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M Deng

Publications and source records attributed to M Deng.

50 records · Page 3Linked to original sources

[Intravascular sonographic findings after orthotopic heart transplantation: comparison with clinical factors].

30 patients (mean age 51.4 +/- 11.6 years; female n = 6) were studied early after orthotopic heart transplantation (11.6 +/- 5.5 weeks). Twelve recipients had undergone specific treatment for biopsy proven rejection. Using a mechanical intravascular ultrasound device (3.5-F catheter), 153 coronary artery segments (16 left coronary main stem, 122 left anterior descending artery, 15 left circumflex artery) were studied. Intimal index and circumferential extension of a three-layer appearance of the vessel wall were assessed. In all segments, systolic-diastolic changes in area (delta A) with respect to vessel area and pressure (delta P) were used to study normalized compliance (normalized compliance = [delta A/A]/delta P [mm Hg-1 x 10(3)]). Intravascular ultrasound findings were correlated to perioperative ischemia time, LDL/HDL-ratio, Lp(a) and donor age. In a subgroup of 13 recipients, intravascular ultrasound investigation was repeated after an interval of 67.4 +/- 10.2 weeks. At first investigation, mean intimal index of all coronary segments was 0.07 +/- 0.10. Mean circumferential extension of a three-layer appearance of the vessel wall was 84 +/- 112 degrees. Normalized compliance was 2.43 +/- 1.90 mm Hg-1 in the left main stem 2.45 +/- 1.47 mm Hg-1 within the left anterior descending artery, and 2.66 +/- 1.72 mm Hg-1 within the circumflex artery (differences n.s.). No correlation was found between intimal index and normalized compliance (r = -0.322), nor between circumferential extension of intimal thickening and normalized compliance (r = -0.362). Furthermore, there was no correlation between normalized compliance and donor age. Normalized compliance was significantly lower in recipients with proven rejection than in those without (1.76 +/- 0.81 versus 2.95 +/- 1.22 mm Hg-1, p = 0.005). Both, intimal index and circumferential extension of intimal thickening, were significantly higher in recipients following rejection periods (p < 0.05). The extent of coronary vessel wall alterations on ultrasound correlated to donor age but not to perioperative ischemia time, LDL/HDL-ratio and Lp(a). Re-investigation of a subgroup of 13 recipients 67.4 +/- 10.2 weeks after the first study showed an insignificant increase of the intimal index (from 0.03 to 0.09) and of the circumferential extension of intimal thickening (from 40 to 111 degrees). Normalized compliance changed from 2.53 +/- 1.48 to 2.87 +/- 1.33 mm Hg-1 (differences n.s.). Early after orthotopic heart transplantation, a significant correlation between atherosclerotic coronary vessel wall alterations assessed by intravascular ultrasound and donor age can be confirmed. Heart recipients following rejection periods present with significantly more atherosclerotic vessel wall alterations and a severely reduced compliance of the coronary vessels.

Adult↗

Cerebrospinal fluid levels of amyloid beta-protein in Alzheimer's disease: inverse correlation with severity of dementia and effect of apolipoprotein E genotype.

Alzheimer's disease (AD) is characterized by formation in brain of neurofibrillary tangles and of amyloid deposits. The major protein component of the former is tau, while the latter are composed of amyloid beta-peptides (A beta), which are derived by proteolytic cleavage of the amyloid beta-protein precursor (APP). Both tau and various secretory APP derivatives including A beta and APPS are present in human cerebrospinal fluid (CSF). To investigate whether clinical signs of AD are paralleled by changes in CSF levels of these proteins, we correlated quantitative measures of dementia severity with CSF concentrations of A beta, of APPS, and of tau. We found that levels of A beta in CSF of AD patients were inversely correlated both to cognitive and to functional measures of dementia severity. In contrast, levels of APPS and of tau did not correlate with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF levels of A beta, APPS, or tau, which were similar among AD patients with Apo E epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF levels of A beta decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype.

Aged↗

Angiographic, intravascular ultrasound and functional findings early after orthotopic heart transplantation.

Accelerated graft atherosclerosis is responsible for increased mortality and morbidity among heart transplant recipients. The aim of this in-vivo study was to evaluate coronary atherosclerotic vessel alterations and endothelial function. Seventeen patients (14 males; mean age 49.3 years; range 24 to 69) were studied an average of 11 weeks (range 5 to 21) after heart transplantation because of coronary artery disease (n = 8), dilative cardiomyopathy (n = 7), mitral valve replacement (n = 1) and left atrial metastases of a leiomyosarcoma (n = 1). Mean age of the donor hearts (9 males) was 29 years (range 12 to 55). All recipients underwent biplane ventriculography and coronary angiography. In this study population, a total of 120 coronary segments (main stem, 21; left anterior descending artery, 85; circumflex artery, 14) were analyzed by intravascular ultrasound (20 MHz, 3.5F). In 13 patients, acetylcholine was infused into the proximal left anterior descending artery (10(-8) to 10(-5) M) to evaluate vasomotion within this segment. Regional contraction abnormalities were documented in 2 patients. Nine segments angiographically showed non-critical stenoses (5 patients). Intravascular ultrasound detected 52 cross-sectional areas with a three-layer pattern indicating intimal thickening. Mean circumferential extension of intimal proliferation was 192 degrees, mean intimal thickness 0.35 mm. Only 5 segments of the sonographically pathological cross-sectional areas showed angiographical evidence of atherosclerotic lesions. Intracoronary administration of acetylcholine at doses of 10(-8) and 10(-7) M resulted in vasoconstriction of the examined coronary segment in only 2 patients; the intracoronary application of acetylcholine at doses of 10(-6) and 10(-5) M revealed coronary vasoconstriction in 10 of the total of 13 patients. Using intravascular ultrasound, coronary artery lesions in heart transplant recipients can already be depicted at a very early stage. The abnormal response to acetylcholine in most of the heart recipients is independent of the extent of atherosclerotic vessel abnormalities documented by ultrasound or angiography.

Acetylcholine↗

[Initial experiences with dobutamine stress echocardiography in heart transplant patients].

UNLABELLED: Cardiac allograft vasculopathy (CAV) has become one of the primary obstacles to long-term survival of patients after heart transplantation. The low sensitivity of currently available noninvasive tests still remains a problem in the early diagnosis of the disease. To assess the feasibility, safety, and usefulness of dobutamine stress echocardiography as a noninvasive predictor of cardiac allograft vasculopathy, we examined 20 patients (3 female) 3-35 months after orthotopic heart transplantation. All patients underwent coronary angiography within 2 weeks of dobutamine stress echocardiography. RESULTS: 89% of the segments examined could be evaluated for wall motion abnormalities. Under increasing doses of dobutamine (5 to max. 30 micrograms/kg/min), heart rate increased from 88 +/- 13 bpm to 141 +/- 16 bpm. and systolic blood pressure from 139 +2- 14 mm Hg to 154 +/- 28 mm Hg. Two of 4 patients with angiographically detected CAV developed new wall motion abnormalities under dobutamine; their wall motion score increased from 1.23 +/- 0.22 to 1.31 +/- 0.24. In the other patients without CAV, the wall motion score remained almost unchanged (1.01 +/- 0.3 to 1.02 +/- 0.4). Dobutamine was well tolerated, and there were no serious complications. Thus, dobutamine stress echocardiography seems to be feasible and safe in patients after heart transplantation. Our results suggest that it might be useful for the detection of cardiac allograft vasculopathy. The final determination of its clinical usefulness in the diagnosis of cardiac allograft vasculopathy needs further extensive investigations.

Adult↗

Regulation of proteolytic processing of the amyloid beta-protein precursor of Alzheimer's disease in transfected cell lines and in brain slices.

beta A4 is the principal component of Alzheimer's disease brain amyloid. It is derived from proteolytic processing of amyloid beta-protein precursors (APP), a family of transmembrane glycoproteins. Secretion of APPs, a secreted proteolytic derivative that is cleaved within the beta A4 domain of APP, is increased many-fold by the activation of cell-surface receptors, like the muscarinic m1 and m3 receptor subtypes, which are coupled to protein kinase C. Concomitantly, their activation decreases the formation of both secreted soluble beta A4 and of endosomal-lysosomal C-terminal APP derivatives. These data suggest that muscarinic m1 and m3 receptors accelerate non-amyloidogenic APP processing and depress the formation of potentially amyloidogenic derivatives. Other receptors that stimulate APPs secretion include those for bradykinin, vasopressin, and interleukin-1 receptors. A similar control mechanism is present in rat brain tissue slices, in which the release of both APPs and endogenous neurotransmitters is increased by electrical depolarization. This increase is tetrodotoxin-sensitive and frequency-dependent, suggesting that APPs release may normally depend on neuronal activity. Taken together, our findings suggest that specific receptor agonists might be effective in reducing the formation of potentially amyloidogenic APP derivatives in vivo.

Alzheimer Disease↗

Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels.

Although progesterone and estrogens are essential to maintain human pregnancy after implantation, the localization of their specific receptors in different uterine cell types during pregnancy has not been investigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues were processed for indirect immunocytochemical staining with specific monoclonal antibodies against estrogen receptors (ER; Abbott Laboratories) and progesterone receptors (PR; Li 417). Specific staining for steroid receptors was only detected in the nucleus. In the endometrium, PR staining remained fairly constant throughout pregnancy, whereas ER staining was initially weak and then undetectable. PR was widely expressed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secretory activity during the first trimester. Spiral arteries of the endometrium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative for both ER and PR (except for one and two specimens, respectively). We conclude the following. 1) Stromal cells retain PR despite the high progesterone levels during pregnancy, in keeping with the role of progesterone in stromal decidualization. The absence of PR from the secretory glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR down-regulation by progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is progesterone secretion. 4) The intense PR staining in smooth muscle cells of spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.

Adult↗

Early diastolic left ventricular function as a marker of acute cardiac rejection: a prospective serial echocardiographic study.

Changes in left ventricular early diastolic time intervals are sensitive indicators of incipient left ventricular dysfunction. We tested the hypothesis that acute rejection in cardiac transplant recipients is associated with alteration of early diastolic myocardial function, as expressed by the time interval Te, a parameter derived from digitized M-mode echocardiograms. Te is defined as the time interval between maximal posterior wall contraction and the point of peak posterior wall endocardium retraction velocity, as determined by the nadir of the computed first derivative curve. In transplant patients without rejection (group A, n = 48), Te was prolonged compared to healthy individuals (group C, n = 35) (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms; p < 0.0001). During acute rejection (group B, n = 18) transplant patients had significantly longer mean Te values compared to transplant patients without rejection (group A) (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p < 0.0001). Longitudinal studies in individual patients (group D, n = 18) demonstrated that rejection is associated with prolongation of Te (94.5 +/- 16.0 ms during rejection vs 79.0 +/- 10.3 ms before rejection; p < 0.0002) and that Te returns to individual baseline values in response to treatment (79.2 +/- 9.4 ms after therapy vs 79.0 +/- 10.3 ms before rejection; NS). In a prospective study, Te changes in transplant patients (group E, n = 96) were correlated with myocardial biopsy results. Sixty-one biopsies showed acute rejection, and 115 biopsies were negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Tungstate, a molybdate analog inactivating nitrate reductase, deregulates the expression of the nitrate reductase structural gene.

Nitrate reductase (NR, EC 1.6.6.1) from higher plants is a homodimeric enzyme carrying a molybdenum cofactor at the catalytic site. Tungsten can be substituted for molybdenum in the cofactor structure, resulting in an inactive enzyme. When nitratefed Nicotiana tabacum plants were grown on a nutrient solution in which tungstate was substituted for molybdate, NR activity in the leaves decreased to a very low level within 24 hours while NR protein accumulated progressively to a level severalfold higher than the control after 6 days. NR mRNA level in molybdate-grown plants exhibited a considerable day-night fluctuation. However, when plants were treated with tungstate, NR mRNA level remained very high. NR activity and protein increased over a 24-hour period when nitrate was added back to N-starved molybdate-grown plants. NR mRNA level increased markedly during the first 2 hours and then decreased. In the presence of tungstate, however, the induction of NR activity by nitrate was totally abolished while high levels of NR protein and mRNA were both induced, and the high level of NR mRNA was maintained over a 10-hour period. These results suggest that the substitution of tungsten for molybdenum in NR complex leads to an overexpression of the NR structural gene. Possible mechanisms involved in this deregulation are discussed.

Journal Article↗

Consequence of Absence of Nitrate Reductase Activity on Photosynthesis in Nicotiana plumbaginifolia Plants.

Chlorate-resistant Nicotiana plumbaginifolia (cv Viviani) mutants were found to be deficient in the nitrate reductase apoprotein (NR(-)nia). Because they could not grow with nitrate as sole nitrogen source, they were cultivated as graftings on wild-type Nicotiana tabacum plants. The grafts of mutant plants were chlorotic compared to the grafts of wild type. Mutant leaves did not accumulate nitrogen and nitrate but contained less malate and more glutamine than wild leaves. They exhibited a slight increase of the proportion of the light-harvesting chlorophyll a/b protein complexes and a lowering of the efficiency of energy transfer between these complexes and the active centers. After a 3 second (14)CO(2) pulse, the total (14)C incorporation of the mutant leaves was approximately 20% of that of the control. The (14)C was essentially recovered in ribulose bisphosphate in these plants. It was consistent with a decline of ribulose bisphosphate carboxylase activity observed in the mutant. After a 3 second (14)CO(2) pulse followed by a 60 second chase with normal CO(2), (14)C was mainly accumulated in starch which was labeled more in the mutant than in the wild type. These results confirm the observation that in the nitrate reductase deficient leaves, chloroplasts were loaded with large starch inclusions preceding disorganization of the photosynthetic apparatus.

Journal Article↗

A broad-spectrum enzyme-linked immunosorbent assay for the detection of human enteric viruses.

An enzyme-linked immunosorbent assay (ELISA) test has been devised for detection of a broad spectrum of human enteric viruses, based on the use of poly-L-lysine as a nonspecific adhesive to hold the virus particles in the test wells and of pooled human immune serum globulin to mark the virus for detection with commercial goat anti-human IgG antibody conjugated with horseradish peroxidase. Detection of five human enteroviruses and a reovirus at levels of 10 most probable number of cytopathogenic units (MPNCU) to 10 PFU per well was achieved, whereas no reaction was seen with two porcine enteroviruses. When two virus types are present in a sample, the ELISA reactions augment each other.

Antigens, Viral↗

Heart transplantation for restrictive cardiomyopathy: development of cardiac amyloidosis in preexisting monoclonal gammopathy.

A 54-year-old woman died 6 months after heart transplantation for treatment of restrictive cardiomyopathy. A monoclonal gammopathy without other signs of malignant disease was present preoperatively, and up to 6 weeks before transplantation no evidence of amyloidosis was established in the rectal, bone marrow, and cardiac specimens. At autopsy there was amyloidosis type AL in the kidneys, bone marrow, liver, spleen, recipient atrium, and donor heart. Retrospectively, the explanted heart also revealed amyloidosis. We conclude that in patients undergoing heart transplantation for treatment of restrictive cardiomyopathy with a preexisting monoclonal gammopathy, a thorough evaluation, including multiorgan biopsy for amyloidosis with electron microscopic workup, should be performed.

Amyloidosis↗