed to cone synapses.

Animals↗
PubMed1993

Colocalization of retinal dystrophin and actin in postsynaptic dendrites of rod and cone photoreceptor synapses.

In this paper we demonstrate immunostaining specific for dystrophin in photoreceptor synapses of human, bovine and rat retinas. Cryosections of retinas incubated with dystrophin-specific monoclonal antibodies displayed a punctuate staining pattern in the outer plexiform layer. This pattern resulted from binding of the antibodies to synaptic complexes of both rods and cones, shown by double-labelling with antibodies to either synaptophysin or actin. Confocal laser fluorescence microscopy demonstrated that dystrophin staining colocalized predominantly with actin, which is concentrated in the postsynaptic portions of the synaptic complex. No significant dystrophin immunolabel was seen in the presynaptic terminals labelled with antibodies to synaptophysin, a marker of synaptic vesicles. Immunoblot analysis confirmed the presence of approximately 420 kDa and approximately 360 kDa dystrophin-like polypeptide bands associated with membranes of the bovine retina. We speculate that retinal dystrophin is involved in the linkage of actin filaments to the postsynaptic plasma membrane. Such a linkage may be important for the generation of synaptic microdomains and for certain phenomena of synaptic plasticity. The absence of dystrophin in patients suffering from Duchenne's muscular dystrophy is accompanied by visual problems and abnormalities of the electroretinogram. Therefore it is likely that retinal dystrophin plays a role in certain stages of synaptic transmission between photoreceptors and the postsynaptic dendritic complex formed by horizontal and bipolar cells.

Actins↗
PubMed1993

Distribution of actin in cone photoreceptor synapses.

The invaginated photoreceptor terminal harbours a great number of postsynaptic dendrites that contact the photoreceptor terminal at morphologically distinct synapses. In this paper we studied the subcellular distribution of actin in cone photoreceptor synapses of light-adapted goldfish and guppy retinas and its relation to ribbon and spinule synapses. In the outer plexiform layer, fluorescent staining for actin by antibodies and also by fluorescently labelled phalloidin was discontinuous and showed large dot-like immunoreactive structures (3-5 microns in diameter). Immunogold electron microscopy of light-adapted retinas isolated 3 h after the onset of light demonstrated that these dot-like structures corresponded to dendritic profiles of bipolar and horizontal cells within the synaptic cavity of cones. A much less intense staining was observed within the presynaptic cone photoreceptor terminal itself. Immunogold particles were also found overlying the tips of horizontal and bipolar dendrites that form the triadic postsynaptic complex of the ribbon synapse. In contrast to the triads light-induced terminal outgrowings of horizontal cells, also known as spinules, remained largely unlabelled. These observations suggest that actin plays a role in maintenance and/or certain steps of the formation of the postsynaptic dendritic complex.

Actins↗
PubMed1991

Influence of Ca2+ on synaptic morphology of fish cone photoreceptors.

Isolated fish retinas were incubated with the Ca(2+)-ionophore A23187 at various Ca2+ concentrations. Computer reconstructions of the ultrastructure of cone synapses revealed pronounced reduction of the presynaptic surface (complete loss of the synaptic invaginations) in response to low intracellular Ca2+ (less than 10(-8) M). No obvious effect on synaptic morphology was noticed at Ca2+ greater than 10(-8) M. Ca(2+)-dependent exocytotic activity appears to be a major factor controlling the invaginated morphology of cone synapses.

Animals↗
PubMed1991

In vivo metabolic action of insulin-like growth factor I in adult rats.

The acute metabolic actions of insulin-like growth factor I were studied in anaesthetized adult rats and its potency was compared to that of insulin. Following an i.v. bolus injection of insulin-like growth factor I a dose-dependent decrease of blood glucose and serum non-esterified fatty acid concentrations was noted with a potency of about 2% that of insulin. Stimulation of total body glucose disposal during euglycaemic clamping required approximately 50 times higher insulin-like growth factor I serum concentrations to achieve an identical half-maximal response. A similar difference in potency was observed for the stimulatory action on 2-deoxyglucose uptake and on glycogen formation in skeletal muscle. Lipogenesis in epididymal fat pads was increased dose-dependently by both hormones requiring approximately 30 times higher half-maximally effective serum concentrations of insulin-like growth factor I. These data demonstrate that insulin-like growth factor I exerted acute insulin-like metabolic actions in vivo with low potency. These effects were probably mediated via insulin receptors. A preferential stimulation of glucose metabolism in skeletal muscle was not observed.

Adipose Tissue↗
PubMed1991

[Waldheim--the difficult task of investigation].

This is a report on a mental hospital--or, rather, a department of a mental hospital--called "Waldheim", (literal meaning: "hostal, or home in the woods") which is a section of the mental hospital at Hochweitzschen in Saxony in the former German Democratic Republic (GDR). Public opinion had been aroused some time ago by an article published in the German weekly "Stern" in which it was stated that psychotic patients were being subjected to leukotomy or stereotactic surgery, and that castration by x-ray treatment was being performed in mentally handicapped women, in that hospital. The article prompted the then Ministery of Health of the GDR to constitute an "expert committee" to investigate into the matter. The magazine's allegations were partly confirmed by the committee. The GDR parliament then constituted a "special parliamentary commission" for another inquiry. Again several allegations were confirmed. It was stated that the events and actions in that hospital had been unsatisfactorily assessed and digested. The authors undertake to make the procedures followed by the medical and nursing staff, accessible to a wider public and to render them more lucid. Important structural characteristics of the patterns that developed there, were the governmentally prescribed segregation of severely diseased persons to "treat" them far away from their residential community, the absence of a critical general public, and the amalgamation of supervisory institutions with those that require to be supervised.(ABSTRACT TRUNCATED AT 250 WORDS)

Commitment of Persons with Psychiatric Disorders↗