Multichannel continuous-wave fiber cavity ringdown gas sensing utilizing frequency-shifted interferometry.

We present a multichannel continuous-wave (CW) fiber cavity ringdown (FCRD) gas sensing method based on frequency-shifted interferometry (FSI). This scheme detects gas concentration by measuring the intensity decay rates of continuous light from different ringdown cavities in the spatial domain, unlike conventional FCRD techniques, which measure the decay rates of pulse light in the time domain. This method shares one CW light source, one slow detector, and one slow data collector. In order to illustrate the theory, acetylene gas concentration measurement in a two-channel FSI-FCRD system was experimentally conducted in the range of 0%-1%. A linear relation was established between concentration and absorption loss, which is proportional to the intensity decay rate, and the measurement resolutions of 3.871%/dB and 3.658%/dB were achieved, respectively. The results reveal that the proposed system has the advantages of low cost, high sensitivity, high precision, and good stability in multichannel gas detection.

CTGF is a therapeutic target for metastatic melanoma.

Metastatic melanoma remains a devastating disease with a 5-year survival rate of less than five percent. Despite recent advances in targeted therapies for melanoma, only a small percentage of melanoma patients experience durable remissions. Therefore, it is critical to identify new therapies for the treatment of advanced melanoma. Here, we define connective tissue growth factor (CTGF) as a therapeutic target for metastatic melanoma. Clinically, CTGF expression correlates with tumor progression and is strongly induced by hypoxia through HIF-1 and HIF-2-dependent mechanisms. Genetic inhibition of CTGF in human melanoma cells is sufficient to significantly reduce orthotopic tumor growth, as well as metastatic tumor growth in the lung of severe combined immunodeficient (SCID) mice. Mechanistically, inhibition of CTGF decreased invasion and migration associated with reduced matrix metalloproteinase-9 expression. Most importantly, the anti-CTGF antibody, FG-3019, had a profound inhibitory effect on the progression of established metastatic melanoma. These results offer the first preclinical validation of anti-CTGF therapy for the treatment of advanced melanoma and underscore the importance of tumor hypoxia in melanoma progression.

Toward an ideal animal model to trace donor cell fates after stem cell therapy: production of stably labeled multipotent mesenchymal stem cells from bone marrow of transgenic pigs harboring enhanced green fluorescence protein gene.

The discovery of postnatal mesenchymal stem cells (MSC) with their general multipotentiality has fueled much interest in the development of cell-based therapies. Proper identification of transplanted MSC is crucial for evaluating donor cell distribution, differentiation, and migration. Lack of an efficient marker of transplanted MSC has precluded our understanding of MSC-related regenerative studies, especially in large animal models such as pigs. In the present study, we produced transgenic pigs harboring an enhanced green fluorescent protein (EGFP) gene. The pigs provide a reliable and reproducible source for obtaining stable EGFP-labeled MSC, which is very useful for donor cell tracking after transplantation. The undifferentiated EGFP-tagged MSC expressed a greater quantity of EGFP while maintaining MSC multipotentiality. These cells exhibited homogeneous surface epitopes and possessed classic trilineage differentiation potential into osteogenic, adipogenic, and chondrogenic lineages, with robust EGFP expression maintained in all differentiated progeny. Injection of donor MSC can dramatically increase the thickness of infarcted myocardium and improve cardiac function in mice. Moreover, the MSC, with their strong EGFP expression, can be easily distinguished from the background autofluorescence in myocardial infarcts. We demonstrated an efficient, effective, and easy way to identify MSC after long-term culture and transplantation. With the transgenic model, we were able to obtain stem or progenitor cells in earlier passages compared with the transfection of traceable markers into established MSC. Because the integration site of the transgene was the same for all cells, we lessened the potential for positional effects and the heterogeneity of the stem cells. The EGFP-transgenic pigs may serve as useful biomedical and agricultural models of somatic stem cell biology.

Inhibition of angiotensin II induced endothelin-1 gene expression by 17-beta-oestradiol in rat cardiac fibroblasts.

OBJECTIVE: To examine whether 17-beta-oestradiol (E(2)) may alter angiotensin II (Ang II) induced cell proliferation and to identify the putative underlying signalling pathways in rat cardiac fibroblasts. DESIGN: Cultured rat cardiac fibroblasts were preincubated with E(2) then stimulated with Ang II. [(3)H]Thymidine incorporation and endothelin-1 (ET-1) gene expression were examined. The effect of E(2) on Ang II induced NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal regulated kinase (ERK) phosphorylation were tested to elucidate the intracellular mechanism of E(2) in proliferation and ET-1 gene expression. RESULTS: Ang II increased DNA synthesis, which was inhibited with E(2) (1-100 nmol/l). E(2), but not 17-alpha-oestradiol, inhibited Ang II induced ET-1 gene expression as shown by northern blotting and promoter activity assay. This effect was prevented by co-incubation with the oestrogen receptor antagonist ICI 182,780 (1 micromol/l). E(2) also inhibited Ang II increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 mediated reporter activity. CONCLUSIONS: The results suggest that E(2) inhibits Ang II induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway through attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of oestrogen on the cardiovascular system.

Effects of cancer therapy on dental and maxillofacial development in children: report of case.

Malignant lymphoma is one of the most common hematological diseases of children. The prognosis is fairly good with multimodal cancer therapy. We reported a boy with Burkitt's lymphoma in the nasal cavity who received chemotherapy and irradiation of the head and neck area at four years of age. During seven years of follow-up, we studied the developmental effects of cancer therapy, including general growth, maxillofacial bones, and dentition. Compared with boys of matching age, the development of his entire body and maxillofacial bones was delayed. In the irradiated areas, the roots of teeth were short or poorly developed and the root apices showed premature closure. After the patient was in remission from the tumor in his early childhood, the long-term effects of cancer therapy on dental and maxillofacial development are worth our further evaluation and follow-up.

Balloon dilatation for critical pulmonary stenosis.

This study was conducted to investigate the outcome of balloon valvuloplasty for critical pulmonary stenosis in young infants. During a 6.2-year period between January 1992 and February 1998, 34 infants with critical pulmonary stenosis, aged 1 to 58 days (16.8+/-16.6 days), underwent attempted balloon valvuloplasty in this institution. The procedure was accomplished in 28 patients, but failed in six. Surgical pulmonary valvotomy was performed in the six patients with one mortality. Immediately following valvuloplasty, the mean right ventricular systolic pressure decreased from 109.2+/-28.6 to 55.1+/-23.6 mm Hg in the 28 patients (P<0.01). The mean pressure gradient decreased from 85.6+/-29.4 to 26+/-21.4 mm Hg (P<0.01). However, one who had a severely hypoplastic right ventricle requiring prolonged prostaglandin E1 infusion after valvuloplasty underwent a right ventricular outflow tract patch. After a follow-up period ranging from 2 months to 6.4 years (30.5+/-19.1 months), one patient developed recurrent pulmonary stenosis and underwent a repeated balloon valvuloplasty. Of the 27 patients (79%) with a definitive success of balloon valvuloplasty, the mean pressure gradient estimated with Doppler echocardiography at most recent follow-up was 15.2+/-6.8 mm Hg. Therefore, balloon valvuloplasty is the procedure-of-choice for critical pulmonary stenosis. Surgery should be reserved for those with unsuccessful balloon valvuloplasty.

Angiographic evidence of long-axis rotation in addition to short-axis aortopulmonary rotation: its implication in transposition of the great arteries.

To assess the pattern of aortic sinus in varied aortopulmonary rotations and its clinical implications, three aortic sinuses at the diastolic phase in true lateral view are identified in 53 angiograms of complete transposition of the great arteries recorded between 1988 and 1993. The patients with the high takeoff of the coronary arteries found at surgery and in the literature were selected for additional investigation. Six regions were defined on the horizontal plane. From left anterior 89 degrees to 61 degrees, the non-facing sinus moved toward the anterior aspect (one patient). From left anterior 60 degrees to left anterior 1 degree, the left-hand sinus moved gradually from an anterior toward a posterior location (two patients). From directly anterior 0 degree to right anterior 59 degrees, the right-hand sinus moved from posterior toward an anterior position (30 patients). From right anterior 60 degrees to right posterior 105 degrees, the non-facing sinus moved posteriorly (20 patients). On approaching directly anterior 0 degree and toward right anterior 60 degrees, the left-hand sinus was the lowest in anterior transposition of the great arteries instead of the non-facing sinus, as in left anterior 90 degrees and in posterior transposition of the great arteries. High takeoff occurred commonly above the lowest left-hand sinus in anterior transposition of the great arteries (2 cases here and 5 in the literature, 100%). In conclusion, aortopulmonary rotations about the short and long axes were both evident on identification of the aortic sinus in various rotations. The aortic sinus did not rotate along the long-axis in anterior transposition of the great arteries, thus making the left-hand sinus, the lowest of this group, vulnerable to the high takeoff of the coronary arteries in anterior transposition of the great arteries.

Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.

The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM-1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer-dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites.

Mediation of lung metastasis of murine melanomas by a lung-specific endothelial cell adhesion molecule.

Organ-specific adhesion molecules expressed by vascular endothelial cells have been implicated in the arrest of blood-borne cancer cells in selective, secondary sites. A lung-specific endothelial cell adhesion molecule (Lu-ECAM-1) localized on endothelia of distinct branches of lung blood vessels has been purified by immunoaffinity chromatography from detergent extracts of lung matrix-modulated endothelial cells using monoclonal antibody (mAb) 6D3. It has a molecular mass of 90 kDa and promotes the selective attachment of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, B16-F10 tumor cells selected for higher lung colonization bind to Lu-ECAM-1 in significantly higher numbers than their low lung metastatic counterpart B16-F0. Binding of B16-F0 and B16-F10 is reduced with mAb 6D3 to slightly lower levels than B16-F0 bound to Lu-ECAM-1. mAb 6D3 injected into C57BL/6 mice 1 hr prior to an i.v. challenge with B16-F10 causes a 90% reduction in the number of lung colonies compared with animals injected with control mAb (6D8 or 3C6). Lu-ECAM-1 neither binds nor effects metastasis of other lung-colonizing tumor cells (e.g., KLN205). Thus, site-specific metastasis of tumor cells is regulated by similar mechanisms as the homing of lymphocytes--namely, by the ability of blood-borne cancer cells to recognize and adhere to distinct endothelial cell adhesion molecules.

Purification and characterization of rat heart and brain catechol methyltransferase.

In an effort to detect the similarities and differences in the properties of rat heart, brain and liver catechol methyltransferase (S-adenosyl-L-methionine:catechol O-methyltransferase, EC 2.1.1.6), we have determined the cellular distribution of this enzyme activity and extensively purified the soluble and microsomal enzymes present in these tissues. Purification of soluble heart (688-fold) and brain enzymes (240-fold) were achieved using an affinity chromatographic system. The properties of these enzymes were compared with respect to their molecular weights, substrate specificities, inhibitor specificities and immunological properties. The characteristics of the enzyme active sites were investigated using various methyl acceptor substrates and various analogs of S-adenosylmethionine as methyl donors. A series of analogs of S-adenosylhomocysteine was also evaluated as inhibitors of these enzymes. The immunological properties of the purified soluble and microsomal enzymes from heart and brain were investigated using an antibody isolated from rabbits which had been immunized with the soluble rat liver enzyme. In general the properties of catechol methyltransferases isolated from heart and brain were similar to the properties of the enzyme isolated from liver. Some minor differences in substrate and inhibitor specificities were observed which might suggest slight differences in the active sites of these enzymes.