Medullary locomotor strip and column in the cat

Responses of lateral medullary neurons to microstimulation of two points in the locomotor strip—rostral and caudal to the obex—were recorded intracellularly in mesencephalic decerebellated uncurarized cats. Excitatory and inhibitory postsynaptic potentials and orthodromic action potentials occurred up to 20 ms after a single stimulus. A number of cells responded to stimulation of a locomotor point by a repetitive discharge, and in some cells synaptic responses were evoked by contralateral stimulation. The responsive neurons were scattered among other cells in the lateral medullary tegmentum. At least one-third of neurons with synaptic responses to stimulation of the rostral locomotor point were antidromically invaded from the caudal one. The characteristic length of these descending axons was between 4 and 9 mm, although there were longer axons too.The lateral medullary cells which give synaptic responses to stimulation of the locomotor strip form the locomotor column located medial to the strip, and a portion of these cells send their axons to the strip. It is suggested that the activity is propagated polysynaptically along the column through axonal collaterals of its neurons. One can assume that when repetitive stimulation achieves a threshold for locomotion such a propagation occurs without decrement. As a result, spinal stepping generators are activated.     

Characterization of idiotopes on MOPC 315 IgA using monoclonal antiidiotypic antibodies

The isologous antiidiotypic response in BALB/c mice to immunization with the DNP-binding IgA myeloma protein, MOPC 315, alters the expression of the anti-DNP antibody repertoire and confers immunity against MOPC 315 myeloma tumors. In order to characterize the idiotopes on MOPC 315 IgA which elicit this response we have isolated four monoclonal antiidiotypic antibodies (AIA), D10 (IgG_2a), A2(IgG₁), G3 (IgG_2b) and F1 (IgG_2a), produced by splenocytes of BALB/c mice immunized with MOPC 315 IgA in three independent fusion experiments. These AIA react with MOPC 315 IgA. reassociated H³¹⁵ L³¹⁵ and F³¹⁵_V but not with free H³¹⁵, L³¹⁵, V³¹⁵_H or V³¹⁵₂. In addition the AIA do not react with the closely related DNP-binding IgA myeloma protein, MOPC 460, suggesting that they are directed against private idiotopes on MOPC 315 IgA. These idiotopes can be divided into two groups. Group I, defined by D10, A2 and G3 consists of two overlapping idiotopes, one of which is related to the hapten-binding site. The two idiotopes are formed by an interaction of amino acids in H³¹⁵ and L³¹⁵. Group II defined by F1 consists of one idiotope which is related to the hapten-binding site. This idiotope is comprised of an aminoacid sequence on H³¹⁵ which requires an interaction with either L³¹⁵ or L⁴⁶⁰ for expression. A2 and G3 react identically with the same idiotope but were derived from two independent fusion experiments. This indicates an identity of AIA clonotypes among individual mice and suggests that the isologous AIA response to MOPC 315 IgA is restricted.     

β Chain deficiency in three patients with dysfunctional C8 molecules

Structural and functional studies were performed on a dysfunctional C8 molecule present in the serum of two siblings and an unrelated individual. The C8 in these three sera exhibited a pattern of partial immunologic identity with C8 in normal serum but was devoid of functional activity. The C8 was immunoprecipitated from the three sera and from a control serum with an antihuman C8 antiserum and analyzed by SDS-PAGE using highly purified human C8 as a reference. A selective absence of a band of 62,000 mol. wt was observed in the immunoprecipitates from the sera containing dysfunctional C8. Experiments performed with the purified α-γ and γ subunits showed that the hemolytic activity of the C8 deficient sera could be reconstituted by the addition of the β chain but not the α-γ dimer. Binding of the dysfunctional C8 to C$\text{567}$ was excluded by the following observations: (1) EAC 1–7 treated with the C8 deficient sera and then washed could not be lysed after the addition of the β subunit and C9; and (2) the abnormal molecules did not interfere with the consumption of normal C8 by the soluble complex SC5b-7.     

丹参-赤芍配伍的化学成分动态变化研究

选择丹参、赤芍药对为研究对象，以HPLC等色谱为研究工具，研究了不同比例配伍的丹参-赤芍共煎液与单煎混合液化学成分的异同，重点关注因两味药共煎煮而产生的化学成分动态变化现象，并运用现代科技手段分离和鉴定了变化明显的化学成分，总结了化学成分动态变化与药材配伍不同比例之间的关系。     

明阴阳，重脾胃，法从三步辨证

[目的]简要总结笔者行医50余年来的一些临证体会,为后学者从事中医临床医疗活动提供一些参考。[方法]通过反复复习经典、整理既往的门诊资料、同行交流等方式,对笔者的临床诊疗进行系统的回顾与反思,总结凝练出笔者的基本中医学术观点并成文。[结果]笔者的中医学术观点可简要概括为五部分,即:阴阳为本、气血为纲;土灌四旁,五脏共调;脾胃分治,燥湿相济;治诸阴邪,化气为先;抓住主症、三步辨证。临床辨治以阴阳为纲,重视气血的重要作用。在治疗脾胃病时,从脾胃与五脏的关系入手,由脾胃而治五脏,治五脏以调脾胃。强调脾胃分治,治脾重在升清燥湿,治胃重在降浊清润。痰湿水饮诸阴邪皆由气化不利而生,治当以化气为先。提出了抓住主症、综合兼症,提炼病机、确定证型,制定治则、选方用药为主线的辨证三步法。[结论]笔者的基本中医学术观点为,明阴阳,重脾胃,法从三步辨证。     

Gentamicin and leucine inhalable powder: What about antipseudomonal activity and permeation through cystic fibrosis mucus?

The aim of this study was to evaluate the permeation properties of gentamicin (G) in a novel dry powder form for inhalation through an artificial mucus model. Moreover, since respiratory infections sustained by Pseudomonas are a major cause of sickness and death in CF patients, the susceptibility of P. aeruginosa to engineered G powders was investigated.     

The modulation by xanthines of the DNA-damaging effect of polycyclic aromatic agents. Part II. The stacking complexes of caffeine with doxorubicin and mitoxantrone

Recently accumulated statistical data indicate the protective effect of caffeine consumption against several types of cancer diseases. There are also reports about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations of this phenomenon is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. In the accompanying paper [Kapuscinski et al., this issue] we provide evidence (flow cytometry and the cell cycle analysis) that the cytostatic effects of caffeine (CAF) on two DNA alkylating agents, which do not require the biological activation, depend on their ability to form stacking (pi-pi) complexes. In this study, we use physicochemical techniques (computer aided light absorption and microcalorimetry), and molecular modeling to examine previously published qualitative data. This is published both by our and other group's data, indicates that CAF is able to modify the cytotoxic and/or cytostatic action of the two well known antitumor drugs doxorubicin (DOX) and mitoxantrone (MIT). To obtain the quantitative results from the experimental data we used the statistical-thermodynamical model of mixed aggregation, to find the association constants K(AC) of the CAF-drug interaction (128+/-10 and 356+/-21M(-1) for DOX-CAF and MIT-CAF complex formation, respectively). In addition, the favorable enthalpy change of CAF-MIT (DeltaH=-11.3kcal/mol) was measured by microcalorimetry titration. The molecular modeling (semi-empirical and force field method) allowed us to obtain the geometry of these complexes, which indicated the favorable energy (DeltaE) of complex formation of the protonated drug's molecules in aqueous environment (-7.4 and -8.7kcal/mol for DOX-CAF.5H(2)O and MIT-CAF.8H(2)O complex, respectively). The molecular modeling calculation indicates the existence of CAF-drug complexes in which the MIT molecules are intercalated between two CAF molecules (DeltaE=-29.9kcal/mol). These results indicate that the attenuating effect of caffeine on cytotoxic or mutagenic effects of some polycyclic aromatic mutagens cannot be the result of metabolic activation in the cells, but simply is the physicochemical process of the sequestering of aromatic molecules (e.g. carcinogens or mutagens) by formation of the stacking complexes. The caffeine may then act as the "interceptor" of potential carcinogens (especially in the upper part of digesting track) where its concentration can reach the mM level). There is, however, no indication, both, in the literature or from our experiments, that the xanthines can reverse the damage to nucleic acids at the point when the damage to DNA has already occurred.     

Immunochemical and biochemical analyses of myosin light chains from normal and denervated cardiac muscle

Rabbit antisera were prepared against the combined low molecular weight subunits (the light chains) of canine cardiac myosin. The antisera reacted specifically with the light chains and with purified myosin. There were no immunochemical reactions with the heavy myosin chains. The antisera were then used to test preparations of light chains isolated from hearts maintained in a denervated condition for 12, 4, or 2 weeks prior to killing the animals. Denervation was accomplished by mediastinal neural ablation. The light chains prepared from the denervated hearts all reacted with the antisera and showed immunological identity with the light chains from control muscle. The specific adenosine triphosphatase activity of myosin prepared from hearts denervated for 12, 4, or 2 weeks exhibited a marked deviation from control activity. We concluded that, although cardiac denervation did not affect the immunological properties of myosin light chains, the biological activity of cardiac myosin was greatly reduced after 2 weeks of denervation and recovered somewhat after 4 weeks.