Noncoplanar PCB 95 alters microsomal calcium transport by an immunophilin FKBP12-dependent mechanism

Activation of the Ras/MAPK signaling cascade is essential for growth factor-induced cell proliferation and differentiation. In this report, we describe the purification, cloning, and characterization of a novel protein, designated FRS2, that is tyrosine phosphorylated and binds to Grb2/Sos in response to FGF or NGF stimulation. We find that FRS2 is myristylated and that this modification is essential for membrane localization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK activation. FRS2 functions as a lipid-anchored docking protein that targets signaling molecules to the plasma membrane in response to FGF stimulation to link receptor activation with the MAPK and other signaling pathways essential for cell growth and differentiation. Finally, we demonstrate that FRS2 is closely related and probably indentical to SNT, the long-sought target of FGF and NGF receptors.     

SC-29333: a potent inhibitor of canin gastric secretion

The gastric antisecretory effects of SC-29333, a novel prostglandin E1 analogs, were compared to the reference standard PGE1 methyl ester (PGE1ME) in gsstric fistula and Heidenhain pouch dogs. Secretion was stimulated submaximally by continuous intravenous infusion of either histamine or pentagastrin. Meal-stimulated gastric secretory studies were also conducted. SC-29333 effectively inhibited volume, acid output, and papsin secretion, in a dose-dependent manner. Intravenously (i.v.), SC-29333 was found to be approximately 30 times more potent than PGE1ME. The ranges of active i.v. bolus doses for SC-29333 and PGE1ME were 0.3-3.0 and 10-30 mug/kg, respectively. Unlike PGE1ME, SC-29333 was orally effective at doses of 10-30 mug/kg and was considerably better tolerated and longer acting than PGE1ME at active antisecretory doses. It is concluded, therefore, that SC-29333 is a potent, long-acting, orally effective inhibitor of gastric secretion in the dog.     

Dopamine depletion augments endogenous opioid-induced locomotion in the nucleus accumbens using both mu 1 and delta opioid receptors

The aim of this study is to analyze further the opioid receptor subtypes involved in the augmentation of behavioral activity after dopamine depletion in the nucleus accumbens of rats. Initially, the opioid receptors involved in the augmentation of locomotion produced by endogenous opioids were evaluated by microinjection of kelatorphan, an inhibitor of proteolytic enzymes that inactivates enkephalin, with or without specific antagonists for mu 1 or delta-opioid receptors, naloxonazine or naltrindole, respectively. Kelatorphan produced a dose-dependent increase in horizontal photocell counts and vertical movements. At all doses examined the behavioral response was augmented in rats sustaining accumbal dopamine lesions. The augmentation in dopamine-depleted rats was partially blocked by naloxonazine or naltrindole. Since the motor stimulant response to intra-accumbens microinjection of the delta-opioid agonist, [D-penicillamine2,5]-enkephalin, was not augmented in a previous study, we tested the behavioral response to a new endogenous delta-opioid agonist, [D-Ala2] deltorphin I. The locomotor response to deltorphin was slightly augmented in dopamine-depleted rats. These data suggest that the augmentation in the motor response elicited by endogenous opioids after dopamine lesions in the nucleus accumbens involves both mu 1, and delta-opioid receptors.     

Kinetic studies of Bacillus polymyxa nitrogenase

Nitrogenase from the facultative anaerobe Bacillus polymxa was separated into its component proteins, which were recombined in the ratio that produced optimal specific activity (125 to 175 nmol of C2H2 reduced/min per mg of total protein). The apparent Michaelis constants (Km)for the magnesium adenosine triphosphate complex, reducible substrates azide, acetylene, and N2 and the nonphysiological electron donor hydrosulfite (S2O42-) were determined to be 0.7, 0.7, 0.2, 0.06, and 0.03 MM, respectively. These apparent Km values are in reasonable agreement with those reported for the nitrogenases of Azotobacter vinelandii and Klebsiella pneumoniae. Either a total lack of cooperativity between binding sites or a single binding site for reducible substrates is indicated by analysis of Hill plots. Hill plot slopes of approximately 1.7 suggest that multiple binding sites exist for both ATP and S2O42-.     

Differences in restenosis propensity of devices for transluminal coronary intervention. A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty. CARPORT, MERCATOR, MARCATOR, PARK, and BENESTENT Trial Groups

With the increasing clinical application of new devices for percutaneous coronary revascularization, maximization of the acute angiographic result has become widely recognized as a key factor in maintained clinical and angiographic success. What is unclear, however, is whether the specific mode of action of different devices might exert an additional independent effect on late luminal renarrowing. The purpose of this study was to investigate such a difference in the degree of provocation of luminal renarrowing (or 'restenosis propensity') by different devices, among 3660 patients, who had 4342 lesions successfully treated by balloon angioplasty (n = 3797), directional coronary atherectomy (n = 200), Palmaz-Schatz stent implantation (n = 229) or excimer laser coronary angioplasty (n = 116) and who also underwent quantitative angiographic analysis pre- and post-intervention and at 6-month follow-up. To allow valid comparisons between the groups, because of significant differences in coronary vessel size (balloon angioplasty = 2.62 +/- 0.55 mm, directional coronary atherectomy = 3.28 +/- 0.62 mm, excimer laser coronary angioplasty = 2.51 +/- 0.47 mm, Palmaz-Schatz = 3.01 +/- 0.44 mm; P < 0.0001), the comparative measurements of interest selected were the 'relative loss' in luminal diameter (RLoss = loss/vessel size) to denote the restenosis process, and the 'relative lumen at follow-up' (RLfup = minimal luminal diameter at follow up/vessel size) to represent the angiographic outcome. For consistency, lesion severity pre-intervention was represented by the 'relative lumen pre' (RLpre = minimal luminal diameter pre/vessel size) and the luminal increase at intervention was measured as 'relative gain' (relative gain = gain/ vessel size). Differences in restenosis propensity between devices was evaluated by univariate and multivariate analysis. Multivariate models were constructed to determine relative loss and relative lumen at follow-up, taking account of relative lumen pre-intervention, lesion location, relative gain, vessel size and the device used. In addition, model-estimated relative loss and relative lumen at follow-up at given relative lumen pre-intervention relative gain and vessel size, were compared among the four groups. Significant differences were detected among the groups both with respect to these estimates, as well as in the degree of influence of progressively increasing relative gain, on the extent of renarrowing (relative loss) and angiographic outcome (relative lumen at follow-up), particularly at higher levels of luminal increase (relative gain). Specifically, lesions treated by balloon angioplasty or Palmaz-Schatz stent implantation (the predominantly 'dilating' interventions) were associated with more favourable angiographic profiles than directional atherectomy or excimer laser (the mainly 'debulking' interventions). Significant effects of lesion severity and location, as well as the well known influence of luminal increase on both luminal renarrowing and late angiographic outcome were also noted. These findings indicate that propensity to restenosis after apparently successful intervention is influenced not only by the degree of luminal enlargement achieved at intervention, but by the device used to achieve it. In view of the clinical implications of such findings, further evaluation in larger randomized patient populations is warranted.     

Cloning and sequencing of a gene from the archaeon Pyrococcus furiosus with high homology to a gene encoding phosphoenolpyruvate synthetase from Escherichia coli

A gene from the hyperthermophilic archaeon Pyrococcus furiosus, strain Vc1 (DSM 3638), contains an 817-amino-acid open reading frame which shows 42% identity to the phosphoenolpyruvate (PEP) synthetase of Escherichia coli. This putative P. furiosus PEP synthetase is slightly larger than the E. coli enzyme, the region between residues 58 and 89 being absent from the latter.     

Tracheal leiomyosarcoma: a unique cause of stridor

A 26-year-old man presented with a 2-week history of hemoptysis and progressive upper airway obstruction. Roentgenograms and bronchoscopy confirmed a tracheal tumor, and a primary leiomyosarcoma was resected.     

Massive gastric enlargement with delayed presentation of congenital diaphragmatic hernia: report of three cases and review of the literature

In three cases of congenital diaphragmatic hernia presenting long after the newborn period, there was striking enlargement of the intraabdominal stomach. In each case there was herniation of the entire small bowel into the thorax and absence of a hernial sac. Despite the enormous capacity of the stomach, which was suggestive of obstruction preoperatively, no site of obstruction could be demonstrated at operation. This enlargement disappeared following surgical repair of the hernia.