Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours

This paper describes a method for matching high-temperature superconducting nuclear magnetic resonance (NMR) signal pickup coils to field-effect transistor (FET) preamplifiers using amplifier-specific noise figure and gain parameters to obtain a matching compromise that improves gain flatness for a given permissible noise figure. A technique for obtaining these parameters is also described in an appendix.     

Domain swapping in G-protein coupled receptor dimers

Computer simulations were performed on models of the beta2-adrenergic receptor dimer, including 5,6-domain swapped dimers which have been proposed as the active, high affinity form (here the dimer interface lies between helices 5 and 6). The calculations suggest that the domain swapped dimer is a high energy structure in both the apo dimer and in the presence of propranolol. In the presence of agonist the energy of the domain swapped dimer is significantly lowered. Analysis of the dimer structure suggests that the agonist-induced conformational change optimizes the helix-helix interactions at the 5-6 interface. An antagonist on the other hand has little effect on these interactions. These observations are consistent with the hypothesis that the agonist functions by shifting the equilibrium in favour of the domain swapped dimer. Indirect support for the domain swapping hypothesis was obtained from the correlated mutations amongst the external residues of the known beta2-adrenergic receptors. These occur mainly at the 5-6 interface at precisely the locations predicted by the simulations; site-directed mutagenesis data in support of a functional role for these lipid-facing correlated residues is presented. The article includes a review of the experimental evidence for G-protein coupled receptor dimerization. Many other aspects of G-protein coupled receptor activation are discussed in terms of this domain swapping hypothesis     

Subfornical organ: forebrain site of pressor and dipsogenic action of angiotensin II

Intracranial injection of angiotensin II (AII) at three brain sites elicited near simultaneous dipsogenic and pressor effects in rats. Both effects were maximal, occurred with the shortest latencies, and at the lowest doses of AII when the cannula terminated precisely within the parenchyma of the subfornical organ (SFO). Pressor effects were produced by SFO injection of a dose of AII (0.1 pg) which approximates plasma AII concentrations at the high end of the physiological range. Both the drinking and pressor effects were blocked by saralasin. Injections of AII at sites immediately adjacent to SFO produced smaller effects with longer latencies. These results ruled out the possibility that SFO injections were effective via leakage to alternative sites. The pressor effect of AII at the SFO remained in animals under chloralose anesthesia, demonstrating that it is not an artifact of drinking behavior. These results indicate that the SFO is a site of AII pressor action, and confirm previous demonstrations that the structure is a site of AII drinking action.     

Delayed hydrogen embrittlement in Zr-2.5 wt % Nb

Delayed failures at welds in components of Zi-2.5 wt % Nb are attributed to zirconium hydride forming at the root of a notch adjacent to the welds. Residual tensile stresses provide the driving force for growth of the hydride. The observed rate of growth is considerably higher than the rate calculated by techniques which give good quantitative agreement with experiments at about 575 K. Failures of the type studied here are inhibited by stress relief of the component in question.     

Study of grain boundary fracture surfaces in doped tungsten-rhenium alloys

The combination of Auger electron spectroscopy and scanning electron microscopy has identified the source of the unique interlocked elongated grains responsible for the high temperature sag resistance in doped tungsten and tungsten-rhenium alloys as due to bubbles which are formed by the volatilization of potassium during sintering. By pinning grain boundaries these bubbles raise the recrystallization temperature (from 1300†C to 2100†C) and their distribution within the material controls the recrystallized grain morphology. There is a thin layer of potassium remaining on the bubble surfaces. The size and distribution of the bubbles is related to the amount of material deformation during processing. Increasing rhenium content does not affect the concentration or distribution of residual potassium. It has no noticeable effect on bubble size, distribution or density. The presence of a thermal gradient during annealing does affect bubble density and recrystallization temperature. Formerly with the Air Force Materials Laboratory, Wright-Patterson AFB, Ohio Formerly with the Aerospace Research Laboratory, Wright-Patterson AFB, Ohio     

Coronary artery spasm in the denervated transplanted human heart: a clue to underlying mechanisms

The mechanism of coronary artery spasm has been poorly understood but there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient's heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic of hormonal products may play an important role.     

Comparative effects of cadmium, zinc, and lead in vitro on pulmonary, adrenal, and hepatic microsomal metabolism in the guinea pig

The in vitro effects of Cd, Zn, and Pb on pulmonary, adrenal, and hepatic microsomal enzyme activities in guinea pigs were compared. Cd and Zn produced concentration-dependent (20-200 microM) decreases in benzphetamine demethylase and biphenyl hydroxylase activities in adrenal, liver, and lung. Pb had no significant effect on either enzyme in any of the tissues studied. Adrenal and pulmonary enzymes were more sensitive to the effects of Cd and Zn than were hepatic enzymes. Benzo[a]pyrene hydroxylase and ethoxycoumarin deethylase activities were decreased by Zn, Cd, and Pb in adrenal, liver, and lung microsomes. The inhibitory effect on benzo[a]pyrene and ethoxycoumarin metabolism were far greater than those on benzphetamine or biphenyl metabolism. The relative potencies of the metals as inhibitors of xenobiotic metabolism were Zn greater than Cd greater than Pb. Cd and Zn also inhibited steroid 21-hydroxylase activity in adrenal microsomes, but Pb had no effect on steroid metabolism. In addition, microsomal epoxide hydratase activity in adrenal, liver, and lung was inhibited by Cd but not by Zn or Pb. The results demonstrate that adrenal and pulmonary microsomal enzymes, like those in liver, are inhibited by various metals. Inhibition of mixed-function oxidases by metals in vitro is apparently not related to changes in cytochrome P-450 levels or substrate binding to cytochrome P-450. In addition, the actions of Cd, Zn, and Pb in each tissue are highly dependent on the substrates employed.