PubMed Health⌕ Search

Biomedical subjects

Shimon Moses

Publications and source records attributed to Shimon Moses.

6 recordsLinked to original sources
PubMed2003

Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter.

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT). In addition to disrupted glucose homeostasis, GSD-Ib patients have unexplained and unexpected defects in neutrophil respiratory burst, chemotaxis and calcium flux, in response to the bacterial peptide f-Met-Leu-Phe, as well as intermittent neutropenia. We generated a G6PT knockout (G6PT-/-) mouse that mimics all known defects of the human disorder and used the model to further our understanding of the pathogenesis of GSD-Ib. We demonstrate that the neutropenia is caused directly by the loss of G6PT activity; that chemotaxis and calcium flux, induced by the chemokines KC and macrophage inflammatory protein-2, are defective in G6PT-/- neutrophils; and that local production of these chemokines and the resultant neutrophil trafficking in vivo are depressed in G6PT-/- ascites during an inflammatory response. The bone and spleen of G6PT-/- mice are developmentally delayed and accompanied by marked hypocellularity of the bone marrow, elevation of myeloid progenitor cell frequencies in both organs and a corresponding dramatic increase in granulocyte colony stimulating factor levels in both GSD-Ib mice and humans. So, in addition to transient neutropenia, a sustained defect in neutrophil trafficking due to both the resistance of neutrophils to chemotactic factors, and reduced local production of neutrophil-specific chemokines at sites of inflammation, may underlie the myeloid deficiency in GSD-Ib. These findings demonstrate that G6PT is not just a G6P transport protein but also an important immunomodulatory protein whose activities need to be addressed in treating the myeloid complications in GSD-Ib patients.

Animals↗
PubMed2002

Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1.

UNLABELLED: Life expectancy in glycogen storage disease type 1 (GSD-1) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and therefore experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on data from the European Study on Glycogen Storage Disease Type 1, discussions within this study group together with those at the International SHS Symposium 'Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome', Fulda, Germany (2000) and on data from the literature, a series of guidelines were drawn up. CONCLUSION: the following guidelines for the management of patients with glycogen storage disease type 1b are in addition to those general guidelines for glycogen storage disease type 1 and address specific problems related to neutropenia and neutrophil dysfunction.

Glycogen Storage Disease Type I↗
PubMed2002

Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1.

UNLABELLED: Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in GSD-1b, a retrospective registry of GSD-1 patients born between 1960 and 1995 in 12 European countries was established. Included were 57 GSD-1b patients. Unglycosylated GCSF was given to 18 patients, median age of starting therapy was 8 years, longest duration of therapy 7 years. Dose varied between 2-10 micro g/kg, with a frequency from daily to twice per week. Neutropenia (defined as an absolute neutrophil count <0.5 x 10(9)/l) was found in 49 patients. In untreated patients, a significant decrease of haemoglobin, platelet counts and leucocyte counts with increasing age ( P<0.032, P<0.04 and P<0.001 respectively) was noted, whereas neutrophil counts remained low but stable with increasing age. In nine patients who were treated longer than 1 year, median neutrophil counts increased significantly and simultaneously median leucocyte counts and platelet counts decreased significantly. In all patients treated, the number and severity of infections decreased and the severity of IBD improved subjectively. The most serious complication of GCSF treatment was marked splenomegaly (four patients). CONCLUSION: in this retrospective study a significant haematological effect was documented and a subjective improvement of infections and inflammatory bowel disease. In view of the uncertainty, prospective controlled trials seem warranted to clarify the indication for the use of granulocyte colony-stimulating factor in this disease.

Child↗
PubMed2001

The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome.

We report a total of 23 novel mutations of the SLC2A2 ( GLUT2) gene in 49 patients with a clinical diagnosis of Fanconi-Bickel syndrome (FBS). Molecular genetic analysis has now been performed in more than 50% of the 109 FBS cases from 88 families that we have been able to locate world-wide since the original report in 1949. In these 49 patients, 33 different SLC2A2 mutations (9 missense, 7 nonsense, 10 frameshift, 7 splice-site) have been detected. Thus, our results confirm that mutations of SLC2A2 are the basic defect in patients with FBS. Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time. Mutations were also found in patients with atypical clinical signs such as intestinal malabsorption, failure to thrive, the absence of hepatomegaly, or renal hyperfiltration. No single prevalent SLC2A2 mutation was responsible for a significant number of cases. In a high percentage (74%) of FBS patients, the mutation is homozygous, so we conclude that the prevalence of SLC2A2 mutations is relatively low in most populations. No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected.

Alternative Splicing↗