Mediation of platelet adhesion to fibrillar collagen in flowing blood by a proteolytic fragment of human von Willebrand factor

The effect of purified von Willebrand Factor (vWF) fragments, SpII (dimer of two 110 kd subunits) and SpIII (dimer of two 170 kd subunits) obtained with S aureus V-8 protease was tested upon platelet adhesion to collagen. Purified fibrillar human collagen coated onto cover slips was incubated with SpII, SpIII, or undigested vWF and exposed to reconstituted human blood in a parallel-plate perfusion chamber at a high shear rate. Platelet-collagen interactions were estimated using 51Cr-platelets and quantitative morphometry. When blood was reconstituted with citrated autologous plasma, SpIII and vWF strikingly enhanced platelet adhesion to collagen whereas SpII had no effect. When blood was reconstituted with human albumin and divalent cations, SpIII and vWF again promoted platelet adhesion to collagen. In conclusion, our data suggest that (1) SpIII, the N-terminal portion of vWF which binds to platelet membrane glycoprotein Ib, functionally substitutes for vWF in supporting platelet adhesion to collagen; (2) SpII, the C- terminal portion which binds to glycoprotein IIb/IIIa, has no such effect; (3) in addition to its platelet binding domain, SpIII contains another site for binding to collagen; and (4) the multimeric structure of vWF is not required for platelet adhesion to collagen.     

Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels

Interstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels. The female neonate was born at 37 weeks of gestation as the second child to a 31-year-old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double-outlet right-ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium. Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long-term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery.     

Deficiency of platelet membrane glycoprotein Ia associated with a decreased platelet adhesion to subendothelium: a defect in platelet spreading

A bleeding disorder with absent collagen-induced platelet aggregation and adhesion has been described in a patient whose platelets failed to express surface glycoprotein Ia. We studied the interaction of her platelets with subendothelium in an annular perfusion chamber and the interaction with purified human collagen type III in a rectangular perfusion system under flow conditions. Platelet adherence was almost completely absent both at low and high shear rates. The few platelets which adhered remained in the contact stage without subsequent spreading and aggregate formation. Addition of a monoclonal antibody, which was directed against the von Willebrand moiety of FVIII-VWF, to the blood, completely abolished platelet adherence at high shear rates and had a partial effect at low shear rates. These data indicate that von Willebrand factor plays a role in the initial attachment (contact stage) of platelets to subendothelium. We conclude that the bleeding disorder and excessively prolonged bleeding time in our patient are caused by a new specific defect of the platelet-vessel wall interaction.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

血清中INF-γ、MMP-9对多发性硬化患者病情及远期生活质量的影响

目的:观察血清中干扰素-γ(INF-γ)、基质金属蛋白酶-9(MMP-9)不同含量水平对多发性硬化间歇、发作期及远期生活质量的影响。方法:采用ELISA测定76例每次发作期入院第2天血清中INF-γ、MMP-9含量水平。以每例患者3 a内复发间歇期、发作期为观察统计指标,3 a后采用多发性硬化生活质量-54(MSQOL-54)、神经功能残疾量表(EDSS)进行评分。结果:MS患者血清中INF-γ、MMP-9含量水平越高,间歇期越短、发作期越长、MSQOL-54各项评分越低及EDSS评分越高(P<0.05)。结论:MS患者每次发作期血清中INF-γ、MMP-9含量水平越高,则发作频率增加,发作期越长,远期生活质量越差。     

Associations between Dynamic Vitamin D Level and Thyroid Function during Pregnancy

Optimal Vitamin D (VitD) status and thyroid function are essential for pregnant women. This study aimed to explore associations between dynamic VitD status and thyroid function parameters in each trimester and throughout the pregnancy period. Information on all 8828 eligible participants was extracted from the Peking University Retrospective Birth Cohort in Tongzhou. Dynamic VitD status was represented as a combination of deficiency/sufficiency in the first and second trimesters. Thyroid function was assessed in three trimesters. The associations between VitD and thyroid function were assessed by multiple linear regression and generalized estimating equation models in each trimester and throughout the pregnancy period, respectively. The results indicated that both free thyroxine (fT4; β = 0.004; 95%CI: 0.003, 0.006; p < 0.001) and free triiodothyronine (fT3; β = 0.009; 95%CI: 0.004, 0.015; p = 0.001) had positive associations with VitD status in the first trimester. A VitD status that was sufficient in the first trimester and deficient in the second trimester had a lower TSH (β = −0.370; 95%CI: −0.710, −0.031; p = 0.033) compared with the group with sufficient VitD for both first and second trimesters. In conclusion, the associations between VitD and thyroid parameters existed throughout the pregnancy. Maintaining an adequate concentration of VitD is critical to support optimal thyroid function during pregnancy.     

Diagnostik und Prognose der fetalen Kardiomegalie

Ohne Zusammenfassung     

Mandibular canine with two roots and three root canals

Abstract – A rare case of root canal retreatment in a lower canine with two roots and three canals is presented. While the presence of two roots and two canals in one root is not uncommon, the finding of three canals in a lower canine appears not to have been reported previously.