乙型肝炎病毒基本核心启动子T1762A1764 联合突变的临床意义

目的:研究乙型肝炎患者乙型肝炎病毒(HBV)基本核心启动子(BCP)T^1762A^1764联合突变情况及其临床意义。方法:采用聚合酶链反应(PCR)与限制性长度片段多态性分析(RFLP)相结合，检测130例乙型肝炎患者BCP区核苷酸(nt)1762碱基A→T和1764碱基G→A联合突变。结果：HBeAg( )和HBeAb( )两组患者中BCP T^1762A^1764联合突变率的不同频率分别为慢性乙型肝炎患者(Chronic hepatitis B，CHB)40．0％和85．7％，无症状携带者(Asymptomatic carrier，ASC)22．2％和65．0％，献血员为5％。BCP T^1762A^1764双点联合突变组HBV-DNA≥10^5 cps／ml检出例数81例(96．4％)，非突变组HBV-DNA≥10^5 cps／ml检出例数25例(54．3％)。结论：BCP T^1762A^1764联合突变与乙型肝炎的发生、发展以及预后有关，可能是CHB与ASC患者HBeAg(-)的原因之一，可促进乙肝病毒繁殖。对慢性乙型肝炎患者检测HBV BCP T^1762A^1764联合突变有一定的临床意义。     

Skeletal muscle involvement in Escobar syndrome

In addition to the clinical characteristics of Escobar syndrome, including an anomalous facial expression, multiple joint contractures, multiple pterygia and a short stature, two female siblings developed proximal dominant muscle weakness from birth and slowly progressive scoliosis. Biopsied specimens obtained from the paravertebral and gluteus maximums muscles at the time of spinal surgery showed variation in fiber size, increased numbers of fibers with central nuclei, interstitial fibrosis and disorganized intermyofibrillar networks with occasional core/targetoid formations. The most outstanding histochemical abnormality in both cases was an abnormal fiber type distribution (type 2 fiber deficiency) which might be the result of an abnormal or deficient neural supply to the developing muscles. The defective neural influence on the muscle is assumed to produce the above-mentioned muscle changes, inducing multiple joint contractures and scoliosis.     

大白鼠大中缝核至脊髓的体部定位投射——HRP逆行法

将HRP或WGA-HRP溶液分别注入18只大白鼠的预、腰一侧灰质或颈、腰一侧背角,观察大白鼠大中缝核(NRM)到脊髓的体部定位投射。本实验发现NRM尾侧部投射到脊髓背角以腹的部位,背角接受NRM头侧部的投射。NRM至背角投射有明确的体部定位关系,投射到颈髓的细胞偏头侧分布,投射至腰髓者偏尾侧,二者之间有较大范围的重叠。本实验不支持NRM至脊髓投射有裂隙定位方式的结论。本文并就NRM脊髓投射及其体部定位的功能意义作了讨论。     

Iontophoresis of amphetamine in the neostriatum and nucleus accumbens of awake, unrestrained rats

When administered systemically to ambulant animals, amphetamine (AMPH) has both excitatory and inhibitory effects on single-unit activity in the neostriatum and nucleus accumbens. To determine the extent to which these results reflect a direct action of the drug, AMPH was applied iontophoretically to neostriatal and accumbal neurons under naturally occurring behavioral conditions. AMPH dose-dependently (5–40 nA) inhibited the vast majority of spontaneously active units. The inhibition, which was evident at low ejection currents (5–10 nA), had relatively short onset (4–12 s) and offset (6–24 s) latencies, and was positively correlated with basal firing rate. Even stronger dose-dependent inhibitory responses were recorded when neurons having no or a very low rate of spontaneous activity were tonically activated by continuous, low-current applications of glutamate (Glu). Systemic injection of either SCH-23390 (0.1 mg/kg) or haloperidol (0.2 mg/kg), relatively selective D₁ and D₂ receptor antagonists, respectively, blocked the AMPH-induced inhibition. Prolonged AMPH iontophoresis (2–3 min; 5–30 nA) inhibited both spontaneous impulse activity and Glu-induced excitations, resulting in a complete blockade of the Glu response at relatively high AMPH ejection currents (≥20 nA). Taken together, these results suggest that although dopamine is largely responsible for the inhibitory effects of iontophoretic AMPH, dopamine alone cannot account for the complex response of neostriatal and accumbal neurons to systemic AMPH administration.     

CCK-B receptors in the limbic system modulate the antidepressant-like effects induced by endogenous enkephalins

Systemic administration of RB 101, a complete inhibitor of enkephalin catabolism, has been reported to induce antidepressant-like responses in mice which were potentiated by an ineffective dose of a CCK-B antagonist. The aim of this study was to investigate the neuroanatomical substrate involved in the facilitatory effects induced by CCK-B antagonists on RB 101 behavioural responses. Thus, the CCK-B antagonist PD-134,308 was locally administered into different brain structures (anterior nucleus accumbens, central amygdala and caudate nucleus) and its effects on the antidepressant-like response induced by systemic administration of RB 101 were evaluated in the conditioned suppression of motility (CSM) test in rats. RB 101 administered alone by the IV route decreased the CSM in rats, as previously obtained in mice. Systemic administration of a non effective dose of PD-134,308 facilitated the antidepressant-like effect induced by RB 101. Local injection of PD-134,308 into the anterior nucleus accumbens, the central amygdala or the caudate nucleus did not modify CSM. The antidepressant-like effects elicited by RB 101 in this test were potentiated by PD-134,308 after microinjection in the anterior nucleus accumbens and central amygdala, but not in the caudate nucleus. All these effects were observed only in shocked animals. The present results suggest that the mesolimbic system, particularly the anterior nucleus accumbens and the central amygdala, seems to play an important role in the interaction occurring between the endogenous CCK and opioid system in the control of behavioural responses. Received:14 October 1996 /Final version:21 February 1997     

Corticotropin-releasing factor and systemic capsaicin-sensitive afferents are involved in abdominal surgery-induced Fos expression in the paraventricular nucleus of the hypothalamus

We previously reported that abdominal surgery induces Fos expression in specific hypothalamic and medullary nuclei and also causes gastric stasis. The gastric ileus is reduced by systemic capsaicin and abolished by central injection of corticotropin-releasing factor (CRF) antagonist. We studied the influence of systemic capsaicin and intracerebroventricular (i.c.v.) injection of the CRF antagonist, α-helical CRF_9–41, on Fos expression in the brain 1 h after abdominal surgery in conscious rats using immunocytochemical detection. In control groups (vehicle s.c. or i.c.v.), abdominal surgery (laparotomy with cecal manipulation) performed under 7–8 min of enflurane anesthesia induced Fos staining in neurons of the spinal trigeminal, C1/A1 group, ventrolateral medulla, central amygdala, parabrachial nucleus, cuneate nucleus, nucleus tractus solitarii (NTS), paraventricular nucleus of the hypothalamus (PVN) and supraoptic nucleus (SON). Capsaicin (125 mg/kg s.c., 2 weeks before) or α-helical CRF_9–41 (50 μg i.c.v., before surgery) reduced the number of Fos-positive cells by 50% in the PVN while not modifying the number of Fos-labelled cells in the other nuclei. These results indicate that capsaicin-sensitive primary afferents and brain CRF receptors are part of the pathways and biochemical coding through which abdominal surgery activates PVN neurons 1 h post surgery.     

Changes in cortical EEG and cholinergic function in response to NGF in rats with nucleus basalis lesions

We examined whether recovery of cholinergic function in response to nerve growth factor (NGF) results in restoration of electrocortical activity. Rats received unilateral lesions of the nucleus basalis and were infused intracerebroventricularly (i.c.v.) over 3 weeks with NGF or vehicle. Cortical electrical activity was assessed at postoperative days 4, 7, 14, and 21 from 8 epidural electrodes. On day 21, choline acetyl transferase (ChAT) activity was measured in cortical tissue underlying each electrode site. Lesions resulted in increases in slow-wave (δ) power and decreases in high-frequency (β₂) power in the lesioned, as well as the non-lesioned hemisphere. Changes correlated topographically and in magnitude with losses of ChAT activity and suggested that regional electrocortical function was affected by cholinergic activity originating in the ipsilateral, as well as the contralateral hemisphere. NGF attenuated changes in cholinergic and electrocortical function bilaterally, though in the lesioned hemisphere, function did not return to control levels. Likewise, intact animals receiving NGF showed increases in β₂-power, as well as modest increases in ChAT activity. Changes in brain electrical activity in response to NGF occurred within 4–7 days without significant changes during the 2 weeks thereafter. Our results suggest that outcomes of future animal and human trials using unilateral i.c.v. infusions of NGF need to consider the reciprocal influences of hemispheric cholinergic function, as well as possible effects of NGF on intact brain.     

The critical role of nucleus accumbens dopamine systems in the mediation of fixed interval schedule-controlled operant behavior

Microinjections of the irreversible dopamine antagonist EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline), into nucleus accumbens but not into dorsal striatum, markedly decreased response rates on a fixed interval schedule of reinforcement. These preferential effects in nucleus accumbens could be prevented by selectively activating either D₁ or D₂ receptors. These data demonstrate a critical role for mesolimbic dopamine systems in the mediation of fixed interval schedule-controlled operant behavior.     

Operant behavior during sessions of intravenous cocaine infusion is necessary and sufficient for phasic firing of single nucleus accumbens neurons

The activity of individual accumbens neurons in rats was recorded in relation to intravenous cocaine infusions that were either response (i.e., lever press) contingent or response non-contingent. Neural firing was additionally recorded in relation to non-reinforced lever presses. Comparisons of firing under the three conditions showed that operant behavior was necessary and sufficient for preinfusion firing to occur. Surprisingly, the same was true, in many cases, for firing that occurred during the infusion. For other neurons, firing during the infusion was unrelated to operant behavior and possibly related to infusion stimuli. The relationship to operant behavior exhibited by the majority of NAcc neurons is consistent with previous studies that demonstrated a necessary relationship between NAcc neurons and cocaine reinforced operant behavior.     

Role of dopamine D1- and NMDA receptors in regulating neurotensin release in the striatum and nucleus accumbens

Stimulation of dopamine D₁-receptors by SKF 82958 increased extracellular neurotensin (NT) levels in the striatum and nucleus accumbens as measured by in vivo microdialysis while blockade of D₁-receptors had no effect. Antagonism of NMDA receptors with MK 801 completely prevented the increased NT release induced by D₁-stimulation in both structures. Tissue content of striatal NT anterior and posterior to the microdialysis probe was oppositely altered by D₁-stimulation: increases were observed in the anterior striatum with decreased NT levels in the posterior striatum.