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Primary Site (primary + site)
Kinds of Primary Site Selected AbstractsPurification of Matrix Gla Protein From a Marine Teleost Fish, Argyrosomus regius: Calcified Cartilage and Not Bone as the Primary Site of MGP Accumulation in Fish,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003DC Simes Abstract Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins, and in mammals, birds, and Xenopus, its mRNA was previously detected in extracts of bone, cartilage, and soft tissues (mainly heart and kidney), whereas the protein was found to accumulate mainly in bone. However, at that time, it was not evaluated if this accumulation originated from protein synthesized in cartilage or in bone cells because both coexist in skeletal structures of higher vertebrates and Xenopus. Later reports showed that MGP also accumulated in costal calcified cartilage as well as at sites of heart valves and arterial calcification. Interestingly, MGP was also found to accumulate in vertebra of shark, a cartilaginous fish. However, to date, no information is available on sites of MGP expression or accumulation in teleost fishes, the ancestors of terrestrial vertebrates, who have in their skeleton mineralized structures with both bone and calcified cartilage. To analyze MGP structure and function in bony fish, MGP was acid-extracted from the mineralized matrix of either bone tissue (vertebra) or calcified cartilage (branchial arches) from the bony fish, Argyrosomus regius,, separated from the mineral phase by dialysis, and purified by Sephacryl S-100 chromatography. No MGP was recovered from bone tissue, whereas a protein peak corresponding to the MGP position in this type of gel filtration was obtained from an extract of branchial arches, rich in calcified cartilage. MGP was identified by N-terminal amino acid sequence analysis, and the resulting protein sequence was used to design specific oligonucleotides suitable to amplify the corresponding DNA by a mixture of reverse transcription-polymerase chain reaction (RT-PCR) and 5,rapid amplification of cDNA (RACE)-PCR. In parallel, ArBGP (bone Gla protein, osteocalcin) was also identified in the same fish, and its complementary DNA cloned by an identical procedure. Tissue distribution/accumulation was analyzed by Northern blot, in situ hybridization, and immunohistochemistry. In mineralized tissues, the MGP gene was predominantly expressed in cartilage from branchial arches, with no expression detected in the different types of bone analyzed, whereas BGP mRNA was located in bone tissue as expected. Accordingly, the MGP protein was found to accumulate, by immunohistochemical analysis, mainly in the extracellular matrix of calcified cartilage. In soft tissues, MGP mRNA was mainly expressed in heart but in situ hybridization, indicated that cells expressing the MGP gene were located in the bulbus arteriosus and aortic wall, rich in smooth muscle and endothelial cells, whereas no expression was detected in the striated muscle myocardial fibers of the ventricle. These results show that in marine teleost fish, as in mammals, the MGP gene is expressed in cartilage, heart, and kidney tissues, but in contrast with results obtained in Xenopus and higher vertebrates, the protein does not accumulate in vertebra of non-osteocytic teleost fish, but only in calcified cartilage. In addition, our results also indicate that the presence of MGP mRNA in heart tissue is due, at least in fish, to the expression of the MGP gene in only two specific cell types, smooth muscle and endothelial cells, whereas no expression was found in the striated muscle fibers of the ventricle. In light of these results and recent information on expression of MGP gene in these same cell types in mammalian aorta, it is likely that the levels of MGP mRNA previously detected in Xenopus, birds, and mammalian heart tissue may be restricted toregions rich in smooth muscle and endothelial cells. Our results also emphasize the need to re-evaluate which cell types are involved in MGP gene expression in other soft tissues and bring further evidence that fish are a valuable model system to study MGP gene expression and regulation. [source] Who merits a neck dissection after definitive chemoradiotherapy for N2,N3 squamous cell head and neck cancer?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2003Scott A. McHam DO Abstract Background. The role of neck dissection (ND) after definitive chemoradiotherapy for squamous cell head and neck cancer is incompletely defined. We retrospectively reviewed 109 patients with N2,N3 disease treated with chemoradiotherapy to identify predictors of a clinical complete response in the neck (CCR-neck), pathologic complete response after ND (PCR-neck), and regional failure. Method. All patients were given 4-day continuous infusions of 5-fluorouracil (1000 mg/m2/d) and cisplatin (20 mg/m2/d) during the first and fourth weeks of either once daily (n = 68) or twice daily (n = 41) radiation therapy. ND was considered for all patients after completion of chemoradiotherapy and was performed in 32 of the 65 patients achieving a CCR-neck after chemoradiotherapy and in all 44 patients with residual clinical evidence of neck disease. CCR-neck, PCR-neck, and regional failure were then correlated with potential predictors, including T, N, largest lymph node size (<3 cm, ,3 cm), primary tumor site, and radiation fractionation schedule. Results. Achievement of a CCR-neck was predicted by N, N2 vs N3 (53 of 80 vs 12 of 29, p = .019) and by largest lymph node size, <3 cm vs ,3 cm (19 of 25 vs 46 of 84, p = .06). Achievement of a PCR-neck could not be predicted by any clinical parameter. Regional failure occurred both in patients undergoing ND and those not dissected (5 of 76 vs 4 of 33, p = .33) and proved more likely only in the ND patients with residual positive pathology compared with those achieving a PCR-neck (5 of 25 vs 0 of 51, p < .001). Primary site was not a useful predictor of CCR-neck, PCR-neck, or regional failure. Most importantly, CCR-neck (vs Primary small cell carcinoma of the lung initially presenting as a breast mass: A fine-needle aspiration diagnosisDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2009Wei Liu M.D. Abstract The incidence of metastases to the breast from extramammary sites is relatively low compared with the incidence of primary breast carcinoma. Primary sites which have a predilection for metastases to the breast include, in the order of decreasing frequency, malignant melanoma, lymphoma, lung carcinoma, ovarian carcinoma, and soft tissue sarcoma, followed by gastrointestinal and genitourinary primaries. Most lung primaries metastasizing to breast represent adenocarcinoma. Other types of lung carcinoma, including small cell carcinoma, are relatively rare. We report a case of lung small cell carcinoma metastasizing to the breast and initially presenting with a breast mass in a 50-year-old female. The tumor was first diagnosed on a fine-needle aspiration biopsy specimen (FNAB) from the breast lesion and subsequently supported by core biopsy. A discussion of the differential diagnoses to consider on FNAB follows. Because of the difference in treatment for primary small cell carcinoma of breast versus primary small cell carcinoma of the lung, as well as the difference in prognosis for both malignancies, determining the site of primary malignancy is crucial to adequate patient care. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Cutaneous melanoma: therapeutic lymph node and elective lymph node dissections, lymphatic mapping, and sentinel lymph node biopsyDERMATOLOGIC THERAPY, Issue 6 2005David B. Pharis ABSTRACT:, Early clinical observation in cancer patients suggested that tumors spread in a methodical, stepwise fashion from the primary site, to the regional lymphatics, and only then to distant locations. Based on these observations, the regional lymphatics were believed to be mechanical barriers, at least temporarily preventing the widespread dissemination of tumor. Despite evidence now available disputing its validity, this barrier theory has guided the surgical management of the regional lymphatics in cancer patients for more than a century, influencing the use of such surgical modalities as therapeutic lymph node dissection, elective lymph node dissection, and most recently lymphatic mapping and sentinel lymph node biopsy. No published randomized controlled trial exists that demonstrates improved overall patient survival for cancer of any type, including melanoma, after surgical excision of regional lymphatics. This article will review the biology of lymphatics as it relates to regional tumor metastasis, and based on available information, offer practical recommendations for the clinical dermatologist and their patients who have cutaneous melanoma. [source] Cutaneous melanoma: estimating survival and recurrence risk based on histopathologic featuresDERMATOLOGIC THERAPY, Issue 5 2005David E. Elder ABSTRACT:, The prognosis of melanoma is best understood in terms of a model of tumor progression, in which most melanomas may evolve through two major phases of progression: from a lesion that is nontumorigenic and has little or no capacity for metastasis; to a more advanced lesion that is tumorigenic and may have capacity for metastasis. The likelihood of metastasis varies with a number of attributes of the primary melanoma, including the phase of progression, the Breslow tumor thickness, mitotic rate, and host response to the tumorigenic compartment of the lesion, Clark's level of invasion, and other factors. When distant metastasis has occurred, the prognosis for the patient is very poor. In this monograph, the focus will be the discussion of factors related to the prognosis of melanomas that at diagnosis are clinically localized to the primary site. [source] An adipocentric view of signaling and intracellular traffickingDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2002Silvia Mora Abstract Adipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-,, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter. Copyright © 2002 John Wiley & Sons, Ltd. [source] Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 1 2010Danielle E. Westfall M.D. Abstract There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005,2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 ± 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Role of fine-needle aspiration cytology in evaluation of cutaneous metastasesDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009Sonal Sharma M.D. Abstract Skin is an uncommon site for metastasis. This study was done to evaluate the role of FNAC as an important tool for investigating cutaneous and subcutaneous nodules in patients with known malignancy or as a primary manifestation of an unknown malignancy. All the FNAC done from January 2003 to August 2008 were reviewed (n = 55,556). Ninty-five patients (49 males and 46 females with age range of 4,96 years) with cutaneous/subcutaneous nodules which were diagnosed as metastasis were analyzed. Primary tumors of skin/subcutis were excluded from the study. In our study, 63 out of 95 cases had a known primary malignancy. Of these, five had underlying hematological malignancy and 58 patients had solid organ tumors. Lung carcinoma was seen to metastasize most commonly to skin in males and breast carcinoma in females. The most common site for a cutaneous/subcutaneous metastasis was chest wall [40 followed by abdominal wall (14) and scalp (9)]. Multiple site involvement was also observed (8). In 32 cases primary site was not known. They were most commonly diagnosed as poorly differentiated carcinoma followed by adenocarcinoma. FNAC can diagnose a variety of tumors in the skin and support the diagnosis of a metastasis in case of a known primary and offer a clue to underlying malignancy in case of an occult primary. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Fine-needle aspiration biopsy of metastatic malignant melanoma resembling a malignant peripheral nerve sheath tumorDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008Svetoslav Bardarov M.D. Abstract We report a case of metastatic malignant melanoma resembling a malignant peripheral sheath tumor, which posed a significant diagnostic challenge. The patient is a 76-year-old male, who presented in the emergency room with bilateral chest pain exacerbated by inspiration. The pain was present for 3 week and was not exacerbated by physical exercise. The diagnostic workup revealed bilateral parenchymal pulmonary infiltrates. The CT-scan guided fine-needle aspiration and the core biopsies of the largest pulmonary lesion revealed high-grade spindle cell neoplasm with individual cell apoptosis and necrosis. The immunohistochemical profile on the cell block showed that the cells are positive for Vimentin. The S-100 stain showed only focal positivity. The immunohistochemical stains for HMB45, Melan A, pancytokeratin, and smooth muscle actin were negative. Five years ago the patient was diagnosed with melanoma on the back with Clark level of IV. The melanoma was excised with clear margins and sentinel lymph nodes were negative. Careful examination of patient's previous slides revealed an area of spindle cell melanoma adjacent to a nodular type melanoma. Based on the patient's previous history, current clinico-pathologic presentation and immunohistochemical profile, the diagnosis of metastatic malignant melanoma resembling peripheral nerve sheath tumor was favored over the diagnosis of metastatic malignant spindle cell neoplasm of unknown primary site, which by itself is very rare clinical scenario. Diagn. Cytopathol. 2008;36:754,757. © 2008 Wiley-Liss, Inc. [source] Fine-needle aspiration of metastatic prostatic neuroendocrine carcinomas: Cytomorphologic and immunophenotypic featuresDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2008Guoping Cai M.D. Abstract Metastatic prostatic carcinoma may, in rare occasions, present as a neuroendocrine tumor. Its recognition is crucial to avert a wrongful exclusion of prostate as a primary site. We report five cases of metastatic prostatic neuroendocrine carcinoma diagnosed by image-guided fine-needle aspiration biopsy. The aspirate smears showed loosely cohesive or dyscohesive clusters of tumor cells with scanty (three cases) to moderate amount (two cases) of cytoplasm, speckled or coarse chromatin and inconspicuous nucleoli. Nuclear molding and necrosis were focally present in two cases. Immunohistochemically, the tumor cells were positive for synaptophysin or/and chromogranin, but negative for prostatic specific antigen and prostatic specific acid phosphatase. Review of prior prostate biopsies/resections revealed adenocarcinoma with focal neuroendocrine differentiation in all cases, with two cases being newly recognized on retrospective review. Confirming neuroendocrine differentiation in the prior biopsy/resection may help to establish a link between metastasis and prostate primary. Diagn. Cytopathol. 2008; 36: 545,549. © 2008 Wiley-Liss, Inc. [source] Intracytoplasmic lumina in invasive micropapillary carcinoma of the lungDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2006Naoto Kuroda M.D. Abstract Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3,20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site. Diagn. Cytopathol. 2006;34:224,226. © 2006 Wiley-Liss, Inc. [source] Detection of a subset of CD30+ anaplastic large cell lymphoma by interphase fluorescence in situ hybridizationDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2003Hyung Ju C. Shin M.D. Abstract T/null-cell anaplastic large cell lymphoma (ALCL) is a morphologically and clinically heterogeneous group of non-Hodgkin's lymphoma; to date several morphologic variants have been described on histologic specimens. However, the cytologic features of these variants in the fine-needle aspiration (FNA) specimens have not been well evaluated. The t(2;5)(p23;q35) has been identified in a subset of T/null-ALCL and is known to be associated with a favorable prognosis. We reviewed the cytomorphologic characteristics in 24 FNA specimens of ALCL. In all cases, the diagnosis was confirmed on histologic specimens, and immunohistochemical studies for anaplastic lymphoma kinase (ALK) protein expression were performed on the aspirates. The presence of ALK breakpoints were evaluated in nine cases, using a DNA break-apart probe on chromosome 2 covering the ALK gene by fluorescence in situ hybridization (FISH) techniques. Two hundred cells per case were examined. The results were expressed as the percentage of cells containing more than two signals of chromosome 2 to the total number of cells counted. FNA sites included lymph nodes (20), lung (2), breast (1), and soft tissue (1). The median age of the patients was 56 yr (range, 17,75 yr). Twenty cases had systemic involvement; in four cases, skin was the primary site with secondary involvement of the lymph nodes. All cases were CD30+ by immunohistochemistry; 20 were of T-cell phenotype and 4 were null cell type. The cytologic evaluation revealed typical anaplastic morphology (common type) with many "hallmark cells" in 16 (67%) cases. Other morphologic variants identified were small cell pattern in five cases, monomorphic pattern in two cases, and lymphohistiocytic pattern in one case. FISH studies showed that six (66.7%) of nine cases had at least two signals of chromosome 2, consistent with ALK breakpoints. With careful cytomorphologic evaluation in conjunction with appropriate immunohistochemical studies, a diagnosis of ALCL can be confidently made in the FNA specimens in the cellular aspirates and its morphologic variants also can be recognized. Furthermore, the FNA specimen is suitable in detecting ALK breakpoints by FISH study, permitting rapid identification of a subset of patients with ALCL, who may have a favorable prognosis. Using a commercially available probe, detection of ALK breakpoints in the FNA specimens is simple and can be a useful diagnostic adjunct in cases where distinction from other lymphomas or lymphoid lesions is morphologically difficult. Diagn. Cytopathol. 2003;29:61,66. © 2003 Wiley-Liss, Inc. [source] 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP),induced mutagenesis in cultured Big BlueÔ rat mammary epithelial and fibroblast cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Heather M. McDiarmid Abstract Epithelial cells are the primary site of carcinogenesis in most tissues, including the mammary gland. As an alternative to the study of mutation induction in whole tissues in vivo, we have established Big BlueÔ transgenic rat cell lines from the mammary epithelium (BBR/ME) and the mammary stroma (BBR/MFib), to permit a comparison of their mutagenic responses to carcinogens. We previously demonstrated their responsiveness to the alkylating agent N -ethyl- N -nitrosourea (ENU) (McDiarmid H et al. [2001]: Mutat Res 497:39,47). Here, we examined the responses of cultured epithelial and stromal cells to the protein pyrolysis product and mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Rat hepatic S9 was used as a source of bioactivation enzymes. Mutant induction (cII locus) and clonogenic survival were measured as a function of PhIP concentration. PhIP mutagenicity was observed in the fibroblast cells, but the greater toxicity of PhIP to the epithelial cells prevented a definitive evaluation of mutagenicity. Since PhIP may be detoxified by conjugation with glutathione, we measured glutathione levels and glutathione- S -transferase expression and activities in both cell lines. The epithelial cells had higher glutathione- S -transferase enzyme activity and protein expression than did the fibroblast cell line. Because the epithelial cells were more sensitive to toxicity, glutathione conjugation evidently plays only a minor role in PhIP toxicity and mutagenicity in our cell lines. Environ. Mol. Mutagen. 39:245,253, 2002. © 2002 Wiley-Liss, Inc. [source] Tissue-specific distribution and whole-body burden estimates of persistent organic pollutants in the bottlenose dolphin (Tursiops truncatus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010Jennifer E. Yordy Abstract Most exposure assessments for free-ranging cetaceans focus on contaminant concentrations measured in blubber, and few data are available for other tissues or the factors governing contaminant distribution among tissues. The goal of this study was to provide a detailed description of the distribution of persistent organic pollutants (POPs) within the common bottlenose dolphin (Tursiops truncatus) body and assess the role of lipid dynamics in mediating contaminant distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney, mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and testis/uterus) were sampled during necropsy from bottlenose dolphins (n,=,4) and analyzed for lipid and 85 POPs, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers. Significant correlations between tissue POP concentrations and lipid suggest that distribution of POPs is generally related to tissue lipid content. However, blubber:tissue partition coefficients ranged widely from 0.753 to 6.25, suggesting that contaminant distribution is not entirely lipid-dependent. Tissue-specific and whole-body contaminant burdens confirmed that blubber, the primary site of metabolic lipid storage, is also the primary site for POP accumulation, contributing >90% to the whole-body burdens. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue concentrations. These results suggest that individuals with reduced blubber lipid may be at increased risk for exposure-related health effects. However, this study also provides evidence that the melon, a metabolically inert lipid-rich structure, may serve as an alternate depot for POPs, thus preventing the bulk of blubber contaminants from being directly available to other tissues. This unique physiological adaptation should be taken into consideration when assessing contaminant-related health effects in wild cetacean populations. Environ. Toxicol. Chem. 2010;29:1263,1273. © 2010 SETAC [source] Preemptive effect of nucleus of the solitary tract stimulation on amygdaloid kindling in freely moving catsEPILEPSIA, Issue 3 2010Victor M. Magdaleno-Madrigal Summary Purpose:, The nucleus of the solitary tract (NTS) is a primary site where vagal afferents terminate. The aim of this study was to analyze the preemptive effect of NTS electrical stimulation on daily amygdaloid kindling (AK) in freely moving cats. Methods:, Seven adult male cats were used. Bipolar electrodes were stereotaxically implanted into both amygdalae, lateral geniculate bodies, hippocampi, and prefrontal cortices. In addition, a bipolar stainless steel electrode was implanted in the left NTS. Cats were recorded under the following experimental conditions: The NTS was stimulated for 6 days before the initiation of AK (1 min on/5 min off, 1 h total). AK was performed by stimulating the amygdala every 24 h (1 s, 60 Hz, 1 ms) until behavioral stage VI was reached. Results:, The number of stimulations to reach stage VI in control animals was 23.4 ± 3.7, in lateral tegmental field (LTF) animals was 17.0 ± 2.1 days. Animals subjected to preemptive NTS stimulation showed a significant increase (53.8 ± 5.9). In addition, behavioral development was retarded, with an increase in the number of stimulations required to reach stage III. In this group, overall kindling development was delayed, and amygdaloid afterdischarge duration did not show a progressive increase as was observed in the control group. Discussion:, Our results indicate that preemptive NTS electrical stimulation interferes with epileptogenesis. This anticonvulsive effect could be related to the activation of certain structures that inhibit seizure development. Therefore, results suggest that NTS mediates the anticonvulsive effect of vagus nerve stimulation. [source] Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neuronsGLIA, Issue 10 2010Nader D. Halim Abstract Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDH,). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorlyated PDH,. Dephosphorylation of astrocytic PDH, restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed. © 2010 Wiley-Liss, Inc. [source] Advanced-staged tonsillar squamous carcinoma: Organ preservation versus surgical management of the primary site,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2006Haider Ali Shirazi MD Abstract Background. Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site. Methods. The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy ± chemotherapy. Results. No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group. Conclusion. Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] PET-CT vs contrast-enhanced CT: What is the role for each after chemoradiation for advanced oropharyngeal cancer?,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2006Amy Y. Chen MD Abstract Purpose. The aim of our study was to assess the utility of positron emission tomography (PET) and 2 fluoro-2-deoxy- D -glucose coupled with neck CT compared with contrast-enhanced CT in predicting persistent cancer either at the primary site or cervical lymphatics in patients with oropharyngeal cancer treated with concurrent chemoradiation Methods. Thirty consecutive patients underwent clinical examination, PET-CT, and contrast-enhanced CT to assess response after the completion of the treatment. The outcome variable was positive tissue diagnosis or negative disease at 6 months. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for the primary site as well as cervical disease. Results. Contrast-enhanced CT alone showed the best accuracy in detecting disease at the primary site after treatment (85.7%). Accuracy in evaluating residual tumor in the cervical lymphatics for contrast-enhanced CT and PET-CT was 59.3% and 74.1%, respectively. For evaluating the neck, PET-CT and contrast-enhanced CT demonstrated 100% NPV, but the PPV was 36.3% and 26.6%, respectively. Conclusions. In this preliminary study, PET-CT seems to be superior to contrast-enhanced CT in predicting persistent disease in the neck after chemoradiation for oropharyngeal or unknown primary cancer, but not at the primary site. However, the possibility of a false-positive result in the neck remains high, and thus overtreatment may result. Even more concerning are the false-negative results. Larger, prospective studies will be important in defining the role of PET-CT in obviating the need for salvage neck dissections after chemoradiation. © 2006 Wiley Periodicals, Inc. Head Neck 28:487,495, 2006 [source] Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: A case seriesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2005Erich M. Sturgis MD Abstract Background. Squamous cell carcinoma of the oral tongue (SCCOT) in the young population has emerged as a growing worldwide health problem. Standard therapies, consisting primarily of surgery with possible adjuvant radiotherapy, have resulted in only modest improvements in survival in recent decades, whereas the treatments for SCCOT continue to impair oral function. With the increased use and improved functional results of neoadjuvant chemotherapy in the treatment of squamous cell carcinoma of other upper aerodigestive tract sites, we have reviewed our experience with neoadjuvant chemotherapy in young patients with SCCOT. Methods. A retrospective review was conducted of all patients younger than 45 years (N = 49) with previously untreated SCCOT evaluated at a comprehensive cancer center from July 1995 to August 2001. Charts were reviewed to obtain demographic data, comorbidities, nutritional status, tumor status, treatment and response information, and follow-up data. Results. Fifteen patients were identified who received neoadjuvant chemotherapy with taxane-based regimens before undergoing glossectomy and neck dissection. Thirteen of these patients (87%) exhibited stage III or IV disease at presentation, and all exhibited at least a partial response at the primary site. Pathologically positive nodes were identified in only six patients (40%), although 13 (87%) had clinically or radiographically suspicious nodes at presentation. Adjuvant radiation therapy was administered to seven patients (47%). With a median follow-up of 39 months, no patient has had local or regional recurrence, although three patients (20%) have had distant metastases develop; one patient with an isolated distant metastasis was successfully salvaged with radiation. By comparison during the same period, 34 young adult patients with SCCOT were treated with surgery with or without postoperative radiotherapy but without the use of chemotherapy. Although these patients had lower T classifications (18% vs 67% T3/T4; p = .0007), incidence of nodal metastases (15% vs 87% N+; p < .0001), and overall disease stage (24% vs 87% stage III/IV; p < .0001) than the neoadjuvant chemotherapy group, the overall survival (82%), disease-specific survival (88%), and recurrence-free survival (82%) of the surgery-first group was similar to that of the neoadjuvant chemotherapy group (87%, 87%, and 80%, respectively). Conclusions. This retrospective investigation demonstrates that neoadjuvant chemotherapy with taxane-based regimens may play a role in the successful treatment of SCCOT in young adult patients. Ultimately, this treatment plan may lead to improved functional outcomes in young patients with SCCOT by allowing function-sparing surgery and avoiding postoperative radiotherapy, without sacrificing disease control and survival, but a prospective trial is needed. We have initiated a prospective clinical trial to further investigate the impact of neoadjuvant chemotherapy in patients younger than 50 with SCCOT. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Impact of young age on prognosis for head and neck cancer: A matched-pair analysisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2005Jeffrey S. Gilroy MD Abstract Background. The purpose of this study was to review outcomes of young patients (age <40 years) treated with definitive radiotherapy alone for squamous cell carcinoma of the oropharynx, and larynx, and to compare these results with an older matched patient cohort. Methods. Since 1983, 30 previously untreated young patients underwent definitive radiotherapy at the University of Florida and were matched with an older group of patients (age >45 years) with respect to primary site, stage of disease, and sex. Results. There was no difference in cause-specific survival, locoregional control, or long-term complications between the two groups; however, there was a significant difference in overall survival favoring young patients (p = .0174). Older patients had twice as many second malignancies. Conclusion. Young age does not confer a worse prognosis in patients treated with definitive radiotherapy for squamous cell carcinoma of the oropharynx and larynx. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2005FRANZCR, Sandro V. Porceddu MBBS Abstract Background. This study evaluates the utility of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with a node-positive mucosal head and neck squamous cell carcinoma who achieved a complete response at the primary site but had a residual mass in the neck 8 weeks or more after definitive (chemo)radiotherapy. Methods. Between October 1996 and July 2002, 39 eligible patients were identified. The reference PET scan was performed at a median of 12 weeks (range, 8,32 weeks) after treatment. Results. PET showed no metabolic activity in the residual mass in 32 patients. Five of these patients had a neck dissection and were all pathologically negative. The remaining 27 patients were observed for a median of 34 months (range, 16,86 months), with only one locoregional failure. The negative predictive value of PET for viable disease in a residual anatomic abnormality was 97%. Conclusion. Patients who have achieved a complete response at the primary site but have a residual abnormality in the neck that is PET negative approximately 12 weeks after treatment do not require neck dissection and can be safely observed. © 2004 Wiley Periodicals, Inc. Head Neck27: 175,181, 2005 [source] Disease control, survival, and functional outcome after multimodal treatment for advanced-stage tongue base cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2004James P. Malone MD Abstract Background. Surgical resection and postoperative radiation for advanced-stage malignancies of the oral cavity, oropharynx, and hypopharynx result in a dismal overall survival of 38%. Patients with carcinoma of the tongue base frequently have advanced disease at the time of presentation, and combined-modality therapy is usually required to achieve cure. Because of the poor survival rates with advanced malignancies with standard therapy, new and innovative approaches continue to be developed in an attempt to have a greater impact on disease control, patient survival, and functional outcome after therapy. This study examines functional outcome, survival, and disease control in patients receiving an intensified treatment regimen with concomitant chemoradiotherapy, surgery, and intraoperative radiotherapy for previously untreated, resectable, stage III and IV squamous cell carcinoma (SCC) of the tongue base. Methods. Forty patients with previously untreated, resectable, stage III and IV squamous cell carcinoma of the tongue base were treated in one of three sequential phase II intensification regimens (IRs). Treatment consisted of perioperative, hyperfractionated radiotherapy (9.1 Gy) with concurrent cisplatin followed by surgical resection with intraoperative radiotherapy boost (7.5 Gy). Postoperative treatment involved concurrent chemoradiotherapy (40 Gy to the primary site and upper neck and 45 Gy to the supraclavicular areas) with cisplatin with or without paclitaxel. Locoregional and distant disease control, 2-year overall, and disease-specific survival rates were calculated. The Performance Status Scale (PSS) for Head and Neck Cancer Patients was administered to 25 of the surviving patients. The effects of the method of surgical reconstruction, surgery involving the mandible and/or larynx, and early versus advanced T stage on PSS score were evaluated with the Wilcoxon rank-sum test. Results. Median follow-up in months for IR1, IR2, and IR3 were 83.6, 75.2, and 26.8. The locoregional control rate was 100%, and the rate of distant metastases was 7.5% for all patients. Two-year overall and disease-specific survival rates for the entire study population were 74.7% and 93.6%, respectively. Mean PSS scores by subscales Eating in Public, Understandability of Speech, and Normalcy of Diet were 55 (range, 0,100), 73 (range, 25,100), and 49 (range, 0,100), respectively. PSS scores were significantly higher in patients with primary closure of the surgical defect, no mandibular surgery, and early T-stage lesions. Conclusions. Although functional outcome may be decreased by certain surgical interventions and advanced T stage, the high rate of locoregional and distant disease control and excellent 2-year disease-specific survival supports an aggressive treatment regimen for advanced tongue base cancer. © 2004 Wiley Periodicals, Inc. Head Neck26: 561,572, 2004 [source] Adjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2004Jiade J. Lu MD Abstract Background. The value of high-dose-rate intracavitary brachytherapy (HDRIB) for persistent or recurrent nasopharyngeal carcinoma has been well described; however, the benefit of routine adjuvant fractionated HDRIB following external beam radiation therapy (EBRT) has not been completely determined. The objective of this analysis was to evaluate the outcome of two fractions of adjuvant HDRIB treatment in Tl and T2 nasopharyngeal carcinoma. Methods. Thirty-three consecutive and nonselected patients who had Tl and T2 non-disseminated nasopharyngeal carcinoma were treated according to an IRB approved institutional research protocol between March 1999 and July 2001. By the 1997 AJCC cancer staging classification, 22 patients (67%) had Tl disease and 11 patients (33%) had T2 disease. Seventeen of these patients who had stage I or stage II disease (i.e., NO or Nl) were treated with EBRT followed by two fractions of adjuvant HDRIB (group 1); 16 patients who had stage III or stage IV disease (i.e., N2 or N3) were treated with concurrent cisplatin, EBRT and adjuvant HDRIB and subsequent adjuvant cisplatin and fluorouracil (5-FU) chemotherapy (group 2). EBRT was delivered by daily conventional fractionation to a total dose of 66 Gy to the primary tumor. Nodal disease received 66 Gy if it was less than 3cm in maximum diameter and 70 Gy if larger or there was palpable residual disease after 66 Gy. A total of 10 Gy of HDRIB in 2 equal fractions of 5 Gy spaced 1 week apart was delivered starting 1 week after the completion of EBRT. All patients were assessed for treatment response, local control, survival, and toxicity. Results. The median follow up for all 29 surviving patients is 29 months (range: 17,38 months). One patient died 7 months and one died 18 months after radiation therapy from the effects of distant metastases; two died of unrelated causes. At the time of this analysis, one patient (3%) had persistent local disease and one patient (3%) developed pathologically confirmed local recurrence in the nasopharynx. In addition, one patient (3%) developed recurrence only in a neck node followed by distant metastasis, and two patients (6%) developed distant metastasis without locoregional relapse. The 2-year local control rate at the primary site was 93.6%, and the overall survival and disease-free survival rates were 82% and 74% respectively. All patients experienced some degree of acute and/or late toxicity related to radiation therapy. Ten patients (30%) experienced grade 3 acute and/or late toxicity and six patients (18%) developed grade 4 acute and/or late toxicity. No grade 5 toxicity occurred. No unexpected damage of structures within the HDRIB fields was detected. Conclusions. EBRT supplemented by two fractions of adjuvant HDRIB produced a 93.6% local control rate for Tl and T2 nasopharyngeal cancer at 2 years of follow up, with acceptable rates of acute and late toxicity. Brief adjuvant HDRIB appears to permit dose escalation safely, even in patients who receive chemotherapy concurrently with conventional radiation therapy. This strategy needs to be optimized and then tested in a prospective randomized phase III trial to learn if it can improve outcome. © 2004 Wiley Periodicals, Inc. Head Neck26: 389,395, 2004. [source] Salvage laryngectomy and pharyngocutaneous fistulae after primary radiotherapy for head and neck cancer: A national survey from DAHANCAHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2003Cai Grau MD, DMSc Objective. In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae. Patients. A total of 472 consecutive patients undergoing postirradiation salvage laryngectomy in the period July 1, 1987,June 30, 1997 were recorded at the five head and neck oncology centers in Denmark. Age ranged from 36 to 84 years, median 63 years, 405 men and 67 women. Primary tumor site was glottic larynx (n = 242), supraglottic larynx (n = 149), other larynx (n = 45), pharynx (n = 27), and other (n = 9). All patients had received prior radiotherapy. Results. Median time between radiotherapy and laryngectomy was 10 months (range, 1,348 months). A total of 89 fistulae lasting at least 2 weeks were observed, corresponding to an overall average fistulae risk of 19%. The number of performed laryngectomies per year decreased linearly (from 58 to 37), whereas the annual number of fistulae increased slightly (from 7 to 11), which meant that the corresponding estimated fistulae risk increased significantly from 12% in 1987 to 30% in 1997. Other significant risk factors for fistulae in univariate analysis included younger patient age, primary advanced T and N stage, nonglottic primary site, resection of hyoid bone, high total radiation dose, and large radiation fields. Multiple logistic regression analysis of these parameters suggested that nonglottic tumor site, late laryngectomy period (1987,1992 vs 1993,1997), and advanced initial T stage were independent prognostic factors for fistulae risk. Surgical parameters like resection of thyroid/tongue base/trachea or radiotherapy parameters like overall treatment time or fractions per week did not influence fistulae risk. Conclusions. The risk of fistulae is especially high in patients initially treated with radiotherapy for nonglottic advanced stage tumors. A significant decrease in the number of performed salvage laryngectomies over the 10 years was seen. Over the same time period, the annual number of fistulae remained almost constant. The resulting more than doubling of fistulae rate could thus in part be explained by less surgical routine. © 2003 Wiley Periodicals, Inc. Head Neck 25: 711,716, 2003 [source] Distant metastases after definitive radiotherapy for squamous cell carcinoma of the head and neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2003Majid O. F. Al-Othman MD Abstract Purpose. To analyze parameters that influence the risk of distant metastases after definitive radiotherapy. Methods. Between 1983 and 1997, 873 patients were treated with definitive radiotherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate risk factors that might influence the risk of distant metastases. Results. The 5-year distant metastasis-free survival rate was 86%. Univariate analyses revealed that the risk of distant metastases was significantly influenced by gender (p = .0092), primary site (p = .0023), T stage (p < .0001), N stage (p < .0001), overall stage (p < .0001), level of nodal metastases in the neck (p < .0001), histologic differentiation (p = .0096), control above the clavicles (p < .0001), and time to locoregional recurrence (p < .0001). Multivariate analysis of freedom from distant metastases revealed that gender (p = .0390), T stage (p < .0001), N stage (p = .0060), nodal level (p < .0001), and locoregional control (p < .0001) significantly influenced this end point. Multivariate analysis revealed that gender (p = .0049), T stage (p < .0001), N stage (p < .0001), and locoregional control (p < .0001) significantly influenced cause-specific survival. Conclusions. The risk of distant metastases after definitive radiotherapy is 14% at 5 years and is significantly influenced by gender, T stage, N stage, nodal level, and locoregional control. © 2003 Wiley Periodicals, Inc. Head Neck 25: 629,633, 2003 [source] Metastatic squamous cell carcinoma of the neck from an unknown primary: Management options and patterns of relapse,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2002Shahrokh Iganej MD Abstract Purpose Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. Methods and Materials From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. Results Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p = .006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. Conclusions Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated. © 2002 Wiley Periodicals, Inc. Head Neck 24: 236,246, 2002; DOI 10.1002/hed.10017 [source] Serial positron emission tomography scans following radiation therapy of patients with head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2001Kathryn M. Greven MD Abstract Background A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. Methods Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. Results Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. Conclusions PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer. © 2001 John Wiley & Sons, Inc. Head Neck 23: 942,946, 2001. [source] Aedes aegypti transducing densovirus pathogenesis and expression in Aedes aegypti and Anopheles gambiae larvaeINSECT MOLECULAR BIOLOGY, Issue 5 2001T. W. Ward Abstract Aedes aegypti densovirus (AeDNV) is a small DNA virus that has been developed into an expression and transducing vector for mosquitoes [Afanasiev et al. (1994) Exp Parasitol 79: 322,339; Afanasiev et al. (1999) Virology 257: 62,72; Carlson et al. (2000) Insect Transgenesis: Methods and Applications (Handler, A.M. & James, A.A., eds), pp. 139,159. CRC Press, Boca Raton]. Virions carrying a recombinant genome expressing the GFP gene were used to characterize the pathogenesis of the virus in 255 individual Aedes aegypti larvae. The anal papillae of the larvae were the primary site of infection confirming previous observations (Afanasiev et al., 1999; Allen-Muira et al. (1999) Virology 257: 54,61). GFP expression was observed in most cases to spread from the anal papillae to cells of the fat body, and subsequently to many other tissues including muscle fibers and nerves. Infected anal papillae were also observed to shrink, or melanize and subsequently fall off in a virus dependent manner. Three to four day-old larvae were less susceptible to viral infection and, if infected, were more likely to survive into adulthood, with 14% of them still expressing GFP as adults. Higher salt concentrations of 0.10,0.15 m inhibited viral infection. Anopheles gambiae larvae also showed infection of the anal papillae (17%) but subsequent viral dissemination did not occur. The persistence of the reporter gene expression into adulthood of Aedes aegypti indicates that transduction of mosquito larvae with recombinant AeDNV may be a means of introducing a gene of interest into a mosquito population for transient expression. [source] Primary malignant melanoma of the bladderINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2006MAURO PACELLA Abstract, Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder. There was no history of previous or regressed cutaneous malignant melanoma. Margins of the bladder lesion contained atypical melanocytes similar to those commonly seen in the periphery of primary mucous membrane lesions. Clinical studies and radiological examinations were negative for other primary site of melanoma. The patient had a bladder recurrence that was consistent with primary tumor and died of widespread disease 9 months after diagnosis. [source] Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisalJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2004Sadia Saeed Background:, Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed. Methods:, Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy. Results:, Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38,83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month,22 years), and the average survival following diagnosis was 7.5 months (range: <1 month,8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK-7, CK-20, and S-100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients. Conclusions:, Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late-developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK-7, CK-20, and S-100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas. [source]
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