Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.     

Endorphin mediated increase in pain threshold induced by long-lasting exercise in rats

Rats were trained to run spontaneously, without stress, in running wheels. The running activity increased gradually and could reach a plateau of 7 km/night after 3–4 weeks. During the first hour of running in the dark phase the squeak threshold increased significantly and remained high in the morning. The degree of increased threshold was correlated to the amount of running activity. The squeak threshold declined during the following 6 hours of inactivity. A rapid decrease in threshold occurred after naloxone (1–2 mg/kg i.p.). It is suggested that long-lasting muscle exercise (e.g. jogging), acupuncture, and low frequency electrical stimulation of afferent nerve fibres produce discharges in muscle afferents which influence central endorphin mechanics giving analgetic effects.     

Effects of phorbol esters on endothelial cell microfilaments: Laser scanning confocal microscopy and quantitative morphometry of dose dependent changes

Phorbol esters are known to alter microfilaments but it is not clear if the changes correspond to modulation of the phosphoinositide turnover/protein kinase C system. The novel technique of laser scanning confocal epifluorescence was used to study fiber orientation in phorbol ester treated cells. We treated endothelial cells with control agents and agents known to stimulate protein kinase C: 4 alpha-phorbol, phorbol 12-myristate 13-acetate (PMA), phorbol dibutyrate (PDB), or lipopolysaccharide. After incubation with the test agents, the endothelial cell microfilaments were stained with rhodamine pholloidin and viewed by conventional epifluorescence and by laser scanning confocal epifluorescence microscopy. The images obtained by the confocal microscopy corresponded to a thin optical section through the cells, 300 nm or more in thickness. The microfilaments extended predominantly in the plane of focus. After exposure of the cells to phorbol esters, the stress fibers became more nearly parallel in arrangement or were shortened, but remained in the plane of focus. The modification of microfilaments in response to phorbol esters was quantitated by a single blind analysis. In order to compare the morphological changes with a biochemical action of the phorbol esters, we measured phosphoinositide turnover. The dose-dependence of morphological changes was compared and contrasted to the dose-dependent effect of phorbol esters on bradykinin-stimulated phosphoinositide turnover. PMA had about the same EC50 (1-5 nM) for both biochemical and morphological processes. PDB was less potent in inducing the disruption of microfilament structure than in inhibiting phosphoinositide turnover. Lipopolysaccharide was ineffective in inducing a morphological change under these conditions. A simple activation of protein kinase C is insufficient to explain the dose-dependent effects of phorbol esters. Thus a morphometric analysis can help distinguish the potency of cytoskeleton modulators.     

Immunologic and clinical improvement of progressive coccidioidomycosis following administration of transfer factor

Three patients with progressive coccidioidomycosis were given preparations of transfer factor (TF). Adverse reactions to TF were minimal. Following TF administration two of these patients had prolonged clinical remissions in their coccidioidal disease. Cellular immune responses were sequentially evaluated by coccidioidininduced delayed-type skin tests, lymphocyte blast transformation and macrophage inhibition factor production (MIF). These three patients each exhibited different cellular immune patterns before and after TF administration. Two patients converted their coccidioidin skin tests, and one converted lymphocyte transformation response to coccidioidin. Also, TF apparently favorably affected the MIF response in all three patients.     

Effects of vagal neuromodulation and vagotomy on control of food intake and body weight in rats.

Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.     

Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3

Eight Icelandic breast cancer kindreds were subjected to linkage analyses with respect to 28 microsatellite loci dispersed along the short arm of chromosome 3. Breast tumors derived from these kindreds were concurrently scored for allelic imbalance with ten of the markers. Linkage to most markers could be excluded on the basis of negative LOD scores and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was seen with two of the markers in comparison with results obtained from sporadic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not significantly elevated in the familial tumors. We suggest that the genetic defect responsible for breast cancer susceptibility in these families either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.     

Behavioral adaptations of two phytophagous insects feeding on two species of phototoxic Asteraceae

Two phototoxic plants of the Asteraceae family were studied in relation to species of phytophagous insects for which they are hosts:Argyrotaenia velutinana Wlk. feeding onChrysanthemum leucanthemum L. andChlorochlamys chloroleucaria (Guenée) colonizingRudbeckia hirta L. The toxicity of these two plants is related to the presence of acetylenes and thiophenes that induce a light-mediated production of deleterious singlet oxygen and other free radicals (phototoxicity). Results showed that females ofA. velutinana laid their eggs preferentially in the shade and the larvae adopted hiding behaviors, such as bending of ligulate corollas and silk spinning to build opaque shelters. By avoiding direct exposure to the sun, both behaviors may reduce phototoxicity associated with ingested plant materials. Furthermore, larvae ofC. chloroleucaria demonstrated a preference in the field for pollen, which constitutes a nonphototoxic tissue of their host plant. Experimental alterations of these specific behaviors induced important biological consequences for larvae of both insects such as mortality or reduction of larval growth rate. These results reinforce the idea that behavior may constitute an efficient adaptation to avoid phototoxicity.     

Einige neue oder bemerkenswerte Flechten mit gyalectoiden Apothecien von Nord-Indien und Nepal

This paper presents the results of taxonomic investigation of 8 species of lichens with gyalectoid apothecia collected in North-India and Nepal. Four species are recognized as new:Dimerella isidiata (sp. nova),D. nepalensis (sp. nova),Gyalideopsis lithophila (sp. nova) andRamonia nepalensis (sp. nova). Four species are reported for the first time from Nepal:Coenogonium moniliforme, Gyalectidium caucasicum, Gyalidea lecideopsis andG. scutellaris.     

Mineral cycling in a tropical palm forest

Nutrient cycling and biomass characteristics of a tropical palm forest dominated byOrbignya cohune were found to be different from thsoe of hardwood dominated forests. The cohune palm forest had a high proportion of biomass in leaves (5%), a reduced sapling layer, a large amount of standing forest litter and an exceptionally low decomposition rate factor (0.1 year^–1). Mineral concentrations in palm leaves were generally lower than in hardwood species with the exception of Na, which was exceptionally high inOrbignya cohune. Biomass was estimated at 226 tons ha^–1 containing 1173 kg ha^–1 N; 126 kg ha^–1 P; 437 kg ha^–1 K; 1869 kg ha^–1 Mg; 125 kg ha^–1 Ca, and 2177 kg ha^–1 Na. Soils of cohune association did not differ significantly from those of neighbouring hardwood dominated associations with the exception of Na which occurred in higher concentration because of bioaccumulation in the dominant. The results suggest that the growth habits and physiology of a dominant can strongly influence some of the ecological parameters used to describe aforest association.