N-α-biotinylated-neuropeptide Y analogs: Syntheses, cardiovascular properties, and application to cardiac NPY receptor visualization

Two monobiotinylated analogs of neuropeptide Y (NPY) were synthesized by coupling the N-hydroxysuccinimidyl esters of biotin and (6-biotinylamido)-hexanoic acid, respectively, to the free alpha-NH2 group of the side chain protected NPY peptide resin. Crude peptides obtained by HF cleavage were purified by RPLC and their integrities were confirmed by amino acid and mass spectral analysis. As with NPY, both biotinylated analogs inhibited 125I-NPY binding and adenylate cyclase activity of rat cardiac ventricular membranes in a dose-dependent manner. N-alpha-[(6-biotinylamido)-hexanoyl]-NPY exhibited potencies comparable to that of NPY whereas N-alpha-biotinyl-NPY was slightly less potent. In the in vivo experiments, however, both the biotinylated analogs exhibited responses comparable to NPY in increasing arterial blood pressure and decreasing heart rate in anesthetized rats. The responses of the biotinyl analogs were longer lasting than those of NPY. Histochemical studies revealed that N-alpha-[(6-biotinylamido)-hexanoyl]-NPY could label the NPY receptors in rat cardiac ventricular tissues. This labeling was specific since intact NPY inhibited the staining. These studies show that biotinyl-NPY analogs exhibit biological potencies comparable to intact NPY and can therefore be used to further probe the NPY-receptor interaction.     

家兔脊髓蛛网膜下腔注射乙酰胆碱对血压和心率的影响

将乙酰胆碱(ACh)注入麻醉家兔脊髓蛛网膜下腔,观察其对心血管活动的影响。结果表明:(1)脊髓蛛网膜下腔注射50～100μg ACh可使血压下降,心率减慢;(2)预先由脊髓蛛网膜下腔注射阿托品,可阻断ACh引起的降压和降心率作用;(3)脊髓蛛网膜下腔注射六甲双铵、酚妥拉明或心得安均不能阻断上述ACh的心血管反应;(4)切断两侧颈部迷走神经,ACh不再使心率减慢,但其降低血压的作用不受到任何影响。 脊髓中ACh水平升高可通过激活胆碱能M-受体引起血压下降和心率减慢。ACh的这种降压作用既没有中枢肾上腺素能受体活动参与,也不是通过迷走神经实现的,可能是由于脊髓交感血管中枢紧张性降低所造成的。     

Comparative character of the deep-water and inshore cottoid fishes endemic to Lake Baikal

Lake Baikal's 29 endemic species of cottoid fishes form three groups: shallow-water species in depths to 350 m; eurybathic species from 50 to 1300 m; and abyssal species from 400 to 1600 m. These groups differ in their abilities to withstand high hydrostatic pressure. As in marine deep-water fishes, abyssal cottoids in Baikal have few or no cones in the retina, and some have tubular eyes. Their seismosensory systems predominate, based chiefly on free neuromasts. The proportion of species with canal systems decreases with depth. Diversity of the predominantly gammarid foods also decreases from 45 species in shallow water to five species in deep water, and the lateral line system plays the dominant role in food detection at all depths. Two abyssal cottoids have become secondary pelagic, achieving close to neutral buoyancy through high lipid levels and reduced skeletal mineralization. These forms take advantage of the abundant pelagic planktonic amphipod populations. The adaptations of abyssal forms parallel those seen in deep-water marine fishes.     

Increased Neural Cell Adhesion Molecule in the CSF of Patients with Mood Disorder

Abstract: Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system. Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble N-CAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder.     

Meteorological factors and the time of onset of chest pain in acute myocardial infarction

Analysis of the time of onset of chest pain in 2254 patients with a myocardial infarction admitted to a coronary care unit in Leicester during a 10-year period shows an association with temperature and humidity. During both the most cold and humid times of the year, the relationship is a strong one. A generalized linear model with a log link was used to fit the data and the backward elimination selection procedure suggested a humid, cold day might help to trigger the occurrence of myocardial infarction. In addition, cold weather was found to have a stronger effect on the male population while those men aged between 50 and 70 years were more sensitive to the effect of high humidity.     

心率与血压的变异性：分析方法,生理意义及其应用

本文回顾了关心回顾变异性及血压变异性的最新进展。在分析方法方面介绍了单一生理变量多变量系统的线性分析技术及其主要结果。对ＨＲＶ／ＢＰＶ谱的生理意义及其应用问题,也进行了回顾了评述。     

Thiol-induced oligomerization of α-lactalbumin at high pressure

Denaturation and aggregation of-lactalbumin at high pressure (up to 10 kbar, 1000 MPa) were studied by means of circular dichroism, gel-permeation chromatography, sodium dodecyl sulfate and gel electrophoresis. It was found that the unfolding of-lactalbumin at high pressure is reversible even in basic pH and at a protein concentration as large as 10%. In these conditions only a negligible fraction of the protein is denatured irreversibly and aggregates. The rate of aggregation of-lactalbumin at high pressure increases significantly in the presence of low-molecular reducing agents such as cysteine, 2-mercaptoethanol, and dithiothreitol. Maximal yield of-lactalbumin oligomerization (over 90%) was achieved in the presence of cysteine at the molar cysteine/protein ratioq=2 and atpH 8.5. Apparent molecular weight of the obtained oligomers was over 500 kDa. It was shown that the size distribution of oligomers can be modulated by varyingpH and reducing agent. The size distribution shifts in the direction of very large, poorly soluble particles whenpH decreases. Maximal content of the insoluble fraction (about 30%) can be reached at pH 5.5 when cysteine (q=2) is used as reducing agent. The oligomers of-lactalbumin are stabilized mainly by nonnative interchain disulfide bridges. Circular dichroism measurements point to an additional mechanism of cohesion of polypeptide chains in the oligomers, which is formation of intermolecular-sheets.     

Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms

Marked concentration differences of noradrenaline (NA) between the vascular and the interstitial compartment were detected by sampling interstitial transudate from isolated perfused rat hearts. The ratios of vascular/interstitial concentration amounted to 7.4 to 1.3 depending on the concentration of NA administered (3 × 10^–9 to 10^–6 M). These concentration differences were abolished by inhibitors of uptake₁ desipramine (DMI) I and uptake, (O-methyl-isoprenaline (OMI)). Neuronal uptake, was characterized by a K_m of 0.22 mol/l and a V_max of 370 pmol × min^–1 × gWWT^–1, extraneuronal uptake₂ by a K_UPTAKE of = 0.313 min^–4.The apparent permeability surface area (P×S)-product calculated from uptake rate and transcapillary concentration difference was significantly decreased by administrating 100 mol/l (NA) in presence of DMI. A presumed endothelial uptake mechanism contributing to catecholamine translocation was investigated in endothelial cells in culture. These cells showed a specific noradrenaline uptake with a K_m of 4.35 mol/l and a V_max of about 75 pmol × min^–1 x gWWT^–1. Any inhibiton by inhibitors of both of the two noradrenaline uptakes was lacking. The uptake rate of this mechanism is insufficient to contribute to the diffusive conductivity of the capillary wall (P × S-product). We conclude from our investigations on interstitial concentrations of catecholamines and transcapillary concentration differences, that the capillary wall, owing to its metabolic and diffusional characteristics, influences the exchange of catecholamines to a substantial and physiologically relevant extent.     

Complete mechanical impedance increases the turgor of cells in the apex of pea roots

In this paper we describe an experimental approach which allows turgor (p) in an impeded root to be measured without the need to remove the root from the impeding environment. The maximum axial growth pressure (σ_max) generated by completely impeded pea (Pisum sativum L.) roots was measured using a novel apparatus incorporating a force transducer. The apparatus was designed so that it was possible to gain access to the impeded root with the microcapillary of a pressure probe and so obtain in situ measurements of P. Turgor in cells in the apical region of impeded roots was 0.78 MPa, compared with 0.55 MPa in unimpeded roots. In impeded roots, σ_max was 0.52 MPa, showing that the pressure component resulting from cell wall tension (W, where W=P–σ) decreased from 0.55 to 0.26 MPa as the roots became impeded. When impeded roots were removed from the apparatus, there was no decrease in P over the following 90 min. Impedance did not cause P to change in the non-elongating part of the roots further from the apex.     

Callus formation from protoplasts of Artemisia sphaerocephala Krasch and some factors influencing protoplast division

Round wormwood (Artemisia sphaerocephala Krasch) seeds were germinated on Murashige & Skoog (1962) medium without plant growth regulators. The hypocotyls of seedlings were sliced and cultured on M1 medium with 2,4-dichlorophenoxyacetic acid (9.05 M) to induce callus. The induced calluses were subcultured on the same medium. Ten day old calluses were used to isolate protoplasts in an enzyme solution with 0.65 M mannitol. Protoplast yield strongly depended upon the state of callus cultures. Certain amount of hemicellulase could improve protoplast isolation. Purified protoplasts were cultured in modified Kao & Michayluk (1975) medium with 0.60 M mannitol as osmoticum, suggesting that protoplasts of A. sphaerocephala need a high initial osmolarity. Protoplasts generally divided evenly and the percentage of first division could reach 10%. Kinetin exhibited a positive effect on initial cell division. Furthermore, we studied the effect of protoplast density and vitamin C on sustained growth of protoplasts. After forty days, 1 mm calluses in diameter formed.Abbreviations CH casein hydrolysate - 2,4-D 2,4-dichlorophenoxyacetic acid - KM8P Kao & Michayluk (1975) protoplast medium - MS Murashige & Skoog (1962) medium - MES-2 (N-morpholino)ethanesulfonic acid