Billroth in Zurich.

Billroth came to the Kantonspital in Zurich as a disciple of v. Langenbeck. He changed that hospital from a largely privately controlled and state-dominated chronic disease hospital to an active teaching center with full-time personnel, a residency system, and its own equipment. He instituted a system of follow-up surgical statistics and criteria for certain surgical procedures. His technical ability and scholarship in pathology, anatomy, and surgical techniques made that institution a sought-after school. The marked swings in moods that were to characterize Billroth's entire career started in Zurich and had their source in his musical, professional, and personal interrelationships. Most important, this apprenticeship in surgery and administration made it possible for him, after 7 years, to be accepted to the Professorship at the University of Vienna, at that time the outstanding surgical school on the continent.     

Pulmonary arterial hypertension: the key role of echocardiography

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.     

Differential cannabinoid-induced electrophysiological effects in rat ventral tegmentum

Cannabinoids are known to exert mainly excitatory effects on dopaminergic cells of the ventral tegmental area (VTA). We have utilized an in vivo multiple-single unit electrophysiological approach to assess different neuronal contributions that may ultimately lead to excitation in this area. Baseline neuron recordings, using low impedance microwires, showed a variety of waveforms with a wide range of durations (0.8-3.2 ms). In the first experiment systemic injection of the potent cannabinoid agonist HU210 (100 microg/kg, i.p.) led predominantly to an increase in firing rate (approximately 214%, compared to pre-drug) in slowly firing cells with broad action potentials, possibly driven by a majority of presumed dopaminergic neurons (n = 31). However, the firing rate of some units was either unaffected (<25%, n = 9) or even decreased (approximately 67%, n = 9) following cannabinoid injection concomitantly with excitation. Apomorphine (75 microg/kg, i.p.) injected following HU210 produced a marked inhibition of both responses (approximately 76%) in 39 out of 49 cells. The second group of animals was treated with the CB(1) receptor antagonist SR141716A (1 mg/kg, i.p.), which had no effect when injected alone but prevented all HU210-evoked changes in firing rate suggesting that cannabinoid receptors mediated the observed responses (n = 39). Taken together, the present results suggest that the observed actions of cannabinoids may involve complex neurotransmitter interactions leading to differential effects on dopamine release. These heterogeneous neuronal responses are likely to underly the behavioural discrepancies reported in animal models of cannabinoid reinforcement.     

Effects of D3.49A,R3.50A,and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor

In several G protein-coupled receptors (GPCRs), the Asp-Arg-Tyr (DRY) motif at the bottom of third transmembrane domain and the amino acid at position 6.34 in the sixth transmembrane domain have been shown to play important roles in signal transduction. In this study, we propose that in the cannabinoid-2 (CB2) receptor, R3.50 in the DRY motif may be crucial for interacting with G proteins, and D3.49 and A6.34 may be important for constraining the receptor in an inactive conformation. To test our hypothesis, R3.50A, D3.49A, and A6.34E mutations of the human CB2 receptor were made by site-directed mutagenesis. These mutant receptors were stably transfected into human embryonic 293 cells, and their ligand binding and signal transduction properties were analyzed. Similar to other GPCRs, R3.50 of the CB2 receptor is crucial for signal transduction. Unlike other GPCRs, D3.49 and A6.34 of the CB2 receptor do not seem to be important for keeping the receptor in an inactive state. Furthermore, D3.49A and A6.34E mutations abolished ligand binding, and all three mutations abolished constitutive activity of the wild-type CB2 receptor.     

Generalized ℋ︁2 model approximation for differential linear repetitive processes

This paper investigates the generalized ??₂ model approximation for differential linear repetitive processes (LRPs). For a given LRP, which is assumed to be stable along the pass, we are aimed at constructing a reduced‐order model of the LRP such that the generalized ??₂ gain of the approximation error LRP between the original LRP and the reduced‐order one is less than a prescribed scalar. A sufficient condition to characterize the bound of the generalized ??₂ gain of the approximation error LRP is presented in terms of linear matrix inequalities (LMIs). Two different approaches are proposed to solve the considered generalized ??₂ model approximation problem. One is the convex linearization approach, which casts the model approximation into a convex optimization problem, while the other is the projection approach, which casts the model approximation into a sequential minimization problem subject to LMI constraints by employing the cone complementary linearization algorithm. A numerical example is provided to demonstrate the proposed theories. Copyright © 2010 John Wiley & Sons, Ltd.     

人树突状细胞与K562细胞的融合以及体外诱导p210蛋白特异性CTL的研究

目的：探讨人外周血单细胞来源的树突状细胞（Ｄdndritic cells,ＤＣ）与人白血病细胞 Ｋ５６２融合后，能否诱导同p２１０蛋白特异性的ＣＴＬ，为ＤＣ疫苗的临床应用提供理 论基础。方法：外周血来源的巾附单核细胞，在人ＧＭ－ＣＳＦ（１０００Ｕ/ml）作用下，培养５～７天后，与人白血病细胞Ｋ５６２进行融合，融合细胞再与自体的淋巴细胞共同孵育１０～１４天，采用乳酸脱氢酶释放试验分析其对p２１０蛋白阳性细胞的杀伤效果。     

ℋ︁∞ control of discrete‐time Markov jump systems with bounded transition probabilities

This paper deals with the class of discrete‐time linear systems with random abrupt changes and unknown transition probabilities but varying between known bounds for each mode. The ℋ︁_∞ control problem of this class of systems is revisited and new sufficient conditions are developed in the linear matrix inequality (LMI) setting to design the state‐feedback controller that stochastically stabilizes the system under consideration and at the same time guarantees the disturbance rejection with a desired level γ . Sufficient conditions for existence of the state‐feedback controller are developed. It is shown that the addressed problem can be solved if the corresponding developed LMIs are feasible. Numerical examples are employed to show the usefulness of the proposed results. Copyright © 2008 John Wiley & Sons, Ltd.