Cross-linking of surface IgM or IgD causes differential biological effects in spite of overlap in tyrosine (de)phosphorylation profile.

Although displaying similar amounts of surface IgM and IgD, ECH 408-1 cells only succumb to apoptosis after cross-linking of IgM (not IgD), suggesting that different signaling pathways couple to both receptors. Immunoprecipitation studies revealed the presence of several proteins selectively associated with IgM and IgD, thus ruling out that the lack of inhibitory signaling mediated by IgD might be due to membrane expression in the absence of associated proteins belonging to the B cell receptor complex. 32P metabolic labeling and immunoprecipitation studies demonstrated that IgM and IgD are associated with phosphoproteins of 32-33 kDa in an isotype-specific fashion. Kinetic analyses of tyrosine kinase activity showed that cross-linking of surface IgM or IgD resulted in the rapid (1-3 min) phosphorylation of several protein substrates on tyrosine residues, followed by a dephosphorylation step. Isotype-specific changes of the phosphorylation status specifically affected molecules in the 32-33 kDa range, i.e. IgM (not IgD) cross-linking affected a approximately 32-kDa protein, whereas IgD (not IgM) cross-linking induced phosphorylation of a protein exhibiting a slightly lower mobility (33 kDa). These results suggest that isotype-specific immunoglobulin-associated molecules could be involved in the second messenger cascade leading to different biological effects upon IgM and IgD cross-linking.     

Medullary control of the pontine swallowing neurones in sheep

Summary The origin of the inputs from the medullary swallowing centre (dorsal region including the nucleus of the solitary tract, or ventral region corresponding to the reticular formation surrounding the nucleus ambigous) to the pontine swallowing neurones (PSNs) was studied in sheep anaesthetized with halothane.Out of 101 PSNs located in the posterior part of the trigeminal (Vth) motor nucleus, 46 were activated by stimulating either the dorsal (21 neurones) or the ventral (25 neurones) region of the ipsilateral medullary swallowing centre, 3–4 mm rostral from the obex. Thirty-one neurones out of the 46 were identified as a motoneurones supplying swallowing muscles (mylohyoïd, anterior body of digastric and medial pterygoïd). Their average activation latency through stimulation of the dorsal medullary region was about 1 ms longer than through stimulation of the ventral region (3.63 ms±0.81 versus 2.72 ms±0.32).To determine the origin of the medullary input to the PSNs, we tried to activate the medullary swallowing neurones (MSNs) antidromically through stimulating the posterior part of the Vth motor nucleus, which contains the swallowing motoneurones. Seventy-three MSNs were tested (25 located in the dorsal and 48 in the ventral region). None of the dorsal neurones tested could be antidromically activated by pontine stimulation: 15 ventral neurones showed a clear antidromic response (collision test) with an average latency of 2.5 ms±0.73. These neurones, which send their axons into the pons, were all located in the reticular formation, above the nucleus ambiguus, 3–4 mm rostral from the obex.These results suggest that MSNs in the ventral reticular formation connect the medullary swallowing centre to the Vth motor nucleus. They also suggest that during swallowing, inputs originating from the dorsal region of the medullary centre (interneurones programming the motor sequence) are relayed in the ventral region (reticular formation adjacent to the nucleus ambiguus) before reaching the PSNs.This work was supported, in part, by grants from CNRS (LA 205), INRA and M.R.I. (82 E 0685)     

Cenani–Lenz syndrome and other related syndactyly disorders due to variants in LRP4, GREM1/FMN1, and APC: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways

Cenani–Lenz (C–L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the LRP4 gene. Currently, the syndrome carries one OMIM number (212780). However, C–L syndrome‐like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis/phalangeal disorganization are also known to be associated with specific LRP4 mutations, adenomatous polyposis coli (APC) truncating mutations, genomic rearrangements of the GREM1‐FMN1 locus, as well as FMN1 mutations. Surprisingly, patients with C–L syndrome‐like phenotype caused by APC truncating mutations have no polyposis despite the increased levels of β catenin. The LRP4 and APC proteins act on the WNT (wingless‐type integration site family) canonical pathway, whereas the GREM‐1 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C–L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating APC mutations and compare these mutations to the splicing APC mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.     

Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects

Background

Hemihyperplasia (hemihypertrophy) is defined as asymmetric body overgrowth of one or more body parts. Hemihyperplasia can be isolated or be part of well-defined syndromes such as in the case of Beckwith-Wiedemann syndrome (BWS). Isolated hemihyperplasia is usually sporadic, but a number of familial occurrences have been described.

Case presentation

We describe a Tunisian family in which three maternal cousins and their maternal grandfather present with isolated hemihyperplasia.

Conclusions

The etiology of isolated hemihyperplasia is unknown although in BWS, genomic imprinting has been shown to play a role in the asymmetric overgrowth. Given the similarity between these two conditions, it is possible that both may share a common pathogenesis. We also discuss the possible genetic mechanisms leading to the production of hemihyperplasia in this family.     

Role of Periductal and Ductular Epithelial Cells of the Adult Rat Pancreas in Pancreatic Hepatocyte Lineage: A Change in the Differentiation Commitment

Development of pancreatic hepatocytes in adult rats maintained on copper deficient diet containing 0.6% trien (CuDT) has been reported recently. To elucidate the histogenesis of hepatocytes a sequential study was undertaken using morphologic, histochemical, immunochemical, in situ hybridization, and Northern blot analysis. Male F-344 rats weighing 80 to 90 g were fed CuDT for 8 weeks and returned to normal rat chow. Beginning from 4 weeks of copper depletion, there was a progressive loss of acinar cells and by 8 weeks more than 90% of the acinar tissue was lost. During this period, there was an increase in the number of adipocytes in the interstitium, and in the number of interstitial and ductular cells. Morphologic observations were confirmed by immunoblot and Northern blot analysis, in which the amount of pancreatic proteins and their mRNAs decreased between 5 and 8 weeks. During this period, a progressive increase in the level of albumin mRNA was observed. In situ hybridization, performed at 7 weeks of copper deficiency, showed localization of albumin mRNA over interstitial and ductular cells. Pancreatic hepatocytes were identified immediately after the rats were returned to a normal diet and gradually increased in number. The hepatocytes occupied almost 60% of the pancreatic volume by 8 weeks. During the early recovery phase, hepatocytes were identified in ductules as well as in the interstitium. Based on these studies, it is concluded that both the ductular cells and interstitial cells, which resemble oval cells of liver, are capable of transforming into pancreatic hepatocytes and these cells may be considered stem-cell equivalent.     

Intraspecific density-dependent effects on growth and fecundity of <Emphasis Type="Italic">Diplosentis nudus</Emphasis> (Harada, 1938) Pichelin et Cribb, 2001 (Acanthocephala,Cavisomidae)

During June and July of 2007, a total of 130 specimens of the fish Rastrelliger kanagurta Cuvier (Teleostei, Scombridae), ranging between 19–31 cm in total length, were caught in the Red Sea off the coast of Sharm El-Sheikh, South Sinai, Egypt, and examined for infections by acanthocephalans (65 fish/month). Of this number, 29 (22.30%) were slightly or heavily parasitized by the acanthocephalan Diplosentis nudus (Harada, 1938) Pichelin et Cribb, 2001 (Cavisomidae); no other helminth parasites were found in the intestine of R. kanagurta. Twenty-nine infrapopulations of D. nudus, ranging from 23–218 individuals were collected from the infected fishes. These infrapopulations were distributed in a well-defined fundamental niche along the intestine of R. kanagurta, where the distribution of male worms was not random with respect to female worms size and position and suggests that the male-male competition for access to female may be intense and may select for large males. No correlation between fish size and infrapopulation size was observed. Correlations between female-to-male sex ratio and infrapopulation size, numbers of females and their mean lengths, numbers of males and their mean lengths, mean female length and mean male length within infrapopulation were very strong, and clearly suggest that as the infrapopulation size increased, the number of females and their mean lengths decreased and the number of males and their mean lengths increased. Combination of these results strongly suggests density-dependent effects and competition between male worms. The relationship between the mean female length or size and the number of eggs within its pseudocoel was strongly positive; egg production by female worm significantly decreases as the infrapopulation size increases, suggesting density-dependent reduction in female worm fecundity. Tendency for the variability in male testes size was not significant in infrapopulations of D. nudus. All of these results are discussed.     

Kenny–Caffey syndrome: an Arab variant?

We describe 2 unrelated Bedouin girls who met the criteria for the diagnosis of Kenny-Caffey syndrome. The girls had some unusual features--microcephaly and psychomotor retardation--that distinguish the Kenny-Caffey syndrome profile in Arab children from the classical Kenny-Caffey syndrome phenotype characterized by macrocephaly and normal intelligence. The 2 girls did not harbor the 22q11 microdeletion (the hallmark of the DiGeorge cluster of diseases) that we previously reported in another Bedouin family with the Kenny-Caffey syndrome (Sabry et al. J Med Genet 1998: 35(1): 31-36). This indicates considerable genetic heterogeneity for this syndrome. We also review previously reported 44 Arab/Bedouin patients with the same profile of hypoparathyroidism, short stature, seizures, mental retardation and microcephaly. Our results suggest that these patients represent an Arab variant of Kenny-Caffey syndrome with characteristic microcephaly and psychomotor retardation. We suggest that all patients with Kenny-Caffey syndrome should be investigated for the 22q11 microdeletion. Other possible genetic causes for the Kenny-Caffey syndrome or its Arab variant include chromosome 10p abnormalities.     

Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

BACKGROUND: Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. OBJECTIVES: Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. STUDY DESIGN: During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. RESULTS: Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. CONCLUSIONS: The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.