Climate forcing of volcano lateral collapse: evidence from Mount Etna, Sicily.

In this study, we present evidence for early Holocene climatic conditions providing circumstances favourable to major lateral collapse at Mount Etna, Sicily. The volcano's most notable topographic feature is the Valle del Bove, a 5 x 8 km cliff-bounded amphitheatre excavated from the eastern flank of the volcano. Its origin due to prehistoric lateral collapse is corroborated by stürtzstrom deposits adjacent to the amphitheatre's downslope outlet, but the age, nature and cause of amphitheatre excavation remain matters for debate. Cosmogenic (3)He exposure ages determined for eroded surfaces within an abandoned watershed flanking the Valle del Bove support channel abandonment ca 7.5 ka BP, as a consequence of its excavation in a catastrophic collapse event. Watershed development was largely dictated by pluvial conditions during the early Holocene, which are also implicated in slope failure. A viable trigger is magma emplacement into rift zones in the eastern flank of a water-saturated edifice, leading to the development of excess pore pressures, consequent reduction in sliding resistance, detachment and collapse. Such a mechanism is presented as one potential driver of future lateral collapse in volcanic landscapes forecast to experience increased precipitation or melting of ice cover as a consequence of anthropogenic warming.

High resolution autoantibody detection by optimized protein G-horseradish peroxidase immunostaining in a western blotting assay.

We report a procedure for optimisation of Western blotting using protein G-horseradish peroxidase (protein G-HRP) which avoids the false positive reactions often caused by second antibodies and increases the detection of autoantibodies by protein G conjugate. A number of modifications were investigated. Higher concentrations of serum and protein G-HRP at 1:5 to 1:10 and 1:100, respectively, increased the detection to the same order as that obtained with second antibody systems and gold staining with silver enhancement. The role of various detergents in the procedure was established. 3-[(3-Cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) in incubation with protein G-HRP increased the binding between protein G and immunoglobulin G. Addition of Tween-20 for blocking produced little background so that protein blockers could be avoided. Prolonged incubation with serum increased markedly the sensitivity of the procedure when compared with the recommended 2 h incubation period. Polyvinylidene difluoride membrane provided better transfer effect, lower background and higher mechanical strength than nitrocellulose membrane. The utilization of only one antibody-specific ligand increased the simplicity, reliability, economy, efficiency and specificity of the method. These modifications make this method significantly better for detection and screening for autoantibodies.

Massive epistaxis from nasal CPAP therapy.

A 75-year-old man with obstructive sleep apnea and secondary right heart failure was started on nasal CPAP therapy. Shortly thereafter he experienced massive life-threatening epistaxis requiring nasal packing and hospitalization. The epistaxis was thought to be due to the drying effect of nasal CPAP.

The collagenase produced by neoplastic rat epithelial cells: modulation of secretion, molecular weight characteristics, and purification.

The modulation of the production of collagenase by an epithelial cell line derived from a spontaneously arising rat mammary carcinoma has been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, thus avoiding the poorly characterized and variable effects of serum on collagenase production. Piperazine-N,N'-bis-(2-ethanesulfonic acid) (Pipes), retinoic acid and cytochalasin B all stimulated collagenase secretion, while dexamethasone inhibited it and progesterone, prolactin, prostaglandin E2, and estrogen had no effect. This profile of response to exogenous compounds was distinct from that of cells of mesenchymal origin and from human keratinocytes. For the production of large quantities of collagenase, culture medium was supplemented with Pipes (30 mM, pH 6.8), and retinoic acid (1 microM, on alternate feeds). The collagenase secreted by BC1 cells grown under these conditions was latent and had a molecular mass of 59 kDa. Treatment of the 59 kDa form with trypsin or APMA caused a progressive decrease in molecular mass via 54 kDa and 52 kDa intermediates, to a 48 kDa form. This form was purified to electrophoretic homogeneity by heparin-Sepharose, zinc-chelate-Sepharose, and Sephacryl S-200 chromatography. Five milligrams of purified collagenase were recovered per litre of culture medium.

Modulation of anti-tumour immunity and the effect of bacterial endotoxin on the growth of different syngeneic tumours from small inocula in mice.

Studies were undertaken to determine the influence of E. coli lipopolysaccharide (LPS) on the growth of various doses of two antigenically-distinct syngeneic murine fibrosarcomas designated H1 and H7. The 'weakly' antigenic H1 tumour injected subcutaneously (s.c.) along the abdominal wall was profoundly susceptible to the growth-potentiating effects of a single intraperitoneal (i.p.) injection of 2 micrograms LPS, administered concurrently. 'Sneaking through' effects in control mice were observed with doses of 10 and 100 H1 tumour cells. Rejection of medium-sized inocula 25 or 500 H1 tumour cells were abolished by the administration of LPS. In contrast, the 'strongly' antigenic H7 tumour did not exhibit the 'sneaking through' phenomenon and its growth was only temporarily affected by LPS. Studies were also performed to determine the effect of LPS on the kinetics of delayed-type hypersensitivity (DTH) induced by mitomycin C-treated (MCT) H1 or H7 tumour cells inoculated s.c. into the footpads of mice. The 'strongly' antigenic MCT H7 tumour cells induced consecutive waves of footpad swelling of diminishing intensity and corresponded to periods of anti-tumour resistance. The specific phase of MCT H7-induced footpad swelling, maximal at day 6, was delayed in its induction if LPS was administered concurrently with MCT H7 tumour cells. In contrast, the 'weakly' antigenic MCT H1 tumour cells induced only one specific phase of footpad swelling which was rapidly down-regulated. The induction of immunity by MCT H1 tumour cells was also delayed by the concomitant administration of LPS. Because the 'weakly' antigenic H1 tumour was unable to sustain consecutive waves of anti-tumour immunity, the delay in the expression of such immunity by LPS allowed the H1 tumour cells to multiply to eventually overwhelm a rapidly down-regulated immune response. In contrast, the incidence of tumours arising from the 'strongly' antigenic H7 tumour cells was not significantly affected in LPS-treated mice because the tumour cells which escaped the first encounter with delayed anti-tumour immunity, succumbed to subsequent waves of resistance in both normal and LPS-treated mice injected with fewer than 1 X 10(5) H7 tumour cells.

Modulation of anti-tumour immunity induced by syngeneic mitomycin C-treated murine tumour cells.

Experiments were performed to examine the kinetics of delayed-type hypersensitivity (DTH) to mitomycin-C-treated syngeneic murine fibrosarcomas inoculated into the footpads of mice. Evidence is presented to show that a "strongly" antigenic tumour, designated H7, elicits consecutive waves of footpad swelling in both primary and secondary responses. Periods of anti-tumour resistance coincided with the expression of each successive wave of footpad swelling in normal and immune mice. The down-regulation of the response, between the successive peaks of footpad swelling, was accompanied by active tumour growth. In contrast, the non-cross-reacting "weakly" antigenic tumour, designated H1, induced footpad swelling which was expressed only once after either primary or secondary sensitization. Unlike that induced by the "strongly" antigenic H7 tumour, the anti-tumour immunity to the H1 tumour was not sustained beyond its initial specific phase. Consequently, H1 tumour cells which survived the initial phase of anti-tumour immunity appeared to encounter no further resistance. Thus the distinctive feature of the "weakly" antigenic H1 tumour was its inability to sustain consecutive waves of tumour resistance as exhibited by the "strongly" antigenic H7 tumour. It is proposed that "weakly" and "strongly" antigenic tumours are distinguished by their different abilities to down-regulate the anti-tumour immune response. The "weakly" antigenic tumour induces specific immunity which is rapidly down-regulated while that induced by the "strongly" antigenic tumour is sustained by successive waves of anti-tumour activity of diminishing intensity. Suppression of some but not all waves of footpad swelling occurred in mice with growing H7 tumours.

Collagenolytic activity by malignant tumours.

Five carcinomas and 5 sarcomas were investigated in relation to their production of neutral proteases capable of digesting polymeric collagen. The carcinomas were far more active than the sarcomas but all the malignant tumours produced enzymes which were capable of causing collagenolysis in vitro. collagenolytic enzymes were recovered from extracts of neoplastic cells from long-term culture, from the media in which these cells were cultured, from the media of mixed cell cultures (neoplastic, stromal and inflammatory cells from minced tumours), and from normal fibroblasts cultures. In contrast to the cultures of non-neoplastic fibroblasts, the tumour cells produced active enzymes, since limited proteolysis with trypsin or treatment with p-aminophenyl-mercuric acetate (APMA) caused no increase in enzyme activity. These tumours possess collagenolytic ability in vitro which may be partly responsible for their invasive nature in vivo.

Potentiation of tumour growth by endotoxin in serum from syngeneic tumour-bearing mice.

The subcutaneous growth of 2 antigenically distinct syngeneic methylcholanthrene-induced murine fibrosarcomas, designated H1 and H7, were significantly augmented by the concomitant administration of E. coli endotoxin (LPS). Amounts as little as 0.2 micrograms i.p. potentiated tumour growth. The weakly antigenic tumour, H1, was more susceptible to provocation by LPS than the more strongly antigenic H7. Maximum provocation of H1 tumour growth occurred when LPS was injected 1 day before the administration of 5000 tumour cells. In contrast, significant anti-tumour resistance resulted if LPS was administered 6 days before the inoculation of tumour cells. Preliminary evidence indicates that low doses of LPS can facilitate the "sneaking through" phenomenon. Enhancement of tumour growth could not be demonstrated with sera or plasma from tumour-bearing mice, unless the samples were contaminated with endotoxin. The results illustrate the importance of excluding endotoxin from solutions used in studies of experimental tumours.