Myasthenia Gravis: Anesthetic and Surgical Management of the Patient Undergoing Thymectomy

Experience in the anesthetic and surgical management of 25 patients with myasthenia gravis is recorded. These are subdivided into two groups: those operated on during the period 1950-1958 and those operated on during the period 1959-1964. The purpose of this paper is to indicate improvement in mortality and morbidity due to three major advances: (1) use of the decamethonium diagnostic test in a myasthenia gravis clinic; (2) improvements in assessment and management of respiratory insufficiency; and (3) avoidance of anticholinesterase treatment in the immediate and early postoperative recovery period.Fourteen patients with myasthenia gravis, including five with thymoma and two who were refractory to medication, were in the second (1959-1964) group. There were no deaths and no myasthenic or cholinergic crises. Three prophylactic tracheostomies were performed. No emergency bronchoscopies or tracheostomies were required.     

Effect of Desipramine on a Glycoprotein Sialyltransferase Activity in C6 Cultured Glioma Cells

The tricyclic antidepressant desipramine, when added to culture medium, gave rise in C6 rat glioma cells to a decrease of the activity of the enzyme asialofetuin sialyltransferase. The inhibition was dose and time dependent and was observed in both multiplying cells and cells blocked with 2 mM thymidine or depletion of amino acids. This inhibition was rather specific to the sialyltransferase, as under the conditions where this enzyme was inhibited up to 70%, other enzymes such as dolichol phosphate mannose synthetase, glutamine synthetase, and glycerol phosphate dehydrogenase remained unaffected. This inhibition was not reversed after removal of desipramine from the medium and was not observed by direct addition of desipramine to the sialyltransferase incubation assay. Under the same conditions, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], which is known to be a potent calmodulin antagonist and an inhibitor of calmodulin-dependent kinases, gave the same concentration-dependent inhibition profile of sialyltransferase as desipramine, whereas H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], which is an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect. So, it is suggested that desipramine inhibits the sialyltransferase activity in C6 glioma cells through a calmodulin-dependent system.     

Efficacy and stability of wettable powder amitraz in field and laboratory studies against Boophilus annulatus (Acari: Ixodidae) in south Texas

A study was done at the USDA-ARS, Cattle Fever Tick Research Laboratory, Mission, Tex., to determine the efficacy of a 50% wettable powder (WP) amitraz formulation applied as a whole-body spray in a standard dip vat, and in a laboratory bioassay against Boophilus annulatus (Say) on cattle. A study also was done at the King Ranch in Kleberg County, Tex., to determine the stability of 50% WP amitraz in a dip vat under South Texas conditions Cattle were infested with all parasitic life stages of B. annulatus and were sprayed or dipped with a concentration of 0.025% amitraz. As determined by calculations of the index of reproduction, the whole-body spray treatment provided 86% control of the ticks and the dip treatment provided 99.8% control. Laboratory bioassay results compared favorably with those obtained with the dip vat treatment. Amitraz WP settled very rapidly in the freshly charged ranch vat. However, as more cattle were dipped and the vat became polluted with dirt and excrement, settling occurred much more slowly. Overall, amitraz remained stable in the vat during the test period.     

Effect of ozone on the postnatal development of lamb mucociliary apparatus

We determined whether exposure to O3 early in the postnatal period impairs the normal development of the mucociliary apparatus in lambs and whether such changes lead to prolonged abnormalities in mucociliary function. Lambs were exposed to air (controls) or to 1 ppm O3 for 4 h/day for 5 days during the 1st wk of life. Tracheal mucus velocity (TMV), a marker of lung mucociliary clearance, was measured in vivo at birth (0 wk) and up to 24 wk later, and tracheal secretory function was measured (in vitro) and the morphology of the tracheal mucosa was determined at 0 and 2 wk in both groups. In the control group, TMV increased 94% from 0 to 2 wk (P less than 0.05), continued to increase until reaching a plateau at 8 wk, and then remained constant from 8 to 24 wk. In contrast, O3-exposed lambs showed a 24% decrease in TMV from 0 to 2 wk (P less than 0.05 vs. control), and throughout the remaining time TMV remained below (P less than 0.05) that observed in control lambs. O3 exposure partially prevented the age-dependent decrease in basal secretion of tracheal macromolecules normally observed between 0 and 2 wk. These changes in secretory function were associated with a significant increase in tissue conductance (37%, P less than 0.05 vs. 0 wk), predominantly the result of active chloride secretion. The functional changes induced by O3 were associated with a retardation of the normal morphological development of the tracheal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002.

The immunosuppressant, rapamycin, inhibits cell growth by interfering with the function of a novel kinase, termed mammalian target of rapamycin (mTOR). The putative catalytic domain of mTOR is similar to those of mammalian and yeast phosphatidylinositol (PI) 3-kinases. This study demonstrates that mTOR is a component of a cytokine-triggered protein kinase cascade leading to the phosphorylation of the eukaryotic initiation factor-4E (eIF-4E) binding protein, PHAS-1, in activated T lymphocytes. This event promotes G1 phase progression by stimulating eIF-4E-dependent translation initiation. A mutant YAC-1 T lymphoma cell line, which was selected for resistance to the growth-inhibitory action of rapamycin, was correspondingly resistant to the suppressive effect of this drug on PHAS-1 phosphorylation. In contrast, the PI 3-kinase inhibitor, wortmannin, reduced the phosphorylation of PHAS-1 in both rapamycin-sensitive and -resistant T cells. At similar drug concentrations (0.1-1 microM), wortmannin irreversibly inhibited the serine-specific autokinase activity of mTOR. The autokinase activity of mTOR was also sensitive to the structurally distinct PI 3-kinase inhibitor, LY294002, at concentrations (1-30 microM) nearly identical to those required for inhibition of the lipid kinase activity of the mammalian p85-p110 heterodimer. These studies indicate that the signaling functions of mTOR, and potentially those of other high molecular weight PI 3-kinase homologs, are directly affected by cellular treatment with wortmannin or LY294002.     

The new politics of exclusion: Antecedents to the rebellion in Mexico

Thatcherism's search for the enemies within; its operations across the different lines of division and identification in social life...its rooting of itself inside a particularly narrow, ethnocentric and exclusivist conception of national identity; and its constant attempts to expel symbolically one sector of society after another from the imaginary community of the nation-these are as central to Thatcherism's hegemonic project as the privatization programme or the assault on local democracy...     

Elemental microanalysis of fibroblasts by a scanning proton microprobe and application to Menkes’ disease

A scanning proton microprobe has been used for the elemental microanalysis of individual fibroblast cells. Both normal fibroblasts and fibroblasts cultured from patients with Menkes' disease, an X-linked genetic disorder known to be associated with defective copper metabolism, were examined by the probe. The cells were cultured on a thin ultra-clean nylon foil and retained on that surface for analysis. The focused high-energy proton beam was used to irradiate selected individual cells and elemental information was derived from X-ray and backscattered proton data. The sensitivity of the scanning proton microprobe to trace concentrations of heavy elements has allowed this elemental information to be used to identify individual cells as being either normal or a Menkes' mutant. The cell identification was based on the application of discriminate analysis to a data set formed from the ratios of copper to each of the macroelements present in the cell. This method of cell identification offers the promise of rapid diagnosis of Menkes' disease.     

Characterisation of a 5-bp deletion in exon 4 of the factor VIII gene: concordance with slipped-mispairing at DNA replication

In an attempt to characterize disease producing mutations in the factor VIII gene we screened exons 4, 7, 8, 11, 12 and 16 by PCR-SSCP (polymerase chain reactionsingle strand conformation polymorphism), in 12 randomly selected haemophilia A patients. These exons were chosen because they have been reported to harbour a disproportionately high number of mutations relative to their size. Using this strategy we detected a frame-shifting 5-bp deletion (TACCT, involving nucleotides 519–523), which is predicted to result in a severely truncated factor VIII polypeptide, terminating approximately midway through the conserved A1 domain and resulting in the observed severe phenotype. We also showed that the sequence in the vicinity of the observed deletion is concordant with the modified slipped-mispairing at DNA replication model of Krawczak and Cooper.