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Biomedical subjects

A R Kallianpur

Publications and source records attributed to A R Kallianpur.

6 recordsLinked to original sources
PubMed2005

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

The occurrence of toxic complications following hematopoietic stem cell transplantation (HSCT) is highly variable and dependent on a multitude of host, donor, and treatment factors. The increasingly broad indications for HSCT and the need to provide this treatment option to older and/or more debilitated patients emphasizes the importance of refining our methods of predicting and ameliorating these toxicities. Late complications (occurring after day 100) also pose a threat to quality of life after HSCT. Genetic polymorphisms in key molecular pathways in the host are likely to contribute significantly to the observed variability in the development HSCT-associated complications. Hepatic veno-occlusive disease and acute lung injury, two of the most serious organ toxicities that occur, represent useful paradigms for the identification of genetic polymorphisms in enzyme systems that modulate local and systemic responses to oxidant stress during transplant conditioning therapy. Ongoing studies in this area are providing clues to the prevention of adverse clinical outcomes based on the genetic milieu. This review of studies in HSCT that explore genetic risk factors for transplant complications indicates that significant progress is being made in this rapidly evolving area. However, further large-scale clinical and translational studies are needed before genomic screening can be widely used to individualize treatment.

Alleles↗
PubMed2005

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.

Adult↗
PubMed2000

Utility of bone marrow biopsy for rapid diagnosis of febrile illnesses in patients with human immunodeficiency virus infection.

BACKGROUND: Histochemical staining of bone marrow biopsy samples for microorganisms may provide a presumptive diagnosis weeks before culture. METHODS: To identify predictors of histochemical positivity, we reviewed 161 bone marrow biopsies from febrile patients with human immunodeficiency virus (HIV) infection. RESULTS: By multivariate analysis, both hematocrit value <30% and white blood cell count <4,000/mm3 predicted biopsy positivity by culture or staining, but only anemia predicted histochemical stain positivity. Of cases with serum lactate dehydrogenase (LDH) levels >600 U/L, histoplasmosis was diagnosed in 31.6% versus 7.8% with lower LDH levels. Among histoplasmosis cases, staining showed fungi in all, with LDH levels >600 U/L versus 44.4% with lower levels. CONCLUSIONS: Bone marrow biopsy will most likely provide a rapid diagnosis in patients with anemia. Markedly elevated LDH levels suggest stain positivity for Histoplasma capsulatum. Histopathologic patterns may also guide empiric therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.

Activation of the SCL (or TAL-1) gene as a result of chromosomal translocation or deletion is a frequent molecular lesion in acute T-cell leukemia. By virtue of its membership in the basic helix-loop-helix family of transcription factors, the SCL gene is a candidate to regulate events in hematopoietic differentiation. We have used polyclonal antibody raised against a bacterial expressed malE-SCL fusion protein to characterize SCL protein expression in postimplantation embryos and in neonatal and adult mice. SCL protein was detected at day 7.5 post coitum at both embryonic and extraembryonic sites, approximately 24 hours before the formation of recognizable hematopoietic elements. Expression then localized to blood islands of the yolk sac followed by localization to fetal liver and spleen, paralleling the hematopoietic activity of these tissues during development. SCL protein was detected in erythroblasts in fetal and adult spleen, myeloid cells and megakaryocytes in spleen and bone marrow, mast cells in skin, and in rare cells in fetal and adult thymus. In addition, SCL protein was noted in endothelial progenitors in blood islands and in endothelial cells and angioblasts in a number of organs at times coincident with their vascularization. SCL expression was also observed in other nonhematopoietic cell types in the developing skeletal and nervous systems. These results show that SCL expression is one of the earliest markers of mammalian hematopoietic development and are compatible with a role for this transcription factor in terminal differentiation of the erythroid and megakaryocytic lineages. SCL expression by cells in the thymus suggests that the gene may be active at some stage of T-cell differentiation and may be relevant to its involvement by chromosomal rearrangements in T-lymphoid leukemias. Finally, expression of the gene in developing brain, cartilage, and vascular endothelium indicates SCL may have actions in neural development, osteogenesis, and vasculogenesis, as well as in hematopoietic differentiation.

Animals↗
PubMed1990

Immunoreactivity in malignant mesotheliomas with antibodies to basement membrane components and their receptors.

Ten cases of malignant mesothelioma (MM), as diagnosed by clinical history and light and electron microscopy, were studied with polyclonal antibodies directed against the basement membrane-specific proteins, type IV collagen and laminin, as well as with monoclonal antibodies which recognize two epitopes of the laminin receptor (LR). All formalin-fixed, paraffin-embedded mesothelioma tissues examined demonstrated intracytoplasmic immunoreactivity for the basement membrane proteins. Extracellular staining was minimal, analogous to the staining reactions observed in adenocarcinomas of the breast and lung, which on light microscopy mimicked the morphologic appearance of MM. Similarly, LRs were identified on MM cells by intense positive staining. Immunoreactivity was also evident on nonneoplastic mesothelioma and adenocarcinoma cells but with greater heterogeneity and less intensity. It may be concluded from these results that (a) malignant mesotheliomas have the ability to synthesize components of the basement membrane; (b) enhanced attachment to extracellular matrix by MM would be anticipated as laminin receptors are present in large numbers on the surface of mesothelioma cells; (c) the reason for lack of intensiveness by MM cells remains speculative; type IV-specific collagenase may play a role in regulating this function in these tumor cells.

Aged↗