Chy-3 mice are Vegfc haploinsufficient and exhibit defective dermal superficial to deep lymphatic transition and dermal lymphatic hypoplasia.

Recent advances in molecular lymphology and lymphatic phenotyping techniques in small animals offer new opportunities to delineate mutant mouse models. Chy-3 mutant mice were originally named for their chylous ascites, but the underlying lymphatic disorder was not defined. We now re-examined these mice and applied advanced genotyping and lymphatic phenotyping techniques to pinpoint the specific lymphatic defect in this mouse model. We demonstrated that Chy-3 mice carry a large chromosomal deletion that includes Vegfc and narrowed this region by monitoring the heterozygosity of genetic markers. We found that Chy-3 mice not only exhibited chylous ascites but also lymphedema of the hind paws and, in approximately half of the males, lymphedema of the penis. Visual lymphangiography and immunofluorescence staining showed a hypoplastic dermal lymphatic network, whereas the blood vasculature appeared unaffected. This hypoplastic lymphatic network was functional, and all adult Chy-3 mice exhibited a lateral lymphatic pathway directly connecting the inguinal to the axillary lymph node. The dermal superficial to deep lymphatic connections in upper limbs and in all cervical regions were intact and functionally drained the upper body. Lymphatic tracer was not transported from the dermal to the deep truncal lymphatic system in the lower limbs, even though the deep lymphatic vessels and nodes were present and patent. These findings further delineate the lymphatic phenotype of Chy-3 mice, identify a collateral lymph drainage pathway previously undescribed in other genetic models of lymphedema, and demonstrate a predilection for lymphatic abnormalities of the lower limbs.     

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma

High-grade dysplasia was found to extend to an area of pseudoinvasion in the submucosa of a colonic adenoma mimicking invasive carcinoma. The presence of both benign and cytologically malignant epithelium and residual foci of lamina propria among the submucosal glands distinguishes this entity from adenocarcinoma arising in an adenomatous polyp.     

Orphans as a window on the AIDS epidemic in Sub-Saharan Africa: initial results and implications of a study in Uganda

Provisional estimates from a Save the Children Fund enumeration study in four Ugandan districts indicate that the total number of orphans (one or both parents missing) ranges between 620,000 and 1,200,000. Needs assessments with guardians and local administrators show that although extended family networks are absorbing these children according to traditional rules, they may be vulnerable to increased mortality due to economic and health stresses on their caretakers, many of whom are elderly persons. The orphan burden will increase in Uganda and other Sub-Saharan African countries over the next few years. Allocation of additional national and international resources must be considered to avert breakdowns in community and familial support systems and consequent increases in under 5 mortality. The orphan burden is a window on the potential for massive social breakdown and dislocation in Sub-Saharan Africa resulting from high AIDS-related mortality. Methodologies for data collection and planning that use indigenous political systems must be built quickly to avert disaster.     

Cardiac abnormalities in the fragile X syndrome.

Twenty three patients with fragile X syndrome underwent cardiovascular assessment. Echocardiography showed dilatation of the aortic root in 12 (52%) and mitral valve prolapse in five (22%), four of whom had an apical mid-systolic click on auscultation. Patients with fragile X syndrome have cardiac defects similar to those seen in other disorders of connective tissue such as Marfan's syndrome and Ehlers-Danlos syndrome. These, and other somatic features, suggest an underlying connective tissue dysplasia.     

Y chromosome loss in esophageal carcinoma: An in situ hybridization study

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms. © 1993 Wiley-Liss, Inc.