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Biomedical subjects

B Zheng

Publications and source records attributed to B Zheng.

At least 127 records · Page 7Linked to original sources

Immunosenescence and germinal center reaction.

Dysfunction of the immune system in aged individuals includes at least two important factors: accumulation of immunocytes with reduced function and accumulation of lymphocyte clones with self-reactive potential. Coincidently, there is a profound reduction of the germinal center reaction in the aged. While this reduction is likely the result of age-associated impairment in lymphocyte function (e.g. diminished response to costimulus, altered lymphokine production etc.), the reduction of germinal centers may itself make an important contribution to further immunological dysfunction.

Aging↗

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.

Adult↗

[The experimental pathology and clinical treatment of microwave tissue coagulation for ocular superficial lesions].

OBJECTIVE: To investigate the therapeutic effect of a new therapy, microwave tissue coagulation (MTC), for treatment of ocular diseases. METHODS: HSE-5M Mircotaze (manufactured by HEIWA Electronic Industrial Co. Osaka, Japan) was used for the treatment of sixty-four cases with ocular superficial lesions. Animal experiment was performed with this technique before application in patients. Twelve rabbit monocular eyeballs were coagulated just posterior to the corneoscleral limbus in order to find a dose which is effective and safe for the human eye ball. The models of microwave coagulative lesions were made in the contralateral eyes of the twelve rabbit eyeballs. RESULTS: The coagulation-induced "ulcers" were exfoliated gradually and healed finally from three to seven days. Histopathology of the coagulative areas showed coagulative necrosis with infiltration of lymphocytes and plasma cells. The results of sixty-four cases treated with MTC technique show that the damaging effect of coagulation on tissues is very mild, so that it heals very soon and the clinical process is consistent with the experimental pathological process. CONCLUSIONS: If the dosage of the technique is controlled in the range of safety and effectiveness, the MTC therapy is effective for the treatment of superficial ocular disease. The clinical and pathological examinations demonstrate that the therapy does not damage the ocular structure.

Animals↗

Detection of neuroblastoma cells in blood by reverse transcriptase-polymerase chain reaction.

OBJECTIVE: To determine whether circulating tumor cells are present in patients with localized or disseminated neuroblastoma (NB). METHODS: Sixteen pediatric malignant tumor cell lines, including 10 NB, 4 primitive neuroectodermal tumor (PENT), 2 Wilms' tumor and 39 samples (tumor tissue, bone marrow and peripheral blood) from 8 patients with NB, were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) using two markers: neuroendocrine protein gene products 9.5 (PGP 9.5) and tyrosine hydroxylase (TH). RESULTS: Analysis of RT-PCR products by agarose electrophoresis demonstrated that in culture cell lines the specificity for NB was highest in TH (9/10 with NB, 3/4 with PNET, 0/2 with Wilms' tumor) and the sensitivity was highest in PGP 9.5 10(-7). PGP 9.5 and TH mRNA were undetectable in the peripheral blood mononuclear cells (PBMNC) from normal children. Expression of these markers in 8 patients with NB at diagnosis and during treatment was found positive in 5 out of 8, all had been proved paralleling with their disease status. Two of the 5 became negative after further treatment. CONCLUSIONS: These systems allow the detection of circulating NB cells with higher sensitivity and specificity. When RT-PCR is clinically used for the detection of NB cells in blood, that both PGP 9.5 and TH should be selected is recommended. The assessment of bone marrow alone might not be used as a single index of tumor dissemination.

Biomarkers, Tumor↗

Color Doppler imaging diagnosis of intra-ocular tumor.

OBJECTIVE: To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors and its importance in the diagnosis of these tumors. METHODS: Ninety-two patients with intra-ocular tumors (105 eyes) were examined by using CDI to observe the vasculature of these tumors, and using SAS soft ware to analyze the results. RESULTS: Blood flow signal was found in retinoblastoma, melanoma of choroid, angioma of choroid, angioma of optic disc, Coats' disease, persistent hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases in central retinal artery in choroidal melanoma and also in ophthalmic artery, central retinal artery and posterior ciliary artery in angioma of choroid (P < 0.01). It was found that blood velocity is much faster in choroidal melanoma than in choroidal angioma (P < 0.05). CONCLUSIONS: CDI is very important and helpful in the diagnosis of intra-ocular tumors.

Adolescent↗

Neoteny in lymphocytes: Rag1 and Rag2 expression in germinal center B cells.

The products of the Rag1 and Rag2 genes drive genomic V(D)J rearrangements that assemble functional immunoglobulin and T cell antigen receptor genes. Expression of the Rag genes has been thought to be limited to developmentally immature lymphocyte populations that in normal adult animals are primarily restricted to the bone marrow and thymus. Abundant RAG1 and RAG2 protein and messenger RNA was detected in the activated B cells that populate murine splenic and Peyer's patch germinal centers. Germinal center B cells thus share fundamental characteristics of immature lymphocytes, raising the possibility that antigen-dependent secondary V(D)J rearrangements modify the peripheral antibody repertoire.

Animals↗

Alternative pathways for the selection of antigen-specific peripheral T cells.

In the thymus, maturing lymphocytes receive activation signals mediated by the T-cell antigen receptor (TCR) that either promote clonal survival (positive selection) or induce apoptosis (negative selection). This balance between life and death is mirrored by the sensitivity of cortical thymocytes to apoptotic death induced by antibodies against the CD3 component of the TCR signal-transduction complex, bacterial superantigens that bind to the TCR beta-chain, and corticosteroids. In contrast, mature peripheral T cells are positively activated by anti-CD3 antibody or superantigens and are resistant to steroid-induced death. Here we show that in splenic germinal centres, T cells regain thymocyte-like sensitivity to TCR- and steroid-induced apoptosis and undergo antigen-driven positive and negative selection. T-cell responses elsewhere in the spleen are unaccompanied by programmed cell death. Our observations define a new differentiation pathway for peripheral T cells and suggest that germinal centres induce a lymphocyte phenotype necessary for the maintenance of self-tolerance.

Animals↗

Gamma delta T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells.

BACKGROUND: gamma delta T cells, like alpha beta T cells, are components of all well-studied vertebrate immune systems. Yet, the contribution of gamma delta T cells to immune responses is poorly characterized. In particular, it has not been resolved whether gamma delta cells, independent of any other T cells, can help B cells produce immunoglobulin and form germinal centers, anatomical foci of specialized T cell-B cell collaboration. RESULTS: TCR beta-/- mice, which lack all T cells except gamma delta T cells, routinely displayed higher levels of antibody than fully T cell-deficient mice. Repeated parasitic infection of TCR beta-/- mice, but not of T cell-deficient mice, increased antibody levels and induced germinal centers that contained B cells and monoclonal gamma delta cells in close juxtaposition. However, antibody specificities were more commonly against self than against the challenging pathogen. gamma delta T cell-B cell help was not induced by repeated inoculation of TCR beta-/- mice with mycobacterial antigens. CONCLUSIONS: In the absence of any other T cells, gamma delta T cell-B cell collaboration can be significantly enhanced by repeated infection. However, the lack of obvious enrichment for antibodies against the challenging pathogen distinguishes gamma delta T cell help from alpha beta T cell help induced under analogous circumstances. The increased production of generalized antibodies may be particularly relevant to the development of autoimmunity, which commonly occurs in patients suffering from alpha beta T cell deficiencies, such as AIDS.

Animals↗

Long-term survival of solid organ allografts by brief anti-lymphocyte function-associated antigen-1 monoclonal antibody monotherapy.

Strategies targeting lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule-1 (ICAM-1) have previously been shown to produce long-term survival of solid organ allografts in animals only when both CD11a and ICAM-1 are targeted for a brief (6-7 days) time or when extended (14 weeks) treatment with anti-CD11a monoclonal antibody (mAb) is administered. We show that recipient pretreatment followed by a brief (13 days) treatment course with high-dose anti-CD11a mAb alone produces long-term survival of cardiac allografts in the rigorous, nonprimarily vascularized heart allograft model in mice. This treatment regimen induces specific unresponsiveness in our model. In recipients bearing long-term beating cardiac grafts after treatment with anti-CD11a mAb, there still exists a high frequency of potentially antigen-reactive T cells in isolated peripheral blood lymphocyte fractions. Therefore, clonal deletion does not appear to explain the induction of specific unresponsiveness by treatment with anti-CD11a mAb in this model. These findings support the further investigation of the use of high-dose anti-LFA-1 mAb monotherapy in the pre- and early postoperative period to promote solid organ allograft survival.

Animals↗

T helper cells in murine germinal centers are antigen-specific emigrants that downregulate Thy-1.

After immunization, activated splenic T cells proliferate in periarteriolar lymphoid sheaths (PALS) and subsequently migrate to the lymphoid follicle where they enter nascent germinal centers. Analysis of TCR V(D)J gene rearrangements indicates extensive emigration, frequently involving more than a single white pulp region. These migrants constitute a unique set of T helper cells that express antigen-specific alpha beta TCR, CD3, and CD4, but little or no Thy-1, a differentiation antigen present on the great majority of peripheral murine T lymphocytes. The origin of CD4+ Thy-1 follicular T cells appears to be the Thy+ population in the PALS, as both sets commonly share identical V(D)J rearrangements.

Animals↗

Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.

Animals↗

Adaptive computer-aided diagnosis scheme of digitized mammograms.

RATIONALE AND OBJECTIVES: We investigated an adaptive rule-based computer-aided diagnosis (CAD) scheme for digitized mammograms that can be optimized by using an image difficulty index as determined from global measures of image characteristics. METHODS: First, we defined an image "difficulty" index based on image feature measurements in both the spatial and frequency domains. The CAD scheme then segmented the database into three groups. An image database of 428 digitized mammograms with 220 verified masses was randomly divided into two subsets, one for training (rule-setting) and the other for testing the adaptive CAD scheme. Each of the image difficulty groups in the training set was optimized independently to achieve a low false-positive detection rate while maintaining high detection sensitivity. Scheme performance was then evaluated with the test set, and the results were compared with a global rule-based system that was optimized without the adaptive method. RESULTS: In this preliminary study, a relatively simple adaptive scheme reduced false-positive mass detections compared with the nonadaptive scheme from 0.85 to 0.53 per image. At the same time sensitivity was not significantly changed. CONCLUSION: This adaptive CAD scheme has distinct advantages in improving CAD scheme performance as long as the training database includes a large number of cases in each image difficulty group with a variety of true-positive abnormalities.

False Positive Reactions↗

Computerized identification of suspicious regions for masses in digitized mammograms.

RATIONALE AND OBJECTIVES: A simple and effective computerized detection scheme was developed to identify suspicious mass regions in digitized mammograms. METHODS: This method identifies a maximum of five suspicious mass regions per image and was tested with a database of 510 images, including 162 verified masses. It includes a series of five rule-based processes that select one region with each of the following characteristics: 1) a global minimum of optical density in a smoothed image; 2) a local minimum of optical density in the original image; 3) a local minimum of optical density in a filtered image; 4) a small "mass" of low contrast; and 5) a small "mass" of high contrast. RESULTS: This multi-stage process achieved a sensitivity of 95% while limiting false-positive detection rates to below an average of two per image. CONCLUSION: Because this method limits the initial number of suspicious mass regions while retaining high sensitivity, it may be applicable to clinically usable computer-aided diagnosis schemes.

Breast Diseases↗

Robustness of computerized identification of masses in digitized mammograms. A preliminary assessment.

RATIONALE AND OBJECTIVES: The authors assess the robustness of a computer-aided diagnosis (CAD) scheme with five rule-based stages to identify regions suspicious for mass in digitized mammograms. METHODS: With a database of 428 mammograms, 234 of which had not been analyzed by this scheme before, the authors evaluated the performance robustness of their CAD scheme. The following four issues were investigated to assess the variability of the scheme's performance due to: (1) the maximum permissible number of "masses" detected at each stage; (2) exclusion of selected individual rule-based stages; (3) added image noise; and (4) repeated digitizations of the same image. RESULTS: Enabling the CAD scheme to select a maximum of two suspicious mass regions at any one stage increased sensitivity by as much as 4% (from 93% to 97%), but it increased the false-positive detection rate by as much as 1.2 per image (from 1.7 to 2.9). Eliminating any individual stage decreased sensitivity by as much as 6%, but this reduced the false-positive detection rate by as much as 0.4 per image (from 1.7 to 1.3). The addition of reasonable noise levels decreased sensitivity by as much as 4% without substantially affecting the false-positive detections. Repeated digitizations of selected images demonstrated a scheme sensitivity of 93% +/- 1.8% with more than a 90% overlap of the false-positive regions. CONCLUSIONS: The results of this preliminary study clearly indicate that this scheme is reasonably robust to the variables investigated here.

Breast Neoplasms↗