IntroductionLimited data exists describing impact of hypertrophic cardiomyopathy (HCM) on quality of life (QOL) or exercise performance. The Valsartan for Attenuating Disease in Early Sarcomeric ...Hypertrophic Cardiomyopathy (VANISH) trial provides an ideal cohort to investigate whether QOL or exercise performance is influenced by genotype + HCM. Our study aims to compare QOL and exercise in preclinical to early HCM disease.MethodsBaseline demographic, PedsQL, exercise stress test and physical activity data were compared in the VANISH cohort between those with early (G+/LVH+) or no left ventricular hypertrophy (G+/LVH-). Standard statistical analysis was performed.ResultsAnalysis included 212 subjects; 34 (16%) were G+/LVH- and were younger (16 years, IQR 12-20) than G+/LVH+ group (n=178; 20 years, IQR 15-31); p-value <0.001. G+/LVH+ had trend towards lower overall QOL, lower emotional and school functioning status (Table). G+/LVH+ had decreased daily physical activity (p=0.02) and overall lower aerobic exercise capacity (p<0.01) that worsened with age (< vs. > 18 yrs). Only 8% G+/LVH+ reported refraining from vigorous or moderate intensity physical activity.ConclusionIn children and young adults with genotype positive HCM, those with LVH+ phenotype had lower emotional and academic QOL. They had a trend towards lower perceived physical functional status and significantly lower aerobic exercise capacity, potentially driven either by their underlying disease or medical exercise restrictions. Future study is needed to determine the contributions of lower exercise capacity and to encourage physical activity in patients with HCM.
A series of pyrroloquinazolines has been discovered that represent novel small molecule inhibitors of the intramolecular ligand of the thrombin receptor. Analogs were prepared to study the ...structure-activity relationships of substitution at the N1, N3, and N7 positions of the heterocycle. Compounds
4e and
4f have been identified with IC
50's of 56 and 52 nM, respectively.
A series of pyrroloquinazolines has been discovered that represent novel small molecule inhibitors of the intramolecular ligand of the thrombin receptor. Analogs were prepared to study the structure-activity relationships of substitution at the N1, N3, and N7 positions of the heterocycle. Compounds
4e and
4f have been identified with IC
50's of 56 and 52 nM, respectively.
Altered mucin glycosylation occurs in colonic adenomas and can correlate with risk for malignant transformation. The purpose of this study was to determine if immunoreactivity of core tandem repeat ...peptides of specific mucin genes correlates with histopathologic criteria of malignant potential in the colon. Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19). An immunohistochemical scoring system that takes into account specimen heterogeneity and yields an integrated numerical score subject to statistical analysis was used. RNA message levels from tubular and tubulovillous adenomas (n = 13), normal colon (n = 12), and moderately differentiated adenocarcinomas (n = 8) were determined using RNA slot blot analysis with mucin-specific cDNA probes. MUC1 staining was rarely present in normal colon. MUC2 immunoreactivity was limited to goblet cells in most normal colonic crypts, and MUC3 staining was weakly expressed in the upper crypt regions only. In comparison with normal and hyperplastic specimens, MUC1 and MUC3 immunoreactivity scores were significantly increased in adenomas of increasing villous histology, size, and dysplasia. MUC2 scores were significantly increased in adenomas of greater villous histology and size. Comparable MUC1, MUC2, and MUC3 mRNA levels were present in adenomas and normal colon, whereas mucin mRNA levels were decreased in adenocarcinomas. We conclude that enhanced immunoreactivity of MUC1, MUC2 and MUC3 mucin tandem repeats occurs in adenomatous polyps and is associated with an increased risk for malignant transformation.
The normal pancreas consists of three major cell types or lineages that share a common embryologic origin from pluripotent endodermal precursors. the type of cell that undergoes neoplastic ...transformation to form a pancreatic carcinoma is controversial and may influence the phenotype and biologic behavior of the tumor. in this study, immunohistologic techniques were used to determine the cell lineage differentiation expressed in 29 primary exocrine pancreatic adenocarcinomas, five metastatic exocrine pancreatic adenocarcinomas, and five islet cell neoplasms. Specimens of normal pancreas and chronic pancreatitis were used for comparison. the cell lineage markers consisted of monoclonal and polyclonal antibodies against trypsin and lipase (acinar cells); secretory component, carbonic anhydrase II, and pancreatic cancer mucin SPan‐1 (ductal cells); and chromogranin‐A and somatostatin (islet cells). the expression of carcinoembryonic antigen (CEA) and lysozyme were also determined. This collection of markers allowed the differentiation between acinar, ductal, and islet cells of normal pancreas and chronic pancreatitis specimens. the expression of cell lineage markers in islet cell tumors was homogeneous and restricted to chromogranin‐A. in contrast, the expression of these markers in primary and metastatic exocrine pancreatic adenocarcinomas was variable. Reactivity with monoclonal anti‐CEA was absent in normal pancreas, and was present in 83% of chronic pancreatitis specimens as well as 90% of exocrine pancreatic adenocarcinomas. in addition, lysozyme reactivity was absent in normal pancreas; however, lysozyme was expressed in one case of chronic pancreatitis, 17 cases of primary carcinoma, and three cases of metastatic carcinoma. These findings support the concept that the original transformed cell type in many pancreatic exocrine carcinomas resemble endodermal “stem cells” that retain the capability of differentiation along more than one cell lineage pathway.
Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation
of mononuclear phagocytes, and locally regulates maternal-fetal interactions ...during pregnancy. It exerts these actions through
a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene.
Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas.
To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective
study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1
levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients
with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls
(3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated
in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High
serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed
in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%),
with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells
involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive
correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated
(P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these
tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1
in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial
adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome,
and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role
in endometrial adenocarcinoma development and proliferation.
Colorectal cancer generally affects men and women in the later decades of life. Typically patients present with bowel obstruction and/or chronic anemia. The epidemiology, presentation, and prognosis ...of cecal carcinoma, the third most common colorectal cancer, is similar to other cancers of the large bowel. Cecal and other colorectal cancers rarely present in adolescence. In this case report, we describe a 19-year-old woman presenting with a pelvic mass and elevated tumor markers with the presumed diagnosis of ovarian cancer, who was found to have cecal carcinoma at laparotomy. This case illustrates that colorectal cancer, although rare, should be considered in the differential diagnosis of a pelvic mass in young women who present with anemia, constitutional symptoms, and elevated tumor markers.
The effect of a variety of 6-substituted purines on development of Drosophila melanogaster, eggs and larva, were studied. Purine and 2,6-diaminopurine both were very toxic to egg development. Adenine ...and 2,6-diaminopurine were moderately and equally toxic to larva development. Substitution on the 6-position of the purine ring was very effective in regulating metamorphosis of Drosophila.
Nucleic acid-based diagnostic assays for the quantitation of plasma HIV-1 RNA levels are used to monitor disease progression and the response of patients to antiretroviral drug therapy. The LCx® HIV ...RNA Quantitative Assay (Abbott Laboratories, North Chicago, IL) is an assay for the quantitation of HIV type 1 RNA in plasma that uses competitive reverse transcription PCR (RT-PCR) followed by Microparticle Enzyme Immunoassay, and includes an internal control for inhibition and RNA recovery, that is taken through the entire sample preparation procedure. The performance of the assay was assessed for 1 and 0.2 ml sample volumes. For a 1 ml sample volume, the lower limit of detection was found to be 50 copies/ml with a linear range from 50 to 1 million copies/ml. For a 0.2 ml sample volume, the lower limit of detection was found to be 178 copies/ml with a linear range from 178 to 5 million copies/ml. The assay is able to detect and quantitate HIV subtypes A–G and group O. LCx® HIV RNA assay quantitation results are highly correlated to the standard and ultrasensitive Amplicor® HIV-1 Monitor assay (Roche Molecular Systems) quantitation results. Assay performance is consistent with the use of this test for routine quantitation of HIV-1 RNA in plasma.
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