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L Adler

Publications and source records attributed to L Adler.

At least 19 recordsLinked to original sources
PubMed1995

Cloning and characterization of GPD2, a second gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) in Saccharomyces cerevisiae, and its comparison with GPD1.

We have cloned and characterized a homologue of the previously isolated GPD1 gene, encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) in Saccharomyces cerevisiae. This second gene, called GPD2, encodes a protein of 384 amino acids that shares 69% sequence identity with GPD1. Like GPD1 it has an amino-terminal extension of unknown function. GPD2 is located on chromosome VII and cross-hybridizes with GPD1 at chromosome IV as well as with an unknown homologue at chromosome XV. Disruption of the GPD2 gene did not reveal any observable phenotypic effects, whereas overexpression resulted in a slight, but significant, increase of GPD enzyme activity in wild-type cells. Analysis of gene transcription by a CAT-reporter gene fused to the GPD promoters revealed decreased transcriptional activity of the GPD2 promoter in cells grown on nonfermentable as opposed to fermentable carbon sources, and no induction in cells exposed to high osmolarity or heat shock. Similar analysis of GPD1 demonstrated an 8-17-fold higher basal level of transcription compared to GPD2. Furthermore, such analysis revealed that the GPD1 promoter was induced by increased osmolarity essentially independent of the type of stress solute used, the level of GPD1 transcription being increased about sevenfold in cells growing at 1.4 M NaCl.

Amino Acid Sequence↗
PubMed1995

Mediocrates.

Explore the source record for details and available documents.

Health Maintenance Organizations↗
PubMed1994

[General practice of acute inpatient treatment of mania. Retrospective comparative study of 100 patients at each of 2 psychiatric centers].

We reviewed the literature regarding acute therapy of manic patients and compared these recommendations with actual practice by reviewing 399 therapies in 100 patients each from two psychiatric care centres between 1975 und 1991. Higher age, more serious disease and a higher percentage of compulsory commitments are typical of patients treated in institutions with a mandatory admission policy as compared to university clinics, which are not compelled to admit patients. The treatment methods practised in both centres deviated greatly from recommendations in the literature. In spite of widespread therapeutic recommendations, lithium and carbamazepin are seldom employed for acute treatment; neuroleptic agents were preferred for all grades of severity. Combinations of more potent antipsychotics with more sedative neuroleptics were preferred. In contrast, the chosen substances, the preferred combinations and the application form varied considerably. The state mental hospital preferred haloperidol and levomepromazin; in the university clinic clozapin and perphenazineoenanthate were important adjuncts. Both clinics remained in the low therapeutic range of dose recommendations. There were no statistically meaningful differences with regard to either the total amount of chlorpromazine equivalents applied or the duration of inpatient care. In the first one-tenth of the total treatment period, 85% of the maximal dose reached in the second tenth is already given. A continual reduction begins thereafter, until app. 40% of the peak dose in reached. Active treatment of side effects as well as more common use of depot neuroleptics in order to minimize custodial treatment, may explain the lower number of compulsory admissions in the university hospital. Extreme interindividual differences in both dosage and length of stay help in elucidating the apparently contradictory results of comparative investigations with small patient groups. Previous treatments have little or no predictive value due to large intraindividual variations.

Adult↗
PubMed1994

[Are there predictors for impulsive, homicidal-suicidal acts of violence].

Patient's statements or fears that they may "go crazy" and harm themselves or persons around them are rare, but extremely difficult for all participants to deal with. On the basis of the existing, unsatisfactory literature as well as an analysis of 196 incidents of homicidal-suicidal violence designated by German media as "running amok" and fulfilling defined criteria, we examined whether or not there are predictors for the degree of potential danger inherent in such threats. Impulsive, homicidal-suicidal acts of violence among patients with psychiatric disorders often occur in environments characterised by chronic psychosocial estrangement and isolation. Extremely distressing situations may trigger the course of violence, but the actual act is often planned during a seemingly peaceful interval. Personalities with a high affinity to weapons and a tendency toward acting out seem to increase the potential risks. Such events should be treated analogous to suicidal crises, with a strategy that takes the individual disorder into consideration. The parameters investigated in this paper are not sufficient, even in different combinations, to offer a satisfactory explanation or predict the occurrence of this extremely rare behaviour; further research is necessary.

Acting Out↗
PubMed1993

Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats.

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, +/- 3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Use of laser energy to treat central pulmonary emboli: a preliminary report.

We evaluated the ability and safety of a laser fiber placed percutaneously into a pig's lobar pulmonary artery to lyse pulmonary artery blood clots that were created in situ. We developed a model to create blood clots in situ that could be placed in any desired location with a radio-opaque marker at the clot position. An excimer laser delivered energy to a flexible 600 microns fiber in three experiments and a coaxial 1.6 mm multifiber catheter in the last experiment. Pre- and postprocedure angiograms obtained from each experiment demonstrated that partial laser dissolution of central pulmonary emboli in four pigs was accomplished successfully. To avoid perforation, it is imperative that the laser fiber remain coaxial during the entire lasing process. These results suggest that laser dissolution may become an adjunctive procedure for the treatment of central pulmonary emboli in those patients who cannot be treated medically.

Animals↗
PubMed1993

Acute renal allograft dysfunction in the setting of deep venous thrombosis: a case of successful urokinase thrombolysis and a review of the literature.

Acute renal allograft vein thrombosis is a rare but serious complication of renal transplantation. When occurring in the early posttransplant period it is usually associated with surgical complications and often results in the loss of the graft. At later stages, when graft function has stabilized, its development may then be associated with underlying disorders such as glomerulonephritis, immunosuppressive therapy, increased hematocrit, acute rejection, or extension of lower extremity venous thromboses. We report a case of acute allograft dysfunction occurring in the setting of extensive deep vein thrombosis. In our patient, thrombosis in the setting of acute graft tenderness and swelling, anuria, and an increasing creatinine strongly suggest a diagnosis of acute allograft renal vein thrombosis. We describe a successful reversal of acute renal failure through urokinase thrombolysis and review the current literature on the use of thrombolytic agents for the treatment of acute renal allograft vein thrombosis.

Acute Kidney Injury↗
PubMed1993

["Running amok"--content analytic study of 196 news presentations from industrialized countries].

We performed a content analysis study based on 196 reports in the German press published during the last decade on acts of violence designated as "going berserk" or "running amok (amuck)" and meeting defined criteria. With less than one person per one million men per year running berserk or amok, this is a very rare act of violence, albeit a very dangerous one involving 1.3 deaths and 1.7 injuries per case. Offenders differ from the normal population in regards to the small percentage of women (5%) and high unemployment (40%), and from other violent offenders in that they are normally occupationally well-qualified. Severe psychiatric disorders are overrepresented. A total of 108 cases were classified according to specific syndromes either by specialists or experts on the spot, or on the basis of a description of the signs and symptoms. Of the syndrome-related acts, the most dangerous offences were committed by 10 delusionally ill and 2 psychopathic individuals. 30 less dangerous offenders suffered from paranoid-hallucinatory syndromes. 28 crimes committed in a state of intoxication and 11 "crimes of passion" were the least dangerous. Another 25 persons with an extensive incidence of suicide in the family, without any apparent pre-existing psychiatric disorder, may have gone berserk in the course of a depressive syndrome. Although psychotically ill individuals tend to overreact more often following a minimal slight, under delusions or with no apparent reason at all, on the whole the causes for both the psychotic and other offenders are of a serious nature. Object loss and private disputes on the one hand and social conflicts on the other were of approximately equal significance. The relationship between the offender and his victim is more essential for the course of the occurrence than motives or the type of the psychopathological syndrome. If only family members are attacked, the offenders have usually been inconspicuous, elderly individuals, two thirds of whom can not be allocated to a given syndrome and may be depressive. They kill deliberately and on-target, do not merely injure their victims--hardly ever, in fact--and then commit suicide practically without exception. If strangers are the target of violence, the crimes are generally committed by younger, passive-aggressive, psychopathic, paranoid or intoxicated offenders. They kill only about half of their victims, but injure many, also causing a great deal of damage. They rarely commit suicide.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

A gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) complements an osmosensitive mutant of Saccharomyces cerevisiae.

Osmoregulatory mutants of Saccharomyces cerevisiae with a defect in their capacity to readjust the cell volume/buoyant density after osmotically induced dehydration were enriched by density gradient centrifugation. Colonies derived from cells that remained dense after dehydration were screened for sensitivity to high concentrations of NaCl and defects in their osmotically induced production and intracellular accumulation of glycerol. The isolated osg (osmosensitive glycerol defective) mutants were recessive in heterozygous diploids and fell into four complementation groups (osg1-osg4). The osg1-1 mutant, described in this work, is unable to grow at low water potential and shows a decreased capacity for glycerol production and a strongly reduced activity of NAD(+)-dependent sn-glycerol 3-phosphate dehydrogenase (GPD), an enzyme in the glycerol-producing pathway. Complementation of the osg1-1 salt sensitivity defect with a low copy yeast genomic library led to the cloning of GPD1, encoding an S. cerevisiae GPD consisting of 391 amino acids and sharing 47-50% identity with GPD from other sources. Micro-sequencing of the N-terminus of purified S. cerevisiae GPD revealed a 20-amino-acid sequence that was identical to a nucleotide-deduced amino acid sequence in GPD1, but indicated that the enzyme is produced with an N-terminal extension that is removed from the functional enzyme. Subcellular fractionation does not indicate, however, that the putative pre-sequence targets GPD to any organelle; the enzyme appears to be located in the cytoplasm. Chromoblot and tetrad analysis were used to position the GPD1 gene to chromosome IV, with a distance of about 18 cM from trp1.

Amino Acid Sequence↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗