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Tissue Blocks (tissue + block)
Selected AbstractsHomogeneity of active demyelinating lesions in established multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2008Esther C. W. Breij PhD Objective Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS. Methods All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging,guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions. Results Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found. Interpretation The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fc, receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS. Ann Neurol 2008;63:16,25 [source] Effect of systemic administration of nicotine on healing in osseous defects.CLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2006An experimental study in rabbits. Abstract Objectives: The aim of the present study was to analyze the effect of systemic administration of nicotine on bone healing in osseous defects in the tibia of rabbits. Material and methods: Sixteen female rabbits received nicotine (n=8; test group) or saline (n=8; control group) via subcutaneously placed mini-osmotic pumps for 8 weeks. The animals underwent three surgical operations during the experimental period, and body weight was registered weekly. Blood samples were collected to determine cotinine and prostaglandin E2 levels. Bone preparations were made in the right leg of all rabbits after 4 weeks and in the left leg after 6 weeks of nicotine/placebo exposure. Thus, 2- and 4-week healing groups were created for the bone defects. After 8 weeks, the animals were killed. Tissue blocks including the bone defects were prepared for histological analysis. Results: The animals in the test group lost weight, while the control group gained weight during the experiment. The prostaglandin E2 levels in plasma increased significantly following nicotine exposure in the test group. No significant differences in the percentage of vessels and bone density in the osseous defects were found between the test and the control groups after 2 and 4 weeks of healing. Conclusions: In this experiment, systemic administration of nicotine over 4 or 6 weeks, respectively, influenced body weight and systemic prostaglandin E2 levels but not the amount of blood vessels and the bone mineral density in bone defects after 2 or 4 weeks of healing. [source] A Comparison of Four Mohs Tissue Preparation Methods Using Porcine SkinDERMATOLOGIC SURGERY, Issue 9 2010FRCPC, WILLIAM LEAR MD OBJECTIVE Mohs surgery relies on high-quality, rapid tissue preparation and processing. This study evaluated four currently performed tissue preparation and processing methods for speed of processing and depth of cut into the tissue block to achieve a complete high-quality section. METHODS The following four methods were tested: cryoEMBEDDER, float, heat sink, and slide. Standardized specimens of porcine skin were used to ensure uniformity. We measured the time required for a technician to flatten, embed, and cut to the first complete section of each specimen. Additionally, we measured the depth in microns required to cut into an embedded specimen to achieve a complete section. RESULTS There were advantages and disadvantages of each method, and our findings suggest that the heat sink and float methods are more time efficient but that the slide and cryoEMBEDDER methods require less cutting into the specimen to obtain a complete section. The cryoEMBEDDER device used in this study was loaned by cryoEMBEDDER (Salt Lake City, Utah). [source] Phosphoinositide 3-kinase is not overexpressed in melanocytic lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2007Rajendra S. Singh Background:, Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. Objective:, To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. Results:, Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p = 0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p = 0.2). Conclusion:, PI3K is not overexpressed in melanocytic lesions. [source] Expression of insulin-like growth factor-binding protein 2 in melanocytic lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2003Huamin Wang Background:, Insulin-like growth factor-1 (IGF-1) is one of the most critical proteins required for the survival, migration, and growth of melanoma cells. IGF-binding protein 2 (IGFBP2), which binds and regulates the function of IGF-1, is upregulated in a dose-dependent manner in melanoma cells treated with IGF-1, suggesting a possible role of IGFBP2 in the pathogenesis of melanoma. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 94 melanocytic lesions: 20 benign nevi, 20 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. IGFBP2 expression was evaluated immunohistochemically using a polyclonal antibody against the C-terminus of IGFBP2. The number of cells and labeling intensity were assessed semiquantitatively. Results:, Positive IGFBP2 labeling was observed in 5.0% of benign nevi, which was significantly lower than in dysplastic nevi (35.0%), primary melanomas (52.2%), or metastatic melanomas (54.8%) (p < 0.05). Among the IGFBP2-positive cases, moderate-to-strong immunostaining was observed in 64.7% of metastatic melanomas and 33.3% of primary melanomas. But none of the dysplastic nevi had moderate-to-strong immunostaining (p < 0.05). Conclusions:, Our study shows that IGFBP2 expression increases from benign and dysplastic nevi to primary and metastatic melanomas and suggests that it may play a role in melanoma progression. [source] Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcomaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2008Saminathan S. Nathan Abstract We have previously shown that osteosarcomas (OS) have states of increased interstitial fluid pressure (IFP), which correlate with increased proliferation and chemosensitivity. In this study, we hypothesized that constitutively raised IFP in OS regulates angiogenesis. Sixteen patients with the clinical diagnosis of OS underwent blood flow and IFP readings by the wick-in-needle method at the time and location of open biopsy. Vascularity was determined by capillary density in the biopsy specimens. We performed digital image analysis of immunohistochemical staining for CD31, VEGF-A, VEGF-C, and TPA on paraffin-embedded tissue blocks of the biopsy samples. Clinical results were validated in a pressurized cell culture system. Interstitial fluid pressures in the tumors (mean 33.5,±,SD 17.2 mmHg) were significantly higher (p,=,0.00001) than that in normal tissue (2.9,±,5.7 mmHg). Pressure readings were significantly higher in low vascularity tumors compared to high vascularity tumors (p,<,0.001). In the OS cell lines, growth in a pressurized environment was associated with VEGF-A downregulation, VEGF-C upregulation, and TPA upregulation. The reverse was seen in the OB cell line. Growth in the HUVEC cell line was not significantly inhibited in a pressurized environment. Immunohistochemical assessment for VEGF-A (p,=,0.01), VEGF-C (p,=,0.008), and TPA (p,=,0.0001) translation were consistent with the findings on PCR. Our data suggests that some molecules in angiogenesis are regulated by changes in IFP. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1520,1525, 2008 [source] Remyelination can be extensive in multiple sclerosis despite a long disease courseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2007R. Patani Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR+ macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought. [source] Homogeneity of active demyelinating lesions in established multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2008Esther C. W. Breij PhD Objective Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS. Methods All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging,guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions. Results Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found. Interpretation The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fc, receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS. Ann Neurol 2008;63:16,25 [source] Human herpesvirus-6 in patients with Crohn's diseaseAPMIS, Issue 5 2010RADHAKRISHNA SURA Sura R, Gavrilov B, Flamand L, Ablashi D, Cartun R, Colombel J-F, Van Kruiningen HJ. Human herpesvirus-6 in patients with Crohn's disease. APMIS 2010; 118: 394,400. Human herpesvirus-6 (HHV-6) infections are usually asymptomatic reactivations in immunocompetent persons, but may be severe in immunocompromised individuals. Although primary HHV-6 infection is mainly associated with roseola infantum, it has also been associated with gastroenteritis, diarrhea, and nausea in children. In this study, we investigated the potential role of HHV-6 in Crohn's disease (CD). Evidence of HHV-6 infection in CD patients and controls was determined by immunohistochemistry (IHC), polymerase chain reaction (PCR), and quantitative real-time PCR (qPCR). Fifty-one tissue blocks from 23 CD patients and 20 tissue blocks from 20 controls were examined. Quantitativereal-time PCR was used to assess HHV-6 viral loads. IHC, PCR and qPCR indicated the presence of HHV-6 in both CD patients and controls. Immunohistochemistry of tissues revealed an almost equal frequency and distribution of positive cells; however, non-specific immunostaining confounded interpretation. HHV-6 DNA was detected in 52% (12/23) of CD and 55% (11/20) of control patients by PCR and in 69.5% (16/23) of CD cases and 65% (13/20) of controls by qPCR. Mean viral load in intestinal tissues was similar in CD and controls (33.4 and 57.9 copies ,g,1 DNA, respectively). Finding equal evidence of HHV-6 in patients and controls by multiple methods suggests that this virus is ubiquitous and probably not a cause of CD. [source] Prostate-specific antigen-positive extramammary Paget's disease,,association with prostate cancer,APMIS, Issue 1 2008ANNE HAMMER Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5 of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease,two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens from the prostate revealed an immunoprofile which was very different from that of the primary skin lesion. In our study, no cases of EMPD with PSA positivity seem to represent an extension of an underlying prostatic adenocarcinoma. PSA positivity can be seen in cases of EMPD without associated adenocarcinoma of the prostate. [source] Prognostic significance of erythropoietin expression in human renal cell carcinomaBJU INTERNATIONAL, Issue 2 2007Agniezka Michael OBJECTIVES To investigate, in a retrospective study, the expression of erythropoietin (Epo) in human renal cell carcinoma (RCC) and its correlation with overall survival, as Epo (an haematopoietic cytokine that regulates the production of red blood cells), with its receptor, was recently localized in non-haematopoietic tissues, e.g. liver, uterus, central nervous system, vascular endothelial cells and solid tumours. PATIENTS AND METHODS We used data from 113 patients who had radical nephrectomy for RCC between 1990 and 2000, taking sections from formalin-fixed and paraffin wax-embedded tissue blocks. The association between Epo staining and the patients' characteristics was assessed by either chi-squared tests (for categorical variables) or two-sample independent t -tests (for continuous variables). RESULTS Tissue from 37 patients (33%) was positive for cytoplasmic Epo expression; 76 (67%) samples were negative. Univariate hazard ratio analysis confirmed that those with positive Epo staining were more than twice as likely to die as those with negative staining (hazard ratio 2.34, 95% confidence interval 1.27,4.3). CONCLUSION This study shows that the expression of Epo in RCC is adversely associated with overall survival. This is the first report of such an association, and might be explained by the loss of Von Hippel-Lindau protein function in clear cell RCC. The expression of Epo might have potential use in clinical trials when stratifying high-risk patients for adjuvant therapy after nephrectomy. [source] Cerebral Microinfarcts Associated with Severe Cerebral ,-Amyloid AngiopathyBRAIN PATHOLOGY, Issue 2 2010Virawudh Soontornniyomkij Abstract Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. Eighteen brains with severe SCAA (SCAA) were compared with 21 brains with mild CAA (MCAA) to investigate whether the presence of SCAA in the brains of demented patients was associated with a higher burden of old microinfarcts than those with MCAA. Immunohistochemistry for CD68 was employed to highlight old microinfarcts in tissue blocks from various brain regions. Old microinfarcts, manually counted by light microscopy, were present in 14 of 18 SCAA brains and in 7 of 21 MCAA brains (P = 0.01, two-tailed Fisher's exact test). The average number of old microinfarcts across geographic regions in each brain ranged from 0 to 1.95 (mean rank 24.94, sum of ranks 449) in the SCAA group, and from 0 to 0.35 (mean rank 15.76, sum of ranks 331) in the MCAA group (P = 0.008, two-tailed Mann,Whitney U-test). Frequent old microinfarcts in demented individuals with severe CAA may contribute a vascular component to the cognitive impairment in these patients. [source] Anatomic site evaluation of the palatal bone for temporary orthodontic anchorage devicesCLINICAL ORAL IMPLANTS RESEARCH, Issue 7 2008Heinrich Wehrbein Abstract: Objectives: The aim of the present study was to assess the micromorphologic characteristics of the palatal bone from an implantologic standpoint. Materials and Methods: The material consisted of tissue blocks of autopsy material from 22 subjects (18 males, three females) between 18 and 63 years of age. The specimens comprised the anterior median palatal region from 5 to 10 mm behind the incisive foramen. They were prepared in the transversal plane according to ground thin-section technology. The midpalatal area as well as an area of 3 mm bilateral to the midline were assessed, and a classification of quantitative palatal bone availability was developed. Results: The findings could be divided into three classes: (1) class I palatal bone consists almost of compact bone; (2) class II cortical bone layer on oral and nasal sides of palate, broad compact bone in the suture area (,3 mm), loose trabecular bone lateral to the suture area; and (3) class III cortical bone on oral and nasal side, thin compact bone in the suture area (<3 mm) and loose-structured trabecular bone lateral to the suture area. In most sections (72.7%), class I characteristics were found (16 subjects). 18.2% of sections were assigned to class II (four subjects) and only 9.1% of sections were assigned to class III (two subjects). Conclusion: These results document that in most cases a good primary stability of temporary orthodontic anchorage devices should be achieved in the midpalatal and paramedian area of the anterior palate, as the bone quantity available is high. [source] | ||||||||||||||||||||||