Susceptibility to DNA damage induced by antibiotics in lymphocytes from malnourished children

Infectious disease and malnutrition in children are public health problems in developing countries. Malnutrition is associated with higher levels of DNA damage, and this increased damage could be due to different factors, including the possibility that cells from malnourished children could be more susceptible to environmental damage. The aim of the present study was to evaluate the susceptibility of lymphocytes from malnourished children to DNA damage induced by antibiotics by using the comet assay. The same group of malnourished infected children were studied before and after a treatment period, and compared to a group of well-nourished infected children. Results showed that before and after drug treatment, tail length migration was two times greater in malnourished than in well-nourished children. The proportion of cells with high damage was also increased in malnourished children. Additionally in well-nourished and malnourished children, a cell subpopulation (non-damaged cells) more resistant to DNA damage induced by antibiotics was observed; this was more prevalent in the well-nourished children. Meanwhile, in malnourished children, a cell population seems to be more susceptible and reaches higher levels of DNA damage. This might help explain the impaired immune response observed in malnourished children. The increased DNA migration and the increased proportion of cells with higher levels of damage seem to indicate that malnourished children are more susceptible to DNA damage induced by drugs.     

T-cell epitopes in variable segments of Chlamydia trachomatis major outer membrane protein elicit serovar-specific immune responses in infected humans

We previously identified 18 stimulatory Chlamydia trachomatis major outer membrane protein (MOMP) peptides containing at least 23 epitopes presented with various HLA class II allotypes. Only one peptide contained an epitope localized in a variable segment (VS2). Continued studies reported here identified a total of five VS peptides containing T-cell epitopes that are distributed among MOMPs VS1, VS2, and VS4. Only MOMP-primed T-cell cultures from subjects infected with serovar E responded to the serovar E VS peptides, while the response of such cultures to constant-segment peptides was independent of the infecting serovar. Furthermore, MOMP-primed T cells proliferated in response only to the VS peptides encoded in serovar E but not to the corresponding peptides derived from serovar F, I, or J, confirming that these responses were serovar specific.     

Lectin histochemistry on the dorsal epidermis of the Breton dog

Expression of sugar residues and the nature of oligosaccharide linkage during keratinocyte maturation in the epidermis of the Breton dog were studied with the use of lectin histochemistry. Thirteen lectins were used. Labelling was not observed with GSA I-B4, GSA II, UEA-I, and LTA. The cytoplasm of keratinocytes reacted with PNA, HPA, Con A, and WGA from the basal layer to the granular layer. PNA and Con A showed highest reactivity in the granular cell layer. The cell surface showed increased reactivity with PNA, HPA, and WGA with maturation of keratinocytes. KOH-neuraminidase treatment (KOH-Neu) increased PNA and RCA120 staining during keratinocyte differentiation thus indicating an increase in oligosaccharides terminating with sialic acid-Galbeta(1,3)GalNAc and sialic acid-Galbeta(1,4)GlcNAc, respectively. Labelling of the glycocalyx of basal and spinous keratinocytes with SNA and MAA revealed terminal Neu5acalpha(2,6)Gal/GalNAc and Neu5acalpha(2,3)Galbeta(1,4)GlcNAc. KOH-Neu-DBA showed oligosaccharides terminating with sialic acid-GalNAcalpha(1,3)GalNAc in the spinous and granular layers. A selective glycocalyx labelling of granular keratinocytes was observed with DBA and SBA. Reactions with MAA, PNA, DBA, RCA120, SBA, HPA, and WGA disappeared after the beta-elimination reaction. Our findings indicate that Breton dog epidermis contains more O-linked than N-linked oligosaccharides and confirm that different subpopulations of keratinocytes can be distinguished by lectin histochemistry.     

The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates

C57BL/10Bg sps/sps mice display behavioral arrest, similar to generalized absence seizures. Compared with the parent strain C57BL/10Bg SPS/SPS, the activities of glutamate decarboxylase (GAD, E. C. 2.6.1.15), GABA aminotransferase (GABA-T, E. C. 2.6.1.19), aspartate aminotransferase (ASP-T, E. C. 2.6.1.1), and glutamate dehydrogenase (GDH, E. C. 1.4.1.3) in whole brain crude supernatant were significantly reduced in the sps/sps mice. Alanine aminotransferase activity (ALA-T, E. C. 2.6.1.2), was not altered in any of the strains, and normalization of GAD, GABA-T and GDH activities by that of ALA-T, further revealed significant differences between the normal strain (SPS/SPS), the heterozygotes (SPS/sps), and behavioral arrest (sps/sps) mice. These results suggest the possible involvement of GABAergic and glutamatergic neurotransmission in the absence-like behavior displayed by sps/sps mice. Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates.     

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.     

HLA-C revisited

During the past 10 years knowledge about the interactions between major histocompatibility complex (MHC) class I molecules and the T-cell receptor (TCR) complex of cytotoxic T-cells (CTL) has developed dramatically. But the primary interest, both with respect to structure as well as function, has concentrated on HLA-A and -B molecules because of their high sequence polymorphism and their dominating presence at the cell surface. In contrast, HLA-C molecules seemed to be of only minor importance in the cascade of immune reactions owing to their more limited polymorphism and reduced levels of surface expression. The inability to define a number of antigen specificities had the result that HLA-C molecules were often neglected in studies of immune response, transplantation, and disease association. More recently a new function has been identified for HLA class I molecules where they act as inhibitors of the lytic capacity of natural killer (NK) cells and non-MHC-restricted T-cells. Moreover, the understanding of this novel mode of negative regulation of cytotoxicity was remarkably influenced by HLA-C since these were the first HLA class I molecules found to have such inhibitory potential. With this new inhibitory function serving as an essential component of the immune system, HLA-C molecules can no longer be neglected.     

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000

BACKGROUND: Meta-analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C-section). OBJECTIVE: The objective of this study was to examine recent trends in and factors associated with C-section deliveries among HIV-infected women in the United States. DESIGN: A multisite pediatric medical record review of a cohort of HIV-exposed and HIV-infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. SETTING/PATIENTS: All infants born between 1994 and 2000 to HIV-positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. RESULTS: The proportion of deliveries by C-section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C-section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02-1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase in C-section rates mainly among HIV-infected women in the United States after the release of the meta-analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C-section when indicated to reduce the likelihood of HIV transmission.