Targeted gene replacement at the endogenousAPRT locus in CHO cells

We demonstrate the feasibility of targeted gene replacement at an endogenous, chromosomal gene locus in cultured mammalian cells, employing a two-step strategy similar to an approach routinely used for genetic manipulation in yeast. Utilizing an APRT⁺ recombinant generated by targeted integration of plasmid sequences (including a functional copy of the gpt gene) at the CHO APRT locus, we have been able to select gpt^– pop-out recombinants that have arisen by intrachromosomal recombination between APRT direct repeats at the targeted integration site. Reciprocal exchanges leading to pop-out of integrated plasmid/gpt gene sequences occur at a rate of 6.3×10^–6 per cell generation. Depending on the site of crossover, such pop-out events result in either replacement or restoration of the original APRT target gene sequence.     

Biophysical studies of teschen disease virus (Talfan strain)

Summary Studies have been made of the heterogeneity of infectivity and CFA in Teschen virus (Talfan strain) suspensions. Most of the infectivity was contained in two components of densities 1.46 gm./ml. and 1.35 gm./ml. The physical, chemical and immunological properties of these components have been compared. It was possible, however, to convert a large proportion of 1.46 component to 1.35 component by treating the 1.46 component with sodium dodecyl sulphate. This would indicate that the 1.46 component was a complex formed between the infective particles and cellular debris.Further studies on the growth characteristics and electron microscopy of the virus have been made.     

Causal dimensions of college students' perceptions of physical symptoms

According to attribution theory, controllability, locus, and stability are important dimensions underlying causal explanations. The extent to which these theoretical dimensions underlie lay explanations for physical symptoms is unclear. Accordingly, in this study, attributes relevant to the lay public were empirically derived using a multidimensional scaling (MDS) procedure. Undergraduates (N=194) provided similarity judgments for 18 potential causes of physical discomfort. The MDS analysis yielded a three-dimensional solution. The first dimension captured the distinction between physical and nonphysical causes. The second dimension distinguished either variable versus stable causes or those that are controllable versus uncontrollable by health care professionals. The third dimension differentiated causes under low versus high personal control. These findings empirically confirm the theoretically proposed dimensions of personal control and stability and suggest the utility of considering the physical/nonphysical and controllability by health care professional distinctions in future work on attributions in the health domain.     

Foraging strategies ofDrosophila melanogaster: A chromosomal analysis

Two larval foraging strategies inDrosophila melanogaster were identified, rover and sitter. Rovers traverse a large area while feeding whereas sitters cover a small area. The difference between rovers and sitters was analyzed genetically by chromosomal substitutions between isogenic stocks. Differences in larval locomotor behavior (crawling behavior) can be attributed to the second chromosome, the rover strategy being dominant over the sitter strategy. Differences in feeding rate (shoveling behavior) are affected additively by both the second and third chromosomes. Natural populations ofDrosophila larvae were sampled three times over a 2-month period; rovers and sitters were at constant frequencies in these populations. The two foraging strategies are discussed in the light of resource utilization in environments where food is distributed continuously or discontinuously.     

An ultrastructural and morphometric study of bladder tumours (III)

Summary Quadrant biopsies were taken at cystoscopy from 12 male patients previously diagnosed on light microscopy as having flat carcinoma in situ (CIS) of the urinary bladder. There was also material available from 3 cystectomy specimens with widespread CIS associated with papillary or solid urothelial tumours.Sections of normal ureter from kidney transplant donors and biopsies from two patients investigated for non-malignant bladder conditions servered as controls.The biopsies from 4 patients were classified as mild dysplasia of the urothelium, while those from 11 patients were categorised as CIS.Biopsies categorised as mild dysplasia on light microscopy showed an increase in the number of cells with large nuclei and nucleoli when compared to controls. The number of desmosomes was significantly reduced compared to controls, while the frequency of abnormalities of the basal lamina was increased. These features were more pronounced in the CIS group.Biopsies from the CIS group could be divided into classical and large cell CIS, the latter showing a higher frequency of ultrastructural abnormalities than the classical type.The patients diagnosed as having CIS fell into two clinical categories, the early onset and the late onset group. The five patients in the former had been diagnosed as having CIS with or without urothelial tumours elsewhere within 3 months of presentation. In the remaining four patients CIS was observed after recurring episodes of papillary or solid tumours during the previous 9 months to 20 years.The biopsies of 3 out of 5 patients with early onset CIS had been classified large cell CIS, wheras only one patient out of 4 in the late onset group came into this category. An early appearance of CIS is thought to have a worse prognosis, and it is therefore suggested that large cell CIS is a more severe form of the disease.     

Corticoliberin Protects Neurons from the Negative Influences of “Dysfunctins” in Living Olfactory Cortex Slices

The protective effects of corticoliberin on living rat olfactory cortex slices during perfusion with dysfunctins extracted from cerebrospinal fluid of drug addicts were studied. Isolated perfusion of slices with medium containing dysfunctins led to irreversible suppression of the amplitude of individual components of focal potentials induced by electrical stimulation of the lateral olfactory tract. The maximum level of depression was seen for the AMPA and NMDA components of EPSP. Preliminary perfusion of slices with medium containing corticoliberin (100 nM) for 15 min partially, and for 30 min completely protected processes mediated by activation of AMPA and NMDA receptor mechanisms from the negative influences of dysfunctins. It is suggested that corticoliberin can induce its protective effects either via its own specific receptors or non-specifically via glutamate receptors. It is also possible that both of these mechanisms act in combination.     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Zur Frage der organspezifischen cytostatischen Wirkung von Diäthylstilböstroldiphosphat auf das Prostatacarcinom

Zusammenfassung Bei Implantationen von Diäthylstilböstrol in einen ventralen Prostatalappen der Ratte konnte im Gegensatz zum Bayer E 39 keine direkte zellschädigende Wirkung auf das Prostatagewebe beobachtet werden. Ein antigonadotroper und damit antimaskuliner Effekt war dagegen neben einer Nebennierenrindenstimulierung sicher nachweisbar. Es wird daraus geschlossen, daß auch das wasserlösliche Diäthylstilböstroldiphosphat bei der Behandlung des Prostatacarcinoms nicht als Cytostaticum sondern als Östrogen wirkt.Eingeführt als St-52 von Asta, Brackwede; jetzt Honvan (Asta) bzw. Cytonal (VEB Beropharm, Berlin-Johannisthal).     

Scope for the “eye — hand” psychophysiological test in screening for cerebrovascular insufficiency

Conclusions 1. During performance of the eye hand PPT the reaction time to input signals at the same time contains information on the trend and level of noise and pulsation of the afferent and efferent pathways of the CNS in man.2. The eye — hand PPT is best performed for detecting subjects with possible CVI, and also to determine the precise degree of its severity.3. Introduction of the eye — hand PPT during mass prophylactic examinations is of economic importance because it enables the early discovery of abnormalities of the workers' health and optimal implementation of the tests in industry characterized by two or three shifts.Riga Medical Institute. Translated from Meditsinskaya Tekhnika, No. 2, pp. 5–7, March–April, 1991.     

An improved apparatus for the optical recording of contraction of single heart cells

An optical system for measuring changes in cell length during unloaded contractions of cardiac myocytes is described. A one-dimensional video image of a cell is obtained every 4 ms with a linear photodiode array, which is aligned with the longitudinal axis of the cell. The circuit used to process the image from the photodiode array has a variety of features to aid in the accurate determination of the distance between the ends of the cell, i.e. the cell length. First, the video image of the cell is divided into two windows, one encompassing the front edge of the cell, the other encompassing the rear edge. Other cells or debris beyond the cell edges are excluded. Changes in the general light level, for example as a result of debris floating above the cell, have little effect because within the windows the background light level is subtracted from the signals before they are processed further. To detect the cell edges, the system determines when the signals within the windows exceed (front edge) or drop below (rear edge) chosen threscholds, which are different for the front and rear edges. The system has memory and it identifies the rear edge of the cell as the last time the signal falls below the threshold; because of this bright spots within the cell are not mistaken for the end of the cell. The system has hysteresis, which enables it to ignore small fluctuations in brightness around the threshold. The system is easy to use, accurate, readily calibrated, and it has good spatial and time resolution (about 0.25 m and 4 ms respectively).     

Intratypic antigenic heterogeneity of Coxsackie B viruses

Summary Neutralization tests, employing the cytopathogenic effect in tissue culture tubes, with a variety of homotypic antisera and strains of Coxsackie B viruses often yielded high titers in early readings and low titers in late readings — the break-through phenomenon — and occasionally also low, early-reading titers with heterologous, homotypic sera, which gave high titers with the homologous strains. Of 27 strains of Goxsackie B 1 to B 5, that were tested, 10 showed no break-through tendency while others showed varying degrees of break-through, without reference to any evidence of intratypic antigenic variation. There was a positive correlation between a small number of tissue culture passages away from man or mouse brain and the break-through tendency. Moreover, strains without break-through tendency yielded viral populations with marked break-through properties after a single intracerebral passage in newborn mice, and even after two subsequent tissue culture passages. Plaque-purified progeny exhibited the break-through phenomenon to the same extent as the original, unpurified cultures.The early readings yielded reproducible titers, which could be used for analysis of antigenic variation. Prime antigenic variants, of broader antigenic constitution than their non-prime relatives, were found among the Coxsackie B 2, B 3, and B 4 strains that were tested. These prime strains (e. g., B. V. A. 96- B2; Stevens - B 3, and Burrier or J. V. B. - B 4) were found to be antigenically broader than the prototype strains (Ohio 1 - B 2, Nancy - B 3, Powers or Texas 13 - B 4) generally used for the preparation of diagnostic antisera. The broader antigenicity of the prime variant was also present in plaque-purified progeny.Aided by grants from The National Foundation, Inc.The work reported here was carried out in 1957–1958 during Dr.Wigand's tenure of a fellowship in the Cincinnati Laboratory.     

Präzisierung der Reizwirkung mittelfrequenter Wechselströme

Zusammenfassung Bei der Mittelfrequenz-Impuls-Reizung ist streng darauf zu achten, daß keine polaritären Reizkomponenten auftreten. Die diesbezügliche Kontrolle wird am besten mit Hilfe des Konvertibilitätstestes vorgenommen, d. h., es darf beim Vertauschen der Zuführungen zu den Reizelektroden weder die Reizschwelle bzw. die Größe des kollektiven Reizerfolges noch dessen Latenzzeit eine signifikante Änderung erfahren. Auf diese Weise wird die Phasenunabhängigkeit des echten Mittelfrequenz-Reizeffektes nachgewiesen.Diesen Anforderungen entsprechen Mittelfrequenz-Impulse, deren Trägerfrequenz über einige wenige Perioden sich aufschaukelt und ebenso wieder abklingt. Demgegenüber sind Mittelfrequenz-Stromstöße mit phasenstarrem Einsatz und Ende nicht unbedingt frei von polaritären Ein- bzw. Ausschalt-effekten, indem sowohl die erste als auch die letzte Trägerperiode einen polaritären Wechselimpuls-Reizeffekt ergeben kann, je nach Phasenlage bezogen auf die wirksame Reizelektrode und Art der Ansprechbarkeit des Reizobjektes (Nerv) auf entsprechend kurze gleitspiegelsymmetrische Wechselimpulse. Für eine echte Mittelfrequenz-Stromstoß-Reizung ist demnach ebenfalls ein Aufschaukeln und Abklingen der Trägerfrequenz über einige wenige Perioden erforderlich.Es besteht ein prinzipieller Unterschied zwischen der echten Mittelfrequenz-Reizung, die phasen -bzw. periodenunabhängig ist und schon früher als apolaritär bezeichnet wurde, und der konventionellen polaritären Reizung, die als polaritäre Komplikation der Mittelfrequenz-Reizung auftreten kann.Diese Präzisierung der Reizwirkung mittelfrequenter Wechselströme wurde angeregt durch zwei im Text erwähnte Publikationen, in denen in keineswegs überzeugender Weise versucht wird, die Mittelfrequenz-Reizung letzten Endes auf das polare Gesetz der Erregung zurückzuführen.

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Summary The particular excitatory action exerted by middle-frequency alternating current can only be revealed if care is taken to eliminate the occurrence of so-called polarity effects. Such effects are produced by the short alternating impulses represented by the first and the last period of a middle-frequency current pulse and are based on the polar law of excitation.In order to prevent such polarity intrusions, it is necessary to increase and decrease the amplitude of the middle-frequency current pulses over a few carrierperiods, or, to use amplitude-modulated middle-frequency impulses of variable shape and duration of envelope.A true middle-frequency excitatory effect is easily demonstrated by resorting to the convertibility test. It will then become evident that stimulation threshold, magnitude as well as latency of response do not change during reversal of the stimulating poles. This means, that no significant phase change of the response with regard to the carrier-frequency occurs when the leads to the stimulating electrodes are commuted, and that, as a result, true middle-frequency effects do not depend upon one particular catelectrotonic variation among the carrier-periods of a middle-frequency current pulse.It can thus be concluded that a fundamental difference exists between true middle-frequency stimulation, which is based on a non-polarity or apolarity principle, and the conventional stimulation of the polar or polarity type.This paper has been written in the hope of dispelling some errors of interpretation (discussed in the text) tending to ascribe the excitatory effects of middle-frequency impulse stimulation to the classical polar law of excitation.

     

Application of the polymerase chain reaction to study the M protein(-like) gene family in beta-hemolytic streptococci

Evaluation of homologous regions of published M protein (emm) gene sequences from group A streptococci (GAS; Streptococcus pyogenes) was used to design three primer pairs for polymerase chain reaction (PCR) and three oligonucleotide probe sequences internal to the amplified products. One set of primers and corresponding probe should detect and lead to amplification of emm(-like) genes of virtually every type (all M), another (SOR^-M) should only amplify emm(-like) genes from GAS negative for serum opacity reaction (SOR) and the third (SOR⁺M) should expand only emm(-like) genes from SOR⁺ GAS. Using the all M primer pair for PCR on the genomic DNA from GAS of 29 different M types as well as from a group C and a group G streptococcal isolate, DNA fragments within the expected size range were amplified in every assay. All PCR products reacted with the all M probe. Related sequences were not detected in genomic DNA of an S. agalactiae and an Enterococcus faecalis isolate. Applying the SOR^-M and SOR⁺M primers to identical assays led to mutually exclusive amplification products. The SOR⁺M and SOR⁺M probes hybridized only to their corresponding products. Exceptions to this exclusivity were the SOR⁺ GAS of M types 3, 8, 27, 34, 42, 67, and 69, which consistently reacted only with the SOR⁺M primer/probe set. Analysis of sequence data from the amplified emm(-like) 2, 3, 18, and 19 genes revealed interesting specific features such as conserved gaps in the C-terminal sequence regions from SOR⁺ and the exceptional SOR^- GAS strains. These data indicate the existence of a subgroup of strains among SOR^- GAS and may advance our understanding of phylogenetic relationship between different serotypes of GAS.     

A cyclin protein modulates mitosis in the budding yeast Saccharomyces cerevisiae

Summary For the budding yeast Saccharomyces cerevisiae the mitotic cell cycle is coordinated with cell mass at the regulatory step start. The threshold amount of cell mass (reflected as a critical size) necessary for start is proportional to nutrient quality. This relationship leads to a transient accumulation of cells at start, termed nutrient modulation, upon enrichment of nutrient conditions. Nutrient enrichment abruptly increases the critical size needed for start, causing the smaller cells, produced in the previous cell cycle, to be delayed at start while growing larger. Here we show that, in S. cerevisiae, a second cell-cycle step, at mitosis, also exhibits nutrient modulation, and is, therefore, another point of cell-cycle regulation. At both mitosis and start, nutrient modulation was found through mutation to be regulated by the activity of the cyclin-related WHI1 (CLN3) gene product.     

Effect of the degree of myocardial hypertrophy associated with an experimental heart defect on the resistance to altitude hypoxia

Summary Experimental coarctation of the abdominal aorta with constriction of its lumen to one-third of the original diameter was created in 18 albino rats. Four months later various degrees of myocardial hypertrophy developed in the animals with a relative weight of the heart ranging from 0.0033 to 0.0069. In elevation in the barochamber, the altitude ceiling of the animals with a relative cardiac weight below 0.0040, did not differ from the normal one. The altitude ceiling proved to be considerably decreased in animals with a relative cardiac weight of over 0.0040. Analysis of ECG recorded during the elevation demonstrated that in the animals with a considerable myocardial hypertrophy reduced resistance to the acute high altitude hypoxia depended on the reduction of the functional resistance of the heart.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 5, pp. 37–40, May, 1963     

Further study of spontaneous interferon produced by hamster peritoneal cells

Summary Cells of peritoneal exudate of hamster have been found capable of spontaneously producing an inhibitor which suppresses virus multiplication in cell culture. Mobilization of macrophagesin vivo with starch inoculated into the peritoneal cavity slightly increased production of the inhibitor. Investigation of some biological, physical and chemical properties of the inhibitor demonstrated its similarity with interferon produced under the effect of endotoxin. The molecular weight of the inhibitor was 100,000. No effect of antimetabolites (actinomycin D and cycloheximide) on production of spontaneous interferon or responsibility of any latent virus of hamsters for its production could be demonstrated.     

”Reflexes of purpose and freedom” in the comparative physiology of higher nervous activity

The most complex unconditioned reflexes of aim and freedom, discovered by I. P. Pavlov, are compared with the competence drive and the motivation of the resistance to coercion, respectively, described by contemporary ethologists. On the basis of the unconditioned reflex of purpose, conditioned reflexes were developed in which positive emotions arising in connection with the perfection of a skill, irrespective of its pragmatic significance at a given moment, serve as the reinforcement. The unconditioned reflex of freedom is regarded as a phylogenetic precursor of the will, and its acute extinction as the physiological mechanism of hypnosis. It was demonstrated experimentally that the appearance of the state of animal hypnosis (immobilization catatonia) in rabbits is accompanied by the predominance of electrical activity and heat production in the right hemisphere, i. e., by symptoms which are found in hypnosis in man.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 3, pp. 415–420, May–June, 1989.     

Comparison of the estrous cycles in mice of high and low cancer lines

Summary In February and May the author studied the duration of the estrous cycle stages in female mice of high A and low C₅₇ cancer lines. It was established that the average duration of the estrus is much greater and of diestrus much shorter in the A than that of the corresponding stages in the C₅₇ line.The estrous cycles of the C₅₇ line females do not undergo any significant seasonal changes while in the A line they approach the character of the normal mice spring cycles.Desviations from the normal duration of the estrous cycle stages in the high cancer line mice denote a disturbed hypophyseal — ovarian hormonal balance.Presented by Active Member AMN SSSR V. N. Chernigovskii     

Selective neuronal discharge in monkey putamen reflects intended direction of planned limb movements

Summary Single cell activity was recorded from the putamen in rhesus monkeys (Macaca mulatta) performing limb movements made both with and without a preceding preparatory set concerning the impending direction of movement. The monkeys were trained to perform an elbow step-tracking task, each trial of which required the subject to make two sequential movements that were virtually identical in terms of their direction, amplitude, velocity and muscle pattern. The first movement was preceded by a foreperiod, the pre-instruction period, during which the monkey could not predict the direction (flexion/extension) of the forthcoming movement. The second movement was also preceded by a variable foreperiod, the post-instruction period, but during this interval the monkey was aware of the impending direction of movement because it was always required to match that of the first movement. To dissociate the directions of motor set (and limb movement) from the patterns of tonic (and phasic) muscular activation associated with task performance, some trials included the application of torque loads that either opposed or assisted the movements required by the behavioral paradigm. Two principal forms of task-related activity were observed among the 232 putamen neurons (all located within the region of arm representation) whose discharge patterns showed significant relations to one or more features of the behavioral paradigm. Movement-related neurons (178/232, 76.7%) discharged selectively in association with either flexion or extension movements of the elbow. Set-related neurons (47/232, 20.3%) manifested sustained, selective changes in discharge throughout the post-instruction period, while the monkey was required to maintain a preparatory set concerning the impending direction of movement. Extensive limb and axial EMG recordings showed no evidence of task-related activity patterns comparable to those that characterized the set-related neurons, and scleral search coil recordings showed no relationship between set-related neuronal activity and either the direction of gaze or the direction and timing of eye movements during task performance. Only a small percentage (7/232, 3.0%) of the task-related neurons showed both movement-and set-related activity. In most cases (37/47, 79%), set-related activity was directionally selective, with the magnitude of discharge reflecting the impending direction of movement. Exhibiting no dependence upon the loading conditions, the directionally selective, set-related activity appeared to reflect only the intended direction of forthcoming, planned movements, and not the anticipated force or pattern of muscular activation that such movements would require.     

Untersuchungen zur kurzzeitigen Induktions- und zyklischen Erhaltungstherapie beim inoperablen kleinzelligen Bronchialkarzinom

Zusammenfassung Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium limited disease (n=64) erfolgte während des zweiten Chemotherapiekurses eine prophylaktische Schädelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium limited disease fanden sich 72%, im Stadium extensive disease nur 33% komplette Remissionen. Im Stadium limited disease betrug die hochgerechnete mediane Überlebenszeit 15,8, im Stadium extensive disease 9,3 Monate (p<0.005). Es leben noch 29 Patienten, 4 rezidivfrei länger als 24 Monate. Patienten mit kompletter Remission hatten eine statistisch signifikant (p<0.001) längere Überlebenszeit als Patienten mit geringerem Ansprechen. Regelmäßig traten gastrointestinale und hämatologische Nebenwirkungen auf, drei Patienten starben während der Induktionsphase an Infektionen. Die kurzzeitige Induktionsbehandlung verbesserte jedoch den Krankheitsverlauf subjektiv und objektiv. Bisher ist kein positiver Effekt der zyklischen Etoposid-Gabe nach ACO festzustellen.Vorliegende Untersuchungen wurden gefördert im Rahmen des Forschungsprogramms Arzneimittelentwicklung und -testung für die Krebstherapie des BMFT