Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.     

实验性糖尿病对小鼠肝脏酶组织化学和超微结构的影响

实验用四氧嘧啶建造糖尿病动物模型，８周后取肝作组织学、酶组织化学和超微结构的观察，以探讨实验性糖尿病对肝组织结构和功能的影响。表明在糖尿病状态下，肝细胞的结构和功能均受到一定的损害。     

Serological distinction of integral plasma membrane proteins as a class of mycobacterial antigens and their relevance for human T cell activation

This study pertains to classification and antigenic analysis of mycobacterial plasma membrane proteins in relation to human T cell proliferative responses, using a ‘fast grower’ Mycobacterium fortuitum as model. Membrane vesicles, prepared by sonication and differential centrifugation, were subjected to biphasic Triton X-1 14 extraction for isolation of integral (detergent phase) and peripheral (aqueous phase) proteins. Neither protein pool showed any appreciable overlap serologically. SDS-PAGE showed five prominent bands in peripheral and three in the integral protein pool, whereas immunoblotting with rabbit antisera identified only two major antigens (60 and 67kD) in the former and five (24, 34, 42, 51 and 54kD) in the latter, ELISA with a panel of anti-mycobacterial MoAbs revealed that nine out of 12 previously known antigens were present in the peripheral protein pool. Only two of them (33 and 40 kD) were additionally detected amongst integral proteins. The membrane-associated immunosuppressive moiety lipoarabinomannan was semiquantitatively located in aqueous phase. In bulk T cell proliferation assays, seven out of 10 subjects belonging to a ‘responder’ background (BT-BB leprosy patients and healthy contacts) showed high responses for Myco. fortuitum antigens. Proliferative response with integral proteins was comparable to that with whole membrane, hut it was significantly higher (P < 0.0005) than t he response with peripheral proteins. The distinction and relevance of integral membrane proteins as a class of mycobacterial antigens make them worthy of consideration in a subunit vaccine design.     

Characterization of a subtype of primary osteoclastoma: Extracellular calcium but not calcitonin inhibits aggressive HLA-DR-positive osteoclastoma possessing ‘functional’ calcitonin receptors

We report here a case of primary osteoclastoma that despite possessing HLA-DR-positive status and ‘functional’ calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the ‘functional’ calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors.     

Heterotopic heart transplants in Biomphalaria glabrata (mollusca: pulmonata). Fate of congeneric xenografts

Hearts were implanted heterotopically into the hemocoel of NIH albino Biomphalaria glabrata from three xenogeneic donor snails, including two New World (B. obstructa, B. tenagophila) and one Old World (B. alexandrina) species, as well as from wild type allogeneic donors. Recipients were examined histologically at 1, 3, 7, 10, 15, 30, 60, 120, and 180 days postimplantation (PI). Grafts from all four donor species were temporarily infiltrated by recipient hemocytes at early intervals PI and in most instances also became encapsulated. Furthermore, the grafts subsequently showed histopathological alterations and abnormal heartbeat relative to preimplantation controls. However, hemocytic reactions eventually subsided, the implants remained structurally intact, and implant myocardial cells both maintained high levels of intracellular glycogen and continued to contract rhythmically for 6 months. No major differences occurred in fates among different xenografts, or between xenografts and allografts. Our observations of prolonged xenograft survival differ from those of previous investigators, most of whom have reported rapid destruction of implanted xenogeneic tissues in molluscs.     

Signal transduction in human B cells initiated via Ig{beta} ligation

Ig and Igß heterodimers are non-covalently associatedwith Ig to compose the antigen receptor complexes on B cells.The demonstration that different sets of tyrosine kinases bindto the cytoplasmic tails of Ig and Igß suggests thatIg and Igß may activate distinct second messengerpathways. In this study, we examined the effects of mAbs againstan exposed epitope of human Igß on pre-B and B celltriggering. Cross-linkage of Igß on B cells leadsto activation of tyrosine kinases, hydrolysis of phosphatidylinositides,and elevation of intracellular Ca²⁺, effects qualitatively identicalto those of anti-_µ mAbs. Our observations thus indicatethat cross-linking of Igß does not segregate signaltransduction pathways connected with the cytoplasmic talls ofIg and Igß. Ig ligation has been reported to be moreeffective in triggering pre-B than B cells, whereas our resultsindicated that Igß ligation is more efficient in triggeringB than pre-B cells. In addition to their activation properties,the anti-Igß mAbs effectively modulated B cell receptorcomplexes and blocked terminal differentiation of all plasmacell isotypes. The findings support the idea that anti-Igßcould serve as a universal B cell immunosuppressant.     

The molecular basis of Natural Killer (NK) cell recognition and function

Natural Killer cells are likely to play an important role in the host defenses because they kill virally infected or tumor cells but spare normal self-cells. The molecular mechanism that explains why NK cells do not kill indiscriminately has recently been elucidated. It is due to several specialized receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis. Different types of receptors specific for groups of HLA-C, HLA-B, and, very recently, HLA-A alleles have been identified. While in most instances, they function as inhibitory receptors, an activatory form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C-, HLA-B- or HLA-A-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibitory form is characterized by a long cytoplasmic tail associated with a non-polar transmembrane portion, the activatory one has a short tail asociated with a Lys-containing transmembrane portion. Thus, these human NK receptors are different from the murine Ly49, that is a type II transmembrane protein characterized by a C-type lectin domain. A subset of activated T lymphocytes expresses NK-type class I-specific receptors. These receptors exert an inhibiting activity on T cell receptor-mediated functions and may provide an important mechanism of downregulation of T cell responses.     

基于形态学的均值平移算法的神经元干细胞图像的自动分割

在神经元干细胞的图像分析中,准确快速的图像分割是干细胞分化增值自动追踪系统的基础。为了准确地分割低对比度的灰度神经元干细胞图像,本研究提出一种基于形态学运算和均值平移算法的神经元干细胞分割方法,称其为形态学的均值平移算法。此算法可以快速地获得任意形状细胞的图像,并且能检测到图像中多连接边缘不封闭的细胞。将此方法应用于神经元干细胞序列图像分割中并且将其与门限分割、水线分割和活动轮廓进行对比。实验结果证明,与其它的方法相比,此方法获得的细胞分割形状更接近于真实细胞的形状,并且能获得或接近于原始图像中准确的独立细胞数目。此方法可以获得正确的分割结果,为进一步图像处理奠定了良好的基础。     

Early effects of aldosterone on the basolateral potassium conductance of A6 cells

Summary Aldosterone increases the basolateral conductance in target epithelia. The basolateral membrane of tight epithelia contains two different types of K⁺ conductances (G_K), a resting and a volume-activated G_K. We have studied the early effects (at 4 hours) of 500 nmol/l aldosterone on the basolateral membrane G_k of A6 cells (a Xenopus laevis kidney cell line), after the permeabilization of the apical membrane with amphotericin B. In the presence of a 97 to 3 mmol/l apical to basolateral K⁺ gradient, the resting, inward rectifying G_K was similar in control and aldosterone treated cells. In contrast, aldosterone induced a 2-fold increase of the volume-activated quinidine sensitive G_K.     

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hales colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.