Pharmacological control of leukotriene and prostaglandin production from mouse peritoneal macrophages

Leukotriene and prostaglandin production by mouse peritoneal macrophages was investigated. It could be shown that the tumour promoter 12-O-tetradecanoylphorbol-13-acetate initiated the release of prostaglandin E₂ but had little effect on the release of leukotriene C₄-like immunoreactivity. The divalent cation ionophore A 23187 at concentrations between 10^–6 and 10^–8 mol/l initiated prostaglandin as well as leukotriene release. This prostaglandin and leukotriene release could be modulated by drugs. Non-steroidal anti-inflammatory drugs including benoxaprofen inhibited prostaglandin release but simultaneously enhanced leukotriene production. The analgesics paracetamol and 4-methylaminoantipyrine had similar effects at high concentrations. The experimental compound BW 755 c inhibited prostaglandin and leukotriene production while the antithrombotic compound nafazatrom inhibited the production of leukotriene C₄-like immunoreactivity but enhanced prostaglandin E₂ production. Nordihydroguaiaretic acid inhibited prostaglandin and leukotriene production. The results show that the metabolism of arachidonic acid in macrophages via the cyclooxygenase or the lipoxygenase pathway is dependent on the stimulus applied. Both pathways can be inhibited conjointly or selectively by drugs. Our results do not provide evidence that differences in anti-inflammatory activity claimed for some of the drugs tested can be explained by differential inhibition of either pathway. The experimental system described may be used for assessing the potency of drugs to inhibit the lipoxygenase and the cyclooxygenase pathway of arachidonic acid metabolism.     

Cell-surface ganglioside GD2 in the immunohistochemical detection and differential diagnosis of neuroblastoma.

The expression of the disialoganglioside GD2 was analyzed in 67 solid tumors and normal tissues from children by using the GD2-specific murine monoclonal antibody 3A7 and the indirect immunoperoxidase method. GD2 was expressed in all of 28 neuroblastomas and was most abundant in stroma-poor tumors. In differentiating stroma-rich neuroblastomas, neuroblastic clusters, neurofibrils, and most ganglion-like cells were positive, whereas Schwann's-cell stroma did not express GD2. In ganglioneuromas, only a few ganglion-like cells showed GD2, whereas all other structures were negative. Scattered foci of ganglioside GD2 also were found in some non-neuronal tumors, such as rhabdomyosarcomas and osteosarcomas, but not in lymphomas, Askin tumors, or most Wilms' tumors. The monoclonal antibody 3A7 is a useful aid in the immunohistochemical diagnosis of neuroblastoma. In addition, the intense cell surface staining of neuroblastoma cells by this reagent makes it potentially useful for detecting residual neuroblastoma in bone marrow samples and lymph node biopsies.     

DNA content as a prognostic marker in patients with oral leukoplakia

BACKGROUND: Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. METHODS: We identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade. The mean duration of follow-up was 103 months (range, 4 to 165). RESULTS: Among 150 patients with verified epithelial dysplasia, a carcinoma developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25 (17 percent) had aneuploid (abnormal) lesions at the time of the initial diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3 percent), as compared with 21 of the 25 patients with aneuploid lesions (84 percent), yielding a negative predictive value of 97 percent with respect to the diploid lesions and a positive predictive value of 84 percent with respect to the aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid lesions (60 percent). The mean time from the initial assessment of the DNA content to the development of a carcinoma was 35 months (range, 4 to 57) in the group with aneuploid lesions and 49 months (range, 8 to 78) in the group with tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97 percent among the group with diploid lesions, 40 percent among the group with tetraploid lesions, and 16 percent among the group with aneuploid lesions (P<0.001). CONCLUSIONS: The DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.     

Detection of cod (Gadus morhua) subpopulations by chemical and statistical analysis of pollutants

The hypothesis was postulated that various subpopulations may be represented in samples of fish living in an open fjord system. A statistical model based on mercury and octachlorostyrene concentrations in cod from two monitoring programs in a Norwegian fjord, was applied to test the hypothesis. The model was (mercury concentration) = b · (weight), where the coefficient b reflects the mercury concentration in the environment and to is the weight exponent. The effects of weight, time, and sex were considered. The distributions of b values, or normalized b values, were investigated by the normal plot technique. Discontinuities in the graphs were interpreted as indicative of the presence of two subpopulations. Weight-independent concentration ratios were also used in the classification of the fish on the octachlorostyrene data. The two subgroups were the same as those revealed by the mercury data. The statistical analysis of mercury and octachlorostyrene data supported the hypothesis that different subpopulations may be represented in samples of fish found in the present and similar fiord systems. The size of a fish sample must permit the testing of a general hypothesis of nonuniform distribution of concentrations of pollutants in the fish.     

Flattening the quality of life curve? A prospective person-centred study from Norway amid COVID-19

Quality of Life Research - We examined multidimensional, heterogeneous reactions to the COVID-19 pandemic and associated measures to provide further insights into the developmental processes of...     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

The Potential of Anti-Bullying Efforts to Prevent Academic Failure and Youth Crime. A Case Using the Olweus Bullying Prevention Program (OBPP)

Prevention Science - The effectiveness of bullying prevention programs has led to expectations that these programs could have effects beyond their primary goals. By reducing the number of victims...     

The relationship of negative schizophrenia to parkinsonism

The positive-negative distinction of schizophrenia has emerged as a valid means of clarifying its heterogeneity. Despite evidence that the two symptom classes may reflect different dimensions of the disease, there is presently no integrated model for understanding of the pathophysiology of these symptoms and their co-occurrence in schizophrenia. We propose that negative phenomena of schizophrenia may be a variant of Parkinsonism. This view is supported by the overlap with Parkinsonism in terms of clinical features, neurochemistry, pharmacology, as well as neuroradiological and neuropathological aspects. As such, negative symptoms may be a manifestation of disease of the basal ganglia and constitute the core pathology in schizophrenia. Positive symptoms, conversely, may reflect an "accessory" process related to a compensatory increase in striatal and limbic dopamine activity following an injury to the dopaminergic system. In the present communication we present a series of studies that support the association of negative schizophrenia and Parkinsonism. Based on this evidence, we suggest that schizophrenic patients with prominent negative symptoms might be managed like patients with Parkinson's disease, namely, with dopaminergic drugs and MAO-B inhibitors. Finally, the association of negative schizophrenia with Parkinsonism raises the possibility that adrenal medullary tissue transplantation, which may benefit a selected group of Parkinsonian patients, may be a future promising therapy for refractory negative schizophrenia.