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Biomedical subjects

L Adler

Publications and source records attributed to L Adler.

At least 19 recordsLinked to original sources

Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells.

Hypoxia alters endothelial cell function and metabolism. Since PAF is synthesized by endothelial cells and capable of modulating endothelial cell responses, we investigated the effect of hypoxia on synthesis and release of PAF from endothelial cells. We found: (1) Approx. 90% of the radylPAF derivative in stimulated endothelial cells is acylPAF. (2) Acute hypoxic (15 min-1 h) priming increased ionophore- and thrombin-induced radylPAF accumulation. (3) Long-term hypoxic exposure increased radylPAF accumulation at 24 and 48 h in the presence of ionophore. (4) Bioactive PAF was released into media and hypoxia and ionophore synergistically increased PAF release. (5) Hypoxia and ionophore stimulation increased phospholipase A2 activity and decreased acetylhydrolase activity in endothelial cells. We conclude that hypoxia and ionophore increase PAF synthesis and release from endothelial cells.

1-Alkyl-2-acetylglycerophosphocholine Esterase

Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring.

It is well established that an increased availability of tryptophan stimulates serotonin synthesis not only in the adult but also in the developing brain. In order to study the influence of a permanently increased supply of tryptophan on the developing central 5-HT-system, female rats were fed a tryptophan-enriched diet from mating throughout pregnancy and lactation. The effect of this dietary regime was assessed by measurements of neurochemical markers of 5-HT innervation in the developing brain of their offspring. A diminished content of 5-HT, a decreased activity of tryptophan hydroxylase and a reduction of crude synaptosomal high-affinity 5-HT uptake was found in the cortex and in the brain stem of 5 day old rat pups of mothers fed the tryptophan-enriched diet. The postnatal increase of all three markers of serotonergic innervation in the offspring of these mothers was retarded. Both the initial depletion and the delayed maturation of 5-HT content, of tryptophan hydroxylase activity and of synaptosomal serotonin uptake were more pronounced in the cortex than in the brain stem. Apparently, the increased dietary intake of tryptophan throughout pregnancy and lactation caused a delayed outgrowth of 5-HT axons and/or reduced collateral sprouting and synapse formation in the brain of the developing offspring.

Animals

Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects.

Diminished neuronal response to repeated sensory input is a sensory-gating phenomenon that has been found to be deficient in schizophrenic patients. For example, schizophrenic patients fail to decrease the amplitude of the P50 wave of the auditory evoked potential to the second of paired click stimuli. In some studies, however, normal subjects have also failed to decrease their P50 responses. The aim of this study was to determine if accommodation to the recording situation over time would affect the gating of the P50 response. The gating of the P50 wave is measured as the ratio of the amplitude of the second response to the amplitude of the first. Three successive auditory evoked potentials were compiled, each from trains of 32 pairs of stimuli. Twelve normal subjects and 12 schizophrenic patients were studied. Unconjugated catecholamine metabolites were measured from venous samples drawn before and after the electrophysiological recording. Between the first and third trials, the normal subjects significantly increased their gating of P50. This increase in gating of P50 was related to decreased levels of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol. No similar phenomenon was observed in the schizophrenic patients, a number of whom had a further decrease in P50 gating over the three trials. Transient failure to observe gating of P50 in normal subjects may be related to increased state-dependent noradrenergic activity, which is known to disrupt sensory gating. This mechanism does not seem to account for the more persistent failure of sensory gating in schizophrenia.

Acoustic Stimulation

In vitro validation of three-dimensional intravascular ultrasound for the evaluation of arterial injury after balloon angioplasty.

OBJECTIVES: The hypothesis of this study was that three-dimensional ultrasound imaging would facilitate the evaluation of arterial dissection after balloon angioplasty. BACKGROUND: The presence and extent of arterial dissection occurring at the time of balloon angioplasty may be important predictors of abrupt vessel closure or late restenosis. METHODS: Forty-one human arterial segments obtained after death were imaged in an in vitro system at physiologic pressure (80 to 100 mm Hg) before and after balloon angioplasty. Images were acquired with a 20- to 30-MHz mechanical intravascular ultrasound imaging system (Cardiovascular Imaging Systems) with a constant pullback technique (1 mm/s). Standard 0.5-in. (1.27-cm) video tapes were used for data storage and later playback for analog to digital conversion. Digitized data were reconstructed to three-dimensional images with use of voxel space modeling. The vessels were opened longitudinally and subjected to pathologic examination, photographed and classified histologically as normal, fibrous or calcified. Dissection was defined as a disruption and separation of components of the arterial wall. The length and depth of arterial dissection were evaluated grossly and microscopically. RESULTS: Of the 41 arteries studied, 36 (88%) exhibited dissection on pathologic examination after balloon angioplasty. Three-dimensional reconstruction of intravascular ultrasound images identified dissection in 11 (92%) of 12 normal, 8 (100%) of 8 fibrous and 11 (69%) of 16 calcified arteries. Excellent agreement between ultrasound and pathologic findings was achieved in the evaluation of length and depth of dissection for histologically normal and fibrous arteries (kappa = 0.72 to 1.0). When the vessels were severely calcified, the agreement was not as good (kappa = 0.27 to 0.56), particularly in detection of small, non-raised intimal flaps. CONCLUSIONS: This histopathologic validation study suggests that three-dimensional intravascular ultrasound imaging facilitates the evaluation of both quantitative and morphologic features of arterial dissection induced by balloon angioplasty. The advantage of three-dimensional intravascular ultrasound is its ability to assess the length and morphology of arterial injury over an entire vessel segment.

Angioplasty, Balloon, Coronary

Evaluation of a prostacyclin analog in prevention of pulmonary oxygen toxicity.

Prolonged exposure to high concentrations of oxygen can result in significant lung injury, although newborn animals are tolerant relative to adults. We previously reported that relative O2 tolerance in the rabbit is lost by 10 days of age, and is coincident with a decline in lung prostacyclin. In the current study we administered iloprost, a stable prostacyclin analog, by continuous infusion to maturing rabbits exposed to greater than 95% oxygen. Compared to vehicle-treated controls, iloprost-treated rabbits had significantly lower protein in bronchoalveolar lavage fluid at 84 h, a smaller percentage of neutrophils at 65 and 84 h, and lower mortality at 96 h. The partial protection against pulmonary oxygen toxicity afforded by iloprost is likely due to its membrane stabilizing effect, and its inhibitory actions on neutrophil migration, activation, production of oxygen radicals and proteolytic enzymes.

Animals

Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury and has been associated with the development of bronchopulmonary dysplasia. Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic lung injury. This study investigates ICI 198,615 (ICI), an LTD4 and LTE4 receptor antagonist in preventing hyperoxic lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total protein, and cyclooxygenase products 6-keto-PGF1 alpha, and thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the LTD4 and LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of pulmonary edema, reduce mortality or attenuate hyperoxic lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic lung injury process and that the functional inhibition of a portion of the arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic lung injury in newborn rabbits.

Animals

Risk factors in schizophrenia. Season of birth, gender, and familial risk.

The risk for schizophrenia among first-degree relatives of schizophrenic probands obtained from an epidemiological sample using family history methods was examined to determine whether month of birth of the proband was associated with familial risk. The results of this study of the first-degree relatives of 106 female schizophrenics and 275 male schizophrenics suggested that the relatives of probands born in the months February to May had the highest risk, although the association between month of birth and familial risk among the male probands was present only for those relatives who had onset of schizophrenia before the age of 30.

Adult

Season of birth of siblings of schizophrenic patients.

The hypothesis that mothers of winter-spring-born schizophrenics have an unusual pattern of conception which results in an excess of winter-spring births was tested by studying the distribution of birth-dates of 401 siblings of 120 winter-spring-born schizophrenics and 157 siblings of 59 winter-spring-born controls. All analyses were gender-specific. The results suggest there is no association between the probability of a winter-spring date of birth and being a sibling of a winter-spring-born schizophrenic or control.

Adult

["Endogeniform" affective psychoses and normal pressure hydrocephalus].

Four patients with neuroradiological evidence of normal pressure hydrocephalus and psychiatric diagnosis of affective psychoses with major depression--like characteristics are presented. Three patients underwent shunting operations following an observation period of 2 to 6 years. During the post-operative follow-up of 3 to 7 years, resp., no clinical changes were noted. In our opinion, and following critical evaluation of the available literature, major depression--like affective disorders in normal-pressure hydrocephalus are not influenced by shunting operations, unless they occur simultaneously as an additional symptom in an Adams-Hakim syndrome with definite progression.

Affective Disorders, Psychotic

Osmoregulation in Saccharomyces cerevisiae. Studies on the osmotic induction of glycerol production and glycerol-3-phosphate dehydrogenase (NAD+)

Production of glycerol and a key enzyme in glycerol production, glycerol 3-phosphate dehydrogenase (NAD+) (GPD), was studied in Saccharomyces cerevisiae cultured in basal media or media of high salinity, with glucose, raffinose or ethanol as the sole carbon source. At high salinity, glycerol production was stimulated with all carbon sources and glycerol was accumulated to high intracellular concentration in cells grown on glucose and raffinose. Cells grown on ethanol accumulated glycerol to a lower level but showed an increased content of trehalose at high salinity. However, the trehalose concentration corresponded only to about 20% of the glycerol level, and did not compensate for the shortfall in intracellular osmolyte content. Immunoblot analysis demonstrated an increased production of GPD at high salinity. This increase was osmotically mediated but was lower when glycerol was substituted for NaCl or sorbitol as the stress-solute. The enzyme also appeared to be subject to glucose repression; the specific activity of GPD was significantly lower in cells grown on glucose, than on raffinose or ethanol.

Ethanol

Anticardiolipin antibody-positive serum enhances endothelial cell platelet-activating factor production.

Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.

6-Ketoprostaglandin F1 alpha

[Differentiation of suicide and parasuicide. A study of the last letters of suicidal patients].

The paper presents a content-analytical comparison between "last letters" of suicidals (SUI) and parasuicidals (PARA). So far studies on this topic are mostly performed by "external" parameters, e.g. sociodemographic or anamnestic data. The content-analytical approach provides to describe the presuicidal situation on base of "internal" variables. Compared with the suicidal notes the parasuicidal communication can be evaluated as more ambivalent, emotionally disturbed, and cognitively restricted. The successful reclassification of the notes into the two samples by a stepwise discriminant analysis supports the hypothesis, that both groups are distinct even on base of internal variables.

Adolescent

[Validity of the Beck Depression Inventory for cross-cultural comparisons. A study of German and Egyptian patients].

The present study compares self-rated depressive symptoms of 95 inpatients with depressive syndromes: 45 in Germany and 50 in Egypt. In each country, 50 patients suffering from acute internal diseases served as controls. Psychiatric patients were selected according to DSM-III criteria for major depressive disorder (MDD). Depressive symptoms and depth of depression were scored by the Beck Depression Inventory (BDI). The self-rating of depressive symptoms proved sufficient for transcultural comparison, provided controls are used, and was more practicable than observer rating scales. The results indicate higher BDI total scores for Egyptian than for German inpatients. This appear to be due to cultural differences, presumably mostly in language performance ("tendency to hyperbole"). Moreover, Egyptians complained more about somatic symptoms, as has already been frequently suggested on the basis of clinical observations.

Adult

Purification and characterization of glycerol-3-phosphate dehydrogenase (NAD+) in the salt-tolerant yeast Debaryomyces hansenii.

The NAD-dependent glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) of the salt-tolerant yeast Debaryomyces hansenii was purified by poly(ethylene glycol) precipitation and a combination of chromatographic procedures. The enzyme existed in two forms with different ionic characters and specific activity. On SDS-polyacrylamide gel electrophoresis, both forms yielded one predominant band with an apparent molecular weight of 42,000. The specific activity of the enzyme was dependent on the concentration of the enzyme and on the ionic strength of the dissolving medium. All ions tested stimulated the enzyme activity in the ionic strength range 0-100 mM, with glutamate yielding the highest activity. Above these concentrations, the dehydrogenase showed high tolerance for glutamate in concentrations up to 0.9 M, whereas malate, sulfate and chloride were inhibitory. Enzyme activity showed little sensitivity to the type of cation present and was only slightly affected by 5 M glycerol. The true Km values for the substrates were 6.6 microM for NADH, 130 microM for dihydroxyacetone phosphate, 0.3 mM for NAD and 1.2 mM for glycerol-3-phosphate, and the enzyme showed specificity for these four substrates only. It is proposed that the enzyme functions in cellular osmoregulation by providing glycerol 3-phosphate for the biosynthesis of glycerol, the main compatible solute in D. hansenii, and that the enzyme is well adapted to function in yeast cells exposed to osmotic stress.

Cations

A procedure for enrichment and isolation of mutants of the salt-tolerant yeast Debaryomyces hansenii having altered glycerol metabolism.

The salt-tolerant yeast Debaryomyces hansenii produces and accumulates glycerol when subjected to salt stress, whereby the buoyant density of the cells is changed. This property allows for enrichment of mutants with altered glycerol metabolism by density gradient centrifugation. Colonies derived from cells with rapidly changing density following an osmotic shock were screened for increased glycerol production by observing their ability to support growth of a glycerol-requiring strain of Escherichia coli. The glycerol overproducting phenotype of two isolates was confirmed by chemical analysis.

Centrifugation, Density Gradient

In vivo ultrasound arterial recanalization of atherosclerotic total occlusions.

The purpose of this study was to assess the potential of intraarterial ultrasound for in vivo recanalization of atherosclerotic total occlusions. Ultrasound energy at a frequency of 20 kHz was applied with a prototype solid wire probe to 12 surgically implanted occluded human atherosclerotic arterial xenografts, 9 of which were calcified, as well as to the intimal surface of 12 normal canine arteries. In both the normal canine arteries and the atherosclerotic occluded xenografts, there was no angiographic evidence of vasospasm, thrombosis or arterial dissection. Eleven of the 12 atherosclerotic complete arterial occlusions were resistant to passage of a conventional guide wire or probe without ultrasound energy. However, the occlusions were recanalized after administration of 15 s to 4 min (mean 1.5 +/- 1.3 min) of intermittent ultrasound energy. After ultrasound, 8 of the 12 vessels underwent balloon angioplasty. Angiographic residual stenosis after ultrasound alone was 62 +/- 24% and after combined ultrasound and balloon angioplasty, 29 +/- 13%. Although routine angiography did not reveal arterial emboli, high resolution cut films did demonstrate a few distal nonocclusive thrombi of a size similar to that reported with other recanalization methods. Histologic studies demonstrated changes similar to those after balloon angioplasty, with focal cracking of the fibrotic and calcified plaque. The findings demonstrate that ultrasound energy applied through a catheter delivery system can be used in vivo to open completely obstructed atherosclerotic vessels. These studies suggest that it might be clinically feasible to use the ultrasound probe to create a lumen, allowing subsequent balloon dilation.

Animals

Nifedipine in the treatment of tardive dyskinesia.

There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists.

Adult