G proteins (Gi,Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change

Summary We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.     

Characterization of an anti-idiotypic MoAb bearing an internal image of the receptor-binding epitope of cholera toxin.

A mouse anti-cholera toxin (CT) MoAb, mAb1, specific for the GM1-binding epitope of CT, was used to raise a syngenic anti-idiotypic MoAb, mAb2. Purified mAb2 was specific for mAb1 as shown by latex particle counting immunoassay and ELISA. Several experiments of competition between mAb2 and CT for binding to mAb1 demonstrated that mAb2 bore an internal image of the GM1-binding epitope of CT. Binding of mAb2 to GM1 unambiguously corroborated the mAb1-paratopic specificity of mAb2. Furthermore, mAb2 acted as a CT-surrogate antigen: rabbits injected with mAb2 produced some anti-CT antibodies, Ab3, which resembled mAb1 in specificity as expected. The potential use of this mAb2 as vaccine or as prophylactic agent to prevent CT from binding to its cellular receptor is discussed.     

Botulinum toxin injection in patients with hereditary spastic paraparesis

In an open label study, we analyzed the efficacy of botulinum toxin injection at the lower limbs of patients with hereditary spastic paraparesis (HSP). Fifteen patients who showed disabling spasticity with no or poor effect of oral treatment were recruited consecutively. Botulinum toxin was injected (400 U; Botox^®) into the spastic muscles identified by clinical examination (equinus, varus, and pathological hip adduction). Patients were regularly assessed from the first day to the fifth month: spasticity (Ashworth), motor strength, range of movements, Functional Ambulation Categories (FAC), gait parameter, Rivermead Motor Assessment, self-analysis of benefit and satisfaction. We observed a moderate and significant ( P  < 0.05) reduction of ankle plantar flexor and hip adductor spasticity, with a partial increase in the range of the active and passive motion at the ankle and in gait velocity. At an individual level, six of 15 patients showed an increase in gait velocity. The FAC and RMA did not change. Patients often reported partial improvement in foot position and lower limb propulsion, and fair satisfaction. In conclusion, botulinum toxin injection can be effective in HSP patients with relatively ancient spasticity. This technique can be introduced into the therapeutic panel, which also includes physiotherapy, oral treatment and baclofen pump.     

Difficult myotomy is not determined by preoperative therapy and does not impact outcome.

OBJECTIVES: The impact of preoperative endoscopic therapy on the difficulty of laparoscopic Heller myotomy and the impact of the difficulty of the myotomy on long-term outcome has not been determined. This study was undertaken to determine whether preoperative therapy impacts the difficulty of laparoscopic Heller myotomy and whether preoperative therapy or difficulty of myotomy impacts long-term outcomes. METHODS: Since 1992, 305 patients, 56% male, median age 49 years, underwent laparoscopic Heller myotomy and were prospectively followed. The difficulty of the laparoscopic Heller myotomy was scored by the operating surgeon for the most recent 170 consecutive patients on a scale of 1 (easiest) to 5 (most difficult). Patients scored their symptoms before and after myotomy using a Likert scale from 0 (never/not bothersome) to 10 (always/very bothersome). RESULTS: Before myotomy, 66% of patients underwent endoscopic therapy: 33% dilation, 11% Botox, and 22% both. Preoperative endoscopic therapy did not correlate with the difficulty of the myotomy (P=NS). Median follow-up was 25 months. Regardless of the difficulty of the myotomy, dysphagia improved with myotomy (P<0.0001). By regression analysis, the frequency and severity of post-myotomy dysphagia correlated with neither preoperative endoscopic therapy nor the difficulty of the myotomy. CONCLUSIONS: Laparoscopic Heller myotomy improves the frequency and severity of dysphagia. The difficulty of laparoscopic Heller myotomy is not impacted by preoperative therapy, and neither preoperative therapy nor difficulty of the myotomy impact long-term outcome.     

Asynchronous blepharospasm, facial and cervical dystonia, and bilateral asynchronous hemifacial spasm.

We present a patient with a facial movement disorder that has characteristics of both blepharospasm and bilateral asynchronous hemifacial spasm. Because of the increased incidence of blepharospasm in patients with hemifacial spasm, our patient's clinical presentation is probably not a chance occurrence, but rather a manifestation of some predisposition for these two movement disorders. This unusual constellation of signs and symptoms challenges the current diagnostic criteria and suggests that some of these facial movement disorders may lie on a spectrum, rather than represent distinct entities.     

Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia.

Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia. In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis. Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site. The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects. The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia. These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia. The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM.     

Botulinum toxin injection inhibits myogenic tone and sympathetic nerve function in the porcine internal anal sphincter

Objective Botulinum toxin is an effective treatment for anal fissure, though there is a lack of agreement over the optimal site for its injection. This reflects our current ignorance of its mechanism, and whether it has any action on the nerves of the internal anal sphincter (IAS). This study set out to resolve this issue through use of a pig model. Materials and methods Eight pigs were studied in pairs: one of each pair received a botulinum toxin injection into the anal sphincter, whilst the other acted as its control. Manometry was performed every two weeks under anaesthesia. Pigs were slaughtered at between four and six weeks after injection and the properties of the IAS compared in vitro. Results Whilst maximum anal resting pressure (MARP) increased slowly in control pigs during the experimental period, reflecting weight gain, a fall was observed in treated pigs. In vitro, IAS strips from control pigs generated 400 mg of spontaneous tone per gram of tissue (± 45; standard error), compared to 250 (± 25) mg/g tissue from treated pigs (P < 0.01). Electric Field Stimulation at 50Hz produced 150 (± 22) mg contraction/gram tissue in IAS strips from control pigs compared to 53 (± 13) mg/g tissue in treated pigs (P < 0.0005). This contractile response was blocked by guanethidine. Conclusion Botulinum toxin has a significant action on the IAS. It reduces myogenic tone and contractile responses of this tissue to sympathetic nerve stimulation. Further studies are required to clarify its mechanism of action more precisely.     

艰难梭茵毒素基因3''''末端重复区域基因片段的PCR克隆

目的探寻一种简单、快速、灵敏的检测艰难梭菌的方法.方法以艰难梭菌毒素A和毒素B基因3'末端高度保守重复区分别设计一对引物,进行PCR反应,同时在同一体系相同反应条件下使用相同引物分别以大肠杆菌和乳杆菌DNA为模板进行扩增,比较二者结果.结果从艰难梭菌成功克隆了毒素A基因3'端重复区域960 bp的基因片段及毒素B基因3'端重复区域1851 bp的基因片段,不同来源的菌株出现了相同的2条电泳带,并通过测序鉴定;而对照的大肠杆菌和乳杆菌株无特异电泳带出现.结论从艰难梭菌毒素A、毒素B基因3'末端重复区域克隆的基因片段具有保守性,可以作为基因探针在临床上进行艰难梭菌检测,该方法简便、灵敏,可直接用粪便标本进行检测.此外,这些基因编码的多肽具有较高的疏水性并存在着膜受体结合区域,可以此为基础进行基因工程蛋白质疫苗的研究.     

T2毒素在灌流大鼠肠肝中的首过效应和代谢动力学

建立并用大鼠在体肠-肝灌流标本研究了T2毒素在大鼠肠肝中的首过效应和代谢转化动力学,T2毒素在大鼠肠肝中的主要代谢产物是HT2,3′-OHHT2和其葡萄糖醛酸结合物,T2毒素具有显著的肠肝首过效应,当毒素(42μg·ml~(-1))由上肠系膜动脉恒速单次灌流(8 ml·min~(-1))肠-肝标本时,穗态肝、肠抽提率分别为0.978和0.454,总有效清除率为7.91 ml·min~(-1),T2毒素在循环灌流大鼠肠-肝标本中的消除半衰期为6.5min,主要代谢产物HT2,3′-OHHT2的生成半衰期分别为8.5和38.5 min,结果表明,T2毒素经消化道中毒后,在肠和肝的首过代谢下能很快地转化为产物,因此,毒素在体内的毒效作用主要由其代谢产物表现出来。     

Delivery of Antigens to the MHC Class I Pathway Using Bacterial Toxins

Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogenously expressed proteins presented on the cell surface in the context of major histocompatibility complex (MHC) class I molecules. Because CTL are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts. Generating CTL by immunization with exogenous proteins is often ineffective because these antigens typically enter the MHC class II pathway. This review focuses on the usefulness of bacterial toxins for delivering antigens to the MHC class I pathway. Several toxins naturally translocate into the cytosol, where they mediate their cytopathic effects, and the mechanisms by which this occurs has been elucidated. Molecular characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer toxic but retained the ability to translocate into the cytosol. Thus, these modified toxins could be examined for their ability to carry peptides or whole proteins into the cytosolic processing pathway. Of the toxins studied—diphtheria, pertussis, Pseudomonas, and anthrax—the anthrax toxin appears the most promising in its ability to deliver large protein antigens and its efficiency of translocation.