The HOX homeodomain proteins are fundamental regulators of organ and tissue development, where they are thought to function as transcription factors, and HOX gene expression has been associated with numerous types of cancers. Previous studies have demonstrated that enforced expression of the HOXB4 protein transforms cultured fibroblasts and leads to a selective expansion of the hematopoietic stem cell pool, suggesting that this protein might play a role in cellular proliferation. In support of this concept, we now show that enforced expression of HOXB4 in human neonatal keratinocytes results in increased cellular proliferation and colony formation as well as decreased expression of the alpha-2-integrin and CD44 cell surface adhesion molecules. We previously have reported HOXB4 gene expression in the basal and suprabasal layers of developing human skin and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within epidermal basal cells and in hair follicle inner and outer root sheath cells, whereas strong nuclear signals were observed in the bulge region. In adult skin, HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly localized to the intermediate and differentiated cell layers. In contrast to the striking gradient patterns of HOX gene and protein expression previously described in developing spinal cord and limb, HOXB4 protein was uniformly detected in all regions of the fetal and adult skin. Although little HOXB4 signal localized to proliferative cell layers, as marked by proliferating cell nuclear antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein expression substantially overlapped with PCNA-positive cell in a series of samples of hyperproliferative skin. Taken together, these data suggest that nuclear HOXB4 protein may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis.Published 2002 Wiley-Liss, Inc. †

BackgroundTuberculosis is a major public health problem with varying prevalence in different settings. National prevalence surveys provide evidence for planning and decision making. However, they lack the capacity to estimate subnational magnitude that affected the capacity to make selected intervention based on the prevalence. Ethiopia is among high TB burden countries with estimated prevalence of 108 per 100,000 population varying by regions. We aimed to study sub national prevalence of smear-positive TB in rural communities of southern Ethiopia.MethodsThis cross-sectional study, enrolled community members aged over 14 years who had cough of at least two weeks duration. Two sputum samples were collected and examined by using smear microscopy.Results38,304 eligible people were enumerated (10,779 from Hadiya, 10,059 from Gurage and 17,466 from Sidama) and indentified 960 presumptive cases. 16, 14 and 14 smear-positive pulmonary TB cases were identified respectively. The point prevalence of smear-positive TB were 148 per 100,000 population (95% CI: 91–241) in Hadiya, 139 per 100,000 population (95% CI: 83–234) in Gurage and 80/100,000 population (95%CI: 48–135) in Sidama zone. Gurage zone had the highest prevalent to notified cases of seven to one.ConclusionsThe prevalence of smear positive TB varies by districts and is high in rural southern Ethiopia compared to the estimated national prevalence. More TB patients remain missed and unreached, impacting negatively on health outcomes. TB case finding approaches should be revisited and innovative approaches and tools to identify missing people with TB should be scaled up.

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