Showing papers by "Michael Meyer published in 1988"

Regulation of the Synthesis of Nerve Growth Factor and Nerve Growth Factor Receptor

Abstract: The importance of Nerve Growth Factor (NGF) for the development and the maintenance of differentiated properties of peripheral sympathetic and neural crest- derived sensory neurons as well as for basal forebrain cholinergic neurons is well established (cf Levi-Montalcini & Angeletti, 1968; Greene & Shooter, 1980; Thoenen & Barde, 1980; Thoenen et al. 1987). NGF interacts with specific neuronal receptors, is internalized and is subsequently retrogradely transported to the perikaryon. During the last few years new methodological approaches allowed the direct analysis of the retrograde messenger function of NGF between target organs and corresponding NGF-responsive neurons. In the adult animal it was demonstrated that the density of sympathetic innervation is correlated with the levels of NGF (Korsching & Thoenen 1983) and mRNANGF (Heumann et al. 1984, Shelton & Reichardt 1984). Thus, the ratio between NGF and mRNANGF in various target tissues of sympathetic or sensory neurons is relatively constant. However, in sympathetic and sensory ganglia containing the cell bodies of NGF-responsive neurons the levels of NGF are (relatively) very high whereas the mRNANGF levels are at the detection limit (Heumann et al. 1984, Davies et al. 1987a). Similarly, in the sciatic nerve (Heumann et al. 1987a) the ratio between NGF and mRNANFG is up to 100–fold higher than in peripheral target tissues of sympathetic and sensory neurons, reflecting the very low contribution of local synthesis to the sciatic NGF content. This is in agreement with the observation that after ligation of the sciatic nerve NGF accumulates distally to the ligature whereas proximaily NGF levels are reduced to the detection limit of the NGF assay (Korsching and Thoenen, 1983b). The importance of the NGF supply from the peripheral target tissues is also demonstrated by the fact that destruction of sympathetic nerve terminals by 6–OH- dopamine results in a rapid decay of NGF levels in the sympathetic ganglia (t1/2 = 4-5 hours) (Korsching and Thoenen, 1985) with a concomitant increase of NGF in the corresponding peripheral target organs.

Pulmonary diffusing capacity for carbon monoxide and nitric oxide.

Abstract: Carbon monoxide (CO) is widely used to determine the diffusive conductance or diffusing capacity (D) of the lungs. Its advantage over O2 is the high affinity of hemoglobin for CO whereby PCO in pulmonary capillary blood is low and the veno-arterial PCO difference is minimal. Thus, the mean PCO difference effective for alveolar-capillary CO transfer is close to alveolar Pco. But since the reaction of CO with hemoglobin is relatively slow, the diffusing capacity for CO includes a reaction component which cannot be easily assessed. The affinity of hemoglobin for nitric oxide (NO) is even higher (about 2000 t imes) than for CO and, more importantly, the association velocity constant of hemoglobin with NO is about 75 times higher than that with CO (1). Thus the diffusing capacity for NO may represent a closer estimate of the true pulmonary diffusing capacity, i.e. not complicated by reaction velocity. Moreover, a comparison with DCO may provide information on the extent of reaction limitation in CO uptake.

Nerve growth factor

Abstract: In contrast to all other molecules which are labelled 'growth factor', NGF is not a mitogen. It is a neurotrophic molecule essential for the development and maintenance of function of specific populations of peripheral and possibly also central neurons. The availability of NGF in large quantities from exocrine glands (e.g. male mouse submandibular gland), where NGF does not play a neurotrophic role, has allowed the purification of NGF, the production of specific antibodies, the determination of its amino acid sequence and finally the molecular cloning of NGF leading to the elucidation of its precursor structure and its genomic organization. Comparison of the biological activities and the immunological properties of NGF isolated from different sources demonstrated that the active centre of the molecule has been highly conserved during evolution, whereas other parts of the molecule determining immunological properties have undergone considerable changes. After a survey of the essential biological actions of NGF, this paper concentrates on two actual questions of NGF research, namely the regulation of NGF synthesis in the target tissues of NGF-responsive neurons, and the molecular mechanism(s) of action of NGF on these neurons.