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1.
PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells 总被引:65,自引:10,他引:55
PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM. 相似文献
2.
From Jan 1, 1978 through Dec 31, 1983, 64 patients with epithelial ovarian tumors, frankly malignant or borderline, were managed at one institution. Nineteen patients (29.7%) were under age 40. The youngest patient was 19 years old. Nulliparity was present in 32% of this group of patients. Of these young patients, 58% had borderline epithelial tumors, compared to 13% of patients over 40 years of age. Twenty-one percent of the young patients were initially managed by unilateral adnexal surgery. The overall cumulative actuarial survival rate of all young patients was 93%. Young patients with epithelial ovarian tumors tend to have earlier grades of epithelial neoplasms, and survival is better than that reported for older patients with similar tumors. 相似文献
3.
Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. 总被引:32,自引:0,他引:32
BACKGROUND. Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS. We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS. Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation. 相似文献
4.
Devang N Patel Francis D Pagani Todd M Koelling David B Dyke Ragavendra R Baliga Robert J Cody Kathleen D Lake Keith D Aaronson 《The Journal of heart and lung transplantation》2002,21(2):204-210
BACKGROUND: Pravastatin and simvastatin prolong survival and reduce transplant-related coronary vasculopathy, although low-density lipoprotein (LDL) lowering with these agents is only modest. The objective of this study was to assess the safety of moderate dose atorvastatin and its efficacy when prior treatment with another statin had failed to lower LDL to < 100 mg/dl. METHODS: Data from 185 patients were retrospectively evaluated for adverse events, duration of exposure (person-days), and the mean atorvastatin dose exposure. Changes in lipid parameters, and prednisone and cyclosporine doses were determined. RESULTS: Safety: 48 patients received atorvastatin for 24,240 person-days at a mean dose exposure of 21 +/- 10 mg. Rhabdomyolysis, myositis, myalgias, and hepatotoxicity occurred in 0, 2, 2, and 0 patients, respectively. All events occurred at the 10-mg dose, within the first 3 months, and were rapidly reversible with atorvastatin discontinuation. Efficacy: Thirty-four patients evaluable for efficacy analyses had a pre-atorvastatin LDL of 145 +/- 38 mg/dl on the following statins: pravastatin (n = 30, 40 +/- 0mg), fluvastatin (n = 3, 33 +/- 12 mg), simvastatin (n = 1, 40 mg). After atorvastatin (21 +/- 9 mg/day) for 133 +/- 67 days, LDL was reduced to 97 +/- 24 mg/dl (relative reduction 31 +/- 20%, p < 0.0001). At the end of the observation period (418 +/- 229 days, atorvastatin final dose 24 +/- 14 mg/day), LDL was further decreased to 88 +/- 23 mg (relative reduction 37 +/- 17%, p < 0.0001). CONCLUSION: Atorvastatin, when used at moderate doses and with close biochemical and clinical monitoring, appears to be safe and is effective in aggressively lowering LDL in heart transplant recipients when treatment with other statins has failed to achieve LDL goals. 相似文献
5.
Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy 总被引:2,自引:0,他引:2
The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer. 相似文献
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8.
The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation 总被引:5,自引:0,他引:5
Wetzels AM; Bastiaans BA; Hendriks JC; Goverde HJ; Punt-van der Zalm AP; Verbeet JG; Braat DD 《Human reproduction (Oxford, England)》1998,13(5):1325-1330
In a human in-vitro fertilization (IVF) programme, the effect of co-
culture of embryos with human fibroblasts was evaluated with respect to
pregnancy rate and embryo development. Patients were included in the study
after giving informed written consent. The IVF treatments were randomly
assigned by stratification of both age (<36 versus > or =36 years)
and previous IVF attempts (yes versus no). After fertilization was
established, the zygotes were transferred to a 4-well dish with or without
fibroblasts and cultured for 2 days. On the third day after ovum pick-up
(OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were
scored and a maximum of three embryos was transferred. Supernumerary
embryos of good quality were cryopreserved. The design of this study was a
group sequential trial with the objective of detecting differences between
pregnancy rates following IVF with conventional incubation or incubation in
co-culture with fibroblasts. This design included one evaluation at
half-way data collection. In the study, 148 patients had an OPU, of whom 77
were allocated to the co-culture group. There was no statistically
significant difference in pregnancy rate, cell number and embryo quality
between the two groups. The ongoing pregnancy rate per embryo transfer was
27% in co-culture and 30% in the conventional culture group. The
implantation rates per transferred embryo were 17 and 18% respectively.
Using a multivariate logistic regression model for the probability of
ongoing pregnancies, the odds ratio of co-culture, adjusted for age and
previous IVF attempts, was not statistically significant. In conclusion,
co-culture with human fibroblasts does not contribute to an improvement of
embryo quality nor to a higher pregnancy rate after IVF in an unselected
group of patients.
相似文献
9.
A functional analysis of the components of the mesencephalic nucleus of the fifth nerve in the cat 总被引:3,自引:5,他引:3
1. The mesencephalic nucleus of the trigeminal nerve has been studied using extracellular micro-electrode recording and the constituent cell types identified.2. Two types of unit were found, namely, muscle spindle first order afferents of ipsilateral jaw-closing muscles and mechanoreceptor afferents of ipsilateral maxillary and mandibular teeth.3. No evidence was found for representation of extra-ocular muscle stretch receptors, of temporo-mandibular joint receptors or of tendon organs of jaw muscles.4. Spindle units of each of the jaw-closing muscles were recorded in all parts of the nucleus and there was no evidence of their segregation according to muscle of origin.5. Attempts to classify spindle units by their dynamic response to ramp stretches, their following of high frequency vibration and their interspike interval variability at constant length gave no indication of two populations when fusimotor activity was suppressed.6. Following the injection of suxamethonium, however, units fell into two groups according to their dynamic index. Their behaviour resembled that described for primary and secondary spindle afferents. In data pooled from all of the jaw-closing muscles there were approximately equal numbers of units in each group. 相似文献
10.
Dohle GR; Ramos L; Pieters MH; Braat DD; Weber RF 《Human reproduction (Oxford, England)》1998,13(3):620-623
Male genital tract obstructions may result from infections, previous
inguinal and scrotal surgery (vasectomy) and congenital bilateral absence
of the vas deferens (CBAVD). Microsurgery can sometimes be successful in
treating the obstruction. In other cases and in cases of failed surgical
intervention, the patient can be treated by microsurgical or percutaneous
epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction
(TESE) and intracytoplasmic sperm injection (ICSI). We present the results
of 39 ICSI procedures for obstructive azoospermia in 24 couples. The
aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD
in nine and genital infections in four. Sperm retrieval was accomplished
via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was
only applied when PESA failed to produce enough spermatozoa for
simultaneous ICSI. In six patients, the ICSI procedure was performed with
cryopreserved spermatozoa after an initial PESA procedure. Fertilization
occurred in 47% of the metaphase II oocytes; embryo transfer was performed
in 92% of procedures and resulted in a clinical pregnancy in 13/39
procedures. Ongoing pregnancy was achieved in 10/39 procedures. One
pregnancy was terminated early after prenatal investigation showed a
cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine
pregnancies resulted in the live birth of 10 children, without any
congenital abnormalities. Epididymal and testicular retrieved spermatozoa
were successfully used for ICSI to treat obstructive azoospermia, and
resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI
procedures, a success rate of 25.6% per treatment cycle and of 27.7% per
embryo transfer.
相似文献