This study aims to examine the levels of circulating endothelial progenitor cells (cEPCs) in the peripheral blood of patients with non-Hodgkin lymphoma (NHL) and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 (VEGFR-2, CD309) and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group (P=0.000). The cEPCs counts in patients with NHL of stage III-IV were significantly greater than in stage I-II (P=0.010). FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender (P=0.401) or the pathological category (P=0.852). It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.
Blood Cell Count ; Cells, Cultured ; Endothelial Cells ; pathology ; Female ; Humans ; Lymphoma, Non-Hodgkin ; blood ; pathology ; Male ; Neoplastic Cells, Circulating ; pathology ; Statistics as Topic ; Stem Cells ; pathology

Cancer stem cells (CSCs) and angiogenesis play important roles in generation and development of malignant tumours. The number of researches concerned both of them is increasing rapidly and many impressive conclusions have been achieved based on recent studies. It is indicated that the CSCs have complicated interaction with the adjacent vascular microenvironment and they act on the disease progression together. CSCs may enhance angiogenesis while the vascular microenvironment has effects on maintenance and even induction of stemness, and new illustrations of mechanisms are constantly obtained. In this review, we summarize the current research status of mutual actions between CSCs and the vascular microenvironment, and also overview the latest progresses about relevant targeted therapies, to provide advisable information for future preclinical and clinical explorations.
Humans ; Neoplasms ; blood supply ; pathology ; Neoplastic Stem Cells ; pathology ; physiology ; Neovascularization, Pathologic ; pathology ; physiopathology ; Tumor Microenvironment

OBJECTIVETo evaluate the clinical and pathological features of IgG4-related disease (IgG4RD).

METHODSThe clinical data, laboratory profiles, radiological, pathological and therapeutic features of eight cases of IgG4RD were analyzed. This cohort included two cases of common bile duct and partial hepatectomy specimens, two of submandibular gland excision specimens, one from lung biopsy specimen, one from open lung biopsy specimen, one from renal biopsy specimen, and one from renal excision specimen. In all cases, adequate lesion tissues were obtained. They were paraffin embedded, HE stained, and additional special stains and immunohistochemistry performed (MaxVision method).

RESULTSThis series consisted of five males and three females, with a mean age of onset of 60 years. Five cases were suspected to be malignant pre-operatively, including two cases suspected of common bile duct carcinoma, two suspected of salivary gland tumor, and one suspected of renal pelvic carcinoma. Elevated serum levels of IgG4 and IgE were detected in five cases and eosinophilia in four cases. Multi-organ involvement was noted in four cases. The major histopathological features associated with IgG4-RD were: dense lymphoplasmacytic infiltrate, with lymphoid follicle formation. Extensive eosinophilic infiltrate (> 10/HPF) was seen in four cases; fibrosis that was arranged at least focally in a storiform pattern was also noted. The numbers of IgG4 positive plasma cells were > 20-50/HPF, while the IgG4 to IgG ratio was more than 40%. Obliterative phlebitis was present in four cases. Other pathological changes such as necrotizing vasculitis or lymphoma were not found. Five patients responded well to glucocorticoids.

CONCLUSIONSIgG4RD has relatively specific histopathological features; accurate evaluation of the absolute and relative number of IgG4 positive plasma cells in lesional tissue, combining with clinical examination and exclusion of other causes of elevated IgG4, allows the diagnosis of IgG4RD. IgG4RD has complicated clinical manifestation, and glucocorticoids therapy is efficacious.

Biopsy ; Common Bile Duct Neoplasms ; blood ; pathology ; Female ; Fibrosis ; pathology ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Immunohistochemistry ; Kidney Neoplasms ; blood ; pathology ; Kidney Pelvis ; pathology ; Lung ; pathology ; Male ; Middle Aged ; Plasma Cells ; Salivary Gland Neoplasms ; blood ; pathology

OBJECTIVETo investigate the relationship between vascular endothelial dysfunction and serum homocysteine (HCY) level in patients with coronary lesions.

METHODSSerum HCY, serum nitric oxide (NO), plasma endothelin-1 (ET-1), and circulation endothelial cell (CEC) were measured in 76 patients who received coronary angiography. Fifty-four patients with a stenosis of 50% or more at least in one coronary atery were as coronary artery disease (CAD) group. Other 22 cases with no recognizable plaque and/or stenosis were as control group. HCY level was detected using an enzyme immunoassay kit. NO concentration was measured using a nitrate reductase kit. Radio-immunoassay was applied to analyse the ET-1 level, and CEC was measured by flow cytometry.

RESULTSThe levels of HCY, ET-1, and CEC in patients with coronary lesions were significantly increased in comparison with control group (P < 0.01), while NO level in CAD group was significantly lower compared with that in control (P < 0.01). Using a multivariate stepwise regression analysis, HCY level had a positive correlation with ET-1 level (r = 0.420, P < 0.05) and CECs number (r = 0.423, P < 0.05); and had a negative correlation with NO/ET-1 (r = -0.403, P < 0.05). But there was no significant correlation between HCY and NO levels.

CONCLUSIONSHCY might lead to endothelial cell injury, which would provide a plausible mechanism for the relationship between hyperhomocysteinemia and development of coronary artery disease. HCY can be considered as a predictor for preliminary or active coronary lesion.

Aged ; Biomarkers ; blood ; Cell Count ; Coronary Artery Disease ; blood ; pathology ; Endothelial Cells ; pathology ; Endothelin-1 ; blood ; Female ; Homocysteine ; blood ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood

To investigate the morphological changes of megakaryocytes with nuclear extrusion and nucleocytoplasmic separation, the morphological characteristics of megakaryocytes in peripheral blood films, bone marrow smears, and bone marrow biopsies from 4 newly diagnosed patients with primary myelofibrosis (PMF), myelodysplastic syndrome (MDS), myeloblastic leukemia with maturation (M(2)) and erythroleukemia (M(6)) were studied by using light microscope. The results showed that many kinds of dysmegakaryocytes were observed in bone marrow smears of 4 cases, while in case A (PMF) and case D (M(6)) micromegakaryocytes were ripped apart; in case B (MDS) and case C (M(2)) megakaryocytes were accompanied by nuclear extrusion or nucleocytoplasmic separation, and their bodies were large or giant, the part of nucleus separated from their body and little cytoplasm remained as micromegakaryocytes. The nucleocytoplasmic separation could be displayed by immunocytochemistry stain. It is concluded that the phenomenon of nuclear extrusion and nucleocytoplasmic separation in megakaryocytes suggested the process that dispersed multinuclear releasing towards surround or even totally left the cell body during the megakaryocyte maturation. It also showed that the micromegakaryocytes may be the result of nucleocytoplasmic separation or splittings from multi-separated nucleus.
Aged ; Bone Marrow Cells ; pathology ; Cell Nucleus ; pathology ; Cytoplasm ; pathology ; Female ; Hematologic Diseases ; blood ; Humans ; Male ; Megakaryocytes ; pathology ; Middle Aged

OBJECTIVETo study the pathological alteration of the cochlear microcirculation and the role of endothelin (ET) in the process of the noise-induced injury of inner ear.

METHODSThirty rats were randomly divided into five groups: control group and 1, 4, 8, 15 d noise exposure groups (115 dB, white noise, 8 h daily). The cilium of hair cell was observed by scanning electron microscope, the cochlear microcirculation was determined by stretched preparation of the stria vascularis. The level of ET in plasma was measured through radio-immunity. The distribution of ET-1, ETA, ETB, in cochlea were detected through immunohistochemistry staining.

RESULTSIn the 4, 8, 15 d group, severe ischemia appeared on the capillary of stria vascularis and the cilium of hair cell displayed significantly disorder. The level of ET in plasma rose temporarily in the 4 d group. ET-1 activity distributed widely in the rat cochlea, there was no significant difference between the control group and the noise exposure groups. ETA expressed in the plasma of the intermediate cells and the capillary walls in the stria vascularis. The control group and the 1 d group showed weak positive staining, while the 4, 8, 15 d groups showed strong positive. The ETB, activity distributed on the endothelial cells of the capillary of stria vascularis and the alteration of the staining intensity was similar to the manifestation of ETA.

CONCLUSIONSSevere disturbance of the cochlear circulation occurred during the course of the noise injury to the inner ear. At the same time, the activity of the ET system of the cochlea stepped up significantly. It coincided with the ischemia of the stria vascularis. These findings suggest that ET may play an important role in the process of the cochlear microcirculation disorder caused by noise.

Animals ; Cochlea ; pathology ; Ear, Inner ; pathology ; Endothelins ; blood ; Hair Cells, Auditory ; pathology ; Hearing Loss, Noise-Induced ; blood ; pathology ; Male ; Microcirculation ; Rats ; Rats, Sprague-Dawley ; Stria Vascularis ; pathology

OBJECTIVETo investigate the role of mast cells and interleukin-9 (IL-9) in B-cell non-Hodgkin lymphoma (B-NHL) development and its clinical significance.

METHODSThe expression level of CD117 in tumor tissues of 32 B-NHL patients was determined by Western blot. The infiltration of CD117⁺ mast cells (MCs) in human B-NHL tumor tissues was observed by immunohistochemistry staining. To evaluate the correlations between the data from CD117⁺ MCs and biological markers of human B-NHL, a Spearman correlation coefficient (rs) was calculated. IL-9 levels in sera of B-NHL patients were measured by ELISA. Effects of IL-9 on expressions of functional genes of mouse bone marrow-derived mast cells (BMMCs) were detected by real-time quantitative RT-PCR.

RESULTSThe expression of CD117 was upregulated significantly in human B-cell NHL involved tissues when compared with that of controls (0.0551±0.0064 vs 0.0192±0.0072, P<0.01). Infiltration of more CD117⁺ MCs was found in tissues from B-cell NHL subjects compared with that of controls. IL-9 level in serum samples from patients with B-cell NHL was higher than that from healthy controls. Addition of rIL-9 to the culture gave rise to increase in the purity of mouse BMMCs in the first three weeks. In vitro culture experiments showed that the addition of IL-9 could induce the differentiation of mouse BMMC and the expressions of MC-related genes, including CD117, Fcer1α, Mcpt1 and Mcpt5.

CONCLUSIONOur study showed that IL-9 promoted immune response mediated by MCs, and probably played important roles in B-NHL growth. Pharmacological or targeted inhibition of mast cells or IL-9 activity may provide new strategy for B-cell NHL therapy.

Animals ; Cells, Cultured ; Humans ; Interleukin-9 ; blood ; Lymphoma, B-Cell ; pathology ; Male ; Mast Cells ; immunology ; Mice

Immune thrombocytopenia (ITP) is recognized as a multifactorial cell-specific autoimmune disorder, and its pathogenesis is still not very clear. Traditional concept suggests that the platelet destruction mediated by autoantibodies is the pathophysiology mechanism of ITP, while many studies in recent years have shown that the abnormities of T lymphocyte, dendritic cell (DC), natural killer cell (NK), cytokine, programmed cell death (PCD), oxidative stress (OS), infection, pregnancy and drugs etc play an important role in the pathogenesis of ITP. Since the study of ITP has made a series of important achievements in recent years, this review focuses on the latest advance of studies on pathogenesis of ITP.
Apoptosis ; Autoantibodies ; blood ; Cytokines ; blood ; Dendritic Cells ; pathology ; Humans ; Killer Cells, Natural ; pathology ; Oxidative Stress ; Purpura, Thrombocytopenic, Idiopathic ; physiopathology ; T-Lymphocytes ; pathology

Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by dysplasia and ineffective hematopoiesis. The dysplasia is crucial in the diagnosis of MDS, but the morphologic abnormalities of bone marrow cells are not specific for MDS. When the morphological evaluation of marrow dysplasia and cytogenetics can not give enough informations, for diagnosis of MDS, the application of flow cytometry (FCM) for immunophenotyping in MDS will become particularly important. Multiparametric evaluation of myeloid, monocytic maturation and antigen expression pattern contribute to the identification of two or more aberrancies in MDS cases. FCM evaluation of erythroid dysplasia is particularly difficult, because of the limited availability of specific markers. By analyzing the proteins involved in cellular iron metabolism, MDS erythroid cells present an "iron-loaded" phenotype characterized by increased ferritin contents and reduced transferrin receptor, which reflects the degree of dysplasia assessed by morphology. The proportion of CD34(+) cells increased, abnormal expression of surface antigen is also important. The application of flow cytometry in detecting dysplasia of myelodysplastic syndrome is discussed in this article.
Bone Marrow Cells ; pathology ; Erythroid Cells ; metabolism ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; blood ; diagnosis ; pathology ; Receptors, Transferrin ; metabolism

Blood Cells ; immunology ; pathology ; Bone Marrow Cells ; immunology ; pathology ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Immunophenotyping ; Leukemoid Reaction ; diagnosis