Saturable function of P-glycoprotein as a drug-efflux pump in multidrug-resistant tumour cells

In the past, Mycobacterium avium complex (MAC) was considered a colonizing microbe in the immunocompetent host. Today it should be considered a potential pathogen. We present a case of MAC necrotizing pneumonia in a 27-year-old man who tested negatively for the human immunodeficiency virus, had no typical granulomas, and responded rapidly to antimicrobial therapy.     

Oral-motor patterns of rhythmic trigeminal activity generated in fetal rat brainstem in vitro

Development of neural circuits generating fetal oral-motor activity was characterized in an in vitro isolated brainstem block preparation. Rhythmical trigeminal activity (RTA) at E20-E21 resembled either the pattern or rhythm of neonatal RTA. Conversely, at E18-E19, RTA displayed a different pattern of discharge from neonatal RTA, and output was not regular but intermittent with another slow rhythm.     

Serum human hepatocyte growth factor (hHGF) is elevated in patients with metastatic gastric carcinoma

BACKGROUND/AIMS: Hepatocyte growth factor (HGF) is a stromally derived protein growth factor that modulates epithelial cell proliferation and motility. HGF may therefore be involved in tumor progression. METHODOLOGY: We measured the immunoreactive (ir)-HGF concentration in the sera of 56 patients with human gastric carcinoma, using an enzyme-linked immunosorbent assay and evaluated its association with clinical and histopathologic factors. Clinical stages were classified in accordance with The General Rules for TNM Classification (International Union Against Cancer). RESULTS: The serum hHGF concentrations from patients with gastric carcinoma significantly increased with increasing pathologic tumor grades. Also, there were significantly higher concentrations in patients with nodal metastasis compared to patients without metastasis. The serum hHGF concentrations in patients with liver metastasis were significantly higher than in patients without liver metastasis. CONCLUSIONS: These data show that the serum hHGF concentration is elevated in gastric carcinoma patients with liver and nodal metastasis. In multivariate analysis, the serum hHGF concentration was found to be the most important independent factor in predicting overall survival. Thus, the current results suggest that HGF may be important in the progression and metastasis of gastric carcinoma.     

Exocytotic stimulation promotes association of the ADP-ribosylation factor with PC12 cell membranes

Recombinant Der f2 (rDer f2) has recently been developed as a promising allergen for the diagnosis and immunotherapy of house-dust mite allergy, and studies in immunology. The aim of the present study was to evaluate whether oral administration of rDer f2 could suppress an immediate allergic reaction in mice sensitized with mite allergen. We developed a murine allergic model that showed bronchoconstriction after inhalation of rDer f2, and studied the effect of oral administration of rDer f2 on the reaction. Seven week old male A/J mice were intranasally immunized with rDer f2 12 times. Sensitized mice showed anti-rDer f2 immunoglobulin (Ig)E production and immediate airway constriction after inhalation of 10 mg.mL(-1) of rDer f2, as determined by the Konzett-R?ssler method. Immunized animals were divided into three groups, and fed phosphate-buffered saline (PBS), 0.1 mg.day(-1), or 1 mg.day(-1) of rDer f2 for 4 weeks, respectively. Seven days after the last feeding, the mice were examined for their immediate response. Animals fed with 1 mg.day(-1) rDer f2 showed significantly reduced bronchoconstriction after inhalation of both 2 mg.mL(-1) and 10 mg.mL(-1) of rDer f2 compared with PBS-fed mice. Similar results were obtained when we examined mice 10 weeks after the last feeding. Reactions in the 0.1 mg.day(-1) rDer f2-fed group also tended to decrease in comparison with PBS-fed animals. Plasma anti-rDer f2 IgE, IgG1, IgG2a, and IgG2b levels were not changed by feeding with rDer f2. We conclude that recombinant Der f2 exhibits both sensitizing and hyposensitizing activities in mice. rDer f2 may be useful in immunotherapy and diagnosis of house-dust mite allergy.     

Characterization of [3H]staurosporine binding in protein kinase C-II purified from rat brain

The type II protein kinase C (PKC-II) densely present in mammalian brain plays functional roles in CNS. We examined the characteristics of [3H]staurosporine binding to PKC-II purified from rat brain, compared to [3H]phorbol 12, 13-dibutyrate (PDBu) binding. In brief, [3H]staurosporine binding increased by phosphatidylserine (PtdSer) in a concentration-dependent manner and the binding was enhanced by Ca2+ and phorbol 12-myristate 13-acetate (PMA). In the presence of Ca2+, PMA and PtdSer, Bmax of these bindings markedly increased, but KD did not change. These characteristics of binding were similar to [3H]PDBu binding to PKC-II. Although [3H]PDBu binding was not affected by protein kinase inhibitors such as staurosporine, H-7, K-252a and K-252b, [3H]staurosporine binding was inhibited by these inhibitors. [3H]staurosporine binding was inhibited by several ATP analogues, but was not by guanine nucleotides. PtdSer-induced increase in [3H]PDBu binding was inhibited by Zn2+, but Zn2+ induced increase in [3H]staurosporine binding as well as PtdSer and/or Ca2+. Staurosporine would thus appear to bind to a domain different from phorbol ester-binding one in PKC, interactions between both domains may regulate kinase activity, and 1 mol staurosporine and 4 mol phorbol ester may bind to 1 mol PKC-II.