B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors

The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function.     

Long-Term Follow-Up of the Changes in Circulating Cytokines, Soluble Cytokine Receptors, and White Blood Cell Subset Counts in Patients with Rheumatoid Arthritis (RA) After Monoclonal Anti-TNFα Antibody Therapy

To investigate the mechanism of the long-lasting efficacy of chimeric monoclonal anti-TNF antibody (cA2) therapy for rheumatoid arthritis (RA), eight patients with refractory RA were treated with a single infusion of cA2 and the changes in circulating cytokines (IL-1, IL-6, TNF, and IL-10), soluble cytokine receptors (TNF-RI, RII, and sIL-6R) and peripheral white blood cell (WBC) subset counts were followed up long-term (12 weeks) after cA2 therapy in them. Significant clinical responses (>20% improvement according to Paulus' criteria) were observed just after cA2 infusion and lasted more than 4 weeks in all patients, as reported elsewhere. Moreover, five of the eight patients showed prolonged clinical responses (>12 weeks). The elevated serum IL-6 and sTNF-RI (or RII) levels before treatment rapidly decreased after treatment. The serum IL-10 levels also significantly elevated before treatment. The elevations of serum IL-10 levels were augmented after treatment and stayed higher than the baseline in four patients with prolonged clinical responses. No significant TNF, IL-1 and -, or sIL-6R were detected in the sera of the patients before treatment and during the whole study period. On the other hand, peripheral lymphocytes as well as total WBC and neutrophils increased for 4 weeks after treatment. However, thereafter, only the lymphocyte count decreased gradually and stayed below the baseline long-term (12 weeks). FACS analysis revealed the predominance of T lymphocytes in the decrease in lymphocyte counts. These results suggest that the augmentation of IL-10 production and the decrease in T cells might partly contribute to the long-lasting efficacy of cA2 treatment in RA.     

CYTOLOGIC FEATURES OF ASCITES IN MALIGNANT FIBROUS HISTIOCYTOMA OF THE COLON

The cytologic features of ascitic fluid in a case of malignant fibrous histiocytoma (MFH) of the colon are described. At autopsy, two solid tumor masses were found around the ascending and transverse colon, accompanied by about 3,000 ml of ascites. Tumor cells had infiltrated diffusely into the outer layers of almost all of the gastrointestinal wall, simulating peritonitis carcinomatosa. Cytologic examination of the ascites revealed various kinds of tumor cells; short spindle-like cells, multinucleated giant cells, and round cells with an invaginated nuclear margin, forming small clusters. These cytologic findings were considered to be very useful in the diagnosis of MFH, especially in cytologic examinations of ascites. ACTA PATHOL JPN 38: 921 ∼ 928, 1988.     

Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma

To evaluate the clinical applicability of galectin-3 and CD44 variant 6 (CD44v6) immunostaining in fine-needle aspiration cytology (FNAC) of thyroid follicular tumors, 79 cytological specimens (35 follicular carcinomas and 44 follicular adenomas) were studied. The positive rates of galectin-3 and CD44v6 were 89 and 74% in follicular carcinoma, respectively, and 25 and 30% in follicular adenoma, respectively. There were no significant correlations between the expression of galectin-3 or CD44v6 in follicular carcinoma and characteristics such as capsular invasion, vascular invasion, metastasis, or tumor size. Positive staining of either galectin-3 or CD44v6 resulted in a diagnostic sensitivity of 97% and a specificity of 52% for follicular carcinoma among follicular tumors. Immunostaining of galectin-3 or CD44v6 using cytological specimens can provide independent information on conventional morphological findings of cytology to distinguish follicular carcinoma from adenoma.     

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women

Intending to clarify the true Incidence of Invasive lobular carcinoma of the breast In Japanese women as well as the frequency of unilateral multlcentriclty, 362 cases of clinically defined monocentrlc breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologlc types: Invasive lobular carcinoma (ILC) or Invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which Is more than In most previous Japanese studies. Unilateral multicentric breast carcinoma was detected In 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently In variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast In Japanese women is low and that unilateral multicentricity Is not significantly higher in ILC than in IDC.     

LIGHT AND ELECTRON MICROSCOPIC STUDY OF NONFUNCTIONING PARATHYROID CARCINOMA

A case of nonfunctioning parathyroid carcinoma in a 69-year-old female has been studied by light and electron microscopy. The tumor, located on the left side of the anterior neck, was well encapsulated by connective tissue but showed invasion to the capsule and to the thyroid. The tumor cells exhibited a trabecular arrangement surrounded by capillary networks but focally showed several ductal structures. They were polygonal in shape, had a large nucleus showing frequent mitosis and poor cytoplasm containing glycogen. Some tumor cells had clear and abundant cytoplasm, and resembled water-clear cells of the parathyroid. Immunohistochemically, no thyroglobulin was demonstrated in the tumor tissue. Electronmicroscopically, the tumor cells with high N/C ratio contained poorly developed cell organelles and abundant glycogen particles. They were poor in secretory granules and had no conglomeration of lipid. Desmosomes and tonoflbrils were observed. The ratio of the reported number of nonfunctioning parathyroid carcinoma to that of functioning one in Japan was compared with that in western countries. No difference of the ratio was found between these two, when identical criteria were employed.     

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sj?gren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.     

Case of postradiation osteosarcoma with a short latency period of 3 years

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.     

Growth of Bacteroides fragilis in Rabbit Tracheal Organ Culture: Anaerobiosis and Tissue Respiration

Rabbit tracheal explants supporting growth of inoculated Bacteroides fragilis in air were shown to keep low oxygen tension. Treating the explants with sodium azide induced high oxygen tension and arrested reversibly the growth of B. fragilis.