Home, training and work: mobility of British doctors

This study examines the locations of family homes, medical schools and places of specialist training, and work of doctors qualifying from UK medical schools in 5 calendar years between 1974 and 1993. The contribution of each UK region to the medical workforce relative to its population is assessed and trends over time are examined. The relationship between place of family home and medical school attended is examined for 14,108 doctors. Career appointment location and its relationship to medical school and family home loc‐ation are examined for over 4000 doctors. For the qualifiers of 1983, an additional analysis incorporating place of training is included. Large differences were found in the percentage of medical students from local family homes attending each regional medical school. In some cases differences reflected local populations but other cases had no obvious cause. Over all cohorts studied, 38% of respondents attended a medical school in the region of their family home (32% of 1993 qualifiers), 42% held a career post in the same region as their medical school, and 38% held a career post in the same region as their family home. Among the qualifiers of 1983, 65% had a career post in the same region as their postgraduate training, 34% also attended medical school in the same region, and 19% also came from family homes in the same region. More women than men took up a career post in the same region as their postgraduate training. The relationships to family home and medical school did not differ by gender. Consultants appeared slightly less likely than GPs to have stayed within a region, but this difference was not statistically significant.     

Differences in a K current in schwann cells from normal and neurofibromatosis-infected damselfish

Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K⁺ current (K current), with a strong dependence on the Nernst potential for K⁺. This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (K_d ? 1 mM) and by dendrotoxin (15 μM) but were insensitive to extracellular tetraethyammonium (≤ 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of ?40 mV, while in tumored cells this average was 12%, a significant difference. © 1994 Wiley-Liss, Inc.     

黄皮酰胺促钾通道开放

一种新发现的具有促智作用的药物——黄皮酰胺能抑制去甲肾上腺素(NE)或KCl引起的血管平滑肌收缩。本研究旨在应用膜片钳(patch clamp)技术探讨黄皮酰胺对Wistar大鼠尾动脉平滑肌细胞膜钾离子通道的作用。单个平滑肌细胞用酶法分离,以细胞封接方式记录离子通道活动。在细胞池内注入2μM黄皮酰胺后,钾离子通道活动明显增强。用本实验室开发的计算机软件(patch clamp analysis system,Version 1.0)计算分析通道活动的特征参数。     

How do patch clamp seals form? A lipid bleb model

Individual ion channels are electrically isolated and studied in living cells with the tight patch voltage clamp method. Channels are identified, categorized, and sometimes named on the basis of the biophysical properties obtained with this method. Although it is usually presumed that these recordings are from native, undisturbed membrane, the physical basis of this technique is not well established. Observations that lipid blebs readily form when suction is applied to patch clamp electrodes suggest that many single channel recordings are from ion channels in these blebs.     

Analysing ion channels with hidden Markov models

Ion channel current amplitudes () and open probabilities (P _o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of , P _o, and mean dwell times () of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K⁺ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The value of the intermediate-conductance K⁺ channel (i-K⁺) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P _o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K⁺ (s-K⁺) channels, which were found in the same membrane patches as the i-K⁺, an accurate analysis of P _o and was not possible with the SM. The value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P _o was 16.6±4.6%, the open value was 11.1±2.8 ms, and the closed value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P _o, and mean values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.     

Tonic inhibition of neuronal calcium channels by G proteins removed during whole-cell patch-clamp experiments

The barium current through voltage-dependent calcium channels was recorded from cultured rat cortical neurons with the whole-cell configuration of the patch-clamp technique. The maximal current evoked by depolarising pulses from –80 mV to 0 mV was divided into inactivating and non-inactivating fractions. During the first minutes of whole-cell recording, the amplitude of the inactivating fraction increased from less than 0.1 nA to an average value of 1 nA, whereas the amplitude of the non-inactivating component remained essentially the same. This increase in amplitude was prevented when the perforated-patch technique was used, suggesting that some intracellular factor that inhibited the barium current was lost or destroyed during conventional whole-cell experiments. When GTP[-S] or GTP was added to the pipette solution, no increase or only a weak rise of the inactivating current was seen, whereas GDP[-S] accelerated its increase. The results suggest that some of the calcium channels expressed in cultured cortical neurons are inhibited by a G protein even in the absence of added neurotransmitter. The current increase observed during whole-cell recordings may be due to a loss of intracellular GTP and the subsequent inactivation of an inhibitory G protein.     

家庭环境因素对青少年精神分裂症的影响

目的 探讨精神分裂症和家庭环境的关系。方法 用自编“家庭环境调查问卷”、修订的父母养育方式评价量表（ＥＭＢＵ）对８２例青少年患者和８２个正常青少年家庭进行调查,用Ｃａｍｂｅｒｗｅｌｌ家庭会谈表（ＣＦＩ）评定患者亲属的情感表达（ＥＥ）水平。结果 （１）病例组父母关系、亲子关系差,父母有不良行为习惯者多（Ｐ〈０．０５）;家庭性患者父母文化水平低、经济收入低、健康状况差（Ｐ〈０．０１）。（２）病例组父母     

Unitary delayed rectifier channels of rat hippocampal neurons: properties of block by external tetraethylammonium ions

Patch-clamp recording was used to characterise a delayed rectifier potassium channel and the effects of external tetraethylammonium (TEA) in neurons isolated from the CA1 region of cultured neonatal rat hippocampus. A preliminary kinetic analysis is presented. Very low concentrations of TEA included in the patch pipette solution had two effects on unitary currents: first unitary currents were reduced in amplitude, with an associated increase in open channel noise, and second channel mean open time was reduced. The reduction in unitary amplitude was consistent with a single TEA molecule blocking the channel with a voltage-independent K _d of 53.4 M. The blocking and unblocking rate constants, estimated using two independent methods, were approximately 350 mM^–1 ms^–1 and 20 ms^–1, both rate constants being independent of voltage. Channels blocked in this way appeared able to close normally without first having to become unblocked. The reduction in mean channel open time was probably due to a second, kinetically slower blocking reaction with a much lower K _d, probably between 300 and 800 M. The voltage-independent blocking rate constant of the slower block was at least 25 times slower than that of the faster block.     

Potassium-selective channels in the basolateral membrane of single proximal tubule cells of frog kidney

The membrane potential of proximal tubule cells is dominated by the potassium conductance of the basolateral membrane. In the present paper the nature of this conductance is investigated by the patch-clamp technique. Only one type of K channel was found in the basolateral membranes of freshly isolated proximal cells. In cell-attached patches, the current/voltage relationship is markedly non-linear with much larger inward (30 pS) than outward ( 6 pS) conductances, even in the presence of roughly symmetrical K concentrations. Thus the channels show inward rectification. The determination of the conductance for outward current flow is complicated since the current/voltage curves show an area of negative conductance. Nevertheless, taking the conductance for outward current flow and the density of the channels it is possible to account for all of the previously reported potassium conductance of amphibian proximal tubule cells. The open probability of the channels was found not to depend upon the membrane potential. However, the non-linearity of the current/voltage relationships will confer upon the channel the same voltage dependence as that seen in intact proximal tubules, i.e. the conductance decreases with depolarisation. Incubation of cells in Ringer with no substrates or in the presence of alanine and/or glucose showed no change in the activity of the channels. These findings suggest that, although these channels may represent the basolateral conductance of frog proximal tubule cells, they are not involved in the well-established coupling between transport rate and potassium conductance.This work was supported by the Wellcome Trust