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BACKGROUND: Fine-needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules. However, FNA-induced secondary changes completely replacing thyroid tumors (vanishing tumors) may create a novel problem. In this study, we highlight the diagnostic and management issues associated with the unintended consequences of ultrasonography (US)-guided FNA. METHODS: Fourteen thyroid glands (11 women and 3 men, ages 33–64 years) with vanishing tumors were prospectively identified between 2009 and 2012 upon surgical resection. Cytology and histopathology slides were reviewed, and second opinions were obtained when necessary. RESULTS: The cytology of the 14 vanishing tumors was suspicious/positive for papillary thyroid carcinoma (PTC) in 5, indeterminate (atypia of unknown significance) in 5, benign in 2, follicular neoplasm in 1, and nondiagnostic in 1 nodule. Upon thyroidectomy, the vanishing tumors ranged in size from 0.4 to 3.5 cm (median 0.7 cm). Microscopically, the nodules showed cystic degeneration, organizing hemorrhage, granulation tissue, fibrosis, and microcalcifications. In seven tumors, a few residual malignant cells (PTC in five) or residual benign follicles (hemorrhagic cyst in two) at the periphery of the vanishing tumors helped with the final diagnosis. The remaining seven tumors were completely replaced by FNA-induced secondary changes, and had the cytology diagnosis of benign in one, follicular neoplasm in one, and suspicious/positive for PTC in five. Of the latter five, two showed additional separate foci of PTC, while three vanishing tumors (0.5, 1.2, and 1.6 cm) had no residual malignant cells and no additional carcinoma leading to a final diagnosis of negative for malignancy. CONCLUSIONS: US-guided FNA may lead to complete obliteration of thyroid nodules, rendering final diagnosis upon thyroidectomy difficult or impossible. In these unusual circumstances, the possibility that the surgical pathology may be nonrepresentative should be considered if the cytologic features on FNA are sufficient by themselves to support a definitive diagnosis of PTC.

SummaryBovine vWF cDNA has been cloned from a bovine endothelial cell library. A fragment of this cDNA, corresponding to amino acid sequence Leu 469-Ser 723, called primary adhesion domain (PAD-1), and containing the binding sites for platelet glycoprotein Ib (GPIb), heparin and collagen, has been expressed in E. coli. The reduced and alkylated form of fragment PAD-1 inhibited native vWF binding to GPIb. Fragment PAD-1 bound to heparin and botrocetin in a specific and dose dependent manner as did the native vWF. In a solid-phase assay, fragment PAD-1 bound to calf skin collagen in contrast to a human vWF recombinant fragment (Ser 445-Val 733) which was inactive in the same assay. The studies presented in this paper demonstrated that the A1 domain of bovine vWF contained the GPIb, heparin, botrocetin as well as collagen binding sites and that integrity of the disulfide bond (Cys 509-Cys 695), did not seem to be essential for binding of bovine vWF fragment to GPIb.

The distinction of Crohn's disease from ulcerative colitis is based on clinical, endoscopic, radiological, and histological findings, a paradigm that remains unchanged despite the advent of new understanding of the immunological and genetic basis of inflammatory bowel disease. There is a strong correlation between inflammatory bowel disease, predominantly ulcerative colitis, and autoimmune pancreatitis. We hypothesized that colonic biopsies from patients with inflammatory bowel disease would demonstrate increased numbers of IgG4-positive plasma cells and that this elevation might be restricted to ulcerative colitis. We examined a cohort of 78 cases of inflammatory bowel disease: 50 ulcerative colitis and 38 Crohn's disease. We identified treatment-naive biopsies. Additionally, four cases of inflammatory bowel disease associated with autoimmune pancreatitis and 15 cases of lymphocytic/collagenous colitis were also identified. Immunohistochemical stains for IgG4 were performed. Biopsies from patients with ulcerative colitis showed significantly higher numbers of IgG4-bearing plasma cells than those with Crohn's disease (mean IgG4 counts per high-power field (hpf) 9.8 vs 2.8, P=0.001). Samples from 19 (38%) ulcerative colitis patients had IgG4 counts >10/hpf, compared with only two (5%) patients with Crohn's disease; the sensitivity and specificity of a cutoff at 10 IgG4-positive plasma cells per hpf was 38 and 95%, respectively. Among individuals

Introduction Body mass index (BMI) and indicators of central adiposity have been associated with cardiovascular disease (CVD) risk factors, but ambiguity remains about which measure optimally predicts CVD risk and is best suited for different racial/ethnic groups. We sought to characterize excess adiposity among New York City adults and assess the potential associations between multiple adiposity indicators and CVD risk factors, by race/ethnicity. Methods The New York City Health and Nutrition Examination Survey (NYC HANES) is a population-based survey of noninstitutionalized New York City adult residents aged 20 years or older. We compared the prevalence of obesity (BMI ≥30 kg/m2), elevated waist circumference (>102 cm for men, >88 cm for women), and elevated waist-to-height ratio (≥0.5) for participants in the 2004 NYC HANES (n = 1,912) and the 2003-2004 National Health and Nutrition Examination Survey (n = 4,075). Logistic regression was used to assess potential associations between each of these indicators of excess adiposity and CVD risk factors (diabetes, impaired fasting glucose, hypertension, and hypercholesterolemia), overall and by race/ethnicity. Results The prevalence of obesity among NYC HANES participants was 26% and of elevated waist circumference was 46%, both significantly lower than national estimates (31% and 52%, respectively), whereas the prevalence of elevated waist-to-height ratio was higher (82% vs 79%). Most measures of excess adiposity were significantly associated with all CVD risk factors. No single measure of excess adiposity emerged as most consistently predictive of CVD risk in the general population or by race/ethnicity. Conclusion New York City has a lower prevalence of obesity and elevated waist circumference but a higher prevalence of elevated waist-to-height ratio than found nationally. Further investigation into the optimal adiposity measure to predict CVD risk across racial/ethnic populations may be warranted.

Automated pharmacy databases are increasingly available for assessing medication use, but research on the validity of these data is incomplete. This study aimed to measure agreement on warfarin and aspirin use between medical records and automated pharmacy data among patients with newly detected atrial fibrillation (AF).Patients with newly detected AF (n = 1953) were previously identified in a cohort study at Group Health (GH) in Washington State. Medical records were reviewed for information on risk factors and medication use, as well as clinical care during the 6 months after AF onset. Medication data were also obtained from the GH pharmacy database. We determined the sensitivity, specificity, and positive predictive value (PPV) as measures of the validity of the GH pharmacy database as compared with medical records for warfarin and aspirin use during the first 6 and 3 months after AF onset. We also calculated the κ statistic.For warfarin use, in comparison with the medical record review, the sensitivity, specificity, and PPV for the GH pharmacy database were excellent, and agreement was almost perfect in the 3- and 6-month periods after AF onset (κ = 0.92 and 0.93, respectively). For aspirin use, the GH pharmacy database had low sensitivity but high specificity, and agreement was only fair for these two periods (κ = 0.28 and 0.31, respectively).The GH pharmacy database is a valuable source of data for pharmacoepidemiologic research on warfarin use among patients with AF. However, the database cannot be recommended for assessment of aspirin use. Copyright © 2010 John WileySons, Ltd.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign, proliferative mesenchymal lesion with possible hormonal etiology. It typically affects women in the reproductive age group. Pseudoangiomatous stromal hyperplasia is frequently an incidental histologic finding in breast biopsies performed for other benign or malignant lesions. Rarely, it can present as a firm, painless breast mass, which has been referred to as nodular or tumorous PASH. Grossly, tumorous PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slitlike spaces in dense collagenous stroma. The spaces are lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. The most important differential diagnosis on histopathology is angiosarcoma. Pseudoangiomatous stromal hyperplasia discovered incidentally does not require any additional specific treatment. Tumorous PASH is treated by local surgical excision with clear margins and the prognosis is excellent, with minimal risk of recurrence after adequate surgical excision.

Introduction: We describe smoking prevalence and second- hand smoke (SHS) exposure among adult nonsmokers in New York City (NYC) across key demographic strata and compare exposure estimates with those found nationally. Methods: We used serum cotinine data from the 2004 NYC Health and Nutrition Examination Survey ( n = 1,767 adults aged 20 years or older) and the 2003 - 2004 National Health and Nutrition Examination Survey ( n = 4,476 adults aged 20 years or older) to assess and compare smoking prevalence and the prevalence of elevated cotinine levels ( ≥ 0.05 ng/ml) among nonsmokers. We conducted multivariate logistic regression to assess independent predictors of elevated cotinine levels in NYC. Results: Although the smoking prevalence in NYC was lower than that found nationally (23.3% vs. 29.7%, p < .05), the pro- portion of nonsmoking adults in NYC with elevated cotinine levels was greater than the national average overall (56.7% vs. 44.9%, p < .05) and was higher for most demographic sub- groups. In NYC, the highest cotinine levels among nonsmokers were among adults aged 20 - 39 years, males, and Asians. Discussion: Although NYC enacted comprehensive smoke- free workplace legislation in 2003, fi ndings suggest that expo- sure to SHS remains a signifi cant public health issue, especially among certain subgroups. The fi nding of a higher prevalence of SHS exposure in NYC despite lower smoking rates is puzzling but suggests that SHS exposure in dense, urban settings may pose a particular challenge.

Hepatitis C virus (HCV) is the leading cause of chronic liver disease in the United States. Accurate hepatitis C prevalence estimates are important to guide local public health programs but are usually unavailable to local health jurisdictions. National surveys may not reflect local variation, a particular challenge for urban settings with disproportionately large numbers of residents in high-risk population groups. In 2004, the New York City Department of Health and Mental Hygiene conducted the NYC Health and Nutrition Examination Survey, a population-based household survey of non-institutionalized NYC residents ages 20 and older. Study participants were interviewed and blood specimens were tested for antibody to HCV (anti-HCV); positive participants were re-contacted to ascertain awareness of infection and to provide service referrals. Of 1,786 participants with valid anti-HCV results, 35 were positive for anti-HCV, for a weighted prevalence of 2.2% (95% confidence interval [CI] 1.5% to 3.3%). Anti-HCV prevalence was high among participants with a lifetime history of injection drug use (64.5%, 95% CI 39.2% to 83.7%) or a lifetime history of incarceration as an adult (8.4%, 95% CI 4.3% to 15.7%). There was a strong correlation with age; among participants born between 1945 and 1954, the anti-HCV prevalence was 5.8% (95% CI 3.3% to 10.0%). Of anti-HCV positive participants contacted (51%), 28% (n = 5) first learned of their HCV status from this survey. Continued efforts to prevent new infections in known risk behavior groups are essential, along with expansion of HCV screening and activities to prevent disease progression in people with chronic HCV.

A 62-year-old woman with a pre-existing psoriasis was treated with oral imatinib (400 mg/day) for a metastatic gastrointestinal stromal tumour. Within 4 weeks of starting therapy, she developed a guttate psoriasis flare. The eruption markedly improved within 2 weeks following cessation of imatinib. However, it recurred when imatinib was recommenced. She has been able to continue on imatinib (400 mg/day) with low-dose oral methotrexate (12.5 mg/week) controlling the psoriasis.

Objectives. We sought to evaluate the contribution of the New York City Health and Nutrition Examination Survey (NYC-HANES) to local public health surveillance. Methods. Examination-diagnosed estimates of key health conditions from the 2004 NYC-HANES were compared with the National Health and Nutrition Examination Survey (NHANES) 2003–2004 national estimates. Findings were also compared with self-reported estimates from the Community Health Survey (CHS), an annually conducted local telephone survey. Results. NYC-HANES estimated that among NYC adults, 25.6% had hypertension, 25.4% had hypercholesterolemia, 12.5% had diabetes, and 25.6% were obese. Compared with US adults, NYC residents had less hypertension and obesity but more herpes simplex 2 and environmental exposures (P < .05). Obesity was higher and hypertension was lower than CHS self-report estimates (P < .05). NYC-HANES and CHS self-reported diabetes estimates were similar (9.7% vs 8.7%). Conclusions. NYC-HANES and national estimates differed for key chronic, infectious, and environmental indicators, suggesting the need for local data. Examination surveys may provide more accurate information for underreported conditions than local telephone surveys. Community-level health and nutrition examination surveys complement existing data, providing critical information for targeting local interventions.

OBJECTIVE—To determine the prevalence of diabetes and impaired fasting glucose (IFG) and to assess clinical management indicators among adults with diabetes in a representative sample of New York City adults. RESEARCH DESIGN AND METHODS—In 2004, New York City implemented the first community-level Health and Nutrition Examination Survey (NYC HANES), modeled after the National Health and Nutrition Examination Survey (NHANES). We used an interview to determine previously diagnosed diabetes and measured fasting plasma glucose to determine undiagnosed diabetes and IFG in a probability sample of 1,336 New York City adults. We assessed glycemic control and other clinical indicators using standardized NHANES protocols. RESULTS—The prevalence of diabetes among New York City adults was 12.5% (95% CI 10.3–15.1): 8.7% diagnosed and 3.8% undiagnosed. Nearly one-fourth (23.5%) of adults had IFG. Asians had the highest prevalence of impaired glucose metabolism (diabetes 16.1%, IFG 32.4%) but were significantly less likely to be obese. Among adults with diagnosed diabetes, less than one-half (45%) had A1C levels CONCLUSIONS—In New York City, diabetes and IFG are widespread. Policies and structural interventions to promote physical activity and healthy eating should be prioritized. Improved disease management systems are needed for people with diabetes.

Sertoli-Leydig cell tumor (SLCT) is a rare tumor involving the ovary. Approximately 20% of SLCT are associated with heterologous elements that are either of endodermal or mesodermal origin. The gastrointestinal-type epithelium is the most commonly described endodermal heterologous element. SLCT with benign and borderline mucinous neoplasm has been reported in the literature. However, SLCT with mucinous adenocarcinoma as heterologous element has been rarely documented. Herein, we describe a rare case of intermediately differentiated Sertoli-Leydig cell tumor with mucinous adenocarcinoma as the heterologous element in a 21-year-old woman. She presented with throbbing lower abdominal pain and was found to have a large, complex left ovarian mass on imaging studies. She underwent left salpingo-oophorectomy, appendectomy and lymph node staging. Gross examination of the surgical specimen showed a large, encapsulated, solid-cystic mass completely replacing the ovary. Microscopically, the tumor was composed of intermediately differentiated Sertoli-Leydig cell tumor and well-differentiated mucinous adenocarcinoma. Interestingly, the bulk of the tumor (more than 90%) was composed of mucinous adenocarcinoma, whereas the SLCT component comprised less than 10% of the total tumor. The mucinous adenocarcinoma expressed positivity for CK20, CEA, CDX2 and CK7, and the SLCT component was positive for inhibin expression. The histopathological features and results of immunostaining were consistent with the diagnosis of the intermediately differentiated SLCT with mucinous adenocarcinoma as the heterologous element. This case was a diagnostic challenge as more than 90% of the tumor was composed of mucinous adenocarcinoma and SLCT constituted only the minor part of the tumor. This feature was in contrast to the previously described two cases, where mucinous adenocarcinoma as heterologous element was present as microscopic foci. This case highlights the importance of identifying the SLCT component in a case of an apparently pure mucinous adenocarcinoma in a young patient.

Diffuse cavernous hemangioma of the uterus in pregnant woman is an extremely rare condition. A total of eight cases have been described in the literature till date. The antenatal diagnosis as well as management requires considerable skill. Although it is a benign condition but it can have serious consequences for the mother as well as the baby.Here we describe an interesting case of diffuse cavernous hemangioma of the uterus in a 21-year-old G3, P2-0-0 pregnant woman, who underwent hysterectomy for uncontrollable bleeding during third cesarean section. The diagnosis of diffuse cavernous hemangioma was made only on histopathological examination of the hysterectomy specimen.Diffuse hemangioma of the uterus in a pregnant woman is a serious condition, which may not be detected early during the pregnancy. This can result in uncontrolled bleeding especially during operative delivery and may require hysterectomy.

Background: Surveillance for HIV likely underestimates infection among the general population: 25% of US residents are estimated to be unaware of their HIV infection. Objective: To determine the prevalence of HIV infection and risk behaviors among New York City (NYC) adults and compare these with surveillance findings. Methods: The NYC Health and Nutrition Examination Survey (HANES) provided the first opportunity to estimate population-based HIV prevalence among NYC adults. It was conducted in 2004 among a representative sample of adults > 20 years. Previously reported HIV infection was identified from the NYC HIV/AIDS Surveillance Registry. A blinded HIV serosurvey was conducted on archived blood samples of 1626 NYC HANES participants. Data were used to estimate prevalence for HIV infection, unreported infections, high-risk activities, and self-perceived risk. Results: Overall, 18.1% engaged in one or more risky sexual/needle-use behaviors, of which 92.2% considered themselves at lowor no risk of HIV or another sexually transmitted disease. HIV occurred in 21 individuals (prevalence 1.4%; 95% confidence interval (Cl), 0.8-2.5]; one infection (5%; 95% Cl, 0.7-29.9) was not reported previously and possibly undiagnosed. HIV infection was significantly elevated in those with herpes simplex virus 2 (4%), men who have sex with men (14%), and needle-users (21 %) (P < 0.01). Conclusions: Among NYC adults, HIV prevalence was consistent with surveillance findings overall. The proportion of unreported HIV was less than estimated nationally, but findings were limited by sample size. Most adults with risky behaviors perceived themselves to be at minimal risk, highlighting the need for risk reduction and routine HIV screening.

Purpose: Epigenetic events are a critical factor contributing to cancer development. The purpose of this study was to identify tumor suppressor genes silenced by DNA methylation and histone deacetylation in non–small cell lung cancer (NSCLC). Experimental Design: We used microarray analysis to screen for tumor suppressor genes. Results: We identified Per1, a core circadian gene, as a candidate tumor suppressor in lung cancer. Although Per1 levels were high in normal lung, its expression was low in a large panel of NSCLC patient samples and cell lines. Forced expression of Per1 in NSCLC cell lines led to significant growth reduction and loss of clonogenic survival. Recent studies showed that epigenetic regulation, particularly histone H3 acetylation, is essential for circadian function. Using bisulfite sequencing and chromatin immunoprecipitation, we found that DNA hypermethylation and histone H3 acetylation are potential mechanisms for silencing Per1 expression NSCLC. Conclusions: These results support the hypothesis that disruption of circadian rhythms plays an important role in lung tumorigenesis. Moreover, our findings suggest a novel link between circadian epigenetic regulation and cancer development.

Aggregation chaperones, consisting of secretory proteins that contain a hexa-histidine epitope tag, enhance the calcium-induced aggregation of regulated secretory proteins and their sorting to secretory granules. The goal of this study was to gain a better understanding of this unusual aggregation mechanism. Hexa-histidine-epitope-tagged secreted alkaline phosphatase, an aggregation chaperone, enhanced the in vitro aggregation of chromogranin A in the presence of calcium, but not in the presence of magnesium or other divalent cations. As an exception, chromogranin was completely aggregated by zinc, even in the absence of the aggregation chaperone. In addition, fluorescence spectroscopy of the aggregation reaction mixture showed an increase in fluorescence intensity consistent with the formation of protein aggregates. The calcium-induced aggregation of chromogranin A was completely inhibited by 0.2% Triton X-100, suggesting that it involves hydrophobic interactions. In contrast, the detergent did not affect chaperone-enhanced aggregation, suggesting that this aggregation does not depend on hydrophobic interactions. EDTA-treated chaperone did not enhance chromogranin A aggregation, indicating that divalent cations are necessary for chaperone action. Although the structure of the aggregation chaperone was not important, the size of the chaperone was. Thus the free His-hexapeptide could not substitute for the aggregation chaperone. Based on these results, we propose that the hexa-histidine tag, in the context of a polypeptide, acts as a divalent cation-dependent nucleation site for chromogranin A aggregation.

Jak3, a member of the Janus kinase family of cytoplasmic tyrosine kinases, is expressed at low levels in immature hematopoietic cells and its expression is dramatically up-regulated during the terminal differentiation of these cells. To better understand the role of Jak3 in myeloid cell development, we have investigated the role of Jak3 in myeloid cell differentiation using the 32Dcl3 cell system. Our studies show that Jak3 is a primary response gene for granulocyte colony-stimulating factor (G-CSF) and the accumulation of tyrosine phosphorylated Jak3 correlated with cell growth inhibition and terminal granulocytic differentiation in response to G-CSF. Ectopic overexpression of Jak3 in 32Dcl3 cells resulted in an acceleration of the G-CSF–induced differentiation program that was preceded by G1 cell cycle arrest, which was associated with the up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 and down-regulation of Cdk2, Cdk4, Cdk6, and Cyclin E. In addition, ectopic overexpression of Jak3 appears to result in the inactivation of PKB/Akt and Stat3-mediated proliferative pathways in the presence of G-CSF. Similarly, overexpression of Jak3 in primary bone marrow cells resulted in an acceleration of granulocytic differentiation in the presence of granulocyte-macrophage colony-stimulating factor, which was associated with their growth arrest in the G1 phase of the cell cycle. Taken together, these results indicate that Jak3-mediated signals play an important role in myeloid cell differentiation.

Endocrine, neuroendocrine and exocrine cells store regulated secretory proteins in secretory granules, while constitutive and constitutive-like secretory proteins are secreted directly without storage. Sorting of secretory proteins takes place in the trans-Golgi network (sorting for entry) or immature secretory granules (sorting by retention). The relative contribution of these sorting steps and the sorting signals and mechanisms involved in each step has been the subject of intense studies and debate in recent years. New evidence now suggests that: (1) two proteins with structurally similar sorting signals can use different sorting mechanisms; (2) one protein with multiple sorting signals can be sorted differently in different cell types; and (3) one cell type can recognize different sorting signals and use different sorting mechanisms. The latter finding suggests that sorting must be a regulated event. While the current image of sorting is complex, recent findings are pointing to common features that form a mosaic of related sorting mechanisms.

Aims/hypothesis. Sorting of proinsulin to the regulated secretory pathway of pancreatic beta cells and retention of insulin in dense-core granules of this pathway is remarkably efficient. To monitor the specificity of these events, the secretion of two exogenous secretory proteins not known to carry information for sorting or retention in the regulated pathway was investigated in INS-1 cells. Methods. SEGFP, a fusion protein consisting of a signal peptide N-terminal to EGFP (mutant green fluorescent protein with enhanced fluorescence) and secreted alkaline phosphatase (SEAP) were expressed in INS-1 cells by transfection and by infection with recombinant adenovirus, respectively. Secretion of SEGFP was monitored by quantitative western blotting and that of SEAP by its activity. Results. Secreted alkaline phosphatase showed high basal secretion (6.6 % total) but only modest (3.6-fold) stimulation of secretion by secretagogues, in keeping with secretion largely through the constitutive pathway. By contrast SEGFP had a secretory pattern similar to insulin, with low basal secretion (0.8 % total) and 16-fold stimulation by secretagogues. Granular localization of SEGFP was confirmed by high resolution electron microscopy immunocytochemistry. Pulse-chase experiments indicated retention of SEGFP in granules at least 24 h after synthesis. The secretory SEGFP, but not cytosolic EGFP, formed disulphide-linked oligomers. This could be implicated in its regulated secretion. Conclusion/interpretation. These data indicate that in INS-1 cells SEGFP, but not SEAP, is unexpectedly handled as a regulated secretory protein and stored along with insulin in granules. This raises questions about the specificity and mechanism of the sorting of proteins to granules in INS-1 cells or their retention therein or both. [Diabetologia (2000) 43: 1157–1164]

A mutant PAD-1(D514→Q) of the recombinant fragment PAD-1 comprising Leu469-Ser723 Of the A1 domain of bovine von Willebrand factor (vWF) neither inhibited the binding of [125I]vWF to platelets nor the agglutination of human platelets induced by bovine VWF. PAD-1, on the other hand, inhibited human platelet agglutination induced by bovine VWF and [125I]vWF binding to human platelets. Collagen binding properties of the mutant, however, were indistinguishable from those of PAD-1. These results suggested that Asp514 within the A1 domain of vWF is required for interaction of bovine vWF with GPIb receptor on human platelets.