以磷酸肌醇3激酶通路为靶点的抗肿瘤药物

磷酸肌醇3激酶(PI3K)通路是一个关键的信号转导系统,它可将癌基因和多种受体与许多细胞功能联系在一起,还是肿瘤中最常被激活的通路。靶向PI3K同工酶和通路中包括AKT和mTOR在内的其他主要节点的抑制剂已进入临床试验阶段,但存在一定问题。本文重点阐述人们在理解PI3K通路方面取得的进展,并讨论研发靶向这条通路的抗肿瘤药物的机遇与面临的挑战。     

The occurrence of arthropods in processed rice products in Malaysia

ObjectiveTo determine distribution of arthropods in processed rice products such as rice flour and rice cereal-based infant food.MethodsRandom samples of rice flour and rice cereal-based infant food purchased from commercial outlets were examined for the presence of arthropods using a modified Berlese Tullgren Funnel Method. Mites were mounted prior to identification and weevils were directly identified.ResultsFor non-expired products, infestation was found in 6.7% of rice flour and none was found in rice cereal-based infant food samples. The arthropods found in the flour samples were Cheyletus spp., Suidasia pontifica (S. pontifica), Tarsonemus spp., Tyrophagus putrescentiae (T. putrescentiae), Sitophilus granarius (S. granarius) and Sitophilus oryzae (S. oryzae). Others which cannot be identified were Oribatid and Prostigmatid mites. The most common mites in rice flour were Tarsonemus spp. (69.1%), followed by S. pontifica (18.2%). For expired products, only one sample of rice cereal-based infant food was infested and the infestation was by mites of the family Tydeidae.ConclusionsThis study demonstrates the presence of 4 allergenic species of S. pontifica, T. putrescentiae, S. granarius and S. oryzae in rice flour. These arthropods can contribute to the incidence of anaphylaxis upon consumption by atopic individuals. There was no infestation of arthropods in rice cereal-based infant food surveyed except for an expired product in a moderate rusty tin container.     

Risk factors for adverse outcomes of bacterial meningitis

Objective : To identify risk factors for adverse outcomes from bacterial meningitis.
Methodology : From a cohort of 166 children with bacterial meningitis who were studied prospectively, 130/158 (82%) survivors underwent neurological, neuropsychological, audiological and behaviour assessments 5–9 years following their illness.
Results : Major adverse outcomes included 8/166 (4.8%) deaths and severe neurological, intellectual or audiological sequelae in 11/130 (8.5%) children followed. Another 24 (18.5%) had cognitive, auditory or behaviour disorders. Bivariate analysis found age ≤12 months, tertiary referral, symptoms >24 h before diagnosis, seizures, focal neurological signs, deteriorating conscious state in hospital, Streptococcus pneumoniae infection and serum sodium concentration < 130 mmol/L were associated with adverse outcomes. Multivariate analysis showed age ≤12 months, symptoms >24 h, seizures after 72 h in hospital and focal neurological signs as independent risk factors. These were present in 18/19 (95%) children with major sequelae, but absent in 9/24 (37.5%) children with minor disabilities.
Conclusions : As minor disabilities following meningitis cannot be predicted, all survivors require assessment during their early school years.     

Beliefs and practices concerning twins, hermaphrodites, and albinos among the Bamana and Maninka of Mali

The Bamana and Maninka of Mali greatly value twins, and have elaborated a range of cultural beliefs and practices to assure their survival. Rates of twinning among these two ethnic groups average from 15.2/1000 to 17.9/1000 births compared to 10.5/1000 births (without assisted reproduction) in the United States and Great Britain. Twins (flaniw) are regarded as extraordinary beings with unusual powers, and as a gift from the supreme deity. A small altar (sinzin) is maintained in the home of twins, and periodic sacrifices of chicken blood, kola nuts, millet paste and millet beer regularly made to assure their protection. Albinos (yéfeguéw) and true and pseudo-hermaphrodites (tyétémousotéw) are also considered twin beings. However, they are believed to be the result of aberrant parental social behavior. The Bamana and Maninka believe that all four groups (twins, albinos, hermaphrodites, and pseudo-harmaphrodites) are closely linked to Faro, an androgynous supernatural being who provides equilibrium in the world. Faro is the original albino and hermaphrodite who gave birth to the first pair of twins after self-impregnation. Whenever a twin dies, a small wooden statue is sculpted called a flanitokélé (twin that remains). This commemorative figure is kept close to the surviving twin, reflecting a belief in the inseparability of twins. Eventually, the surviving twin takes responsibility for the figure. When a surviving twin marries, another figure is often sculpted in the opposite sex from the deceased twin, and placed with the original sculpture. Such commemorative sculptures are not created upon the death of those who are albinos, hermaphrodites, or pseudo-hermaphrodites. In recent years, transformational belief patterns have evolved as increasing numbers of Bamana and Maninka embrace Islam. Traditional beliefs are often given Islamic myths of origin. However, even in this Islamic context, many practices that assure twin survival are maintained.Gavin H. Imperato, MS completed his graduate studies in biology at New York University, and recently conducted field research on twinning in Mali; Pascal James Imperato, MD, MPH & TM is Distinguished Service Professor and Chair of the Department of Preventive Medicine and Community Health, State University of New York, Downstate Medical Center.     

Cross-sectional anatomy of the pericardial sinuses,recesses, and adjacent structures

Detailed drawings of four cross sections through the mediastinum which pass through the sinuses and recesses of the pericardial cavity, are presented. The drawings depict the location and extent of the pericardial sinuses, recesses, and their closely associated extrapericardial structures. Two previously unnamed recesses within the serous pericardium are defined and named, one the inferior aortic recess of the transverse sinus and the other, the right pulmonic recess of the transverse sinus. The terminology of the pericardial sinuses and recesses has been inconsistent, and the authors propose a nomenclature for standardizing the names of the recesses of the serous pericardium. Important anatomic pericardial relationships with regard to pericardial effusions and lymphadenopathy are discussed.     

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy and a number of neurological symptoms including deafness, ataxia and peripheral neuropathy. Mitochondrial DNA deletions have been described in a few patients and a locus has been mapped to 4p16 by linkage analysis. Susceptibility to psychiatric illness is reported to be high in affected individuals and increased in heterozygous carriers in Wolfram syndrome families. We screened four candidate genes in a refined critical linkage interval covered by an unfinished genomic sequence of 600 kb. One of these genes, subsequently named wolframin, codes for a predicted transmembrane protein which was expressed in various tissues, including brain and pancreas, and carried loss-of- function mutations in both alleles in Wolfram syndrome patients.      

Biomarkers in lysosomal storage diseases: a review

A biomarker is generally an analyte that indicates the presence or extent of a biological process, which is itself directly linked to the clinical manifestations and outcome of a particular disease. An ideal biomarker provides indirect but ongoing and specific determinations of disease activity. These characteristics emphasize the value of surrogate biomarkers for non-invasive and detailed monitoring to demonstrate the efficacy of orphan drugs in clinical trials. The emergence of novel laboratory methods has facilitated the search for biomarkers in lysosomal storage diseases (LSDs), by allowing the systematic identification of molecules whose expression is altered as a result of the primary storage pathology. In Gaucher disease, for example, a chemokine, CCL18, has been identified as a biomarker for clinical development that reflects disease severity and response to treatment.
Conclusion: New methods for the identification of novel biomarkers have the potential to provide mechanistic insights into the molecular pathogenesis of LSDs, including Fabry disease and Gaucher disease.