The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap‐frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin‐fixed paraffin‐embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine

The lymphocyte-dendritic cell system

Antigens provoke immune responses. The group of immunocompetent cells related directly to this response includes T and B cells, macrophages (MO) and dendritic cells (DCs). DCs acting as antigen-presenting cells have been recently recognized to be important in initiating the immune response. B cells and follicular dendritic cells (FDCs), the major immunocompetent cells in the B-cell dependent area, play an important role in humoral immunity, while T cells and interdigitating cells (IDCs), which are the major immunocompetent cells in the T-cell dependent (TD)-area, play an important role in cellular immunity. The B cell-IDC interaction in the TD-area is also essential for the B-cell response against TD-antigen. Consequently, the lymphocyte-DC interaction is essential in the response to antigenic stimulation and in inducing the potent effector cells. B cell-DC, T cell-DC and DC-B cell-T cell interactions are regulated in predetermined sites by complex and varied mechanisms. Much recent evidence demonstrates that DCs modulate lymphocyte biology in its broadest aspects, including generation, differen-tiation, proliferation, and activation. In this review, we outline recent studies on the generation, structure, and function of lymphatic tissues, propose the concept of the "Lymphocyte-Dendritic Cell System (LDS)", and finally describe the significance and functions of this system in health and disease

Development of follicular dendritic cells: A study using short-term bone marrow cell grafting in SCID mice

To evaluate the cellular origin of follicular dendritic cells (FDC) in lymphoid follicles (LFs), severe combined immunodeficient (SCID) mice (H-2d) were grafted with 5-bromo-2'-deoxyuridine (BrdU)- incorporated bone marrow cells from CB-17 mice (H-2'9 and with non-BrdU-incorporated bone marrow cells from C3H mice (H-2k) and Wistar rats (RTIU). This procedure was followed by antigenic stimulation with horseradish peroxidase and related immune complex (mouse peroxidase anti-peroxidase) administration. Secondary LFs in the lymph nodes and spleen of the reconstructed SCID mice were examined morphologically and immunocytochemically. LFs reconstructed with CB-17 mouse bone marrow cells contained FDCs capable of trapping and/or retaining mouse peroxidase anti-peroxidase as immune complexes. Secondary LFs contained BrdU-incorporated germinal center lymphocytes but not non-lymphoid stromal cells. A cell grafting study in SCID mice using bone marrow cells from C3H mice and Wistar rats demonstrated that FDCs in reconstructed LFs exhibited a marker specific for the recipient but not for the donor. These data indicate that functionally active FDCs occur de novo in reconstructed LFs in SCID mice, and do not support the view that FDCs originate from bone marrow cells in short-term reconstructed LFs

Endogenous sex hormone and estrogen binding activity in thyroid cancer

Summary. The reactions of four anti-sex hormone (Estrone, Estradiol, Estriol and Testosterone) antisera were immunohistochemically examined in 109 cancerous and 80 normal and benign thyroid tissues. Four kinds of sex hormones were detected in the tumour cells of 61 cases (56%) of thyroid cancer and in the follicular epithelial cells of 4 cases (5%) of normal and benign thyroid tissues. Among the thyroid cancers, 54 female (61%) and 7 cases in males (33%) were positive for sex hormones. Furthermore, estrogen binding activity was screened histochemically in 36 thyroid tissues of various types, and detected not only in thyroid cancer (6115 cases), but in normal and benign thyroid tissues (3121 cases) as well. It was concluded that endogenous estradiol was located in thyroid cancers more frequently in females than in males and that there was estrogen binding activity in the cells of not only thyroid cancers, but also normal and benign thyroid tissues. This is the first report of the dernonstration of endogenous sex hormones in thyroid cancer

Modeling and Identification of Data Center HVAC System with Super-Multipoint Temperature Sensing System

This paper investigates a heating, ventilation, and air-conditioning (HVAC) system in a data center equipped with a previously developed super-multipoint temperature sensing system. This system is expected to be a key technology for reducing the total power consumption of the HVAC system by controlling the inlet temperature distribution of the servers in real time. For this purpose, we present an overview of our fan-control system based on model predictive control. The main objective of this paper is to identify a dynamical model of temperature variations, in order to predict the future evolution of the distribution. However, the spatially high-density temperature data provided by the sensing system is not suited to the needed model accuracy, and the present modeling problem is differentiated from standard ones. We thus present a systematic scheme for the spatial density reduction of sensors by using spectral clustering and graph theory and associated techniques to acquire the dynamical model. Through simulation with real data, we finally show that the developed model achieves an accuracy of 0.58 degrees Celsius on average

IBL-like T cell lymphoma expressing monoclonal gammopathy (macroglobulinemia) in the serum

A case of IBL-like T cell lymphoma with serum monoclonal gammopathy was reported. A 58- year-old woman, who had suffered from heart failure. was admitted because of asthma attack, fever and lyrnphadenopathy. Leucopenia with a small amount of atypical lymphocytes was detected. Serum analysis showed monoclonal elevation of IgM-K (M-protein) and hv~erviscositv. Urinarv Bence-Jones urotein was diiected. Lymph &de biopsy rAealed the disappearance of normal structure and proliferation of T cells with pale cells which characterized IBL-like T cell lymphoma. Immunocytochemistry revealed the pale cells to bear T cell markers (MT-1, CD 5, CD 8 or CD 4) and IgM-positive cell distribution. Tonsilar biopsy showed the infiltration of atypical lymphoids and pale cells. Bone marrow biopsy showed moderate lymphoplasmacytoid proliferation with lymph follicles. Clinical data and serum analysis suggested macroglobulinemia. Additional lymph node biopsy was performed and revealed IBL-like T cell lymphoma. IBLlike T cell lymphoma is characterized by polyclonal hypergammaglobulinemia. The present case probably occurred initially as IBL-like T cell lymphoma and lymphoplasmacytoid cell proliferation might have followed due to an excess of CD 4' cell

Function of the follicular dendritic cell in the germinal center of lymphoid follicles

The authors made an immunocytochemical examination of the germinal centers (GCs) of (1) lymph follicles in physiological lymph nodes and (2) extra-nodal tissues of divergent diseases including thyroid disorders, rheumatoid arthritis, Warthin's tumor and Kimura's disease (Eosinophilic lymphfolliculoid granuloma). In these germinal centers, the presence of immunoglobulins (IgG and IgM), early acting complement components (Clq, C4, C3c,C3d), receptors for C3b and C3d and dendritic reticulum cell-l was demonstrated in lace-like network patterns which were proven electron-microscopically to coincide with the surface of follicular dendritic cells. IgE was distributed in a lace-like pattern in the GCs of proliferating follicles of Kimura's disease, in which the lysis of follicles was frequently observed. This lysis appeared to be related to the presence of complement components. In the germinal centers of extra-nodal tissues, including the thyroid tissues accompanying the lymph follicles, rheumatoid arthritis synovial tissues as well as Warthin's tumors, thyroglobulin, rheumatoid factor and salivary amylase were detected as specific antigens, occurring in lacelike patterns. It is possible that follicular dendritic cells may play a role in the genesis of GCs and be responsible for the immune response through C3 receptors