Biomedical subjects

Reena Rani

Publications and source records attributed to Reena Rani.

4 recordsLinked to original sources

PubMed2006

Nucleophosmin regulates cell cycle progression and stress response in hematopoietic stem/progenitor cells.

Nucleophosmin (NPM) is a multifunctional protein frequently overexpressed in actively proliferating cells. Strong evidence indicates that NPM is required for embryonic development and genomic stability. Here we report that NPM enhances the proliferative potential of hematopoietic stem cells (HSCs) and increases their survival upon stress challenge. Both short term liquid culture and clonogenic progenitor cell assays show a selective expansion of NPM-overexpressing HSCs. Interestingly, HSCs infected with NPM retrovirus show significantly reduced commitment to myeloid differentiation compared with vector-transduced cells, and majority of the NPM-overexpressing cells remains primitive during a 5-day culture. Bone marrow transplantation experiments demonstrate that NPM promotes the self-renewal of long term repopulating HSCs while attenuated their commitment to myeloid differentiation. NPM overexpression induces rapid entry of HSCs into the cell cycle and suppresses the expression of several negative cell cycle regulators that are associated with G(1)-to-S transition. NPM knockdown elevates expression of these negative regulators and exacerbates stress-induced cell cycle arrest. Finally, overexpression of NPM promotes the survival and recovery of HSCs and progenitors after exposure to DNA damage, oxidative stress, and hematopoietic injury both in vivo and in vitro. DNA repair kinetics study suggests that NPM has a role in reducing the susceptibility of chromosomal DNA to damage rather than promoting DNA damage repair. Together, these results indicate that NPM plays an important role in hematopoiesis via mechanisms involving modulation of HSC/progenitor cell cycle progression and stress response.

Animals↗

PubMed2005

An update in recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The etiology of recurrent spontaneous abortion is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Reasonably accepted etiologic causes include, genetics, anatomical, endocrine, placental anomalies, hormonal problems, infection, smoking and alcohol consumption, exposure to environmental factors, psychological trauma and stressful life event, certain coagulation and immunoregulatory protein defects. Detection of an abnormality in any of these areas may result into specific therapeutic measures, with varying degrees of success. However, the majority of cases of RSA remains unexplained and is found to be associated with certain autoimmune (APA, ANA, ACA, ATA, AECA) and alloimmune (APCA, Ab2, MLR-Bf) antibodies that may play major role in the immunologic failure of pregnancy and may lead to abortion. Alteration in the expression of HLA-G molecules, T-helper-1 (Th-1) pattern of cytokines and natural killer (NK) cells activity may also induce abortion. Various forms of treatment like antithrombotic therapies such as aspirin and heparin, intravenous immunoglobulin (IVIg) therapy, immunotherapy with paternal lymphocytes and vitamin D3 therapy are effective mode of treatment for unexplained cause of fetal loss in women with RSA.

Abortion, Habitual↗

PubMed2003

Effect of lead exposure on the immune response of some occupationally exposed individuals.

Lead is a ubiquitous pollutant in the industrial environment, which poses serious threats to human health. In the past 20 years increasing attention has been paid to the effects of lead exposure on health. This toxic metal alters the immune response of animals as well as humans. To study the immunological effects of occupational exposure to lead, we examined lymphocyte proliferation, natural killer (NK) cell cytotoxicity and interferon-gamma production with peripheral blood mononuclear cells (PBMCs) of individuals occupationally exposed to lead. We selected three different groups of individuals exposed to lead: three-wheeler drivers (30), battery workers (34) and silver jewelery makers (20); and unexposed healthy volunteers (30) as control for comparison. Our results indicate that though lymphocyte proliferation to phytohaemagglutinin (PHA) is inhibited in lead exposed individuals as compared with unexposed volunteers, there is no correlation between inhibition of lymphocyte proliferation and blood lead level. NK cell cytotoxicity remains unaffected in individuals exposed to lead as compared with controls. On the other hand, we observed that interferon-gamma (IFN-gamma) was significantly elevated in T cell mitogen, PHA, stimulated PBMCs culture supernatant of lead exposed individuals. We found significant positive correlation between blood lead levels and IFN-gamma produced in culture supernatant on stimulation with PHA. In brief, this study demonstrates that lead can affect the immune response of the occupationally exposed individuals such as three-wheeler drivers, battery reconditioning workers and silver jewelery makers.

Cytotoxicity Tests, Immunologic↗

PubMed2003

Immunomodulation by lead.

Lead, a potential human carcinogen, is a ubiquitous environmental pollutant in the industrial environment that poses a serious threat to human health. This toxic lead can modulate the immune response of animals as well as humans. In some instances, the immune system appears to be exquisitely sensitive to lead as compared with other toxicological parameters. Both stimulation and suppression of immune response have been demonstrated in lead exposed animals and humans depending on the T helper (Th)1 vs Th2 response. Although the majority of data accumulated to date pertains to the effects of lead in small laboratory rodents, there is little reason to believe that similar quantifiable effects do not occur in domestic and food-producing animals owing to basic functional similarities of the immune system of mammals. In this review, we have discussed the immunomodulatory role of the toxic heavy metal, lead, on cellular and humoral components of the immune system with particular reference to effector cells such as B cells, T cells, natural killer (NK) cells, and soluble mediators such as cytokines, chemokines, and nitric oxide (NO).

Animals↗