The effects of vinblastine in assessment of the influence of age on proliferative activity of murine palate and footpad epithelium

Abstract
Data concerning changes in the rate of cell proliferation of stratified epithelia with increasing age are conflicting. In the present study young (3-month-old) and old (22-month-old) C57B1/6NNia male mice were injected intraperitoneally with 2, 3, 4 or 8 mg vinblastine sulfate/kg body weight and killed after 1.5, 3, 4.5 or 6 h. The number of arrested metaphase figures per 1000 basal cells was counted in histological sections. Data were analysed using a multivariate analysis of variance. There was a significant difference between the accumulation of mitotic figures in footpad epidermis and palate epithelium and both tissues contained an increased number of mitotic figures with increasing periods of accumulation at all dose levels. In the footpad epidermis neither the age of the animal nor the dose of vinblastine had a significant effect on the number of mitotic figures. In contrast, for palate epithelium the accumulation of mitotic figures was significantly less in the old mice compared with the young mice and at a dose of vinblastine of 2mg/kg compared with the higher doses. There was a statistically signifycant interaction between the dose of vinblastine and its period of action. It was concluded that the different tissues manifest a differential sensitivity to vinblastine and that only palate epithelium showed a significant reduction in proliferative activity with age.     

Whole-cell recording of neuroblastoma x glioma cells during downregulation of a major substrate, 80K/MARCKS,of protein kinase C

Summary Differentiated neuroblastoma cells exhibit both the delayed rectifier potassium current (I _K) and the M-current (I _M). The present study was designed to determine the roles of protein kinase C (PKC) and of the calmodulin-binding protein 80K/MARCKS, a prominent substrate for PKC and possible regulator of these currents. Neuroblastoma x glioma (NG108-15) hybrid cells transfected with m1 muscarinic receptors were grown with 1% fetal bovine serum (FBS) without the prostaglandin E₁ (PGE₁) and isobutylmethylxanthine (IBMX) usually added in preparation for electrophysiological studies. Under these conditions, the usual pleomorphism was largely abolished, leaving two populations of small cells with stellate and spherically symmetrical geometries. Whole-cell patch clamping indicated that the two cell types had identical electrophysiological properties, displaying: I _k, a small current through a T-like Ca²⁺ channel, and no M-current.Stimulation with carbachol shifted the distribution of cells to a more stellate morphology within 24 hr and later (after 48 hr) reduced the PKC substrate 80K/MARCKS by 22±7%. In contrast to the stimulation of I _k observed with cardiac cells, PKC activation produced only a small inhibition of I _k, which was independent of carbachol pretreatment. Thus, PKC and 80K/MARCKS can be dissociated from the regulation of I _k in neuroblastoma cells.Supported in part by research grants from the National Institutes of Health (DK-40145 and EY-08343) and from the U.K. Medical Research Council.We thank Dr. Peter J. Parker for his generous gift of PKC, and Yvonne Vallis for her skillful assistance with the cultures and harvesting of the NG108-15 transfected cells.     

Auto and transactivation of FGF expression: Potential mechanism for regulation of myogenic differentiation

Summary Fibroblast growth factors (FGFs) are potent inhibitors of myogenic differentiation. The recent observation that the endogenous expression of acidic and basic FGF by myogenic cells decreases coordinately with differentiation suggests a regulatory role for these growth factors in myogenesis. Inasmuch as other proteins known to influence myogenesis (e.g., MyoD1 and myogenin) activate their own expression as well as the expression of other members of their family, we hypothesized that the FGFs might be capable of similar autoregulation. We examined the effect of exogenously supplied FGF on the abundance of the mRNAs encoding acidic and basic FGF in Sol 8 myoblasts, and demonstrate that either acidic or basic FGF stimulate, through paracrine mechanisms, the accumulation of the mRNAs encoding both of these FGFs. Thus FGFs can auto- and transregulate their own expression in a manner analogous to that observed for the myogenic determination proteins. In addition, similar to that previously observed for MyoD1, both acidic and basic FGF suppress myogenin expression in myoblasts. These results suggest two mechanisms whereby endogenously produced FGFs participate in the maintenance of the undifferentiated state of myogenic cells. These data provide support for paracrine, and suggest potential autocrine, roles for FGFs in the regulation of myogenic differentiation.     

The mutation ofEscherichia coli to resistance to bacteriophages Tl and Tls

Summary The number of phage-resistant mutants in unirradiated and in ultraviolet-irradiated cultures ofE. coli strains B and B/r is usually greater when the selecting agent is Tls. It is shown that this cannot be explained by a) completely independent gene changes, b) the presence of host range phage mutants or c) new mutations due to prolonged survival of wild type bacteria in the prescence of phage. Evidence is presented which indicates that the difference in selection by Tl and Tls may be explained satisfactorily by the presence of incompletely expressed bacterial mutants in the cultures before plating. This constitutes indirect evidence for a phenotypic lag. It is shown further that the development of resistance to Tls probably precedes the development of full resistance to both phages.The appearance of new ultraviolet-induced mutations, selected by Tls, is found to fulfill expectations based on the existence of such a phenotypic lag.

---

Zusammenfassung Die Anzahl der phagenresistenten Mutanten in unbestrahlten und UV-bestrahlten Kulturen derE. coli Stämme B und B/r ist im allgemeinen größer, wenn die Selektion mit Tls durchgeführt wird. Dieses kann nicht erklärt werden durch a) vollständig unabhängige Genveränderungen, b) die Gegenwart von hostrange Phagenmutanten, oder c) neue Mutationen bedingt durch längeres Überleben von Wildtypus-Bakterien in der Gegenwart von Phagen. Es wird gezeigt, daß der Unterschied in der Selektion von Tl und Tls ausreichend erklärt werden kann durch die Gegenwart von unvollständig manifestierten Bakterienmutanten, die vor dem plating in den Kulturen vorhanden sind. Dieses bildet indirekten Beweis für eine phänotypische Lagphase. Es wird weiterhin gezeigt, daß die Entwicklung der Resistenz gegenüber Tls wahrscheinlich der Entwicklung von Vollresistenz gegenüber beiden Phagen vorangeht.Das Auftreten von neuen UV-induzierten, durch Tls selektierten Mutanten stimmt mit dem Vorhandensein einer derartigen phänotypischen Lagphase überein.

---

---

With 6 Figures in the text.     

Sultans of Spin: Syrian Sacred Music on the World Stage

This article examines how the performance of a variety of Islamic music in transnational cultural circuits helps to promote the idea of a style of sacred music within the category of world music. Taking as an example the performance of the mawlawiyya, or "Whirling Dervish," music and dance by a Syrian–based ensemble, I show how the idea of an authentic local Syrian sacred music tradition requires its performance globally. I use the concept of the "world stage" to examine how musical performance practices that are represented as authentic local traditions obtain both their authenticity and their local specificity through their staging in global contexts. I further explore how such musical styles as sacred and Sufi emerge as naturalized categories in world music discourse, and how processes of differentiation and commodification reconfigure both the "local" and "global." [Keywords: world music, globalization, style, Syria, Islam]