Control and isotopic quantification of affinity of antithrombin III for heparin-like surfaces

Heparin-like materials, characterized by a defined superficial density of functional groups which activate antithrombin III (AT III), when in contact with blood specifically inhibit thrombin as soon as it appears. This paper describes an isotopic method to estimate this density and to visualize the distribution of the affinity sites concerned, both directly with AT III labelled with 125Iodine and indirectly with an anti AT III monoclonal antibody labelled with 111Indium.     

Pre-Implantation Multiple Cytokine mRNA Expression Analysis of Donor Lung Grafts Predicts Survival After Lung Transplantation in Humans

While current donor selection with clinical findings is generally effective, the imprecise nature of the assessment forces clinicians to remain on the conservative side. A reliable biological marker would assist donor selection and would improve donor organ utilization. We collected biopsies from 169 donor lungs before implantation. Expression levels of IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and IL-1beta were measured by quantitative real-time RT-PCR (qRT-PCR). Seventeen cases died within 30 days after transplantation. No donor factor was significantly associated with 30-day mortality. Univariate analysis of the 84 cases for development of the prediction model showed that IL-6, IL-8, TNF-alpha and IL-1beta were risk factors for mortality and IL-10 and IFN-gamma were protective factors. We analyzed the cytokine expression ratios of risk to protective cytokines. A stepwise logistic regression for 30-day mortality demonstrated that a model containing the ratio of IL-6/IL-10 was the most predictive (p = 0.0013). When applied to the remaining 85 cases for validation, the test of model fit was significant (p = 0.039). Using the cytokine ratio, we were able to define three risk groups with striking differences in survival (p = 0.0003). Multi-cytokine analysis of the donor lung graft with qRT-PCR shows significant promise as a strategy to biologically evaluate the donor lung prior to implantation.     

Validity and reliability of the infant Behavioral Summarized Evaluation (IBSE): A rating scale for the assessment of young children with autism and developmental disorders

The Infant Behavioral Summarized Evaluation (IBSE) is a rating scale adapted from the Behavioral Summarized Evaluation (BSE) and specifically related to the assessment of behaviors of young children having autistic disorders. Content validity and reliability studies described in the paper were made from behavior ratings of videotapes for 89 children aged from 6 to 48 months. Results show a significant group of 19 items including some characteristic early autistic behaviors (communicative and social abnormalities) and some that are less commonly described in the syndrome (attentional, perceptive, and adaptive disorders). The value of the use of this scale for clinicians and professionals involved in behavioral evaluations and treatment of young children with developmental disorders and the necessity for further psychometric investigations are discussed.This study was supported by INSERM U.316 Nervous System from the Foetus to the Child. Development, Circulation, Metabolism, L. Pourcelot, INSERM, Network INSERM No. 489001, Grant INSERM No. 911182 (D. Savrage) No. 911008 (L. Hameury) MRT. No. 9906 Fondation Langlois. Gratitude is expressed to Professor G. Lelord who initiated and supervised this study. The authors thank Professor J. Fermanian, Department of Biostatistics, CHU Necker, Paris, for his helpful suggestions and assistance. They also thank Dr. Larmande, Dr. Leddet, Dr. Glorion, and Dr. Garreau for their medical participation in the study and C. Richard, C. Fillatre, J. Rabant, and F. Etourneau for the psychological assessments of children. Special thanks to G. Calzas, M. Barré, A. Lardeux, and D. Lioret for their technical assistance.     

Prevalences of herpesviruses DNA sequences in salivary gland biopsies from primary and secondary Sj?gren's syndrome using degenerated consensus PCR primers.

BACKGROUND: Sj?gren's syndrome (SS) is an autoimmune exocrinopathy associated with multiple autoantibodies, lymphocyte infiltration of various organs, and functional deficiency of T cells. Several viruses have been implicated by PCR based studies, but their contribution to the pathophysiology of SS is still controversial. OBJECTIVES: In an attempt to explore the presence of human herpesviruses DNA sequences in salivary glands biopsies from patients suffering of SS, a recently developed strategy based on PCR with consensus degenerated primers that allowed to detect known and eventually unknown herpesviruses was used. STUDY DESIGN: Salivary glands biopsies from 55 patients suffering of primary and SS syndrome were explored by herpesviruses consensus PCR primers and all the PCR products were sequenced. RESULTS: Nine out of 55 salivary glands were positive by PCR and sequence analyses allowed to identify Epstein-Barr virus (EBV) in 6 cases and herpes simplex virus (HSV)-1 in 3 cases. We did not detect any sequences that could be related to a new herpesvirus. CONCLUSION: In view of the good sensitivity of the technique used, our study is not consistent with SS being associated with an unknown herpesvirus. However, our results suggest that EBV and HSV-1 could be implicated in a subset of SS cases and this possibility needs to be explored, to assess the potential benefit of antiviral drugs in some cases.     

Superficial angiomyxoma: report of four cases, including two subungueal tumors

We report four cases of superficial angiomyxomas, including two cutaneous tumors and two subungueal tumors. Histological analysis revealed a recently described tumor, so called superficial angiomyxoma. This is a myxoid paucicellular tumor lobulated and poorly circumbscribed, containing numerous small blood vessels surrounded by a mixed inflammatory cell infiltrate with notable neutrophils. Those tumors are positive for CD34. The differential diagnosis includes myxoid neurothecoma, myxoid neurofibroma and, for ungueal tumors, superficial acral fibromyxoma.     

Hearing impairment as an early sign of alpha‐mannosidosis in children with a mild phenotype: Report of seven new cases

Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDE^R) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.     

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.     

Pre- and postnatal depression and coping: a comparative approach

BACKGROUND: The assessment of perinatal depressions and coping style. Methods: With depression scales (EPDS, GHQ.12) and Carver's BriefCope, the authors compared the prevalence rates of pre and postnatal depression in a cohort of 277 French women. RESULTS: Their work revealed very high levels of prenatal depression (almost 20%) and less important but nonetheless sizeable rates (11%) of postnatal depression, making such perinatal depressions a major public health concern. The coping styles proposed in Carver's public health BriefCope questionnaire make it possible to significantly differentiate during these two periods between depressive women and their non-depressed counterparts. CONCLUSIONS: This enables us to underline factors of risk and protection suggesting the importance of setting up compensatory and preventive systems and evaluating their pertinence in the framework of future research.     

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.