Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in PO2, PCO2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

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New human leukemia cell lines from 4 patients have been established. All are characterized by preferential growth in small clumps and large flat plaques of cells. The cell lines were adapted to suspension cultures and grown in one‐ to 200‐liter containers. The design of practical automated units for continuous culture of leukemia cells has been accomplished. Some of the nutritional requirements of these cell lines are summarized. Cytological studies revealed that all of the cell lines have a normal diploid karyotype with few aberrant cells. None of the cultured cells derived from chronic myelocytic leukemia retained the Ph chromosome. Electron microscopy has shown virus‐like particles in several of these cell lines. Preliminary studies of the value of these cultured leukemia cells in biochemical, viral and clinical immunological studies are discussed.

Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na ϩ K ϩ -ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na ϩ K ϩ -ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)-DNA complexes encoding the ␣ and ␤ subunits of Na ϩ K ϩ -ATPase (160 g per mouse), significantly (P Ͻ 0.01) decreased the wet:dry weight ratios measured 2 h after

Cerebral blood volume and intracranial pressure may be modified by influences on cerebral veins. The known adrenergic innervation of cerebral veins and their sensitivity to norepinephrine raised the question, whether pial veins can be selectively influenced through adrenoceptors in vivo. Therefore, alpha 1 and alpha 2 adrenoceptor agonists and antagonists were locally injected into the perivascular space of pial veins using the microapplication technique. The alpha 1 and alpha 2 adrenoceptor antagonists, prazosin and yohimbine, had only minor effects on pial veins. Both antagonists blocked constrictions induced by norepinephrine (10(-5)M) in a concentration dependent manner (10(-7)-10(-4)M). The alpha 1 adrenoceptor agonist phenylephrine caused significant (10(-7)-10(-3)M) constriction of pial veins, with a maximum of 11.6% of initial diameter at 10(-3)M. Oxymetazoline, an alpha 2 receptor agonist, induced a significant constriction only at 10(-3)M (5.1%). Since both alpha 1 and alpha 2 adrenoceptor agonists are less potent constrictors of pial veins than norepinephrine in vivo, a preferential use of alpha 1 or alpha 2 adrenoceptor agonists cannot be recommended from these experiments, if a therapeutic reduction of intracranial pressure or blood volume is desired.