Wortmannin,an inhibitor of phospholipase D activation,selectively blocks major histocompatibility complex class II-restricted antigen presentation

Wortmannin, a fungal metabolite, is a specific inhibitor of phospholipase D (PLD) activation. Presentation of defined exogenous soluble proteins to specific T cell hybridomas was studied by using different antigen-presenting cells (APC): IA-positive peritoneal macrophages (MΦ?), B lymphoma cells (B) or dendritic cells (DC). Major histocompatibility complex class II-restricted antigen presentation by MΦ? was blocked when cells were pretreated with wortmannin. However, when cells constitutively expressing IA molecules (B. DC) were used as APC, no inhibition was observed. Additionally, MHC class I antigen presentation was not impaired by wortmannin. Moreover, wortmannin does not block either peptide presentation or presentation to autoreactive T cells. This effect was time and dose dependent and occurred at the level of intracellular handling of the antigen. Mainly because it was not a toxic inhibition, it was reversible with time and neither antigen uptake and catabolism, nor IA synthesis were affected. Because MΦ, but not B or DC, express PLD activity and only the former were blocked by wortmannin in antigen presentation, our results strongly suggest that a differential antigen-processing pathway exists in these disparate APC, which could be based essentially on a wortmannin-sensitive, PLD-dependent step present in MΦ but absent and/or unnecessary in both B lymphoma cells and DC.     

Dietary treatment for familial hypercholesterolemia--differential effects of dietary soy protein according to the apolipoprotein E phenotypes

Familial hypercholesterolemia, one form of type IIa hyperlipidemia, usually responds poorly to standard low-lipid diets. To define the responsiveness to a soy-protein diet in this disease, one homozygous and twenty heterozygous type IIa patients were submitted to a 4-wk traditional hypocholesterolemic diet followed by 4 wk in which animal protein was substituted with texturized soy protein. Soy was then withdrawn for a further 4 wk. No significant changes in plasma lipids were observed during low-lipid diets. The soy diet, however, caused a marked decrease in total (-20.8%) and low-density-lipoprotein (-25.8%) cholesterol and in apolipoprotein B (-14.1%). The plasma cholesterol reduction was higher in patients with apolipoprotein E3/E3 or E3/E4 vs an almost negligible effect on E3/E2. These results confirm that soy-protein diets can lower cholesterol in type IIa patients with familial disease. Data on the sensitivity of patients with different apo-E isoforms agree with recent hypotheses suggesting that soy proteins may activate B,E receptors.     

Liquid crystalline epoxy resins containing binaphthyl group as rigid block with enhanced thermal stability

The synthesis and characterization of a novel liquid crystalline difunctional epoxy compound, 6,6′-bis(2,3-epoxypropoxy)-2,2′-binaphthyl ( 4 ), is presented. This epoxide, obtained by glycidyl termination of 2,2′-binaphthyl-6,6′-diol, shows a nematic phase between 240 and 270°C. The curing reaction was carried out in the DSC pan by mixing the epoxy monomer with 4,4'-diaminodiphenyl sulfone (DDS) or phthalic anhydride (FA). The thermal analysis of the cured resins indicated high thermal resistance.     

Immunohistochemical MIB-1 and p27 as Prognostic Factors in Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a tumour that usually presents a short survival time from diagnosis, but in a small number of patients a longer survival time has been observed. We have studied a series of ten long-term and ten short-term survivors with MPM to assess whether the MIB-1 proliferation index and the p27^kip1 expression correlated with survival. Our results show significant difference in MIB-1 and in p27^kip1 expression between the group of short and longer survival patients. It suggests that the difference in tumour growth fractions may express different biological behaviour and therefore indicate important factors in MPM prognosis.     

Motor coordination in children with congenital strabismus: effects of late surgery.

BACKGROUND: Strabismus is one of the most common visual disorders in infancy. While there is a great attention on the effects of the timing of surgery as to the development of binocular vision, little is known about the possible influence of congenital strabismus on perceptual-motor and more generally, on neuromotor development. AIMS: Aim of this study was to investigate perceptual-motor and motor coordination abilities of 19 children with essential congenital esotropia who underwent a late surgery (after 4 years), compared to 23 age-matched controls. METHODS: Children were tested using the Movement Assessment Battery for Children (Movement ABC) that were performed both 1-week before surgery (T1) and about 3 months (+/-2 weeks) after surgery (T2). RESULTS AND CONCLUSIONS: At T1, abnormal or borderline results were found in more than half of the children with strabismus, as opposed to only about 17% of the controls. At T2 none of the children showed abnormal Movement ABC total scores and there was no difference in global scores between the study and the control group. The two groups also did not show any significant difference in individual items of the movement ABC with the exception of those assessing ball skills. Our results suggest that surgical correction of strabismus, even when performed after the 4th year of life, appears to be effective in improving perceptual-motor and motor function.     

A new rat model of small vessel stenting

Objectives: Restenosis is the major complication of coronary angioplasty and stenting. In addition, the small vessel diameter represents a major limitation to the wide use of the technology. The aim of this study was to assess the feasibility and the vascular response of stent deployment in rat small vessels. Methods: In 40 Wistar rats (500–550 g) a Nir stent crimped on a 1.5 mm Comet angioplasty balloon catheter was deployed at high pressure in the common carotid artery. Neointimal area, neointima/media ratio and the arterial dimension were assessed immediately and at 7, 14, 21, and 28 days after stenting. Results: After stent deployment, the neointimal area and the neointima/media ratio increased progressively and peaked at 14 days (p < 0.05 vs 0 and 7 days). Alpha-actin-positive cells were found circumferentially organized on the lumen surface. At 21 and 28 days after stenting, the neointima and the neointima/media ratio were not statistically different compared with the results obtained fourteen days after stent deployment. No significant differences in the area of external elastic lamina were observed during the study period. In contrast, the internal lumen area was reduced significantly at 14, 21, and 28 days after the stent deployment. Subacute thrombosis rate after stent implantation was 26.5%. Conclusions: The results of this study demonstrated that the balloon expandable stents can be safely placed into rat arteries and the reduction of the internal arterial lumen observed after stent deployment was only due to the neointima formation whereas remodeling did not occur. Received: 5 August 1999, Returned for 1. revision: 6 October 1999, 1. Revision received: 23 November 1999, Returned for 2. revision: 7 December 1999, 2. Revision received: 22 December 1999, Accepted: 6 January 2000     

Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome

We report on two brothers with moderate-to-severe mental retardation, severe macrocephaly, obesity, characteristic face, big hands and feet, advanced bone age and brain abnormalities, including frontal cortical atrophy. These two boys resembled the two brothers described by , two maternal cousins subsequently reported by and a Brazilian boy described by . Upon further investigation, we detected a cryptic subtelomeric deletion of chromosome region 22q13, not present in either parent and probably due to a maternal germinal mosaicism. Thus, we describe the first familial case of 22q13 deletion and recommend that patients with a phenotype suggestive of the so-called Clark-Baraitser syndrome be tested for submicroscopic 22qter deletion.     

Laparoscopic neurolysis of the pelvic sciatic nerve in a case of catamenial footdrop

Isolated cases of cyclic sciatica associated with endometriosis have been reported since the 1940s. Surgical intervention, either by laparoscopy for lesions within the pelvis or by open procedures for extrapelvic lesions, has usually been performed. A 37-year-old woman with catamenial footdrop and pain of the right thigh came to our observation. Previously, she underwent laparoscopy for bilateral ovarian endometriomas. In a second laparoscopy, we removed her uterosacral right ligament and recto-vaginal endometriotic nodules. After a temporary improvement, a third surgical procedure was necessary: laparoscopic neurolysis to free the sciatic nerve from fibrotic tissue. Then the patient was treated with gonadotropin-releasing hormone analogs for 6 months, and she is free of symptoms 2 years after last surgery. This is the first described case of laparoscopic neurolysis of the proximal sciatic nerve. The procedure has been successful in treating a patient with endometriosis in whom the cause of the syndrome was probably due to entrapment of the nerve in fibrous tissue.     

Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years

BACKGROUND: Fractional exhaled nitric oxide (FE NO ) is used in monitoring of asthma. OBJECTIVES: The aim of this multicenter study was to establish normal values of FE NO and assess feasibility in children with a standardized method and equipment approved for clinical use. METHODS: FE NO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. RESULTS: Measurement of FE NO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FE NO in 405 children was 9.7 ppb, and the upper 95% confidence limit was 25.2 ppb. FE NO increased significantly with age, and higher FE NO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100% from the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). CONCLUSION: FE NO in healthy children is below 15 to 25 ppb depending on age and self-reported atopy. Measurement of FE NO by NIOX is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.