Atypical fibrous histiocytoma of the scrotum

Atypical fibrous histiocytoma is a rare neoplasm. A scrotal location for this tumor is even more unusual. We report a case of a 90-year-old man with scrotal atypical fibrous histiocytoma. Our case had histologic features consistent with those cases previously reported in the literature. The tumor consists of cells with large hyperchromatic irregular nuclei, bizarre multinucleated cells (monster cells), and xanthomatous cells with large prominent nuclei set in a background of classic fibrous histiocytoma. Rare mitotic figures are identified. Immunohistochemical studies showed the tumor cells to be positive for vimentin, smooth muscle actin, desmin, KP-1, factor XIIIa, and MIB-1 (less than 10%). In addition to the expected immunohistochemical studies, the tumor stained diffusely positive for CD117. To our knowledge, this is the first report of atypical fibrous histiocytoma of the scrotum.     

Amplifying Btk's signal

The Tec kinase Btk is an important regulator of antigen receptor activation of phospholipase C-gamma (PLC-gamma). Data from Carpenter and colleagues (Saito et al., this issue of Immunity) now suggest that Btk also activates phosphatidylinositol-4-phosphate 5-kinase (PIP5K), thereby stimulating a positive feedback loop that generates PI(4,5)P2, the substrate for both phosphoinositide 3-kinase (PI3K) and PLC-gamma.     

Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor

Leukocyte immunoglobulin-like receptor 1 (LIR-1), an inhibitory receptor expressed on monocytes, dendritic cells and lymphocytes, regulates cellular function by binding a broad range of classical and nonclassical major histocompatibility complex (MHC) class I molecules, and the human cytomegalovirus MHC class I homolog UL18. Here we describe the 3.4-A crystal structure of a complex between the LIR-1 D1D2 domains and the MHC class I molecule HLA-A2. LIR-1 contacts the mostly conserved beta(2)-microglobulin and alpha3 domains of HLA-A2. The LIR-1 binding site comprises residues at the interdomain hinge, and a patch at the D1 tip. The structure shows how LIR-1 recognizes UL18 and diverse MHC class I molecules, and indicates that a similar mode of MHC class I recognition is used by other LIR family members.     

Are fitness,activity, and fatness associated with health-related quality of life and mood in older persons?

PURPOSE: This study sought to determine whether levels of fitness, habitual physical activity, and fatness are associated health-related quality of life and mood in older persons. METHODS: The subjects were men (n = 38) and women (n = 44), ages 55 to 75 years, who had milder forms of hypertension, but who were otherwise healthy and not engaged in a regular exercise or diet program. Aerobic fitness was assessed by maximal oxygen uptake during treadmill testing, muscle strength by a one-repetition maximum, habitual activity by questionnaire, fatness by dual-energy x-ray absorptiometry, and body mass index. Health-related quality of life was assessed by the Medical Outcomes Study SF-36, and mood by the Profile of Mood States (POMS). Correlations were determined by bivariate and multivariate regression. RESULTS: Higher aerobic fitness was associated with more desirable outcomes, as indicated by the POMS anger and total mood disturbance scores and by the SF-36 bodily pain, physical functioning, vitality, and physical component scores. Increased fatness was associated with less desirable outcomes, as indicated by the POMS anger, depression, and total mood disturbance scores and by the SF-36 bodily pain, physical functioning, role-emotional, role-physical, social functioning, vitality, and physical component scores. Higher physical activity was associated with an increased POMS score for vigor and a decreased SF-36 score for bodily pain. Strength was not related to health-related quality of life or mood. Aerobic fitness was the strongest predictor of the SF-36 score for vitality and the POMS score for total mood disturbance, whereas fatness was the strongest predictor of the POMS anger score and the SF-36 bodily pain, physical functioning, and physical component scores. CONCLUSIONS: Even in the absence of regular exercise and a weight-loss diet, relatively small amounts of routine physical activity within a normal lifestyle, slight increases in fitness, and less body fatness are associated with a better health-related quality of life and mood.     

No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network

A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a (His)73(Arg) polymorphism (A:G) in HOXA1 contributes substantially to a liability for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they found a significant dearth of G homozygotes and biased transmission of G alleles from parents to affected offspring, especially from mothers. Because the connection between HOXA1 and liability to autism is compelling, we attempted to replicate their finding using a larger, independent sample from the Collaborative Programs of Excellence in Autism (CPEA) network. In our data, genotype frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet Mendelian expectations; and there is no obvious sex-biased allele transmission. Based on our sample size, calculations suggest that we would have at least 95% power to detect linkage and association even if the A:G polymorphism were to account for only 1% of the heritability of autism. Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism.     

Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells

Human breast milk is a rich source of growth factors, including erythropoietin (Epo), the endogenous hormonal stimulant of erythropoiesis. Recombinant human Epo (rhEpo) has been shown to stimulate 1) angiogenesis, the process of new blood vessel growth from preexisting vessels; 2) vasculogenesis, tubule formation from single-cell suspensions; and 3) endothelial cell proliferation in immortalized endothelial cells and vessel explants. We hypothesized that Epo would induce mitogenesis and stimulate vasculogenesis in primary cultures of microvascular endothelial cells (MVECs) from neonatal rat mesentery. Isolation, purification, characterization, and culture of MVECs were performed. Cell proliferative effects of rhEpo were studied by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in cultured MVECs. Vasculogenic effects of rhEpo were examined on cultured MVECs plated on either hormone-rich Matrigel substratum or the extracellular matrix protein, type I collagen. Our findings show that MVECs are isolated and purified, and that rhEpo stimulates MVEC proliferation, with maximal proliferation seen with a concentration of 50 IU/mL rhEpo. Tubule formation assays reveal that an rhEpo concentration of 50 IU/mL produces maximal tubule formation after 12 h on both Matrigel and the simple substratum, type I collagen. Our study is the first to examine the effects of rhEpo on the endothelium of the neonatal gastrointestinal tract. These data suggest that Epo may have a trophic effect on the vasculature of the gastrointestinal tract early in development. Furthermore, as Epo has been measured in breast milk, and its receptor has been shown to exist on the mucosa and gastrointestinal vasculature, Epo may be an endogenous stimulant of vessel growth during neonatal gastrointestinal development.     

The separateness of social and emotional loneliness in childhood

BACKGROUND: Much of the childhood loneliness research is misleading because it confounds objective and subjective measures of loneliness. The overall aim of this research was to examine the relationship between social isolation and emotional loneliness. METHOD: Three extreme groups were identified in a sample of 640 4-9-year-old children. There were two ('rejected' [N=60] and 'lonely' [N=146]) in which social and emotional loneliness were unrelated. The first were socially isolated (rejected) but they did not feel lonely. The second group felt lonely but they were not socially isolated. The third group ('rejected/ lonely') consisted of 61 children who were rejected and also felt lonely. RESULTS: Felt loneliness and social rejection were experienced together by 61 children, but 206 children experienced either one or the other, but not both. The fourth and largest group [N=374] were neither rejected nor lonely. Differences between the groups were found on direct observation measures of solitariness, sociability, and aggression; peer reports of shyness, aggression, prosocial behaviour, disruptive behaviour and inability to take teasing; self-reports of self-worth and competence, self-reports of supportive relationships; and measures of language use. CONCLUSIONS: The results indicate that it is loneliness and not rejection that co-occurs with emotional problems.