Showing papers by "University of Freiburg published in 1991"

Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis.

Abstract: The endothelium plays a critical role in the control of vasomotor tone by the release of vasoactive substances. Because endothelial injury or dysfunction is considered important very early in atherogenesis, we hypothesized that abnormal endothelial function precedes the angiographic detection of coronary atherosclerosis in the human coronary circulation. The coronary vasomotor responses to three different endothelium-mediated stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M, increase in blood flow to induce flow-dependent dilation, and sympathetic stimulation by cold pressor testing) were assessed by quantitative angiography and subselective intracoronary Doppler flow velocity measurements within the left anterior descending coronary artery in 38 patients. All three stimuli elicited epicardial artery dilation in all 11 patients with smooth coronary arteries and absence of risk factors for coronary artery disease (group 1). All nine patients with smooth coronary arteries but with hypercholesterolemia (group 2) demonstrated a selective impairment in endothelial function with vasoconstriction (35 +/- 12.7% decrease in mean luminal area) in response to acetylcholine but showed a preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6% increase in mean luminal area). In all nine patients with an angiographically defined smooth coronary artery segment but with evidence of atherosclerosis elsewhere in the coronary system (group 3), both acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/- 8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively), whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in mean luminal area). In the nine patients with angiographic evidence of wall irregularities (group 4), flow-dependent dilation was also abolished and vasoconstriction occurred in response to acetylcholine and cold pressor testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area, respectively). All coronary artery segments dilated in response to nitroglycerin, suggesting preserved function of vascular smooth muscle. Despite similar reductions in coronary vascular resistance in response to the smooth muscle relaxant papaverin, patients with hypercholesterolemia demonstrated a selective impairment of vasodilation of the resistance vasculature in response to acetylcholine (p less than 0.05 versus groups 1, 3, and 4). Thus, there is a progressive impairment of endothelial vasoactive functioning in coronary arteries of patients with different early stages of atherosclerosis, beginning with a selective endothelial dysfunction in angiographically defined normal arteries in patients with hypercholesterolemia and progressively worsening to a complete loss of endothelium-mediated vasodilation in angiographically defined atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoembryonic antigen gene family: molecular biology and clinical perspectives.

Abstract: The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted Splice variants of individual genes and differential post-translational modifications of the resulting proteins, eg, by glycosylation, indicate a high complexity in the number of putative CEA-related molecules So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis.

Abstract: BACKGROUNDThe vascular endothelium is capable of regulating tissue perfusion by the release of endothelium-derived relaxing factor to modulate vasomotor tone of the resistance vasculature.METHODS AND RESULTSTo test whether atherosclerosis is associated with a functional abnormality of endothelium-mediated microvascular relaxation affecting coronary blood flow regulation, we compared coronary blood flow responses with cold pressor testing with the response of the coronary vasculature to acetylcholine (an endothelium-dependent vasodilator) and to papaverin (a direct dilator of vascular smooth muscle) in 12 normal control patients and in 19 patients with non-flow-limiting epicardial atherosclerosis (CAD). The drugs were subselectively infused into the left anterior descending coronary artery via a Doppler catheter, and the response in coronary blood flow was assessed by measuring intracoronary blood flow velocity and cross-sectional arterial area (quantitative angiography). Coronary vascular resistance decre...

Relaxation and retardation functions of the maxwell model with fractional derivatives

Abstract: A four-parameter Maxwell model is formulated with fractional derivatives of different orders of the stress and strain using the Riemann-Liouville definition. This model is used to determine the relaxation and retardation functions. The relaxation function was found in the time domain with the help of a power law series; a direct solution was used in the Laplace domain. The solution can be presented as a product of a power law term and the Mittag-Leffler function. The retardation function is determined via Laplace transformation and is solely a power law type. The investigation of the relaxation function shows that it is strongly monotonic. This explains why the model with fractional derivatives is consistent with thermodynamic principles. This type of rheological constitutive equation shows fluid behavior only in the case of a fractional derivative of the stress and a first order derivative of the strain. In all other cases the viscosity does not reach a stationary value. In a comparison with other relaxation functions like the exponential function or the Kohlrausch-Williams-Watts function, the investigated model has no terminal relaxation time. The time parameter of the fractional Maxwell model is determined by the intersection point of the short- and long-rime asymptotes of the relaxation function.

Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany.

Abstract: • Little work has been carried out on the epidemiology of the two serious skin reactions—toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, β-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs. ( Arch Dermatol. 1991;127:839-842)

Local mesh refinement in 2 and 3 dimensions

Abstract: An algorithm for local refinement of a given conforming triangulation in 2 or 3 dimensions is presented. Proofs for the finiteness of the algorithm and stability of the obtained triangulations are given.

The dorsolateral, suboccipital, transcondylar approach to the lower clivus and anterior portion of the craniocervical junction.

Abstract: The authors review their experience with a dorsolateral approach to the anterior rim of the foramen magnum and adjacent region. The operative technique includes exposure of the vertebral artery at C1, partial resection of the occipital condyle and lateral atlantal mass, and extradural drilling of the jugular tubercle. This approach has been applied in six patients who harbored intradural space-occupying lesions located ventral to the lower brain stem. Excision of the neoplasm was virtually total in all but one patient, in whom biopsy was the primary goal of the intervention. No morbidity and no mortality were associated with this approach. The main advantage of the dorsolateral, suboccipital, transcondylar route is the direct view it offers to the anterior rim of the foramen magnum without requiring brain stem retraction.

Editing of a chloroplast mRNA by creation of an initiation codon

Abstract: PRIMARY mRNA transcripts in several systems are edited by single base substitutions, small deletions or insertions to yield functional messenger RNA species1,2 Mitochondrial mRNAs in particular, including those from plants3–5, seem to be the subject of extensive editing, unlike mRNAs encoded by chloroplast DNA, for which the prediction of amino-acid sequence from the corresponding gene sequence is generally unambiguous6–8 Occasionally, however, an ACG codon appears at the 5′ terminus of chloroplast genes, where the initiation codon ATG would be expected Here we present evidence for a C → U editing that is responsible for the conversion of the ACG codon to an AUG initiation codon in the mRNA transcript from the rpl2 gene of the maize plastome, showing that mRNA editing can also occur in chloroplasts

Cytogenetics of papillary renal cell tumors

Abstract: Chromosome aberrations were determined in short-term cultures of 18 papillary renal cell tumors, as well as in the cell line ACHN, and the results were evaluated together with 20 previously published cases. We found that chromosomes 7, 17, and 16 and the Y chromosome were specifically involved in the karyotype changes, marks benign papillary renal cell adenomas (ten cases). Malignant papillary renal cell carcinomas (29 cases) were characterized by additional trisomies: trisomy 16 occurred in 20 tumors, and trisomy 12 and 20 in 8 tumors each. Loss of the Y chromosome was observed in 7 of 9 benign and in 23 of 25 malignant tumors that developed in males. None of the papillary renal cell adenomas or carcinomas showed a loss of 3p or gain of a 5q segment, both of which are characteristic of common non-papillary renal cell carcinomas.

Trunk orientation as the determining factor of the ‘contralateral’ deficit in the neglect syndrome and as the physical anchor of the internal representation of body orientation in space

Abstract: The present study examines which egocentric coordinate system determines the border between the disturbed 'contralateral' and the normal 'ipsilateral' side in patients with hemineglect. Based on the observation of significantly longer reaction times for saccades towards stimuli presented in the left visual field (LVF) in right brain-damaged patients with hemineglect, stimuli were presented randomly to the LVF or RVF and the corresponding saccadic reaction times (SRTs) were compared. Beginning with the standard body position generally used for the investigation of neglect patients, where the midlines of head, trunk and visual field are parallel and oriented straight towards the middle of the projection screen, the spatial relation between orientation of head and trunk midlines and location of the target stimuli was systematically varied while holding the retinal projection of the stimuli constant. The deficit in SRTs towards the LVF in 4 right brain-damaged patients with left-sided hemineglect could be compensated for by turning the patients' trunk to the left, such that both LVF and RVF-stimuli were projected to the right, ipsilateral side of trunk space. The results suggest that the spatial orientation of the trunk midline divides our normal perception of space into an egocentric 'left' and an egocentric 'right' sector and seems to be the decisive factor for determining the neglected 'contralateral' part of space in patients with brain-damage. They indicate that the trunk midline constitutes the physical anchor for calculation of the internal egocentric coordinate frame for representing body position with respect to external objects. The hypothesis of Ventre et al. (1984) that deficient reactions to contralaterally located stimuli in neglect patients could be the result of a displacement of these egocentric coordinates towards the non-neglected, ipsilateral side is discussed.

Ki-67 immunostaining in human breast tumors and its relationship to prognosis.

Abstract: Ki-67 labeling was quantified in 37 nonmalignant breast tissues and in 63 breast carcinomas by counting ten random high-power fields each in three section planes (RC) or by evaluation of the area with the highest labeling density (HDC). Both procedures proved to be highly correlated (rs = 0.94). Ki-67-positive fractions of the nonmalignant tissues (mean, 2.1% for RC and 4.1% for HDC) were significantly lower as compared with the carcinomas (mean, 14.5% for RC and 17.5% for HDC). In carcinomas the Ki-67 labeling was significantly associated with pT stage, axillary lymph node status, and tumor grading and inversely related to progesterone receptor status. Using the medians of both counting methods (12% for RC and 17% for HDC) as cutoff points, significantly different curves for overall and disease-free survival (median follow-up, 37 months) were obtained. However, Cox multivariate analysis failed to demonstrate an independent effect of Ki-67 labeling. In contrast, Ki-67 reactivity seems to be of independent prognostic value if a higher cutoff level was selected.

EDRF-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries.

Abstract: In small saline-perfused rabbit mesenteric arteries (diam 221 +/- 4 microns, means +/- SE; n = 48) in situ, the interactions of endothelium-derived relaxing factor (EDRF)-mediated flow-dependent dilation and myogenic constriction were studied. When pump flow was increased two- to fivefold (2.8 +/- 0.1-fold), input perfusion pressure rose by 133 +/- 17%. Vessel diameter first increased passively by 9 +/- 1% and then decreased to or below control values reflecting the vascular myogenic activity. This was followed by a 16 +/- 3% increase in diameter, which was flow dependent, because nonperfused vessels exposed to the same intravascular pressures did not dilate. When the perfusate viscosity was increased with dextran solutions, both the basal diameters and the flow-induced dilator responses were significantly augmented, indicating that the increase in shear stress was the stimulus. The flow-dependent dilation was abolished by inhibition of EDRF with either hemoglobin (10 microM) or NG-nitro-L-arginine (0.3 mM) and also after preincubation with neuraminidase (0.2 U/ml, 30 min), which removes part of the membrane glycocalyx. Thus, myogenic responses in small mesenteric arteries can be effectively opposed by shear-induced release of EDRF. This might be a major mechanism for maintaining adequate tissue perfusion when pressure and shear stress increase simultaneously (e.g., exercise hyperemia, autoregulation) and otherwise myogenic activity would reduce vascular conductivity.

Human perception of horizontal trunk and head rotation in space during vestibular and neck stimulation.

Abstract: The vestibular signal of head motion in space must be complemented by a neck signal of the trunk-to-head excursion in order to provide the individual with information on trunk motion in space. This consideration led us to study psychophysically the role of vestibular-neck interaction for human self-motion perception. Subjects (Ss) were presented with passive horizontal rotations of their trunk and/or head (sinusoidal rotations, f=0.025 –0.4 Hz) in the dark for vestibular and neck stimulation, as well as for combinations of both. Ss' perception was evaluated in terms of gain (veridical perception of stimulus magnitude, G=1), phase, and detection threshold. (1) Perception of trunk rotation in space. During vestibular stimulation (whole-body rotation) and neck stimulation (trunk rotation with the head kept stationary) the frequency-transfer characteristics underlying this perception were very similar. The gain fell short; it was only about 0.7 at 0.4 and 0.2 Hz stimulus frequency and was further attenuated with decreasing frequency. In contrast, the phase was close to that of actual trunk position. The gain attenuation was found to be a function of the peak angular velocity of the stimulus, a fact, which we related to a ‘velocity threshold’ of the order of 1 deg/s. During the various vestibular-neck combinations used, Ss' perception was again erroneous, reflecting essentially the sum of its two non-ideal constituents. However, there was one noticeable exception; during the combination ‘head rotation on stationary trunk’, Ss veridically perceived their trunk as stationary (compatible with the notion that the sum yielded ‘zero’). (2) Perception of head rotation in space. During vestibular stimulation, Ss' estimates showed the same non-ideal gain-vs.-frequency characteristics as described above for the trunk. Neck stimulation induced an illusion as if the head had been rotated in space. This neck contribution was such that, when it was combined with its vestibular counterpart during head rotation on stationary trunk, the perception became almost veridical. On closer inspection, however, this neck contribution was found to reflect the sum of two components; one was the non-ideal neck signal contributing to the perception of ‘trunk in space’, the other was an almost ideal neck signal of head-on-trunk rotation. (3) The results could be described by a simple model. In this model, the erroneous vestibular signal ‘head in space’ is primarily used to create an internal representation of ‘trunk in space’. To this end, it is combined with the closely matching neck signal of ‘trunk to head’. The perception of head rotation in space is achieved by summing this ‘trunk in space’ signal with the almost ideal ‘head on trunk’ signal, again of nuchal origin. These seeming complex interactions have two implications: (i) the head is referred to trunk coordinates, whereas the trunk is referred to space coordinates; (ii) there is at least one condition in the dark where orientation is correct (despite an erroneous vestibular signal), i.e., during head rotation on stationary trunk.

Palmaz stent in atherosclerotic stenoses involving the ostia of the renal arteries: preliminary report of a multicenter study.

Abstract: Palmaz balloon-expandable stents were placed in 28 hypertensive patients with atherosclerosis involving the ostia of the renal arteries. Stents were placed to treat elastic recoil immediately after conventional angioplasty in 20 patients and restenosis after percutaneous transluminal angioplasty in eight patients. Technical success (greater than 30% residual stenosis) was achieved in 27 patients. Complications occurred in five patients. At follow-up (1-25 months), hypertension was cured in three patients and improved in 15 patients, with a cumulative cure or improvement of 64% at 6 months. Of 14 patients with a serum creatinine level of 1.5 mg/dL (132.6 mumol/L) or greater before the placement of stents, five demonstrated improved renal function, five showed stabilization of their condition, and four demonstrated deterioration. Follow-up angiography (2-18 months) was performed in 18 patients. Restenosis was present in seven patients and was accompanied by a relapse of hypertension in only three patients. Of the other four patients with restenosis, two had no initial improvement and two had an initial response without a relapse of hypertension. In this preliminary study, renal stents were beneficial in many patients with poor results from conventional angioplasty for ostial atheroma.

Construction and beam test of the ZEUS forward and rear calorimeter

Abstract: The forward and rear calorimeters of the ZEUS experiment are made of 48 modules with maximum active dimensions of 4.6 m height, 0.2 m width, 7 λ depth and maximum weight of 12 t. It consists of 1 X 0 uranium plates interleaved with plastic scintillator tiles read out via wavelength shifters and photomultipliers. The mechanical construction, the achieved tolerances as well as the optical and electronics readout are described. Ten of these modules have been tested with electrons, hadrons and muons in the momentum range 15–100 GeV/ c . Results on resolution, uniformity and calibration are presented. Our main result is the achieved calibration accuracy of about 1% obtained by using the signal from the uranium radioactivity.

Femtosecond time-resolved molecular multiphoton ionization: The Na2 system.

Abstract: We report here the first experimental study of femtosecond time-resolved molecular multiphoton ionization. Femtosecond pump-probe techniques are combined with time-of-flight spectroscopy to measure transient ionization spectra of ${\mathrm{Na}}_{2}$ in a molecular-beam experiment. The wave-packet motions in different molecular potentials show that incoherent contributions from direct photoionization of a singly excited state and from excitation and autoionization of a bound doubly excited molecular state determine the observed transient ionization signal.

Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms

Abstract: This study determines whether an impaired endothelium-mediated vasodilation in coronary resistance vessels exists in patients with microvascular angina. In 23 patients with clinically suspected coronary artery disease and smooth coronary arteries in the angiogram, coronary flow in response to an endothelium-related (acetylcholine) and endothelium-unrelated (dipyridamole) vasodilation was measured. Coronary flow was determined by the gas-chromatographic argon method (1) before, (2) with intracoronary acetylcholine infusion, and (3) after dipyridamole administered intravenously. In 8 patients, acetylcholine did not significantly increase coronary flow (from 91 +/- 28 to 118 +/- 37 ml/min.100 g), whereas flow was greatly increased after administration of dipyridamole (258 +/- 97 ml/min.100 g), indicating an endothelium-related vasodilator defect. In 6 patients, neither acetylcholine nor dipyridamole caused a significant increase in coronary flow, indicating an impaired coronary vasodilation on the vascular site. In 6 patients, coronary flow increased markedly after both administration of both acetylcholine and dipyridamole (from 81 +/- 26 to 191 +/- 68 and 234 +/- 87 ml/min.100 g). In 3 patients given acetylcholine, coronary artery constriction occurred. No significant correlation was found between the response to acetylcholine and that to dipyridamole (r = 0.40, p = not significant). The results indicate that in a subgroup of patients with smooth coronary arteries angina can be caused by an abnormality of the endothelial function in the microcirculation.

The mossy cells of the fascia dentata: A comparative study of their fine structure and synaptic connections in rodents and primates

Abstract: In this study the fine structure and synaptic connections of mossy cells in the rat and monkey fascia dentata were analyzed. In order to study commissural connections of identified mossy cells in the rat, hilar neurons were retrogradely labeled by horseradish peroxidase (HRP) or Fast Blue (FB) injections into the contralateral hippocampus. Vibratome sections containing retrogradely HRP-labeled hilar neurons were Golgi-impregnated and gold-toned. Hilar commissural neurons identified by contralateral FB injection were intracellularly labeled with Lucifer Yellow (LY). Lucifer Yellow staining was made electron-dense by photoconversion thereby allowing for an electron microscopic analysis of the retrogradely labeled and intracellularly stained neurons. With these two different approaches, we succeeded in identifying rat mossy cells projecting to the contralateral hippocampus. Mossy cells in the fascia dentata of primates (Papio anubis, Macaca mulatto, Saimiri sciureus) were, like mossy cells of rats, either Golgi-impregnated and gold-toned or intracellularly injected with LY. No major differences were found between mossy cells of rats and monkeys. The mossy cell dendrites originated from the two sides of an ovoid cell body and were mainly oriented parallel to the granule cell layer. In contrast to the rat, dendrites of mossy cells in the primate did not respect the granule cell layer and penetrated frequently into the molecular layer. The occurrence of excrescences on proximal dendrites was a characteristic feature of all mossy cells. These large spines were more complex in the primate than in the rat. In both rats and primates they formed numerous asymmetric synapses with large boutons of mossy fibers. Peripheral dendrites were covered with small, simple spines. Interestingly, these peripheral dendrites lacking excrescences also established asymmetric synapses with mossy fiber boutons as well as asymmetric and symmetric contacts with smaller terminals of unknown origin. These findings indicate that in both rats and primates the thorny excrescences are not the only target of the mossy terminals. While the proximal portions of the mossy cell dendrites appear to be exclusively contacted by the granule cells, a larger number of neuron types may converge on the distal dendrites. The axons of mossy cells, in both rats and primates, although incompletely stained with the present methods, were seen to ramify in-the hilar region. Our results demonstrate that, despite minor species differences, the mossy cells of the fascia dentata represent a cell type that is preserved in phylogenetically distant species.

Reflex activity and muscle tone during elbow movements in patients with spastic paresis

Abstract: Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis. During sinusoidal (0.3-Hz) isometric or isotonic elbow tracking, with a control either of joint position or of torque, randomly timed displacements were induced (at one of three velocities) stretching either the activated flexor or the extensor muscles. On the spastic side, exaggerated short-latency reflexes were apparent, but in contrast, the amplitude of long-latency electromyography (EMG) responses was reduced. The latter responses were differentially modulated on the unaffected side, predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque, while the mode of muscle contraction (isometric or isotonic) had little influence on this behavior. This difference in reflex modulation was lost on the spastic side. The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements. The ratio of torque to EMG activity during displacements was higher for both background and reflex-induced EMG on the spastic limb than on the unaffected side. This effect was more pronounced for the flexor than for the extensor muscles. Consequently, the development of spastic muscle hypertonia cannot be attributed to an increase in EMG activity. It is suggested that secondary to a supraspinal lesion, mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched.

Biased Estimation of the Odds Ratio in Case-Control Studies due to the Use of Ad Hoc Methods of Correcting for Missing Values for Confounding Variables

Abstract: The effects of missing values for a confounding variable are investigated in the setting of case-control studies in which, for simplicity, the effect of one binary risk factor and one categoric confounding variable on disease risk is under investigation. Some ad hoc techniques with which to deal with missing values are examined under different assumptions about the missing-data mechanism. Examples are given to illustrate that the magnitude of the bias that is introduced by applying an inadequate procedure can be large under circumstances that occur frequently in empiric research. This is true even for so-called complete case analysis, i.e., when only data on subjects with complete information are used. Appropriate bias corrections are derived. Making use of data on those subjects who are neglected in complete case analysis by creating an additional category always results in biased estimation. An alternative is to allocate these subjects to the cells of the contingency table in an appropriate manner. This approach yields consistent estimates if the data are missing at random. Choosing an appropriate method for dealing with missing values always requires some knowledge of why the data are missing. This suggests that investigators should carry out validation studies to understand whether the missing values occur randomly across the study population or occur more frequently in specific subgroups.

Effects of native and oxidized low density lipoproteins on formation and inactivation of endothelium-derived relaxing factor.

Abstract: The influence of native (N-) and oxidized (Ox-) low density lipoproteins (LDLs) on endothelium-dependent vasomotion is still controversial. We investigated the short-term effects of N-LDL and Ox-LDL on the formation of endothelium-derived relaxing factor (EDRF) in native and cultured endothelial cells and on its inactivation after release from the cells. N-LDL was isolated from fresh human plasma via sequential ultracentrifugation and oxidized by incubation with Cu2+. EDRF released from cultured endothelial cells was inactivated by both N-LDL and Ox-LDL (1 mg/ml) as detected in a bioassay system. N-LDL reduced the EDRF-mediated vasodilations of the detector segments by 38.5 +/- 5.3%, and Ox-LDL, by 55.5 +/- 4.6%. The effects of lipoproteins on EDRF formation were studied in cultured endothelial cells preincubated with either N-LDL or Ox-LDL (1 mg/ml for 1 hour) and stimulated for EDRF release with bradykinin after washout of the lipoproteins. EDRF was assessed by measuring its stimulatory effect on the activity of a purified, soluble guanylate cyclase. Both N-LDL and Ox-LDL did not reduce the bradykinin-induced EDRF formation. Consistent with this finding, acetylcholine-induced, EDRF-mediated dilations of intact rabbit femoral artery segments were not impaired by luminal exposure to N-LDL or Ox-LDL (1 mg/ml for 1 hour). However, these relaxations were significantly reduced by preincubation of aortic ring preparations with the same concentrations of the same charges of N-LDL and Ox-LDL. In conclusion, neither N-LDL nor Ox-LDL acutely impairs the formation of EDRF but does inactivate EDRF after its release from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)