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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 109 records · Page 6Linked to original sources
PubMed1998

cAMP-dependent phosphorylation sites and macroscopic activity of recombinant cardiac L-type calcium channels.

The involvement of cAMP-dependent phosphorylation sites in establishing the basal activity of cardiac L-type Ca2+ channels was studied in HEK 293 cells transiently cotransfected with mutants of the human cardiac alpha1 and accessory subunits. Systematic individual or combined elimination of high consensus protein kinase A (PKA) sites, by serine to alanine substitutions at the amino and carboxyl termini of the alpha1 subunit, resulted in Ca2+ channel currents indistinguishable from those of wild type channels. Dihydropyridine (DHP)-binding characteristics were also unaltered. To explore the possible involvement of nonconsensus sites, deletion mutants were used. Carboxyl-terminal truncations of the alpha1 subunit distal to residue 1597 resulted in increased channel expression and current amplitudes. Modulation of PKA activity in cells transfected with the wild type channel or any of the mutants did not alter Ca2+ channel functions suggesting that cardiac Ca2+ channels expressed in these cells behave, in terms of lack of PKA control, like Ca2+ channels of smooth muscle cells.

Alanine↗
PubMed1998

Interleukin-4 Modulation of Platelet-Derived Growth Factor-Induced Smooth Muscle Cell Urokinase Plasminogen Activator.

Platelet-derived growth factor (PDGF) stimulates smooth muscle cell (SMC) migration owing to stimulation of SMC tissue plasminogen activator (t-PA) production. In this study we examined the effects of the T-cell lymphokine interleukin-4 (IL-4) on PDGF induction of human aortic SMC antigen levels of urokinase-type plasminogen activator (u-PA) and those of plasminogen activator inhibitor-1 (PAI-1), the endogenous inhibitor of t-PA and u-PA, measured by enzyme-linked immunosorbent assays (ELISAs). u-PA antigen levels from human aortic SMC incubated with PDGF 100 ng/mL and IL-4 500 U/mL were significantly greater than those incubated with PDGF 100 ng/mL alone. Coincubation of PDGF with IL-4 did not significantly increase SMC u-PA antigen levels in cellular lysates. Coincubation with PDGF 100 ng/mL and IL-4 500 U/mL did not significantly affect SMC PAI-1 antigen levels in conditioned media or cellular lysates. Therefore, interleukin-4 modulates vascular SMC u-PA production induced by PDGF.

Journal Article↗
PubMed1998

Inflammatory profile in unstable angina versus stable angina in patients undergoing percutaneous interventions.

BACKGROUND: Inflammatory markers have been shown to be elevated in acute coronary syndromes. Recently, interleukin-6 was demonstrated to be elevated in unstable angina compared with stable angina. However, the effect of percutaneous coronary interventions on the levels of inflammatory markers is less well known. METHODS AND RESULTS: In this study, we measured the levels of interleukin-6 and interleukin-1 by using enzyme-linked immunosorbent assays in patients with angina pectoris undergoing coronary interventions and in healthy control subjects. Interleukin-6 was significantly elevated in patients with unstable angina compared with patients with stable angina (P= .01). There were no significant differences between the levels of interleukin-1 in patients with unstable angina versus patients with stable angina and healthy control subjects. Furthermore, at 1-month follow-up after percutaneous coronary interventions, there were no longer any significant differences between the levels of interleukin-6 in patients with unstable angina versus patients with stable angina and healthy control subjects. CONCLUSIONS: These data suggest that interleukin-6 levels may correlate with instability of atheromatous plaques and that the decrease of interleukin-6 levels after percutaneous coronary interventions may represent plaque reendothelialization and stabilization.

Adult↗
PubMed1998

A comparison of guanosine-quartet inhibitory effects versus cytidine homopolymer inhibitory effects on rat neointimal formation.

Phosphorothioate oligodeoxynucleotides (PS oligos) manifest antisense and G-quartet aptameric inhibitory effects on vascular smooth muscle cell (SMC) proliferation. PS oligo cytidine homopolymers also have nonsequence-specific, non-G-quartet inhibitory effects on in vitro and in vivo SMC proliferation. In this study, we compared the effects of S-dC18 and S-dC28, 18-mer and 28-mer cytidine homopolymers, respectively, which lack guanosines, with those of ZK10, a G-tetrad forming compound, on in vitro SMC proliferation and in vivo neointimal formation. ZK10 significantly inhibited in vitro human aortic SMC proliferation. At the same molar concentration, ZK10 had significantly greater inhibitory potency on SMC proliferation than either S-dC18, S-dC28, or 7DG-ZK10, which is a modified ZK10 with ten 7-deaza guanosine substitutions. ZK10 was significantly more potent than S-dC18 and S-dC28 in inhibiting PDGF-induced in vitro SMC migration. S-dC18, S-dC28, and ZK10 treatment significantly reduced the intima/media area ratio after rat carotid artery balloon injury compared with the values of the control groups. ZK10 was a more potent inhibitor of neointimal formation than the same chain length S-dC18. ZK10 formed higher-order structures, as shown on gel electrophoresis, in contrast to S-dC28 and 7DG-ZK10. Therefore, the 18-mer ZK10 has comparable in vivo SMC inhibitory effects to the 28-mer S-dC28, a fact that may have ramifications for the development of optimal PS oligos to inhibit angioplasty restenosis.

Angioplasty, Balloon↗
PubMed1998

Cranial nerve syndrome in thrombosis of the transverse/sigmoid sinuses.

Cerebral venous thrombosis (CVT) is a cerebrovascular disease associated with a wide variety of clinical signs and symptoms, which may often delay appropriate diagnosis. Single or multiple cranial nerve palsies (III-VIII) without evidence of other signs and symptoms have not, so far, been considered a relevant syndrome of CVT. This event turned out to be a characteristic finding in five patients with thrombosis of the ipsilateral transverse/sigmoid sinus, who were recruited prospectively over a 14-month period. The diagnosis was supported by non-invasive MRI with the application of a newly developed subtraction technique. In view of the considerable mimics of the syndrome, and the long-standing need for conventional angiography to confirm the disease, it is likely to have been underestimated in the past; since appropriate treatment seems possible the diagnosis and utility of early MR venography should be considered in patients with single or multiple cranial nerve lesions of uncertain aetiology.

Adult↗
PubMed1998

Reconstructing hominid Y evolution: X-homologous block, created by X-Y transposition, was disrupted by Yp inversion through LINE-LINE recombination.

The human X and Y chromosomes share many blocks of similar DNA sequence. We conducted mapping and nucleotide sequencing studies of extensive, multi-megabase homologies between Yp and Xq21, which do not recombine during male meiosis. We confirmed and built upon previous evidence that a Yp inversion had occurred during evolution: a single contiguous segment of Xq21 is homologous to two non-contiguous segments of Yp. We precisely defined and sequenced the inversion breakpoints, obtaining evidence that the inversion was mediated by recombination between LINE-1 elements in otherwise non-homologous regions. This inversion appears to have followed a single transposition of an approximately 4 Mb segment from the X to the Y chromosome. These events jointly account for the present arrangement of Yp-Xq21 homologous sequences. Based on Southern blotting studies of primates and of humans drawn from diverse populations, we conclude that both the X-Y transposition and the subsequent, LINE-mediated Yp inversion occurred after the divergence of hominid and chimp lineages but before the radiation of extant human populations. This evolutionary scenario is consistent with our finding of 99.3 +/- 0.2% nucleotide identity between the X and Y chromosomes within the transposed region, which suggests that the transposition occurred approximately 3-4 million years ago, near the time of emergence of Homo . Comparative sequencing of the entire human X and Y chromosomes may reveal a succession of transpositions, inversions and other rearrangements underlying the complex pattern of sequence similarities between the present-day sex chromosomes. With the possible exception of cubitus valgus, phenotypic features of Turner syndrome are absent in individuals monosomic for Yp-Xq21 homologous sequences, suggesting that most of the critical 'Turner genes' are found elsewhere on the X and Y chromosomes.

Base Sequence↗
PubMed1998

A comparison of the intubation conditions between mivacurium and rocuronium during balanced anesthesia.

BACKGROUND: Comparisons of the intubation conditions with mivacurium and rocuronium from previous reports are confounded by the use of varied induction regimens. The authors compared intubation conditions of mivacurium, rocuronium, and a placebo at 90 s and their recovery profiles during anesthesia with nitrous oxide, oxygen, and propofol. METHODS: After induction with midazolam, fentanyl, and propofol in a randomized blinded study, 100 patients received one of the following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo. Evoked thumb adduction was measured throughout. Intubation was attempted 90 s after the initial dose of mivacurium and other treatment doses by a "blinded" physician. Intubating conditions were graded as excellent, good, poor, or not possible. Spontaneous recovery was studied until a 25% initial twitch height was reached. Mean arterial blood pressure and heart rate changes between groups were determined before induction through 6 min after administration of the study drugs. RESULTS: There were no important changes or intergroup differences in mean arterial blood pressure and heart rate. Intubation conditions were good or excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27% of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of excellent conditions and the most poor or not possible assessments. Patients given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2 mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2 mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for mivacurium (17.4 +/- 6.2 min). CONCLUSIONS: Mivacurium in a 0.25 mg/kg divided dose and rocuronium at 0.9 mg/kg and 1.2 mg/kg provide good or excellent intubation conditions at 90 s in most patients. Rocuronium was faster in onset at the higher doses (0.9 and 1.2 mg/kg) but had more prolonged recovery times to 25% single twitch height.

Adult↗
PubMed1998

Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic magnetic resonance imaging.

We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL x 100 g(-1) x min(-1), respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL x 100 g(-1) x min(-1). In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.

Acute Disease↗
PubMed1998

Judgment and decision making.

For many decades, research in judgment and decision making has examined behavioral violations of rational choice theory. In that framework, rationality is expressed as a single correct decision shared by experimenters and subjects that satisfies internal coherence within a set of preferences and beliefs. Outside of psychology, social scientists are now debating the need to modify rational choice theory with behavioral assumptions. Within psychology, researchers are debating assumptions about errors for many different definitions of rationality. Alternative frameworks are being proposed. These frameworks view decisions as more reasonable and adaptive that previously thought. For example, "rule following." Rule following, which occurs when a rule or norm is applied to a situation, often minimizes effort and provides satisfying solutions that are "good enough," though not necessarily the best. When rules are ambiguous, people look for reasons to guide their decisions. They may also let their emotions take charge. This chapter presents recent research on judgment and decision making from traditional and alternative frameworks.

Choice Behavior↗
PubMed1998

Leptin attenuates respiratory complications associated with the obese phenotype.

A profile of respiratory complications has been associated with the onset and development of obesity in humans. Similar phenotypes have been routinely demonstrated in genetic animal models of obesity such as the ob mouse (C57BL/6J-Lepob). The objective of the present study was to test the hypothesis that a constellation of respiratory complications are attenuated with leptin (i.e., protein product of the ob gene) replacement. Daily leptin administration during a 6-wk period was conducted to control body weight of mutant ob mice similar to genotypic control groups. During the treatment period, repeated baseline ventilatory measurements were assessed by using whole body plethysmography while quasistatic pressure-volume curves were performed to further explore the role of leptin in improving lung mechanics. Diaphragmatic myosin heavy chain (MHC) isoform phenotype was examined to determine proportional changes in MHC composition. In room air, breathing frequency and minute ventilation were significantly (P < 0.01) different among ob treatment groups, suggesting that leptin opposed the development of a rapid breathing pattern observed in vehicle-treated ob mice. Quasistatic deflation curves indicated that the lung volume of leptin-treated ob mice was significantly (P < 0.05) greater relative to vehicle-treated ob mice at airway pressures between 0 and 30 cmH2O. Diaphragm MHC composition of leptin-treated ob mice was restored significantly (P < 0.05) to resemble the control phenotype. In this genetic mouse model of obesity, the results suggested that respiratory complications associated with the obese phenotype, including rapid breathing pattern at baseline, diminished lung compliance, and abnormal respiratory muscle adaptations, are attenuated with prolonged leptin treatment.

Animals↗
PubMed1998

Acute stroke subtypes--is there a need for reclassification?

Although stroke covers a wide range of diseases and aetiologies, it is currently managed using uniform treatments, such as thrombolysis and neuroprotective drugs, irrespective of the individual stroke pathophysiology. The time-consuming, ineffective and often misleading standard work-up of stroke subtypes is now being augmented with immediate brain and vessel imaging studies and laboratory testing. This approach means that, in addition to distinguishing between haemorrhagic and ischaemic lesions, ischaemic lesions can be assigned to various stroke subtypes. Diffusion-weighted magnetic resonance imaging is useful to detect the cytotoxic oedema occurring early in cerebral ischaemia, and sequential studies are useful in evaluating each patient's prognosis. Both this technique and magnetic resonance angiography are effective in the assessment of an optimal selection of therapy in early stroke. Particular benefit is derived by patients with recent infarction and overlapping signs and symptoms of residual and acute deficits, and those with more than one aetiology. Demonstration of very small versus large ischaemic territories supports the likelihood of a good spontaneous outcome and discourages high-risk treatment procedures. Chronic and acute lesions may be differentiated and potentially salvageable tissue identified in cases of embolic stroke. The micro-embolic nature of lesions formed by the fragmentation of more proximal intracranial artery occlusions may be revealed by ultrasound studies showing high-intensity transient signals. Results from such studies are also useful to re-evaluate present concepts of stroke subtypes: recent data suggest that the 'border zone infarction' concept needs to be largely abandoned.

Acute Disease↗
PubMed1998

Oropharyngeal fatty infiltration in obstructive sleep apnea patients: a histologic study.

It has been suggested that due to fatty infiltration, obstructive sleep apnea (OSA) patients have a narrower pharyngeal airway than normal persons. To identify potential fatty infiltration of pharyngeal tissues that may contribute to OSA, a histologic study of the distal soft palate was performed. Histologic sections of 46 oropharyngeal specimens were evaluated. This included 25 overweight OSA patients (25/31), 6 normal-weight OSA patients (6/31), and a control group of 15 healthy (non-OSA) individuals. A semiquantitative analysis of the fatty tissue was performed. In all 31 OSA patients an excess of fatty infiltration was found in the histologic oropharyngeal specimens in comparison to the control group. No correlation was found between the pharyngeal fatty infiltration degree, the body mass index, and the apnea index. Irrespective of their body weight, in none of the patients without OSA was excessive fatty infiltration seen. It is suggested that excessive pharyngeal fatty infiltration plays a role in upper airway obstruction in OSA and that it can be associated with the development of apnea.

Adipose Tissue↗
PubMed1998

Characteristics of chronic MS lesions in the cerebrum, brainstem, spinal cord, and optic nerve on T1-weighted MRI.

We analyzed the prevalence of severely hypointense lesions on T1-weighted MRI in the brainstem, spinal cord, and optic nerve from 65 patients with MS. About half of 1,274 supratentorial lesions were classified as severely hypointense. Severe hypointensity was not seen in the optic nerve and spinal cord, and in only one of 168 chronic brainstem lesions. Tissue destruction in the brainstem, spinal cord, and optic nerve of MS patients does not usually result in severely hypointense lesions.

Adolescent↗
PubMed1998

Increased release of interleukin-12p40 in MS: association with intracerebral inflammation.

OBJECTIVE: The p40 subunit of interleukin (IL)-12 was recently demonstrated in active lesions in MS. We tested whether the p40 subunit of IL-12 can also be detected in CSF and serum of patients with this disease and, if so, whether release is associated with inflammatory disease activity. RESULTS: This study demonstrates an increased (up to 1,000-fold) compartmentalized release of the p40 subunit but not of the heterodimer p70 in MS. Release of IL-12p40 correlated with classic markers of CNS inflammation (CSF cell counts, immunoglobulin G index) and was significantly increased in patients with gadolinium-enhancing plaques on MRI. Moreover, release of IL-12p40 was associated with CSF levels of myelin basic protein as a measure of myelin degradation. CONCLUSION: These results suggest a role of IL-12p40 in the pathophysiology of MS.

Adolescent↗
PubMed1998

[Rate of complications with systematic exposure of the recurrent laryngeal nerve and parathyroid glands in operations for benign thyroid gland diseases].

OBJECTIVE: The influence of the operation technique on the complication rate of thyroid operations is still a subject of discussions. In this study, we analysed therefore the most important complications, i.e. palsy of the recurrent laryngeal nerve and hypoparathyroidism, specially under the aspect of routine exposition of the recurrent laryngeal nerve and parathyroids. METHODS: 116 patients with goiter operations of the year 1995 (12 different surgeons) were analysed. Age of patients was between 7 and 72 years, mean age 45 years. The operations performed were 70 subtotal resections (benign goiter), 33 near-total-resections (diffuse autonomy or Graves' disease), 33 hemithyroidectomies (scintigraphically "cold" nodules), 4 adenoma resections with combinations of these resections in 24 cases. RESULTS: 4.3% of the patients (5/116 patients) developed an unilateral recurrent nerve palsy immediately after operation. Persisting recurrent nerve palsy occurred only in 1.7% (2/116) of these cases. Postoperative nerve palsy was mainly found after extensive resections (2/33 near-total-resections) or operations of recurrent goiter (2/6 re-operations), rarely after routine operations (1/70 subtotal resections). Hypocalcemia was found in 9.5% of the patients (11/116), of which 9 cases were asymptomatic (7.8%) and 2 symptomatic by tetany (1.7%). Persisting hypocalcemia for longer than one week was found in 3.5% (4/116), permanent hypoparathyroidism in 1.7% (2/116) of the patients. CONCLUSIONS: Routine systematic exposure of recurrent laryngeal nerves and parathyroids reduces the incidence of complications in thyroid surgery to a minimum. The risk of recurrent nerve palsy increases with extent and difficulty of the operation, with the highest risk for nerve lesions seen in re-operations and near-total-resections.

Adolescent↗