Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes

Doublecortin (DCX) is a microtubule-associated protein involved in neuronal migration, which causes X-linked lissencephaly and subcortical laminar heterotopia (SCLH) when mutated. Here we show that DCX interacts with the ubiquitin-specific protease Drosophila fat facets related on X chromosome (DFFRX). This interaction was confirmed by targeted mutagenesis, colocalization, and immunoprecipitation studies. DFFRX is thought to deubiquitinate specific substrates including beta-catenin, preventing their degradation by the proteasome. Interestingly, unlike beta-catenin, no ubiquitinated forms of DCX could be detected, and indeed we show that DCX interacts with a novel recognition domain in DFFRX, located outside of its catalytic site. We also show that DFFRX associates with microtubules at specific subcellular compartments, including those enriched in DCX. These results thus suggest that in addition to vesicular trafficking, DCX may play a role in the regulation of cell adhesion via its interaction with DFFRX in migrating and differentiating neurons.     

Clinical fetal weight estimation and prediction of macrosomia

The purpose of this study is to assess symphysis fundal height measurement in prediction of fetal macrosomia and to search for the error causes. A retrospective study concerning 400 macrosomic newborns was performed. For each pregnant woman before delivery, we have reviewed fundal height, weight, height and newborn weight. Influence of obesity and maternal height were especially studied. Fundal height measurement is not reliable in prediction of fetal macrosomia. Patient body mass and height may be error causes.     

Transovarial transmission of sugarcane white leaf phytoplasma in the insect vector Matsumuratettix hiroglyphicus (Matsumura)

White leaf is a serious disease of sugarcane caused by phytoplasma. The disease is transmitted to the plant by the leafhopper Matsumuratettix hiroglyphicus (Matsumura). The reservoir of phytoplasma was suspected to be weeds that grow in sugarcane farming areas because they can be infected with phytoplasma and show symptoms similar to sugarcane white leaf. However in previous work we have demonstrated by RFLP and sequencing that this is not the case. Here we have reared M. hiroglyphicus through two generations by feeding them phytoplasma free sugarcane grown from tissue culture. By nested-PCR followed by sequencing, we demonstrated the presence of the phytoplasma in eggs, nymphs and adults of the first and second generations thereby showing transovarial transmission. We have also shown by in situ PCR that phytoplasmas were widely distributed throughout the body of the insect. RFLP and sequencing showed that the same phytoplasma was present in the vector and in the plant. Together, these data point to the leafhopper M. hiroglyphicus as the reservoir of phytoplasma that cause sugarcane white leaf disease.     

Laparoscopic aspects of peritoneal tuberculosis. Report of 163 cases

The aim of this study is to report the results, the complications and limits of laparoscopy in patients with tuberculous peritonitis. In a retrospective study of 163 laparoscopy realized from 1970 to 1998. All the patients had exsudative ascites with predominantly of lymphocytes. Miliary nodules were found in 87% of cases, adhesions between the peritoneum and organs were found in 69% of cases and congestion in 63% of cases. Laparoscopically guide peritoneal biopsies detected caseating granulomas in 87% of cases. Laparoscopic appearance of the peritoneum mimicking a carcinosis in 15% of cases. One patient had complication as a bowel perforation. Miliary nodules and adherences are the more frequent appearances into peritoneal cavity in tuberculous peritonitis. With peritoneal biopsies, laparoscopy is always the best method for definitively and rapidly diagnosis of tuberculous peritonitis.     

Splenic arteriovenous fistula and portal hypertension. A case report

The authors report a rare case of portal hypertension following to an arteriovenous fistula. The embolisation of the fistula permitted to treat portal hypertension and liver histologic alterations.     

Cell cloning-based transcriptome analysis in cyclin-dependent kinase-like 5 mutation patients with severe epileptic encephalopathy

Mutations in the human CDKL5 gene have been shown to cause infantile spasms, as well as Rett syndrome-like phenotype. Because CDKL5 is subjected to X chromosome inactivation (XCI), individual cells from CDKL5 mutation girls either express the wild-type or mutant allele, likely resulting in different consequences at both the cellular and molecular levels. To identify these consequences, we carried out gene expression profiling on clonal populations derived from primary cultures of three patients' fibroblasts either expressing the wild-type or mutant allele. A total of 16 up-regulated and 20 down-regulated genes were identified. The differentially expressed gene products, mostly involved in differentiation and oxidative stress may be related to a mechanism underlying mental retardation and epilepsy. Among these, the apoptosis signal-regulated kinase MAP3K5 expression was found to be altered in non-neuronal, but also in neuronal CDKL5-deficient cells. Due to the fact that MAP3K5 activates MAP kinase pathway, which mediates signals leading to both differentiation and survival in neuronal cells, we suggest that a CDKL5 deficit may induce changes in synaptic plasticity in the patient's brain.     

Sudden hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment

Adverse effects associated with peginterferon and ribavirin during hepatitis C treatment are well known. Sudden hearing loss has rarely been reported. Possible mechanisms involved include direct ototoxicity of interferon, autoimmunity, and hematological changes. Hearing loss is frequently fully resolved after discontinuation of antiviral therapy. We report a 47-year- old man with chronic hepatitis C, genotype 2 ac who developed sudden hearing loss 22 wk after starting therapy with peginterferon alpha 2a at a dose of 180 ~g per week and ribavirin 800 mg per day. Since symptoms did not worsen, antiviral therapy was continued for 2 wk, according to the patient＇s wish. Hearing loss resolved within 2 wk after the end of treatment. Serum liver alanine aminotransferase remained normal during and after the end of antiviral therapy. HCV RNA was undetectable at the end of therapy and remained negative 24 wk later. Thus, patients should be aware that hearing loss may occur with peginterferon therapy, but the decision whether to continue or to stop the treatment is based on the clinical judgment of the physician and the wishes of the patient.     

High hepatic glutathione stores alleviate Fas-induced apoptosis in mice

BACKGROUND/AIMS: The agonistic Jo2 anti-Fas antibody reproduces human fulminant hepatitis in mice. We tested the hypothesis that enhancing hepatic glutathione (GSH) stores may prevent Jo2-induced apoptosis. METHODS: We fed mice with a normal diet or a sulfur amino acid-enriched (SAA(+)) diet increasing hepatic GSH by 63%, and challenged these mice with Jo2. RESULTS: The SAA(+) diet markedly attenuated the Jo2-mediated decrease in hepatic GSH and the increase in the oxidized glutathione (GSSG)/GSH ratio in cytosol and mitochondria. The SAA(+) diet prevented protein kinase Czeta (PKCzeta) and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, Bid truncation, Bax, and cytochrome c translocations, the mitochondrial membrane potential collapse, caspase activation, DNA fragmentation, hepatocyte apoptosis, and mouse lethality after Jo2 administration. The protective effect of the SAA(+) diet was abolished by a small dose of phorone decreasing hepatic GSH back to the levels observed in mice fed the normal diet. Conversely, administration of GSH monoethyl ester after Jo2 administration prevented hepatic GSH depletion and attenuated toxicity in mice fed with the normal diet. CONCLUSIONS: The SAA(+) diet preserves GSSG/GSH ratios, and prevents PKCzeta and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, mitochondrial permeabilization, and hepatic apoptosis after Fas stimulation. GSH monoethyl ester is also protective, suggesting possible clinical applications.