GABA A receptors (GABA A Rs) are the principal inhibitory neurotransmitter receptors in the central nervous system. They control neuronal excitability by synaptic and tonic forms of inhibition mostly mediated by different receptor subtypes located in specific cell membrane subdomains. A consensus suggests that α1-3βγ comprise synaptic GABA A Rs, whilst extrasynaptic α4βδ, α5βγ and αβ isoforms largely underlie tonic inhibition. Although some structural features that enable the spatial segregation of receptors are known, the mobility of key synaptic and extrasynaptic GABA A Rs are less understood, and yet this is a key determinant of the efficacy of GABA inhibition. To address this aspect, we have incorporated functionally silent α-bungarotoxin binding sites (BBS) into prominent hippocampal GABA A R subunits which meidate synaptic and tonic inhibition. Using single particle tracking with quantum dots we demonstrate that GABA A Rs that are traditionally considered to mediate synaptic or tonic inhibition are all able to access inhibitory synapses. These isoforms have variable diffusion rates and are differentially retained upon entering the synaptic membrane subdomain. Interestingly, α2 and α4 subunits reside longer at synapses compared to α5 and δ subunits. Furthermore, a high proportion of extrasynaptic δ-containing receptors exhibited slower diffusion compared to δ subunits at synapses. A chimera formed from δ-subunits, with the intracellular domain of γ2L, reversed this behaviour. In addition, we observed that receptor activation affected the diffusion of extrasynaptic, but not of synaptic GABA A Rs. Overall, we conclude that the differential mobility profiles of key synaptic and extrasynaptic GABA A Rs are determined by receptor subunit composition and intracellular structural motifs. Words -248Highlights 1. GABA A Rs mediating synaptic or tonic inhibition all access inhibitory synapses 2. Diffusion and retention of GABA A Rs at synapses depends on the subunit composition 3. Dwell times for α2 and α4 are longer than for α5 and δ at inhibitory synapses 4. A large proportion of extrasynaptic δ-GABA A Rs exhibit restricted diffusion 5. The large intracellular loops of δ and γ2L regulate mobility and synaptic trapping
The results of treatment of 100 patients with bleeding peptic ulcer, using the conservative surgical approach of vagotomy and pyloroplasty with suture of the ulcer, have been analysed. This approach is satisfactory for patients with doudenal ulcer and in selected cases of gastric ulcer. It is not satisfactory in the treatment of erosive gastritis.
man, aged 52, a musician, was referred to me, Jan. 21, 1925, complaining of a painful left shoulder with Fig. 1.-Appearance and size of deposit before treatment (January 19).Fig. 2.-Nearly complete absorption after course of treatment by diathermy (April 6).inability to raise his left arm from his side. He stated that this condition had been present seven years with intermittent attacks of inability to raise the arm. The roentgenograms verified the diagnosis of calcified subdeltoid bursitis (Jan-uary 19). He received his first treatment, January 21, and at the end of two weeks' treatment he was able to resume his occupation, that of a musician, playing a bass viol in a symphony orchestra. Some pain, however, persisted, and it was necessary in all to give him thirty-two treatments, at the end of which time all the symptoms, namely, pain and restricted motion, had disappeared. Roentgenograms were again taken, April 6, and showed an absorption of the greater part of the deposit. These pictures, forming the case record, show the diagnosis and the result of the treatment by diathermy.The accompanying illustrations show conclusively that diathermy is a curative measure and not a palliative one. A long series of cases treated over a period of years has shown a complete restoration of function and an absence of pain.It is therefore fair to assume that in each case the greater part of the deposit has been absorbed by this form of treatment. If not completely absorbed, it has been reduced to such a size that it does not interfere with the function of the shoulder. Up to this time I have not seen a recurrence. I do not hesitate to say that this is the treatment par excellence for this condition.The delivery beds in common use in this country have one or more of the following distinct shortcomings:1. The legs of the patient in labor must be held by attendants. This is a drain on the nursing force, which is none too New delivery bed. ample in any hospital, and seriously cripples the nursing service at night. Moreover, nurses who act as human leg holders are unable to watch the process of labor and thus miss at least one important part of their training. If the second and third stages are at all prolonged, the actual physical effort is not inconsiderable.2. Mechanical leg holders, on the other hand, are by no means satisfactory. Of the various types in use, the straight leg holder, in which the foot of the patient is secured in a vertical elevation, imposes a noticeable strain on the sacroiliac ligaments, leaves the patient with backache for some days after delivery, and may be the cause of protracted sacro-iliac disease. Another type of leg holder provides support only for the knees and leaves the lower limbs and feet hanging free. This almost regularly leads to unpleasant paresthesias ; "the feet fall asleep."In either type of leg holder the legs are elevated and thereby the perineum is put on a stretch which, when superimposed on the pressure exerted by the advancing head, may be conducive to deeper lacerations.3. Whether t...
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