Diabetic Nephropathy and Extracellular Matrix

Diabetic nephropathy (DN) is a serious complication in diabetes. Major typical morphological changes are the result of changes in the extracellular matrix (ECM). Thus, basement membranes are thickened and the glomerular mesangial matrix and the tubulointerstitial space are expanded, due to increased amounts of ECM. One important ECM component, the proteoglycans (PGs), shows a more complex pattern of changes in DN. PGs in basement membranes are decreased but increased in the mesangium and the tubulointerstitial space. The amounts and structures of heparan sulfate chains are changed, and such changes affect levels of growth factors regulating cell proliferation and ECM synthesis, with cell attachment affecting endothelial cells and podocytes. Enzymes modulating heparan sulfate structures, such as heparanase and sulfatases, are implicated in DN. Other enzyme classes also modulate ECM proteins and PGs, such as matrix metalloproteinases (MMPs) and serine proteases, such as plasminogen activator, as well as their corresponding inhibitors. The levels of these enzymes and inhibitors are changed in plasma and in the kidneys in DN. Several growth factors, signaling pathways, and hyperglycemia per se affect ECM synthesis and turnover in DN. Whether ECM components can be used as markers for early kidney changes is an important research topic, whereas at present, the clinical use remains to be established.     

Comparison of radiologic and gross examination for detection of cancer in defleshed skeletons

The reliability of visual examination of defleshed bones was assessed for detection of postcranial metastatic disease in individuals known to have had cancer. This was compared with standard clinical radiologic techniques. The skeletons of 128 diagnosed cancer patients from an early 20th century autopsied skeletal collection (Hamann-Todd Collection) were examined. Radiologic examination detected evidence of metastatic disease in 33 individuals, compared to 11 by visual examination of the postcranial skeletons. Four of these cases were detected by both techniques. Blastic lesions were most commonly overlooked on visual examination, because they were localized to trabecular (internal bone) structures. The ilium was the most commonly affected bone, with lytic or blastic lesions detected in 30 of 33 individuals. While the proximal femur was affected in only nine individuals, x-ray of the proximal femur and ilium detected all individuals with postcranial evidence of metastatic disease. Skeletal distribution of metastases provides no clue to the location of origin or histologic subtype of the cancer. Survey of archeological human remains for metastatic cancer requires radiologic examination. Such skeletal surveys should x-ray at least the ilia and femora. © 1995 Wiley-Liss, Inc.     

Tissue microarrays: fast-tracking protein expression at the cellular level

Tissue microarrays maximize returns in cellular pathology whilst minimizing the use of cells and tissues. They are made by arraying cores of tissue taken from multiple donor blocks into a single recipient block. Accordingly, the histology and pathology of several hundred tissues can be represented in one tissue microarray that, when stained by immunohistochemistry, provides comprehensive topographic information on protein expression. Used with complimentary techniques, such as complementary DNA microarray analysis, tissue microarrays are providing valuable data for the identification of new markers of disease and assisting in the discovery of therapeutic targets. They are also leading a revolution in cellular pathology as high-throughput technology is introduced to maximize the information provided.     

Paleopathology and the origin of agriculture in the Levant

This study addresses changes in health which were consequential to the Neolithic transition in the southern Levant, judged on the basis of the study of specific and nonspecific stress indicators, trauma, and degenerative joint disease in 200 Natufian (hunter‐gatherer) skeletons (10,500–8300 BC) and 205 Neolithic (agricultural) skeletons (8300–5500 BC) from the southern Levant. The comparison of the health profiles of pre‐Neolithic (Natufian) and Neolithic populations reveals a higher prevalence of lesions indicative of infectious diseases among the Neolithic population, and an overall reduction in the prevalence of skull trauma among males. No change over time was observed in the prevalence of degenerative joint disease. These results indicate that in the southern Levant the Neolithic transition did not simply lead to an overall deterioration in health but rather resulted in a complex health profile which was shaped by 1) an increase exposure to disease agents, 2) changes in diet, 3) population aggregation in larger and denser settlements, 4) changes in activity patterns and the division of labor, and possibly 5) a higher resistant immunological system and response capacity to environmental aggressions (mainly infections). Am J Phys Anthropol 143:121–133, 2010. © 2010 Wiley‐Liss, Inc.     

Role of the parasporal body in causing toxicity of Bacillus thuringiensis toward Aedes aegypti larvae

A unique type of microorganism has been found causing an unusual disease in larvae of the clover cutworm, Scotogramma trifolii (Lepidoptera; Noctuidae). The organism contains DNA and reproduces exclusively by self-assembly forming enveloped reniform/bacilliform particles which measure 170 × 450 nm in negatively stained preparations. During initial stages of development, the organism apparently reproduces primarily within vesicles in the cytoplasm of a variety of cell types including hemocytes, and epidermal, fat body, and tracheal matrix cells. Most reproduction, however, occurs in vesicles that circulate in the hemolymph. These vesicles, most of which are derived from host cells, measure 2–10 μm in diameter, are highly refractile, reach populations as high as 10⁸/ml of hemolymph, and are diagnostic for the disease. The pathology caused by this organism, its shape and ultrastructure, and reproduction within vesicles indicate it is either a peculiar type of rickettsia, possibly related to those of the genus Rickettsiella, or a new type of invertebrate virus. Among its unusual features are its ability to induce the formation of reproductive vesicles from host cell components, and its apparent control of de novo ribosome and membrane synthesis within these vesicles as it develops. The possible relationship of this organism to baculoviruses and rickettsia is discussed.     

Aortic dissection in a gorilla

Autopsy findings in a 39-year-old male gorilla included aortic dissection, internal rupture of the aortic arch with axial direction of the tear, external rupture of the ascending aorta, cardiac tamponade, myocardial hypertrophy, cystic and basophilic degeneration of the aortic media, marked obesity, severe degenerative joint disease, focal glomerulonephritis, and widespread hemosiderosis.     

Nongranular vasopressin synthesis and transport in early stages of rehydration

Summary The vasopressin system of the rat was examined in the course of the first 12 h of rehydration after prolonged thirst at light and electron microscopic levels and by use of the peroxidase anti-peroxidase (PAP) method. Light microscopically, the median eminence was the only part of the system that not only displayed distinct differences between animals of different rehydration times but also showed a characteristic pattern of immunohistochemical reactivity in its rostro-caudal distribution. Ultrastructurally, in the perikarya a maximal labeling of the rough endoplasmic reticulum was observed after 2 h of rehydration, whereas an extensive labeling of the enlarged Golgi zones was attained after 4 h of resupplying water. A labeling of the intercellular clefts in the basal glial labyrinth of the supraoptic nucleus (and to a lesser degree in the subependymal neuropil adjacent to the paraventricular nucleus) was increased 30 min after the onset of drinking, as compared with water-deprived animals; it decreased slightly after 12 h of rehydration. The filling of the swollen fibers by increasing amounts of labeled axoplasmic reticulum, evident in the nuclear areas already after 30 min of water supply, begins in the median eminence after 2 h of rehydration and is fully developed after 4 and 8 h. Corresponding results hold true for the neural lobe but are somewhat delayed in comparison to the findings in the median eminence. The discussion considers (i) synthesis and transport of nongranular vasopressin within the axoplasmic reticulum, and (ii) release not only from the neural lobe but also from the nuclear areas and from the fibers of the median eminence.Supported by the Deutsche Forschungsgemeinschaft (Grant Nr. Kr 569/3) and Stiftung Volkswagenwerk     

Quantitative imaging approaches to understanding biological processing of metal ions

Faster, more sensitive, and higher resolution quantitative instrumentation are aiding a deeper understanding of how inorganic chemistry regulates key biological processes. Researchers can now image and quantify metals with subcellular resolution, leading to a vast array of new discoveries in organismal development, pathology, and disease. Metals have recently been implicated in several diseases such as Parkinson's, Alzheimers, ischemic stroke, and colorectal cancer that would not be possible without these advancements. In this review, instead of focusing on instrumentation we focus on recent applications of label-free elemental imaging and quantification and how these tools can lead to a broader understanding of metals role in systems biology and human pathology.     

Taking a look on fungi in cystic fibrosis: More questions than answers

Cystic fibrosis (CF) is one of the most frequent recessive inherited diseases in western countries. Advances in medical care have led to a substantial increase in the life expectancy of CF patients. Survival beyond adolescence has permitted to see fungi not only as late colonizers, but also as potential pathogens responsible of allergic reactions and chronic infections related to lung function deterioration. The role of fungi, nevertheless, has been overlooked until recently. As a result, a number of questions on their epidemiology, clinical significance, or diagnosis, among others, remain unanswered. Besides more in depth studies about the extent of the deleterious effect of fungi on the CF host, new technologies may provide the key to understand its pathogenic role, its interaction with other microbial components of the respiratory microbiota, and should pave the way to define subsets of patients at risk who would benefit from specific therapy. This review is intended to provide a quick overview on what we know about the presence of fungi in the CF airway and its repercussion in the host, and to point out some of the many knowledge gaps needed to understand and advance in the management of fungi in the airway of CF subjects.