Siblings with Imperforate anus and aplastic nasal alae: Johanson-Blizzard syndrome

Johanson-Blizzard syndrome is a rare genetic entity reported in medical literature resulting from mutations in UBR1 gene, affecting pancreas, craniofacial and urogenital development, causing significant morbidity and mortality. We report a neonate presenting with anorectal malformation requiring surgical intervention at birth, with similar surgeries being performed in two elder siblings. Surviving sibling of the proband neonate also has similar dysmorphic features of absent ala nasi, aplasia cutis of scalp along with pancreatic insufficiency, profound sensorineural hearing loss, pheno-type corresponding to Johanson-Blizzard syndrome. Syndromic diagnosis helps in screening for associated potential issues, which can intervened at early stages.

Co-Inocula Assays of Yeasts with “Killer” Pheno-Type and Sensitive Strains of Saccharomyces cere-visiae with Defects in Mannoprotein Synthesis

Yeast mannoproteins have been thoroughly studied in recent years due to their contribution to different properties of wines. Our working group has the aim to establish the possible relationship between the structure of the mannoprotein (size and charge) and its effect on wines. For this, we have different non-transgenic mutants that synthesize mannoproteins with altered but known structures (mnn mutants). We have constructed double mutants with each of the available single mutants, thus obtaining a very diverse collection of mannoproteins that differ in size and charge. Since the mutants are unable to complete wine fermentations satisfactorily, an alternative is to grow mutants in the laboratory, purify their mannoproteins and add them later to wines. Another option would be to use co-inocula of the mentioned mutants, together with “killer” wine yeast strains capable of killing the mutants. In this work, experiments were carried out to determine the behavior of different “killer” wine strains with each one of the defective mutants in mannoprotein synthesis. The yeast Torulaspora delbrueckii Killer (Kbarr1) has been proved to be especially suitable for making this type of co-inoculum.

Pathophysiologic significance of procoagulant microvesicles in cancer disease and progression

SummaryMicrovesicles (MV) are submicrometric membrane fragments (0.1 to 1 μm), released from the plasma membrane of activated or apoptotic cells. They are characterized by most of the antigenic profile of the cells they originate from, and by the presence of procoagulant phospholipids at their surface. MV are detectable in the peripheral blood of mammals and considered as efficient effectors in the haemostatic or thrombotic responses, able to remotely initiate or amplify beneficial or deleterious processes, depending on the circumstances. Variations in their level and pheno-type make them relevant pathogenic markers of thrombotic disorders and vascular damage. To date, MV are recognized as mediators of communication allowing cells to influence a target present in the local microenvironment as well as to at distant sites. The mechanisms by which MV interact with target cells are still unclear, but a number of studies suggest involvement of MV-cell fusion or ligand-receptor interactions. More importantly, MV have been shown implicated in horizontal transfer of genetic material. This review focuses on the role of MV in the context of cancer, and their possible part in cancer associated thrombosis.

Caribou recovery and coexistence with introduced feral reindeer on the Nuussuaq Peninsula (70-71°N), West Greenland

The small native caribou population (Rangifer tarandus groenlandicus) of Nuussuaq Peninsula was supplemented in 1968 with 10 semi-domestic reindeer (Rangifer tarandus tarandus). Hunting was prohibited in the early 1990s, but resumed with a quota of 100 animals in 1996 after the population was estimated to be around 400. Despite local criticism that herd size had increased, managers kept the estimate unchanged and permitted similar quotas for the next 5 years. To ascertain current status of the population, a late winter ground survey for minimum count, recruitment and distribution was done in April 2002 employing local hunters. Data collected included group size, location and animal sex/age. Only two age classes were used; calf (<1 year) and "adult" (>1 year). The 2002 ground survey observed 1164 individuals and a calf percentage of approximately 30%. The bull to cow ratio was 0.32. This data did not allow a calculation of population size, because areas where maximum animal numbers were expected were preferentially sampled. Spatial segregation of these two subspecies is suggested, given the observed and unexpected dissimilar behavior, pheno-type and spatial distribution. If true, then by 2002 feral reindeer had established a successful population, while native caribou had recovered to number several hundred. Genetic sampling is necessary to examine this hypothesis. At current late winter recruitment rates animal density could increase rapidly making both range expansion and genetic mixing likely in future. Since the total non-ice covered area available is about 6000 km2, greater caribou/reindeer densities may not be compatible with sustainable range use. Harvest quotas were increased in 2002 and 2003, and may reduce densities and preserve caribou range for the future.

Anemia, thrombocytopenia, leukocytosis, extramedullary hematopoiesis, and impaired progenitor function in Pten+/-SHIP-/- mice: a novel model of myelodysplasia

The myeloproliferative disorder of mice lacking the Src homology 2 (SH2)-containing 5′ phosphoinositol phosphatase, SHIP, underscores the need for closely regulating phosphatidylinositol 3-kinase (PI3K) pathway activity, and hence levels of phosphatidylinositol species during hematopoiesis. The role of the 3′ phosphoinositol phosphatase Pten in this process is less clear, as its absence leads to embryonic lethality. Despite Pten heterozygosity being associated with a lymphoproliferative disorder, we found no evidence of a hematopoietic defect in Pten+/- mice. Since SHIP shares the same substrate (PIP3) with Pten, we hypothesized that the former might compensate for Pten haploinsufficiency in the marrow. Thus, we examined the effect of Pten heterozygosity in SHIP-/- mice, predicting that further dysregulation of PIP3 metabolism would exacerbate the pheno-type of the latter. Indeed, compared with SHIP-/- mice, Pten+/-SHIP-/- animals developed a myelodysplastic phenotype characterized by increased hepatosplenomegaly, extramedullary hematopoiesis, anemia, and thrombocytopenia. Consistent with a marrow defect, clonogenic assays demonstrated reductions in committed myeloid and megakaryocytic progenitors in these animals. Providing further evidence of a Pten+/-SHIP-/- progenitor abnormality, reconstitution of irradiated mice with marrows from these mice led to a marked defect in short-term repopulation of peripheral blood by donor cells. These studies suggest that the regulation of the levels and/or ratios of PI3K-derived phosphoinositol species by these 2 phosphatases is critical to normal hematopoiesis. (Blood. 2004;103:4503-4510)

Immunologic factors in primary progressive multiple sclerosis

Primary progressive multiple sclerosis (PPMS) is clinically character ized by progression without remission or relapse, in contrast to relapsing forms of MS. Pathologic and imaging findings also indicate that PPMS differs from relapsing forms. Recent studies examining potential immunologic differences among MS forms suggest that cytokine and adhesion molecule expression profiles, but not chemokine recepto r profiles, in PPMS patients resemble those in healthy controls more than those in patients with relapsing MS. However, the significance of these findings remains to be fully elucidated, and there is little additional evidence as yet of marked differences among MS forms based on immunologic characteristics. O f interest are the recent demonstrations that activated immune cells produce brain-derived neurotrophic factor (BDNF), a neuroprotective factor, in MS lesions, that BDNF receptors are located in MS tissue, and that glatiramer acetate (GA)-specific T cells produce BDNF irrespective of T helper cell Th1 or Th2 pheno type. These findings both support the concept of a protective inflammation in MS and suggest an additional mechanism of action for the clinical effects of G A therapy in MS. Whether and to what extent this mechanism is present in different MS forms remain to be clarified.

Duchenne's/Becker's muscular dystrophy: Analysis of genotype-feno-type correlation in 28 patients

Duchenne's and Becker's muscular dystrophy (DMD & BMD) is a X linked disease caused by mutations in the dystrophic gene. DMD is the malign form of the disease, which significantly shortens the lifetime of the patient, while BMD has late onset with slow progression. Sixty five percent of DMD and BMD cases are caused by deletion of one or more exons in the dystrophic gene, while duplications cause these diseases in 6 to 7% of the cases. There are two hot spots for deletions and duplications. These are exons in the proximal part of the gene (3rd to 18th) and exons of a distal part of the gene (45th to 52nd). The remaining 30% of DMD and BMD cases are caused by point mutations, small deletions or inversions in the dystrophic gene. The correlation between School of Medicine, University of Belgrade, Belgrade the severity of the disease and the position of deletion shows that most of the out of frame deletions cause DMD phenotype, while in frame deletions result in BMD pheno-type. We report on the results of 28 non-related DMD and BMD patients. In 57% of cases deletions were detected and all were found in the distal hot spot of the gene. These results suggest that in most of the cases, out of frame deletions produce DMD phenotype while in frame deletions result in BMD phenotype. This is in compliance with data from literature.