Objective To evaluate N‐terminal pro–brain natriuretic peptide (NT‐proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine‐type calcium‐channel blocker (DTCCB) in patients with systemic sclerosis (SSc). Methods We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean ± SD age 56 ± 11 years and mean ± SD duration of cutaneous disease 9 ± 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT‐proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6–9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline). Results At baseline, 13 patients had high NT‐proBNP values for their ages. High NT‐proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT‐proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT‐proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06). Conclusion NT‐proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT‐proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Emerging evidence indicates the presence of tumor-initiating cells (TIC) or cancer stem cells (CSCs) in osteosarcoma. However, no study has demonstrated specific markers to identify osteosarcoma TICs with in vivo tumor formation ability. Additionally, there has been a lack of investigations gauging the contribution of osteosarcoma TICs to metastatic and drug-resistant properties. In this study, we have identified mouse and human osteosarcoma TICs using mesenchymal stem cell (MSC) markers CD117 and Stro-1. These markers were preferentially expressed in spheres and doxorubicin-resistant cells. Both mouse and human cells expressing these markers were sorted and analyzed for their abilities of tumor formation with as few as 200 cells, self-renewability, multipotency, drug resistance, metastatic potential, and enrichment of a metastasis-associated marker CXCR4 and a drug-resistance marker ABCG2. CD117+Stro-1+ cells efficiently formed serially transplantable tumors, whereas CD117−Stro-1− cells rarely initiated tumors. Upon orthotopic injections, CD117+Stro-1+ cell-derived tumors metastasized at a high frequency. Further, CD117+Stro-1+ cells showed high invasive and drug-resistant properties and were efficiently enriched for CXCR4 (20–90%) and ABCG2 (60–90%). These results suggest possible mechanisms for the high metastatic and drug-resistant properties of osteosarcoma TICs. In summary, CD117 and Stro-1 identify osteosarcoma TICs associated with the most lethal characteristics of the disease - metastasis and drug resistance - and these markers offer candidates for TIC-targeted drug delivery aimed at eradicating osteosarcoma.

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.