They're All My Children: Foster Mothering in America

They're All My Children: Foster Mothering in America. Danielle F. Wozniak. New York: NYU Press, 2002. + 245 pp.     

No Increase in Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Patients with HIV-1-HBV Coinfections following HBV-Active Highly Active Antiretroviral Therapy

Following treatment of hepatitis B virus (HBV) monoinfection, HBV-specific T-cell responses increase significantly; however, little is known about the recovery of HBV-specific T-cell responses following HBV-active highly active antiretroviral therapy (HAART) in HIV-HBV coinfected patients. HIV-HBV coinfected patients who were treatment naïve and initiating HBV-active HAART were recruited as part of a prospective cohort study in Thailand and followed for 48 weeks (n = 24). Production of gamma interferon (IFN-γ) and tumor necrosis factor α (TNF-α) in both HBV- and HIV-specific CD8⁺ T cells was quantified using intracellular cytokine staining on whole blood. Following HBV-active HAART, the median (interquartile range) log decline from week 0 to week 48 for HBV DNA was 5.8 log (range, 3.4 to 6.7) IU/ml, and for HIV RNA it was 3.1 (range, 2.9 to 3.5) log copies/ml (P < 0.001 for both). The frequency of HIV Gag-specific CD8⁺ T-cell responses significantly decreased (IFN-γ, P < 0.001; TNF-α, P = 0.05). In contrast, there was no significant change in the frequency (IFN-γ, P = 0.21; TNF-α, P = 0.61; and IFN-γ and TNF-α, P = 0.11) or magnitude (IFN-γ, P = 0.13; TNF-α, P = 0.13; and IFN-γ and TNF-α, P = 0.13) of HBV-specific CD8⁺ T-cell responses over 48 weeks of HBV-active HAART. Of the 14 individuals who were HBV e antigen (HBeAg) positive, 5/14 (36%) lost HBeAg during the 48 weeks of follow-up. HBV-specific CD8⁺ T cells were detected in 4/5 (80%) of patients prior to HBeAg loss. Results from this study show no sustained change in the HBV-specific CD8⁺ T-cell response following HBV-active HAART. These findings may have implications for the duration of treatment of HBV in HIV-HBV coinfected patients, particularly in HBeAg-positive disease.Individuals infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are at increased risk of liver disease progression and liver-related mortality (35). Despite the introduction of effective highly active antiretroviral therapy (HAART), liver disease remains a major cause of non-AIDS-related deaths in HIV-1-infected patients (31). Current guidelines recommend the early consideration of HBV-active HAART in the majority of coinfected individuals (28), and treatment of both HBV and HIV is generally lifelong. This is in contrast to HBV-monoinfected patients, where HBV treatment ceases following production of antibody to HBV e antigen (HBeAg) or HBV surface antigen (HBsAg) (23). HBeAg and HBsAg seroconversions are considered important endpoints of treatment as they are associated with HBV DNA clearance, normalization of alanine aminotransferase (ALT), and a reduction in the risk of liver disease (12).Little is known about the immune events precipitating HBeAg or HBsAg seroconversion. However, a reduction in antigen burden following anti-HBV treatment may reduce T-cell tolerance and exhaustion, allowing for a more efficient HBV-specific T-cell and B-cell immune response against either HBeAg and/or HBsAg (11, 13, 21). Circulating HBV-specific CD4⁺ and CD8⁺ T cells are rarely detected in untreated chronic HBV infection (5, 24). Following treatment of HBV monoinfection with nucleos(t)ide analogues such as lamivudine (LMV), there is an increase in functional HBV-specific CD4⁺ and CD8⁺ T cells both in the peripheral blood (5, 18) and within the liver (32). However, recovery of HBV-specific T cells appears to be transient and has been shown to decline following long-term therapy (5, 14, 20).We have previously shown that the HBV-specific T-cell response is impaired in HIV-HBV coinfection (7, 9). In one small observational study (n = 5), HBV-active HAART was associated with the recovery of CD8⁺ HBV-specific T cells (19); however, in this study, two patients had received prior HAART, and the HBV-specific T-cell responses were examined only during the first 24 weeks of treatment (19). In addition, HBeAg status was not defined, and HBV-specific T-cell responses were measured only by IFN-γ production following stimulation with HLA-A2-restricted epitopes (19).In the present study, we used an overlapping peptide library covering the complete HBV genome to assess change in HBV-specific CD8⁺ T cells following the introduction of HBV-active HAART in treatment-naïve HIV-HBV-coinfected patients in Thailand. Overall, we show that there was no sustained change in the magnitude, frequency, or quality of HBV-specific T-cell responses following initiation of effective HBV-active HAART.     

Mechanism for increased leaf growth in elevated CO2

The effect of exposure to elevated CO₂ on the processes of leafcell production and leaf cell expansion was studied using primaryleaves of Phaseolus vulgaris L. Cell division and expansionwere separated temporally by exposing seedlings to dim red lightfor 10 d (when leaf cell division was completed) followed byexposure to bright white light for 14 d (when leaf growth wasentirely dependent on cell expansion). When plants were exposedto elevated CO₂ during the phase of cell expansion, epidermalcell size and leaf area development were stimulated. Three piecesof evidence suggest that this occurred as a result of increasedcell wall loosening and extensibility, (i) cell wall extensibility(WEx, measured as tensiometric extension using an Instron) wassignificantly increased, (ii) cell wall yield turgor (V, MPa)was reduced and (iii) xyloglucan endotransglycosylase (XET)enzyme activity was significantly increased. When plants wereexposed to elevated CO₂ during the phase of cell division, thenumber of epidermal cells was increased whilst final cell sizewas significantly reduced and this was associated with reducedfinal leaf area, WEx and XET activity. When plants were exposedto elevated CO₂ during both phases of cell division and expansion,leaf area development was not affected. For this treatment,however, the number of epidermal cells was increased, but cellexpansion was inhibited, despite exposure to elevated CO₂ duringthe expansion phase. Assessments were also made of the spatialpatterns of WEx across the expanding leaf lamina and the datasuggest that exposure to elevated CO₂ during the phase of leafexpansion may lead to enhanced extensibility particularly atbasal leaf margins which may result in altered leaf shape. The data show that both cell production and expansion were stimulatedby elevated CO₂, but that leaf growth was only enhanced by exposureto elevated CO₂ in the cell expansion phase of leaf development.Increased leaf cell expansion is, therefore, an important mechanismfor enhanced leaf growth in elevated CO₂, whilst the importanceof increased leaf cell production in elevated CO₂ remains tobe elucidated. Key words: Phaseolus vulgaris L., dwarf beans, elevated CO², biophysics of cell expansion, xyloglucan endotransglycosylase, XET, water relations     

Structural Features of Glycera dibranchiata Monomer Hemoglobins. Primary Sequences of Monomer Hemoglobin Components II and III

Primary sequences for the remaining two members (GMH2, GMH3) of the group of three major monomeric hemoglobins from the marine annelid Glycera dibranchiata have been obtained. Full sequences of each 147-amino acid globin were achieved with a high degree of confidence using standard Edman technology in combination with molecular mass determinations of the intact globins and of the cyanogen bromide cleavage fragments using electrospray ionization mass spectrometry. When minor assumptions concerning Q/E identities are made these new results indicate the likely correspondence of GMG2 with the protein represented by the first Glycera dibranchiata monomer hemoglobin complete sequence [Imamura et al., (1972), J. Biol. Chem.247, 2785–2797]. When these new sequences are combined with the previously determined primary sequence for the third major monomer hemoglobin, GMH4 [Alam et al., J. Protein Chem. (1994), 13, 151–164], it becomes clear that these three (GMG2–4) are truly distinct proteins, contrary to previous suggestions. Surprisingly, our results show that none of these three primary sequences is identical to the published sequence of the refined monomer hemoglobin crystal structure protein; however, there is a strong correspondence to the GMG2 sequence. The present sequencing results, in combination with the published GMH4 sequence, confirm the presence of a distal Leu in place of the more commonly encountered distal His in all three of the major monomer hemoglobins isolated in this laboratory and indicate that the unusual B10 Phe occurs only in GMH4. Analysis of the sequences presented here, along with comparison of amino acid content for Glycera dibranchiata monomer hemoglobins isolated from three different laboratories, and comparison of NMR results from two laboratories suggest further correspondences which unify disparate published isolations.     

The role of parametric linkage methods in complex trait analyses using microsatellites

Many investigators of complexly inherited familial traits bypass classical segregation analysis to perform model-free genome-wide linkage scans. Because model-based or parametric linkage analysis may be the most powerful means to localize genes when a model can be approximated, model-free statistics may result in a loss of power to detect linkage. We performed limited segregation analyses on the electrophysiological measurements that have been collected for the Collaborative Study on the Genetics of Alcoholism. The resulting models are used in whole-genome scans. Four genomic regions provided a model-based LOD > 2 and only 3 of these were detected (p < 0.05) by a model-free approach. We conclude that parametric methods, using even over-simplified models of complex phenotypes, may complement nonparametric methods and decrease false positives.     

The therapeutic potential of blocking the activin signalling pathway

Members of the transforming growth factor β (TGF-β) family regulate fundamental physiological process, such as cell growth, differentiation and apoptosis. As a result, defects in this pathway have been linked to uncontrolled proliferation and cancer progression. Here we explore the signal transduction mechanism of TGF-β focusing on therapeutic intervention in human diseases. Like TGF-β, another member of the TGF-β superfamily, activin has been proven to play an important role in maintenance of tissue homeostasis and dysregulation leads to disease. Several studies showed elevated levels of activin are responsible for the development of gonadal tumours and a cachexia-like weight loss syndrome. Discussing the recent advances in approaches developed to antagonise the activin pathway and the encouraging results obtained in animal models, this review presents a therapeutic rationale for targeting the activin pathway in conditions such as cachexia, neuromuscular and/or musculoskeletal disorders.     

Comparison of the Menopause and Midlife Transition between Japanese American and European American Women

Cross-cultural differences in the meaning and experience of the universal biologic phenomenon of the menopause have been well documented. Very few studies, however, have focused on the response to the midlife transition among ethnic minority women in the United States, and even fewer exist about Asian American women. This exploratory study compared the perceptions and experiences of the midlife transition among Japanese American and European American women. The midlife transition was viewed as a time of self-assurance, maturity, and taking comfort and satisfaction in oneself. Biologically, it was a marker of mortality. Similar to menses, marriage, and motherhood, menopause was viewed as the final identity transformation, but interpreted quite differently by the two ethnic groups. The findings of this study support the cross-cultural theories that emphasize the interaction of biology, society, age, gender, and acculturation in this universal female experience and suggest additional expansion of these theories to incorporate lifestyle choices that may affect the actual health consequences of female aging. [menopause, midlife transition, Japanese American women, ethnicity]