Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.
Antithrombin III ; genetics ; Antithrombin III Deficiency ; etiology ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Protein C ; genetics ; metabolism ; Venous Thromboembolism ; complications ; genetics ; Young Adult

Amino Acid Transport Systems, Basic ; genetics ; Brain Diseases ; diagnosis ; etiology ; Child ; DNA Mutational Analysis ; Diet, Protein-Restricted ; Female ; Humans ; Hyperammonemia ; complications ; diagnosis ; diet therapy ; genetics ; Ornithine ; deficiency ; genetics ; Recurrence ; Severity of Illness Index ; Urea Cycle Disorders, Inborn ; complications ; diagnosis ; diet therapy ; genetics

OBJECTIVETo observe the relationship between vitamin D status and seasons, disease activity, disease location, growth and steroid treatment in children with Crohn's disease (CD). To search for the risk factors of vitamin D deficiency in CD children. To discuss the role of vitamin D in the pathogenesis and treatments of CD.

METHODSixty CD children (63.3% male) and 121 sex- and age-matched healthy subjects were enrolled. Data including growth, clinical characteristics, time for vitamin D blood test, erythrocyte sedimentation rate, C reactive protein, serum 25(OH)D concentration and steroid treatments were collected. The relationship between vitamin D status and disease activity, disease location, growth and steroid treatments in children with CD were analized.

RESULTThe serum concentration of 25(OH)D was 57.2(22.3-246.0) nmol/L, which was significantly lower than that of controls (67.3 (57.3-78.4) nmol/L) (Z=-5.009, P=0.000). Hypovitaminosis D was most prevalent during the winter and spring (November to April, 46.8(31.8-83.4) nmol/L) rather than summer and autumn (May to October, 63.3(22.3-246.0) nmol/L, Z=-1.994, P=0.046). Univariate logistic regression demonstrated that factors increasing the risk of vitamin D deficiency in Crohn's disease were: age over 10 years (OR=4.571, 95% CI: 1.452-14.389), small intestine involved diseases (OR=5.211, 95% CI: 1.278-21.237), high C reactive protein levels (≥8 mg/L) (OR=4.500, 95% CI: 1.094-18.503) and steroid therapy (OR=4.297, 95% CI: 1.413-13.068). Among those risk factors, all but age were determined to be risks of vitamin D deficiency by further multivariate logistic regression. There was no significant correlation between vitamin D deficiency and gender, disease duration, stricture, penetration, perianal disease (fistula, ulcer or abscess), white blood cell counts, hemoglobin, platelet counts, erythrocyte sedimentation rate, serum albumin levels, pediatric Crohn's disease activity index and nutrition therapy (P>0.05).

CONCLUSIONHypovitaminosis D was prevalent in children with CD. Serum concentration of vitamin D was associated with season. Steroid treatment, small intestine involved disease and high C reactive protein (more than 8 mg/L) are risk factors of vitamin D deficiency in CD children.

C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Crohn Disease ; complications ; Female ; Humans ; Logistic Models ; Male ; Prevalence ; Risk Factors ; Seasons ; Vitamin D ; blood ; Vitamin D Deficiency ; complications ; Vitamins ; blood

Acute Disease ; Adult ; Female ; Humans ; Mesenteric Ischemia ; etiology ; surgery ; Pregnancy ; Pregnancy Complications ; surgery ; Protein S Deficiency ; complications ; Remission Induction

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.
Adult ; Anticoagulants/therapeutic use ; Base Sequence ; Blood Proteins/*genetics ; Codon, Terminator ; Exons ; Humans ; Male ; Mesenteric Veins/radiography ; Polymorphism, Restriction Fragment Length ; Portal Vein/radiography ; Protein S Deficiency/complications/*diagnosis ; Sequence Analysis, DNA ; Splenic Vein/radiography ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/drug therapy/etiology

BACKGROUNDIn response to the injury of the central nervous system (CNS), the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP), which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.

METHODSWe generated ephrin-B2 knockout mice specifically in CNS astrocytes. Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates. In both groups, a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury. Twenty-eight days after the injury, Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups. All the data were analyzed by t-test for between-group comparison.

RESULTSWe successfully set up the conditional ephrin-B2 knockout mice strain, which was confirmed by genotyping and ephrin-B2/GFAP double staining. These mice developed normally without apparent abnormality in general appearance. Twenty-eight days following brain injury, histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups. Compared with wild-type group, the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P = 0.005) and hippocampus (P = 0.027). Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P = 0.008).

CONCLUSIONSThe establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes. Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury, which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

Animals ; Atrophy ; Brain ; pathology ; Brain Injuries ; complications ; pathology ; Ephrin-B2 ; deficiency ; physiology ; Glial Fibrillary Acidic Protein ; Gliosis ; etiology ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins ; analysis

OBJECTIVETo study the molecular pathogenesis of protein C (PC) deficiency in a patient with pulmonary embolism and in his family members.

METHODSAnticoagulated blood samples were collected from the proband and his family members to detect PC, PS and AT activities. PC antigen level was measured using ELISA. The genomic DNA was extracted to amplify all the 9 exons and their flanking sequences of PC gene using PCR, and the PCR products were sequenced. The mutated exons identified were amplified and sequenced for the other family members.

RESULTSThe proband and his parents and sister were identified as carriers of PC gene mutation, which led to type II PC deficiency. Sequencing of the proband's PC gene showed two heterozygous point mutations in exon 3 (G5540A) and exon 7 (C10230T) to cause compound heterozygous mutations of PC E29K and PC R147W, which were inherited from his father and mother, respectively. His sister was a heterozygote of PC R147W.

CONCLUSIONThe proband is a compourd heterozygous mutations carrier of PC E29K and PC147W. PC E29K is a novel PC mutation, and PC R147W is a reported PC gene mutation seen in patients with type II hereditary PC deficiency and recurrent thrombosis.

Adolescent ; Base Sequence ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Protein C ; genetics ; Protein C Deficiency ; complications ; genetics ; pathology ; Pulmonary Embolism ; etiology ; genetics

Cerebral Infarction ; etiology ; Enzyme Activation ; Humans ; Infant ; Male ; Protein C Deficiency ; complications ; Protein S Deficiency ; complications

Mesenteric venous thrombosis is a clinically very rare disease, and may cause bowel infarction and gangrene. Difficulty in the dignosis the disease due to its non-specific symptoms and low prevalence can cause a clinically fatal situation. Mesenteric venous thrombosis may be caused by both congenital and acquired factors, and protein C deficiency, which is a very rare genetic disorder, is one of many causes of mesenteric thrombosis. The authors experienced a case of mesenteric venous thrombosis caused by protein C deficiency in a patient with duodenal ulcer bleeding, so here we report a case together with literature review.
Duodenal Ulcer/*complications/diagnosis ; Endoscopy, Gastrointestinal ; Humans ; Male ; *Mesenteric Veins ; Middle Aged ; Peptic Ulcer Hemorrhage/*complications ; Protein C Deficiency/*complications/diagnosis ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/etiology/ultrasonography

OBJECTIVEThis study examined the effects of maternal deficiency of folic acid during pregnancy on pulmonary development and protein A (SP-A) expression in newborn rats in order to explore the possible mechanism of lung developmental disorders.

METHODSThirty-six adult Sprague-Dawley female rats were randomly assigned into two groups: control and study (n=18). The study and the control groups were fed with fodder containing folic acid or not respectively. Two weeks later, the female rats in the two groups copulated with normal male rats. Newborn rats were sacrificed at 1, 7 and 14 days after birth (8 pups at each time point). Lung sections were stained with hematoxylin and eosin for histological examination. SP-A expression of protein and mRNA were determined by immunohistochemistry and real-time quantitative RT-PCR, respectively.

RESULTSThe newborn rats from the study group showed damaged lung tissue structures. The mean optical density of type II cells with positive expression of SP-A decreased significantly from 1 to 14 days in newborn rats of the study group compared with the control newborn rats (P<0.05). The real-time quantitative RT-PCR showed that the expression of lung SP-A mRNA also decreased significantly from 1 to 14 days in newborn rats of the study group compared with control newborn rats (P<0.05).

CONCLUSIONSMaternal deficiency of folic acid during pregnancy can decrease the expression of SP-A in lung tissues of newborn rats, which might lead to the disorder of lung development maturation.

Animals ; Animals, Newborn ; Female ; Folic Acid Deficiency ; metabolism ; Immunohistochemistry ; Lung ; embryology ; Male ; Pregnancy ; Pregnancy Complications ; metabolism ; Pulmonary Surfactant-Associated Protein A ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction