PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

How we do it: Technical note: endoscopic removal of cerumen

? Syringing of ears to remove cerumen is losing favour in primary care owing to the fact that it is carried out ‘blind’ and that the potential exists for serious complications. ? Dewaxing under direct vision is difficult without a microscope. ? A technique is described where wax is removed under direct vision using a rigid endoscope in conjunction with a Jobson–Horne probe and St Bartholomew's wax hook. ? This is a relatively inexpensive technique that could be introduced to primary care practitioners or to ENT surgeons who do not have easy access to an operating microscope in the outpatient department.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Mortality studies of machining-fluid exposure in the automobile industry. II. Risks associated with specific fluid types.

Excesses of digestive and respiratory cancers have been reported previously in association with exposure to machining fluids, agents in widespread use as coolants and lubricants in machining operations. Previous studies have had limited power to distinguish the effects of the different types of machining fluids in use. In a cohort of over 30,000 workers employed at two automotive plants in Michigan, mortality patterns were studied in relation to exposure to each of the three major fluid types--straight oils, soluble oils, and synthetic fluids. Standardized mortality ratios were estimated for subgroups of the cohort ever exposed to each of the three fluid types, and Poisson regression analyses were used to assess trends in risk with duration of exposure. The data suggest modest positive associations between exposure to straight oils and rectal, laryngeal, and prostatic cancer and a negative association between soluble and synthetic fluid exposure and lung cancer.     

Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles

Virus-like particles containing the rotavirus (RV) internal proteins VP2 and VP6 (2/6-VLP) have been shown to induce serum and fecal antibodies as well as protection in mice after intranasal administration with a mutant of E. coli toxin, LT-R192G. To better understand the origin of fecal IgA induced by this protocol, we studied the RV-specific B cell response in systemic and mucosal lymphoid tissues using a flow cytometry assay that allows quantification and phenotypic characterization of RV-specific B lymphocytes. We also assessed the RV-specific antibody-secreting cells in the spleen and intestinal lamina propria (ILP). A remarkably high frequency of RV-specific B cells was found in the respiratory lymphoid tissues and spleen, of which only a minority expressed the alpha4beta7 integrin (intestinal homing receptor). In contrast, but in accordance with alpha4beta7 expression at the induction site, a very low response was observed in intestinal lymphoid tissues (mesenteric lymph nodes and ILP), which did not increase after a second immunization. Thus, intranasal immunization with a nonreplicating antigen does not induce an important number of RV-specific B cells with an intestinal homing profile.