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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 523 records · Page 29Linked to original sources

Nerve growth factor: cellular localization and regulation of synthesis.

1. The role of nerve growth factor (NGF) as a retrograde messenger between peripheral target tissues and innervating sympathetic and neural crest-derived sensory neurons is supported by the observations that (a) the interruption of retrograde axonal transport has the same effects as the neutralization of endogenous NGF by anti-NGF antibodies and (b) the close correlation between the density of innervation by fibers of NGF-responsive neurons and the levels of NGF and mRNANGF in their target organs. 2. In situ hybridization experiments have demonstrated that a great variety of cells in the projection field or NGF-responsive neurons is synthesizing NGF, among them epithelial cells, smooth muscle cells, fibroblasts, and Schwann cells. 3. The temporal correlation between the growth of trigeminal sensory fibers into the whisker pad of the mouse and the commencement of NGF synthesis initially suggested a causal relationship between these two events. However, in chick embryos rendered aneural by prior removal of the neural tube or the neural crest, it was shown that the onset of NGF synthesis in the periphery is independent of neurons, and is controlled by an endogenous "clock" whose regulatory mechanism remains to be established. 4. A comparison between NGF synthesis in the nonneuronal cells of the newborn rat sciatic nerve and that in the adult sciatic nerve after lesion provided evidence for the important regulatory role played by a secretory product of activated macrophages. The identity of this product is currently under investigation.

Animals↗

Blood flow distribution and its temporal variability in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply in 8 gastrocnemius muscles (mean weight 84 g) of 6 anesthetized dogs (20-25 kg body weight). The distribution of 10 micron microspheres in regions of about 0.5 g was very similar to that of the standard 15 micron microspheres, whereas that of 25 micron microspheres was more uneven. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 micron and 15 micron microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 micron microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 ( = square root 0.45(2) - 0.12(2], but there were marked differences between muscles. At equal blood flow levels, the inhomogeneity during reactive hyperemia was similar to that observed during stimulation. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 min into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19, but the differences in the extent of temporal blood flow changes among muscle pieces within a muscle and between different muscles were large. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗

[Direct opto-electronic analysis of the interaction of head and eye movements].

To study interactions of head and eye during various motor tasks in a clinical environment, a recording system is needed which should be characterized by high precision and reliability. A computer-assisted optoelectronic method based on the SELSPOT system is described. All the equipment was specially designed for neuro-ophthalmologic purposes and fulfills the requirements. A range of programs was developed using several types of signal processing algorithms, allowing simultaneous one-dimensional and two-dimensional representation of motor acts of the head and eye, including separate analysis of slow and rapid movements. Thus, the method is suitable for analyzing physiologic and pathologic mechanisms of complex interactions. The quality of this novel SELSPOT application is demonstrated by recordings made during induced circular movements.

Algorithms↗

Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans.

Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta-adrenergic mechanism as regulator of pancreatic secretion.

Adult↗

Inducible and constitutive expression of pMOL28-encoded nickel resistance in Alcaligenes eutrophus N9A.

The nickel and cobalt resistance plasmid pMOL28 was transferred by conjugation from its natural host Alcaligenes eutrophus CH34 to the susceptible A. eutrophus N9A. Strain N9A and its pMOL28-containing transconjugant M220 were studied in detail. At a concentration of 3.0 mM NiCl2, the wild-type N9A did not grow, while M220 started to grow at its maximum exponential growth rate after a lag of 12 to 24 h. When grown in the presence of subinhibitory concentrations (0.5 mM) of nickel salt, M220 grew actively at 3 mM NiCl2 without a lag, indicating that nickel resistance is an inducible property. Expression of nickel resistance required active growth in the presence of nickel salts at a concentration higher than 0.05 mM. Two mutants of M220 were isolated which expressed nickel resistance constitutively. When the plasmids, pMOL28.1 and pMOL28.2, carried by the mutants were transferred to strains H16 and CH34, the transconjugants expressed constitutive nickel resistance. This indicates that the mutation is plasmid located. Both mutants expressed constitutive resistance to nickel and cobalt. Physiological studies revealed the following differences between strain N9A and its pMOL28.1-harboring mutant derivatives. (i) The uptake of 63NiCl2 occurred more rapidly in the susceptible strain and reached a 30- to 60-fold-higher amount that in the pMOL28.1-harboring mutant; (ii) in intact cells of the susceptible strain N9A, the cytoplasmic hydrogenase was inhibited by 1 to 5 nM NiCl2, whereas 10 mM Ni2+ was needed to inhibit the hydrogenase of mutant cells; (iii) the minimal concentration of nickel chloride for the derepressed synthesis of cytoplasmic hydrogenase was lower in strain N9A (1 to 3 microM) than in the constitutive mutant (8 to 10 microM).

Alcaligenes↗

Sample-hold technique for analysis of respiratory gas composition at high breathing frequencies.

A gas sampling device is described for continuous monitoring of respiratory gas composition that is applicable to experimental conditions when the breathing frequency is very high (greater than 2 Hz) and the response time of conventional gas analyzers becomes a critical limiting factor. The system utilizes the principle of discontinuous gas collection at any selected point of the respiratory cycle facilitated by ultraspeed piezoelectric valves and includes provision for sample-hold characteristics. Two distinct modes of operation are supported. In phase-locked mode gas sampling is synchronous with breathing frequency. In scanning mode gas collection is asynchronous with breathing frequency. Phase-locked mode may be used for continuous monitoring of end-tidal gas concentrations, whereas scanning mode is intended for assessing the gas concentration profile throughout the respiratory cycle. The system may be applied to steady breathing encountered in mechanical ventilation at high frequency or during quasi-steady breathing observed in panting animals. Combined with a respiratory mass spectrometer, the system has been used for measurement of gas concentrations in alveolar gas mixtures at breathing frequencies ranging from 3 to 30 Hz that were otherwise not amenable to rapid measuring techniques.

Animals↗

Hereditary dysfibrinogenaemia: structural and functional studies on three fibrinogen variants.

Dysfunctional fibrinogens occurring in three unrelated families were studied. Fibrinogen Erfurt I consists of B beta chains with a slightly lower molecular mass than normal. The same structural abnormality was also detected in fibrin beta chains. The variant is present in platelets too. Fibrinogen Erfurt II is characterized by the absent thrombin-induced release of FPA. With fibrinogen Berlin cleavage of the B beta chains by thrombin is slow but complete. All carriers of the three abnormal fibrinogens seem to be heterozygous for the underlying mutant gene.

Adult↗

A platelet disorder due to a structural abnormality of membrane glycoprotein Ib.

In a patient with mild bleeding symptoms, decreased platelet spreading and defective aggregation, an abnormal membrane glycoprotein (GP) was detected. Staining and surface labelling characteristics, cleavage by calcium-activated protease and decreased content of normal GP Ib in the platelets of the patient and 3 related carriers of the abnormal glycopeptide suggest that the additional component is a genetic GP Ib variant structurally characterized by an increase of about 20,000 in apparent Mr of the large subunit GP Ib alpha. The observed hereditary membrane GP abnormality although present in heterozygous state may be causally related to the defect of platelet function.

Adult↗

[The frequency of hepatocellular carcinoma in autopsy material].

The frequency of liver cell carcinomas (n = 249) in autopsies of adults (n = 36,074) from 1960 to 1981 was 0.69%; in males (n = 19,124) 1% (n = 192) and in females (n = 17,950) 0.34% (n = 57). The development of liver cell carcinoma was associated with cirrhosis of the liver in 87% of the cases (89% in males and 70% in females). The relative frequency of liver cell carcinoma in autopsies is increasing: 1960 to 1966 0.5%, 1967 to 1973 0.89%, 1974 to 1981 1.4%. This increase is mainly the result of the development of carcinoma after cirrhosis in males: 1960 to 1966 0.49%, 1967 to 1973 0.86% and 1974 to 1981 1.2%. Cirrhosis of the liver from 1974 to 1981 showed a continuous increase in the relative frequency and an age-shift towards younger age groups in males. Throughout the study period a history of alcohol abuse was frequently given in the patients history.

Adolescent↗

Endogenous calcium-activated neutral protease in human platelets. Identification of a Mr 70,000 substrate.

Endogenous calcium-activated neutral protease (CAP, calpain), the major proteolytic activity in human platelets, cleaves a number of proteins. Preferential substrates are actin-binding protein, P 235, and a Mr 83,000 component. A fourth substrate completely degraded by CAP in platelet lysate within seconds is a Mr 70,000 protein. This polypeptide has been shown to influence the electrophoretic behaviour of membrane glycoprotein Ib during isoelectric focusing probably by forming a complex. This in vitro effect suggests that cleavage of the Mr 70,000 protein by CAP might modulate glycoprotein Ib receptor function. Proteolysis of known substrates by CAP during thrombin-induced platelet aggregation could not be detected.

Blood Platelets↗