[Magnetic resonance imaging findings of intravascular papillary endothelial hyperplasia].

This paper analyzed the imaging data of intravascular papillary endothelial hyperplasia (IPEH) in 5 cases, with 1 male, 4 females, aged 28-61 years. MRI of IPEH revealed well-demarcated masses with central iso-or hypointensity and peripheral hyperintensity on T2-weighted image(T2WI), as well as peripheral enhancement or hyperintensity on T2WI with/without hypointense foci, as well as homogeneous enhancement or heterogeneous enhancement with nonenhanced foci. CT demonstrated iso-or slightly hyperdense, well-circumscribed mass with bone destruction or calcification.

[Effects of vestibular spontaneous nystagmus on visual smooth pursuit function].

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(ttotal=13.338, tlight=6.184, tmedium=8.436, tstrong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.

Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation.

AKT pathway has a critical role in mediating signaling transductions for cell proliferation, differentiation and survival. Previous studies have shown that AKT activation is achieved through a series of phosphorylation steps: first, AKT is phosphorylated at Thr-450 by JNK kinases to prime its activation; then, phosphoinositide-dependent kinase 1 phosphorylates AKT at Thr-308 to expose the Ser-473 residue; and finally, AKT is phosphorylated at Ser-473 by several kinases (PKD2 and others) to achieve its full activation. For its inactivation, the PH-domain containing phosphatases dephosphorylate AKT at Ser-473, and protein serine/threonine phosphatase-2A (PP-2A) dephosphorylates it at Thr-308. However, it remains unknown regarding which phosphatase dephosphorylates AKT at Thr-450 during its inactivation. In this study, we present both in vitro and in vivo evidence to show that protein serine/threonine phosphatase-1 (PP-1) is a major phosphatase that directly dephosphorylates AKT to modulate its activation. First, purified PP-1 directly dephosphorylates AKT in vitro. Second, immunoprecipitation and immunocolocalization showed that PP-1 interacts with AKT. Third, stable knock down of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta by shRNA leads to enhanced phosphorylation of AKT at Thr-450. Finally, overexpression of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta results in attenuated phosphorylation of AKT at Thr-450. Moreover, our results also show that dephosphorylation of AKT by PP-1 significantly modulates its functions in regulating the expression of downstream genes, promoting cell survival and modulating differentiation. These results show that PP-1 acts as a major phosphatase to dephosphorylate AKT at Thr-450 and thus modulate its functions.

Detecting early breast tumour by finite element thermal analysis.

Thermography has been proved to be an effective technique for indicating breast disease abnormalities or risks. However, the abnormalities might not express clearly due to various factors, such as when a small tumour is located in a deep region, or environmental influences that make breast disease difficult to find. This study aims to solve these problems for early detection of breast tumour. A three-dimensional breast model is presented to investigate the relationship between an embedded tumour and the surface temperature distribution. Then a subtraction technique is used to enhance the thermal signature of breast tumour. It was showed that the surface thermal characteristics of a small tumour even in a deep region could be found easily by this method. Furthermore, it was also found that the surface thermal characteristics of tumour obscured due to environmental cooling effect can be clearly displayed. The results are very useful for analysing breast thermograms.

Long-term survival of cardiac allografts induced by cyclophosphamide combined with CTLA4Ig-gene transfer mediated by adenoviral vector.

There is a need to achieve donor-specific tolerance in clinical organ transplantation, where potential benefits remain overshadowed by chronic rejection and the side-effects of long-term immunosuppressive therapy. It is known that the mature immune system in mice can be reprogrammed to accept a foreign graft as if it was "self". The AdCTLA4Ig-mediated gene transfer (SC) + cyclophosphamide (CP) treatment alone prolongs allograft survival but does not induce tolerance. However, in our study, the AdCTLA4Ig-mediated gene transfer combined with SC + CP treatment yielded significantly prolonged mean survival times (149.7 +/- 18.0 days), while those in the untreated or AdLacZ treated mice were rejected in normal fashion (5.3 +/- 0.5 and 5.2 +/- 0.4 days, respectively), and survival in the AdCTLA4Ig or SC + CP treated groups were 45.7 +/- 9.6 or 50.2 +/- 5.3 days, respectively. In conclusion, a protocol of AdCTLA4Ig + SC + CP improved the survival of DA-->LEW cardiac allografts.

Improving the blood compatibility of polyurethane using carbon nanotubes as fillers and its implications to cardiovascular surgery.

Blood compatibility has been an occlusion for biomaterials used in the cardiovascular system. In this work, a multiwalled carbon nanotubes-polyurethane composite (MWNT-PU) was prepared through a controlled co-precipitation. The surface chemical composition of treated carbon nanotubes was analyzed with XPS and the thermal behaviors of composite were characterized by DSC. The platelet adhesion and activation caused by the composite were evaluated by using SEM and flow cytometric analysis, respectively, and the disruption of red blood cells was analyzed through measuring the absorbance of free hemoglobin. The experimental results demonstrated that: (1) Multiwalled carbon nanotubes (MWNTs) with oxygen-containing functional groups could be well dispersed in polyurethane matrix through a controlled coprecipitation; (2) the composite surface displayed a significantly improved anticoagulant function, which can be indicative of the promising potentials of carbon nanotube-based materials in the implants and medical devices applied in blood-contacting environments.

Antileukemic effect of interleukin-7-transduced bone marrow stromal cells in mice following allogeneic T-cell-depleted bone marrow transplantation.

Impaired immune reconstitution following allogeneic bone marrow transplantation (BMT) remains a major obstacle to its clinical application. In this study, interleukin (IL)-7-transduced bone marrow stromal cells (MSC-IL7, 1 x 10(6)/mouse) were transfused into lethally irradiated C57BL/6 recipient mice. By day 40 after transplantation, the recipient mice were challenged with the lymphoma cell line EL4. MSC-IL7 co-transplantation protected recipient mice from leukemic mortality (MST >120 days after BMT vs mean survival time (MST) 70 days in the PBS group) It enhance the PFC count and DTH responses of recipients after transplantation. In conclusion, MSC mediated IL-7 gene therapy and may be a more feasible strategy to restore immune function following allo-TCD-BMT.

CTLA4-Fas ligand gene transfer mediated by adenovirus induce long-time survival of murine cardiac allografts.

BACKGROUND: Fas ligand gene transfer to induce peripheral allograft tolerance in animal models has shown controversial results. The immunosuppression effects mediated by engineered FasL depend on whether alloreactive T cells are selectively deleted. In the present study, we tested the feasibility of a strategy to induce long-time survival by fusing CTLA4-FasL gene transfer in vivo. METHODS: Cardiac allografts from DA(RT-1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. Plaque units (5x10(9)) of either AdCTLA4-FasL, AdCTLA4Ig, or AdEGFP were administered via the portal vein immediately after cardiac transplantation. The frequencies of helper T lymphocyte precursors (HTLp) and cytotoxic T lymphocyte precursors (CTLp) were determined by a combined single limiting dilution assay on days 5 and 20 after transplantation. RESULTS: Cardiac allograft survival was significantly prolonged by either AdCTLA4-FasL or AdCTLA4Ig treatment(mean survival times [MST] of 71.0 +/- 3.7 and 45.7 +/- 2.4, respectively, n = 6) compared with untreated hosts or animals treated with AdEGFP(MST of 5.7 +/- 0.5 and 5.2 +/- 0.4, respectively, n = 6). In addition, treatment with AdCTLA4-FasL led to significantly prolonged allograft survival compared with AdCTLA4Ig treatment. Furthermore, the frequencies of HTLp and CTLp on day 20 among rats treated with AdCTLA4-FasL was lower than those on day 5, whereas frequencies of HTLp and CTLp on day 20 were similar with those on day 5 in the other groups. CONCLUSION: These results suggest that administration of an adenovirus encoding fusion CTLA4-FasL gene to rat recipients effectively decreased the size of alloreactive T cells and induced long-term survival of cardiac allografts.

Blockade of both CD28/B7 and OX40/OX40L co-stimulatory signal pathways prolongs the survival of islet xenografts.

CTLA4Ig, a recombinant fusion protein composed of the extracellular domain of human CTLA4 and the constant region of human IgG1, inhibits the interaction of CD28/B7 pathway by binding the B7 molecule. OX40Ig, a recombinant fusion protein composed of the extracellular domain of human OX40 and the constant region of human IgG1, abrogates the interaction of OX40/OX40L pathway by binding the OX40L on APCs. So blockade of CD28/B7 or OX40/OX40L co-stimulatory pathways alone in mice with CTLA4Ig or OX40Ig can result in finitely prolonging the survival of islet grafts (43.2 +/- 4.81 and 67.7 +/- 7.74 days, respectively). In this study, a novel replication-defective adenovirus containing both of the CTLA4Ig and OX40Ig genes, AdCTLA4Ig-IRES-OX40Ig, was constructed by homologous recombination and injected into the streptozocin-rendered diabetic BalB/c mouse recipients (H-2d) through the tail vein, at the same day, the freshly isolated islets from Lewis rats (RT-1) were transplanted under the left kidney capsule of the recipients. The results showed that the mean survival time of the islet xenografts in the AdCTLA4Ig-IRES-OX40Ig-treated diabetic mice was significantly prolonged (100.3 +/- 14.94 days), while those in the untreated or AdEGFP-treated mice were rejected in normal fashion (6.7 +/- 0.94 and 7.0 +/- 1.0 days, respectively). In conclusion, utilizing AdCTLA4Ig-IRES-OX40Ig in vivo which can simultaneously express CTLA4Ig and OX40Ig proteins can improve the survival of Lewis-->BalB/c islet xenografts.

Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts.

Co-stimulatory blockade combined with donor bone marrow transfusion engenders stable mixed chimerism and robust tolerance to various organ and cell transplants. However, repeated administration of costly agents to block the co-stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in most protocols are impeding clinical development of this strategy. To circumvent these shortcomings, we developed a plan in which repeated administration of costly agents was replaced by a single injection of adenovirus containing the gene of interest, and the high dose of donor BMCs replaced by a mixture of low-dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT-1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 x 10(6)), and SPLCs (50 x 10(6)) was administered to recipients via the portal vein immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly prolonged cardiac allograft survival in recipient rats, while animals that received no treatment or treatment with control adenovirus (AdLacZ) promptly rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed chimerism, rendering them long-term survivors of cardiac allografts that also accepted skin grafts from the donor but not the third-party strain. We conclude that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism with a potential application for clinical development.

Bicistronic adenovirus-mediated gene transfer of CTLA4Ig gene and CD40Ig gene result in indefinite survival of islet xenograft.

Blockade of CD40-CD154 costimulatory pathway in mice and primates with anti-CD154 monoclonal antibodies results in prolonged survival of vascularized organs and islet grafts. CD40Ig, a recombinant fusion protein comprised of the extracellular domain of human CD40 molecule in frame fused with the site-mutated human IgG1 Fc region, abrogated the cognate interaction of CD40-CD154 pathway by binding the CD154 molecule. In this study, replication-defective adenovirus containing the CD40Ig gene was prepared by homologous recombination and used to infect freshly isolated islets from LEW rats (RT-1(1)) in vitro using a titered dose. The islet transfectants (500 per recipient) were transplanted under the left kidney capsule of streptozocin-rendered diabetic C57BL/6 mouse recipient (H-2(b)). The mean survival time of AdCD40Ig-transfected islet grafts was significantly prolonged, while mock-infected grafts and AdEGFP-transfected grafts were rejected in normal fashion. Additionally, dose-dependent prolongation of islet graft survival was observed in mice receiving AdCD40Ig-transfected grafts. In conclusion, local production of Cd40Ig via adenoviral-mediated gene transfer induced dose-dependent prolongation of LEW --> Balb-c islet xenografts.

[Study on third-type immunoliposomes loaded drugs and the targeting in vitro and in vivo].

AIM: To study the preparation, targeting and pharmacodynamics of third-type immunoliposome loaded anticancer drugs. METHODS: The monoclonal antibody of human bladder cancer was combined with the terminal of PEG-COOH (polyethyleneglycol carboxylic acid) that make the liposomes not only prolong circulation by the membrane protection of PEG, but also target by spreading the antibody on the liposomes surface. That was the third type immunoliposomes. According to this scheme, the IML-ADM (immunoliposome carried adriamycin) wes prepared in which ADM entrapment was efficient and stability was high and the antibody activity was kept. RESULTS: The % survival of the targeting EJ cells treated with IML-ADM (ADM = 45.45 micrograms.mL-1) was 4.3% +/- 1.0%, but 72% +/- 6% for non-targeting LOVO cells in vitro; the tumor weight in nude mice which were implanted by EJ cells after 27 days were (39 +/- 25) mg, (135 +/- 32) mg, (598 +/- 240) mg treated by IML-ADM, SSL-ADM (steric stable lipsomes carried Adriamycin) and normal saline, respectively, in vivo. CONCLUSION: The results confirmed that the immunoliposme-mediated targeting anticancer drug is a feasible way.

[Study on preparation and biodistribution of PEG-immunoliposomes with active carboxylic terminals].

AIM: In order to accumulate into its target specifically, the immunoliposomes must possess two characteristics: specific target efficiency to its target cells and prolonged circulation in blood. A new type of polyethylene glycol (PEG)-immunoliposomes carrying monoclonal antibodies at the distal end of PEG chains should be developed. METHODS: A dipalmitoylphosphatidylethanolamine (DPPE) derivative of PEG with carboxyl group (DPPE-PEG3000-COOH) was newly synthesized. Small unilamellar liposomes were prepared from egg phosphatidyl choline and cholesterol (5:4, mol/mol) containing 6 mol% DPPE-PEG3000-COOH using reverse-phase evaporation method followed with bath sonication. Monoclonal antibody of human bladder cancer cell (BDI-1), which is highly specific to human bladder cancer cell, was conjugated to PEG-liposomes as well as mouse IgG at the distal end of polyethylene glycol chain. Doxorubicin was entrapped into these immunoliposomes by remote (NH4)2SO4 gradient loading method. The specific targeting efficiency of these immnoliposomes was tested by cytotoxicity test in vitro, enzyme-linked immune sorbent assay (ELISA) and indirect fluorescent immunoassay. Its biodistribution was carried out in mice. RESULTS: The specific targeting efficiency of BDI-1 immunoliposomes (BDI-1-IML) to EJ cells has been demonstrated, in contrast to the nonspecific human colon carcinoma cells (LOVO). PEG-liposomes linked with mouse IgG (mouse-IgG-immunoliposomes, IgG-IML) displayed lower reticulo-endothelial systems (RES) uptake and longer circulation time than liposomes without PEG after intravenous injection. CONCLUSION: The long circulation of these PEG-immunoliposomes in vivo, combined with its specific targeting efficiency demonstrated in vitro, guarantees the positive targeting efficiency of these immunoliposomes to its target carcinoma in vivo.

Targeted diagnosis of bladder and ureteral carcinoma using radiolabelled BDI-1.

The aim of this study is to investigate the possibility of radioimmunoimaging (RII) by radiolabelled anti-bladder carcinoma monoclonal antibody BDI-1 applied to diagnosis of bladder cancer and ureteral cancer. BDI-1 was labelled with 131I and 99mTc. The immunoreactivity, pharmacokinetics and biodistribution in mice were studied. RII was performed in 46 patients. The results showed that 131I, 99mTc-BDI-1 have satisfactory immunoreactivity and excellent tumor-locating properties. The blood clearance half-life T1/2alpha and T1/2beta were 35 h in the first phase and 151 h in the second phase, respectively. Thirty-nine patients were studied by an intravesical administration method; the sensitivity was 90.5%. Seven patients were studied by an intravenous administration method. The RII results of three cases with primary or recurrent bladder cancer and three cases with ureteral cancer were confirmed histologically. RII was negative in one patient with suspected lung metastasis that was shown on radiography. The investigation revealed that RII can be used as an auxiliary method for the detection of bladder cancer and may be valuable for the diagnosis of ureteral cancer.

Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury.

Proliferation of type II pneumocytes has been linked to a repair process during the early phase of acute lung injury, and it persists for a variable period. The mechanisms responsible for their dissolution and/or disappearance are not known, but we speculate that it may be partly due to apoptosis. Sections of lung tissue from patients with acute lung injury (n = 7) and chronic interstitial pneumonia (n = 14) were stained for detection of apoptotic cells via specific labeling of nuclear DNA fragmentation. Results were correlated with those of proliferating cell nuclear antigen (PCNA) staining for cell proliferation. Marked apoptosis of CD68-negative type II pneumocytes (30 to 80%) was detected in four of the seven (57%) cases of acute lung injury. In these cases, representing the resolution phase of acute lung injury, PCNA positivity in pneumocytes was extremely rare. In the 3 other cases in the acute/proliferative phase, apoptotic type II pneumocytes were rare whereas PCNA expression was quite evident in these cells. In chronic interstitial pneumonia, only rare type II pneumocytes (< 5%) exhibited apoptosis, and they showed variable staining for PCNA (up to 70%). We conclude that proliferation of type II pneumocytes occurs during the early phase of acute lung injury and is of variable extent and duration. In the resolution phase of acute lung injury, extensive apoptosis of type II pneumocytes is largely responsible for the disappearance of these cells. The time frame within which the apoptotic response occurs is variable and is likely to be dependent upon the specific etiology and extent of the injury. In chronic interstitial pneumonia, type II pneumocytes proliferate continuously, although to a much lesser degree than in the early phase of acute lung injury, and are minimally apoptotic.

Absence of T-cell- and B-cell-specific transcription factors TCF-1, GATA-3, and BSAP in Hodgkin's Reed-Sternberg cells.

Based on the presence of T cell receptor-beta (TcR-beta) gene rearrangements in L428 and HDLM-1 cells, the expression of CD2 in HDLM-1 cells, and the presence of immunoglobulin heavy-chain (IgH) gene rearrangement in KM-H2 cells, some researchers have concluded that these long-term cell lines derived from patients with Hodgkin's disease are lymphoid in nature. The information obtained from these cell lines has also been used in arguments for a lymphoid origin of H-RS cells in tissue despite the frequent absence of lymphoid markers and Ig/TcR gene rearrangements in these cells. We questioned whether one can use the limited expression of lymphoid markers or the limited gene rearrangement to conclude that H-RS cells have a lymphoid origin, because these markers may be aberrant in tumor cells. In this study, we examined the expression of two T-cell-specific transcription factors (TCF-1 and GATA-3) and one B-cell-specific transcription factor (BSAP) in cultured H-RS cells by using a gel mobility shift assay. The sensitivity and specificity of this assay for determination of cell lineage have been established in a large number of cultured human and murine cell lines. All three types of H-RS cell lines were consistently negative for BSAP, TCF-1, and GATA-3. The absence of GATA-3 was confirmed in H-RS cells in tissues by an in situ hybridization technique. Virtually all B-cell lines, with the exception of some myeloma cell lines, are positive for BSAP, which is the transcription factor for promoters for several B-cell markers, including VpreB1, lambda 5, CD19, and CD20. All T-cell lines tested were positive for TCF-1 and GATA-3, which are the transcription factors for promoters for several T-cell-restricted markers, including CD2, CD3, TcR, and lck. The absence of BSAP, TCF-1, and GATA-3 clearly indicates an underlying difference between H-RS cells and lymphoid cells.

Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. ii. from cytokines to cell lineage.

The true identity of Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells has been a subject of controversy for decades. Those who believe that Hodgkin's disease (HD) is a heterogeneous disease may consider it to constitute lymphomas of various origins. However, this theory seems incompatible with the finding of similar phenotypic, biologic, and immunologic properties among most HD. We believe that, in the majority of cases, HD, except for LP and some LD-type HD, is a homogeneous disease despite differences in the degree of fibrosis and/or cellular reaction. The heterogeneity in cellular reactions is a result of secretion of various cytokines by H-RS cells, which may or may not be influenced by the presence of EBV. H-RS cells, and anaplastic large cell lymphoma (ALCL) cells as well, can express a combination of cytokines and cytokine receptors that is not seen in other types of lymphomas. The unique cytokine/receptor profile (e.g. the expression of c-kit-R/CD117), along with various properties associated with H-RS/ALCL cells, leads to a hypothesis that H-RS/ALCL cells are related to similar lymphohematopoietic progenitor cells with different etiologies and somewhat limited differentiation capacity. A number of H-RS cells may differentiate with limited capacity along the B-cell pathway and may be infected by EBV, which further complicates the biologic and immunologic properties of these cells. The majority of H-RS cells may also, however, differentiate along the antigen-presenting dendritic cell pathway, as indicated by the abundant expression of restin, CD15, CD40, CD54, CD58, CD80, and CD86. The majority of ALCL cells clearly differentiate to T cells, but some may acquire B-cell or histiocyte phenotypes. The progenitor cell hypothesis may explain (1) the variable expression of CD117, CD43, and CD34 as well as the absence of CD27, CD45 and CD45RA in H-RS cells; (2) the inconsistent and irregular patterns of phenotype and genotype and the various, often very limited, degrees of differentiation among these two types of lymphoma cells; (3) the existence of secondary HD or ALCL associated with rare types of lymphomas or leukemias, or vice versa; (4) the absence of recombinase and of the B-specific transcription factors BSAP; and (5) the frequent expression of IL-7 and IL-9 in H-RS cells. Copyright 1996 S. Karger AG, Basel

Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. 1. unique cytokine and cytokine receptor profile distinguished from that of non-hodgkin's lymphomas.

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells and anaplastic large cell lymphoma (ALCL) cells are known to express a variety of cytokines, including IL-1, -5, -6, -8, -9, TNF-alpha, GM-CSF, M-CSF, TGF-beta, CD70, CD80, and CD86. Various numbers of H-RS/ALCL cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), TNF-R (CD120), TGF-beta-R (CD 105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS/ALCL cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD) or ALCL. Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this review, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS/ALCL cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD/ALCL from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86- CD28, SCF-CD117, IL-9-IL-9R, and IL-7-IL-7R. The H-RS/ALCL cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS/ALCL cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD/ALCL because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these costimulators (CD70 and CD80/CD86) and other adhesion/constimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as IL-1, IL-6, IL-7, or TNFs by H-RS/ALCL cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD and some ALCL. On the other hand, the expression of CD30L and CD40L by surrounding T cells may affect the proliferation of H-RS/ALCL cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bidirectional, a situation not commonly seen in NHLs. Copyright 1995 S. Karger AG, Basel

[Study on the specific killing activity of albumin nanoparticles containing adriamycin targeted by monoclonal antibody BDI-1 to human bladder cancer cells].

A highly specific immuno-nanoparticle (ADR-NP-Ab) has been constituted by chemically coupling a monoclonal antibody BDI-1 to albumin nanoparticle containing adriamycin (ADR-NP). Different molecular ratios of antibody to ADR-NP were tried to determine the optimal condition for preparing the immuno-nanoparticle. The results of immunoflurecence and microphotographic analysis showed that the activity of ADR-NP-Ab was well preserved. The result of the cytotoxicity of ADR-NP-Ab in vitro assay showed strong killing activity of ADR-NP-Ab to bladder cancer cells (EJ), while no apparent cytotoxic activity to non-targeted human colon carcinoma cells (Lovo) was observed.