GL7 ligand expression defines a novel subset of CD4 T cells in lungs recovered from pneumococcus.

Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains.

Antigen presentation by lung epithelial cells directs CD4 T cell function and regulates barrier immunity.

Barrier tissues are populated by functionally plastic CD4 resident memory T (T) cells. Whether the barrier epithelium regulates CD4 T cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)MHC epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells.

CXCR4 and CXCR7 regulate angiogenesis and CT26.WT tumor growth independent from SDF-1.

Recent studies have shown that the chemokine stromal cell-derived factor (SDF)-1 and its receptor CXCR4 are involved in the metastatic process of colorectal cancer. The impact of SDF-1 on the stimulated metastatic growth during hepatectomy-associated liver regeneration is unknown. With the use of a heterotopic murine colon cancer model, we analyzed whether blockade of SDF-1 inhibits angiogenesis and extrahepatic growth of colorectal cancer after liver resection.

Stromal cell-derived factor-1 promotes cell migration and tumor growth of colorectal metastasis.

Unlabelled: In a mouse model of established extrahepatic colorectal metastasis, we analyzed whether stromal cell-derived factor (SDF) 1 stimulates tumor cell migration in vitro and angiogenesis and tumor growth in vivo.

Methods: Using chemotaxis chambers, CT26.WT colorectal tumor cell migration was studied under stimulation with different concentrations of SDF-1.

Enhanced expression and clinical significance of CC-chemokine MIP-3 alpha in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent visceral neoplasms worldwide. Using RT-PCR, ELISA, microdissection and immunohistochemistry, we investigated the expression profiles of CCL19, CCL20, CCL21 and CXCL12 and their receptors in tumourous and tumour neighbouring tissues from patients with HCC and in nonmalignant liver lesions, respectively. All chemokines were found to be expressed in normal liver and HCC tissues, yet CCL20 was the only chemokine showing significant upregulation in HCC tissues.

Involvement of chemokine receptor CCR6 in colorectal cancer metastasis.

Various chemokine receptors, namely CXCR4, CCR6 and CCR7, have recently been shown to be involved in the regulation of metastasis in malignant tumors. However, little is known about the role of these receptors in promoting tumor metastasis of colorectal cancer (CRC) to the primary site of CRC metastasis in the liver. To investigate this issue, we analyzed the expression of the chemokine receptors CXCR4, CCR6 and CCR7 in colorectal tumors and colorectal liver metastases.

Housekeeping gene variability in normal and cancerous colorectal, pancreatic, esophageal, gastric and hepatic tissues.

Careful normalization is essential for the accurate quantitation of mRNA levels in biopsy-sized tissue samples. Commonly, normalization of the target gene with an endogenous standard, mainly housekeeping genes (HKGs), is applied. However, differences in the expression levels of endogenous reference genes have been reported between different tissues and pathological states.

Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes.

We report that stromal cell-derived factor (SDF)-1 has the remarkable capacity to induce sustained signaling through CXC chemokine receptor 4 (CXCR4). In contrast to other chemokines, such as monocyte chemotactic protein 1 (CC chemokine receptor 2 [CCR2]), macrophage inflammatory protein 1beta (CCR5), liver and activation-regulated chemokine (LARC [CCR6]), Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC [CCR7]), and IP10 (CXCR3), SDF-1 stimulates the prolonged activation of protein kinase B and extracellular signal-regulated kinase (ERK)-2. Activation of protein kinase B is reversed by displacement of SDF-1 from CXCR4 or inhibition of phosphatidylinositol 3-kinase.

A novel candidate oncogene, MCT-1, is involved in cell cycle progression.

Using the arbitrarily primed-PCR (AP-PCR) assay to detect genetic abnormalities that occur in a panel of lymphoid cell lines, we identified an amplified stretch of genomic DNA that contained a putative open reading frame. Northern blot analysis with this genomic clone revealed widespread low level expression in normal human tissue. The full cDNA sequence was obtained with no significant homology to any known genes in the genome database.

G-Protein-coupled receptors and Fcgamma-receptors mediate activation of Akt/protein kinase B in human phagocytes.

Activation of the serine/threonine kinase Akt, also called protein kinase B (PKB), was investigated in human neutrophils. Stimulation of the cells with the chemoattractant fMet-Leu-Phe or the chemokines IL-8 and GROalpha leads to the rapid and transient activation of PKB. Maximum PKB activation correlates with the well documented kinetics of respiratory burst and exocytosis.

Tissue-specific expression of the human prostate-specific antigen gene in transgenic mice: implications for tolerance and immunotherapy.

Human prostate-specific antigen (PSA) has been widely used as a serum marker for cancer of the prostate. The cell type-specific expression of PSA also makes it a potential tumor antigen for prostate cancer immunotherapy. Study of the immunological aspects of PSA within either normal or malignant prostate tissue has been hampered by the lack of a mouse model, because no PSA counterpart has been identified in mice.

Constitutive activation of protein kinase B and phosphorylation of p47phox by a membrane-targeted phosphoinositide 3-kinase.

Background: Phosphoinositide 3-kinase (PI 3-kinase) activity is required for mitogenic signaling and for secretory responses. Cell activation is presumed to cause the translocation of PI 3-kinase from the cytosol to the plasma membrane where the kinase interacts with its substrate phosphatidylinositol (4,5)-bisphosphate. Thus, a membrane-targeted and therefore constitutively active kinase could help elucidate the role of PI 3-kinase in intracellular signaling.

Expression of human prostate-specific antigen (PSA) in a mouse tumor cell line reduces tumorigenicity and elicits PSA-specific cytotoxic T lymphocytes.

Human prostate-specific antigen (PSA) has a highly restricted tissue distribution. Its expression is essentially limited to the epithelial cells of the prostate gland. Moreover, it continues to be synthesized by prostate carcinoma cells.

Fundamental metabolic difference between cold stored lungs and livers and kidneys.

Short preservation times for lungs, are the main obstacle to exchange organs and increase the number of lung transplantations. In abdominal organ preservation UW solution has extended preservation times by including impermeable anions, adenosine and scavengers to prevent parenchymal cell swelling, to improve ATP regeneration and to inhibit reactive oxygen radicals. Metabolic changes in rabbit lungs, cold stored in UW-solution were compared with changes in rabbit livers and kidneys.

Changes in diurnal patterns related to changes in ozone levels.

Ozone is an ubiquitous air pollutant that affects both human health and vegetation. There is concern about the number of hours human populations in nonattainment areas in the United States are exposed to levels of O3 at which effects have been observed. As improvement in air quality is achieved, it is possible that O3 control strategies may produce distributions of 1-h O3 concentrations that result in different diurnal profiles that produce greater potential exposures to O3 at known effects levels for multiple hours of the day.

In vitro metabolism of the antimalarial agent primaquine by mouse liver enzymes and identification of a methemoglobin-forming metabolite.

From a mouse liver microsomal system, we have isolated and identified a methemoglobin-forming metabolite of primaquine (PQ). Evidence has been found for both O-dealkylation and hydroxylation of PQ to form a metabolite, 5,6-dihydroxy-8-(4-amino-1-methylbutylamino)quinoline, which is highly active in forming methemoglobin in both normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes. It also actively decreases glutathione levels in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Metabolism of 8-aminoquinoline antimalarial agents.

Some of the most effective antimalarial agents are derivatives of 8-aminoquinoline. The metabolic products of many of these compounds appear to be toxic to the erythrocytes of certain human subjects, especially those deficient in glucose-6-phosphate dehydrogenase. Although a number of studies have been conducted over many years, the metabolism of most of these compounds has not been determined.

Antiviral effect of cyclic amines on a 1969 isolate of A2 influenza.

Cyclooctylamine and amantadine inhibit the growth of 1969 isolates of A(2) influenza virus to a significant degree. There was slightly more inhibition of the virus by the cyclooctylamine (COA) than the amantadine; however, the dose of COA used was greater than the dose of amantadine. There was no significant difference between flasks treated 3 or 4 hr and those treated 2 hr.