The role of cytokines and transcription factors on the regulation of megakaryocy topoiesis and platelet production are reviewed in this article. Megakaryocytopoiesis involves the proliferation and differentiation of megakaryocytic pro genitor cells into immature megakaryocytes, and the differentiation of immature megakaryocytes to mature megakaryocytes which produce platelets. The former is regulated mainly by thrombopoietin (TPO) and to a lesser degree by other cytokines such as interleukin-1 (IL-1), IL-3 and platelet-derived growth factor (PDGF), the later by TPO and probably IL-6 and IL-11. A number of transcription factors have been implicated in the control of megakaryocyte differentiation. GATA-1, FOG-1 and Fli-1 are essential regulators in early- and mid-stages of megakaryocytopoiesis. NF-E2 regulates late-stage of megakaryocytopoiesis and platelet production. However, the platelet release mechanism is poorly understood. Nitric oxide (NO) may act in the stage of platelet release through induction of apoptosis in megakaryocytes.
Animals ; Cytokines ; physiology ; DNA-Binding Proteins ; physiology ; Erythroid-Specific DNA-Binding Factors ; GATA1 Transcription Factor ; Hematopoiesis ; Humans ; Interleukins ; physiology ; Megakaryocytes ; physiology ; NF-E2 Transcription Factor ; NF-E2 Transcription Factor, p45 Subunit ; Platelet-Derived Growth Factor ; physiology ; Thrombopoiesis ; physiology ; Thrombopoietin ; physiology ; Transcription Factors ; physiology

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.
Adult ; Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; CD13 Antigens ; immunology ; Cell Adhesion Molecules ; Child ; Hematologic Diseases ; immunology ; physiopathology ; Hematopoiesis ; physiology ; Humans ; SARS Virus ; Severe Acute Respiratory Syndrome ; immunology ; physiopathology ; virology

Ultrasonography is pivotal in triage thyroid biopsy in the era after the identification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This pictorial essay illustrates the pathologic basis of the sonographic features that distinguish NIFTP from thyroid cancers. In this study, we present the correlations of ultrasonography to ×1 histopathology to assess shape and margin characteristics. Markedly hypoechoic nodules correlate to microfollicular/solid nodules, while isoechoic/hyperechoic thyroid nodules correlate to normofollicular/macrofollicular nodules. The ultrasound findings of NIFTP and minimally invasive encapsulated thyroid cancers are similar. Both are well-circumscribed, oval-to-round nodules with regular margins. Blurred or microlobulated margins indicate infiltrating tumors, while lobulated margins are characteristic of expansile tumors. Overtly invasive encapsulated tumors are characterized by oval-to-round nodules with irregular or lobulated margins. The ultrasound findings for infiltrative thyroid cancers show at least one of the following malignant features: marked hypoechoicity, taller-than-wide shape, microcalcifications, and blurred or microlobulated margins.
Biopsy ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule ; Triage ; Ultrasonography*

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.
Animals ; Apoptosis ; drug effects ; Brain Chemistry ; Cell Line ; Cell Proliferation ; drug effects ; Erythropoietin ; pharmacology ; Humans ; Mice ; Neoplasm Proteins ; analysis ; Neurons ; drug effects ; Oncogene Proteins ; analysis ; Proto-Oncogene Proteins ; analysis ; Receptors, Cytokine ; analysis ; Receptors, Thrombopoietin ; Thrombopoietin ; pharmacology

The immunological role of megakaryocytes is not well known. This project studies the involvement of megakaryocytes on immuno-inflammatory processes and the possible mechanism via the adhesion molecule CD36 and the synthesis of relevant cytokines. The expression of adhesion protein CD36 on human platelets, megakaryocytes and megakaryocytic cell lines (Meg-01, Dami, CHRF-288-11 and M-07e) was analyzed by using flow cytometry, ELISA and immunocytochemical methods. The expression of interleukin-1 (IL-1) to interleukin-10 (IL-10), TNF-alpha, TNF-gamma and IFN-gamma on the four megakaryocytic cell lines was also determined by RT-PCR. The effect of IL-1beta, IL-3, IL-6 and TPO on murine megakaryocyte colony formation (CFU-MK) was studied by using a plasma clot culture system. The CFU-MK was confirmed by acetylcholine esterase staining. The results showed that: (1) CD36 was expressed on platelets, megakaryocytes and the four megakaryocytic cell lines, the relative expression level is as follows: platelets > megakaryocytes > Meg-01 > Dami > CHRF-288-11 > M-07e, suggesting that the level of CD36 expression correlates with the degree of maturity of megakaryocytic differentiation; (2) inflammatory cytokines TNF-alpha, IL-1beta, IL-3 and IL-6 were detected in all the four megakaryocytic cell lines, suggesting that different stages of megakaryocytes can be as a source of inflammatory cytokines; and (3) IL-1beta, IL-3 and IL-6, as well as TPO, play a stimulating effect on CFU-MK formation, suggesting that there is an "autocrine" effect on megakaryocytopoiesis. The data obtained suggest that megakaryocytes may involve in immuno-inflammatory processes via the synthesis of platelet adhesion molecules and inflammatory cytokines.

OBJECTIVE: To evaluate uterine and ovarian cancer mortality trends in East Asian countries. METHODS: For three Asian countries and one region (Japan, Korea, Singapore, and Hong Kong), we extracted number of deaths for each year from the World Health Organization (WHO) mortality database, focusing on women > or =20 years old. The WHO population data were used to estimate person-years at risk for women. The annual age-standardized, truncated rates were evaluated for four age groups. We also compared age-specific mortality rates during three calendar periods (1979 to 1988, 1989 to 1998, and 1999 to 2010). Joinpoint regression was used to determine secular trends in mortality. To obtain cervical and uterine corpus cancer mortality rates in Korea, we re-allocated the cases with uterine cancer of unspecified subsite according to the proportion in the National Cancer Incidence Databases. RESULTS: Overall, uterine cancer mortality has decreased in each of the Asian regions. In Korea, corrected cervical cancer mortality has declined since 1993, at an annual percentage change (APC) of -4.8% (95% confidence interval [CI], -5.3 to -4.4). On the other hand, corrected uterine corpus cancer mortality has abruptly increased since 1995 (APC, 6.7; 95% CI, 5.4 to 8.0). Ovarian cancer mortality was stable, except in Korea, where mortality rates steadily increased at an APC of 6.2% (95% CI, 3.4 to 9.0) during 1995 to 2000, and subsequently stabilized. CONCLUSION: Although uterine cancer mortality rates are declining in East Asia, additional effort is warranted to reduce the burden of gynecologic cancer in the future, through the implementation of early detection programs and the use of optimal therapeutic strategies.
Adult ; Age Distribution ; Aged ; Databases, Factual ; Far East/epidemiology ; Female ; Genital Neoplasms, Female/*mortality ; Humans ; Middle Aged ; Mortality/trends ; Ovarian Neoplasms/mortality ; Uterine Neoplasms/mortality ; Young Adult

Objective: Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers. Methods: Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing. Results: We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). BRCA1 and BRCA2 were the most dominant genes associated with hereditary breast and ovarian cancer, whereas ATM was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories. Conclusion The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.

BACKGROUNDPrevious animal and neuroimaging studies have demonstrated that brain function in heroin addicted users is impaired. However, the posterior cingulate cortex (PCC) has not received much attention. The purpose of this study was to investigate whether chronic heroin use is associated with craving-related changes in the functional connectivity of the PCC of heroin addicted users.

METHODSFourteen male adult chronic heroin users and fifteen age and gender-matched healthy subjects participated in the present study. The participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and a cue-induced craving task fMRI scan. The activated PCC was identified in the cue-induced craving task by means of a group contrast test. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the correlation between brain regions. The relationship between the connectivity of specific regions and heroin dependence was investigated.

RESULTSThe activation of PCC, bilateral anterior cingulate cortex, caudate, putamen, precuneus, and thalamus was significant in the heroin group compared to the healthy group in the cue-induced craving task. The detectable functional connectivity of the heroin users was stronger between the PCC and bilateral insula, bilateral dorsal striatum, right inferior parietal lobule (IPL) and right supramarginal gyrus (P < 0.001) compared to that of the healthy subjects in the resting-state data analysis. The strength of the functional connectivity, both for the PCC-insula (r = 0.60, P < 0.05) and for PCC-striatum (r = 0.58, P < 0.05), was positively correlated with the duration of heroin use.

CONCLUSIONThe altered functional connectivity patterns in the PCC-insula and PCC-striatum areas may be regarded as biomarkers of brain damage severity in chronic heroin users.

Adult ; Female ; Gyrus Cinguli ; physiopathology ; Heroin Dependence ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged