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The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity. [ABSTRACT FROM AUTHOR]

Alterations in the immune system with aging are considered to underlie many age-related diseases. However, many elderly individuals remain healthy until even a very advanced age. There is also an increase in numbers of centenarians and their apparent fitness. We should therefore change our unilaterally detrimental consideration of age-related immune changes. Recent data taking into consideration the immunobiography concept may allow for meaningful distinctions among various aging trajectories. This implies that the aging immune system has a homeodynamic characteristic balanced between adaptive and maladaptive aspects. The survival and health of an individual depends from the equilibrium of this balance. In this article, we highlight which parts of the aging of the immune system may be considered adaptive in contrast to those that may be maladaptive. [ABSTRACT FROM AUTHOR]

Focuses on a study which investigated the presence of zinc drops at a silicon surface by using the refracted x-ray fluorescence method when the silicon wafer was implanted with zinc ions. Comparison of the roughness of the silicon surface at the implanted ion and silicon substrate without zinc-ion implantation; Measurement of nondestructive depth profile of implanted zinc ions; Requirements to detect zinc drop.

OBJECTIVE:: Intakes of soy, fat, and dietary fiber may be associated with the symptoms of dysmenorrhea through their biological effects on estrogens or prostaglandin production. The present study was to examine the relationships between intakes of soy, fat, and dietary fiber and the severity of menstrual pain. DESIGN:: Cross-sectional study. SETTING:: Three colleges and two nursing schools. SUBJECTS:: A total of 276 Japanese women aged 19-24?y. METHODS:: Intakes of nutrients and foods including soy products, isoflavones, fats and dietary fiber were estimated by a validated semiquantitative food frequency questionnaire. Severity of menstrual pain was assessed by the multidimensional scoring system reported by Andersch and Milson. RESULTS:: Intake of dietary fiber was significantly inversely correlated with the menstrual pain scale (r=-0.12, P=0.04) after controlling for age, smoking status, age at menarche and total energy intake. Neither soy nor fat intake was significantly correlated with menstrual pain after controlling for the covariates. CONCLUSIONS:: The cross-sectional difference in dietary fiber intake across the level of menstrual pain was small in magnitude but warrants further studies. SPONSORSHIP:: None.European Journal of Clinical Nutrition (2005) 59, 88-92. doi:10.1038/sj.ejcn.1602042 Published online 1 September 2004 [ABSTRACT FROM AUTHOR]

Members of the inhibitor of apoptosis protein (IAP) family including survivin, are expressed in many tumors. However, age-related changes in their expression in cancer have not been clarified. Thus, we investigated the expression of mRNA-coding for IAP family proteins in colon cancer samples from young (<70 years of age) and elderly (>70 years) patients by real-time quantitative RT-PCR. Samples were collected from cases with well-differentiated adenocarcinoma or moderately differentiated adenocarcinoma and their adjacent normal epithelial tissue. Well-differentiated adenocarcinoma tended to express higher levels of survivin than normal mucosa, and expression in moderately differentiated adenocarcinoma was significantly greater than in normal mucosa in samples from both groups of patients (p<0.05, respectively). When samples were compared between the different age groups, the normal mucosa exhibited similar levels of survivin expression. However, samples from older patients showed a significantly higher level of expression than those from younger patients in well and moderately differentiated adenocarcinomas (p<0.05, respectively). In contrast, the levels of expression of cIAP1, cIAP2, and NAIP in the cancerous tissues were lower than those found in normal mucosa regardless of age. As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group (p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group (p<0.05). XIAP expression was similar in normal and cancerous tissues in both the young and elderly groups. These results suggest that the expression of IAP family proteins, especially survivin, is associated with the age-related biological characteristics of colon cancer. [ABSTRACT FROM AUTHOR]

Summary. Ecotropic infection by Murine leukemia virus (MuLV) infection is initiated by the interaction between the receptor-binding domain of the viral surface glycoprotein (SU) and the cell-surface receptor, mCAT-1. To study the in vivo localization of viral binding site in mice, green fluorescence protein (GFP)-tagged Friend SU (F-SU/GFP) was incubated with tissue sections. Lymphohematopoietic organs and a part of the glandular tissues of C3H as well as C57BL/6 mice revealed positive signals for F-SU/GFP binding on the cell surface. In contrast, C4W mice, which is a partial congenic mouse strain carrying the Fv-4r gene on a BALB/c genetic background, exhibited negative signals in most of the organs except for a very weak binding in the pancreas. The expression of mCAT-1 mRNA determined by reverse transcriptase (RT)-polymerase chain reaction (PCR) revealed a similar distribution in C3H, C57BL/6 and C4W mice. Most of the organs including lymphohematopoietic organs and glandular organs revealed significant expression of mRNA for mCAT-1 gene, while the liver, heart and muscle did not. The results from binding assay were consistent with the fact that Friend MuLV-induced pathogenesis was usually associated with lymphohematopoietic systems, although mRNA expression for mCAT-1 was rather ubiquitous. The discrepancy between F-SU/GFP binding and mRNA expression for mCAT-1 in lymphohematopoietic organs of C4W mice would support the receptor interference effect by the Fv-4r gene causing the resistance of C4W mouse to Friend MuLV infection. [ABSTRACT FROM AUTHOR]

Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4 + CD8 + double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging. [ABSTRACT FROM AUTHOR]

To determine the efficacy of cyclosporin A (CysA) for the treatment of steroid-resistant interstitial pneumonitis (IP), we enrolled 25 patients with various rheumatic diseases and steroid-resistant IP in a pilot study [4 patients with rheumatoid arthritis (RA), 2 with systemic lupus erythematosus (SLE), 11 with polymyositis/dermatomyositis (PM/DM), 4 with systemic sclerosis (SSc), 1 with mixed connective tissue disease (MCTD), 3 with Sjögren syndrome (SS)]. Twelve patients (48%) showed a persistent response to CysA therapy, and 7 of them had PM/DM, including so-called amyopathic DM. Patients with a persistent response had moderately elevated lactate dehydroxygenase (LDH) levels, whereas patients who died had much higher LDH levels and hypoxia. Even patients with low blood levels of CysA achieved a persistent response. In responding patients, the symptoms, chest X-ray findings, arterial oxygen tension, and LDH level all improved after less than 4 weeks. In conclusion, CysA seem to be useful for treating patients with steroid-resistant IP, whose duration is short and severity is mild. [ABSTRACT FROM AUTHOR]

We studied the characteristics of anti-Ki antibodies that react with a synthetic peptide (KILT) which has homology with SV40 large T antigen nuclear localization signal (SV40 T NLS). Immunoreactivity of antibodies to KILT was tested by enzyme-linked immunosorbent assay (ELISA), and this reactivity was compared with results obtained by immunoblotting using purified Ki and ELISA using purified or recombinant Ki antigen. The clinical significance of anti-KILT antibodies in lupus patients was also studied. Twenty percent of anti-Ki sera reacted with KILT, and all sera that reacted with KILT recognized both purified and recombinant Ki antigen in all our assay systems. A significant correlation was observed between reactivities in ELISA using KILT and with these using purified and recombinant Ki. Some sera with low titers by double immunodiffusion (DID) reacted with KILT, whereas high-titer anti-Ki sera showed a tendency to react with Ki antigen in different assays. The prevalence of discoid rash and sicca complex was higher in the anti-KILT-positive group. The amino acid sequence homologous to SV40 T NLS is an immunologically active epitope on the Ki antigen; reactivity to this epitope is associated with characteristic clinical features allied with anti-Ki antibodies in lupus patients. [ABSTRACT FROM AUTHOR]

At the initial stage of retroviral infection, virion envelope glycoprotein (env product) binds to cell surface receptors. Cells infected with retrovirus or into which the env gene was introduced, become resistant to superinfection by other retroviruses with the same receptor specificity, a phenomenon known as receptor interference. We have demonstrated previously that the introduction of an env gene from a truncated endogenous ecotropic murine leukemia virus (MuLV), the Fv-4 resistance (Fv-4r) gene, into the bone marrow hematopoietic cells of Fv-4 sensitive (Fv-4s) mice protected mice from ecotropic retrovirus-induced disease. Using the gene transfer system under the control of the retroviral vector and bone marrow transplantation (BMT), here we could show that the expression of an introduced Fv-4r gene in hematopoietic cells continued for more than 1 year after BMT. To determine the inhibitory mechanism of Fv-4r env gene expression against FLV-infection in this model system, peripheral blood mononuclear cells (PBMCs), or spleen cells from chimeras with various degrees of env-expression, were mixed with green fluorescence protein (GFP)-conjugated Friend MuLV envglycoprotein (GFP-Fr-ENV). The amount of GFP-Fr-ENV bound to these cells inversely correlated with the expression intensity of the transduced env gene indicating the receptor interference effect. Next, to see whether transduction of the Fv-4r gene would protect an immunosuppressed host from FLV-induced leukemogenesis, we generated immunocompromised chimeras by transplanting env-transduced bone marrow cells into a thymectomized host. These chimeras also resisted FLV-induced leukemogenesis, indicating that receptor interference-based gene therapy could become a therapeutic basis for immunodeficiency virus-induced diseases in vivo. [ABSTRACT FROM AUTHOR]

The role of the electronegativity of atoms in inorganic compounds in TOF–SIMS fragmentation is discussed. From a study of approximately 30 inorganic compounds – chlorides, oxides, nitrates, and sulfates – a simple rule has been proposed for the dependence of fragment pattern appearance on the electronegativity (electron affinity), which can be easily obtained from handbooks, and the valence of positive and negative ions in these compounds. TOF–SIMS measurements of metal and alloy surfaces, should be corrected for the ionization potentials and/or electronegativities of atoms present in surface contaminants. [ABSTRACT FROM AUTHOR]

Summary Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-γ (IFN-γ). IFN-γ production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-γ in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction. [ABSTRACT FROM AUTHOR]

Auger transition probabilities were experimentally derived from dominant XAES and related XPS peaks observed in XPS spectra. Some values of derived probabilities were higher than 1, because of addition or subtraction of background signal from the XAES or/and XPS peak intensity. However, the probabilities obtained are recognized to be useful for practical quantification by XAES and AES. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). We have studied the expression of the inducible NOS (iNOS) by bone marrow cells from the patients with myelodysplastic syndromes (MDS) at the mRNA level by RT-PCR assay and at the protein level by immunohistochemical staining using a specific anti-iNOS monoclonal antibody. The iNOS message was present in 92% of bone marrow tissues from MDS patients (11 out of 12) by an examination using RT-PCR. Basically, iNOS message was negative or very weak in control (1/9) and AML (0/7) cases. This was supported by immunohistochemical findings that the iNOS was positive in most of the bone marrow samples from MDS patients (9 out of 12), while bone marrow cells of control (O out of 12) and AML (O out of 5) cases were basically negative. Double immunostaining for CD68 antigen, which is a marker for macrophage lineage cells, and iNOS was performed on MDS bone marrow sections. iNOS was dominantly localized to bone marrow macrophages, although a part of myeloid cells were also positively stained with anti-iNOS antibody in a part of cases. These results indicated that there is some in vivo induction of iNOS expression for local NO production that might be involved in the dysregulation of hematopoiesis in bone marrow of MDS. [ABSTRACT FROM AUTHOR]

Immunohistochemical and clinicopathological studies were performed in 27 autopsy cases with indisputable DIC, which had been selected from 1,800 autopsy cases of elderly people based on the following two criteria; 1. presence of fibrin thrombi in glomeruli, and 2. presence of fresh patchy necrotic foci in myocardium and/or fibrin thrombi in splenic sinuses. A high incidence of liver lesions (22/27) was revealed in autopsy cases with indisputable DIC. The liver lesions could be classified into four groups. Group-I (Central degeneration) was characterized by massive precipitation of fibrin irregularly around the central vein, causing parenchymal damage. Group-II (Central necrosis), showed coagulation necrosis in the cental zone due to circulatory disturbance caused by either shock as a cause of DIC or abrupt cessation of blood flow into the lobules following fibrin thrombus formation in vessels of Glisson's sheath. Both group-I and -II showed a short clinical duration of DIC. Group-III (Sinusoidal thrombosis), showed the presence of fibrin thrombi in sinusoids with mild parenchymal damage and long clinical duration of DIC. Group-IV (No thrombosis), showed neither parenchymal damage nor fibrin thrombi in sinusoids, but a long clinical duration of DIC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Forty five human thymomas were studied immunohistochemically using antibodies to thymosin a-1, thymosin β-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin α-1 (80%) and thymosin β-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of the mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were considered to be of cortical origin. [ABSTRACT FROM AUTHOR]

1The Japanese pharmaceutical administration system, and recommendations for the improvement of clinical trial methodology following the implementation of GCP guidelines in Japan are described with special reference to three recent developments in Japanese drug regulation. 2The implementation of GCP guidelines has not been fully satisfactory and clinical trials in Japan still run into problems. The Ministry of Health and Welfare has recently established a Committee on Safety of Medicines after serious trouble with a new drug was experienced. The Committee released an interim report on the reform of clinical trials supervision and the system for examination of New Drug Applications. 3ICH-GCP guidelines will be implemented in Japan in the next few years. The principal differences between Japanese GCP and ICH-GCP guidelines, and their effects on clinical trials in Japan with reference to the acceptability of ICH-GCP, are discussed. 4The final proposals on the National Health Insurance drug pricing method and the appropriate use of drugs by the Central Social Insurance Medical Council are anticipated to have a significant impact on the drug market. The changes in pricing system, especially premiums for innovative drugs, and the implications for the drug market are considered. 5In these changed circumstances, the importance of the role of clinical pharmacologists in the framework of the new drug regulations in Japan is reviewed. [ABSTRACT FROM AUTHOR]

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Necropsy findings of an acute fatal case of idiopathic interstitial myocarditis were reported. The patient was a 33 year old housewife who had acute cardiac failure on the sixteenth day after the onset of the disease. Necropsy showed important pathological changes confined to the heart. Both ventricles were affected by confluent granulomas with an ill defined patchy appearance. Histologically these lesions consisted of round cells, histiocytes, eosinophils and myogenic giant cells. The findings were compatible with those of interstitial myocarditis associated with a proliferation of giant cells. Both atriums were also affected to a minor extent, detectable only by histological examination. Electron microscopy and cytochemistry showed that most giant cells noted in the lesion showed myofibrils and primary lysosomes in the cytoplasm. Giant cells were positive for myoglobin. Though the macrophage origin of the giant cell in this disorder has been emphasised in a recent report, these cytological results suggest that giant cells observed in the cardiac granulomatous lesions of this case were mainly myogenic in origin. [ABSTRACT FROM PUBLISHER]

Apoptosis of murine thymocytes was examined either in intact fetal thymus lobes or in thymus cell suspensions, both cultured alone or in the presence of either a cortical (TEC 1.4) or a medullary (TEC 2.3) thymic epithelial cell line. Both TECs induced a pronounced increase of apoptosis in 24-h cultivated single thymus cell suspensions but not in spleen or bone marrow cell cultures. Co-culture of thymocytes with murine fibroblasts did not enhance apoptosis of the thymus cells. A similar enhancement of thymocyte apoptosis was observed with dialysed culture supernatants derived from both TEC lines, the active component(s) having a molecular weight of >30 kDa. In contrast, the cortical TEC 1.4 had a pronounced apoptosis inducing effect on intact fetal thymus lobes cultivated for six days, whereas the medullary TEC 2.3 had only a marginal influence. TEC 1.4 also induced a significant alteration in the ratio of CD4CD8to CD4CD8cells. It is concluded that both the cortical and medullary epithelial cell lines are able to induce thymocyte apoptosis but that a large proportion of the cells within the intact thymus stroma is refractory to the respective signal(s) of the medullary epithelial cell line. [ABSTRACT FROM AUTHOR]

Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes (MDS) was demonstrated on frozen sections using the terminal deoxytransferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS cases showed expression of Fas mRNA (12/12) and most exhibited an expression of FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive signals for Fas and FasL mRNA, however, a very weak band was detected in three cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR. Immunohistochemical examination revealed positive staining for Fas (11/12) and FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15) antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive cells which were macrophage lineage cells, did not express Fas antigen strongly. In contrast, positive staining for FasL was detected in hematopoietic cells and CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas-FasL system plays an important role in inducing apoptosis in the bone marrow of MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction) and/or paracrine (hematopoietic cell-stromal cell interaction) manner. [ABSTRACT FROM AUTHOR]

To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-α and IFN-γ by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-α was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-γ was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-γ mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-α or IFN-γ producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-α and occasionally IFN-γ by bone marrow macrophages. [ABSTRACT FROM AUTHOR]

We have shown that spontaneously occurring, organ-specific autoimmune lesions develop in aged C57BL/6 mice of both sexes, especially in 24-month-old senescent mice. The inflammatory lesions were found in the multiple organs such as salivary gland, kidney, pancreas, lung, and liver, associated with ageing process. Organ-specific autoimmune lesions first appeared in 6-month-oid C57BL/6 mice, and were aggravated with advancing age. In contrast, significant inflammatory changes did not develop in the thyroid, stomach, testis, ovary, and prostate in aged C57BL/6 mice. The incidence and severity of organ-specific autoimmune lesions in this strain of non-autoimmune mice increase with advance of age. The most severely affected lesion was sialadenitis developed in the submandibular salivary gland of aged mice, and a significant difference between male and female mice was noted only in the salivary gland. The infiltrating cells within the lesions of multiple organs consisted mainly of Thy 1.2+ and L3T4+ cells. Autoantibodies were detected in the sera of the mice with each corresponding organ-specific autoimmune lesions. [ABSTRACT FROM AUTHOR]

The incidence of mononuclear cell infiltration in the adrenal cortex was examined in autopsy cases of young and old subjects, and the infiltrating mononuclear cells were immunohistologically characterized by monoclonal antibodies, Histologically, 110 of 174 autopsy cases of persons > 60 years (63.2%) were shown to have mononuclear cell infiltration of varying degree within the adrenal cortex, whereas such a lesion was observed in lesser incidence (7.4%) in the 54 younger, control subjects aged < 49 years. In addition, severely infiltrating lesions in the adrenal cortex were found frequently in the elderly > 70 years, Immunohistochemical study revealed that the infiltrating mononuclear cells were mainly composed of CD3+ T cells. The major proportion of CD3+ T cells expressed CD4. whereas CD8+ T cells were less in number. Moreover, a considerable proportion of CD4+ T cells was activated as judged by interleukin 2 receptor expression. These findings indicate that T lymphocytes infiltration in aged human adrenal cortex may represent a pre-clinical manifestation of organ-specific autoimmune adrenalitis which is based on autoimmunity associated with ageing process. [ABSTRACT FROM AUTHOR]

We have shown that autoallergic sialadenitis develops in C3H/He (H-2k) mice thymectomized 3 days after birth and then immunized at 4 or 6 weeks of age with a homogenate of the submandibular salivary gland emulsified in Freund's complete adjuvant. Significant inflammatory changes did not develop in other inbred strains, such as BALB/c (H-2d), and C57BL/6 (H-2b) mice, examined by the same experimental protocol, or in the control groups, i.e. animals thymectomized at day 3 but not immunized, and animals not thymectomized but immunized. The cellular infiltrates observed in C3H/He mice with sialadenitis consisted of small and medium-sized lymophocytes stained with anti-Thy-1.2 antibody (the major proportion positive with anti-L3T4 and the lesser, with anti-Lyt 2). Anti-salivary duct antibodies were detected frequently in the seraof the C3H/He mice with sialadenitis. [ABSTRACT FROM AUTHOR]

Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-αβ cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor β-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice. [ABSTRACT FROM AUTHOR]

CD24 antigen is a glycoprotein expressed on haematopoietic cells, including B cells, T cells and granulocytes and on non-haematopoietic cells, including neural cells, ganglion cells and the cells of the adrenal medulla. The antigen is also expressed on renal cell carcinoma, small cell lung carcinoma and neuroblastoma. We have cloned rat cDNA encoding core polypeptide of CD24 antigen from embryonic brain and shown that the core molecule is highly expressed in embryonic brain and non-neural tissues. Rat tissue and various human neoplastic cell lines were investigated for the gene expression of CD24 core polypeptide by in situ hybridization. The transcript was localized in gastrointestinal epithelia, ductal and acinar epithelia of the salivary gland, the bronchiolar epithelium, renal tubular epithelium, the epithelium of the oviduct, follicular cells of the thyroid, medullary cells of the adrenal gland, Auerbach's plexus, B blastoid cells in lymph nodes, hair follicles, and the sweat glands of the skin. Among the various human neoplastic cell lines investigated, the transcript was detected in squamous cell carcinoma of the lung, gastric carcinoma, colon carcinoma, choriocarcinoma and renal cell carcinoma. The result suggest that the core molecule of CD24 antigen may be expressed in a wider range of epithelial cells and carcinoma cell lines than has been reported. Furthermore, we show that gene expression of CD24 core polypeptide is confined to the proliferative zone of the gastrointestinal mucosa, suggesting that core molecule is transiently expressed on the surface of epithelial cells in the process of cellular maturation. We discuss a possible role for CD24 antigen in the maturation of epithelial cells in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]