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.     

Mother's understanding of allergen induced asthma

Forty-nine children with asthma and their mothers were interviewed regarding their knowledge of asthma, factors that precipitated attacks, and how they attempted to reduce the probability of an attack. Many mothers and children were well aware of factors that precipitated attacks, but took little positive action to reduce attacks. The data suggest that much ill-health in asthmatic children could be reduced by improving education available to mothers and children.     

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.     

Revisiting the Relationship between Managed Care and Hospital Consolidation

Objective. This paper analyzes whether the rise in managed care during the 1990s caused the increase in hospital concentration.
Data Sources. We assemble data from the American Hospital Association, InterStudy and government censuses from 1990 to 2000.
Study Design. We employ linear regression analyses on long differenced data to estimate the impact of managed care penetration on hospital consolidation. Instrumental variable analogs of these regressions are also analyzed to control for potential endogeneity.
Data Collection. All data are from secondary sources merged at the level of the Health Care Services Area.
Principle Findings. In 1990, the mean population-weighted hospital Herfindahl–Hirschman index (HHI) in a Health Services Area was .19. By 2000, the HHI had risen to .26. Most of this increase in hospital concentration is due to hospital consolidation. Over the same time frame HMO penetration increased three fold. However, our regression analysis strongly implies that the rise of managed care did not cause the hospital consolidation wave. This finding is robust to a number of different specifications.     

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.     

人力资源战略在医院管理中的运用及价值探讨

人力资源是医院最重要的资源,随着国内医疗市场的逐步开放和"三医"联动医药卫生体制改革的实施,医院之间的竞争愈加表现为人才的竞争,作为医院的高层管理者在战略决策管理中如何通过合理的人才战略和管理机制,吸引、培养、留下更多的人才并最大程度地调动他们的积极性和创造性显得十分重要.本文重点阐述了医院实施人力资源战略管理的方法,认为个人目标与组织目标保持高度一致,设计合理、灵活、富有激励的绩效考核办法是医院人力资源战略管理的关键所在.     

Stability of insulin mixtures in disposable plastic insulin syringes

The miscibility of short and long acting porcine, human and bovine insulins has been investigated using HPLC. Soluble insulin is rapidly lost from solution when mixed with both isophane and zinc insulin, although the mechanism may be different in these two cases. The time for up to 50% or more to be lost is often less than 2 min. The percentage lost is dependent upon the ratio of the mixture and the type and origin of the insulin. In the case of soluble: zinc mixtures it is greatest for porcine and least for bovine, in the case of soluble: isophane mixtures it was least for human and greatest for bovine. The greater the original amount of soluble insulin present the less the loss. The results help explain recent clinical reports that mixtures of soluble and zinc insulins fail to achieve satisfactory control of post-prandial blood sugar levels.     

KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall that express the receptor tyrosine kinase KIT. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of studies of GISTs, although the reported frequency of these mutations has varied over a wide range (20 to 92%). Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 11 of KIT are a negative prognostic factor. To maximize sensitivity for KIT mutations we have adapted denaturing high-pressure liquid chromatography as a method for screening polymerase chain reaction amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was used to assess the frequency of KIT mutations in 13 morphologically benign, incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy for unrelated disease. Representing the smallest pathologically recognizable GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence-confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9, 11, and 17; one of these was also analyzed for exon 13 and was wild type in this exon as well. The mutations found in the incidental GISTs were identical to those that have been documented in larger GISTs. In addition, the overall frequency of mutations in the incidental tumors (85%) did not differ significantly from that we previously reported in a series of 72 advanced/metastatic GISTs (86%), strongly supporting the view that activating mutations in KIT are acquired very early in the development of most GISTs. The findings suggest that KIT mutations per se are of little prognostic importance in GISTs.