Hisako Tanaka

COMPARISON OF THE EFFECTS OF VARIOUS FINE PARTICLES ON IgE ANTIBODY PRODUCTION IN MICE INHALING JAPANESE CEDAR POLLEN ALLERGENS

The adjuvant effects of various fine particles [Kanto loam dust, fly ash, carbon black, diesel exhaust particles (DEP), and aluminum hydroxide (alum)] on immunoglobulin E (IgE) antibody production in female BDF1 mice were examined. In experiment 1, animals both received 25 micrograms of each particle intranasally and were exposed to aerosolized Japanese cedar pollen allergens (JCPA) for 30 min/d at 1-wk intervals for the first 8 wk. This was followed by exposure for 30 min every 3 wk for the next 9 wk. As parameters of allergic rhinitis, measurements were made of JCPA-specific IgE and IgG antibody titers, the protein-adsorbing capacity of each type of particle, and nasal rubbing movements. The increases in anti-JCPA IgE and IgG antibody production in mice treated with aerosolized JCPA plus respective particles were significantly greater than that found with aerosolized JCPA alone. This was associated with no marked differences in the other allergic rhinitis parameters. In experiment 2, after the administration of particles as in experiment 1, about 160,000 grains of Japanese cedar pollen (JCP, native dry pollen) were dropped onto the tip of the nose of mice twice a week for 16 wk. Six weeks after the first immunization, the anti-JCPA IgE antibody titers of groups treated with the respective particles were greater than 1:20, whereas those of mice treated with JCP alone were 1:10. No significant differences in the anti-JCPA IgE and IgG antibody productions, nasal rubbing counts, or histopathological changes were observed after 18 wk. These results suggested the nature of the particles, their capacity to adsorb antigens, and/or their size may not be related to enhancement of IgG antibody production nor symptoms of allergic rhinitis. However, IgE antibody production seemed to occur earlier in mice treated with particles than in mice immunized with allergens alone.

Histopathological Study of Human Cisplatin Nephropathy

The present study was conducted to obtain detailed information on the morphological changes in the human kidney as related to cisplatin therapy. The kidneys of ten autopsy cases showing impaired renal function following cisplatin therapy with hydration were examined histologically. Sporadic lesions of degeneration, necrosis, and regenerative changes were observed in the pars convoluta and pars recta of the proximal tubule, distal tubule, and collecting duct. Enlarged and pleomorphic nuclei in regenerated epithelial cells and hyperplasia of the collecting duct lining cells were considered to be specific histological findings in renal injury related to cisplatin therapy. Electron microscopic examination of a case receiving a large dose of cisplatin without signs of renal insufficiency showed an increased number of cytosomes containing electron dense granules in all tubular portions and conspicuous nuclear indentation in the thin limb of the loop of Henle and collecting duct. The platinum concentration in autopsy organs and biopsy cases was analyzed, but no correlation could be found between the concentration level of platinum in the kidney and impairment of renal function.

Mechanism of Hematuria in Glomerular Disease

From an electron-microscopic study in a case of diffuse membranous glomerulonephritis, we would like to propose a possible mechanism of hematuria in glomerular disease. There are several factors we sh

Immunohistochemical Demonstration of Surface Antigen of Human Lymphocytes with Monoclonal Antibody in Acetone-fixed Paraffin-embedded Sections

Although the majority of reported studies have used fresh-frozen sections in detecting surface antigen of lymphocytes in tissue via monoclonal antibody, detailed histological figures can not be obtained by this method. Nor can the antigenicity be preserved for any length of time. A new method for detecting the surface antigen of lymphocytes using fixed and embedded material is presented. Human spleens were fixed in cold acetone, embedded in low melting point paraffin wax, and the thin sections treated with hyaluronidase. Anti-T lymphocyte monoclonal antibody (anti-Leu-1, anti-Leu-2, anti-Leu-3) and anti-HLA-DR were applied on these sections, and the antigen was detected by the ABC (avidin-biotin-peroxidase complex) method. The results were then compared with those of fresh-frozen sections. There was no great difference in detecting T and B cells or their subsets, but the histological figures were substantially better preserved in sections prepared by the present method. Furthermore, the antigenicity was retained in the materials fixed and embedded for more than two years.

A pathological study on eosinophilic lymphfolliculoid granuloma (Kimura's disease).

The present study Included 46 cases of eosinophilic lymphfolliculoid granuloma(Kimuras disease), which occurred mainly in males between the ages of 11 to 52 years. The common sites were the soft tissue of the head and neck region. Although recurrence was not infrequent, the clinical course was benign. Laboratory findings revealed eosinophilia and frequent elevation of serum IgE. The histological characteristics consisted of proliferation of lymphoid follicles and granulation tissue with infiltration of eosinophils, mast cells, plasma cells, lymphocytes, and histiocytes, some degree of vascular proliferation, and fibrosis. With the appliance of unlabeled peroxidase‐antiperoxidase method, a marked reticular reaction of IgE was confirmed in the germinal center of the folliculoid structure, and there were quite a number of IgE producing plasma cells. Many mast cells with IgE bound to their cell surface were seen in the granulation tissue. Toluidine blue staining and electron microscopy revealed fairly well preserved granules in mast cells, being quite different from the changes seen in type I allergy.

Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human lymph nodes

Monoclonal antibodies specific for the adhesion molecules participating in lymphocyte homing, lymphocyte function associated antigen‐1 (LFA‐1) and very late antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1), were used to characterize their expression pattern in human lymph nodes by immunohistochemical and immunoelectron microscopic techniques. The location of LFA‐1‐positive lymphocytes and selective expression of ICAM‐1 on the luminal plasma membrane of high endothelial venule endothelium suggested that the LFA‐1/ICAM‐1 adhesion pathway participates only in the initial step of the lymphocyte migration process. Lymphocytes passing through endothelium appear not to be influenced by this pathway. VCAM‐1 was detected occasionally on the endothelium of high endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in peripheral lymph nodes. VLA4‐positive lymphocytes tended to be more frequently observed within high endothelial venules in mesenteric lymph nodes than in peripheral ones. Strong expression of both ligands, ICAM‐1 and VCAM‐1, was noted on the plasma membrane of follicular dendritic cells, and was especially prominent on their labyrinthine folding, and on the interdigitating cells in the paracortex. Furthermore, both LFA‐1‐and VLA4‐positive lymphocytes localized around these cells. This suggests that LFA‐1/ICAM‐1 and VLA4/VCAM‐1 adhesion pathways play an important role in the lymphocyte recognition of antigen‐presenting cells.

IMMUNOHISTOCHEMICAL STUDY ON THE DISTRIBUTION AND SIGNIFICANCE OF MONONUCLEAR CELLS IN HUMAN BREAST CARCINOMA

Lymphocyte subsets in the tumor nests of breast carcinoma were immunohistochemically investigated and a quantitative analysis was added. The majority of cases showed predominance of T cell and suppressor T cell (T8). A decrease in number of lymphocyte subsets and the helper T (T4)/T8 ratio in the stroma of tumor nests correlated well with the progression of clinical stage and the presence of metastasis. This correlation could not be found in the peripheral region of the tumor nests. Macrophages and NK cells were infrequently observed only in the peripheral region of ductal carcinoma. T cell infiltration was prominent in medullary carcinoma with lymphocyte infiltration (MC), and macrophages, NK cells, and T zone histiocytes were frequently encountered. For the purpose of knowing the activity of T cells, IL‐2 receptor (Tac) and transferrin receptor were examined irnmunohistochemically. The fact that a few activated T cells were found only in the peripheral region of tumor nest suggested the local immune response in ductal carcinoma not to be so active as to reject the tumor cells. Since numerous activated T cells were recognized in the tumor nests of MC, this type of breast carcinoma was thought to have a higher immune reactivity. There was little evidence indicating NK cells to play a role for natural cytotoxicity in breast carcinoma. ACTA PATHOL. JPN. 36 1455‐1468, 1968

In vivo Function of Homing Receptors Participating in Lymphocyte Recirculation: Transfer Analysis in SCID Mice

In order to examine the in vivo function of the adhesion molecules implicated in lymphocyte homing, blocking effects of antibodies against various adhesion molecules on lymphocyte migration were tested in SCID mice into which BALB/c donor splenocytes had been transferred. It was proved that the transferred donor splenocytes migrated to peripheral lymph nodes (LNs) of SCID mice. T and B lymphocytes were distributed in the specialized compartments as seen in the LNs of normal mice. Migration of lymphocytes to the local LNs was accelerated by stimulation with ovalbumin and complete Freunds adjuvant. This experimental system with accelerated migration was applied to analyze the in vivo function of adhesion molecules, and the following findings were obtained. Combined use of antibodies against lymphocyte-function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) strongly inhibited the migration of T lymphocytes to the peripheral LNs. Antibodies against very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) led to diminished B lymphocyte migration and disturbed compartmentalization of T lymphocytes in the paracortex. Migration of both T and B lymphocytes to the LNs was completely inhibited by the antibody against L-selectin. These results indicate that L-selectin plays an essential role in migration of both T and B lymphocytes into peripheral LNs but LFA-1/ ICAM-1 and VLA-4/VCAM-1 play different roles in compartmentalization of T and B lymphocytes in the peripheral LNs. In contrast, these adhesion molecules were not involved in lymphocyte migration to the splenic white pulp, indicating that the mechanisms for lymphocyte homing to the white pulp are quite different from those to the peripheral LNs.

Mammary tumor induction in analbuminemic rats by 7,12-dimethylbenz(a)anthracene☆

Induction by 7,12-dimethylbenz(a)anthracene of mammary tumors was studied in analbuminemic rats, a mutant strain established from Sprague-Dawley rats which are characterized by the absence of serum albumin and hyperlipidemia. Twenty-three weeks after carcinogen administration, the incidence and average number of mammary tumors and the tumor weight per tumor-bearing rat were respectively 35.0%, 1.7 +/- 0.2 (S.E.) and 8.9 +/- 0.5 g in analbuminemic rats and 69.2%, 2.3 +/- 0.2 and 12.2 +/- 2.8 g in the controls. Associated with this lower mammary tumorigenic response, analbuminemic rats had significantly lower plasma prolactin levels than controls during proestrus at 7-8 weeks of age when carcinogen was given (176 +/- 62 vs 308 +/- 52 ng/ml).

High endothelial venule and immunocompetent cells in typical medullary carcinoma of the breast

The characteristics of immunocompetent cells and their role in killing tumour cells in typical medullary carcinoma of the breast (TMC) have been investigated morphologically. Formation of high endothelial venule (HEV)-like vessels in tumour cell nests, the distribution of macrophages, T-zone histiocytes, T- and B-lymphocytes, the ratios of CD4+/CD8+, and natural killer (NK) or NK-like T-cells were examined in five cases of TMC. These results were compared with controls which consisted of three cases of ductal carcinoma with intense lymphocytic infiltration (control I) and four cases of ductal carcinoma with scanty lymphocytic infiltration (control II). An increased incidence of HEV-like vessels with migration of lymphocytes and a higher number of CD8+lymphocytes with interleukin-2-receptor expression, as well as numerous CD57 cells, were noted in the tumour nests of TMC as compared with those of control groups. Furthermore, large granular lymphocytes, large lymphocytes invaginating tumour cells and necrotic tumour cells were observed electron microscopically. These findings indicate that infiltrating lymphocytes in TMC are activated and become effector cells that can kill the tumour cells by mechanisms similar to those of NK cells. The activities of immunocompetent cells in TMC appear to contribute to a favourable prognosis in TMC of the breast.