Structure of the functional interleukin-2 receptor: Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line

The structural basis of the high affinity interleukin-2 receptorwhich was previously reconstituted in a cultured murine T cellline, EL4 by expressing either wild-type Tac antigen complementaryDNA (cDNA) or a chimeric cDNA was characterized. The chimericcDNA encodes a membrane portion whose extracellular portionconsists of that of Tac antigen whereas transmembrane and cytoplasmicportions consists of those the human insulin beta chain. TheTac antigen/anti-Tac antibody complex was treated by chemicalcrosslinking reagents, purified by goat anti-mouse immunoglobulin(lg), and was analysed by SDS–PAGE. We here demonstrated the presence in mouse EL4 transfectantsof a novel membrane protein which is closely associated withthe products of transfected cDNAs in the absence of interleukln-2.The protein is 75 kDa in size and is detected in cells whichexpress high affinity interieukln-2 receptor but not in cellswhich only express low affinity interleukin-2 receptor. Thetransmembrane region and the cytoplasmic region of Tac antigenis not necessary for the formation of the complex consistingof Tac antigen and 75 kDa molecule, indicating that a murine75 kDa molecule associates with Tac antigen extra-cellularly.     

Survival of patients with HTLV-I-associated lymph node lesions

Adult T-cell leukaemia/lymphoma (ATLL), is a malignant condition associated with human T-cell leukaemia virus type I (HTLV-I). Usually, although not uniformly, histopathological examination of the lymph nodes shows a pleomorphic type. In addition, some patients with pre-overt ATLL show a Hodgkin's disease-like morphology and lymph nodes in non-neoplastic carriers show features of lymphadenitis. To characterize further the clinicopathological features of HTLV-I-associated lymphadenopathy, the histopathological features of the lymph nodes of 289 patients were classified into five types: lymphadenitis ( n=14), Hodgkin's-like (Hodgkin's) ( n=18), pleomorphic (medium and large cells) ( n=219), pleomorphic small cell ( n=11), and anaplastic large cell (ALC) ( n=27). Survival data were analysed according to the histopathological features of the lymph nodes. The pleomorphic type, which showed typical features of ATLL, was associated with a highly aggressive course and an initially high mortality, followed by a rapid decrease in survival. This pattern was also observed in patients with the ALC type. All cases with lymphadenitis were still alive at the end of the study, while survival progressively decreased in the Hodgkin's type. The small cell type showed an initial rapid decrease in survival followed by a plateau. These results show that the survival trends of patients with pleomorphic and anaplastic lymph node lesions are similar to those with ATL lymphoma, while patients with the lymphadenitis type of lesion were considered to have a non-neoplatic status. There is at present no effective therapy for ATLL, but in the future, these classification and survival data might be useful for the selection of appropriate chemotherapeutic regimens for patients with ATLL.     

Characterization of two distinct antigens expressed on either resting or activated human B cells as defined by monoclonal antibodies.

Two antigen systems (L29 & L30) expressed on two distinct human B cell subpopulations were identified by using BL1-4D6 and TB3-7D5 monoclonal antibodies, respectively. L29 was expressed on approximately one-third of B cells in human lymphoid tissues. These B cells associated with L29 were large activated B cells located in the germinal centres of lymphoid follicles. L30, on the other hand, existed on approximately two-thirds of B cells mainly located in the mantle zone of lymphoid follicles, most of which also expressed IgM and IgD on their cell membrane. In addition, L30 was shared on mature granulocytes. With the use of polyclonal activators such as pokeweek mitogen (PWM) and protein A-bearing staphylococci (SAC), L29 antigen was inducible on PWM- or SAC-stimulated B cells in correspondence with the emergence of Tac and T10 antigens of these B cells. In contrast, L30 antigen on the B cells stimulated by the polyclonal activators was decreased in its expression and was finally lost from these B cells. Although none of L29 and L30 was expressed on normal, non-activated human thymus and peripheral T cells, L29 but not L30 was expressed on concanavalin A-activated T cells. Immunochemical studies showed that L30 consist of a single polypeptide with mol. wt of 40,000. L29 antigen is presently under study.     

Detection of the Epstein-Barr virus in primary gastric lymphoma by in situ hybridization

The Epstein-Barr virus (EBV) has been shown to be associated with numerous human malignancies including Burktt's lymphoma and nasopharyngeal lymphoepithelioma. In addition, some typical gastric adenocarcinomas were also recently reported to demonstrate EBV relevance. The present study was designed to detect EBV in primary gastric lymphoma, using the in situ hybridization (ISH) method, in which oligo-nucleotide probes for the EBERl RNA and the EBV DNA W region have been used. Of the 49 cases of primary gastric lymphoma studied, which all showed B cell immunopheno-type, EBER1 sequences could only be found in four cases, including two low-grade cases and two high-grade cases of histological subtypes while the number of positive cells was less than 50% of the tumor cells. In one case of low-grade mucosa associated lymphoid tissue (MALT) lymphoma, the EBER1 -positive neoplastic cells were found in the regional lymph node, but the primary site of the stomach showed no positive signals. The EBV presence was further confirmed by the EBV DNA ISH. Using the ISH method, rare or occasional positive lymphoid cells (probably non-tumorous bystander cells) could be detected in 10 other cases including all histological subtypes. The present study shows that only a small proportion of primary gastric lymphoma is associated with EBV, and such positive cases could be found in both high- and low-grade histological subtypes. It is also suggested that the EBV presence in the neoplastic cells of some cases of primary gastric lymphoma is most likely a secondary phenomenon.     

Effects of cimetidine on tumor growth and immune function in nude mice bearing human ovarian carcinoma

The effects of cimetidine on the growth of a human ovarian cancer cell line inoculated into BALB/c nude mice were examined. The cell line, designated "KK," was derived from a cystadenocarcinoma of the ovary. The passage number was about 40, and its tumorigenicity in nude mice was 100% even when 10(5) cells were inoculated. About 2 weeks after inoculation, the KK cells formed palpable tumors, and the tumor volume reached 2.29 cm3 on day 36. Conversely, the nude mice given cimetidine (100 mg/kg/day) orally with drinking water had about one-third the tumor volume (0.81 cm3) of that in untreated nude mice on day 36. The natural killer activity against the YAC-1 (a T-cell lymphoma) cell line in spleen cells of the nude mice challenged with human xenogeneic tumor (KK cell line) was not affected by treatment with cimetidine while inhibiting the tumor growth. The capacity to lyse the KK cells did not exist in the spleen cells of nude mice challenged with the KK cell xenograft and not treated with cimetidine. The cimetidine-treated spleen cells acquired the capacity to lyse the KK cells on day 14. Thereafter, the capacity was maintained at the same level as long as cimetidine was administered, whereas that in untreated nude mice remained undetectable.     

Histological studies concerning the development of gastric stump carcinoma by endoscopic mucosal biopsies

225 patients who received partial gastrectomies more than five years ago were examined by endoscopy with mucosal biopsies. In the biopsies taken from mucosa close to the anastomosis, hyperplasia of the foveolar epithelium and glandular cysts, findings identical with "gastritis cystica polyposa", were most often seen following Billroth II resection. Cases in which more than 20 years had elapsed since Billroth II resection revealed the highest rate (65.2%) of such mucosal changes. A close relationship between 2 cases (B-II Group) of gastric stump carcinoma detected near the gastro-enteric anastomosis and such mucosal changes is suggested.     

Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).