Allopeptide-Specific CD4+ T Cells Facilitate the Differentiation of Directly Alloreactive Graft-Infiltrating CD8+ T Cells

To investigate the mechanism of CD4(+) T-cell help during the activation and differentiation of directly alloreactive CD8(+) T cells, we examined the development of obliterative airways disease (OAD) following transplantation of airways into fully mismatched recipient mice deficient in CD4(+) T cells. BALB/c trachea allografts became fibrosed significantly less frequently in B6 CD4(-/-) recipients as compared to wildtype controls. Furthermore, class I-directed cytotoxicity failed to develop in the absence of CD4(+) T cells. The infiltration of graft tissue by primed L(d)-specific directly alloreactive 2C CD8(+) T cells was not found to depend on the presence of CD4(+) T cells. Nevertheless, graft-infiltrating 2C CD8(+) T cells failed to express CD69 and granzyme B when CD4(+) T-cell help was unavailable. Importantly, reconstitution of B6 CD4(-/-) recipient mice with graft peptide-specific TCR-Tg CD4(+) T cells (OT-II or TEa) capable of recognizing antigen only on recipient APC allowed for full expression of CD69 and granzyme B by the directly alloreactive CD8(+) T cells and restored the capacity of recipients to reject their allografts. These results demonstrate that indirectly alloreactive CD4(+) T cells ensure the optimal activation and differentiation of graft-infiltrating directly alloreactive CD8(+) T cells independent of donor APC recognition.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

按压骨穴调节围绝经期妇女心脏植物神经功能的研究

目的观察按压骨穴对围绝经期妇女心脏植物神经功能的影响。方法设按压骨穴组30例、空白对照组30例。用美国BraemarDL700型动态心电检测仪,检测试验前后的心率变异性(HRV):TF代表总频,LF代表交感神经活性,HF代表迷走神经活性,LF/HF代表交感神经与迷走神经均衡性。结果按压骨穴后4项指标均有显著下降(P<0.01,P<0.05)。空白对照组变化不显著(P>0.05)。骨穴组4项指标的变化率与对照组比较均有显著性差异(P<0.01)。结论按压骨穴有抑制心脏交感神经活性的良性调整作用,此效应具有相对的特异性。     

Hypophyseal Non-Hodgkin's Lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy

Summary A patient is described with a testicular Non-Hodgkin's Lymphoma (NHL) presenting with panhypopituitarism caused by a hypophyseal localization. A⁶⁷Gallium scintigraphy showed avid uptake in the hypophyseal region. Obviously⁶⁷Gallium could reach the tumor, by the intravenous route, which was the reason to treat the patient with intravenous chemotherapy. A complete remission was induced, which seems to be lasting (+ 25 months). As far as we know this is the first report of panhypopituitarism caused by a hypophyseal NHL in the hypophysis and successfully treated by intravenous chemotherapy.     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Hemophagocytic syndrome and T-cell lymphoma after kidney transplantation: a case report

Lymphoma in immunocompromised transplant patients is a feared cause of morbidity and mortality. Superimposed on the lymphoma and the transplantation immunosuppression is a rare condition: hemophagocytic syndrome (HS). HS is characterized by fever, hepatosplenomegaly and lymphadenopathy, skin rashes, jaundice, coagulopathy, and phagocytosis of blood elements with pancytopenia. Here we describe a rare but fatal case of a kidney transplant patient who developed T-cell lymphoma and HS, without evidence of EBV replication. A short review of the diagnosis, treatment, and prognosis of HS is given. Received: 4 March 1997 Received after revision: 6 June 1997 Accepted: 30 June 1997     

43例鼻咽,鼻腔恶性淋巴瘤的临床病理及免疫表型研究

本文对遵义地区４３例鼻咽、鼻腔恶淋巴瘤的临床病理及免疫学表型进行了研究，结果显示：全部病例均为弥漫型，无１例滤泡型，组织学类型以多表细胞性淋巴瘤为主，共３３例（包括小细胞型１３例，中多形１５例，大多形５例），占７６．７％。用ＵＣＨＬ－１、ＣＤ２０和Ｍａｃ３８７等多单克隆抗体进行免疫表型研究。显示Ｔ细胞淋巴瘤３７例（８６％），Ｂ细胞淋巴瘤４例（９．３％），无１例组织细胞性淋巴瘤。鼻咽部Ｔ．Ｂ淋巴瘤比     

氟对人体T细胞数目的影响及硼砂拮抗作用的观察

将３８例地氟病人分为硼砂治疗组和治疗对照组，通过对病人外周血Ｔ淋巴细胞亚群含量的检测，观察了氟对人体Ｔ３、Ｔ４、Ｔ８淋巴细胞含量的影响以及硼砂的拮抗作用。结果表明，在本研究条件下，地氟病人外周血Ｔ３、Ｔ４淋巴细胞数目明显减少，硼砂对此变化无明显的拮抗作用。