Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells

Mitomycin C and hyperthermia are both toxic to chronically hypoxic EMT6 tumor cells. Combinations of this drug and heat were tested in vitro in normally aerated and chronically hypoxic EMT6 mouse mammary tumor cells to establish whether greater than additive cytotoxicity could be achieved by combined treatment. Cell survival was measured at four concentrations of mitomycin C (0.01, 0.1, 1.0, and 10 microM) at 37 degrees or at elevated temperatures (41, 42, and 43 degrees) for durations of 1, 2, 3, and 6 hr. At 42 degrees, exposure to mitomycin C for 3 and 6 hr produced a 2- to 3-fold increase in hypoxic tumor cell kill at all drug concentrations over that expected for strict additivity. A 15-fold enhancement in the kill of hypoxic tumor cells was obtained at 1.0 and 10 microM mitomycin C at 43 degrees for 6 hr of exposure. Under most conditions, additivity was observed for the antibiotic and heat in oxygenated cells, except at 43 degrees with 0.01 and 0.1 microM mitomycin C following 3 and 6 hr of treatment, conditions under which a 5- to 10-fold potentiation of tumor cell kill was obtained. The rate of formation of reactive metabolites from mitomycin C under anaerobic conditions in EMT6 cell-free preparations was measured. A 30 to 50% increase in alkylating activity was observed at elevated temperatures, suggesting that the enhanced cytotoxicity of mitomycin C with heat toward hypoxic cells may, in part, be due to an increase in activation of the drug.     

Cost of management of patients with haemophilia

The cost of managing 114 adult haemophiliacs in the west of Scotland was assessed for the period 1 March 1971 to 28 February 1974. Altogether 23 of them (20%) accounted for 80% of the resources used. The cost of hospital treatment of these patients during the period was compared with the predicted cost of home treatment, given the availability of freeze-dried factor VIII concentrate in sufficient amounts. We calculate that adequate on-demand home treatment would cost only 16% more than the present treatment, which is substantially less efficient.     

Nuclear distribution in Alternaria tenuis

Renal functional abnormalities constituting the syndrome of postobstructive diuresis imply both altered tubular and glomerular membrane properties. To determine the morphologic and ultrastructural correlates of this disorder a rat model was developed and 32 postobstructed kidneys were studied by light and electron microscopy at the midpoint of diuresis and compared to 22 controls. The abnormal morphology was: dilated distal tubules and collecting ducts, isolated proximal and distal tubule cells that allowed free access of luminal contents to the basement membrane, widened terminal bars and intercellular spaces, thickening of the glomerular basement membrane and, depending upon the portion of nephron, normal or reduced adenosine triphosphatase and acid phosphatase content. In order to confirm the functional nature of the nephrons studied as well as to assess glomerular and tubular permeability, horseradish peroxidase and cytochrome c were infused. These tracers, normally permeable to the glomerular basement membrane, were found in the intercellular spaces and to a lesser extent within cell organelles in the postobstructed diuretic animals whereas controls demonstrated a retarded filtration of horseradish peroxidase, no tracer in the intercellular spaces and large amounts of tracer contained within cell organelles. Absence of enzyme activity in the medulla and reduced dark to light cell ratios in the cortical collecting ducts correlated with prior observations made by others of diminished concentration and acidification processes, respectively. An increase in adenosine triphosphatase activity and renin granules within the juxtaglomerular cells indicated increased renin activity. These observations suggest that the renal functional abnormalities of postobstructive diuresis are attributable to altered glomerular and tubular permeabilities as well as with changes in metabolic activity.     

Overselectivity, developmental level, and overtraining in autistic and normal children

Thirteen autistic children were compared to 13 normal children matched to them in mental age, on performance of a visual discrimination task. Form, color, and size were relevant and redundant cues. The groups did not differ significantly in mean trials to reach criterion or in breadth of learning, and both groups increased their breadth of learning after 50 trials of overtraining. Form was preferred to color and size by both autistic and normal children. Within each group, rank on mental age was highly correlated with rank in breadth of learning. Verbal and nonverbal autistic children did not differ in breadth of learning or in dimensional preference. Even nonverbal autistics equaled the performance of their normal controls. Our results suggest that overselective attention is better understood as part of a general developmental lag in cognition in autistic children than as a specific deficit underlying psychotic behavior.     

Implicit self-esteem compensation: Automatic threat defense.

Four experiments demonstrated implicit self-esteem compensation (ISEC) in response to threats involving gender identity (Experiment 1), implicit racism (Experiment 2), and social rejection (Experiments 3-4). Under conditions in which people might be expected to suffer a blow to self-worth, they instead showed high scores on 2 implicit self-esteem measures. There was no comparable effect on explicit self-esteem. However, ISEC was eliminated following self-affirmation (Experiment 3). Furthermore, threat manipulations increased automatic intergroup bias, but ISEC mediated these relationships (Experiments 2-3). Thus, a process that serves as damage control for the self may have negative social consequences. Finally, pretest anxiety mediated the relationship between threat and ISEC (Experiment 3), whereas ISEC negatively predicted anxiety among high-threat participants (Experiment 4), suggesting that ISEC may function to regulate anxiety. The implications of these findings for automatic emotion regulation, intergroup bias, and implicit self-esteem measures are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The urinary ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid in surgical patients with chronic alcohol misuse

Interactions among growth factors are important in a variety of physiological and pathological processes. The regulation of IGF-I mRNA expression by bFGF was investigated in cultured rat Müller cells and the mechanism of regulation studied. Müller cells from 1- to 3-day-old Sprague-Dawley rats were isolated and cultured with Eagle MEM+10% FCS. Cultured cells were identified by immunocytochemistry using antibodies against vimentin, carbonic anhydrase C, and glutamine synthetase. Cells of passage 1-4 were treated with bFGF, the PKC inhibitor H-7, calphostin C, the PKC activator PMA or the PKA inhibitor H-89, as well as the adenylate cyclase activator forskolin, or adenylate cyclase inhibitor SQ22536. IGF-I and bFGF expression levels were assessed by Northern blot analysis. The addition of bFGF to culture medium down-regulated IGF-I expression in a dose- and time-dependent manner. Decrease of IGF-I expression started at a bFGF concentration of 1 ng ml-1. IGF-I mRNA level declined to 44% of baseline level at 10 ng ml-1 of bFGF, and reached a trough of 40% at 50 ng ml-1. At 10 ng ml-1 of bFGF, down-regulation of IGF-I expression was observed as early as 4 hr (60%) after treatment, and reached a trough of 42% by 8 hr. The temporal and concentration dependence of IGF-I expression by addition of the PKC activator PMA, to culture medium was similar to that due to the addition of bFGF. The down-regulation of IGF-I expression by bFGF (10 ng ml-1) and PMA (0.1 microM) was blocked by the PKC inhibitors H-7 (30 microM) and calphostin C (1 microM). Forskolin (5 microM), an adenylate cyclase activator, had activator, had no effect on IGF-I expression. SQ22536 (100 microM), an adenylate cyclase inhibitor, and H-89, a PKA inhibitor, had no inhibitory effect on bFGF-induced down-regulation of IGF-I expression. These results indicate that bFGF down-regulates IGF-I expression in cultured rat M uller cells through PKC activation.