Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells

Recent studies have demonstrated that Apaf-1 is the adaptor molecule which in the presence of cytosolic cytochrome c (cyt c) and dATP interacts with procaspase-9, resulting in the sequential cleavage and activity of caspase-9 and caspase-3, followed by apoptosis. In the present studies, we determined the effect of enforced overexpression of Apaf-1 on the apoptotic threshold in the human myeloid leukemia HL-60 cells. Our findings demonstrate that both transient and stable transfections resulted in a 2.5-fold higher expression of Apaf-1, which was associated with approximately a 5-fold increase in the percentage of apoptosis in the transfectants (HL-60/Apaf-1) as compared with the control HL-60/neo cells. In cells overexpressing either Bcl-2 or Bcl-xL, transient overexpression of Apaf-1 did not induce apoptosis. Stably overexpressing Apaf-1 levels significantly sensitized HL-60/Apaf-1 cells to apoptosis induced by clinically achievable concentrations of paclitaxel or etoposide (P < 0.01). This increase in paclitaxel- or etoposide-induced apoptosis of HL-60/Apaf-1 cells was not associated with any significant alterations in Bcl-2, Bcl-xL, Bax, Fas, or Fas ligand expression. It was, however, clearly associated with caspase-9 cleavage, as well as the poly(ADP-ribose) polymerase and DFF45 cleavage activity of caspase-3. Coexpression of the catalytically inactive, dominant-negative, mutant caspase-9, XIAP, or treatment with the caspase inhibitor, zVAD, significantly inhibited the increase in apoptosis of HL-60/Apaf-1 cells (P < 0.01). These data indicate that the intracellular levels of Apaf-1 is an important molecular determinant of the threshold for apoptosis induced by paclitaxel and etoposide.     

Postpartum amenorrhoea in rural eastern Uttar Pradesh, India

This paper calculates the mean duration of the postpartum amenorrhoea (PPA) and examines its demographic, and socioeconomic correlates in rural north India, using data collected through 'retrospective' (last but one child) as well as 'current status' (last child) reporting of the duration of PPA. The mean duration of PPA was higher in the current status than in the retrospective data; the difference being statistically significant. However, for the same mothers who gave PPA information in both the data sets, the difference in mean duration of PPA was not statistically significant. The correlates were identical in both the data sets. The current status data were more complete in terms of the coverage, and perhaps less distorted by reporting errors caused by recall lapse. A positive relationship of the mean duration of PPA was found with longer breast-feeding, higher parity and age of mother at the birth of the child, and the survival status of the child. An inverse relationship was found with higher education of a woman, higher education of her husband and higher socioeconomic status of her household, these variables possibly acting as proxies for women's better nutritional status.     

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function

N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where it is concentrated in the cytosol. Although NAA is devoid of neurophysiological effects, it serves as an acetyl donor, an initiator of protein synthesis or a carbon transfer source across the mitochondrial membrane. The concentration of NAA in human brain increases 3-fold between midgestation and adulthood. In Canavan's Disease, an autosomal recessive disorder due to a null mutation in amino acylase II, NAA levels in brain are markedly increased and disrupt myelination. NAA levels have been found to be reduced in neurodegenerative disorders, including Alzheimer's Disease and Huntington's Disease. Since endogenous NAA can be readily detected in human brain by magnetic resonance spectroscopy, it is increasingly being exploited as a marker for functional and structural integrity of neurons in an expanding number of disorders.     

Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTalpha-, and LTbeta-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.     

Acute upper limb ischemia resulting from cleidocranial dysostosis

A case is reported of a woman with an ischemic arm as a result of damage to the subclavian artery by the clavicular anomaly associated with cleidocranial dysostasis. Only one similar case has been reported previously.     

Inhibition of proliferation and expression of T-antigen in SV40 large T-antigen gene-induced immortalized cells following transplantations

In this paper the Authors reviewed the recent literature for a more comprehensive and clear vision of the epidemiological and pathological aspects of retroperitoneal sarcomas. The most effective procedures for a an early and accurate diagnosis were identified. Moreover, the different therapeutic choices were taken into account focusing on those provided of the major potential in terms of oncologically valid treatment.     

Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy?

Monoclonal antibodies which recognize antigenic determinants expressed by T-cells and Ig-bearing cells, respectively, allowed lymphocyte subpopulations involved in allograft rejection of muscle transplants to be identified in the teleost fish Dicentrarchus labrax (L.). The monoclonal antibody DLT15 first allowed recognizing T-cells involved in an in vivo antigen-driven cellular response in teleosts. Immunohistochemical studies showed a high density of lymphocytes in allografts and provided evidence of predominance of T-cells. The heterogeneity of the cell populations recognized by the antibodies was evidenced by the different size, cytology, and staining patterns of T-cells and Ig-bearing cells.