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.     

Supraoptic nucleus afferents from the main olfactory bulb--II. Intracellularly recorded responses to lateral olfactory tract stimulation in rat brain slices

To establish the functional nature of the anatomically demonstrated main olfactory bulb inputs to the supraoptic nucleus, electrophysiological responses of intracellularly recorded supraoptic neurons to lateral olfactory tract stimulation were recorded in horizontal slices of basal forebrain and hypothalamus. A total of 71 synaptically influenced neurons were studied in slices from adult rats of both sexes. Of these, 60 cells (84%) were monosynaptically activated by olfactory tract stimulation; seven cells (10%) were activated via polysynaptic pathways; and four cells (6%) were characterized by long latency inhibitory responses. Lucifer Yellow was injected into 64 cells and subsequent immunocytochemical identification of 44 of these neurons showed that both oxytocin and vasopressin cells, in approximately equal numbers, were excited by olfactory stimulation. Polysynaptically mediated excitation, however, was only associated with oxytocin cells (six of the six identified cells). These results corroborate anatomical tract tracing data showing main olfactory bulb efferents to both supraotic neurons and to neurons of the perinuclear zone. Also supported are earlier speculations of olfactory participation in release of oxytocin and vasopressin during various physiological states.     

Volumetric analysis of a specific language region - the planum temporale.

Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.     

Death certificate coding practices related to diabetes in European countries--the 'EURODIAB Subarea C' Study.

The objective of this study was to compare and analyse coding practices for diabetes mortality data in nine European countries (Belgium, Republic of Ireland, France, Germany, Malta, The Netherlands, Northern Ireland, Scotland and Switzerland). In each country, a sample of 200 coded death certificates, which mentioned diabetes, was randomly sampled. All death certificates were recoded at the WHO Collaborating Centre for the Classification of Diseases in the French language. The results show wide differences between national coding and central coding. Discrepancies in the underlying cause of death existed at the 3-digit coding level for 26% of all death certificates and for 44% at the 4-digit level. Coding in Northern Ireland and Malta was characterized by a marked tendency to choose diabetes less frequently. In contrast, in The Netherlands and, to a lesser extent, in the Republic of Ireland and France, diabetes was more frequently selected as the underlying cause of death. Most of the differences concerned the coding of an association involving diabetes and circulatory system diseases. In some countries, these coding differences influence the reported level of diabetes mortality. For Northern Ireland and Malta, the number of certificates with diabetes as the underlying cause of death was more than doubled after central recoding and for The Netherlands, in contrast, it was almost halved. To explain the differences a number of factors are considered: a lack of information from the International Classification of Diseases (ICD), on the application of the coding rules, between-country differences in cause of death certification practices, a divergence of opinion about the causal role of diabetes when it is associated with other conditions, a lack of homogeneity between countries in data collection procedures.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Neurosecretory endings in the rat neurohypophysis are en passant

A combination of Golgi, Phaseolus vulgaris leucoagglutinin, and transmission electron microscopic (EM) techniques was used to investigate the morphology of neurosecretory axons and their endings in the neurohypophysis of the rat. Light microscopy indicated that the neurosecretory processes are very tortuous, varicose, and branched, often running in close association with blood vessels. EM, as well as reconstruction from serial thin sections, demonstrated that the combination of synaptoid membrane specializations, dense core vesicles, and accumulations of microvesicles, thought to indicate areas of preferential hormone release, can occur anywhere that the axons contact the basal lamina (BL) lining the perivascular space. Usually, but not always, this was accompanied by some degree of axonal dilation. Individual neurosecretory axons frequently entwined around, or ran adjacent to, blood vessels, a short length of axon forming multiple "endings." Thin glial (pituicyte) processes were interposed between these endings. Axonal processes were also seen to end blindly as end-bulbs suspended in the perivascular space where they were often surrounded by pituicyte processes. The morphology observed suggests that reductions in the contact length of individual nerve terminals could be mediated through increased pituicyte coverage along BL. Conversely, a reduction of pituicyte coverage along the BL could lead to more areas of axonal contact with the BL inducing or allowing the formation of more endings, such as has been reported to occur during lactation or prolonged elevation of plasma testosterone levels.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

Problem behavior in boys with fragile X syndrome

This study examines problem behavior over time in 59 boys with fragile X syndrome (FXS), aged 4-12 years, using the Child Behavior Checklist (CBCL). Approximately 49% of the boys scored within the borderline or clinical range on total problem behavior, while 56-57% scored in the borderline or clinical range on the attention and thought problems subscales, and 26% scored in this range on the social problems subscale. With a mean of 2.5 assessments per child, behavior problems were stable during the 3-year period of study. Total problem behavior was higher for children who displayed autistic behavior, were rated as low in adaptability, had mothers with higher maternal education levels, and were on medication. Mothers with more education also rated their children as having more attention, thought, and total problems. Children taking medication differed from boys who were not taking medication on social problems, but not on attention and thought problems. Low adaptability and more autistic characteristics predicted thought problems.