A thymoma is a tumor which arises from the epithelial cells of the thymus. Despite the progressive involution of the thymus post-puberty, the peak incidence of thymomas is in adults, after the age of 40. Owing to the normal anatomic location of the thymus in the antero-superior mediastinum, thymomas account for 20-30% of masses in that situation, and, they have to be differentiated from other neoplasms which may be found in the anterior mediastinam, such as, lymphocytic lymphoma, Hodgkin's disease, Germinoma (seminoma), Thymic carcinoid tumor, oat cell carcinoma and parathyroid adenoma.

Embryologically, the thymus develops as an outgrowth of epithelial cells from the third pharyngeal pouches in association with the inferior parathyroid glands and migrates from the neck to the mediastinum. In embryonic life, blood borne stem cells from the yolk sac are seeded into the thymus which becomes the primary lymphoid organ. Within the thymus, the primitive stem cells differentiate into lymphocytes, which proliferate and differentiate into T-lymphocytes (thymus-dependent, thymocytes). Some of the T-lymphocytes are released into the blood stream and populate peripheral lymphoid organs. They constitute 60-70% of circulating lymphocytes.

Angiogenesis, the process of new blood vessels formation, is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of pronostic value in several types of malignancies, because it indicates a tumor's capacity for inducing angiogenesis. However, scarce data are available on angiogenesis in gastrointestinal tumors. Our previous work has revealed that gastrointestinal adenocarcinomas (GADC) vessels are anatomically heterogeneous structures. Additionally, it has been suggested that tumor-induced neovascularization in human carcinomas does not simply mean proliferation of capillaries, but it is also associated with certain functional changes in the vascular endothelial cells. Factor VTlI/von Willebrand factor (vWF) has been widely used for the demonstration of vascular endothelial cells as a representative marker. The aims of the present study were a) to determine whether the vascular density in GADC can be correlated to tumor aggressivness and provide prognostic information, and b) to clarify the ultrastructural immunolocalization of vWF in microvessels in the stroma of these tumors.

In investigating pathological changes that occur during development of fibrosis in lungs exposed to silica, we found a significant increase in apoptotic cells in rats exposed to silica by inhalation for 80 days. Since silica is not definitively detected at the light level, we sought to use SEM backscatter imaging to correlate the presence of silica with apoptosis identified by fluorescent assays. To accomplish this, paraffin sections of lungs from rats that had been exposed to silica were placed on carbon planchets. Serial sections were placed on glass slides, immediately before and after the section on the planchet. Using a fluorescein apoptosis detection system (Promega G3250), a TdT-mediated dUTP nick-end labeling (TUNEL) assay was performed on both planchets and slides. The planchets and slides were cover slipped with gel/mount (Biomedia) and viewed in an Olympus AZ70 fluorescent photomicroscope with a wide band blue filter cube. Apoptotic nuclei could be seen in similar regions in both the slide and the planchet preparations.

Epidemiological studies have associated exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 10 microns, especially the finer fraction PM2.5, with increases in morbidity and mortality in persons with preexisting cardiopulmonary disease. However, whether exposures to PM10 cause lung disease in uncompromised individuals is a topic of debate, especially since mechanistic and toxicological studies have failed to define cause and effect relationships between exposures to PM10 and phenotypic changes associated with the development of pulmonary diseases. PM10 is a complex mixture of soot and natural minerals, metal oxide particles, sea salt grains and aeroallergens (Fig. 1). Our interest lies with the carbonaceous components (Fig. 2), since insoluble particles may be more efficiently retained in the peripheral lung and be potentially more bioreactive due to their accumulation over time. We are interested in the ultrafine (UF) fraction (<1.0um diameter) since the number of particles in this size range are known to increase during pollution episodes and they have a greater reactive surface area per unit weight.

Fibrillary and immunotactoid glomerulonephritis (FGN & IGN) are uncommon glomerular diseases, diagnosed by electron microscopic identification of fibril deposits which are negative by the Congo red stain. Micro-fibrils are similar to normal structures in glomerular basement membrane and matrix and they can be missed by EM. Pathogenesis of these glomerulopathies is unclear but they are not believed to be associated with monoclonal gammopathies as in AL amyloidosis. Immunofluorescense (IF) on FGN indicates the fibrils typically are positive for IgG and both immunoglobulin light chains while IGN fibrils are light chain monoclonal. We did immunogold labeling on four cases of FIGN in to improve the diagnosis of these diseases and investigate fibril protein composition.

Renal biopsies from four patients consisted of one IGN and 3 FGN. Tests included frozen section IF (IgG, IgA, IgM, C3), paraffin section histology (Congo Red) and conventional EM (osmium fixation and epoxy embedding).

Tau is a microtubule-associated protein that promotes polymerization and stabilization of microtubules. It is the major component of fibrillary neuronal and glial inclusions in Alzheimer's disease (AD) and the tauopathies. An autosomal dominant familial tauopathy, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), has been shown to be caused by pathogenic tau mutations. Neuropathologic features of FTDP-17 are filamentous tau aggregates in neurons and glia. Previous transgenic mice carrying the normal human tau gene developed motor neuron disease and had dystrophic axons, but no neurofibrillary tangles (NFT). In this report we describe ultrastructural features of NFT in transgenic mice carrying a mutant human tau gene. The mice were generated with a tau cDNA containing exon 1, 4, 5, 7, 9, 10, 11-13, intron 13 and exon 14, driven by the mouse prion promoter (MoPrP) and containing the most common FTDP-17 mutation, P301L. The transgenic construct was generated by ligating the P301L tau cDNA with the mouse prion promoter.

A cerebral aneurysm is a dome or sac-like structure budding from weakened arterial walls in the brain. Cerebral aneurysms have no known specific cause currently. Considering the risks of surgery, when surgery should be performed on unruptured aneurysms is a very controversial issue. Some clinicians feel that an aneurysm should be surgically removed immediately upon discovery regardless of the size, if surgery is possible. While others feel that small aneurysms should be watched or treated with endovascular insertion of soft platinum coils, avoiding the risks associated with any brain surgery. To further study this question examination was done of specimens from surgical clip ligation of middle cerebral artery aneurysms and normal specimens.

Specimens of ruptured and unruptured aneurysm as well as normal artery removed from surgical patients were immediately preserved in cold 2.5% glutaraldehyde in 0.1 M PBS. The specimens were rinsed in PBS, post-fixed in 1% Osmium Tetroxide with 0.1% potassium ferricyanide,

Proliferation, polymorphism and papillary hyperplasia of the follicular cells and endothelial cells can be often observed on the benign structural background of the thyroid follicular adenoma and this makes it difficult to find out the malignancy with Ught microscopy (1,2,3). The ultrastructural anaplastic changes of the cells and organelles called our attention. Recently some of the authors think that any papillary change in thyroid is the evidence of malignancy.

Twenty cases with follicular adenoma, ten cases with papillary carcinoma of the thyroid diagnosed with light microscopy were re-evaluated with electron microscopy in classical methods. In papillary carcinoma cases anaplastic changes of the tumour cells was showed ultrastructurally (Fig 1). Two of them, with no capsular or vascular invasion observed with Ught microscopy, there were proliferation of the microvilli in the apical parts of the thyrocites, and papiUary projections observed obviously. There were cystic dilations in cytoplasm and a lot of indentations of the nuclei.

The goals were to define the clinical and morphological characteristics of cataract formation in the OXYS strain of rats which are genetically susceptible to oxidative stress. The predominately inherited feature is the high cellular level of glucose uptake. The OXYS strain displays pathological changes in many tissues including blood vessels, liver and lung, which are consistent with increased oxidative damage. Early cataract formation is a prominent feature of this strain.

Rats were examined periodically from birth through the development of mature cataracts with slit lamp biomicroscopy. The morphology of selected stages of cataract development was studied using light and transmission electron microscopy (TEM) as well as immunohistochemical localization of lipid oxidation and DNA oxidation products. Lenses from normal rats of the same age were used as controls. OXYS rats developed cataracts as young as two weeks of age with progression to maturity by one year. Clinically, cataracts appeared initially as either nuclear or subcapsular cortical changes and developed into pronounced nuclear cataracts within months.

The cryopreservation is the method of selection of long-term skin preservation used for the closure of large wound defects and the only possibility of long preservation of graft skin material in the viable state. For the lowtemperature preservation of human skin was successfully used cryoprotectant Polyethylene oxide -400, which was confirmed by the clinical evaluation during autotransplantation /1/. At the same time many aspects of the influence of low temperatures on the ultrastructural skin components were unclear /2/. The investigation of subcellular elements during step of low-temperature preservation specifies mechanisms of influence on the tissue preservation factors and determine the condition of skin cellular elements /3,4,5/. The aim of this work is to study ultrastructural characteristics of human cadaverous skin during the stages of low-temperature preservation by PEO-400.

In this investigation epidermal skin grafts with the thickness of 0.4-0.6 mm were studied in 6 hours after the accidental death divided in 3 series:

Detection of polychlorinated biphenyls (PCBs) in the environment in the late 1960s along with increasing scientific data on their detrimental health effects led to a voluntary ban on these chemicals for industrial uses except in closed systems such as dielectric fluids. Commercial mixtures of the chemicals were manufactured extensively from the mid-1950s to the 1970s for use as flame retardants, lubricants, and dielectric fluids. It was not until the late 1970s that the manufacture of PCBs ceased. Environmental contamination of PCBs, however, continues to be a pervasive problem because of their lipophilic nature and resultant bioaccumulation in the food chain. PCB 118 (2,3',4,4',5-pentachlorobiphenyi) is one member of the chemically inert group of compounds composed of 209 congeners, effects of which are described in current work as a quantitative analysis of hepatocyte ultrastructure using stereology techniques. We determined the mean volume fractions of mitochondria and glycogen particles in the liver cells following exposure of PCB 118 to weanling Sprague-Dawley rats.

Recent study demonstrated that decrease signal transducer and activator of transcription-3 (STAT3) phosphorylation and increase apoptosis might be a critical point in the transition between compensatory cardiac hypertrophy and heart failure. To date, the protein expression of STAT3 in normal and failing human heart remains unclear. Therefore, the current study was designed to investigate the protein expression of STAT3 in human myocardium with end-stage congestive heart failure (CHF) and compared with that in normal human cardiac tissue.

Human cardiac atrial tissue was obtained from normal subjects (n=5) and end-stage CHF patients (n=5) during cardiac transplantation. To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. An average of 1000 nuclei was analyzed for TUNEL study. STAT3 protein expression and phosphorylation of STAT3 were determined by immunohistochemical staining (IHCS) with total STAT3 and phospho-specific STAT3 antibodies.

Brain natriuretic peptide (BNP) is a peptide of cardiac origin which regulates plasma volume as well as vascular tone and growth. Recently, we have reported that brain natriuretic peptide is a potent inhibitor of endothelin-1-mediated proliferation in human coronary vascular smooth muscle cells (HCoVSMC). While brain natriuretic peptide has been reported to be produced and released from atrial and ventricular myocardium, we hypothesize that brain natriuretic peptide may be present and secreted from human coronary vascular smooth muscle cells.

Therefore, the present study was designed to investigate the secretion of brain natriuretic peptide in cultured human coronary vascular smooth muscle cells (HCoVSMC: Clonetics, San Diego, CA). The concentration of brain natriuretic peptide, and its second messenger cGMP, in culture media (48 hours) was determined by radioimmunoassay (Phoenix, Mountain View, CA). The presence of brain natriuretic peptide was determined by immunohistochemical staining using a human brain natriuretic peptide polyclonal antibody.

C-type natriuretic peptide (CNP) is an endothelium-drived vasorelaxing factor which is present in human plasma, urine and renal epithelial cells. Endothelin (ET) is a potent renal and systemic vasoconstrictor and sodium regulating peptide. To date, the localization of C-type natriuretic peptide and endothelin gene expression in human kidney remains poorly defined.

We determined the co-localization of C-type natriuretic peptide and endothelin mRNA in normal human kidney using in situ hybridization (ISH) with synthesized human C-type natriuretic peptide or human endothelin oligonucleotide probes together with immunohistochemical staining (IHCS) with human CNP-22 and ET-1 antibodies with no crossreactivity. The sections treated with nonimmune rabbit serum (NRS) demonstrated no immunoperoxidase activity. Human renal tissue (n=7) was obtained from biopsy of normal cadaveric donor kidneys and normal autopsy specimens.

In situ hybridization (Figure 1) demonstrated that C-type natriuretic peptide and endothelin mRNA presence in human kidney which was localized to proximal and distal tubes with similar intensities.

Natriuretic peptides include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). ANP, BNP and CNP are structure related but genetic distinct 1 natriuretic peptide family. ANP and BNP are cardiac cell origin and CNP are endothelial cell and kidney origin. Natriuretic peptides have potent vasoactive and natriuretic actions through generation of cGMP. On the other hand, renal graft rejection is major problem after kidney transplantation with severe renal damage and renal vasoconstriction. We hypothesized that renal tissue level of natriuretic peptides increase in renal graft rejection through compensatory mechanism. Therefore, the present study was designed to determine the expression of natriuretic peptides by immunohistochemical staining (IHCS) in human renal tissue with rejection and compare with normal renal tissue.

Human renal biopsy (n=5) were obtained after kidney transplantation with mild and moderate renal rejection. Normal kidney biopsy was obtained during nephrectomy. ANP, BNP and CNP levels in renal tissue were determined by IHCS.

Cyclosporine-A (CsA) is the widely used immunosuppressant drug in renal transplantation. However, the effects of cyclosporine-A are limited by a significant nephrotoxicity. The mechanisms of CsA-induced allograft nephropathy are remaining controversial. Recent study indicated that cellular apoptosis may contribute to the cyclosporine A-mediated cytotoxic action. To date, regarding the effects of cyclosporine A on renal cell apoptosis-related gene expression remain poorly defined. p53 is an important gene in control of renal cell growth and death. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that has anti-proliferative as well as fibrogenic properties.

We hypothesized that cyclosporine-A may increase p53 and TGF-β expression in renal tubular cells. These actions of cyclosporine-A may contribute to the cellular apoptosis, fibrosis and CsA-induced nephrotoxicity. Therefore, current study was designed to determine the effects of cyclosporine-A on the p53 and TGF-βl protein expression by immunohistochemical staining (IHCS) in cultured human tubular cells.

Esophageal cancer is the fastest growing malignancy of any tumor in the United States with an increased incidence of adenocarcinoma across all socioeconomic boundaries. The stage and the residual tumor classification are the most important prognostic factors. However, patients with similar stage of disease show a marked difference in survival. Therefore, there are needs to identify new molecular prognostic markers that may help to better assess the survival probability.

The recently introduced genetic diagnosis of cancer micrometastasis is quite attractive because of its high detection sensitivity. Not infrequently, however, there are marked discrepancies between genetic and conventional histologic diagnoses, especially concerning lymph nodes from carcinoma patients. Alterations in the p53 tumor suppressor gene are the most frequent genetic changes found in breast and lung cancer. The p53 gene functions as a negative regulator of cell growth. Alterations in the gene lead to loss of its usual negative growth regulation and more rapid cell proliferation.

Endothelin-1 (ET-1) is a potent endothelial cell-drived vasoconstrictive peptide which is increased in congestive heart failure (CHF). ET-1 is converted from its precursor big ET-1 by activation of endothelin converting enzyme (ECE). ET-1 binding to ET-A receptor in vascular smooth muscle cells stimulates vasoconstriction and binding to ET-B receptor in vascular endothelial cells mediates vasodilation. In previous studies, we and others demonstrated that plasma ET-1 was significantly increased in congestive heart failure. However, the presentation and localization of endothelin converting enzyme and endothelin receptors (ET-A and ET-B) in human cardiac tissue with and without heart failure remain unclear. Therefore, the current study was designed to investigate the expression and localization of endothelin receptors and endothelin converting enzyme in human myocardium in the absence or presence of congestive heart failure.

Human atrial tissues (n=6) were obtained from normal subjects and end-stage CHF patients during cardiac transplantation. The expression of ECE, ET-A and ET-B were determined by immunohistochemical staining (IHCS).

Endothelin (ET-1) is a potent renal and systemic vasoconstrictor and sodium regulating peptide. Endothelin synthesis in the kidney have been reported in glomerulus endothelial, epithelial and mesangial cells as well as in inner medullary collecting duct. Factors stimulating the production of endothelin include shear stress, hypoxia, vasoactive agents and cytokines. Endothelin binding to ET-A receptor in vascular smooth muscle cells stimulates vasoconstriction.

Renal graft rejection is a major problem after kidney transplantation with severe renal damage and renal vasoconstriction. We hypothesized that renal tissue level of endothelin-1, endothelin receptors and endothelin converting enzyme (ECE) may increase in renal tissue with rejection after kidney transplantation. Therefore, the current study was designed to determine the endothelin-1 and endothelin receptors (ET-A and ET-B) as well as endothelin converting enzyme level by immunohistochemical staining (IHCS) in human renal tissue with rejection after kidney transplantation.

Transforming growth factor-beta (TGF-β) is a growth-regulating peptide that has been shown to enhance collagen production both in vivo and in vitro. The previous studies demonstrated that TGF-β 1 is present in the normal animal myocardium. However, the expression and localization of TGF-β 1 and TGF-P receptor in human myocardium remain unclear. Therefore, the present study was designed to determine the TGF-β 1 and its receptor in human myocardium in normal subjects and in patients with end-stage congestive heart failure (CHF).

Human ventricular tissues were obtained from five normal subjects and five patients with end-stage CHF during cardiac transplantation. TGF-β 1 and TGF-beta type I receptor (TGF-βRI) were determined by immunohistochemical staining (IHCS). The results of IHCS was evaluated by staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining). The positive staining area (+%) in entire section was also determined.