A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins

Protein kinase casein kinase 1 (CK1) phosphorylates Ser-45 of beta-catenin, "priming" the subsequent phosphorylation by glycogen synthase-3 of residues 41, 37, and 33. This concerted phosphorylation of beta-catenin signals its degradation and prevents its function in triggering cell division. The sequence around Ser-45 does not conform to the canonical consensus for CK1 substrates, which prescribes either phosphoamino acids or acidic residues in position n-3 from the target serine. However, the beta-catenin sequence downstream from Ser-45 is very similar to a sequence recognized by CK1 in nuclear factor for activated T cells 4. The common features include an SLS motif followed two to five residues downstream by a cluster of acidic residues. Synthetic peptides reproducing residues 38-65 of beta-catenin were assayed with purified rat liver CK1 or recombinant CK1 alpha and CK1 alpha L from zebrafish. The results demonstrate that SLS and acidic cluster motifs are crucial for CK1 recognition. Pro-44 and Pro-52 are also important for efficient phosphorylation. Similar results were obtained with the different isoforms of CK1. Phosphorylation of mutants of full-length recombinant beta-catenin from zebrafish confirmed the importance of the SLS and acidic cluster motifs. A search for proteins with similar motifs yielded, among other proteins, adenomatous polyposis coli, previously found to be phosphorylated by CK1. There is a strong correlation of beta-catenin mutations found in thyroid tumors with the motifs recognized by CK1 in this protein.     

层流洁净技术在烧伤治疗中的应用

目的 探索层流洁净技术治疗大面积烧伤的价值。方法 对室内空气及创面进行细菌培养；监测病房使用时间的细菌微粒数比较，各洁净级别杀菌率。不同级别地点细菌培养结果比较。结果 千级以上层流病房细菌培养为“0”，与普通病房对照有较大差别，患者死亡率明显降低，疗程缩短，医疗费用下降，手术植皮及其他伤口均达Ⅰ期愈合，无交叉感染。结论 层流洁净病房应用于烧伤治疗，疗效非常满意。     

Videolaparoscopic treatment of varicocele: retrospective study of 165 cases

Idiopathic varicocele is a common condition that is present in approximately 15% of the general male population. The mechanism by which varicocele exerts a deleterious effect on testicular function and semen quality remains unknown. Nevertheless, it is generally regarded as a significant factor in male infertility. Varicocelectomy is accomplished with a variety of approaches: the inguinal and high retroperitoneal procedures are still commonly accepted methods, but laparoscopic varicocelectomy is currently proving an increasingly popular procedure. The authors report the results of a retrospective study of 165 laparoscopic varicocelectomies performed from 1993 to 2000 and conclude that this approach is simple, safe and effective and should be recommended as the treatment of choice.     

Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

Vertical transmission of Kaposi's sarcoma

AIDS related Kaposi's sarcoma is commonly seen in homosexual men, only occasionally in men and women with heterosexually acquired HIV, and extremely rarely in children. The case of an HIV infected mother and her vertically infected child who both developed visceral Kaposi's sarcoma is reported. It is proposed that the putative Kaposi's sarcoma agent may also be transmitted vertically.     

Extracorporeal life support in paediatrics

Extracorporeal membrane oxygenation (ECMO) is a life support technique based on modifications of heart-lung bypass technology. It is used to support severe but potentially reversible pulmonary or cardiopulmonary failure. There is increasing use of the technique for neonates and a return of interest in its use for adults. The number of non-neonatal paediatric patients receiving pulmonary support with ECMO worldwide is, however, small, and survival rates average less than 50%. Initial experience in 15 patients aged 3 months to 5 years with a high survival and low morbidity is reported.     

Reproducibility of the six-minute walking test in chronic heart failure patients

The six-minute walking test (WT) is used in trials and clinical practice as an easy tool to evaluate the functional capacity of chronic heart failure (CHF) patients. As WT measurements are highly variable both between and within individuals, this study aims at assessing the contribution of the different sources of variation and estimating the reproducibility of the test. A statistical model describing WT measurements as a function of fixed and random effects is proposed and its parameters estimated. We considered 202 stable CHF patients who performed two baseline WTs separated by a 30 minute rest; 49 of them repeated the two tests 3 months later (follow-up control). They had no changes in therapy or major clinical events. Another 31 subjects performed two baseline tests separated by 24 hours. Collected data were analysed using a mixed model methodology. There was no significant difference between measurements taken 30 minutes and 24 hours apart (p = 0.99). A trend effect of 17 (1.4) m (mean (SE)) was consistently found between duplicate tests (p < 0.001). REML estimates of variance components were: 5189 (674) for subject differences in the error-free value; 1280 (304) for subject differences in spontaneous clinical evolution between baseline and follow-up control, and 266 (23) for the within-subject error. Hence, the standard error of measurement was 16.3 m, namely 4 per cent of the average WT performance (403 m) in this sample. The intraclass correlation coefficient was 0.96. We conclude that WT measurements are characterized by good intrasubject reproducibility and excellent reliability. When follow-up studies > or = 3 months are performed, unpredictable changes in individual walking performance due to spontaneous clinical evolution are to be expected. Their clinical significance, however, is not known.     

Pathological complications of non-survivors of newborn extracorporeal membrane oxygenation

The pathology was reviewed of the early deaths identified from the first 50 neonates treated with extracorporeal membrane oxygenation (ECMO) during its introduction to the UK. Fifteen neonates died during or shortly after ECMO between August 1989 and June 1992. Data on 12 are presented (three did not have a postmortem examination). The clinical diagnoses at referral for ECMO were as follows: persistent pulmonary hypertension of the newborn (six infants), primary congenital pneumonia (one infant), community acquired pneumonia (two infants), birth asphyxia (one infant), respiratory distress syndrome (one infant), and meconium aspiration syndrome (one infant). In our group, at necropsy, five had significant haemorrhage (three intracranial, one pulmonary, one pericardial and intraventricular). Three of five infants with evidence of haemorrhage also had signs of sepsis. Six infants had evidence at necropsy of systemic sepsis, five showed evidence of severe anoxic brain injury, and four infants had cerebellar haemorrhages. Three infants had evidence of myocardial ischaemia. It is difficult to discriminate between the relative influence of the primary diagnosis, the mode of treatment, and the severity of presentation in the genesis of this pathology. It is likely that the extent and severity of some of the findings represent a pathological progression that would have been interrupted by the death of the patient, had ECMO not been instituted.