E- and N-cadherin distribution in developing and functional human teeth under normal and pathological conditions

Cadherins are calcium-dependent cell adhesion molecules involved in the regulation of various biological processes such as cell recognition, intercellular communication, cell fate, cell polarity, boundary formation, and morphogenesis. Although previous studies have shown E-cadherin expression during rodent or human odontogenesis, there is no equivalent study available on N-cadherin expression in dental tissues. Here we examined and compared the expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth. Both proteins were expressed in the developing teeth during the cap and bell stages. E-cadherin expression in dental epithelium followed an apical-coronal gradient that was opposite to that observed for N-cadherin. E-cadherin was distributed in proliferating cells of the inner and outer enamel epithelia but not in differentiated cells such as ameloblasts, whereas N-cadherin expression was up-regulated in differentiated epithelial cells. By contrast to E-cadherin, N-cadherin was also expressed in mesenchymal cells that differentiate into odontoblasts and produce the hard tissue matrix of dentin. Although N-cadherin was not detected in permanent intact teeth, it was re-expressed during dentin repair processes in odontoblasts surrounding carious or traumatic sites. Similarly, N-cadherin re-expression was seen in vitro, in cultured primary pulp cells that differentiate into odontoblast-like cells. Taken together these results suggest that E- and N-cadherins may play a role during human tooth development and, moreover, indicate that N-cadherin is important for odontoblast function in normal development and under pathological conditions.     

The human renal lymphatics under normal and pathological conditions

AIMS: The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. METHODS AND RESULTS: Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. CONCLUSIONS: Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics.     

Asymmetry of human brain in early embryogenesis under normal and pathological conditions

The effect of some developmental abnormalities on the morphogenesis of human brain asymmetry during early embryonic stages was studied. Insignificant predominance of the left hemisphere (1–3%) was revealed in human embryos. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 442–444, October, 2000     

Leukocyte cytoskeleton under normal and pathological conditions

Like other cells, leukocytes have the cellular skeleton comprising microtubules, actine, myosine, and intermediate filaments. Elements of the cellular skeleton are connected with receptors on the plasma membrane surface and determine the distribution density of these receptors. There is functional relationship between microtubules and actine filaments, in particular, microtubules determine uniform distribution of actine filaments in the cell cytoplasm. The basic principle of functioning of the cellular skeleton consists of the process of polymerization and reversible depolymerization of proteins forming components of the cellular skeleton. These processes are regulated by Ca2+, calmoduline, as well as by the ratio of cyclic adenosine monophosphate and guanidine monophosphate in the cell. The cellular skeleton determines the most important functions of leukocytes: their mobility, binding and absorption of various substances, processes of degranulation, fusion of granules with phagocytic vacuole. Cellular skeleton defects are accompanied by recurrent bacterial infections. Several such defects are known: leukocyte actine dysfunction syndrome, Chediak-Higashi syndrome, syndrome with marked increase in the content of cGMP and microtubules in leukocytes. In these syndromes, the therapeutic effect is achieved with the substances which regulate the level of cyclic nucleotides in leukocytes, among them large doses of ascorbic acid.     

Sialosyl-Tn expression in normal and pathological conditions of human endometrium. An immunohistochemical study

To assess the clinico-prognostic relevance of the cell surface carbohydrate glycoprotein in normal and pathological conditions of human endometrium, Sialosyl-Tn (STn) antigen was immunohistochemically studied in normal (n = 10), hyperplastic (n = 18), and neoplastic (n = 60) endometrial lesions. There was no STn antigen reactivity in the proliferative endometrial slides, while weak staining was observed in all secretory endometria. STn expression was noted in 8/18 (44%) hyperplastic endometrial cases and in 40/60 (67%) endometrial carcinomas. Positive staining was observed throughout the cytoplasm of the glandular cancer cells, at the cell membranes, and in an intraluminar mucus. This antigen was mostly expressed heterogeneously as far as the distribution of positive cells is concerned. There was a statistically significant association between STn expression and the histological grading of cancer (p = 0.019). Advanced clinical stage (III-IV; p = 0.014) and infiltration of the myometrial wall (more than 1/2 of the myometrial wall; p = 0.004), but no STn immunoreactivity, were reported to be independent prognostic variables during follow-up. Our study shows that a) STn is not constantly expressed during the menstrual cycle, and is increased at the secretory phase of the cycle; b) Sialosyl-Tn reactivity decreases with the degree of tumor differentiation, but there was no relationship with other clinicopathological variables of cancer; c) this cell surface carbohydrate glycoprotein does not appear to predict the outcome of endometrial cancer patients.     

Action of UV radiation on human blood serum under normal and pathological conditions

The effect of a broad UV spectrum on the level of diene conjugates in blood serum lipids of donors and of patients with various diseases was studied. The level of diene conjugates in the blood serum lipids of the donors rose after UV irradiation, whereas in patients with inflammatory diseases it fell. In patients with benign and malignant tumors UV irradiation had virtually no effect on the level of diene conjugates in the blood serum lipids. This method can be used for the development of differential diagnostic criteria for diseases of neoplastic and inflammatory nature.Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 427–429, April, 1977.     

Cytokeratin expression in cells of the rodent bile duct developing under normal and pathological conditions

A polyclonal anti-cytokeratin antibody has been used to examine the expression of this intermediate filament both during normal development in the rat and in a variety of pathological states in the rat and mouse. Bile duct proliferation induced by the administration of alpha-naphthylisothiocyanate (ANIT) as well as the oval cell proliferation induced by 3'-methyl-4-dimethylaminoazobenzene (3-MeDAB) have been used to examine the expression of the rodent cytokeratins in the proliferating cells regarded as being of bile duct origin. Examples of cholangiofibrosis and cholangiocarcinomas were also examined for evidence of cytokeratin expression using this antibody, as well as proliferations of a morphological intermediate type between epithelial and mesenchymal. In all cases we have been able to demonstrate continuity of phenotypic expression of the cytokeratins recognized by this antibody in cells which are recognized as bile duct in origin, even where their morphological appearance does not resemble an epithelial cell type. Because this antibody can be used on formalin-fixed, paraffin-processed tissues, after trypsin treatment, it is proposed that it can be used routinely in the toxicological evaluation (even retrospectively) of bile duct related proliferations and tumours.     

Cytokeratin expression in cells of the rodent bile duct developing under normal and pathological conditions.

A polyclonal anti-cytokeratin antibody has been used to examine the expression of this intermediate filament both during normal development in the rat and in a variety of pathological states in the rat and mouse. Bile duct proliferation induced by the administration of alpha-naphthylisothiocyanate (ANIT) as well as the oval cell proliferation induced by 3''-methyl-4-dimethylaminoazobenzene (3-MeDAB) have been used to examine the expression of the rodent cytokeratins in the proliferating cells regarded as being of bile duct origin. Examples of cholangiofibrosis and cholangiocarcinomas were also examined for evidence of cytokeratin expression using this antibody, as well as proliferations of a morphological intermediate type between epithelial and mesenchymal. In all cases we have been able to demonstrate continuity of phenotypic expression of the cytokeratins recognized by this antibody in cells which are recognized as bile duct in origin, even where their morphological appearance does not resemble an epithelial cell type. Because this antibody can be used on formalin-fixed, paraffin-processed tissues, after trypsin treatment, it is proposed that it can be used routinely in the toxicological evaluation (even retrospectively) of bile duct related proliferations and tumours.     

Distribution and expression of CD200 in the rat respiratory system under normal and endotoxin-induced pathological conditions

In vivo and in vitro studies have clearly demonstrated that signaling mediated by the interaction of CD200 and its cognate receptor, CD200R, results in an attenuation of inflammatory or autoimmune responses through multiple mechanisms. The present results have shown a differential expression of CD200 in the respiratory tract of intact rats. Along the respiratory passage, CD200 was specifically distributed at the bronchiolar epithelia with intense CD200 immunoreactivity localized at the apical surface of some ciliated epithelial cells; only a limited expression was detected on the Clara cells extending into the alveolar duct. In the alveolar septum, double immunofluorescence showed intense CD200 immunolabeling on the capillary endothelia. A moderate CD200 labeling was observed on the alveolar type II epithelial cells. It was, however, absent in the alveolar type I epithelial cells and the alveolar macrophages. Immunoelectron microscopic study has revealed a specific distribution of CD200 on the luminal front of the thin portion of alveolar endothelia. During endotoxemia, the injured lungs showed a dose‐ and time‐dependent decline of CD200 expression accompanied by a vigorous infiltration of immune cells, some of them expressing ionized calcium binding adapter protein 1 or CD200. Ultrastructural examination further showed that the marked reduction of CD200 expression was mainly attributable to the loss of alveolar endothelial CD200. It is therefore suggested that CD200 expressed by different lung cells may play diverse roles in immune homeostasis of normal lung, in particular, the molecules on alveolar endothelia that may control regular recruitment of immune cells via CD200‐CD200R interaction. Additionally, it may contribute to intense infiltration of immune cells following the loss or inefficiency of CD200 under pathological conditions.     

Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.     

Microenvironment of the peripheral nervous system under normal and pathological conditions

The peripheral nervous system (PNS) is composed of neurons and their processes which are located in a special fluid microenvironment. As is well known, complex biological functions such as those going on in peripheral nerves are best carried out when there is homeostasis, i.e., in a constant internal milieu. This paper is concerned with the maintenance of the homeostasis in the PNS under normal and pathological conditions. Diffusion barriers located in the intrinsic vessels of the PNS and the perineurium have the capacity to regulate the environment around the nerve fibers and to keep it away from the blood and the extracellular fluid outside the PNS. Endoneurial vascular permeability has similarities to that in the central nervous system, but compared with the blood-brain barrier the blood-nerve barrier is less efficient. This implies that toxic and infectious agents as well as some drugs have easier access to the parenchyma in nerves than to the brain parenchyma. However, ganglionic vessels lack an efficient vascular barrier to many substances which is important in intoxications caused by, e.g., doxorubicin, lead, mercury, and cadmium. It has also a significance in herpes zoster infection and presumably in Guillain-Barré syndrome. The diffusion barriers may themselves be influenced by pathologic processes and can then respond with an increased permeability. This may lead to the formation of edema in the PNS, i.e., one of the cardinal features of many diseases in nerves of traumatic, toxic, and inflammatory nature. Such a response had negative as well as positive implications. Severe edema may disturb the normal microcirculation in the endoneurial vessels and stimulate collagen production and fibrosis. However, the presence of a protein-rich endoneurial edema may well be important in repair processes such as reduplication of Schwann cells and growth of axons.