Subpopulations of CD4+ cells in lpr/lpr mice: differences in expression of T cell receptor/CD3 complex and proliferative responses.

CD4+ cells from autoimmune-prone C57BL/6 lpr/lpr mice contain two subpopulations, B220-CD4+ and B220+CD4+ cells. Highly purified B220-CD4+ cells from C57BL/6 +/+ and lpr/lpr mice were examined by comparing functional characteristics and expression of cell surface antigens and T cell receptor (TcR)/CD3 complex. Both lpr B220+CD4+ and B220+CD4-CD8- cells, most of which were PgP-1 positive, expressed TcR/CD3 complex on the cell surface at lower level as compared with B220-CD4+ cells of age-matched normal mice. In addition, the B2200-CD4+ cells were heterogeneous on the basis of surface expression of PgP-1 and CD3 antigens. Normal levels of TcR C alpha-, C beta- and V beta 8-specific mRNA were found in the B220-CD4+ cells and B220+CD4+ cells as compared with normal B220-CD4+ cells, while V beta 8-specific mRNA was preferentially expressed only by B220+CD4-CD8- cells. Either B220+CD4+ cells and B220+CD4-CD8- cells failed to respond to anti-CD3 monoclonal antibody (MoAb) as assessed by proliferative responses and production of interleukin-2 (IL-2). However, appreciable levels of reactivity to anti-CD3 MoAb were detected in the B220-CD4+ cells, although the responsiveness of this subset to such stimuli were reduced, compared with those of normal control. These results indicate that the B220-CD4+ cells in lpr mice are phenotypically and functionally distinct from normal B220-CD4+ cells.     

Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3⁺, CD4⁺ and CD8⁺ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis. Received: 14 April 1999     

Establishment and characterization of αs1-casein–specific T-cell lines from patients allergic to cow’s milk: Unexpected higher frequency of CD8 T-cell lines

To study cow’s milk allergy at the cellular level, we assessed the reactivity of peripheral blood mononuclear cells from patients allergic to cow’s milk to α_s1-casein, which is one of the major allergens in cow’s milk. Proliferation of the cells to α_s1-casein activation showed a rather weak response. Therefore to understand T-cell reactivity to α_s1-casein in more detail, we prepared α_s1-casein–specific T-cell lines from patients allergic to cow’s milk and established 26 T-cell lines. These T-cell lines could be classified into three groups by analyzing their surface marker expression: those containing predominantly CD4⁺CD8^- T cells, those containing both CD4⁺CD8^- and CD4^-CD8⁺ T cells, and those containing predominantly CD4^-CD8⁺ T cells. The CD8⁺ T cells were obtained at an unexpectedly higher frequency from the patients. These T-cell lines produced interferon-γ and IL-4. These results suggest that CD8⁺ T cells specific for α_s1-casein and CD4⁺ T cells were primed by the stimulation with α_s1-casein in patients allergic to milk and that both T cells may play a key role in the onset, progression of, or recovery from cow’s milk allergy. (J ALLERGY CLIN IMMUNOL 1996;97:1342-9.)     

MORPHOLOGICAL DIFFERENCES IN HEARTS OF RATS WELL ADAPTED AND POORLY ADAPTED TO CHRONIC HYPOXIA

We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4-week-old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high. These data showed that in well developed rats under chronic hypoxia, there is good development of capillary supply with corresponding restriction of cardiac hypertrophy, while hematocrit count and mitochondria are also affected.     

MALIGNANT LYMPHOMA OF THE PAROTID GLAND WITH MONOCLONAL CYTOPLASMIC IMMUNOGLOBULIN

A 56-year-old Japanese man with a malignant lymphoma of the parotid gland was reported. The tumor was located in the superficial lobe of the parotid gland, and somewhat invaded the surrounding soft tissues, but the regional lymph nodes were not involved. Histologically, the tumor was composed of round cells with plasmacytoid configurations and small lymphocytes. The plasmacytoid cells showed eccentric nuclei with fairly marked irregularities and perinuclear halos. In a large number of tumor cells, a monoclonal cytoplasmic immunoglobulin (CIg), IgG-Kappa type, was demonstrated by the PAP method. Ultrastructurally, some of the tumor cells showed welldeveloped endoplasmic reticulum. From these findings, this tumor was diagnosed as a diffuse B-cell lymphoma, mainly composed of lymphoplasmacytoid cells. And this tumor may bear a similar nature to an extramedullary plasmacytoma of the classical terminology. Malignant lymphoma of the parotid gland is rare but a case with the demonstration of monoclonal CIg is considered very rare. ACT A PATHOL. JPN. 34: 1459–1467, 1984.     

Malignant mesenchymoma of the esophagus

This is a case report of a malignant mesenchymoma of the esophagus in a 50?year-old Japanese man. The tumor was a sessile polypoid mass showing a downward invasion limited to the submucosa of the esophagus. Histologically, the lesion contained rhabdomyosarcomatous and osteosarcomatous areas, in addition to an ill-defined fibrosarcomatous element. In contrast with reports of carcinosarcoma up to the present, this tumor lacked any invasive lesion of an epithelial malignancy. The morphogenesis of these tumor groups was discussed from a hamartoblastomatous standpoint. Acta pathol. jpn. 34: 925～933, 1984.     

Sex difference in delayed footpad reaction to syngeneic testicular cells in C3H/He mice.

Delayed footpad reaction against syngeneic testicular cells was compared between males and virgin females of C3H/He mice. Mice were immunized subcutaneously with 1 x 10(7) of syngeneic testicular cells and the reaction was elicited with 1 x 10(6) of syngeneic testicular cells 6 days after the immunization. When mice were pretreated with 0, 25 or 50 mg/kg of cyclophosphamide (CY), the delayed footpad reaction was detected in female mice, but not in male mice under the same conditions. This sex difference in the reaction to testicular cells was not attributed to the recognition of H-Y antigen by female mice. A sex difference in the reaction to sheep red blood cells (SRBC) was not observed. The sex difference in the reaction to testicular cells was attributed to testicular cells other than sperm because a sex difference was not detected against sperm. The implications of these findings are discussed in relation to the tolerance phenomena of autologous testicular cells.     

Mechanisms of in vivo generation of cytotoxic activity against syngeneic tumours. I. Local differentiation of mature cytotoxic T lymphocytes in the rejection of tumours.

Mature cytotoxic T lymphocytes (CTL) were detected in the peritoneal cavity of syngeneic mice immunized intraperitoneally (i.p.) with mitomycin C (MC)-treated EL-4 or X5563 cells, but were not found in their spleens or lymph nodes. Mature CTL appeared among PE cells after transfer of spleen cells from those immune mice, along with MC-treated tumour cells, to the peritoneal cavity of syngeneic mice. These results lead us to the hypothesis that immature CTL primed in the spleen and lymph nodes may migrate to the site of tumour inoculation and differentiate into mature CTL after antigenic or non-specific stimulation at that site. Inability of primed CTL to differentiate to mature CTL in the spleen might be explained by the effect of splenic suppressor cells, since mature CTL became detectable in the spleen of immune mice by treatment with cyclophosphamide.     

An Autopsy Case of Peritoneal Malignant Mesothelioma in a Radiation Technologist

A case of peritoneal maligant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, welt developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mosothelioma. Acta Pathol Jpn 40: 57–62, 1990.     

Synthesis and properties of thermotropic liquid-crystalline polymers containing transition metals

New thermotropic, liquid-crystalline polyesters ( 5a, b, 6a, b ) with mesogenic bipyridinediyl units were synthesized. They form complexes with Fe(II) and Cu(II) salts. Homopolyesters 5a, b , containing no metal or less than a certain amount of metal, are smectic. A nematic mesophase was observed in the case of copolyester 6a, b . The structural properties of a polyester complex 5a with Cu, as crystal, liquid-crystal and isotropic liquid, were examined by ESR.