Publications

The alpha(4)beta(1) integrin VLA-4 (very-late activation antigen-4) and the lineage-specific CD4 and CD8 receptors have been proposed as putative co-stimulatory receptors on T cells. To assess the relative contribution of signaling through the TCR, CD28 and these accessory molecules, we activated human T cells using soluble antibodies recognizing all four of these T-cell receptor classes (CD3, CD28, CD4/CD8, and VLA-4), and we assessed the degree of activation using higher-order flow cytometry detecting intracellular Erk1/2 phosphorylation and production of IL-2 and IFN-gamma. We found that: (1) co-stimulation via CD4/CD8, in addition to CD28, is required for optimal T-cell activation; (2) VLA-4 binding consistently potentiates CD4(+) and CD8(+) T-cell activation; (3) augmentation of T-cell activation through VLA-4 binding is most pronounced following engagement of CD4/CD8. These results confirm that multiple signals, including VLA-4 engagement, are necessary for maximal T-cell activation beyond that induced via the TCR and CD28.

PURPOSE

This qualitative study explored women's experiences with counseling about medication-induced birth defects, as well as how and when they would like to receive information on medication-induced birth defects from their health care providers (HCPs).

METHODS

We conducted four focus groups with 36 women of reproductive age (18-45 years old) in Pittsburgh, Pennsylvania. Twenty-one women were using medications to treat a chronic health condition, and two were pregnant. Content analysis was performed by three independent coders using a grounded theory approach. Discrepancies were resolved by consensus.

RESULTS

Women reported depending on their HCPs for information about the risks of teratogenic effects of medications on a pregnancy, but felt the information they had been provided was not always comprehensive. Women want HCPs to initiate discussions about potentially teratogenic medications at the time the medications are prescribed, regardless of whether the woman is sexually active or planning a pregnancy. Women want clear information about all potential outcomes for a fetus. Factors women reported as being critical to effective teratogenic risk counseling included privacy, sufficient time to discuss the topic, and a trusting relationship with their HCP.

CONCLUSIONS

Women of reproductive age think that providing information about the possible teratogenic effects of medications could be improved by routine discussions of teratogenic risks at the time medications are prescribed.

OBJECTIVE

To examine the relationship between lactation and subclinical cardiovascular disease in a population free of clinical cardiovascular disease.

METHODS

We conducted a cross-sectional analysis of 297 women who reported at least one live birth on enrollment in the Study of Women Across the Nation-Heart Study. Participants were mothers aged 45-58 years who were free of clinical cardiovascular disease. History of lactation was self-reported. Electron beam tomography was used to assess coronary and aortic calcification. B-mode ultrasonography was used to assess carotid adventitial diameter, intima-media thickness, and carotid plaque. Multivariable linear and logistic regression models were used to estimate whether lactation was independently associated with markers of subclinical cardiovascular disease.

RESULTS

In unadjusted models, compared with mothers who had breastfed all of their children for at least 3 months, mothers who had not breastfed were more likely to have coronary artery calcification (17% compared with 32%), aortic calcification (17% compared with 39%), carotid plaque (10% compared with 18%), and larger carotid adventitial diameters (mean+/-standard deviation 6.63+/-0.59 compared with 6.87+/-0.60 mm). After adjusting for measures of socioeconomic status and lifestyle and family history variables, mothers who had not breastfed remained more likely to have aortic calcification (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.47-10.00) and coronary artery calcification (OR 2.78, 95% CI 1.05-7.14) than mothers who had consistently breastfed. After further adjustment for body mass index and traditional risk factors for cardiovascular disease, mothers who had not breastfed remained more likely to have aortic calcification than mothers who had consistently breastfed (OR 5.26, 95% CI 1.47-20.00).

CONCLUSION

Mothers who do not breastfeed their infants seem to be at increased risk of vascular changes associated with future cardiovascular disease.

LEVEL OF EVIDENCE

II.

There is increasing evidence that the numerous mechanisms that regulate cell differentiation during normal development are also involved in tumorigenesis. In breast cancer, differentiation markers expressed by the primary tumor are routinely profiled to guide clinical decisions. Indeed, numerous studies have shown that the differentiation profile correlates with the metastatic potential of tumors. The transcription factor GATA3 has emerged recently as a strong predictor of clinical outcome in human luminal breast cancer. In the mammary gland, GATA3 is required for luminal epithelial cell differentiation and commitment, and its expression is progressively lost during luminal breast cancer progression as cancer cells acquire a stem cell-like phenotype. Importantly, expression of GATA3 in GATA3-negative, undifferentiated breast carcinoma cells is sufficient to induce tumor differentiation and inhibits tumor dissemination in a mouse model. These findings demonstrate the exquisite ability of a differentiation factor to affect malignant properties, and raise the possibility that GATA3 or its downstream genes could be used in treating luminal breast cancer. This review highlights our recent understanding of GATA3 in both normal mammary development and tumor differentiation.

The dermal-epidermal basement membrane zone is an important epithelial and stromal interface, consisting of an intricately organized collection of intracellular, transmembrane, and extracellular matrix proteins. The basement membrane zone has several main functions including acting as a permeability barrier, forming an adhesive interface between epithelial cells and the underlying matrix, and controlling cellular organization and differentiation. This article identifies key molecular players of the dermal-epidermal membrane zone, and highlights recent research studies that have identified structural and functional roles of these components in the context of various blistering, neoplastic, and developmental syndromes.

OBJECTIVE

This study evaluated the association between depression and hospitalization among geriatric home care patients.

METHODS

A sample of 477 patients newly admitted to home care over two years was assessed for depression. Bivariate and logistic regression analyses examined the likelihood of hospitalization during a 60-day home care episode.

RESULTS

The hospitalization rate was similar for the 77 depressed patients and 400 nondepressed patients (about 7%). However, mean time to hospitalization was 8.4 versus 19.5 days after start of care, respectively. Hospitalization risk was significantly higher for depressed patients during the first few weeks. A main effect for depression and a depression-by-time interaction was found when analyses controlled for medical comorbidity, cognitive status, age, gender, race, activities of daily living and instrumental activities of daily living, and referral to home care after hospitalization.

CONCLUSIONS

Depression appears to increase short-term risk of hospitalization for geriatric home care patients immediately after starting home care.