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101.
102.
We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average threefold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. In contrast, the larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. However, their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. These studies provide evidence that the different subtypes of von Willebrand's disease represent distinct abnormalities of factor VIII/von Willebrand factor. They also suggest that complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand's disease, and only if factor VIII/von Willebrand factor can be raised to normal levels. 相似文献
103.
Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome 总被引:2,自引:0,他引:2
In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered. 相似文献
104.
Eagle SH Chu Myth TS Mok Minnie YY Go Kwan Man Rainer Heuchel Hui Yao Lan Zhijie Chang Joseph JY Sung Jun Yu 《The Journal of pathology》2013,230(4):441-452
Smad7 is a principal inhibitor of the TGFβ–Smad signalling pathway. We have investigated the functional significance of Smad7 in hepatocellular carcinoma (HCC). Smad7 knockout (KO) and wild‐type (WT) mice were injected with diethylnitrosamine (DEN) to induce HCC. The effects of Smad7 on cellular features were examined in HCC cells, using a Smad7 over‐expression or deletion approach. Signalling pathway components modulated by Smad7 in HCC were evaluated using luciferase reporter assay and co‐immunoprecipitation. Smad7 was down‐regulated in human HCCs compared with the adjacent normal tissues (p < 0.001). Smad7 KO mice were more susceptible to DEN‐induced HCC than WT mice (78% versus 22%, p < 0.05). HCCs from KO mice displayed a greater proliferation activity (p < 0.05) and a reduced apoptotic index compared with WT littermates (p < 0.05). Deletion of Smad7 promoted cell proliferation in primary cultured HCC cells. In addition, over‐expression of Smad7 in HCC cell lines markedly suppressed cell growth (p < 0.0001) and colony formation (p < 0.01). Cell cycle analysis revealed an increase in the G1 phase and a reduction in the S‐phase populations, accompanied by up‐regulation of p27Kip1 and down‐regulation of cyclin D1. Smad7 increased cell apoptosis (p < 0.01) by mediating an intrinsic [caspase‐9, caspase‐3 and poly(ADP‐ribose) polymerase] apoptotic pathway. Moreover, Smad7 inhibited NF‐κB signalling by interacting with TAB2, an upstream activator of NF‐κB, and inhibited TGFβ signalling by suppressing phosphorylation of Smad3. In conclusion, loss of Smad7 enhances susceptibility to HCC. Smad7 suppresses HCC cell growth by inhibiting proliferation and G1–S phase transition and inducing apoptosis through attenuation of NF‐κB and TGFβ signalling. Smad7 acts as a potential tumour suppressor in liver. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
105.
Purpose
The relationship between congenital talipes equinovarus (CTEV) and developmental dysplasia of the hip (DDH) remains uncertain. The role of routine hip screening in children with CTEV is debated. A recent study has found a high incidence of DDH in patients with CTEV. The aim of our study was to determine the true prevalence of radiographic hip dysplasia and identify the need for routine hip screening in patients treated for CTEV.Methods
From a single centre database of 165 children consisting of 260 CTEV, a prospective radiological prevalence study of 101 children was performed over a period of 3 months. A single anterior-posterior pelvic radiograph was performed at a minimum age of 5 months. The DDH was determined by a single senior investigator based on the age-adjusted acetabular index (AI) as described by Tonnis.Results
There were no dislocations or subluxations. According to the age-adjusted AI, 16 children had ‘light’ dysplasia and one child had ‘severe’ dysplasia. The child with severe dysplasia was known to have DDH and had already undergone treatment. The 16 children with light dysplasia did not require any form of treatment.Conclusion
Out of one hundred and one children with CTEV, only one had DDH requiring treatment. This is consistent with the majority of the literature supporting the premise that there is no true association between CTEV and DDH. We, therefore, feel that routine hip screening for children with CTEV is not supported by current evidence and cannot be recommended. 相似文献106.
The existence of a layer IV in the rat motor cortex 总被引:1,自引:1,他引:0
We have reconstructed the laminar pattern of rat primary motor cortex (Fr1)
using a computerized analysis system based on the so-called 'optical
dissector'. Data were visualized on a graphics terminal. In contrast to
current views, which state that there is no prominent layer IV in the motor
cortex of the rat, our method of analysis revealed a genuine layer IV
consisting of densely packed small neurons.
相似文献
107.
108.
109.
An analytical technique has been developed for the isoelectric focusing (IEF) of plasma von Willebrand factor (vWF) in agarose gels containing urea. Under these conditions, vWF freely enters the gel and focuses without artifact. The focused vWF is visualized by staining fixed gels with 125I-labeled affinity-purified heterologous antibody. Utilizing a pH gradient of 5.0-6.5, normal vWF in plasma or purified preparations focuses into at least three bands with apparent isoelectric points (pI) between pH 5.7 and 5.9. A reproducible difference in the IEF pattern of vWF has been established between normal plasmas and those of individuals with variant von Willebrand's disease (vWd) type IIA and type IIB. In type IIA, vWF has a distinctly lower pI than normal. This difference may be related to the presence of smaller vWF multimers in IIA plasma because forms of vWF of corresponding size contained in normal cryoprecipitate supernatant have a similar pI. Type IIB von Willebrand factor has a pI intermediate between normal and IIA. Neuraminidase treatment of plasma samples before IEF results in an increase in pI in normal, type IIA, and type IIB vWF. The data suggest that none of the 16 type IIA and 9 IIB plasmas studied here contain significantly decreased amounts of sialic acid. 相似文献
110.
Ablation of renal tumors with absolute ethanol: a new technique 总被引:5,自引:0,他引:5