The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.     

Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome

X-chromosome inactivation in mammals is a regulatory phenomenon whereby one of the two X chromosomes in female cells is genetically inactivated, resulting in dosage compensation for X-linked genes between males and females. In both man and mouse, X-chromosome inactivation is thought to proceed from a single cis-acting switch region or inactivation centre (XIC/Xic). In the human, XIC has been mapped to band Xq13 (ref. 6) and in the mouse to band XD (ref. 7), and comparative mapping has shown that the XIC regions in the two species are syntenic. The recently described human XIST gene maps to the XIC region and seems to be expressed only from the inactive X chromosome. We report here that the mouse Xist gene maps to the Xic region of the mouse X chromosome and, using an interspecific Mus spretus/Mus musculus domesticus F1 hybrid mouse carrying the T(X;16)16H translocation, show that Xist is exclusively expressed from the inactive X chromosome. Conservation between man and mouse of chromosomal position and unique expression exclusively from the inactive X chromosome lends support to the hypothesis that XIST and its mouse homologue are involved in X-chromosome inactivation.     

Form and functions of the regular surface array (S-layer) of Aeromonas salmonicida

The principal virulence factor of Aeromonas salmonicida is its S-layer (A-layer) which is comprised of tetragonally arrayed approximately 50,000 Mr protein subunits tethered to the cell surface via LPS. The detailed composition of its LPS is known, as is the primary sequence, and three-dimensional disposition of the A protein subunits. The A-layer physically protects the cell against bacteriophage, proteases, as well as immune and non-immune complement. The A-layer appears to be uniquely adapted towards binding biologically important molecules such as heme, and to various basement membrane proteins. In addition, the A-layer is required for macrophage infiltration and resistance. Specific mutants containing a disorganized A-layer are avirulent and provide significant protection to salmonids when applied by immersion.     

In vivo rupture of the imidazole ring of histamine

Zusammenfassung Es wird gezeigt, dass Histamin auch durch das Aufreissen des Imidazolringes im Vormagen von Schafen katabolisiert werden kann. C¹⁴-markiertes Histamin wurde in den Pansen des Schafes oral eingeführt und annähernd 30% davon in der Atmungsluft (CO₂) aufgefangen.     

Immunization of mice against transplantable tumor

Zusammenfassung Nach i.p. Injektionen von mit Tween 80 behandelten Ehrlich-Lettré Ascites Krebszellen immunisierten Mäusen ergab sich bei diesen eine Widerstandsfähigkeit gegenüber Transplantaten von lebensfähigen Tumorzellen, woraus geschlossen wird, dass diese Behandlung die spezifischen Antigene der Zelloberfläche freisetzt.

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The research was supported by a grant from the Medical Research Council of Canada. I wish to thank Mrs.I. Gower for valuable technical assistance.     

Blood 5-hydroxytryptamine in rats with pulmonary hypertension produced by ingestion ofCrotalaria spectabilis seeds

Zusammenfassung Der pulmonare Blutdruck in Ratten kann durch Abfütterung vonCrotalaria spectabilis erhöht werden, ohne die Konzentration des plasmafreien und an die Thrombozyten gebundenen 5-Hydroxytryptamins zu verändern.