Fibroblast growth factor receptor expression reflects cellular differentiation in human oral squamous carcinoma cell lines

This study examined the expression of fibroblast growth factor receptor 2 (FGFR 2) splice variants, IIIb and IIIc, in normal and malignant human oral keratinocytes and in normal oral fibroblasts by RT-PCR using both exon-specific primers and primers common to both FGFR 2 isoforms. Fibroblasts expressed exclusively FGFR 2/IIIc whilst the normal and malignant keratinocytes co-expressed FGFR 2/IIIb and FGFR 2/IIIc. Well-differentiated keratinocytes expressed proportionally more FGFR 2/IIIb than IIIc whereas the poorly-differentiated cells expressed more FGFR 2/IIIc than IIIb. The normal and malignant keratinocytes, but not fibroblasts, expressed an additional amplification product, which consisted of both IIIb and IIIc of FGFR 2 joined by an extra base pair and with the intronic sequence removed. The results indicate that the expression of FGFR 2 isoforms reflects the degree of cellular differentiation in normal and malignant human oral keratinocytes and that receptor complexes of FGFR 2/IIIb and IIIc may regulate ligand-receptor interactions.     

Solitary rectal ulcer syndrome

BACKGROUND: Solitary rectal ulcer syndrome is a rare disorder characterized by erythema or ulceration of the rectal wall, associated with typical histological features, and disturbed defaecatory behaviour with the passage of blood and mucus. METHODS: This is a review based on a literature search using a computer database (Medline) and manual cross-referencing. RESULTS: The pathogenesis is likely to vary in different patients; it includes trauma from straining, direct digital trauma and possibly primary neuromuscular pathology. The histological findings of extension of the muscularis mucosa between crypts and muscularis propria disorganization on full-thickness specimens are characteristic. Biofeedback defaecation retraining, including habit training, can lead to symptom improvement and return to work in a majority of patients. Abdominal rectopexy offers long-term symptom improvement in approximately 50 per cent of patients. Rectal ulceration may persist after any treatment, even if symptoms improve. CONCLUSION: Behavioural therapy and carefully considered operations offer the best treatment results. Further work on psychological factors and neuromuscular and vascular pathology is required.     

Mitotic Raf-1 is stimulated independently of Ras and is active in the cytoplasm

Raf-1 is a Ser/Thr protein kinase that is involved in regulation of proliferation, differentiation, and apoptosis. Recently, we and others showed that Raf-1 is not only activated in mitogenic pathways leading to cell cycle entry but also during mitosis. Transient expression studies in COS cells now demonstrate that, in contrast to growth factor-dependent activation of Raf-1, mitotic activation of Raf-1 is Ras-independent. Dominant negative RasS17N does not interfere with mitotic activation of Raf-1, whereas epidermal growth factor-dependent stimulation of Raf-1 is inhibited. In addition, the Raf-1 mutant RafR89L, which cannot bind to activated Ras, is still stimulated in mitotic cells. Mitotic activation of Raf-1 seems to be partially dependent on tyrosine phosphorylation since the kinase activity of the Raf mutant RafYY340/341FF, which can no longer be activated by Src, is reduced in mitotic cells. Surprisingly, cell fractionation experiments showed that mitotic-activated Raf-1 is predominantly located in the cytoplasm in contrast to the mitogen-activated Raf-1 that is bound to the plasma membrane. In addition, mitotic activation of Raf-1 does not lead to stimulation of the mitogen-activated protein kinase kinase (MAPKK or MEK) and the extracellular signal-regulated protein kinase (ERK). These data demonstrate that in mitotic cells a Ras-independent mechanism results in a cytoplasmic active Raf-1 kinase which does not signal via the MEK/ERK pathway. These data demonstrate that in mitotic cells a Ras-independent mechanism results in a cytoplasmic active Raf-1 kinase which does not signal via the MEK/ERK pathway.     

Social support and hostility as predictors of depressive symptoms in cardiac patients one month after hospitalization: a prospective study

OBJECTIVE: Hospitalization for cardiac disease is associated with an increased risk for depression, which itself confers a poorer prognosis. Few prospective studies have examined the determinants of depression after hospitalization in cardiac patients, and even fewer have examined depression within the weeks after hospital discharge. The present study assessed the prospective relations among perceptions of social support and trait hostility in predicting symptoms of depressive symptoms at 1 month after hospitalization for a diagnostic angiography in 506 coronary artery disease (CAD) patients. METHOD: A series of structural equation models 1) estimated the predictive relations of social support, hostility, and depressive symptoms while in the hospital to symptoms of depression 1 month after hospitalization, and 2) compared these relations across gender, predicted risk classification, and age. RESULTS: Social support assessed during hospitalization was independently negatively associated with depressive symptoms 1 month after hospitalization, after controlling for baseline symptoms of depression, gender, disease severity, and age. Hostility was an indirect predictor of postdischarge depressive symptomology by way of its negative relation with social support. This pattern of relations did not differ across gender, predicted risk classification, and age. CONCLUSIONS: Our findings suggest that a patient's perceived social support during hospitalization is a determinant of depressive symptoms 1 month later. The relation of social support and hostility to subsequent depressive symptoms was similar across a variety of populations.     

Tetrachromacy, oil droplets and bird plumage colours

Survival rates in childhood cancer now approach approximately 65%, depending on the specific cancer. Success has been achieved through the use of increasingly aggressive treatments (chemotherapy, radiotherapy, bone-marrow transplantation). These are now recognised to be associated with a range of physical late effects, including problems associated with growth and endocrine function, sensory function, fertility, liver, cardiac, and kidney damage. Recognition of these physical late effects raises the issue of related problems in psychological, educational, and behavioural functioning. There is considerable evidence to suggest that children who are younger on diagnosis are more at risk in terms of cognitive and behavioural late effects compared with those who are diagnosed later. Cancer remains a rare disease in children and consequently only those professionals attached to centres specialising in the care of children with cancer are likely to receive a significant number of referrals. It is important to establish a psychological support service as an integral part of long-term care in order to (a) establish more accurately the incidence of social and psychological late effects and (b) offer advice to the individual about the possible long-term effects of cancer treatment on future health, social, and employment prospects.     

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.     

Gene-for-gene disease resistance without the hypersensitive response in Arabidopsis dnd1 mutant

The cell death response known as the hypersensitive response (HR) is a central feature of gene-for-gene plant disease resistance. A mutant line of Arabidopsis thaliana was identified in which effective gene-for-gene resistance occurs despite the virtual absence of HR cell death. Plants mutated at the DND1 locus are defective in HR cell death but retain characteristic responses to avirulent Pseudomonas syringae such as induction of pathogenesis-related gene expression and strong restriction of pathogen growth. Mutant dnd1 plants also exhibit enhanced resistance against a broad spectrum of virulent fungal, bacterial, and viral pathogens. The resistance against virulent pathogens in dnd1 plants is quantitatively less strong and is differentiable from the gene-for-gene resistance mediated by resistance genes RPS2 and RPM1. Levels of salicylic acid compounds and mRNAs for pathogenesis-related genes are elevated constitutively in dnd1 plants. This constitutive induction of systemic acquired resistance may substitute for HR cell death in potentiating the stronger gene-for-gene defense response. Although cell death may contribute to defense signal transduction in wild-type plants, the dnd1 mutant demonstrates that strong restriction of pathogen growth can occur in the absence of extensive HR cell death in the gene-for-gene resistance response of Arabidopsis against P. syringae.     

MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults

We have recently reported the isolation of a rat cDNA encoding a receptor-type tyrosine phosphatase, which appears to be a marker of thyroid differentiation. To elucidate the molecular mechanisms underlying r-PTPeta expression in normal thyroid cells both in vitro and in vivo, we investigated the regulation of r-PTPeta expression in cultured thyrocytes (the rat cell line PC Cl 3) and in an animal model of TSH-dependent thyroid goitrogenesis. In vitro studies showed that mRNA expression of r-PTPeta in thyroid cells is induced in a time- and dose-dependent manner by the activation of growth- and differentiation-linked PKA pathways (TSH and forskolin), whereas it is down-regulated by the activation of the proliferative dedifferentiating PKC-dependent transduction pathway (TPA). However, the regulation of r-PTPeta expression by TSH and TPA, respectively, is observed only in normal thyroid cells, but is lost in transformed thyroid cells. In vivo studies with thiouracil-fed rats demonstrated that increased serum levels of TSH up-regulated r-PTPeta mRNA expression in parallel with the stimulation of thyroid growth and function. The reduction of blood TSH levels due to iodide refeeding to goitrous rats determined a marked down-regulation of r-PTPeta expression, in parallel with involution of thyroid hyperplasia. Taken together these results demonstrate that the phosphatase r-PTPeta is regulated by the two main thyroid regulatory pathways and suggest that it may play an important role in the growth and differentiation of thyroid cells.     

Early diagnosis of carpal tunnel syndrome: comparison of sensory conduction studies of four fingers

Sensory studies of four fingers were performed on 72 patients with early (distal motor latency <4.2 ms) carpal tunnel syndrome (CTS) and on 43 control subjects. Results demonstrate that sensory studies of digit 4 yields the highest sensitivity (88%) for diagnosis of early CTS. The sensitivity of digit 1, digit 2, and digit 3 was 61%, 22%, and 50%, respectively.