Newly established MST-1 tumour cell line and tumour-infiltrating lymphocyte culture from a patient with soft tissue melanoma (clear cell sarcoma) and their potential applications to patient immunotherapy

The establishment and characterisation of paired autologous tumour cell line (MST-1) and tumour-infiltrating lymphocyte (TIL) culture from a tumour mass of a 14-year-old Taiwanese girl with soft tissue melanoma are described. MST-1 cells grown in vitro were heterogeneous in morphology, ranging from floating round cells, loosely attached round/oval or elongated cells with prominent pseudopod-like processes, to well-attached spindle and elongated dendritic cells without obvious pseudopods. Immunostaining revealed that major melanoma-associated antigens, such as S100 protein, HMB-45, melanotransferrin, chondroitin sulphate proteoglycan, and the gangliosides GD2 and GD3, were consistently expressed by the tumour tissue, severe combined immunodeficiency (SCID) mouse xenograft and derived cell lines. Flow cytometric analysis of the tumour DNA content showed an index of 1.8 relative to normal peripheral blood lymphocyte DNA. Chromosome analysis revealed all cells at a hypotetraploid level with several clonal chromosome aberrations, including deletions at 10p and 12q, an addition at 12q, translocations t(1;14) and t(5;6). Electron microscopy showed melanosome structures. This observation and the expression of the major melanoma-associated antigens were all indicative of the melanocytic origin of MST-1 tumour. Interleukin-2 (IL-2) expanded TILs had the predominant CD8+ phenotype and the capacity to lyse cells of the cultured autologous tumour. The availability of the soft tissue melanoma cell line, the SCID mouse xenograft tumour system as well as autologous TILs described herein would provide useful materials for identifying T-cell-defined antigens as well as a model system for devising individualised cancer biotherapeutic strategies. This cell line can also be used for further studies aimed at uncovering the histogenesis of this rare cancer.     

Technologies for in situ cleanup of contaminated sites

Groundwater contamination by non-aqueous phase liquids (NAPLs) and denser than water non-aqueous phase liquids (DNAPLs) poses one of the greatest remedial challenges in the field of environmental engineering. Due to low water solubilities and aqueous diffusivities, conventional pump-and-treat technologies have a poor record of success in remediation of DNAPL contaminated aquifers. Better success has been found with the removal of volatile LNAPLs due to higher gaseous diffusivities, propensity for aerobic biodegradation, and ease of pumping and handling large quantities of gas. An evaluation of in situ cleanup technologies on the basis of their applicability to in situ treatment of NAPL contaminated aquifers is presented. Emphasis is placed on treatment of the separate phase occurring in the saturated zone. Soil washing, air sparging, biodegradation, electro-osmosis, enhanced steam extraction, stabilization/solidification, treatment walls, radio frequency heating, and containment systems and barriers are among the in situ technologies reviewed. In the context of the governing contaminant fate and transport processes, the relative merits of each technology are assessed on the basis of its theoretical background, field implementability, level of demonstration and performance, waste, technical and site applicability/limitations, commercial availability, and cost and residuals management.     

Occupational asthma due to latex in health care workers

Immediate hypersensitivity reactions ranging from mild urticaria to life threatening anaphylaxis after exposure to natural rubber latex have been reported frequently in health care workers while occupational asthma due to latex exposure is less well studied. The results of specific challenge tests and immunological tests in four health care workers with work related respiratory and skin disorders induced by the use of latex gloves are described. Occupational asthma was confirmed in three subjects by specific challenge tests. All had a positive skin test reaction to the latex extract; specific IgE antibodies were detected in only one subject. The fourth subject had a negative specific inhalation and skin test reaction to the latex extract. Peak expiratory flow monitoring at work and away from work showed a pattern consistent with work related asthma. These findings confirm that latex is a cause of occupational asthma in health care workers.     

Partial disruption of fear conditioning in rats with unilateral amygdala damage: correspondence with unilateral temporal lobectomy in humans

Conditioned fear in rats was assessed for the effects of pretraining amygdala lesions (unilateral vs. bilateral) across unconditioned stimulus (US) modalities (white noise vs. shock). In contrast to sham controls, unilateral amygdala lesions significantly reduced conditioned freezing responses, whereas bilateral amygdala lesions resulted in a nearly complete lack of freezing to both the conditioned stimulus (CS) and the context. The lesion effects were more pronounced for CS conditioning but were consistent across US modalities. It was concluded that white noise can serve as an effective US and that unilateral amygdala lesions attenuate but do not eliminate conditioned fear in rats. The results support our interpretation of a recent fear conditioning study in humans (K. S. LaBar, J. E. LeDoux, D. D. Spencer, & E. A. Phelps, 1995).     

Effects of feeding on protein turnover in healthy children and in children with cystic fibrosis

In 24 patients presenting with 55 renal lesions (mean size, 20.8 mm), single-breath-hold (SBH) fast spin-echo (FSE) techniques allowing T1 and T2 images to be produced within 20 and 23 sec, respectively, were compared with routine non-breath-hold (NBH) spin-echo (SE) T1 and NBH-FSE T2 sequences. Contrast-to-noise ratios (CNRs) measured from SBH-FSE T1 images were an average of 97% higher than their NBH counterparts (P = .0001) and allowed an improved lesion conspicuity in 80% of the cases (P = 0.0001). For T2 imaging, SBH-FSE and NBH-FSE sequences were not statistically different with respect to lesion conspicuity (P = .55) and CNR values (P = .19). This was observed despite a 35% average decrease in CNR of SBH-FSE compared to NBH-FSE images. By reducing respiratory motion artifacts while preserving SE-like image contrast, SBH-FSE techniques have the potential to replace routine NBH sequences for an optimal diagnosis of renal masses.     

The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis

Cremophor EL (CR) is a solubilizing agent and a modulator of P-glycoprotein (P-gp)-mediated anticancer multidrug resistance. The present study was undertaken to evaluate whether doxorubicin (Dox) pharmacokinetics, therapeutic activity and cardiotoxicity in Swiss albino mice is modified when combined with CR treatment. CR (2.5 ml/kg, i.p) given simultaneously with Dox (20 mg/kg, i.p.) increased Dox levels in plasma, heart, liver and kidneys of healthy mice. Using an Ehrlich ascites carcinoma (EAC)-bearing mice experimental model, CR (2.5 ml/kg) improved the survival and antitumor activity of Dox. The enhanced antitumor activity of Dox was related to a significant increase in EAC tumor cellular Dox content by CR. Furthermore, CR (1 microg/ml) potentiated the in vitro cytotoxicity of Dox in cultured EAC cells. In healthy mice, Dox-induced mortality was markedly reduced by simultaneous treatment with CR. CR enhanced DOX-induced increase in plasma lactate dehydrogenase, creatine phosphokinase (CPK) and CPK-MB isozyme activities, as well as the cardiac malondialdehyde level. CR also increased Dox-induced focal necrotic myocardial lesions. These findings suggest that CR increased DOX antitumor activity and cardiotoxicity as a result of enhancing its bioavailability, and decreased Dox-induced mortality in mice by a mechanism not yet defined.     

Cyanobacterial tRNA(Leu)(UAA) group I introns have polyphyletic origin

Insecticide susceptibility of field populations of stable flies, Stomoxys calcitrans (L.), was assayed using 3 exposure techniques: treated filter papers, treated glass petri dishes, and topical applications. Both topical applications and residual exposure to treated glass surfaces were suitable for testing susceptibility of stable flies to permethrin, stirofos, or methoxychlor. Residues on filter papers yielded inconsistent results with stirofos and methoxychlor. Significant concentration-mortality regression lines were generated with permethrin residues on filter papers, but approximately 1,000 times more insecticide was required to produce a toxic response when compared with permethrin residues on glass. Because of higher variability in response and the greater amount of insecticide required, residues on filter papers do not appear appropriate to test insecticide susceptibility in stable flies. Paired comparisons of field (F) and susceptible (S) stable flies resulted in field to susceptible ratios significantly > 1.0 only when the flies were treated topically, which suggests that topical application is more sensitive than residues on glass for the insecticides tested. Topical treatment with permethrin resulted in one FS(LD90) of 1.8-fold. Topical treatment with methoxychlor resulted in one FS(LD90) of 3.4-fold. However, the magnitude of these ratios is not larger than the significant differences observed within the susceptible laboratory colony from one generation to another. Intense exposure to insecticides is not known to have occurred in these field populations, indicating that the observed differences are the result of natural variation among stable fly populations and unrelated to prior selection with insecticides.