Connexins and Gap Junctions in Cancer of the Urinary Tract

This review focuses on connexins and nexus or gap junctions in the genesis, progression, and therapy of carcinomas of the human urinary tract. Some decades ago, the idea was born that gap junctional intercellular communication might prevent both the onset and the progression of cancer. Later evidence indicated that, on the contrary, synthesis and the presence of connexins as a prerequisite for gap junctional intercellular communication might promote the occurrence of cancer and metastases. The research history of urinary bladder cancer is a good example of the development of scientific perception. So far, the role of gap junctional intercellular communication in carcinogenesis and cancer progression, as well as in therapeutical approaches, remains unclear

Minireview and case report: Duplication of the portal vein and combinations

This is a minireview and case report on a concurrent duplication of the portal vein and a duplication of the left renal vein. The portal vein system supplies about seventy five percent of the blood for the liver and is involved in the manifestation of several liver diseases such as portal hypertension and portosystemic shunts. The vitelline veins and their anastomoses are involved in this anatomical variation during development. Similar to that also variations or malformations of the renal veins resulted from early primitive structures and their obliteration or non obliteration, respectively. Two rather rare anomalies of two venous systems might have been a coincidence or a common cause

UV-C Irradiation Reduces the Experimentally Induced Bacterial Load on the Surface of a Human Cadaver: An Additional Option for the Preservation of Cadavers in Anatomy

Safety is a major issue in the embalming procedures of human cadavers. Reduced application of formaldehyde is often recommended. The aim of this study was to investigate the potency of ultraviolet light (UV-C irradiation) on the bacterial load on the surface of a conserved human cadaver. To test UV-C irradiation, the cadaver was laid out in the dissection hall and, after preparation of the muscles, was covered with linen sheets moistened with water. Swabs of the surface and microbiological analysis revealed sporadic bacterial colonies. The surface area was then spiked with bacteria and irradiated by a UV lamp for 15 or 60 min. Half of the area was covered by aluminum foil to serve as a control. After exposition, swabs were taken and analyzed. The exposition had reduced the number of colonies to one third (15 min exposition) and to one tenth (60 min exposition) of the control area. Thus, UV-C irradiation could be used in the preservation of cadavers without chemical pollution of the environment and without any risk for the employees. Clin. Anat. 32:113–116, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care

What is the clinical relevance of different lung compartments?

The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense

Facets of Communication: Gap Junction Ultrastructure and Function in Cancer Stem Cells and Tumor Cells

Gap junction proteins are expressed in cancer stem cells and non-stem cancer cells of many tumors. As the morphology and assembly of gap junction channels are crucial for their function in intercellular communication, one focus of our review is to outline the data on gap junction plaque morphology available for cancer cells. Electron microscopic studies and freeze-fracture analyses on gap junction ultrastructure in cancer are summarized. As the presence of gap junctions is relevant in solid tumors, we exemplarily outline their role in glioblastomas and in breast cancer. These were also shown to contain cancer stem cells, which are an essential cause of tumor onset and of tumor transmission into metastases. For these processes, gap junctional communication was shown to be important and thus we summarize, how the expression of gap junction proteins and the resulting communication between cancer stem cells and their surrounding cells contributes to the dissemination of cancer stem cells via blood or lymphatic vessels. Based on their importance for tumors and metastases, future cancer-specific therapies are expected to address gap junction proteins. In turn, gap junctions also seem to contribute to the unattainability of cancer stem cells by certain treatments and might thus contribute to therapeutic resistance

Lipopolysaccharide induced inflammation in the perivascular space in lungs

<p>Abstract</p> <p>Background</p> <p>Lipopolysaccharide (LPS) contained in tobacco smoke and a variety of environmental and occupational dusts is a toxic agent causing lung inflammation characterized by migration of neutrophils and monocytes into alveoli. Although migration of inflammatory cells into alveoli of LPS-treated rats is well characterized, the dynamics of their accumulation in the perivascular space (PVS) leading to a perivascular inflammation (PVI) of pulmonary arteries is not well described.</p> <p>Methods</p> <p>Therefore, we investigated migration of neutrophils and monocytes into PVS in lungs of male Sprague-Dawley rats treated intratracheally with <it>E. coli </it>LPS and euthanized after 1, 6, 12, 24 and 36 hours. Control rats were treated with endotoxin-free saline. H&E stained slides were made and immunohistochemistry was performed using a monocyte marker and the chemokine Monocyte-Chemoattractant-Protein-1 (MCP-1). Computer-assisted microscopy was performed to count infiltrating cells.</p> <p>Results</p> <p>Surprisingly, the periarterial infiltration was not a constant finding in each animal although LPS-induced alveolitis was present. A clear tendency was observed that neutrophils were appearing in the PVS first within 6 hours after LPS application and were decreasing at later time points. In contrast, mononuclear cell infiltration was observed after 24 hours. In addition, MCP-1 expression was present in perivascular capillaries, arteries and the epithelium.</p> <p>Conclusion</p> <p>PVI might be a certain lung reaction pattern in the defense to infectious attacks.</p

Corneae from body donors in anatomy department: valuable use for clinical transplantation and experimental research

Background: Explanted corneae are highly needed for the surgical management of patients with severe corneal diseases. The aim of this study was to determine whether the body donors from the Institute of Anatomy are a suitable source of donor corneae. Methods: At the Institute of Anatomy at Saarland University Medical Center in Homburg, corneae are prelevated from body donors who had consented to the removal of tissues for transplantation purposes during their lifetime. Following the report of death, the LIONS Eye Bank is informed and the contraindications of corneal explantation are clarified. Obtaining a blood sample within 24 h postmortem is mandatory. Results: The Institute of Anatomy had 150 body donors in the time period from January 2018 to June 2019. Out of these, 68 (45.3%) were reported to the Eye Bank. The age of the donors (median 82 years (range: 57–96)) is not critical since the quality of the corneae depends on the number of endothelial cells (mean: 2109 ± 67 cells/mm2 (range: 511–2944 cells/mm2)). Contraindications were present in 19 (12.6%) cases. The corneae were extracted from 49 (32.7%) body donors. Out of these 98 corneae, 46 (46.9%) were successfully transplanted. Of all non-transplanted corneae, 6 (6.1%) were microbiologically contaminated, 10 (10.2%) had a positive serology, 22 (22.5%) had an endothelial cell count < 2000 cells/mm2 and 6 (6.1%) are at time of this analysis still in culture medium. The non-transplanted tissues were used for research. Conclusions: Explanted corneae from the Institute of Anatomy are a valuable option in obtaining grafts for corneal transplantation, which is why we are working toward on expanding cooperation with this department

Elderly with Varying Extents of Cardiac Disease Show Interindividual Fluctuating Myocardial TRPC6-Immunoreactivity

Both particular myocardial locations in the human heart and the canonical transient receptor potential 6 (TRPC6) cation channel have been linked with cardiac pathophysiologies. Thus, the present study mapped TRPC6-protein distribution in select anatomic locations associated with cardiac disease in the context of an orienting pathological assessment. Specimens were obtained from 5 body donors (4 formalin fixation, 1 nitrite pickling salt-ethanol-polyethylene glycol (NEP) fixation; median age 81 years; 2 females) and procured for basic histological stains and TRPC6- immunohistochemistry. The latter was analyzed descriptively regarding distribution and intensity of positive signals. The percentage of positively labelled myocardium was also determined (optical threshold method). Exclusively exploratory statistical analyses were performed. TRPC6-protein was distributed widespread and homogenously within each analyzed sample. TRPC6-immunoreactive myocardial area was comparable regarding the different anatomic regions and sex. A significantly larger area of TRPC6-immunoreactive myocardium was found in the NEP-fixed donor compared to the formalin fixed donors. Two donors with more severe heart disease showed smaller areas of myocardial TRPC6-immunoreactivity overall compared to the other 3 donors. In summary, in the elderly, TRPC6-protein is widely and homogenously distributed, and severe cardiac disease might be associated with less TRPC6-immunoreactive myocardial area. The tissue fixation method represents a potential confounder