Biomedical subjects

T Zenz

Publications and source records attributed to T Zenz.

11 recordsLinked to original sources

PubMed2004

hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies.

The family of immune associated nucleotide binding proteins (Ian) is a distinct family of GTP-binding proteins conserved in plants, mice, rats and humans that are associated with immune functions, suggesting involvement in conserved defense mechanisms. Recently, the rat Ian4 (rIan4) was cloned and it appears to be identical to the gene Iddm1/lyp responsible for severe lymphopenia and the development of insulin-dependent diabetes in the BB-DP rat. Here we describe the characterization of a new human member of the Ian family: hIan5. hIan5 is highly homologous to rIan4, has a predicted molecular weight of 35 kDa and contains distinct G motifs of GTP-binding proteins (G-1 to G-4) in the N-terminus. Human Ian5 is anchored to the mitochondria by the hydrophobic COOH-terminal domain. Human Ian5 is highly expressed in lymph node and spleen. Different blood fractions show high hIan5 expression in CD4- and CD8-positive T cells and monocytes, but not in B lymphocytes. In contrast, in B-CLL (chronic lymphocytic leukemia) and mantle cell lymphoma samples, hIan5 mRNA was upregulated. The current data underline the role of hIan5 in T-lymphocyte development and function, and for the first time suggest that upregulation of Ian proteins is associated with B-cell malignancy, possibly by inhibiting apoptosis.

Amino Acid Sequence↗

PubMed2003

Transfusion-free reduced-intensity conditioned allogeneic stem cell transplantation in a Jehovah's witness.

With an estimated 6000000 Jehovah's witnesses worldwide, haematologists may encounter patients who decline blood transfusions as a matter of personal belief. Here, we describe the first case of a transfusion-free allogeneic stem cell transplant (SCT) in a Jehovah's witness with CML. The patient underwent HLA-identical peripheral blood SCT after reduced-intensity conditioning with total body irradiation and fludarabine. Conditioning and the period after transplantation were uneventful, complete donor chimerism was achieved and the patient continues to be in molecular remission without significant chronic graft-versus-host disease. When treating Jehovah's witnesses with diseases that may be cured by allogeneic SCT, this approach should be kept in mind.

Adult↗

PubMed2001

Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity.

Using the representation difference analysis technique, we have identified a novel gene, Ian4, which is preferentially expressed in hematopoietic precursor 32D cells transfected with wild-type versus mutant forms of the Bcr/Abl oncogene. Ian4 expression was undetectable in 32D cells transfected with v-src, oncogenic Ha-ras or v-Abl. Murine Ian4 maps to chromosome 6, 25 cM from the centromere. The Ian4 mRNA contains two open reading frames (ORFs) separated by 5 nt. The first ORF has the potential to encode for a polypeptide of 67 amino acids without apparent homology to known proteins. The second ORF encodes a protein of 301 amino acids with a GTP/ATP-binding site in the N-terminus and a hydrophobic domain in the extreme C-terminus. The IAN-4 protein resides in the mitochondrial outer membrane and the last 20 amino acids are necessary for this localization. The IAN-4 protein has GTP-binding activity and shares sequence homology with a novel family of putative GTP-binding proteins: the immuno-associated nucleotide (IAN) family.

Amino Acid Sequence↗

PubMed2001

Severe veno-occlusive disease after allogeneic bone marrow or peripheral stem cell transplantation--role of transjugular intrahepatic portosystemic shunt (TIPS).

AIMS: Veno-occlusive disease of the liver is a severe complication of allogeneic bone marrow or peripheral stem cell transplantation with a high mortality. In its severe form, the portal vein is used as an outflow tract for the arterial hepatic perfusion. A portosystemic side-to-side shunt, e.g. a transjugular intrahepatic portosystemic shunt, may facilitate portal outflow thus increasing hepatic (i.e. arterial) perfusion. METHODS: The effect of a transjugular shunt on liver function and blood flow was studied in three patients receiving shunt treatment 0-2 days after the diagnosis of severe veno-occlusive disease occurring 28, 20, and 17 days after allogeneic transplantation for acute myeloid leukemia, Hodgkin's disease and chronic myeloid leukemia, respectively. RESULTS: The transjugular shunt reduced the portosystemic pressure gradient from 23 to 8, 18 to 5, and 33 to 13 mmHg in patients 1, 2, and 3, respectively, increased the stagnant portal vein flow to normal, and decreased the arterial resistive index, indicating an increase in the arterial perfusion of the liver. This was accompanied by rapid relief from abdominal pain and removal of ascites. The AST concentration dropped from 1230, 417, and 2930 U/l before to 93, 20, and 41 U/l and the PT-time ratio improved 3-7 days after shunt treatment while the bilirubin concentration continued to rise until the patients died 26, 42, and 33 days after transplantation from multiorgan failure (two patients) or intracerebral hemorrhage. CONCLUSIONS: The transjugular shunt may have improved abdominal and hepatic perfusion and prevented further necrosis of hepatocytes. It did not, however, affect jaundice or survival, which was limited by extrahepatic complications.

Adult↗

PubMed2000