Antigen presentation by a B-cell line transfected with cloned immunoglobulin heavy- and light-chain genes specific for a defined hapten.

The rearranged genes encoding immunoglobulin heavy (mu) and light (kappa) chains specific for the hapten 2,4,6-trinitrophenyl (Tnp) were introduced into a B-lymphoma line that bears surface IgG with an unknown specificity and expresses surface Ia molecules. A transformant expressing surface IgM specific for Tnp was obtained. The transformant was found to present Tnp-proteins to antigen (protein)-specific T cells far more efficiently than the parenteral B-lymphoma line. This artificial system, utilizing recombinant DNA technology and gene transfer, provides several approaches for the study of T-cell-B-cell interactions.     

Effect of ACTH,adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)₂ receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the B_max values for³H-ketanserin binding without any change in the K_d values. Moreover, this ACTH-induced increase in the B_max values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT₂ receptor density in the neocortex of rat forebrain. 5-HT₂ (and 5-HT_1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT₂ receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI.     

Anatomy and pathophysiology of the popliteal tendon area in the lateral meniscus: 1. Arthroscopic and anatomical investigation

An arthroscopic and anatomical investigation was performed to define the abnormal conditions of the popliteal tendon area in a lateral meniscus. Arthroscopic findings for 100 patients and anatomical observations of 10 amputated knees were analyzed. Five of the 10 dissected menisci were also examined histologically. Menisco-tibial coronary ligaments were classified into two types, as follows: type I--a coronary ligament covering an entire popliteal tendon beneath the meniscus; type II--a popliteal tendon visible beneath the meniscus through defects of the coronary ligament. Twenty-one of 100 cases were classified as type I, and 79 were classified as type II. Three of the 10 anatomical dissections were type I, and the remaining 7 were type II. Menisci in which the type I coronary ligaments were thought to be torn and menisci with type II coronary ligaments showed a rather marked mobility, but no conclusion could be reached.     

Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis

Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.     

Differentiation therapy of hematologic malignancies: principles, current status and perspectives]

There is increasing evidence that various tumor cells can be induced by differentiation inducers including biological response modifiers, synthetic chemicals and conventional anticancer drugs to differentiate terminally both in vitro and in vivo into cells with normal characteristics. The differentiated cells lose their abilities for proliferation and transplantation in animals. Furthermore, survival times of the animals inoculated with various tumors were found to prolong by administration with the differentiation inducers. These basic findings suggest that induction of terminal tumor cell differentiation is another strategy for cancer therapy: differentiation therapy of cancer. Principles, current status and perspectives of the differentiation therapy of leukemia are reviewed in this article.     

Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo

Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.     

A stereomicroscopic study of the mastopathic human breast

Summary The stereomicroscopic study of cystic disease of the breast revealed the presence of abnormal ductules near the terminal sites of the original lactiferous ducts. This alteration was the key feature of cystic disease since the involution of abnormal ductules possibly may have induced the stricture of the original duct by increasing fibrosis around the site of duct evolution. The phenomenon could contribute to the creation of cystic dilatation of distal ducts and acini. Multiple large cysts characterizing the morphology of cystic disease may represent the end stage of distended ducts and acini. Prolonged and repeated unbalanced stimulation of hormones could produce progressive and regressive alternations in the same breast. This modifies the original alteration into more pleomorphic and complicated types.

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Stereomikroskopische Studie der durch Mastopathie veränderten menschlichen MammaII. Die peripherische Form der Milchgangsevolution und ihre Beziehung zur Cystenmamma

Zusammenfassung Die stereomikroskopische Untersuchung sog. Cystenmmamen zeigt, daß die Cysten durch Ektasie der sog. Kanälchen-Endäste entstehen. Dagegen werden die Stamm-Milchgänge einer Involution zugeführt. An der Cystenbildung beteiligen sich auch die Acini. Als morphogenetische Reize kommen hormonelle Dysregulatonen in Frage. Durch die unterschiedliche Ausbildung der Kanälchen proliferation einerseits, die Involution sowie Cystenbildung andererseits resultiert ein buntes, wenig einheitliches Bild.

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Clinical Investigator, Veterans Administration Hospital, San Francisco, California, U.S.A., Former Postgraduate Student, Faculty of Medicine, Tokyo Medical and Dental University, Japan.

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This investigation was carried out at the Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University from 1958 to 1960 and was partially supported by a special research grant of the Japanese Ministry of Education.     

The expression of vascular endothelial growth factor-A and -C, and receptors 1 and 3: correlation with lymph node metastasis and prognosis in tongue squamous cell carcinoma

We determined whether the expression of VEGF-A and -C and their receptors, Flt-1 and Flt-4, are associated with primary tumor size, regional lymph node metastasis, distant metastasis and prognosis in patients with tongue carcinoma. The expression of VEGF-A and -C, and their receptors, Flt-1 and Flt-4, in biopsy specimens taken from 73 patients with tongue carcinoma were examined by immunohistochemical staining. VEGF-A expression was associated with distant failure and VEGF-C expression correlated with locoregional recurrence and distant failure. Furthermore, VEGF-C expression was associated with lymph node recurrence in N0 cases. Multivariate analysis revealed that VEGF-C expression was an exclusively independent factor influencing lymph node metastasis. In terms of the overall 5-year survival rate, there was no significance correlation between the overall 5-year survival rate and expression of VEGF-A, Flt-1 and Flt-4 expression, whereas there was a significant difference between VEGF-C-positive and VEGF-C-negative cases (VEGF-C-positive, 51.7% vs VEGF-C-negative, 94.2%). Furthermore, there was a significant difference between positive and negative expression for both VEGF-A and VEGF-C. Multivariate analysis revealed that lymph node metastasis and VEGF-C expression were exclusive, independent factors influencing the overall survival rate. VEGF-C expression may be a predictive factor of regional lymph node recurrence and prognosis in patients with tongue carcinoma.     

Effect of Mycoplasma arthritidis superantigen on enzymatically induced arthritis in mice.

The objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intra-articular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intra-articular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis.