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Biomedical subjects

G Fuhrmann

Publications and source records attributed to G Fuhrmann.

At least 19 recordsLinked to original sources

Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells.

We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum effects were similar for HEL and megakaryocytic colony formation. The effect of aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of both FGFs was found to be synergistic with interleukin-3 (IL-3), and was abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor complex of approximately 120 Kd was detected for FGF by crosslinking experiments on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF. Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was confirmed by polymerase chain reaction, which also showed the presence of FGF receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets. Together, these results indicate that FGF is involved in megakaryocytopoiesis and suggest that this interaction may be mediated via FGF receptor type 1 and type 2 located on the megakaryocytic lineage or on accessory cells responsible for the release of megakaryocytic growth-promoting activities.

Animals

[Spontaneous fracture of an implanted anterior chamber lens].

This report deals with an 83-year-old patient who presented with visual deterioration. The patient had had an intracapsulary extraction with anterior chamber lens implantation. The break in the anterior chamber lens happened without any history of traumatic accident and led to dislocation of the lens and corneal decompensation. Scanning electron microscopy of the break area after explantation of the fragments revealed changes in the break zone that were characteristic of alternating tensile and compressive stress. Localization of the break at the transition of the optical part and the haptic where there is the greatest stress in the material points to insufficient strengthening in this critical part of the intraocular lens.

Aged

Tissues at the surface of the new composite material titanium/glass-ceramic for replacement of bone and teeth.

A new composite implant material titanium/glass-ceramic was tested in rabbits using light microscopy, histomorphometry, and biomechanical testing methods. Two rabbit implant models were used. The first premolar tooth was replaced and cylinders inserted into the trabecular bone of the distal femur below the patella sliding plane. There was bone bonding to the glass-ceramic component and additional mechanical interlocking, due to bone ingrowth between the titanium matrix into secondary pores. This was proved by measuring the tensile strength at the interface of the new composite material which was in the same range as compared to pure glass-ceramic implants. In tooth replacement there was a tight attachment of gingival epithelium and stroma to composite titanium/glass-ceramic. These results are of particular clinical interest: physicochemical bone bonding and additional mechanical interlocking result in a resistance of the implant material against shear and tensile loads at the interface. Therefore this new composite material should be suitable for further load-bearing applications.

Animals

Influence of mouse genotype on responses on central neurotransmitters to long-term alcohol exposure in striatum and hippocampus.

A striking strain dependency in response of central neuromediators (dopamine, serotonin, acetylcholine activities and somatostatin) to various periods of alcohol treatment has been noted in striatum and hippocampus in mice. For biogenic amines the C57Bl strain loses tolerance to prolonged alcohol injury earlier than the Balb/c strain. At the opposite the Balb/c strain exhibits a remarkable long lasting tolerance for cholinergic activity. The unequal capacity to adapt, also appears to depend on the nervous structure and the neurotransmitter considered. Such discrepancies may underly differences in behavioral changes observed in alcoholics.

Animals

Effects of hormone therapy on the central cholinergic neurotransmission of the Snell dwarf mouse.

Effects of growth and thyroid hormone therapy on central cholinergic neurotransmission has been followed in the cholinergic-deficient Snell dwarf mouse. Growth hormone and thyroxine can reverse the neurotransmission impairment even in adulthood. Furthermore, it appears that in the dw/dw mouse, hormone deficiency becomes determinant only after the critical period of neurogenesis, in a late postnatal developmental stage. At first sight, these observations show that the disturbed cholinergic neurotransmission of the mutant might be linked to the pituitary and thyroxine deficiency that is characteristic of this mouse. Hormone therapy selectively stimulates cholinergic activity in cholinergic-deficient structures, where it reactivates presynaptic markers. The differential responsiveness of the neuroanatomical and neurochemical targets could be linked to different regulatory hormone effects or to timing in respect to sensitivity to hormones during development.

Acetylcholinesterase

Genotypic differences in age and chronic alcohol exposure effects on somatostatin levels in hippocampus and striatum in mice.

Somatostatin contents of striatum, hippocampus, and pons medulla have been followed in two inbred strains of mice (C57B1/6J and Balb/cJ) with aging and long term alcohol exposure (over a 25 month period of intoxication). Marked strain dependent differences in basic levels of somatostatin and genotypic variations in reactivity of this neuropeptide to aging processes and chronic alcohol exposure were demonstrated. The Balb/c strain exhibits a significant age dependent decrease in striatal and hippocampal somatostatin levels whereas the C57B1 mice remain unchanged until the 27 month. Moreover, only the Balb/c strain reacts to chronic alcohol exposure, showing a significant increase in somatostatin levels in those structures affected by the aging process. Such genotypic differences may be involved in man in specific pathologies in aged individuals and in alcohol induced behavioral alterations in alcoholics.

Aging

Somatostatin levels in the central nervous system of the Snell dwarf mouse; is somatostatin excess the primary molecular defect in the dw/dw dwarfism?

The Snell dwarf mouse (dw/dw) shows significantly decreased somatostatin levels in the hypothalamus whereas more or less increased somatostatin concentrations are observed in any central extrahypothalamic sites studied. These opposite results in hypothalamus and extrahypothalamic areas may be linked to the apparently distinct neurohormonal and neuromodulatory functions of somatostatin in the brain. They also provide arguments for the assumption of a primary somatostatin excess which could be related to the dwarf mutation. In hypothalamus, the severe defect in growth hormone of the dwarf mutant may rapidly lead, by failure of a pituitary retro-control, to a reduction in the presumed initially elevated somatostatin levels. In central extrahypothalamic sites, known to escape to GH retro-action, higher somatostatin levels remain.

Animals

Cholinergic neurotransmission in the central nervous system of the Snell dwarf mouse.

An unequal decrease in cholinergic activity has been evidenced in discrete brain areas in the growth hormone, thyroid-stimulating hormone and prolactin deficient Snell dwarf mouse. The effect of the mutation's pituitary deficit on central cholinergic mechanisms appears to be selective: Normally high cholinergic activity areas such as striatum, olfactory tubercles, and hippocampus show strong alterations in this neurotransmitter system. Structures which appear earlier in ontogenesis are less affected, if at all. The lack of pituitary hormones seems to have effects on choline acetyltransferase activity and/or synthesis as well as on the development of high affinity (H.A.) cholinergic uptake mechanisms, both strongly defective in hippocampus and striatum. Therefore, a lower density of cholinergic terminals can be inferred. Furthermore, our observations are consistent with a close functional coupling of the choline H.A. transport and of subsequent choline acetylation. Acetylcholinesterase activity does not seem to be affected. Moreover, a compensatory effect at the postsynaptic level may have occurred due to developmental or functional plasticity for cholinergic responsiveness. In conclusion, the dwarf mouse seems to be a useful model for a better understanding of the influences of growth hormone and thyroid hormones on the development of central cholinergic mechanisms. It also provides the possibility to attempt a functional restoration of the deficient cholinergic neurotransmission and the behavioral disturbances which may be linked to them, by hormone replacement.

Acetylcholinesterase

Dopamine and serotonin metabolism in striatum and in the septohippocampal pathway of the Snell dwarf mouse.

Dopamine and serotonin neurotransmission has been investigated in striatum and in the septohippocampal pathway of the locomotor activity and memory deficient Snell dwarf mouse. In striatum a sharp decrease in 3-MT levels with a concomitant decrease in DA turnover is indicative of a strong decrement in the functional activity of striatal dopaminergic terminals in the mutant mouse. The observed enhancement in serotoninergic markers (5HT, 5HIAA, 5 HTP), at the opposite, provide evidence for an altered relationship between serotonin and dopamine striatal neurotransmission in the mutant mouse as compared to the normal mouse. Impairment in dopamine and serotonin neurotransmission has also been observed in the septohippocampal pathway where the removal of acidic metabolites of these neurotransmitters from brain appears to be disturbed. The data presented here are discussed with regard to previously noted alterations in cholinergic activity as well as to the behavioral disturbances of the dwarf mutant.

Animals

Mathematical approach to integrating the "neuron-module" and the "cell-assembly".

The structural and functional unit of neuropsychic activity is approached in a mathematical way referring to some basic features of both the "neuron-module" and the "cell-assembly." The proposed units, called modules, have specific synchronous inputs and outputs, more abundant inner than outer connectivity, and their states are assumed representing concepts. Neurons in the model possess finite, discrete scales of states with inhomogeneous distances. Neighbouring relations are asymmetric (like the synapses) and of both intra- and inter-modular type. The actual states of neighbouring cells form a collective state. This is an emergent phenomenon, formally a complex, not necessarily explicit function of the cellular variables. Collective states belonging to the neurons in a module form the modular state. Thus, the influence of different cells on the modular state depends on their arborization, reflecting that the organization of the module holds greater significance than its size. Some of the modular states are assumed as "known", others are described by fuzzy sets representing definite and ambiguous concepts, respectively. A specified version of the model with application to visual pattern recognition is summarized for illustration.

Brain

Arithmetic model for the distributed encoding in the neuron-module.

A class of arithmetic code defined in residue number system (RNS) is proposed as a mathematical model of neural encoding. The formalism of RNS provides for a vectorial representation in which the digits in the code-words (the "coordinates") contain the information in a distributed manner. These digits and the code-words are assumed to represent the states of the neurons and neuron-modules, respectively. The involved mechanism appears physiologically possible. After the number-theoretical background is summarized in a brief though self-contained way, mathematical assertions are drawn on the error detecting and correction capacities of the formalized modules. It is concluded that RNS provides an appropriate model of neural encoding though drawing inference by the neurons (the evaluation of the encoded information) requires another formalism.

Brain

[Psychosocial dwarfism].

A 4 year old girl with psychosocial dwarfism showed hepatomegaly, abdominal distension and behavioral disturbances. Laboratory tests revealed a reversible elevation of serum liver enzymes and a reversible partial growth hormone deficiency. The child's family was characterised by severe social problems and all signs of a depriving and child abusing environment. All pathologic findings were reversed by removing the child from her depriving family background. This case demonstrates that psychosocial dwarfism represents an aspect of child abuse (battered child syndrome).

Body Height

Influence of mouse genotype on responses of central cholinergic neurotransmission to long term alcohol intoxication.

Cholinergic neurotransmission has been followed in striatum and hippocampus in two inbred strains of mice (C57Bl/6 and Balb/c) during long term alcohol exposure (over a 25 month period) and with aging. Marked strain dependent differences in reactivity of pre- and postsynaptic cholinergic markers to chronic alcohol exposure and aging were demonstrated in both structures. The Balb/c strain exhibits a remarkable long lasting tolerance to alcohol injury for striatal and hippocampal cholinergic markers (choline acetyltransferase, high affinity choline uptake, muscarinic receptors affinity, acetyl cholinesterase), whereas C57Bl mice appear more sensitive to alcohol intoxication. Likewise aging affects the C57Bl mouse more severely than the Balb/c, a phenomenon which may be involved in the sensitivity of these mice to alcohol intoxication. Moreover long term alcohol exposure, in addition to aging show unequal effects on the diverse cholinergic markers studied. Also divergences of specific brain areas have been noted and should be related to their particular neuroanatomy. Such discrepancies may, in part, explain differences observed in the behavioral effects of chronic alcohol intoxication in alcoholics.

Acetylcholinesterase

Influence of mouse genotype on responses of central biogenic amines to alcohol intoxication and aging.

Dopamine and serotonin responses to various periods of alcohol treatment have been followed in striatum and hippocampus of two inbred strains of mice and related to the effect of aging. A striking strain dependency was noted for chronic alcohol effects and also for senescence. For both neurotransmitters studied the C57Bl strain loses tolerance to prolonged alcohol injury earlier than the Balb/c strain. This loss of tolerance accompanying aging may be indicative of more widespread changes in CNS adaptability in this strain. The unequal capacity to adapt also appears to depend on the nervous structure and the neurotransmitter considered. Alcohol and aging induced changes are not identical. In a given mouse strain, significant effects of either drug or aging induced disturbances are noted. A similar molecular process could operate in both aging and alcohol abuse, but the neurochemical effect might depend on the nervous structure or neurotransmitter involved. Such a phenomenon may be the basis of differences in behavioral changes observed in alcoholics.

Aging

[Biomechanic and histomorphometric studies of HIP titanium glass ceramic, a new implant material, compared with glass ceramics, titanium and titanium alloy].

Interfacial tensile strength and quantitative histomorphological properties of alloplastic implant materials for hard tissue application were studied in animal models. Physico-chemical bonding in the order of 1 N/mm2 of bone to glass-ceramic (Ceravital) was demonstrated independent of magnitude of surface roughness with mineralized bone in excess of 80% at the implant interface. No bone-bonding, but contact of mineralized bone at the metal surface was observed in pure titanium and titanium alloys (Ti6Al4V, Ti5Al2, 5Fe) with smooth surfaces. Rough or porous surfaced specimens, however, exhibited mechanical interlocking and interdigitation, thus yielding interfacial tensile strength of up to 4 N/mm2 in geometrically porous or madreporic surfaces. The new composite material HIP-Titanium-glass-ceramic (Ceravital) displayed physico-chemical bonding to bone as well as mechanical interdigitation within the secondary porous structure, thus giving support to expectations that HIP-Titanium-glass-ceramic coated implants should perform superior than bulk materials.

Animals