Age-related involution and terminal disorganization of the human thymus

The terminal involution pattern of the human thymus was studied based on autopsy cases (both sexes, age range 63-91 years). Large sections through the entire thymic fat body were examined with the help of both conventional histological and immunohistochemical techniques. The findings demonstrate that thymic atrophy in old humans (a) goes far beyond the degree of involution observed in small rodents; (b) results in a system of thin, branching, in part interrupted, non-keratinizing epithelial plates containing no typical Hassall bodies; (c) concerns all components of the thymus except fat tissue which progressively replaces original thymic structures; and (d) involves various types of disorganization of individual lobules with T and B lymphocytes often located outside rather than within epithelial remnants. Effects of low-level radiation on this final regression of the human thymus are unknown.     

Age-related characteristics of the human acromioclavicular joint

By birth in the acromioclavicular joint the acromial end of the clavicle is osseous, and the acromion of the scapula is cartilaginous. The most intensive formation of the relief and configuration of the articular surfaces of the joint occurs from 1 to 3 years of age. In mature persons the form of the articular surface of the acromial end of the clavicle is often oval and that of the acromion of the scapula--ellipsoid. In newborns the areas of the articular surfaces are nearly equal. The area of the articular surface of the acromial end of the clavicle is significantly more than that of the acromion of the scapula during the periods from 1 to 3, from 13 to 17 and from 21 to 30 years of age. The articular cleft is revealed in the roentgenograms by 17 years of age, when synostosis process of the acromion of the scapula is completed. The thickness of the articular cartilage at different poles of the articular surfaces from birth up to 70 years of age is not equal and therefore it is possible to judge about nonequivalent functional loading on different areas of the articular cartilage. The articular cartilage of the acromial end of the clavicle from birth to 16 years of age is hyaline, after 17 years of age, they acquire the structure of the fibrous cartilage. In the articular cartilage of the acromion of the scapula, this rearrangement is realized more slowly: its fibrous structure is revealed after 23-24 years of age. Involutional changes in the joint are revealed during the fourth decade.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related decrease of somatostatin receptor number in the normal human thymus

The thymus exhibits a pattern of aging oriented toward a physiological involution. The structural changes start with a steady decrease of thymocytes, whereas no major variations occur in the number of thymic epithelial cells (TEC). The data concerning the role of hormones and neuropeptides in thymic involution are equivocal. We recently demonstrated the presence of somatostatin (SS) and three different SS receptor (SSR) subtypes in the human thymus. TEC selectively expressed SSR subtype 1 (sst(1)) and sst(2A). In the present study we investigated whether SSR number is age related in the thymus. Binding of the sst(2)-preferring ligand (125)I-Tyr(3)-octreotide was evaluated in a large series of normal human thymuses of different age by SSR autoradiography and ligand binding on tissue homogenates. The score at autoradiography and the number of SSR at membrane homogenate binding (B(max)) were inversely correlated with the thymus age (r = -0.84, P < 0.001; r = -0.82, P < 0.001, respectively). The autoradiographic score was positively correlated with the B(max) values (r = 0.74, P < 0.001). Because the TEC number in the age range considered remains unchanged, the decrease of octreotide binding sites might be due to a reduction of sst(2A) receptor number on TEC. The age-related expression of a receptor involved mainly in controlling secretive processes is in line with the evidence that the major changes occurring in TEC with aging are related to their capabilities in producing thymic hormones. In conclusion, SS and SSR might play a role in the involution of the human thymus. These findings underline the links between the neuroendocrine and immune systems and support the concept that neuropeptides participate in development of cellular immunity in humans.     

Age-related characteristics of capsular angioarchitectonics of large human joints

Angioarchitectonics of 127 capsules of large joints in superior (brachial, ulnar, radiocarpal) and inferior (coxofemoral, genicular, talocrural) extremities have been studied using a complex of anatomical and histological techniques and morphometry. As demonstrate the investigations, in the fibrous and synovial membranes of the capsules in these joints, there are certain differences in the architectonics and in depth of the blood network arrangement. In accordance with the diameter of these vessels, density and character of distribution in the capsule membranes of the joints, it is possible to distinguish four circulatory networks. They have numerous anastomoses and form a united volumetric network of vessels. Certain general regularities are noted in the structure of the vascular networks of the capsule membrane in the extremity joints, as well as changes of their angioarchitectonics are revealed as adaptations to age morphofunctional changes in the connective tissue formations of the capsules.     

Structural and immunomorphological characteristics of the human thymus in embryogenesis]

The thymus glands from one hundred of 4--34-week-old human fetuses were studied by the histologic, histochemical, immunomorphologic and electron microscopic methods. The development of the organ is described from the standpoint of systemogenesis. The laying of the gland is defined at the 5th week of the fetus development, and it reflects the features of the epithelium of the head intestine organs. The differentiation of the reticuloepithelium, the population of the gland by lymphocytes and emergence of antigenic specificity on their surface state at the age of 7--8 weeks. The growth zone of the thymus reticuloepithelium, the significance of Hassal's bodies, the appearance and quantitative dynamics of two subpopulations of T-lymphocytes are described. From 11--12 till 34 weeks of fetal development the percentage of T-lymphocytes forming rosettes with sheep red blood cells virtually does not change (70--90%), while the percentage of lymphocytes forming rosettes with their own red cell increases during the same period from 23 to 70%.     

Age-related characteristics of the electrical activity of the cardiac fibers in the human embryo

Transmembrane action potential and intercellular electric coupling have been studied in isolated heart during various stages of intrauterine growth of human embryos as well as in heart preparations of human adults. Formation of electrical properties of ventricular myocardium was slower than that of atrial fibres and was found to be fully completed in the first 14 weeks of intrauterine growth. Intercellular electrical coupling enhanced in the course of the embryonic development as indicated by a drop in the input resistance and an increase in electronic length.     

Age-related hyperplasia of the thymus and T-cell system in the Buffalo rat

This report describes the development of hyperplasia of both the thymus and the peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats do not show age-related thymic involution, but rather develop thymic hyperplasia with advancing age. This thymic growth is expansile and there is no infiltration of the surrounding tissues. Because the enlarging thymus occupies the thoracic cavity, most of the rats die of respiratory failure by the age of 24 months. Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and the large number of proliferating lymphocytes. The hyperplastic epithelial cells are bizarre in shape and strongly positive when stained with Th-3 monoclonal antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes within the hyperplastic thymus are similar to those seen in young rats of other species. The high level of T-cell emigration from the thymus to the periphery appears to persist throughout life, since the percentage of normal splenic T-cells also increase with advancing age and exceed 70% of the total by 24 months of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial cells can be prevented by hypophysectomy.     

Age-related characteristics of the structure of renal arteries

The investigation has been performed on 337 preparations of human kidneys and on 129 clinical angiograms of kidneys at different age without renal and cardiovascular system pathology. A complex of morphological techniques, mathematical method including, has been used. Peculiarities in architectonics of the intraorganic renal arterial vessels have been described during various age periods of postnatal ontogenesis; essential variations of the renal artery index have been revealed in newborns and adolescents. They reflect functional rearrangement of the vessels during these age periods. Six periods in formation of the renal arterial intraorganic vessels have been determined, when probability of decrease and failure of their compensatory potentialities is especially great.     

Molecular aspects of stromal-parenchymal interactions in malignant neoplasms

Carcinomas are composed of parenchymal and stromal elements, and the malignant behavior is principally dictated by the cancer cells. However, the malignant tumors not merely grow into a preexisting interstitial tissue, but they actively form a new stroma and modify their composition. Thus, the tumor stroma is significantly different from that of the neighboring tissues. Cancer cells may alter their stroma by cell-to-cell contact, soluble factors or by modification of the extracellular matrix (ECM), they induce myofibroblast differentiation and govern the desmoplastic stroma reaction. On the other hand, the stromal cells (especially the myofibroblasts) are able to modify the phenotype, invasiveness, metastatic capacity of carcinomas, typically promoting the progression. Regarding pancreatic cancer, the pancreatic stellate cells (PSCs) seem to be the key elements in the cross-talk between the parenchymal cells and the desmoplastic stroma. The tumor stroma is also rich in tumor-associated macrophages (TAM), but their role in the malignant process is contradictory and may be different in various tumor types, but most studies suggest a negative impact on the tumor growth. The relationship between the parenchymal and stromal elements is highly complex, they mutually alter their characteristics. Because the neostroma of the carcinomas largely seems to promote the invasiveness of the malignant tumors, novel therapeutic strategies are being evaluated targeting the stromal elements, with some encouraging, but still fragmentary results.     

Age-related growth and protein turnover in the thymus of normal and glucocorticoid-treated rats

Possible derivatives of the amino acids tryptophan, tyrosine and histidine were examined as to their effect on protein metabolism in isolated rat hepatocytes. One of the substances tested, kynurenine (a main product of the catabolism of tryptophan), might be a physiological regulator of the lysosomal degradation of endogenous protein, because of the following. (a) Kynurenine decreased the lysosomal (i.e. methylamine-sensitive) pathway of degradation to a much greater extent than its parent amino acid, without interfering with the non-lysosomal pathway. (b) Kynurenine did not appreciably reduce the (lysosomal) degradation of the endocytosed protein asialo-fetuin, or the rate of protein synthesis, indicating a specificity of action. (c) Electron micrographs revealed a reduction in secondary lysosomes due to kynurenine.     

Age-related characteristics of the myeloarchitectonics of the peripheral nerves

By means of macromicroscopy and microscopy myeloarchitectonics of morphologically and functionally different somatic and visceral nerves (branches: mandibular nerve, cervical spinal nerves, inferior laryngeal nerve, hepatic plexus) have been studied in 11 age groups. During the prenatal period of ontogenesis asynchronism of myelogenesis is stated in various muscle branches of the nerves, dependent on formation of function in corresponding muscles and muscle groups. As demonstrate investigations on peculiarities of myelogenesis course in the somatic and visceral nerves studied, during the period of pre- and postnatal ontogenesis, its dynamics embraces three stages of myelogenesis, determined by G. B. Stovichek for visceral nerves: productive myelogenesis, stages of stabilization and involution. The stage of productive myelogenesis in the somatic nerves studied lasts up to the end of the adolescent period. Two phases are determined in it: the first lasts up to 2-3 years; the second--up to the end of the adolescent period and is characterized with a complete formation of the myelin fibers spectrum. In the visceral nerves studied increase of general amount of myelin fibers and their differentiation are completed simultaneously during the adolescent age. The stabilization stage of myeloarchitectonics of the nerves studied corresponds to the mature age (I and II periods) and the involution stage--to the elderly (and old) age.     

Age-related characteristics of postradiation regeneration of the blood system

This study was pursued on hybrid (CBA X C57Bl)F1 mice at the ages of 17 and 27 months irradiated at a dose of 4 Gy. It was shown that the postirradiation recovery of haemopoiesis in old mice was the same as in the young (2-3 month-old), and in some respects (for instance, granulocytic and erythroid cells of the bone marrow, and CFUc) the recovery was even more active exhibiting a period of a pronounced hyperregeneration.     

Age-related characteristics of RNA transport through the nuclear membrane

The effect of cytosol and ATP-regenerating system on RNA, transport was studied in isolated liver nuclei of adult and old rats. The stimulating effect of cytosol was found not to depend on the age of animals. The release of RNA from old rat liver nuclei activated by the ATP-regenerating system was more expressed compared to adult rats. It is assumed that the age changes of energy-delivering system of the RNA transport through nuclear membrane may be conditioned by the deficit of endogenous energetic substrates in the hepatic cells of old animals.     

Germinal centers in the human thymus

Summary This study reports the normal thymus of a 3 year old girl in which four germinal centers have been found in different lobules. They are located in the medulla, three of them in the cortico-medullary junction. Reticular cells, medium-sized and occasionally large lymphocytes, reticular macrophages and a large number of immature and mature thymocytes occupy the germinal centers. The medium-sized lymphocytes divide and give rise to smaller cells which appear to move to the peripheral zone to become thymocytes.     

Age-related characteristics of poststress DNA repair in the myocardium

It has been demonstrated that young and adult rats had age-associated differences in stress-induced lesions and in poststressor repair of DNA synthesis in the myocardium. In both age groups, the DNA repair systems perform an identical scope of work aimed at abolition of poststressor lesions with the difference that in young rats, the repair is completed 2 days and in adult rats 3 days after exposure to stress is discontinued.