Humans ; Infant, Newborn ; Male ; Protein C ; metabolism ; Protein C Deficiency

Anemia, Hypochromic ; etiology ; Humans ; Iron ; metabolism ; Protein Deficiency ; complications ; congenital ; Transferrin ; deficiency

Animals ; Fasting ; metabolism ; Membrane Proteins ; metabolism ; Mice ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Transcription Factors ; deficiency ; metabolism

Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the tumor suppressor proteins, such as Rb or p53. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-beta-galactosidase (SA-beta-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. p41-Arc has been known to be a putative regulatory component of the mammalian Arp2/3 complex, which is required for the formation of branched networks of actin filaments at the cell cortex. In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes.
Actin Cytoskeleton/metabolism ; Actin-Related Protein 2-3 Complex/*metabolism ; *Cell Aging ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Fibroblasts/physiology ; Humans ; Recombinant Proteins/genetics/*metabolism ; Retinoblastoma Protein/*deficiency/genetics ; Tumor Suppressor Protein p53/*deficiency/genetics

OBJECTIVETo explore the hemolytic mechanism of glucose-6-phosphate dehydrogenase (G6PD) deficient erythrocytes in the view of phosphorylation of membrane protein.

METHODSThe alternation of membrane protein phosphorylation and the effect of dithiothreitol (DTT) on protein phosphorylation were analysed by Western blot technique. The activity of phosphotyrosine phosphatase (PTPs) was determined by using p-nitrophenyl phosphate as substrate.

RESULTSTyrosine phosphorylation of band 3 protein was obviously enhanced in G6PD-deficient erythrocytes. The activity of PTPs was low compared to the normal erythrocytes. The level of phosphotyrosine in G6PD-deficient erythrocytes incubated with DTT was almost the same as in those without DTT. The results were consistent with the activity of PTPs.

CONCLUSIONSPTPs activity reduction and tyrosine phosphorylation enhancement induced by oxidation in G6PD deficiency play an important role in erythrocytes hemolysis. However, the alternation of thiol group is not the only factor affecting the activity of PTPs in G6PD-deficient erythrocytes.

Anion Exchange Protein 1, Erythrocyte ; metabolism ; Blotting, Western ; Erythrocyte Membrane ; metabolism ; Glucosephosphate Dehydrogenase Deficiency ; enzymology ; metabolism ; Humans ; Phosphorylation ; Protein Tyrosine Phosphatases ; metabolism ; Tyrosine ; metabolism

OBJECTIVETo investigate the prevalence and the risk of natural anticoagulants such as plasma protein C (PC), protein S (PS) and antithrombin (AT) deficiency in thromboembolic patients with no evident acquired factors.

METHODSClotting assays on French STAGO autoanalyzer were used to detect the activity of plasma PC, PS and AT in 85 patients with thrombotic disease and 50 sex and age matched healthy controls.

RESULTSAmong the 85 enrolled patients (18 arterial and 67 venous thromboembolism), male to female ratio was 1.4 and the median age was 42 years (17-69). The activity of plasma PC, PS and AT in the pre-therapy thrombotic disease group, the thrombo-recurrence group, and the age < or = 45 years group were significantly lower than that is the healthy control group, the first thrombotic episodes group and the age > 45 years group respectively (P < 0.001, P < 0.01, P < 0.01). The overall deficiency rate of these three natural anticoagulants was 30.6%, PS deficiency was the commonest (10.6%), the second was PC deficiency (8.2%), AT deficiency and combined deficiency each accounted for 5.9%.

CONCLUSIONThe PC, PS and AT protein deficiencies are frequent in Chinese thromboembolic patients, they are the independent risk factors for the thrombotic events and recurrence.

Adolescent ; Adult ; Aged ; Antithrombins ; blood ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Protein C ; metabolism ; Protein C Deficiency ; blood ; Protein S ; metabolism ; Protein S Deficiency ; blood ; Risk Factors ; Thrombosis ; blood ; etiology ; Young Adult

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Adaptor Proteins, Signal Transducing/deficiency/metabolism ; Adenosine Triphosphatases/deficiency/metabolism ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; *DNA Mismatch Repair ; DNA Repair Enzymes/deficiency/*metabolism ; DNA-Binding Proteins/deficiency/*metabolism ; Endometrial Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; MutS Homolog 2 Protein/deficiency/metabolism ; Neoplasm Proteins/deficiency/metabolism ; Nuclear Proteins/deficiency/metabolism ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*metabolism

OBJECTIVETo explore the distribution and influence factors of protein C (PC), protein S (PS) and antithrombin (AT) activities and to determine the prevalence of their deficiencies in the Chinese Han healthy population.

METHODSHealthy volunteers including blood donors and individuals for routine check-up were recruited from 4 Chinese medical centers. The plasma levels of PC, PS and AT activities were measured. The plasma levels of activities were measured by chromogenic substrate assay (AT and PC) and clotting assay (PS).

RESULTSA total of 3493 healthy Chinese adults had been recruited in this study. Males had higher PS and PC activities than females, especially for PS (P < 0.01). PC activities increased with age in both sexes but decreased in men after 50 years old. There was no significant change with age were of PS in 50 years old, while there was a decline in males and a rise in females above 50 years old. AT tended to increase with age in women but decreased with age in men after 50 years old. Based on the age and gender, the general prevalence of PC, PS and AT deficiencies in the general Chinese Han population were 1.15%, 1.49% and 2.29%, respectively.

CONCLUSIONPC, PS and AT activities have correlation with age and gender in Chinese Han population. Reference range should be laid down and deficiencies should be identified

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antithrombin III ; metabolism ; Antithrombin III Deficiency ; epidemiology ; Antithrombins ; metabolism ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Plasma ; metabolism ; Prevalence ; Protein C ; metabolism ; Protein C Deficiency ; epidemiology ; Protein S ; metabolism ; Protein S Deficiency ; epidemiology ; Young Adult

OBJECTIVESTo study the expression of Smad1 and Smad5 in the testis of infertile rats with adenine-modeled kidney-yang deficiency and the pathological mechanism of infertility with kidney-yang deficiency, attempting to obtain experimental evidence for the prevention and treatment of male infertility.

METHODSForty-eight 60 d male SD rats were divided randomly into 6 groups with 8 in each: 7 d, 14 d and 21 d kidney-yang deficiency groups, and 7 d, 14 d and 21 d control groups. The experimental rats had been fed with adenine (300 mg/kg) and the expression levels of Smad1 and Smad5 were measured with immunohistochemical SABC method at the 7th, 14th and 21st day.

RESULTSSmad1 immunoreactivity was mainly located in the spermatogonia, spermatocytes and spermatids, and the reactive substance distributed in cytoplasm with negative nuclei. Sertoli cells and Leydig cells were negative. Compared with the control, the expression level of Smad1 was decreased significantly at the 21st day (P < 0.05), but with no significant difference at the 7th and 14th day (P > 0.05). Smad5 immunoreactivity was mainly located in the spermatogonia and spermatocytes, and the reactive substance distributed in cytoplasm with negative nuclei. Compared with the control, the expression level of Smad5 was not significantly different at the 7th day (P > 0.05). The expression of Smad5 was negative at the 14th and the 21st day.

CONCLUSIONThe weaker expression of Smad1 and no expression of Smad5 may be one of the pathological mechanisms of infertility with adenine-modeled kidney-yang deficiency.

Animals ; Infertility, Male ; metabolism ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Smad1 Protein ; biosynthesis ; Smad5 Protein ; biosynthesis ; Testis ; metabolism ; Yang Deficiency ; metabolism ; pathology

OBJECTIVETo investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage.

METHODSFifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombin III (AT-III), as well as activated protein C resistance (APC-R). The control group consisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for, measuring serum activity of protein C, protein S, AT-III, and APC-R. Patients with positive APC-R were tested for factor V (FV) Leiden gene mutation by PCR-RFLP method.

RESULTSOf the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-III deficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-III deficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FV Leiden gene mutation was identified in all the patients with positive APC-R results. Late spontaneous abortion cases had higher incidence of anticoagulation protein defect than the early cases.

CONCLUSIONAnticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurring in late stage of pregnancy.

Abortion, Habitual ; blood ; etiology ; Activated Protein C Resistance ; blood ; complications ; genetics ; Adult ; Antithrombin III ; metabolism ; Antithrombin III Deficiency ; blood ; complications ; Factor V ; genetics ; Female ; Humans ; Point Mutation ; Protein C ; metabolism ; Protein C Deficiency ; blood ; complications ; Protein S ; metabolism ; Protein S Deficiency ; blood ; complications