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Normal Histology (normal + histology)
Selected AbstractsHuman Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin CancerDERMATOLOGIC SURGERY, Issue 3 2004Ingo Nindl PhD Background. P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV),infected cervical (pre)cancer lesions. Objective. To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods. Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only ,-globin,positive patients were included in this study. Results. HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion. P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted. [source] Functional estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effectsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2009Maria Tsinti Salivary gland epithelial cells (SGECs) have been shown to participate in immunological responses and have been implicated in the pathogenesis of Sjögren's syndrome (SS). Experimental evidence from animal models indicates that estrogen deficiency may also participate in SS pathogenesis. However, the expression and functionality of the estrogen receptors alpha (ER,) and beta (ER,) in normal human salivary epithelium is unknown. To investigate these points, formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC lines derived from nine minor salivary gland (MSG) biopsies with normal histology were studied. Immunohistochemical analyses detected the epithelial expression of ER,, ER,1, and ER,2 protein isoforms both in MSG tissues and in cultured SGECs. Such epithelial expression was verified by immunoblotting of various ER proteins in cellular extracts of cultured SGECs (full-length-ER,, ER,-,3, ER,1-long, ER,1-short, and ER,2-long isoforms). Estrogens did not induce growth or apoptosis in cultured SGECs. However, similarly to other cellular systems, treatment of cultured SGECs with estrogens (17,-estradiol and the ER,- and ER,-selective agonists propylpyrazole-triol and diarylpropiolnitrile, respectively) inhibited the interferon-,-inducible expression of intercellular adhesion molecule-1. This finding corroborated the functionality of ER expressed by SGEC. Our results suggest that salivary epithelium expresses constitutively functional ER, and ER, proteins that apparently mediate immunomodulatory effects. [source] Comparison of High Resolution Magnifying Endoscopy and Standard Videoendoscopy for the Diagnosis of Helicobacter pylori Gastritis in Routine Clinical Practice: A Prospective StudyHELICOBACTER, Issue 1 2009Can Gonen Abstract Background:, It has been shown that standard endoscopic features often labeled as gastritis has a poor correlation with histopathology. Recently, high resolution magnifying endoscopy has been reported to be an effective method to diagnose gastritis. The aim of the present study was to compare standard endoscopy with magnifying endoscopy for the diagnosis of Helicobacter pylori gastritis, and to determine whether gastritis can be diagnosed based on findings at magnification endoscopy. Materials and Methods:, A total of 129 patients were enrolled into the study. Erythema, erosions, prominent area gastrica, nodularity, and regular arrangement of collecting venules (RAC) were investigated by standard endoscopy. Standard endoscopy was followed by magnifying endoscopy in all patients, and repeated in 55 patients after indigo carmine spraying. Results:, None of the standard endoscopic features showed a sensitivity of more than 70% for H. pylori gastritis, except RAC pattern analysis. Absence of a corporal RAC pattern had 85.7% sensitivity and 82.8% specificity for predicting H. pylori infection. Under magnification, the sensitivity and specificity of regular corporal pattern (regular collecting and capillary vascular structures with gastric pits resembling pinholes) for predicting normal histology were 90.3% and 93.9%, respectively. Loss of collecting venules, or both collecting and capillary structures was correlated with chronic inflammation and activity. With the progression of mucosal atrophy, irregular collecting venules became visible. The values for irregularly arranged antral ridge pattern for the prediction of antral gastritis were 89.3% and 65.2%, respectively. Indigo carmine staining increased sensitivity and specificity up to 97.6% and 100% for corporal gastritis, and up to 88.4% and 75.0% for antral gastritis, respectively. Indigo carmine staining significantly increases the detection of intestinal metaplasia. Conclusions:, High resolution magnifying is superior to standard endoscopy for the diagnosis of H. pylori gastritis, and identification of specific histopathologic features such as atrophy and intestinal metaplasia seems possible. [source] Discrimination of Normal Gastric Mucosa from Helicobacter pylori Gastritis using Standard Endoscopes and a Single Observation Site: Studies in Children and Young AdultsHELICOBACTER, Issue 2 2004Yoshiko Nakayama ABSTRACT Background., In the Helicobacter pylori -negative normal stomach, collecting venules are visible in the gastric corpus as numerous minute points. This finding has been termed ,regular arrangement of collecting venules' (RAC). The aim of the present study was to investigate the reliability of the presence of the RAC pattern for discrimination of normal gastric mucosa from H. pylori gastritis in pediatric patients. Methods., Fifty-two consecutive children, adolescents and young adults (male:female 24 : 28; median age 15 years, range 8,29 years) referred for endoscopy and assessed for H. pylori infection were prospectively studied. The lower lesser curvature of the corpus near the incisura was evaluated for the RAC pattern using a standard endoscope with the tip close to, but not in contact with, the gastric surface. Gastric biopsies were taken after the endoscopic observation. Results., In all the 29 RAC-positive patients, active H. pylori gastritis was absent, whereas H. pylori gastritis was found in 20 of 23 RAC-negative patients (86.9%). Conclusions., Identification of the RAC pattern at the lower lesser curvature of the corpus using close observation with a standard endoscope proved to be an effective and practical marker to discriminate normal histology from H. pylori gastritis among both children and young adults. Absence of the RAC pattern should prompt gastric mucosal biopsies despite otherwise normal-appearing gastric mucosa. [source] Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in ChildrenHELICOBACTER, Issue 2 2004Seiichi Kato ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source] Childhood coeliac disease: towards an improved serological mass screening strategyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010C. E. HOGEN ESCH Aliment Pharmacol Ther,31, 760,766 Summary Background, In 1997,1998, 6127 asymptomatic children aged 2,4 years were screened for coeliac disease (CD) by anti-endomysium (EmA) testing in the Netherlands. After 6 (±2) months, biopsies were performed in 57 seropositive children; 31(54%) had villous atrophy, but 26 (46%), all HLA-DQ2/DQ8 positive, had normal histology. Aims, To reduce the number of unnecessary biopsies after serological mass screening for CD in asymptomatic young children by optimizing screening procedures. Methods, Comparing different tests and optimizing their cut-off point: screening samples were tested for EmA, tissue-transglutaminase (tTGA), antigliadin and deamidated-gliadin-peptides (anti-DGP) antibodies. Determining serological persistence over time: persistence of EmA and tTGA was determined by testing serological samples obtained at biopsy. Results, Tissue-transglutaminase and anti-DGP correlated with EmA. Optimization of standard cut-off points not only reduced unnecessary biopsies by 50,96% but also reduced sensitivity. EmA persisted in all CD children, but in only 50% of the non-CD children. tTGA persisted in 83% of CD, but in only 15% of non-CD children. Conclusions, Coeliac disease antibodies may be present transiently in genetically predisposed children. To avoid unnecessary biopsies, serological mass screening procedures may be improved by repeating EmA and/or tTGA in initially seropositive young children after 6 months, before proceeding to biopsy. This may reduce the number of unnecessary biopsies that are performed. [source] Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive responseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2004A. V. Emmanuel Summary Background :,Chronic intestinal pseudo-obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy. Aim :,To determine the value of erythromycin treatment in chronic intestinal pseudo-obstruction. Methods :,All patients with proven chronic intestinal pseudo-obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non-responders to identify the factors associated with benefit. Results :,Fifteen consecutive patients (nine females; median age, 37 years; median follow-up, 41 months) were treated with oral erythromycin, 1.5,2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non-responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non-responders to be taking long-term opiates. Conclusions :,Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo-obstruction. [source] Meta-Analyses Qualify Metzincins and Related Genes as Acute Rejection Markers in Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010S. Rödder Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell,mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers. [source] Infusion of Mesenchymal Stem Cells and Rapamycin Synergize to Attenuate Alloimmune Responses and Promote Cardiac Allograft ToleranceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. Ge The inherent immunosuppressive properties and low immunogenicity of mesenchymal stems cells (MSCs) suggested their therapeutic potential in transplantation. We investigated whether MSCs could prolong allograft survival. Treatment involving infusion of MSCs into BALB/c recipients 24 hours after receiving a heart allograft from a C57BL/6 donor significantly abated rejection and doubled graft mean survival time compared to untreated recipients. Furthermore, combination therapy of MSCs and low-dose Rapamycin (Rapa) achieved long-term heart graft survival (>100 days) with normal histology. The treated recipients readily accepted donor skin grafts but rejected third-party skin grafts, indicating the establishment of tolerance. Tolerant recipients exhibited neither intragraft nor circulating antidonor antibodies, but demonstrated significantly high frequencies of both tolerogenic dendritic cells (Tol-DCs) and CD4+CD25+Foxp3+T cells in the spleens. Infusion of GFP+C57BL/6-MSCs in combination with Rapa revealed that the GFP-MSCs accumulated in the lymphoid organs and grafts of tolerant recipients. Thus, engraftment of infused MSCs within the recipient's lymphoid organs and allograft appeared to be instrumental in the induction of allograft-specific tolerance when administered in combination with a subtherapeutic dose of Rapamycin. This study supports the clinical applicability of MSCs in transplantation. [source] There is no clear association between low serum ferritin and chronic diffuse telogen hair lossBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2002R. Sinclair SummaryBackground Low iron stores are considered a possible cause of chronic diffuse telogen hair loss in women. Estimation of serum ferritin is recommended as part of the initial assessment when women present with chronic diffuse telogen hair loss, and iron supplementation therapy is commonly recommended for those found to have low iron stores. Objectives To evaluate the relationship between low serum ferritin (,20 µg L,1) and chronic diffuse telogen hair loss in women. Methods Between 1997 and 1999, 194 consecutive women who presented to a specialist hair clinic were assessed for diffuse telogen hair loss of greater than 6 months duration. All underwent biochemical investigations that included serum ferritin and had two 4-mm punch biopsies taken from the vertex of the scalp. One biopsy was sectioned horizontally and the other vertically. Results Twelve women were found to have a serum ferritin of 20 µg L,1 or less (6·2%). Androgenetic alopecia was found on scalp biopsy in seven of these 12 women, while the other five women had normal histology. The five women with low iron stores and normal histology were treated with iron supplementation alone. This was continued until the serum ferritin was > 20 µg L,1. Cessation or reversal of hair loss was not seen in any of these women. Conclusions No direct relationship between low serum ferritin and hair loss can be established. The usefulness of serum ferritin in the routine investigation of women with chronic diffuse telogen hair loss is unclear, as is the role of iron supplementation therapy in the management of hair loss. [source] Benign breast lesions at risk of developing cancer,A challenging problem in breast cancer screening programsCANCER, Issue 3 2009Five years' experience of the Breast Cancer Screening Program in Verona (1999-2004) Abstract BACKGROUND: Cytology and core-needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen-detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona. METHODS: Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, ,pure' BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele-like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia). RESULTS: Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%. CONCLUSIONS: BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high-risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations. Cancer 2009. © 2008 American Cancer Society. [source] | ||||||||||||||||||||||