基于受体结构的药物分子设计系统:维甲类分子与其结合蛋白之间相互作用的研究

大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。     

Photic driving in migraine: correlations with clinical features

Fifty-eight migraineurs were. studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep .wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.     

Hyponatremia-associated cognitive impairment in traumatic brain injury

The case of a traumatic brain injury (TBI) patient with dramatic cognitive deterioration in the absence of medical aetiology other than simultaneous decline in serum sodium led to an investigation of the association between declines in sodium levels and cognitive status. In a population of 50 persons undergoing TBI rehabilitation, 12 (24%) had relative (3 mEq/L) decreases in serum sodium while five (10%) experienced absolute hyponatremia (136 mEq/L). Correlation with cognitive status was significant when the absolute hyponatremia group was compared with those whose sodium levels remained above 136 mEq/L. A case-matched study of the relative hyponatremia group yielded no significant association between sodium-level decreases and cognitive status. These data support previous conclusions indicating wide variation in individual responses to changes in serum sodium. The threshold for significant effects of hyponatremia may be higher in patients with TBI than in populations studied previously.     

Clostridium difficile in Crohn's disease

Clostridium difficile has been detected in the stools of some patients with relapse of Crohn's disease. The authors looked prospectively for present or previous exposure to C. difficile cytotoxin in 10 patients with mild to severe Crohn's disease. None of 25 stool samples from these 10 patients was positive for C. difficile cytotoxin. These negative stool ultrafiltrates had mild cytotoxin neutralizing activity, but this finding did not differ from that in 30 cytotoxin-negative stools from patients with other diarrheal diseases. Serum from these patients also showed no cytotoxin neutralizing activity. Review of the literature reveals that C. difficile can cause complications ranging from diarrhea to toxic megacolon in a small but variable proportion of patients with Crohn's disease. There is no evidence that C. difficile plays a part in the pathogenesis of the disease.     

Predictors of relapse to harmful alcohol after orthotopic liver transplantation

BACKGROUND: End-stage alcoholic liver disease (ALD) is a common indication for liver transplantation. Outcomes may be limited by return to harmful drinking. Previous studies have identified few predictors of drinking relapse. AIM: This study examined novel postulated predictors of relapse to drinking. METHOD: The case notes of all patients transplanted for ALD at the Royal Prince Alfred Hospital from 1987-2004 were reviewed. Pre-transplant characteristics were rated by a psychiatrist independent of the transplant team, blind to the outcome. Outcomes were rated by a second independent alcohol treatment specialist also blind to the pre-transplant ratings. RESULTS: Of 100 patients, 6 died before discharge from hospital, 4 had <6 months follow-up, 18 relapsed to harmful drinking, 10 drank below harmful levels, and 62 remained abstinent after a mean of 5.6 years follow-up. Univariate analyses identified six potential pre-transplant predictors of return to harmful drinking. These were a diagnosis of mental illness (of which all cases were of depression), the lack of a stable partner, grams per day consumed in the years before assessment for transplant, reliance on 'family or friends' for post-transplant support, tobacco consumption at time of assessment, and lack of insight into the alcohol aetiology. Duration of pre-transplant abstinence and social class by occupation did not predict relapse. A multivariate model based on the above characteristics correctly predicted 89% of the outcomes. CONCLUSION: A model based on readily defined behaviours and psychosocial factors predicted relapse to harmful drinking after transplant for ALD. This model may improve assessment and post-transplant management of patients with advanced ALD.     

Spontaneous resolution of severe aplastic anemia associated with viral hepatitis a in a 6-year-old child

Recovery from acquired aplastic anemia associated with hepatitis is rare. This case of a 6-year-old boy with severe aplastic anemia is the first reported association of this disease with a hepatitis A infection. Antibody to hepatitis A (anti-HA) was not detected on admission, but was detected three weeks later. Infection with hepatitis B virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were excluded. The peak titer of anti-HA was higher than would be expected for passive transfer of antibody resulting from transfusions. The persistence of antibody for more than 20 months after the last transfusion was not consistent with passive antibody, which would be expected to disappear over that time. This child had indications for allogeneic marrow transplant and a sibling donor who was histocompatible. However, the transplant was postponed because the prognosis was considered to be poor in the presence of active hepatitis. There was a spontaneous remission without the necessity of the transplantation procedure.