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Chemical injuries to the eye represent one of the true ophthalmic emergencies that require immediate and intensive intervention to minimize severe complications and visual loss. Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic cytokine that influences the proliferation, survival, maturation, and the functional activation of granulocytes. The present work was performed to evaluate the histological effect of G-CSF in treating rat corneal alkali burn model. Thirty adult male albino rats were divided equally into three main groups: Group I was served as a control group, and in Group II and III, their corneas of the right eyes were injured by applying a piece of filter paper soaked in 1M NaOH. Group II (alkali burn-induced group) was left without any treatment, while Group III (G-CSF-treated group) was injected subcutaneously by 100 µg/kg of G-CSF for 5 consecutive days. All animals were sacrificed after 3 weeks. Cornea specimens were processed for histological and immunohistochemical staining for P63 followed by morphometry. Microscopic examination of Group II revealed marked alterations in the corneal epithelium, inflammatory cellular infiltration, and neovascularization. Treatment with G-CSF showed great improvement of the corneal structure, disappearance of the neovascularization and the inflammatory cells, and decreased p63 reaction of the basal layers. [ABSTRACT FROM AUTHOR]

Since first described, several studies about Myxoinflammatory fibroblastic sarcomas (MIFS) have been published stating the clinicopathological, morphological and immunohistochemical features. However, the ultrastructural findings of these MIFS are limited. Thus, the objective of the present paper is to describe the ultrastructural characteristics of these type of tumors by utilizing tissue that was embedded in paraffin and submitted for immunohistochemistry. The tissue of seven different cases was obtained for ultrastructural study with automatized staining devices, that were later observed by using transmission electron microscopy. Histologically all cases displayed conventional structures of Myxoinflammatory fibroblastic sarcoma (Reed-Sternberg like cells, pseudolipoblasts and emperipolesis). Conversely, two of them exhibited high-grade components, one rich in osteoclastic type giant cells and hypercellular areas, and another one rich in inflammation (Hodgkin-like). After immunohistochemistry, all the samples revealed positivity for CD68 with six cases CD163 and five being positive to CD34, Cyclin-D1, and D2-40. Ultrastructural findings indicated rough endoplasmic reticulum with dilatation of the cisterns that indented the nuclei ("soccer ball" cells), abundant lysosomes, phagolysosomes, and intermediate filaments evidencing this entity as a morphologic continuum that exhibited modified fibroblastic phenotype and variable proportion of macrophagic differentiation. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is the largest membranous network serving as a region for protein, lipid and steroid synthesis, transport and storage. Detailed information about ER-cisternae, ER-tubules and rough endoplasmic reticulum (rER) is scarce in human blood cells. This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system. This paper reveals that in the promyeloblasts of APL, ER is the source of and transforms progressively into giant inclusions and Auer bodies. [ABSTRACT FROM AUTHOR]

It wasn't until 1960 that the dense bodies of the peripheral actin arrays of fibroblasts were finally visualized, i.e., stress fibers (SFs). Mistakenly assumed that its SFs turned the fibroblast into a unique cell situated somewhere in a continuum between it and a smooth muscle cell (SMC), it was descriptively named a "myofibroblast" (MF). Automatically, spindle cells with SFs and/or smooth muscle actin by SMA IHC-staining, became MFs, although endothelial cells, pericytes, modified SMCs (mSMC), and myoepithelial cells all contain SFs. An invisible "intermediate" cell was hypothesized to exist somewhere between SMA-negative and positive fibroblasts, and named a "proto-myofibroblast". The sub-epithelial spindle cells of normal and malignant tumors of the GI, GU, and respiratory tracts are all fibroblasts with SFs. The second erroneous myofibroblast came from a 1971 rat wound healing study and its 1974 human counterpart. Updated analysis of the papers' TEMs proved that the cells are mSMCs and not fibroblasts (AKA: MFs). The pathognomonic cells of Dupuytren's contracture are mSMCs and fibroblasts and that of the stenosing arteriopathy of Kawasaki Disease and other similar arteriopathies are mSMCs. TEM remains a powerful tool. [ABSTRACT FROM AUTHOR]

Roggli and Green have reported their study of the dimensions of fibers extracted from the tissues of cases examined in their laboratory, and have drawn conclusions about the pathogenicity of Elongated Mineral Particles and their classification as asbestiform versus cleavage fragments. There are aspects of their methodology and discussion that would benefit from examination. Roggli and Green have relied upon a paper by Harper et al. for their definitions of asbestiform and cleavage fragments. Unfortunately, they have misinterpreted the work of those authors who have concluded that the best criterion is a particle width <1μm. Roggli and Green conclude that 'Our findings demonstrate the lack of pathogenicity of fibers less than 10 μm long or likelihood of cleavage fragments for fibers less than 10μm long and greater than 1.0μm in diameter has little or no effect on the classification of commercial amphibole fibers using our analytical methodology. On the other hand, both lack of pathogenicity and likelihood of cleavage fragments apply to a significant proportion of noncommercial amphiboles identified using our counting scheme.' This is not true. The study of Roggli and Green was a simple fiber counting study with no control population. The design of such a study does not allow the investigator to draw any conclusions about pathogenicity, or lack thereof. [ABSTRACT FROM AUTHOR]

Giant cell tumor of bone (GCTB) is a primary bone tumor that affects skeletally mature people and whose main treatment is surgical. Because there are few pharmacological alternatives for the treatment of this tumor to find other molecules or compounds that could be potential therapeutic agents is desirable. Quercetin is a flavonoid with described antitumoral effect in different types of cancer cell lines that could be a possible option in GCTB treatment. However, there is no literature about the effect of quercetin on GCTB. In the present paper, we reported the ultrastructural changes in GCTB cells exposed to quercetin and also determined the expression of RIP1K, Caspase 3 and Caspase 8 on the exposed cells. For this purpose, GCTB sample was obtained from one patient and cultured. Quercetin affected all the histological components of the GCTB. The ultrastructural changes consisted mainly in necroptosis, autophagocytosis and secondary necrosis. This is the first report about quercetin effects on giant cell tumor of bone cultured cells. Further studies in other models could be done to support the use of quercetin as a complementary treatment in giant cell tumor of bone. Abbreviations: Giant cell tumor of bone (GCTB); transmission electron microscopy (TEM); reverse transcription – polymerase chain reaction (RT-PCR); receptor interacting protein kinase 1 (RIP1K); Dulbecco's Modified Eagle's Medium (DMEM). [ABSTRACT FROM AUTHOR]

Basal/external lamina is not found over plasma cells or other hemolymphoid cells, and the feature can have diagnostic value in distinguishing the neoplastic counterparts of such cells from epithelium, endothelium, mesothelium, and so on, which do have this feature. In this paper, a material ultrastructurally indistinguishable from basal or external lamina is reported on reactive plasma cells found in a fibrous pseudotumor, intralobular stroma of normal breast, tumor stroma of squamous cell carcinoma, and submucosa of normal human small intestine. It was focal, followed the contours of the cell-surface membrane, was lightly textured, 40-80 nm thick, and separated from the plasma cell surface membrane by a clear space resembling a lamina lucida. Its function remains uncertain, although it may implement adhesion to other cells, as part of the immune functions that plasma cells and other hemolymphoid cells perform in the gut, for example, and elsewhere. [ABSTRACT FROM AUTHOR]

The organotin compound di-n-butyltin dichloride (DBTC) is able to induce an acute and later a chronic pancreatitis in rats. In previous papers the authors demonstrated this DBTC pancreatitis as a rat model for an interstitial pancreatitis with tendency to transduction to the chronic form. DBTC is excreted according to its lipophilic nature by liver and bile. Therefore, the bilio-pancreatic main duct is necrotized by the tin-loaded bile. The duct system is blocked by cell debris and later by epithelial proliferations. In the chronic phase, numerous rats develop concrements in the main duct. In the present paper, the authors report about bacterial growth in some bilio-pancreatic concrements. Whereas the electron microscopic detection of tin by energy-dispersive X-ray analysis (EDX) in SEM or electron energy loss spectroscopy (EELS) in TEM was negative in the parenchyma of pancreas and liver, some concrements with bacterial cells were positive for this element. Tin mapping with energy spectroscopic imaging (ESI) in TEM demonstrated the congruency of tin signals and electron-dense particles inside these bacteria and of electron-dense accumulations in the matrix of these concrements. The low content of tin in pancreatic and liver tissue and the higher quantity of tin inside the bacterial contaminated concrements were supported by atomic absorption spectrophotometry (AAS). The paper discusses the long time preservation of tin in the concrements as an action of heavy-metal-accumulating bacteria, which should be classified in the future by bacteriological methods. [ABSTRACT FROM AUTHOR]

Unfortunately, the issue that was going to be ultrastructure of renal diseases will not be published. The first one on renal amyloids was just published in the previous issue and the second one on processing the renal biopsy will appear in the present issue (first author Dr. David Howell). Discussion between the authors and publisher did not come to an agreement and the authors of the papers decided not to publish them in Ultrastructural Pathology. [Extracted from the article]

Activation of coagulation pathways results in the formation of hemostatic fibrin plugs. Under normal physiologic conditions fibrin clots are gradually, albeit completely, degraded by a fibrinolytic enzyme system to ensure proper wound healing and/or blood vessel patency. Yet in pathological situations, thrombi are not effectively removed, leading to chronic thrombosis. The susceptibility of blood clots to enzymatic degradation depends on the structure and properties of fibrin fibers. Many factors have been suspected as culprits, including red blood cells (RBCs) that become transiently trapped within fibrin mesh. Here, the authors show that there is indeed a specific interaction between RBCs and fibrin-like fibers identified here as dense matted deposits (DMDs) by means of scanning electron microscopy (SEM). It is emphasized that such interactions can be observed in ischemic stroke patients, but not from healthy subjects. However, DMD/RBC aggregates can be induced in normal blood by the additions of trivalent iron ions. The plausible mechanism of the enhanced fibrin-red blood cell interaction is based on the previously described iron-induced generation of hydroxyl radicals. These radicals cause, in turn, non-enzymatic formation of fibrinogen aggregates remarkably resistant to fibrinolysis that are also similar to DMDs described in this paper. In conclusion, this relatively simple SEM analysis may become a convenient tool for diagnosing prothrombotic conditions associated with iron overload. It is suggested that future research on prevention and treatment of ischemic stroke and other thrombosis associated diseases should include testing of iron-chelating and hydroxyl radical-scavenging agents. [ABSTRACT FROM AUTHOR]

Primary and metastatic carcinomas have a reactive stroma characterized by many myofibroblasts. These cells have also been documented in nonepithelial malignancies, such as sarcomas, malignant melanoma, and lymphoid tumors but in generally far fewer numbers. In non-Hodgkin's lymphoma, Hodgkin's disease, and leukemia, myofibroblasts are rather rarely documented. In particular, there appear to be no reports of myofibroblasts in either primary bone-marrow/peripheral blood leukemia or secondary deposits of leukemia. In this paper, a case of a relapsed chronic myeloid leukemia appearing in an inguinal lymph node is described, containing many myofibroblasts. The case is detailed and presented with a discussion on the role of myofibroblasts in the progression of nonepithelial cancers. [ABSTRACT FROM AUTHOR]

This paper explores the connection between paclitaxel, a chemotherapeutic agent, and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel triggers autophagy and inhibits proliferation of gastric cancer cells. An 3–(4,5–dimethyl–2–thiazolyl)–2,5–diphenyl–2–H–tetrazolium bromide (MTT) assay was used to detect cell viability and the IC50of paclitaxel. Western blot was used to detect the expression levels of P62, and to measure the protein expression of autophagy. Immunofluorescence was used to reveal the appearance of punctate structures in the cytoplasm—this ultrastructure associated with autophagy was observed by microscopy. Electron microscopy revealed the formation of double-membrane autophagosomes, a typical structure of autophagy. In conclusion, our research indicates that paclitaxel may influence gastric cancer BGC823 cells by way of inducing autophagy. [ABSTRACT FROM AUTHOR]

Information on several papers discussed at the 14th biennial meeting organized by the Society for Ultrastructural Pathology which was held in Heraklion, Greece on July 6, 2008 is presented. Several papers of medicine researcher were presented in the meeting including chromatin in peripheral blood leukocytes, electron microscopy and technique in the diagnosis of light and heavy chain renal disease. The meeting featured several medical executives including Josep Lloreta, and Voloudakis-Baltatzis.

Lewy bodies are the hallmark of Parkinson disease and their sophisticated analysis will undoubtedly elucidate the pathogenic process. They have been studied by using different microscopic tools. The authors have used atomic force microscopy (AFM) to study the ultramicrotom cut postmortem brain tissue of Parkinson disease patients. Under the same preparation conditions, they have found aggregated fibrillary nanostructures in Lewy bodies, as well as a loss of connections between neurons located in other parts of the substantia nigra. Although these results are preliminary and descriptive in nature, this paper reports the application of a novel and intriguing technique. Further studies including the study of cortical LB and Lewy neurites will be needed to determine the full potential of AFM in the study of the pathogenesis of cell death in Parkinson disease and other synucleinopathies. [ABSTRACT FROM AUTHOR]

Gliomas are typically characterized by their infiltrative nature, and the prognosis can be linked to the invasive nature of the tumoral cells. Glioblastoma multiforme are very invasive cancers and this contributes to their lethality. The invadopodia are considered essential for their motility. Human glioma cell invadopodia were examined with transmission electron and immunofluorescent microscopy. By electron microscopy, in situ gliomas (fibrillary astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, pilocytic astrocytoma) show mitochondria with a dense matrix condensed configuration, indicating an active state. The mitochondria were frequently in close contact with an extended smooth endoplasmic reticulum displaying an endoplasmic reticulum subfraction associated with mitochondria. Mitochondria were seen within the filopodia that were penetrating into the extracellular matrix. The activated mitochondria and smooth endoplasmic reticulum were also detected within the invadopdia, which was associated microblood vessels. Fluorescent microscopy confirmed that D54 and U251 glioma cells growing in vitro also contained filopodia with mitochondria. The U251 glioma cells' filopodia that penetrated through 1.2-μm pores of transwell chambers also contained mitocondria, suggesting that the mitochondria are actively involved in the invasion process. Migration and invasion of tumor cells requires an increase in cellular motility and involves formation of lamellipodia, protrusions of the plasma membrane, and individual filopodia [1]. Gliomas are typically characterized by their infiltrative nature, resulting in a poorly demarcated interface between tumor and normal brain tissue. Their poor prognosis can be linked to the invasive nature of these cells. The motility of these tumor cells is correlated with the presence of invadopodia [2], and, consequently, more insight is necessary into their structural and molecular aspects. Evidence of robust invadopodia activity in glioblastoma multiforme cells has been reported [3,4]. Because of the significant impact of invadopodia in oncological events such as cell invasion and matrix degradation, more insight into structural and molecular aspects is needed [2]. The dynamic assembly of invadopodia is still not well understood [2], and little is known of the alterations in mitochondrial structure and function that contribute to cell mobility [5]. This paper describes two prominent structural features of the mitochondrial network present within the glioma´s invadopodia that we have recently observed. We believe these two features (activated mitochondria and smooth ER, along with mitochondria contained within the filopodia) might provide researchers with possible targets for future therapies that can control glioma invasiveness. [ABSTRACT FROM AUTHOR]

The detection of microscopic hematuria in a child's urine prompts evaluation for renal and urinary bladder causes. Microscopic hematuria identified during a routine physical examination by the pediatrician is much more common than macroscopic hematuria. Persistent microscopic hematuria is particularly worrisome and may require a percutaneous needle core kidney biopsy to determine whether the etiology is secondary to glomerular disease, tubulointerstitial disease, urinary tract infection, urinary tract structural abnormalities, medications, or toxins. This paper reviews the epidemiology, pathologic features, pathogenesis, treatment, and outcome of familial hematuria (Alport syndrome [hereditary nephritis]), thin basement membrane nephropathy), IgA nephropathy, Henoch-Schönlein purpura, and acute postinfectious glomerulonephritis. [ABSTRACT FROM AUTHOR]

Glycogen storage diseases (GSD) affect primarily the liver, skeletal muscle, heart, and sometimes the central nervous system and the kidneys. These unique diseases are quite varied in age of onset of symptoms, morbidity, and mortality. Glycogen storage diseases are classified according to their individual enzyme deficiency. Each of these enzymes regulates synthesis or degradation of glycogen. Interestingly, there is great phenotypic variation and variable clinical courses even when a specific enzyme is altered by mutation. Depending on the specific mutation in an enzyme, a GSD patient may have a favorable or unfavorable prognosis. With neonatal or infantile forms, some GSDs lead to death within the first year of life, whereas other glycogen storage diseases are relatively asymptomatic or may cause only exercise intolerance. The paper provides a brief review and update of glycogen storage diseases, with respect to clinical features, genetic abnormalities, pathologic features, and treatment. [ABSTRACT FROM AUTHOR]

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of fibrosarcoma, described initially by Meis-Kindblom et al. in 1995 (Meis-Kindblom JM, Kindblom L-G, Enzinger FM. Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995;19:979–993): more than 80 cases have been documented clinicopathologically since. Bone is a rare primary site for SEF, with only 2 cases so far reported. This paper documents the detailed clinical, histological, immunohistochemical, and ultrastructural features of a case occurring in the pubic bone of a 57-year-old diabetic woman presenting with a history of pain and compromised mobility involving her hip. Radiology revealed a destructive lesion in the right pubic bone. The lesion was resected, and 7 months postoperatively it recurred. The patient died following metastases to multiple bony sites and liver, some 4 years after the onset of symptoms. Histologically, the tumor was consistent with SEF, although it showed some anomalous immunostaining, which, however, is typical of the tumor (for example, for S-100 protein and epithelial membrane antigen). By electron microscopy, some rough endoplasmic reticulum was present, but also tonofibrils and desmosomes. The overall features were of an SEF with the ultrastructural but incomplete immunohistochemical evidence for divergent epithelial differentiation. The differential diagnosis of this tumor is discussed. [ABSTRACT FROM AUTHOR]

The objective of this paper is to produce an ultrastructural classification of acute monocytic leukemia (AML-M5) in relation to clinical behaviors. The ultrastructural characteristics of blasts of the monocytic series were analyzed in 72 M5 patients by transmission electron microscopy (TEM), in terms of their content of typical monoblasts, atypical monoblasts, atypical promonocytes, and typical promonocytes in bone-marrow aspirates. Four kinds of monocytic blasts were identified by cell size and shape, nuclear profile, nucleocytoplasmic ratio, heterochromatin content, nucleolus, granules, vesicles, and Golgi apparatus. Their characteristics of remission rate, cytochemistry, immunophenotype, and cytogenetics were also investigated. The data obtained permitted M5 patients to be divided into monoblast and promonocyte types. Monoblast-type patients expressed weaker monocytic enzymograms and specific antigen staining for CD14 and CD64, compared with promonocyte-type patients. Monoblast patients had higher CR than promonocyte patients. Therefore, TEM subclassification of patients differs from and improves upon the light microscopical criteria for distinguishing monoblasts and promonocytes and has clinical significance. [ABSTRACT FROM AUTHOR]

The fibronexus is recognized as a characteristic marker of the myofibroblast. However, it is not completely specific for this cell, having been seen in aortic smooth muscle (in attenuated form) and endothelium in experimental animals. This paper documents fibronexus junctions in human in vivo endothelium. Ultrastructural observations were made on the vasculature of a desmoplastic and focally neurotropic malignant melanoma. Cross-sectioned fibronectin fibrils were seen outside the stromal surface of the endothelial plasmalemma. Often, they were positioned directly opposite the actin-filament bundles in the peripheral cytoplasm. Neoplastic and in vitro cultured cells apart, endothelium is the only nonmyofibroblastic cell type to show well-developed fibronexus junctions. Mostly, they have been documented in aortic endothelium in experimental animals, where they possibly constitute an adaptation to hemodynamic stress, and where they might more securely anchor endothelium on to subjacent connective tissue. They might also function as mechanotransducers of extracellular stress in the extracellular milieu. The present observations constitute a further, rare example of endothelium-associated fibronexuses in reactive human vessels. [ABSTRACT FROM AUTHOR]

Although the ultrastructural features of several brain tumor cells have been studied in details, the ultrastructure of glioma stem cells/progenitors cells (GSPC) has rarely been reported. In this paper, the authors describe the ultrastructural features of GSPCs isolated from both a glioma tissue and the human glioma cell SHG-44 cell line. The ultrastructural features of the two kinds of GSPCs were similar, with relatively developed mitochondria, Golgi apparatuses, ribosomes, undeveloped rough endoplasmic reticula, seldom lysosomes and no typical autophagosomes, and high nuclear-cytoplasmic ratio. Their nuclei, frequently containing huge amounts of euchromatin and a small quantity of heterochromatin, were mostly globular; and the majority of the nuclei had only one nucleole. Typical apoptotic cells could hardly be found in tumor spheres, and between adjacent cells there were cell junctions, which probably were incompletely developed desmosomes or intermediate junctions. In conclusion, their ultrastructural features showed that GSPCs were at the primary stage of differentiation, and could even partially reveal the underlying reasons for the malignant proliferation and differential inhibition of GSPCs. [ABSTRACT FROM AUTHOR]

A conference paper about undifferentiated sarcoma is presented. It subdivides undifferentiated sarcomas in broad groups including round cell sarcomas, spindle cell sarcomas, pleomorphic sarcomas, and epithelioid sarcomas. It examines the factors required for labeling sarcomas as undifferentiated sarcoma including availability of immunohistochemistry, tissue sampling, and availability of electron microscopy.

Cooperation between research communities and software-development teams has led to the creation of novel software. The purpose of this paper is to show an alternative work method based on the usage of ImageJ (http://rsb.info.nih.gov/ij/), which can be effectively employed in solving common microscopic and ultrastructural image analysis tasks. As an open-source software, ImageJ provides the possibility to work in a free-development/sharing world. Its very "friendly" graphical user interface helps users to manage and edit biomedical images. The on-line material such as handbooks, wikis, and plugins leads users through various functions, giving clues about potential new applications. ImageJ is not only a morphometric analysis software, it is sufficiently flexible to be adapted to the numerous requirements tasked in the laboratories as routine as well as research demands. Examples include area measurements on selectively stained tissue components, cell count and area measurements at single cell level, immunohistochemical antigen quantification, and immunoelectron microscopy gold particle count. [ABSTRACT FROM AUTHOR]

The ribosome-lamella complex (RLC) is a cylindrical structure composed of annular lamella associated particles, regarded as ribosomes, around a central core, which is best known in hairy cell leukemia. RLC has been presumed to originate from aggregating rER and ribosomes. Incomplete and maturing RLC structures have been called RLC precursors (pre-RLC). The present paper investigates the various architectural aspects of pre-RLC and the ultrastructural characteristics of the blasts in 6 cases of acute monocytic leukemia (M5) in which these structures occur. Blasts bearing pre-RLC contained irregular nuclei with less heterochromatin and a prominent nucleolus, and many cytoplasmic organelles in an abundant cytoplasm. The findings indicate that pre-RLC might result from an asymmetrical differentiation of organelles in blasts associated with expression of CD117 and CD56 but default of CD14 in M5. [ABSTRACT FROM AUTHOR]

Tran and colleagues have taken issue with our use of control or reference ranges in our article regarding 'Talc and Mesothelioma: Mineral Fiber Analysis of 65 Cases with Clinicopathological Correlation'.[1] We did not use a "single" control to establish our background range for talc in the reference population, but instead 20 control cases that had been used as a reference population in prior studies.[2] As clearly indicated in Table 1, talc was detected in 11 of our 20 control cases. Careful reading of our paper as well as most of our other fiber analysis publications indicates that tremolite, actinolite and anthophyllite are combined in all cases in that study, and not just in case 24. [Extracted from the article]

Roggli et al. (2020) dismissed cosmetic talc as a cause of mesothelioma by stating "we have analyzed lung tissue from one mesothelioma case with cosmetic talc exposure, and both talc and tremolite were present in concentrations within our background range."[1] The authors relied on Srebro et al. (1995) to create their "talc background" of 10,500 fibers/gram of wet lung.[2] While talc was used in wall board, paint, food (chewing gum), paper, as an expedient in drugs, molding compound and rubber manufacturing there is no evidence that any of these uses result in airborne exposures to non-workers or consumers. Roggli et al. (2020) selected a single control case (#24) from Srebro et al. (1995) with the highest talc fiber level as the "background" level for lung talc fiber burden.[2],[3] This "control" case does not establish a "background" talc fiber level.[2] Srebro et al. (1995) did not collect information on either industrial or cosmetic talc exposure for either cases or the single control that was used to establish a "background" talc lung burden.[3] The use of this case is problematic. There is no way to correlate published lung fiber levels to any cumulative exposure since fibers are not permanently bioperistent and lung fiber studies have not reported time since last exposure. [Extracted from the article]

In the last two decades, the ability of mesangial cells to respond to various stimuli or injurious agents by altering their phenotype and function has become recognized. The plasticity of these mesangial cells has been linked to the morphological and functional alterations responsible for the pathologic findings. Many of the glomerular disorders target the mesangium as the primary and/or initial site of injury. Understanding how mesangial cells are altered in the various conditions provides a platform for conceptualizing pathologic mechanisms and defining key steps amenable to therapeutic intervention. The present paper reviews the normal and altered mesangium with an emphasis on mechanisms involved in alterations of mesangial homeostasis. Mesangial cells and matrix are very important in maintaining normal glomerular structure, and function and the plasticity of these cells is responsible for pathological manifestations, repair, and scarring. Our more sophisticated understanding of mesangial cell behavior and matrix biology provides very useful information to help design new therapeutic approaches to the treatment of renal diseases. The potential for bone marrow-derived cells to differentiate into mesangial cells and repopulate damaged mesangium, thus “healing” what is today considered to be irreversible damage represents an exciting new area of research. [ABSTRACT FROM AUTHOR]

While murine models of autoimmune (lupus-like) glomerulonephritis have been available for sometime, it is only recently that immune and inflammatory mechanisms and molecular genetics have been extensively investigated. Genes involved in murine and human lupus nephritis have been discovered and provide insight into this disease process and provide avenues for molecular-targeted therapy. Immune modulation of murine nephritis has provided insight into novel therapy that may attenuate this disease or halt disease progression. With the advances in understanding the pathogenesis of lupus nephritis using translational research modalities, including electron microscopy, and molecular genetics, many “designer” therapies have become available for clinical use and for clinical investigational trials. This paper reviews autoimmune (lupus-like) glomerulonephritis in murine models, candidate genes involved in lupus nephritis, adhesion molecules implicated in murine lupus-like nephritis, immune modulation of murine lupus-like nephritis, and novel and potential therapy for immune complex glomerulonephritis. [ABSTRACT FROM AUTHOR]

Previously surgery and irradiation were the only available procedures to treat patients with pituitary tumors. During the last few decades, novel drugs such as dopamine agonists and long-acting somatostatin analogs were developed and, an alternative medical therapy emerged. This paper summarizes the effect of medical therapy on the morphologic features of pituitary tumors and illustrates the ultrastructural alterations on electron micrographs. Currently drugs can be used in the management of pituitary tumors secreting GH, PRL, and/or TSH in excess. No medical therapy is available so far for ACTH-, FSH-, LH-, or alpha-subunit-secreting tumors as well as non-hormone-secreting pituitary tumors. Dopamine agonists are effective in the management of PRL-secreting tumors; they cause marked reversible tumor shrinkage in the substantial majority of patients. Long-acting somatostatin analogs are useful in the management of GH- and TSH-secreting pituitary tumors; they lead to mild to moderate tumor shrinkage in approximately 50% of cases. In patients treated with these drugs reduction of elevated blood hormone levels and amelioration of clinical symptoms ensue. It should be emphasized that no permanent cure is obtained. Blood hormone levels increase and the clinical symptoms reappear after discontinuation of treatment. Recently GH receptor blockers (pegvisomant) were introduced in the treatment of GH-producing pituitary adenomas. To the authors' knowledge the effect of these durgs on the morphology of pituitary tumors has not been revealed so far. [ABSTRACT FROM AUTHOR]

Cellular transformations, reflecting phenotypic plasticity. characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the "normal" fibroblast. In this paper. the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin- staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor ft Investigations into the mechanisms of differentiation in normal fibroblasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention. [ABSTRACT FROM AUTHOR]

Transmission electron microscopy has played a key role in our understanding of the human immunodeficiency virus and the opportunistic infections that accompany HIV disease. This paper describes features of HIV production; HHV-8, the virus that is associated with Kaposi sarcoma; Trachipleistophora anthropophthera, a new disseminating microsporidian; and bacterial enteritis, which causes diarrhea in patients with AIDS. [ABSTRACT FROM AUTHOR]

Although several recent studies deal with various molecular aspects of apoptosis, or programmed cell death, very little information is available on the ultrastructural changes associated with apoptosis in the adenohypophysis and its role in the regulation of pituitary adenoma growth and progression. This paper describes the distinct ultrastructural sequences that develop during the various phases of the apoptotic process. The study is based on the ultrastructural investigation of more than 8,000 surgically removed pituitary biopsies, which were examined by histology and immunocytochemistry for diagnostic purposes. No apoptosis was found in normal adenohypophysis and it is also a rare event in pituitary adenomas. When present, adenomatous adenohypophysial cells exhibit common and characteristic apoptotic changes. The ultrastructural alterations of membraneous organelles associated with apoptosis are similar to those previously reported in other tissues. It is noteworthy that apoptosis is clearly distinguishable from the ubiquitous dark cells denoting the common way of cell death. The findings suggest that apoptosis in pituitary adenomas is not a random event. Practically every specimen containing multiple apoptotic cells represents corticotroph adenoma. Occasional examples occur in lactotroph or gonadotroph adenomas. Although electron microscopic specimens are admittedly small, the large number of investigated cases gives credence to the observations. [ABSTRACT FROM AUTHOR]

The monocytes in acute monocytic leukemia (AML-M5b) were analyzed by scanning and transmission electron microscopy (SEM and TEM) to understand more fully their structure and origin. By SEM, monocytes exhibited localized expansions of the surface, some of which appeared to bud off as surface vesicles (SVs). Filopodial processes and pseudopodia were also present. TEM demonstrated that the SVs were composed of a double-membrane at the pole away from the cell body, and a single membrane nearer to the cell body. In the peripheral cytoplasm, intracellular vesicles (IVs) had the appearance of vacuoles and were enclosed by single membranes. Most SVs were characterized by a notch as a rER edge and an expanded head. Filopodial processes had the same thickness of 40 nm as the SV walls, which suggested a close developmental relationship between the two. Pseudopodia between SVs were irregular in size. Rod-like rER cisternae were prominent in the peripheral cytoplasm and some showed a close physical juxtaposition as to suggest a transition from rER to IVs to SVs. Ultrastructural cytochemistry demonstrated activity of 5'-nucleotidase over rER, SVs, filopodial processes and pseudopodia, and a patchy reaction over other areas of plasma membrane. Overall, the results indicated that rER transforms into SVs, filopodial processes and pseudopodia, as a way of integrating cytoplasmic membranes into the plasma membrane. [ABSTRACT FROM AUTHOR]

Exposure to environmental metal pollutants is linked to oxidative stress and the subsequent development of neurological disease. In this study, the effects of copper, manganese, and mercury, were evaluated at X100 the World Health Organization safety limits for drinking water. Using a Sprague-Dawley rat model, following exposure for 28 days, the effects of these metals on biochemical blood parameters and tissue and cellular structure of the brain were determined. Biochemical analysis revealed no hepatocellular injury with minor changes associated with the hepatobiliary system. Minimal changes were found for renal function and the Na+ /K+ ratio was reduced in the copper and manganese (Cu + Mn) and copper, manganese, and mercury (Cu, Mn + Hg) groups that could affect neurological function. Light microscopy of the brain revealed abnormal histopathology of Purkinje cells in the cerebellum and pyramidal cells in the cerebrum as well as tissue damage and fibrosis of the surface blood vessels. Transmission electron microscopy of the cerebral neurons showed microscopic signs of axonal damage, chromatin condensation, the presence of indistinct nucleoli and mitochondrial damage. Together these cellular features suggest the presence and influence of oxidative stress. Exposure to these metals at X100 the safety limits, as part of mixtures, induces changes to neurological tissue that could adversely influence neurological functioning in the central nervous system. [ABSTRACT FROM AUTHOR]

Kawasaki Disease (KD) is primarily a childhood vasculitis of mid-size muscular arteries, of which the coronary arteries (CA) are most clinically significant. Although timely treatment with pooled intravenous immunoglobulin (IVIG) has significantly reduced CA pathology, as determined by ECHO cardiology, about 30% of children still develop potentially fatal aneurysms, thrombi, or stenosis. This paper describes several additional pathologies and phenomena of undetermined significance, e.g. myocarditis, endocarditis with fibroelastosis, adrenal medullary necrosis, arterial smooth muscle cell transition into proliferating myofibroblasts, pneumonia in patients dying from KD, and calcification of organizing thrombi. [ABSTRACT FROM AUTHOR]

This retrospective, observational study sought to examine the relationship between Ehrenreich-Churg electron microscopy (EM) stages and long-term outcomes in anti-PLA2R membranous nephropathy (MN). Seventy-one patients with anti-PLA2R MN (median titer 185.7RU/mL) were followed for a median of 46 months, with end-stage kidney disease (ESKD) as the primary endpoint, and response to treatment as a secondary endpoint. Patients were grouped into stages I-II (41 patients) and stages III-IV (30 patients) for analytical purposes. Notably, the III-IV group demonstrated a lower eGFR, lower anti-PLA2R titer, but a higher chronicity score. Kaplan-Meier analysis showed shorter mean kidney survival time in stages III-IV compared to I-II (p 0.03). However, multivariate analysis using Cox regression indicated that Ehrenreich-Churg stages did not significantly influence kidney survival, but lower eGFR at diagnosis and higher histopathological chronicity score did. Remission was achieved by 64% of patients and no relationship between Ehrenreich-Churg stages and treatment response was found. The only identified risk factor for not achieving remission was the severity of hyposerinemia at diagnosis. In conclusion, while EM stages III-IV are associated with more chronic lesions and stages I-II with more active immunologic disease, the histological chronicity score seems to be a stronger predictor of long-term outcomes. [ABSTRACT FROM AUTHOR]

A 34-year-old male presented with lung shadow and was asymptomatic during medical examination. The patient had a prior history of thyroid tumors. Imaging manifestation showed a nodule in the medial segment of the right middle lobe, with partial obstruction of the distal bronchus within the lesion. Ground-glass and inflammatory nodules were observed in the anterior segment of the right upper lobe, as well as chronic inflammatory changes in the lower lobe of the right lung. Lung histopathological examination suggested invasive adenocarcinoma. A morphological examination of the bronchoalveolar lavage fluid revealed the presence of Tropheryma whipplei (TW) and Nocardia. Although TW infection has been reported in cancer patients, co-infection with Nocardia is a unique occurrence in this case. Opportunistic pathogens are common in immunocompromised patients but in this case, the patient was a young adult with normal immunity and an early-stage tumor with TW and Nocardia co-infection. We demonstrated the presence of rare microorganisms through imaging findings, combined with different staining methods of bronchoalveolar lavage fluid and lung tissue sections and evaluation of morphological characteristics. The aim of the present study was to provide early diagnosis and treatment of patients by improving microbial morphological detection. [ABSTRACT FROM AUTHOR]

One of the most widely used medications for epilepsy is the broad-spectrum antiseizure levetiracetam. The study aimed to evaluate the impact of levetiracetam on the bodyweight and liver of pregnant rats and their offspring. The study involved treating the rats during pregnancy and lactation and then examining the pregnant rats and their offspring. Two groups of 40 pregnant rats were created (I, II). Each group was split up into two smaller groups (A, B). About 1.5 mL/day of distilled water was gavaged to the rats in group I, either continuously throughout pregnancy (IA) or continuously throughout pregnancy and 15 days after delivery (IB). Group II rats received 1.5 ml/day of distilled water (containing levetiracetam) either during pregnancy (IIA) or during pregnancy plus 15 days postpartum (IIB). At the end of the work, blood samples were taken from the adult rats, body weight of different groups were recorded, and then, their liver was subjected for histological and morphometric analysis. Levetiracetam treatment showed reduction in the body weight of adult rats and their offspring and pathological changes in their liver. These changes were in the form of distortion of the hepatic architecture, cytoplasmic vacuolation, nuclear changes, and swollen mitochondria with loss of their cristae. Such changes were proved by alteration in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels of the liver. It is advised to monitor the liver functions continuously when using levetiracetam. [ABSTRACT FROM AUTHOR]

This study was performed to explore in detail the toxic effects of Tributyltin Chloride (TBT) on the pituitary-testicular axis and the possible amelioration with Hesperidin. Seventy-two adult male albino rats were divided into four groups: Control group (I), TBT-treated group (II), TBT+Hesperidin group (III), and Recovery group (IV). Body and testicular weights were measured. Blood samples were taken to estimate serum levels of testosterone, FSH and LH hormones by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) level was measured in testes homogenates. Tissue samples from the pituitary glands and testes were processed for light, electron microscope examination, and immunohistochemical detection of anti-FSH, and Ki67 proteins. Results showed a statistically significant decrease in testicular weight, serum testosterone, FSH and LH levels and a significant increase in tissue MDA in the TBT group when compared to the control group. TBT treatment caused severe histopathological changes with decreased area percent of PAS-stained basophils, and anti FSH immuno-stained gonadotrophs in the pituitary gland. The testes of group II also showed marked tissue damage, cell loss with decreased epithelial height and decreased number of proliferating spermatogenic cells. Hesperidin supplementation with TBT proved significant amelioration of the previously mentioned parameters in both glands which could improve male fertility. In conclusion: The flavonoid Hesperidin has the potential to protect against the reproductive damage induced by TBT in susceptible individuals. [ABSTRACT FROM AUTHOR]

The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5 g/kg/day), Myl (200 mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities. [ABSTRACT FROM AUTHOR]

The rise in respiratory disease has been attributed to an increase in environmental pollution. Heavy metals contribute to environmental contamination via air, water, soil and food. The effects of atmospheric exposure to heavy metals on pulmonary structure and function have been researched, but the effects through drinking water have been neglected. The aim of this study was to investigate the potential in vivo alterations in the pulmonary tissue of male Sprague-Dawley rats after a 28-day oral exposure to copper (Cu), manganese (Mn) and mercury (Hg), alone and in mixtures, at 100 times the World Health Organization's (WHO) safety limit for each heavy metal in drinking water. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups (n = 6): control, Cu, Mn, Hg, Cu + Mn, Cu + Hg, Mn + Hg and Cu, Mn + Hg. The morphology of lung tissue and the bronchioles were evaluated using light- and transmission electron microscopy. For all exposed groups, morphological changes included thickened inter- and intra-alveolar spaces, stratified epithelium, disrupted smooth muscle and early fibrosis and desquamation of the epithelia of the bronchioles to varying degrees. In all exposed groups, ultrastructurally, an increase in disarranged collagen and elastin fibers, nuclear membrane detachment, chromatin condensation, indistinct nucleoli and an increase in collagen fiber disarrangement was observed. This study has identified that oral exposure to Cu, Mn and Hg and as part of mixtures caused pathogenesis due to inflammation, cellular damage and fibrosis with Mn + Hg being the most potent heavy metal group. [ABSTRACT FROM AUTHOR]

The association between uterine smooth muscle fibroids and systemic arterial hypertension is poorly understood. Therefore, we explored possible concomitant myocyte pathology of systemic resistance-sized arterioles (200 to 400 μm), isolated from omental samples donated by 19 women (mean age 42 y; SE 1) undergoing fibroid surgery. Vessels of 17 women (8 hypertensives) were available for transmission electron microscopy. We found ultrastructural vessel wall abnormalities in all patients, albeit with greater severity in hypertensives. In the endothelium, this ranged from moderate mitochondrial and endoplasmic reticulum stress in normotensives, to necrosis and sloughing in hypertensives. Myocyte-like cells were observed to migrate across the internal elastic lamina, with isolated subendothelial myocytes in normotensives, and focal subendothelial multicellular aggregates or myo-intimal "cushions" in hypertensives. Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria, and myofilament loss involving focal areas or entire cells. To our knowledge, the first study on the ultrastructure of systemic resistance arterioles of women with fibroids indicates that severe abnormalities are present that likely affect blood pressure regulation. Whether these perturbations are induced by fibroids, or represent systemic pathology that affects myocytes of both uterine and vascular tissue warrants further exploration. [ABSTRACT FROM AUTHOR]