Biomedical subjects

Arthur W Zieske

Publications and source records attributed to Arthur W Zieske.

12 recordsLinked to original sources

PubMed2006

Overexpression of SOCS3 is associated with decreased survival in a cohort of patients with de novo follicular lymphoma.

The prognostic significance of SOCS3 protein expression was determined in de novo follicular lymphomas (FL) with t(14;18) and bcl-2 overexpression. Presentation lymph nodes from 82 FL patients for whom clinical information was available were immunohistochemically segregated into SOCS3-positive (n = 42) or -negative (n = 40) cohorts, and overall survival (OS) was analysed. SOCS3-positive FL patients had a median OS of 10 years compared with 22 years in SOCS3-negative patients (P = 0.001, log rank test). After adjusting for Follicular Lymphoma International Prognostic Index subgroups, SOCS3 overexpression remained an independent predictor of decreased OS (P < 0.001). These findings suggest that overexpression of SOCS3 may be an independent poor prognostic variable in patients with de novo FL.

Adult↗

PubMed2005

Risk scores predict atherosclerotic lesions in young people.

BACKGROUND: Atherosclerosis begins in childhood and progresses through young adulthood to form the lesions that cause coronary heart disease. These preclinical lesions are associated with coronary heart disease risk factors in young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from persons aged 15 to 34 years who died of external causes and underwent autopsy in forensic laboratories. We measured the coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the CAs and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95% confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal aorta) and were calibrated. The presence of abdominal aortic lesions increased the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from traditional coronary heart disease risk factors provide a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.

Adolescent↗

PubMed2005

Elevated serum C-reactive protein levels and advanced atherosclerosis in youth.

OBJECTIVE: To determine the associations among serum C-reactive protein (CRP) concentration, age, sex, risk factors for coronary heart disease (CHD), and atherosclerosis in young people. METHODS AND RESULTS: In 1244 subjects 15 to 34 years of age, we measured gross atherosclerotic lesions in the right coronary artery (RCA) and abdominal aorta (AA) and American Heart Association (AHA) lesion grade in the left anterior descending (LAD) coronary artery; serum CRP, lipoprotein cholesterol, and thiocyanate (for smoking) concentrations; intimal thickness of renal arteries (for hypertension); glycohemoglobin (for hyperglycemia); and body mass index (for obesity). Serum CRP levels increased with age, were higher in women than in men, and were positively related to obesity and hyperglycemia. Serum CRP > or =10 mg/L was associated with more extensive gross raised lesions in the RCA after age 25 and in the AA after age 30. Serum CRP > or =3 was associated with a greater prevalence of AHA grade 5 lesions in the proximal LAD coronary artery after age 25. The associations of CRP with lesions were independent of the traditional CHD risk factors. CONCLUSIONS: Serum CRP level is independently associated with advanced atherosclerosis in young persons.

Adolescent↗

PubMed2005

Desmoplastic Infantile Ganglioglioma: cytologic findings and differential diagnosis on aspiration material.

BACKGROUND: Desmoplastic infantile ganglioglioma (DIG) is a rare WHO Grade I tumor of infancy that is characterized by large volume, superficial location, invariable supratentoriality, fronto-parietal lobe predilection and morphologically, by an admixture of astroglial and neuroepithelial elements in a desmoplastic milieu. With over 50 cases described, the histologic and radiographic spectrum of DIG has been well-characterized. The superficial location of DIGs may render them greatly amenable to preoperative assessment utilizing aspiration cytology; however, the cytologic features of this rare tumor have only been reported once previously. CASE PRESENTATION: We present herein cytomorphologic findings from the intraoperative aspiration of a typical case of DIG diagnosed in a 1-year-old male. As evaluated on a single liquid-based preparation, the specimen showed low cellularity and was comprised predominantly of a population of dispersed (occasionally clustered) large neuronal cells with eccentrically located hyperchromatic nuclei (which were occasionally binucleated) and abundant unipolar cytoplasm. Rare smaller astroglial cells were intermixed. Despite the tumor's characteristic desmoplastic histologic appearance, no stromal fragments were identified on the aspiration material. CONCLUSIONS: A differential diagnosis is presented and analyzed in detail and it is concluded that when these large neuronal cells are encountered in an aspirate of a brain mass in a child, a combination of clinical, radiologic and immunohistochemical parameters can eliminate most of the differential possibilities.

Journal Article↗

PubMed2005

ACE insert/delete polymorphism and atherosclerosis.

We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

Adolescent↗

PubMed2004

Smoking is associated with advanced coronary atherosclerosis in youth.

Smoking is linked to atherosclerosis and coronary heart disease (CHD) in older adults. However, evidence that smoking affects coronary atherosclerosis in young people is incomplete. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study collected arteries, blood, and other tissues from persons 15 to 34 years of age dying of external causes and autopsied in forensic laboratories. Lesions in the proximal left anterior descending coronary arteries (LAD) from 1127 subjects were graded microscopically according to the American Heart Association criteria. Among individuals with advanced lesions (Grade 4 or 5), smokers had a greater prevalence of Grade 5 lesions than non-smokers (odds ratio 9.61, 95% confidence interval 2.34-39.57), a difference suggesting that smoking accelerates the transition from Grade 4 to Grade 5 lesions. This association occurred among both men and women, and among persons with and without other CHD risk factors. The difference in qualities of advanced lesions suggests that smoking possibly accelerates the transition from Grade 4 to Grade 5 lesions by promoting thrombosis and accretion on the intimal surface of the plaque.

Adolescent↗

PubMed2004

MMP-1 polymorphic expression in aortic endothelial cells: possible role in lesion development in smokers and nonsmokers.

Matrix metalloproteinase-1 (MMP-1) is involved in the degradation of extra-cellular matrix components and is thought to play a key role in atherogenesis. The objective of the present study was to determine: (1) whether MMP-1 differential gene expression observed in primary cultures of human aortic endothelial cells (HAEC) exposed to cigarette smoke condensate (CSC) was associated with a single nucleotide polymorphism (SNP) in its promoter region and (2) if the SNP altered atherosclerotic lesion development in smokers and nonsmokers. Genotype analysis of six HAEC lines revealed that those homozygous for the 1G-variant exhibited low levels of gene expression. Cells homozygous for the 2G-variant or heterozygous (1G/2G) had elevated levels of both mRNA and protein. These relative levels were also seen after CSC expo-sure. MMP-1 genotypes of 104 Caucasian males acquired from the Pathobiological Determinants of Atherosclerosis in Youth study were compared with the extent of atherosclerotic lesion development in the aorta. The results indicate that, although the MMP-1 SNP influences MMP-1 gene expression in cultured HAEC exposed to CSC, differences in lesion development were not observed based on this polymorphism in young Caucasian males.

Arteries↗

PubMed2004

Bcl-2 overexpression leads to increases in suppressor of cytokine signaling-3 expression in B cells and de novo follicular lymphoma.

The t(14;18)(q32;q21), resulting in deregulated expression of B-cell-leukemia/lymphoma-2 (Bcl-2), represents the genetic hallmark in human follicular lymphomas. Substantial evidence supports the hypothesis that the t(14;18) and Bcl-2 overexpression are necessary but not solely responsible for neoplastic transformation and require cooperating genetic derangements for neoplastic transformation to occur. To investigate genes that cooperate with Bcl-2 to influence cellular signaling pathways important for neoplastic transformation, we used oligonucleotide microarrays to determine differential gene expression patterns in CD19+ B cells isolated from Emu-Bcl-2 transgenic mice and wild-type littermate control mice. Fifty-seven genes were induced and 94 genes were repressed by > or =2-fold in Emu-Bcl-2 transgenic mice (P < 0.05). The suppressor of cytokine signaling-3 (SOCS3) gene was found to be overexpressed 5-fold in B cells from Emu-Bcl-2 transgenic mice. Overexpression of Bcl-2 in both mouse embryo fibroblast-1 and hematopoietic cell lines resulted in induction of SOCS3 protein, suggesting a Bcl-2-associated mechanism underlying SOCS3 induction. Immunohistochemistry with SOCS3 antisera on tissue from a cohort of patients with de novo follicular lymphoma revealed marked overexpression of SOCS3 protein that, within the follicular center cell region, was limited to neoplastic follicular lymphoma cells and colocalized with Bcl-2 expression in 9 of 12 de novo follicular lymphoma cases examined. In contrast, SOCS3 protein expression was not detected in the follicular center cell region of benign hyperplastic tonsil tissue. These data suggest that Bcl-2 overexpression leads to the induction of activated signal transducer and activator of transcription 3 (STAT3) and to the induction of SOCS3, which may contribute to the pathogenesis of follicular lymphoma.

Animals↗

PubMed2002

Obesity accelerates the progression of coronary atherosclerosis in young men.

BACKGROUND: Obesity is a risk factor for adult coronary heart disease and is increasing in prevalence among youths as well as adults. Results regarding the association of obesity with atherosclerosis are conflicting, particularly when analyses account for other risk factors. METHODS AND RESULTS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood, and other tissue from approximately 3000 persons aged 15 to 34 years dying of external causes and autopsied in forensic laboratories. We measured gross atherosclerotic lesions in the right coronary artery (RCA), American Heart Association (AHA) lesion grade in the left anterior descending coronary artery (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal thickness of renal arteries (for hypertension), glycohemoglobin (for hyperglycemia), and adiposity by body mass index (BMI) and thickness of the panniculus adiposus. BMI in young men was associated with both fatty streaks and raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect of obesity (BMI>30 kg/m(2)) on RCA raised lesions was greater in young men with a thick panniculus adiposus. Obesity was associated with non-HDL and HDL (inversely) cholesterol concentrations, smoking (inversely), hypertension, and glycohemoglobin concentration, and these variables accounted for approximately 15% of the effect of obesity on coronary atherosclerosis in young men. BMI was not associated with coronary atherosclerosis in young women although there was trend among those with a thick panniculus adiposus. CONCLUSIONS: Obesity is associated with accelerated coronary atherosclerosis in adolescent and young adult men. These observations support the current emphasis on controlling obesity to prevent adult coronary heart disease.

Adipose Tissue↗

PubMed2002

Atherosclerotic plaque-like lesions in synthetic arteriovenous grafts: implications for atherogenesis.

Atherosclerotic plaque-like lesions are prevalent in synthetic arteriovenous shunts created to provide vascular access for hemodialysis. Similarities to atherosclerotic plaques in native arteries include eccentric location, immunoreactivity for smooth muscle actin, dystrophic calcifications, superimposed thrombi, and foam cells. Fatty streaks were not grossly identified on Sudan IV staining. Because of the similarities to atherosclerosis in native vessels, these findings may have several implications for atherogenesis. The development of raised, fibrous lesions does not require decades. The presence of smooth muscle in atherosclerotic plaque-like lesions does not require a source from tunica media. A precursor fatty streak may not be required for the development of raised, fibrous lesions. Finally, development of atherosclerotic plaque-like lesions does not require putative inflammatory effects from cholesterol or LDL accumulation, or even a native vessel that can respond to injury. The atherosclerotic plaque-like lesions in this study probably developed from organization of mural thrombi.

Arteriosclerosis↗

PubMed2002

The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view. Our results show that 7B2 nulls exhibit a multisystem disorder that includes severe pathoanatomical and histopathologic alterations of vital organs, including the heart and spleen but most notably the liver, in which massive steatosis and necrosis are observed. Metabolic derangements in glucose metabolism result in glycogen and fat deposition in liver under conditions of chronic hypoglycemia. Liver failure is also likely to contribute to abnormalities in blood coagulation and blood chemistry, such as lactic acidosis. A hypoglycemic crisis coupled with respiratory distress and intensive internal thrombosis most likely results in rapid deterioration and death of the 7B2 null.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Natural history and risk factors of atherosclerosis in children and youth: the PDAY study.

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized to document the natural history of athersclerosis and to determine the relation of cardiovascular risk factors to atherosclerosis in young subjects. Pathology laboratories in 15 centers collected coronary arteries, aortas, and other tissues from over 3,000 subjects age 15 to 34 who died of external causes between 1987 and 1994. The extent, prevalence, and topography of arterial lesions were evaluated and risk factors were analyzed in a central laboratory. Postmortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus and body mass index (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. The PDAY study confirmed the origin of atherosclerosis in childhood, showed that progression toward clinically significant lesions may occur in young adulthood and demonstrated that the progression of atherosclerosis is strongly influenced by coronary heart disease (CHD) risk factors. Recent PDAY studies have shown that a significant number of advanced coronary artery lesions have microscopic qualities associated with susceptibility to rupture and that CHD risk factors are associated with the development of these characteristic microscopic qualities. The PDAY archive continues to provide an important resource for new investigators throughout the world that contribute to the understanding of atherosclerosis, the underlying cause of most cardiovascular disease and the leading cause of debilitating illness and death in this country. The PDAY findings emphasize the need to modify risk factors in young people to retard the development of atherosclerotic lesions, particularly clinically significant lesions. Thus, true primary prevention of atherosclerosis must being in childhood or early adolescence.

Adolescent↗