Intracellular processing and toxicity of the truncated androgen receptor: nuclear congophilia-associated cell death

The pathogenesis of the selective motor neuron death in spinal bulbar muscular atrophy (SBMA) is not fully understood. Similar to observations with other mutant polyglutamine (poly Q) expanded proteins, truncated androgen receptor (AR) with expanded poly Q tract cause intracellular aggregates; however, the precise relationship between aggregates and disease pathogenesis is unresolved. In order to have a better understanding of the cellular processing and toxicity of the mutant AR, we focused on a short N-terminal portion of AR containing normal or expanded poly Q repeats, and have carried out biochemical, immunocytochemical, cytochemical and ultrastructural studies of BHK cells at different intervals after transfection. In cells expressing mutant truncated AR, using an anti-AR N-terminal antibody, we observed no immune staining in the nucleus and identified immune negative aggregates surrounded by immunopositive material in the cytoplasm. Congo red staining identified a component of aggregates with a beta-pleated secondary structure in both cytosol and nucleus, while electron microscopy revealed a fibrillary-granular material as the ultrastructural correlate. In addition, acid phosphatase staining and ubiquitin immunocytochemistry demonstrated that in transfected cells, both lysosomal and nonlysosomal degradation systems are actively involved in handling the mutant truncated AR. The temporal relationship of nuclear congophilia to a subsequent massive cell death suggests that entry of proteolytic cleavage products into the nucleus, perhaps the expanded poly Q stretch itself, may play an important role in cell toxicity.     

Effects of support group intervention in postnatally distressed women. A controlled study in Taiwan

Objective: The symptoms of depression experienced by women during the postnatal period may have profound effects on the lifelong health of both the mother and the child. In this randomized controlled study, we systematically evaluated the effects of weekly supportive group meetings for women with postnatal distress. Methods: Sixty postnatally distressed women were randomly assigned to support (n=30) and control (n=30) groups. Women assigned to the support group participated in four supportive group sessions that comprised discussions concerning transition to motherhood, postnatal stress management, communication skills, and life planning. Results: Subjects who attended the support sessions had significantly decreased scores on the Beck Depression Inventory (BDI) and the Perceived Stress Scale (PSS), and significantly increased scores on the Interpersonal Support Evaluation List (ISEL) as evaluated at the end of the fourth weekly session. In contrast, no significant changes were observed in the control group during this period. Conclusion: This is the first controlled study to provide evidence that participation in support groups for postnatally distressed women provides quantifiable psychosocial benefits.     

Psychiatric morbidity and illness experience of primary care patients with chronic fatigue in Hong Kong

OBJECTIVE: The authors' goal was to examine the prevalence and experience of psychiatric morbidity among primary care patients with chronic fatigue in Hong Kong. METHOD: One hundred adult patients with medically unexplained fatigue for 6 or more months were assessed with the Explanatory Model Interview Catalogue, psychopathological rating scales, and an enhanced version of the Structured Clinical Interview for DSM-III-R. RESULTS: The lifetime prevalence of DSM-III-R depressive and anxiety disorders was 54%. Current depressive and anxiety disorders were identified in 28 patients, who exhibited more psychopathology and functional impairment than other patients. Thirty-three patients had somatoform pain disorder, and 30 had undifferentiated somatoform disorder, but most of them could also be diagnosed as having shenjing shuairuo (weakness of nerves) and, to a lesser extent, ICD-10 neurasthenia. Chronic fatigue syndrome diagnosed according to the 1988 Centers for Disease Control criteria was rare (3%) and atypical. Generally, patients mentioned fatigue if asked, but pains (36%), insomnia (20%), and worries (13%) were the most troublesome symptoms. Most patients attributed illness onset to psychosocial sources. CONCLUSIONS: Psychiatric morbidity was common among primary care patients with chronic fatigue. Subthreshold psychiatric morbidity was very common and was more validly represented by the disease construct of shenjing shuairuo or neurasthenia than somatoform disorder.     

Empirical examination of current depression categories in a population-based study: symptoms, course, and risk factors

OBJECTIVE: Research studies on the validity of current diagnostic and subthreshold categories of depression that use a population-based follow-up design are rare. The authors examined the validity and utility of four current depression categories by examining subject transition between categories and the symptoms, course, and risk factors of each. METHOD: A general population sample of 1,920 adults from the Baltimore Epidemiologic Catchment Area 13-year follow-up study were examined. Data on diagnoses, symptoms, course, and risk factors were collected by using the National Institute of Mental Health Diagnostic Interview Schedule, the Life Chart Interview, and an office visit. Polychotomous regression was used to examine the heterogeneity of four diagnostic categories: major depressive disorder, depressive syndrome, dysthymia, and a comorbid depression condition (major depressive disorder and dysthymia). RESULTS: Transitions between the four depression categories occurred over the 13 years. Symptom profiles for the four categories were parallel but differed in severity. Course characteristics among the four categories slightly differed. Risk factor profiles showed significant differences. Family history was associated with both depressive syndrome and major depressive disorder. Stressful life events were most strongly associated with depressive syndrome. Female gender was most strongly associated with the comorbid depression category. CONCLUSIONS: The evidence suggests that except for dysthymia, the depression categories are genetically homogeneous and environmentally heterogeneous. Stress is associated with mild depression, and gender is associated with severe depression. The apparent familial transmission of the subthreshold entity, depressive syndrome, needs further investigation.     

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.     

Behavioral evidence for brain-based ability factors in visuospatial information processing

The present study examined possible parallels between the structure of human visuospatial abilities and the organization of the neural systems. Forty-eight participants were tested on seven speeded visuospatial tasks. Three of these tasks were constructed so as to rely primarily on known ventral stream functions and four were constructed so as to rely primarily on known dorsal stream functions. Both sets of tasks spanned approximately the same range of difficulty as indexed by both the speed and accuracy of decision making. Factor analysis of response times on the seven tasks revealed only two significant factors. The putative ventral stream tasks all loaded heavily on one factor (mean loading=0.843) but only weakly on the other factor (mean loading=0.222); the putative dorsal stream tasks showed the opposite pattern in that they all loaded heavily on the second factor (mean loading=0.828) but only weakly on the first factor (mean loading=0.229). These findings are consistent with the hypothesis that human visuospatial abilities can be classified using categories based on the specializations of underlying neural structures and systems.     

Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery

Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII, are similarly toxic to mice when administered by a subcutaneous route, but in mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in central nervous system (CNS), peripheral preparations and expressed sodium channels revealed the basis for their differential toxicity. In rat brain synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII strongly inhibits sodium current inactivation of brain rBII subtype expressed in HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII affects sodium channel subtypes other than rBII in the brain. In the periphery, both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal root ganglion neurons, and are strongly active directly on the muscle and on expressed muI channels. Only LqhII, however, induced repetitive end-plate potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in peripheral nervous system (PNS) serve as the main targets for LqhII but are mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be attributed to the direct effect on muscle. Our data elucidate, for the first time, how different toxins affect mammalian central and peripheral excitable cells, and reveal unexpected subtype specificity of toxins that interact with receptor site 3.     

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.     

高效液相色谱法同时测定复方对乙酰氨基酚维生素C泡腾片中2组分含量

目的 :建立同时测定复方对乙酰氨基酚维生素C泡腾片中对乙酰氨基酚和维生素C含量的高效液相色谱法。方法 :色谱柱 :YWG -C18柱 (10 μm,2 5 0mm× 4 .6mm) ;流动相 :甲醇 乙腈 0 .0 5mol·L-1磷酸二氢铵 磷酸缓冲液 (5 0∶11∶2 5 0 ) ;流速 :1.0mL·min-1;检测波长 :2 5 4nm。结果 :对乙酰氨基酚线性范围为 8～ 16 0mg·L-1;维生素C线性范围为 5～ 10 0mg·L-1。对乙酰氨基酚回收率为 10 0 .4 % (RSD =2 .4 0 % ) ,维生素C回收率为 10 1.2 % (RSD =1.90 % )。结论 :应用本法同时测定对乙酰氨基酚和维生素C含量 ,具有简便、快速、准确、可靠的特点     

小儿肺炎电超导治疗的研究

目的 评价电超导辅助治疗小儿肺炎的临床疗效。方法 所有144例，治疗组84例，对照组64例，对照组应用抗生素，同时止咳，化痰，平喘对症处理，治疗组在以照组的基础上超导辅助治疗，疗程一周。结果 治疗组总有效率100％，总痊愈率92．86％。而对照组总有效率仅为71．67％。结论 在原有治疗基础上加用电超导，可明显提高治愈率及总有效率。