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H E Kaiser

Publications and source records attributed to H E Kaiser.

143 records · Page 8Linked to original sources
PubMedDate not supplied

Racial variation in lung cancer.

Lung cancer claimed about 153,000 lives in 1994 in the United States. Despite research overall lung cancer survival has still not improved during the last 20 years, with 5-year relative survival remaining about 13%. In addition several epidemiologic and molecular studies showed a difference in the incidence of lung cancer in the three major races. The aim of our study was to investigate the variations of race in lung cancer patients, in order to identify potential risk factors linked to the different racial status. In this light we compared a 10 years lung cancer data of black population from Howard University Hospital, Washington D.C., U.S.A. and a 20 years data of white population from the Vienna University Hospital, Austria. Our results did not show any significant difference in mean age or tumor localization in both groups, but highlighted a remarkable difference in the incidence of the lung cancer histological types also according to the sex. In this respect it could be more successful to consider carcinogenesis like a protracted process of gene function deregulation in response to cell injury from exposure to genotoxic substances with individual specificity.

Adult↗
PubMedDate not supplied

Ethnic variations in lung cancer.

Cancer of the lung is the most frequent cancer in the world, but with wide geographical variation in risk. It is most spread among males of all races worldwide, the only exception being its incidence among Chinese women aged 70 years and older. When comparing the different ethnic groups we have to consider that besides inhaling cigarette smoke actively or as a passive smoker the exposure to occupational carcinogens varies considerably according to different work places. In our study we compared 10 years of data from African-Americans in Howard University Hospital, Washington D.C. with 20 years of data from the white population in the University Hospital of Vienna, Austria. Ethnic patterns are generally consistent within each group in terms of both incidence and mortality. The difference in susceptibility between the sexes, the three major racial groups and already proven differences in genetic variations indicate the difference between individuals concerning the initiation and progression of lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Dendritic type, accessory cells within the mammalian thymic microenvironment. Antigen presentation in the dendritic neuro-endocrine-immune cellular network.

During mammalian ontogenesis, the thymic "pure" endodermal epithelial anlage develops and differentiates into a complex cellular microenvironment. Beginning the 7-8th week of intrauterine development, thymic epithelial cells chemotactically regulate (induce) numerous waves of migration of stem cells into the thymus, including the CD34+, yolk sac-derived, committed hematopoietic stem cells. In vitro experiments have established that CD34+ CD38dim human thymocytes differentiate into T lymphocytes when co-cultured with mouse fetal thymic organs. Hematopoietic stem cells for myeloid and thymic stromal dendritic cells (DCs) are present within the minute population of CD34+ progenitors within the mammalian thymus. The common myeloid, DC, natural killer (NK) and T lymphocyte progenitors have also been identified within the CD34+ stem cell population in the human thymus. Interactions between the endocrine and immune systems have been reported in various regions of the mammalian body including the anterior pituitary (AP), the skin, and the central (thymus) and peripheral lymphatic system. The network of bone marrow derived DCs is a part of the reticuloendothelial system (RES) and DCs represent the cellular mediators of these regulatory endocrine-immune interactions. Folliculo-stellate cells (FSC) in the AP, Langerhans cells (LCs) in the skin and lymphatic system, "veiled" cells, lympho-dendritic and interdigitating cells (IDCs) in a number of tissues comprising the lymphatic system are the cell types of the DC meshwork of "professional" antigen presenting cells (APCs). Most of these cells express the immunocytochemical markers S-100, CD1. CD45, CD54, F418, MHC class I and II antigens, Fc and complement receptors. FSCs are non-hormone secreting cells which communicate directly with hormone producing cells, a form of neuro-endocrine-immune regulation. As a result, an attenuation of secretory responses follows stimulation of these cells. FSCs are also the cells in the AP producing interleukin-6 (IL-6), and they have also been identified as the interferon-gamma responsive elements. FSCs also express lymphatic DC markers, such as DC specific aminopeptidase, leucyl-beta-naphthylaminidase, non-specific esterase, MHC class I and II molecules and various other lymphatic immunological determinants [platelet derived growth factor-alpha chain (PDGF-alpha chain), CD13, CD14 and L25 antigen]. There is strong evidence that such DCs in the AP, and similar ones in the developing thymus and peripheral lymphatic tissue are the components of a powerful "professional" antigen presenting DC network. These APCs contain a specialized late endocytic compartment, MIIC (MHC class II-enriched compartment), that harbors newly synthesized MHC class II antigens en route to the cell membrane. The limiting membrane of MIIC can fuse directly with the cell membrane, resulting in release of newly secreted intracellular MHC class II antigen containing vesicles (exosomes). DCs possess the ability to present foreign peptides complexed with the MHC molecules expressed on their surfaces to naive and resting T cells. There are a number of "molecular couples" that influence DC and T lymphocyte interaction during antigen presentation: CD/1/CD18 integrins, intercellular adhesion molecules (ICAMs), lymphocyte function associated antigen 3 (LFA-3). CD40, CD80/B7-1, CD86/B7-2, and heat-stable antigen. The "molecular couples" are involved in adhesive or co-stimulatory regulations, mediating an effective binding of DCs to T lymphocytes and the stimulation of specific intercellular communications. DCs also provide all of the known co-stimulatory signals required for activation of unprimed T lymphocytes. It has been shown that DCs initiate several immune responses, such as the sensitization of MHC-restricted T lymphocytes, resistance to infections and neoplasms, rejection of organ transplants, and the formation of T-dependent antibodies. (ABSTRACT TRUNCATED)

Animals↗
PubMedDate not supplied

Involution of the mammalian thymus, one of the leading regulators of aging.

During the past century of research on the thymus, the fact that every mammalian thymus undergoes marked morphological changes during the complex process of aging has been defined as a basic histogenetical rule. In characterizing the physiological (i.e. chronic) involution of the mammalian thymus, the term "Altersinvolution" referring to age-related involution is used. All other types of thymic involution are associated with an initial trigger and a relatively "acute" mechanism. In all of these factor-dependent cases of thymic involution, we use the term "akzidentelle Involution" (i.e. acute accidental thymic involution). Temporary thymic involution occurs during pregnancy, with a full restoration of the cellular microenvironment at the end of lactation. It is now clear that pregnancy alters the well established adaptational homeostasis between the neuroendocrine and immune axes. Such nonprogressive involution has also been observed during various seasons in various animals (i.e. seasonal involution). Changes characteristic of thymic involution begin during or soon after the first year of birth, and continue progressively throughout the entire life span. The 3% to 5% annual reduction rate of the cells of the human thymic microenvironment continues until middle age, when it slows down to less than 1% per year. According to the extrapolation of these results total loss of thymic reticuloepithelial tissue and the associated thymocytes should occur only at the age of 120 years in humans. This serious reduction of the thymic cellular microenvironment is a well controlled physiological process and is presumably under both local and global regulation by the cells of the RE meshwork and the neuroendocrine system, respectively. In humans, the age related decline in serum "facteur thymique sérique" (FTS) levels begins after 20 years of age and FTS completely disappears from the blood between the 5th and 6th decade of life. In contrast, the serum levels of thymosin-alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years of age. The influences of a variety of other hormones on the involution of the thymus have also been characterized: testosterone, estrogen and hydrocortisone treatment results in marked involution, cortisone and progesterone administration causes slight to moderate, while use of desoxycorticosterone has no effect. The experimental administration of thyroxine yielded dose dependent results: low doses resulted in thymic hypertrophy, higher doses produced slight hypertrophy and the highest employed doses caused thymic atrophy. The atrophy was of apicnotic type, very different from that detected after treatment with corticoid hormones. Thymus transplantation experiments indicate that age-related, physiological thymic involution has been genetically preprogrammed. Grafting of the thymus from one week old C3H leukemic strain mice into 6 month old hosts resulted in changes in thymic weight and an involution pattern that was synchronous in all recipients, in direct correlation with the glands in the donor, but not in the host. These data strongly suggest that the stimulus for thymus cell proliferation and differentiation is genetically determined within the organ implant. Since the thymus is the primary T-lymphopoietic organ during ontogenesis in the mammalian organism, its age-related involution with the already mentioned morphological alterations can be held responsible only for a decline in antigen-specific T lymphocyte immune functions. Thymic involution and diminished T lymphocyte proliferation can be partially restored by thymic tissue transplantation or use of thymic hormones. The leading physiological role of the thymic cellular microenvironment as a "clock" of the mammalian aging process is also discussed. "If present cells have come from pre-existing cells, then all cells can trace their ancestry back to the first formed cell in an unbroken line of descent."--Rudolf Virchow, 1858(1) "I have neve

Adaptation, Physiological↗
PubMedDate not supplied

Recent advances, prospects and problems in designing new strategies for oligonucleotide and gene delivery in therapy.

The field of gene therapy has been in rapid expansion since the first submissions of gene therapy trials in the early 1990s which provided encouraging results. Since then, many gene therapy protocols have been approved for phase I clinical trials for the treatment of inherited genetic diseases and cancer. The possibility of employing gene transfer technology to treat AIDS and neurologic diseases is currently under evaluation. Many gene delivery systems have been developed for in vivo studies and therapy. The efficiency of in vivo gene transfer, however, still needs to be optimized, even though significant advances have recently been achieved in improving gene delivery, gene regulation and avoidance of immune responses. This review provides a general outline focusing on the description of the most common gene delivery systems and on their current applications in therapeutics.

Adenoviridae↗
PubMedDate not supplied

The etiology of second primary neoplasms.

Neoplasms are derived from normal tissues of the body by cellular transformation. Tumors often represent a less differentiated or an undifferentiated version of the histology of the neoplasms original tissue. Primary tumor(s) may spread by direct extension or by metastasis. For the purpose of this review, second primary tumors will be defined to exclude metastatic lesions or recurrences from an original primary tumor. Second primary tumors arise in several different clinical situations that basically are the result of either inherited or acquired genetic mutations. Second primary tumors may develop soon or very late after treatment of the first primary tumor and may reflect an underlying genetic or immunologic defect in the patient, treatment related genetic damage, or environmental exposure to carcinogens. With the greater success of modern chemotherapy and radiotherapy in achieving long-term remissions in many patients, second primary tumors are a rapidly developing disease-category. This paper will review the clinical circumstances associated with a significantly higher incidence of second primary tumors in patients with an initial primary tumor.

Humans↗
PubMedDate not supplied

The spontaneous regression of neoplasms in mammals: possible mechanisms and their application in immunotherapy.

In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, with the mutation, loss or simple inactivation of the function of tumor suppressor genes, and the production of certain growth factors. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various cancers. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in the spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may be neither complete nor permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed.

Animals↗
PubMedDate not supplied

Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions.

Programmed cell death (PCD), also known as apoptosis, is a genetically controlled cellular response, manifested in morphologically distinct non-necrotic cellular destruction: cell shrinkage, cytoplasmic "boiling", condensation of chromatin, loss of nuclear membrane followed by DNA fragmentation and cell membrane blebbing, all of which initiate the formation of apoptotic bodies. During the early stages of PCD, cell membrane phospholipid asymmetry is altered, resulting in the dislocation of phosphatidylserine (PS) to the cell surface. During apoptosis, DNA is cut by endonucleases at DNA-linked sites between nucleosomes, producing a number of multimers of nucleosomal DNA units in the cell nuclei. The mechanism of apoptosis and the cellular signals involved in its induction have been studied during thymic prenatal ontogenesis and postnatal development, mainly in immature thymocytes and in the cells of the reticulo-epithelial (RE) network. In thymocytes or resting T lymphocytes, p53 tumor suppressor protein was identified to be a critical mediator of apoptosis in response to DNA damage. The cellular interaction of immature, cortical thymocytes (characterized by a double positive CD4+CD8+TCRlow immunophenotype) with thymic RE cells induces positive selection of T lymphocytes that recognize, but are not activated by self-MHC molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo Fas-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCRdull thymocyte subpopulation. T-lymphocytes which do not undergo positive selection are killed by apoptosis in response to a number of intrinsic and extrinsic factors, such as chemical toxins, viral infections, X- and UV irradiation, mild hyperthermia, the actions of various hormones, extracellular survival factors, calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin, actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor) complex. Immature thymocytes also undergo a second selective process, so-called negative selection, when thymic stromal cells eliminate autoreactive T lymphocytes. This process has been termed clonal deletion and also involves apoptosis. In addition to the two intrathymic T lymphocyte selection mechanisms, Immunocompetent, but autoreactive T lymphocytes which have already reached the periphery are also eliminated by apoptosis. All the divers stimuli of PCD are associated with an increase in the concentration of cytosolic calcium ions (Ca+2), which activate an endogenous endonuclease. This trigger for PCD results in rapid cleavage of DNA, a hallmark of apoptosis. Despite the diversity of the signals that can trigger apoptosis, the changes in cellular morphology characteristic of PCD are very similar. The uniformity of the morphological changes suggests the existence of a predetermined, final and common cell suicide pathway. Apoptosis requires energy in the form of ATP, indicating that PCD, as opposed to necrosis, is an energy dependent, active physiological and pathophysiological phenomenon.

Adolescent↗
PubMedDate not supplied

Upregulation of endoglin (CD105) expression during childhood brain tumor-related angiogenesis. Anti-angiogenic therapy.

During postnatal development, the formation of new blood vessels is possible only through angiogenesis. The initial growth of solid neoplasms, including childhood brain tumors, during the genetically determined stages of carcinogenesis, even at clinically undetectable sizes (a few mm3), depends upon the continuous formation of new blood capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during brain tumor related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PAA) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded (3-5 microns thick), as well as frozen tissue sections (6 microns thick) of 62 childhood brain tumors [34 medulloblastomas (MEDs) and 28 astrocytomas (ASTRs)], were employed for the assessment of EDG expression. Both an indirect, four-step, alkaline phosphatase (AP) conjugated, biotin-streptavidin based (or a diamino-benzidine [DAB]) conjugated immunoperoxidase antigen detection technique were employed, utilizing the SN6h anti-EDG monoclonal antibody (DAKO Corp.). Another antigen detection method, based on the Histogold (Zymed) reaction was also employed using the same antibody on formalin fixed, paraffin-wax embedded tissues. Strong expression (A; +3 to +4) of EDG on endothelial cells and demonstrated in all 62 childhood brain tumor cases. The most striking feature of the newly formed tumor-related capillaries was the presence of a markedly enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. A close apposition between the capillaries and the adjacent parenchyma was also observed. Brain tumors, especially glioblastoma, are among the most vascularized human neoplasms, and thus are candidates for antiangiogenic therapy. VEGF/PF-R1 (flt-1) and VEGF/PF-R2 (flk-1) are formed de novo in a glioma progression-dependent manner. Further studies should substantiate the importance of EDG in the earliest possible detection, diagnosis and NRA inhibition-based treatment of mammalian solid neoplasms, especially childhood brain tumors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Immunocytochemical detection of endoglin is indicative of angiogenesis in malignant melanoma.

The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including malignant melanomas, depends upon the continuous de novo formation of capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a dedifferentiated, malignant, highly invasive cellular immunophenotype (CIP) and distant metastases, as aspects of constant neoplastic progression, are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during malignant melanoma (MM) related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PAA) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 microns thick) of 25 MMs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diamino-benzidine [DAB]) conjugated, biotin-streptavidin based, antigen detection technique, employing the SN6h anti-EDG monoclonal antibody was conducted. Zymed's Histogold System was also utilized for immunocytological antigen detection. Strong expression (A; +3 to +4) of EDG on endothelial cells was demonstrated in all MM cases. The most striking feature of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. MMs, like most mammalian neoplasms, are characterized by extensive neovascularization, and thus are candidates for anti-angiogenic therapy. Further studies should substantiate the importance of EDG expression in the earliest possible detection, diagnosis and NRA inhibition-based treatment of solid tumors, including MMs. The importance of TGF-beta in all of the various aspects of neoplastic transformation, as well as malignant disease progression should also be studied more extensively in the future.

Antibodies, Monoclonal↗
PubMedDate not supplied

Over-expression of endoglin (CD105): a marker of breast carcinoma-induced neo-vascularization.

The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including breast carcinomas (BCs), depends upon the continuous de novo formation of capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases, as aspects of tumor progression, are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during mammary carcinoma-related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PM) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 microns thick) of 15 BCs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diamino-benzidine [DAB]) conjugated, biotin-streptavidin based, antigen detection technique, employing the SN6h anti-EDG monoclonal antibody was conducted. Zymed's Histogold System was also utilized for immunocytological antigen detection. Strong expression (A; ++ + to ++ ++) of EDG on endothelial cells was demonstrated in all 15 BC cases. The most striking feature of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. BCs, as most mammalian neoplasms, are characterized by extensive neovascularization and thus are candidates for anti-angiogenic therapy. Further studies should substantiate the importance of EDG expression in the earliest possible detection, diagnosis and NRA inhibition-based treatment of solid tumors, including BCs.

Antigens, CD↗
PubMedDate not supplied

Intrathymic non-lymphatic hematopoiesis during mammalian ontogenesis.

Histogenetically, the thymus is the primary lymphopoietic organ and provides an optimal microenvironment for the differentiation of T lymphocytes, independently of the influence of foreign antigens. Lymphocytes with diverse potential are produced in a protective microenvironment optimal for their maturation, whose dual cellular network is provided by endodermally derived RE cells and numerous ectomesenchymal cells derived from the neural crest. The full development of intrathymic hematopoiesis depends upon the successful completion of a series of well coordinated cellular interactions between widely divergent (in terms of origin) cells [epithelium (primitive pharynx); ectomesenchyrne (neural crest); and PHSCs (yolk sac, fetal liver)]. The cells of the thymic epithelial primordium do not proliferate in the absence of "inductive" interactions with the ectomesenchyme. Moreover, the nature of the mesenchyme determines the behavior of the thymic epithelial anlagen. The ectomesenchymal origin of chemotactic stem cell factor secretion, responsible for hemopoietic stem cell immigration, is a distinct possibility. The human thymus is a generalized hematopoietic tissue with between 7 to 9 weeks of ontogenesis. In human and dog fetuses various elements of mammalian hematopoiesis were identified intrathymically: B lymphocytes, plasma cells, erythropoietic and granulocytopoietic (neutrophils and eosinophils) cells, antigen presenting dendritic cells, and mast cells. Our light and ultrastructural (transmission and scanning), as well as immunocytochemical observations have established that during the embryonal and fetal period, the thymus is seeded by pluripotent, yolk sac derived PHSCs characterized by the following immunophenotype CD34+CD43+CD38-Lin-HLA-DR+CD69+. Stem cell c-kit tyrosine kinase (also referred to as mast cell growth factor, stem cell factor, or steel factor) in combination with autocrine and paracrine growth factors and cytokines (IL-3, IL-4, IL-5, IL-6, IL-7, G-CSF, etc.) stimulates myelopoiesis, including erythropoiesis, as well as lymphopoiesis. These hematopoietic growth factors are produced by activated lymphoblastic cells and stromal RE cells under the influence of immunoneuroendocrine regulation, supported by the finding that experimental or spontaneous, in vivo neural crest ablation during early mammalian ontogenesis always results in an abnormal development of the thymus, as well as the heart and great vessels, thyroid, and parathyroid glands.

Adolescent↗
PubMedDate not supplied

Guidelines for the development of comparative pathology.

The purpose of comparative pathology is to develop a fuller understanding of pathologic processes in individuals of various species. Historically, we distinguish between direct and indirect findings. Direct sources are paleopathologic fossils. Indirect findings are historic and/or religious descriptions of epidemics. The philosophy behind the comparative approach depends primarily on the individuals of the species as units. The individual represents a concrete reality, whereas the other taxonomic categories are only theoretical entities contrived by human thought. Intraspecies-specific comparison and the interspecies-specific comparison are distinguishable. In intraspecies-specific comparison different individuals (races, breeds) of one species are compared, whereas in the interspecies-specific comparison individuals of several species are compared. Evolution and the comparative ontogenetic development of recent organisms explains how the variability of species came into existence. Consistency in evolution and uniformity is given by the fact that members of all phyla are still represented by some remaining species. Heterogeneity of organismic structures are more numerous but secondary. With the exception of the virus, the cell is remaining the unit of living matter, but viruses depend on cells for their existence. The majority of species, the eumetazoans and vascular plants, are built of true tissues developed by cell division, whereas higher fungi and some algae exhibit plectenchymata which develop by the fusion of cells. This short article presents some thoughts and principles underlining the importance of development of guideline for the study of comparative pathology.

Animals↗
PubMedDate not supplied

Aging and neoplastic progression.

Aging is the gradual development of individuals of a particular species in time. Interspecies comparison shows the variability of the aging processes in ontogeny which is species-specifically fixed. e.g. a mouse will never be able to reach the life expectancy of a blue whale or man. Certain changes of the life span have been observed in aging human populations, on an individual basis, or in zoo animals under the care of veterinarians. Cells of different tissues exhibit a varying senescence additionally influenced by concomitant diseases. The age spectrum of neoplasms cannot be simplified. It is misleading to state that neoplasms are diseases of the elderly because this is the case only in certain, very common neoplastic diseases, such as colon cancers, but not regarding pediatric neoplasms as retinoblastoma, nephroblastoma, or Ewing sarcoma, and osteosarcoma in the young. This paper evaluates the diversified age changes in the development of selected neoplastic diseases.

Age Factors↗
PubMedDate not supplied

The role of zinc in pre- and postnatal mammalian thymic immunohistogenesis.

Mammalian thymic histogenesis can be morphologically divided into three consecutive stages: a) epithelial, b) lymphopoietic or lympho-epithelial, and 3) differentiated cellular microenvironmental, with formation of Hassall's bodies (HBs). Immunomorphological changes characteristic of human thymic involution begin during or soon after the first year after birth, and continue progressively throughout the entire life span. The 3% to 5% annual reduction in the number of cells of the human thymic microenvironment continues until middle age, when it slows down to less than 1% per year. According to the extrapolation of these results, total loss of thymic reticulo-epithelial (RE) tissue and the associated thymocytes should occur at the age of 120 years in humans. The marked reduction of the thymic cellular microenvironment is a well- controlled physiological process and is presumably under both local and global regulation by the cells of the RE meshwork and by the neuroendocrine axis, respectively. In humans, the age related decline of facteur thymique serique (FTS) levels in blood begins after 20 years of age and FTS completely disappears between the 5th and 6th decade of life. In contrast, serum levels of thymosin-alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years of age. The influences of a variety of other hormones on the involution of the thymus have also been characterized: testosterone, estrogen, and hydrocortisone treatment results in marked involution, cortisone and progesterone administration have a slight to moderate effect while use of desoxycorticosterone has no effect. The experimental administration of thyroxin yielded dose dependent results: low doses resulted in thymic hypertrophy, higher doses produced a slight hypertrophy, while the highest employed doses caused thymic atrophy. The atrophy was of apicnotic type, very different from that detected after treatment with corticoid hormones. Thymus transplantation experiments indicate that age-related, physiological thymic involution has been genetically preprogrammed. Grafting of the thymus from one week old C3H leukemic strain mice into 6 month old hosts resulted in changes in thymic weight and involution patterns that were synchronous in all recipients, in direct correlation with the glands in the donor, but not in the host. These data strongly suggest that the stimulus for thymus cell proliferation and differentiation is genetically determined within the organ implant. Since the thymus is the primary T-lymphopoietic organ during mammalian ontogenesis, its age-related involution with typical immunomorphological alterations can be held responsible only for the decline in antigen-specific T lymphocyte immune functions. Thymic involution and diminished T lymphocyte proliferation can be partially restored by thymic tissue transplantation or use of thymic hormones. The only partial reconstitution of CD4+ T helper lymphocyte subset after antineoplastic chemotherapy and bone marrow transplantation represents a significant, therapy complicating, clinical problem. After high-dose chemotherapy, restoration of thymus dependent CD4+ T lymphocyte genesis was reported only in children. Our radiation, stem cell transplantation, and hormone treatment experiments in animals strongly suggest age and time dependent regeneration of the cytoarchitecture of the thymic cellular microenvironment, as well as intrathymic lymphopoiesis. The human body's zinc pool undergoes progressive reduction, resulting in low zinc plasma levels and a negative crude zinc balance in older rodents, as well as humans. Previous research suggests that the diminished bioavailability of zinc in older mammals may represent one of the major factors for the involution of the thymus and consequent cellular immunological dysfunction. In PBMCs, zinc induces several cytokines, predominantly IL-1, IL-6 and TNF-alpha, and therefore, has an immense immunoregulative capacity. (ABSTRACT TRUNCATED)

Adolescent↗