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31.
Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure. 相似文献
32.
Prolactinoma and body weight: a retrospective study 总被引:1,自引:0,他引:1
L B Creemers P M Zelissen J W van 't Verlaat H P Koppeschaar 《Acta endocrinologica》1991,125(4):392-396
Body weight and weight history in association with hormone levels were studied retrospectively in 47 patients with prolactinoma; macroprolactinoma was diagnosed in 36, microprolactinoma in 11 patients. At the time of diagnosis a weight history could be traced in 14 patients, 9 patients having gained weight (11.8 +/- 2 kg), 1 with a weight loss of 5 kg, and 4 reporting unaltered body weight. Body weight and Body Mass Index before treatment were 83 +/- 2.4 kg and 27.3 +/- 0.6 kg/m2, respectively. In the male patients the prevalence of BMI greater than or equal to 25 was greater than in the average Dutch male population (p less than 0.001). After 6 months of treatment, mainly with bromocriptine, patients with macroprolactinoma had lost 5.5 +/- 1.6% (p less than 0.002) of initial body weight. No significant weight change occurred in patients with microprolactinoma. Weight loss did not correlate with degree of hyperprolactinemia, nor with decrease of prolactin levels during treatment, in either group of patients. Thyroid or gonadal function were not associated with weight loss either. It appears that prolactinoma is associated with a higher frequency of overweight, as far as patients with macroprolactinoma are concerned. 相似文献
33.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
34.
Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity 总被引:1,自引:5,他引:1
Broxterman HJ; Sonneveld P; Feller N; Ossenkoppele GJ; Wahrer DC; Eekman CA; Schoester M; Lankelma J; Pinedo HM; Lowenberg B; Schuurhuis GJ 《Blood》1996,87(11):4809-4816
We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies. 相似文献
35.
Wijnhoven Lieke A. M. W. Engels Rutger C. M. E. Onghena Patrick Otten Roy Creemers Daan H. M. 《Journal of autism and developmental disorders》2022,52(1):150-168
Journal of Autism and Developmental Disorders - The aim of the present study was to examine the additive effect of elements of cognitive behavioral therapy (CBT) on the video game Mindlight in... 相似文献
36.
N. De Vos L. Van Hoovels A. Vankeerberghen K. Van Vaerenbergh A. Boel I. Demeyer L. Creemers H. De Beenhouwer 《Clinical microbiology and infection》2009,15(4):358-363
Herpes simplex virus (HSV) has increasingly been associated with pulmonary disease in critically ill patients. However, the clinical relevance of HSV is still a topic of debate. Monitoring of HSV in a quantitative way could potentially give relevant information on its role in the pathogenesis of lower respiratory tract infection. A fast and reliable quantitative real-time PCR (Q-PCR) for the quantitative detection of HSV-1 and HSV-2 DNA was developed. A prospective observational study was performed in an intensive-care unit (ICU) to monitor the HSV viral load in lower respiratory tract aspirates of long-term mechanically ventilated patients. HSV was common in the lower respiratory tract (LRT) of critically ill patients with mechanical ventilation for at least 48 h (62%, n = 65/105). Detection of HSV was significantly associated with prolonged mechanical ventilation (p <0.01), prolonged ICU stay (p <0.01), and development of ventilator-associated pneumonia (p = 0.02). Corticosteroid administration (p <0.01) in the ICU and anti-HSV IgG seropositivity (p <0.01) were risk factors for the occurrence of HSV in the LRT. The fact that no HSV-seronegative patient became positive suggests that all HSV DNA-positive patients had HSV reactivations. Monitoring the HSV viral load in the LRT of critically ill patients showed a typical homogeneous pattern of HSV kinetics. HSV emerged in tracheal and bronchial aspirates after a median of 7 days of intubation (5–11 days), and this was followed by an exponential increase ( c. 1 log copies/mL/day) to reach very high HSV peaks (106 –1010 copies/mL) in 78% of the HSV DNA-positive patients. 相似文献
37.
G Low GJ Irwin G Haddock SV Maroo 《Journal of Medical Imaging and Radiation Oncology》2006,50(3):249-251
The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings. 相似文献
38.
Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver 总被引:1,自引:0,他引:1
Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver
tumors in a chronic bioassay and exhibited tumor-promoting activity in
N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen
inhibited mouse liver tumor development and the hepatocarcinogenic and
tumor-promoting dose of UG produced uterine changes suggestive of estrogen
antagonism. To directly test the hypothesis that UG-induced tumor-promoting
ability is secondary to its interaction with the mouse liver tumor
inhibitor, estrogen, we compared the tumor-promoting ability of UG in
ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG
in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure
to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting
conditions began at 8 weeks of age. After 4 months of exposure, UG
increased relative liver weight and hepatic microsomal cytochrome P450
pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to
a similar extent in intact and Ovex mice. Non-focal hepatocyte
proliferation, as measured by the incorporation of bromo-deoxyuridine, was
not changed by UG exposure and was similar in all treatment groups. After 4
months of exposure to DEN-initiated mice, UG significantly increased the
volume fraction of liver occupied by foci (three-fold) as compared to
control intact mice. As expected, volume of foci was elevated in
DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex
mice UG did not significantly increase the focal volume fraction. Thus, the
tumor promoting activity of UG, as demonstrated by increased volume
fraction of liver occupied by hepatic foci in intact mice, is greatly
attenuated in Ovex mice. The volume fraction data in Ovex mice support the
hypothesis that the tumor promoting activity of UG is dependent upon the
interaction of UG with ovarian hormones. These data also indicate that
hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly
and non-focal hepatic LI are not specific markers of hepatic tumor
promoting activity of UG.
相似文献
39.
Zhang GJ; Tsuda H; Adachi I; Fukutomi T; Yamamoto H; Hirohashi S 《Japanese journal of clinical oncology》1997,27(6):371-377
Patients with primary breast carcinoma with one to three axillary lymph
node metastases but without distant metastases (n1-3) in Japan have been
shown to have a 10-year disease-free survival rate of > 60%. It would be
reasonable to divide n1-3 Japanese breast cancer patients into groups with
high- or low-risk for recurrence and to consider post-operative adjuvant
therapy. In the present study, we analyzed 228 consecutive Japanese
patients with n1-3 breast cancer who underwent radical mastectomy and were
followed up for a median time of 11.0 years. The expression of bcl-2, p53
and c-erbB-2 proteins in the primary tumors was examined
immunohistochemically and their prognostic roles were also analyzed along
with conventional clinicopathologic indicators. bcl-2 expression was
correlated with positive estrogen receptor status and inversely correlated
with p53, c-erbB-2 and histologic grade. Univariate analysis showed that
bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the
patient's group as well as node status, histologic grade, tumor size, age
at diagnosis, menopausal status and estrogen receptor status. Cox's
regression analysis demonstrated that the number of nodes involved,
menopausal status, p53 and bcl-2 were independent predictors for overall
survival and that histologic grade and the number of nodes involved were
independent predictors for disease-free survival. These results suggest
that bcl-2 expression in combination with p53 and c-erbB-2 expression, the
number of lymph node metastases, histologic grade and menopausal status are
useful in selecting subgroups of n1-3 breast cancer patients with good or
poor prognoses.
相似文献
40.
Risk factors for deaths in under-age-five children attending a diarrhoea treatment centre 总被引:2,自引:0,他引:2
Few case-control studies have examined possible risk factors for diarrhoeal deaths in under-age-five children in the developing countries. We analysed data from the surveillance system of our diarrhoea treatment centre/hospital for the period 1990-94 on 928 children less than 5 years of age. In univariate analysis, 11 factors were significantly associated with death: lack of breastfeeding, severe malnutrition, complicated diarrhoea, pneumonia, xerophthalmia, duration of diarrhoea 7-14 days, moderate or severe dehydration, recent history of measles, Shigella flexneri infection, maternal illiteracy, and very low household income. Rotavirus diarrhoea was negatively associated with fatal outcome. In the assessment of severe malnutrition, weight-for-height measurement discriminated mortality risk better than weight-for-age or height-for-age indices. Only two factors retained their significance, severe malnutrition and non-breastfeeding in the multivariate analysis with adjusted odds ratio (95% confidence interval) of 84.2 (9.1, 775.9) and 4.2 (1.3, 13.2) respectively. 相似文献