First Author: Anavelys Ortiz-SuĂˇrez
All Authors: Ortiz-SuĂˇrez A, Miller RA
Journal Title: The journals of gerontology. Series A, Biological sciences and medical sciences
Abstract: Memory CD8+ T cells from old mice can proliferate in nonirradiated recipients. Transfer of labeled cells from aged donors into young recipients showed that proliferation of aged donor CD8 cells requires host cells that can both respond to interferon-gamma and produce interleukin-15. Reisolation of transferred CD8 cells from host mice showed that LAT (linker for activated T cells) translocation to the immunological synapse, and translocation of NF (nuclear factor)-kappaB to the nucleus were diminished in recovered CD8 T cells from old donors, whether they had divided in vivo or not. Cells able to proliferate in vivo could be isolated based on their unusually high levels of CD28 expression, but were found not to differ from other aged CD8 cells in their low levels of LAT and protein kinase C-theta (PKC-theta) translocation to the immunological synapse. Thus in vivo proliferation of CD28hi CD8 cells from aged mice cannot be attributed to retention of T-cell receptor signaling.
Authors: Strömqvist M, Schatteman K, Leurs J, Verkerk R, Andersson JO, Johansson T, Scharpé S, Hendriks D
Abstract: The importance of carboxypeptidase U as a novel regulator of the fibrinolytic rate has attracted a lot of interest recently. In the present work, an ELISA was developed using polyclonal antibodies raised against recombinant proCPU, expressed in DON cells. The assay determines the antigen concentration of the zymogen of carboxypeptidase U, procarboxypeptidase U, in human citrated plasma or EDTA plasma. No interference is observed with plasma carboxypeptidase N. The assay is very reproducible (within-run: 4.6% CV, between-run: 6.8% CV). In a group of 479 healthy individuals the mean proCPU antigen concentration is 13.4 microg/ml (SD 2.5 microg/ml). A good correlation is found with the functional procarboxypeptidase U assay described earlier (r = 0.82, p < 0.0001) (Schatteman K, Goossens F, Scharpé S, Neels H, Hendriks D Clin Chem 1999: 45: 807-813). The significant correlation between the proCPU antigen concentration and the 50% clot lysis time stresses its importance as a player in fibrinolysis control.
Authors: Wu WL, Liang JY, Zhu MQ, Xue YQ, Chen ZX
Abstract: To explore the characteristics of morphology, immunophenotype and cytogenetics (MIC) of myeloid surface antigen-expressing acute lymphoblastic leukemia (My+ ALL).One hundred and twenty untreated acute lymphoblastic leukemia (ALL) patients were diagnosed by standard bone marrow smear morphologic analysis and peroxidase staining. Flow cytometry and myeloid monoclonal antibodies (McAb) were used to analyze immunophenotype. Chromosome karyotypes were analyzed by R-band technique.Of 120 cases, 66 (55%) were My+ ALL, including 50 cases of My+ B-ALL (56.8% of B-ALL ), 14 cases of My T-ALL (50% of T-ALL) and 2 cases of My+ T and B-ALL (50% of T and BALL). Of 66 My+ ALL, 10 cases (15.1%) were misdiagnosed as acute non-lymphoblastic leukemia (ANLL), the other 54 My- ALL cases were correctly diagnosed. The inconsistent rate between morphological and immunophenotype classifications was higher in My+ ALL than in My- ALL , and there were more atypical morphology cases in My+ ALL than in My- ALL (P < 0.01). In My+ ALL cases 95.5% expressed CD13, 81.8% CD33, 77.3% CD13 and CD33 simultaneously, and 1.5% CD117, but none CD14, CD15 and MPO. CD34 expression rate in My+ ALL cases was significantly higher than that in My- ALL (P < 0.01 ). Cytogenetic abnormalities rates in My+ ALL and My- ALL were 72.3% and 66.7% (P > 0.05) respectively. t(9;22) and t(9;22) plus other cytogenetic abnormalities were detected more frequently in My+ LL cases than in My- B-ALL (P < 0. 01), and not in My+ T-ALL and My- T-ALL cases. The complete remission (CR) rates was 83.9% in My+ ALL and 79% in My- ALL(P > 0.05).My+ ALL had a specific characteristics in morphology, immunophenotype and cytogenetics. Some cases have a myeloid morphologic appearance and might be misdiagnosed as acute myeloid leukemia (AML). My+ ALL have a higher CD34 expression rate than My- ALL. t(9;22) abnormality was more frequently observed in My B-ALL than in My- B-ALL. There was no significant difference in CR rate between My+ ALL and My- ALL.
Authors: Long C, Guo W, Zhou H, Wang J, Wang H, Sun X
Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) can establish a life-long persistence in the host after primary infection and is associated with certain malignancies, which are resistant to conventional chemotherapeutic agents with a poor prognosis. Latency-associated nuclear antigen 1 (LANA1) encoded by KSHV is essential for segregation, replication and maintenance of viral genome. In addition, LANA1 upregulates the transcriptional activity of signal transducer and activator of transcription 3 (STAT3), which plays an important role in promoting survival of KSHV-associated primary effusion lymphoma (PEL) cells. Furthermore, LANA1 mediates transcriptional modulation of KSHV and host genome in host cells. In the present study, the antitumor effect of triptolide was assessed. CCK-8 assays were performed to demonstrate that the proliferations of PEL cells were efficiently inhibited by triptolide in a dose- and time-dependent manner. Flow cytometric results indicated that triptolide induced cell cycle arrest and apoptosis. Western blot results suggested that triptolide downregulated LANA1 expression and reduced half-life of LANA1 in the KSHV-infected malignant cells. Viral titer experiments indicated that triptolide treatment impaired the number of viral DNA copies and the production of virions in BCBL-1 cells. Triptolide also suppressed STAT3 activity and inhibited secretion of IL-6 in PEL cells. In a mouse xenograft model of primary effusion lymphoma by BCBL-1 cells, triptolide treatment significantly inhibited ascites formation and diffused organ infiltration. These results indicate that triptolide impairs the expression of LANA1 and shows antitumor activity against PEL in vitro and in vivo. Triptolide may be a potential agent for treatment of PEL.
Authors: Wang B, Oleschuk RD, Petkovich PM, Horton JH
Abstract: Poly(methylmethacrylate) (PMMA) is a versatile polymer that displays desirable properties for development of cheap and disposable microfluidic devices for sensing biomolecular interactions. Atomic force microscopy (AFM) and chemical force titrations were used to determine the efficacy of surface modifications made to accommodate protein-substrate linkage. AFM images show the effects on surface morphology of carboxylated-, amine-, hCG antigen- and anti-hCG antibody-modified PMMA substrates. Confocal microscopy was used to determine the fluorescent intensity of labeled antibody species on the PMMA substrate, confirming the success of surface antigen/antibody immobilization. Surface pK(1/2) value for carboxylic acid and amine species grafted on PMMA were determined. When carboxylic acid or amine-terminated tips were titrated against PMMA samples terminated with the hCG antigen and anti-hCG antibody, peaks appeared in the force titration curve consistent with the pI range of the antigen or antibody species. Strong adhesive forces were present at pH values above 7.0 when the antigen was present on the PMMA substrate, and these were attributed to hydrophobic interactions between the antigen and the alkane "linker" chain attaching the amine or carboxylate group to the AFM tip. Such hydrophobic interactions were not observed with the carboxylic acid or amine/antibody combinations suggesting that the surface-linked antibody was more resistant to denaturation under higher pH. The results demonstrated the feasibility of using AFM approaches for interrogating protein grafting strategies in the fabrication of PMMA-based microsystems.
Authors: Tosaka M, Hirato J, Miyagishima T, Saito N, Nakazato Y, Sasaki T
Abstract: Calcification in vestibular schwannoma is extremely rare. A 36-year-old man presented with a history of decreased hearing on the left since childhood. Computed tomography showed a left cerebellopontine angle lesion protruding into the porus acousticus and enlarging the internal auditory meatus, with significant deposits of calcification. Histological and immunohistochemical examination, including staining for CD-34, a myeloid progenitor cell antigen, found highly degenerated schwannoma with collagen-rich tissue, calcification, formation of bone, abnormal vessels of various sizes, and old haemorrhage with marked haemosiderin-laden macrophages. Most of the surgical specimen was sclerotic collagenous tissue containing sparse spindle-shaped cells which formed approximately 90% of the total specimen. However, the spindle-shaped cells were partly concentrated into islands forming the cellular part (approximately 10% of the total). The spindle-shaped cells in both parts showed almost typical immunohistochemical characteristics of schwannoma. However, many spindle-shaped cells in only the sclerotic part were positive for CD-34, which is widely used for the diagnosis of solitary fibrous tumours. Cerebellopontine angle tumour showing fibromatous tissue, including calcification, may contain foci of typical schwannoma. Careful histological examination with detailed immunohistochemical staining is required for the correct diagnosis. In particular, spindle-shaped cells occasionally show positive immunoreactivity for CD-34 antigen in the areas of degenerated and calcified schwannoma characteristic of our case.
Authors: Saka T, Sofikerim M, Demirtas A, Kulaksizoglu S, Caniklioglu M, Karacagil M
Abstract: To determine whether cycling has an effect on serum PSA, gonadotropins, and uroflowmetric parameters.A total of 34 healthy male athletes from the National Cycling Team and 24 healthy male student volunteers from University and medical staff were prospectively enrolled in the study. Blood samples for serum total prostate-specific antigen (tPSA), free PSA (fPSA, fPSA/tPSA, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone determinations were obtained before and after cyclists completed 300 km bicycle ride and with each cyclist seated without changing posture and with minimal movement for 10 minutes before blood collection. The cyclists also performed uroflowmetric and postvoid residual urine volume analysis before, and 1 hour after cycling course. Blood samples from the control group were drawn for serum hormones. They also underwent uroflowmetric and postvoid residual analysis.The athletes and the control group were well matched by age. There was no significant difference between the 2 groups in terms of serum tPSA, fPSA, f/t PSA values, FSH, LH, and testosterone levels and uroflowmetric parameters (P >.05). The differences between pre- and postcycling values for tPSA, fPSA, f/t PSA, FSH, LH, and uroflowmetric parameters were not statistically significant. The postcycling serum testosterone level was significantly lower than precycling levels (mean, 603.6 ng/dL [range, 300-949] vs 424.8 ng/dL [range, 193-723], P = .001]. There was no correlation between body mass index values, postcycling serum FSH, LH levels, age, and testosterone levels.There is no effect of professional bicycle riding on serum total and fPSA levels and uroflowmetric parameters.
Authors: Cochran JB, Panzarino VM, Maes LY, Tecklenburg FW
Abstract: The hemolytic uremic syndrome (HUS) is most commonly associated with Escherichia coli, but has been associated with other infections such as Streptococcus pneumoniae. Pneumococcus-induced HUS carries an increased risk of mortality and renal morbidity compared with E. coli-induced HUS. The pneumococcal organism produces an enzyme, which can expose an antigen (T-antigen) present on erythrocytes, platelets, and glomeruli. Antibodies to the T-antigen, normally found in human serum, bind the exposed T-antigen, and the resultant antigen-antibody reaction (T-activation) can lead to HUS and anemia. Clinicians need to be aware to request specific testing when pneumococcus-induced HUS/anemia is suspected, as current blood banking techniques do not routinely test for the presence of the T-antigen. Once this association is documented, washing all blood products and avoiding plasma products, if possible, is recommended. Plasmapheresis can be considered for the more critically ill patient. The incidence of pneumococcus-induced HUS may be increasing. We report six cases of pneumococcus-induced HUS/anemia presenting at our hospital.
Authors: Pecher G, Schirrmann T, Kaiser L, Schenk JA
Abstract: Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system and are currently being investigated in clinical applications as cancer vaccines. An efficient cryopreservation method would greatly contribute to their use in clinical trials. We have established a method for freezing of DCs derived from peripheral blood mononuclear cells using the plasma expander Gelifundol. This enabled us to reduce the concentration of the toxic DMSO to 5%. The method could be performed without the addition of fetal calf serum or any other serum. After freezing, the viability of the DCs was 90%. The cells exhibited all the phenotypic characteristics (CD11c+, HLA-DR+, CD80+, CD83+, CD86+) of DCs, as tested by flow cytometry. Cells transfected with cDNA for the tumour antigen mucin expressed this protein on their surfaces in the same manner as before freezing. The stimulating capacity of a mixed lymphocyte culture was also preserved. These findings offer an efficient method for the cryopreservation of DCs for use in clinical trials.
Authors: Zheng B, Li T, Lin Q, Huang Z, Wang M, Deng W, Liao Z, Gu J
Abstract: To investigate the prevalence of hepatitis B surface antigen (HBsAg), a seromarker for current infection of hepatitis B virus, in patients with ankylosing spondylitis (AS) from south China and to evaluate its association with human leukocyte antigen (HLA)-B27. The prevalence of HBsAg was retrospectively investigated in 439 patients with AS, 606 age- and sex-matched general individuals, 172 patients with other spondyloarthropathy (SpA), 698 patients with rheumatoid arthritis (RA), and 220 patients with osteoarthritis (OA). The positive rate of HBsAg in AS group was compared with those of the general population group and other disease groups, respectively, and the prevalence of HBsAg was compared between HLA-B27-positive and HLA-B27-negative patients with AS. The positive rate of HBsAg in AS patients, general population, other-SpA, RA, and OA patients were 25.39, 12.87, 14.53, 9.60, and 8.18%, respectively. The HBsAg prevalence of AS group was statistically higher than those of any other groups (P < 0.05). The prevalence of HBsAg in HLA-B27-positive and HLA-B27-negative AS patients were 26.68 and 14.49%, respectively, the positive rate of HBsAg in HLA-B27-positive AS patients was statistically higher than that of HLA-B27-negative AS patients (P < 0.05). The prevalence of HBsAg in AS patients was higher than those in general population, patients with other-SpA, RA, and OA. The high HBsAg prevalence in AS patients might be associated with their high frequency of HLA-B27 gene.
Authors: Zhou J, Yang J, Zhang G, Nishikawa Y, Fujisaki K, Xuan X
Abstract: A cDNA encoding the apical membrane antigen-1 (AMA-1) homologue was obtained by immunoscreening a cDNA expression library prepared from Babesia gibsoni merozoite mRNA. The complete nucleotide sequence of the gene was 2062bp. Computer analysis suggested that the sequence contains an open reading frame of 1794bp with a coding capacity of approximately 66kDa. Based on the homology analysis, this putative protein was designated as B. gibsoni AMA-1 (BgAMA-1). The BgAMA-1 gene was expressed in the Escherichia coli BL21 strain and used as the antigen in Western blotting and the enzyme-linked immunosorbent assay (ELISA). The results indicated that BgAMA-1 was recognized as an immunodominant antigen by the host immune system and that it induced a strong antibody response only in chronic B. gibsoni infection in dogs; however, the antibody response could not be detected in the early infection stage (within 15 days). This phenomenon might be explained by the limited stimulation with the low-abundance protein in the early infection stage. This result shows that BgAMA-1 is a new member of the AMA-1 family and that its immune response is characteristic of canine B. gibsoni infection.