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Showing papers by "University of Marburg published in 1987"


Journal ArticleDOI
TL;DR: The fundamental relationship between radiative lifetime and spectral linewidth of freeexcitons is demonstrated theoretically and experimentally for quasi 2D excitons in GaAs/AlGaAs quantum wells.
Abstract: The fundamental relationship between radiative lifetime and spectral linewidth of free excitons is demonstrated theoretically and experimentally for quasi 2D excitons in GaAs/AlGaAs quantum wells.

820 citations


Journal ArticleDOI
TL;DR: The location, orientation, and structure of the hormone regulatory elements (HRE) in nine hormonally modulated genes is described and a model for the interaction is proposed in which a dimer of the receptor in head-to-head orientation binds to the inverted symmetry element of the HRE.

600 citations


Journal ArticleDOI
TL;DR: Results indicate that FGF has neurotrophic activity in the adult central nervous system, and that this molecule is able to rescue adult retinal ganglion cells from axotomy induced cell death.

355 citations


Journal ArticleDOI
TL;DR: Preliminary results suggest that local accumulation of neurotrophic activities at the proximal nerve stump elicited by NGF and, possibly bFGF, might be involved in the beneficial effects of these proteins on the maintenance of axotomized sensory neurons.

287 citations


Journal ArticleDOI
TL;DR: The results did not support the classification of panic attacks recently proposed by Sheehan and Sheerhan, which requires three symptoms as a cutoff for panic attacks, and the comparison of concurrent diary and retrospective interview and questionnaire descriptions showed that panic patients have a tendency toward retrospective exaggeration.
Abstract: Despite much recent research, there is still little systematic information about the phenomenology of panic attacks, and their possible causes remain obscure. We investigated panic attacks in the natural environment using an event sampling approach. Twenty-seven panic attack patients and 19 matched normal controls kept panic attack and self-exposure diaries for 6 days and wore an ambulatory heart rate/physical activity recorder for 3 days. Patients reported 175 attacks, generally of moderate severity. The most frequent symptoms were palpitations, dizziness/lightheadedness, dyspnea, nausea, sweating, and chest pain/discomfort. The results did not support the classification of panic attacks recently proposed by Sheehan and Sheehan, which requires three symptoms as a cutoff for panic attacks. Panic attacks classified by the patients as situational (i.e., occurring in feared situations) were more severe and occurred in situational contexts different from spontaneous attacks, but were otherwise phenomenologically similar. Heart rates did not change during spontaneous attacks and were only mildly elevated during situational attacks or during the 15 minutes preceding these attacks. These heart rate changes were interpretable as effects of anxiety, although physical activity showed a similar pattern of changes. Some normal control subjects reported on the panic diary primarily situational anxiety episodes that were phenomenologically similar to, albeit less severe than, the patients' episodes. Panic patients may sometimes fail to perceive environmental triggers for their attacks because many attacks classified as spontaneous occurred in classical "phobic" situations. Furthermore, the comparison of concurrent diary and retrospective interview and questionnaire descriptions showed that panic patients have a tendency toward retrospective exaggeration. Implications for the assessment, definition, and classification of panic attacks are discussed.

221 citations


Journal ArticleDOI
TL;DR: Interpretation de donnees experimentales sur Y(T) qui varie comme exp[(T 0 /T 2 ] dans un large domaine de temperatures jusqu'a la transition vitreuse consideree comme un phenomene de localisation cinetique.
Abstract: Viscosity data for supercooled liquids are reexamined in terms of the random-potential model with use of the concept developed for treatment of electronic transport in random media with energetic disorder. \ensuremath{\eta}(T) is found to obey the predicted exp[(${\mathrm{T}}_{0}$/T${)}^{2}$] law covering 10 decades in \ensuremath{\eta} and extending to the glass transition which is considered to be a kinetic localization phenomenon. The crucial system paramter is the width \ensuremath{\sigma} of the (Gaussian) distribution of states which determines both the glass transition temperature and the T dependence of \ensuremath{\eta} via the characteristic temperature ${\mathrm{T}}_{0}$\ensuremath{\propto}\ensuremath{\sigma}.

214 citations


Book ChapterDOI
01 Jan 1987
TL;DR: The chapter reviews the information available on the structure and function of multiple and variable amounts of subunits in cy tochrome-c oxidase from different organisms and explains the role of cytochrome- c oxidase in energy metabolism.
Abstract: Publisher Summary This chapter provides an overview of evolution of cytochrome-c oxidase. A large variety of oxygen-linked enzymes evolved, but only cytochrome-c oxidase couples the reduction of oxygen to water with the production of adenosine triphosphate (ATP). Cytochrome-c oxidase occurs in all eukaryotic organisms and in some aerobic bacteria. Studies on the mechanism of electron transfer from cytochrome c to oxygen could not detect basic functional differences between the enzyme from prokaryotes, unicellular eukaryotes, and animal tissues. With the improvement of separation methods, it was possible, however, to demonstrate differences in the protein composition of cytochrome-c oxidase from lower and higher developed organisms. A variable number of subunits, ranging from 2 to 13, have been identified in the enzyme complex from prokaryotes and mammalian tissues, respectively. The chapter reviews the information available on the structure and function of multiple and variable amounts of subunits in cytochrome-c oxidase from different organisms. It explains the role of cytochrome-c oxidase in energy metabolism.

196 citations


Journal ArticleDOI
TL;DR: The size dependence of the ionization potentials provides the first direct experimental evidence that a heretofore undetected size-dependent gradual transition from van der Waals-type to metallic properties occurs for mercury clusters in the size range between 20 and approximately 70 atoms.
Abstract: Single-photon ionization thresholds are reported for mercury clusters with up to 70 atoms prepared in a supersonic beam. The size dependence of the ionization potentials provides the first direct experimental evidence that a heretofore undetected size-dependent gradual transition from van der Waals--type to metallic properties occurs for mercury clusters in the size range between 20 to approximately 70 atoms.

191 citations


Journal ArticleDOI
TL;DR: It is concluded that acetone is degraded by a coculture of an eubacterium and an acetate-utilizing methanogen and that acetate is the only intermediate transferred between both.
Abstract: An anaerobic enrichment culture degraded 1 mol of acetone to 2 mol of methane and 1 mol of carbon dioxide. Two microorganisms were involved in this process, a filament-forming rod similar to Methanothrix sp. and an unknown rod with round to slightly pointed ends. Both organisms formed aggregates up to 300 micron in diameter. No fluorescing bacteria were observed indicating that hydrogen or formate-utilizing methanogens are not involved in this process. Acetate was utilized in this culture by the Methanothrix sp. Inhibition of methanogenesis by bromoethanesulfonic acid or acetylene decreased the acetone degradation rate drastically and led to the formation of 2 mol acetate per mol of acetone. Streptomycin completely inhibited acetone degradation, and neither acetate nor methane was formed. 14CO2 was incorporated exclusively into the C-1 atom of acetate indicating that acetone is degraded via carboxylation to an acetoacetate residue. It is concluded that acetone is degraded by a coculture of an eubacterium and an acetate-utilizing methanogen and that acetate is the only intermediate transferred between both. The energetical problems of the eubacterium converting acetone to acetate are discussed.

133 citations


Journal ArticleDOI
TL;DR: A capillary tube was developed in which an inoculum of magnetotactic bacteria that contained only a few contaminants could be separated from crude sediment in a few minutes.
Abstract: A capillary tube was developed in which an inoculum of magnetotactic bacteria that contained only a few contaminants could be separated from crude sediment in a few minutes. Sterile fluid was placed on one side of a wetted cotton plug and sediment was placed on the other side. Magnetotactic bacteria migrated quickly through the cotton toward the south pole of a stirring-bar magnet placed at the closed end of the capillary. Protozoa and chemotactic bacteria were significantly delayed in passage through the cotton.

127 citations


Journal ArticleDOI
TL;DR: Redirection in the final step of the secretory pathway provides in part the biological basis for the increased appearance of pancreatic (pro)enzymes in the interstitial fluid and serum during supramaximal secretagogue stimulation.

Journal ArticleDOI
TL;DR: It is shown that the fluorescence kinetics of C-Phycocyanin is expected to be characterized by three exponential kinetic components, independent of the aggregation state, which allows for a detailed understanding of the origin of the different kinetic components and their associated time-resolved spectra.

Journal ArticleDOI
TL;DR: The Biochemistry of Degradation of Polyethers: Critical Reviews in Biotechnology: Vol. 6, No. 3, pp. 273-307 as discussed by the authors, was published in 1987.
Abstract: (1987). The Biochemistry of Degradation of Polyethers. Critical Reviews in Biotechnology: Vol. 6, No. 3, pp. 273-307.

Journal ArticleDOI
TL;DR: Chlamydomonas cells sucked onto micropipettes were filmed at 500 frames/sec and analyzed as to their forward beating mode, revealing that the flagella of the sucked cells beat in a normal threedimensional manner, with beat frequencies that correspond to those of freely swimming cells.
Abstract: Chlamydomonas cells sucked onto micropipettes were filmed at 500 frames/sec and analyzed as to their forward beating mode. A comparison with freely swimming cells revealed that the flagella of the sucked cells beat in a normal threedimensional manner, with beat frequencies that correspond to those of freely swimming cells. Most beats were synchronous. but not symmetrical; cis- and trans-flagellum appear to beat in a slightly different manner. Some cells beat synchronously throughout, but mostly synchrony was interrupted by a single asynchrony or up to incessant asynchronies, caused by transient accelerations of the trans- (fo-) flagellum. Only rarely did cis- and trans-flagella have different but constant beat frequencies. Helical swimming of Chlamydomonas more likely is due to the beat asymmetries of the two flagella than to differences of beat frequencies. In our records, the stigma is on the inside of the helical swimming path.

Journal ArticleDOI
TL;DR: The hypothesis that the spectral balance of the song can be used for range determination is supported and the poor correlation between the measured song variables and morphology suggests that song in this species advertises the status of the male rather than other single attributes such as size or weight.

Book ChapterDOI
01 Jan 1987
TL;DR: Together with neutral glycolipids, glycoproteins and glycosaminoglycans, gangliosides comprise the glycocalix of the cell surface.
Abstract: Gangliosides (= amphiphilic sialic acid containing glycosphingolipids) are components of all plasma membranes and as such ubiquitous in vertebrate tissues. They are especially abundant and complex in neuronal membranes, where they are anchored in the outer leaflet of the membrane bilayer by their hydrophobic ceramide moiety, while exposing their negatively charged hydrophilic and spacious sialo-oligosaccharide residue into the extracellular space (Fig. 1). Together with neutral glycolipids, glycoproteins and glycosaminoglycans, gangliosides comprise the glycocalix of the cell surface.

Journal Article
TL;DR: It is concluded that beyond the oncogenes myc and myb, oncagenes whose gene products are GTP binding proteins and phosphokinases may also be necessary to develop and keep the malignant state of SCLC.
Abstract: Amplification and expression of 16 protooncogenes were examined in 12 established small cell lung cancer (SCLC) cell lines. Seven of 12 cell lines showed a 20- to 35-fold amplification of the c-myc oncogene, 3 cell lines showed an 80- to 130-fold amplification of N-myc oncogene, and one cell line had a simultaneous amplification of the c-myb and N-myc oncogene. In this cell line both oncogenes were transcriptionally highly active at the same time. A variant subpopulation of SCLC expressed an 8.5-kilobase v-fms homologous transcript at high levels but without amplification of the c-fms gene. All cell lines examined had similar RNA levels of the N-ras, Ki-ras, Ha-ras, and c-raf1 oncogenes. DNA amplification, however, was undetectable. The protooncogenes c-fes, c-fos, and c-erbB were expressed very weakly and the transcripts of the oncogenes c-mos, c-sis, c-erbA, c-src, and c-abl were not observed in any of the 12 SCLC-cell lines. From these data we conclude that beyond the oncogenes myc and myb, oncogenes whose gene products are GTP binding proteins and phosphokinases may also be necessary to develop and keep the malignant state of SCLC. The v-fms homologous transcript found may be involved in the transition of the classic cell type to the variant cell type of SCLC.

Journal ArticleDOI
TL;DR: In this paper, the effects of monochromatic light of various wavelengths on adaptation and function of the photosynthetic apparatus have drawn increasing attention, and the existence of plants with the capability to adapt to high and low intensities of white light has been known for a long time and has been summarized frequently.
Abstract: All photosynthetic organisms depend on light. The development, adaptation and function of the photosynthetic apparatus are known to be subjected to intensity and quality of incident and absorbed light. But plants have very limited capabilities to choose locations with optimum light conditions. Thus they have developed the ability to adapt their photosynthetic apparatus to given, sometimes unfavourable, light conditions. The existence of plants with the capability to adapt to high and low intensities of white light has been known for a long time and has been summarized frequently (cf. Boardman, 1977 or Wild, 1979). However, shaded biotops (canopee, deep water) change not only the intensity but also the spectral quality of light. In recent years the effects of monochromatic light of various wavelengths on adaptation and function of the photosynthetic apparatus have drawn increasing attention. Currently three areas of the photosynthetic apparatus are mainly considered for a photoregulation: (i) the biosynthesis of Chl b and the light harvesting protein (LHCP), (ii) the biosynthesis of ribulose bisphosphate carboxylase/oxygenase (Rubisco) and (iii) the photoregulation of the herbizide binding QB protein. The extent of knowledge about the wavelength dependency decreases from (i) to (iii). Approaches to study the light regulation in these areas come as well from the physiological as from the molecular biological side. Since photoregulations by the red

Journal ArticleDOI
01 Oct 1987-Planta
TL;DR: The supramolecular structure of the exoplasmic freeze-fracture particles of thylakoids of the thermophilic cyanobacterium Synechococcus sp.
Abstract: The supramolecular structure of the exoplasmic freeze-fracture particles of thylakoids of the thermophilic cyanobacterium Synechococcus sp. is compared with that of isolated photosystem-II complexes. The in-situ EF particles are scattered on the thylakoids or organized in rows of variable length; the latter aligned particles measure 10 nmx20 nm and are separated perpendicular to their long axis into two parts. We propose that they represent dimers composed of two monomeric 10-nm EF particles side by side. Isolated photosystem (PS)II particles correspond in size to the monomeric 10-nm EF particles as analysed by negative contrast and freeze-fracture electron microscopy. Dimeric PSII particles, very similar to the in-situ 10 nmx20 nm EF particles, are obtained after incorporation of purified PSII complexes into liposomes made from phospholipid and cholesterol. Each monomeric complex consists of the reaction center, the water-splitting system, the chlorophyll antennae and phycobilisome-binding polypeptides. We propose that the dimeric complexes bind one hemidiscoidal phycobilisome at their domains exposed to the external side of the thylakoids. The implications of this arrangement of the PSII-phycobilisome complexes within the thylakoids upon excitation-energy distribution are discussed.

Journal ArticleDOI
TL;DR: A methylviologen and 8-hydroxy-5-deazaflavin(F420)-reducing hydrogenase was purified over 800-fold to near homogeneity from the archaebacterium Methanococcus voltae with 10 U mg-1 F420-reducing activity, which is the only hydrogenase in this organism.
Abstract: A methylviologen and 8-hydroxy-5-deazaflavin(F420)-reducing hydrogenase was purified over 800-fold to near homogeneity from the archaebacterium Methanococcus voltae with 10 U mg−1 F420-reducing activity. It is the only hydrogenase in this organism. The enzyme showed Km values of 16 μM for F420 and 1.2 mM for methylviologen. A turnover number of 1050 min−1 was calculated for the minimal active unit. The protein tends to aggregate. The molecular mass of the minimal active unit is 105 kDa. Larger molecules of 745 kDa were regularly observed. The enzyme was resolved into subunits with molecular masses of 55 kDa, 45 kDa, 37 kDa and 27 kDa by SDS/polyacrylamide gel electrophoresis. Reversible conversion of an anionic into an uncharged form was observed by DEAE-cellulose chromatography with concomitant changes in substrate specifities. The methylviologen-reducing activity was heat-resistant up to 65°C and was not affected by antiserum raised against the native enzyme, while F420 reduction was inactivated by both treatments. Nickel and selenium contents were determined as 0.6–0.7 mol each, FAD content as 1 mol and iron as 4.5 mol/mol protein (105 kDa), respectively. Electron micrographs taken from the purified enzyme show ring-shaped molecules of 18 nm diameter, which represent the high-molecular-mass species of the enzyme.

Journal ArticleDOI
TL;DR: It is concluded that apart from the well-known influence of advanced tumor stages and tumor localization, nipple involvement correlates with multicentricity and multifocality of breast cancer as a disease of the whole organ.
Abstract: Our study examined 166 patients with breast cancer with a mean age of 63 years. Each patient underwent mastectomy with the organ being investigated by histological giant sections and additional small sections from the nipple. Nipple involvement was found in 64 cases (38%). Multifocal carcinoma occurred in 76 patients. Further multicentric carcinomatous foci (36 cases) demonstrated a significant increase in affected nipples. Additional atypical ductal or lobular hyperplasia was observed in 53 cases and showed involvement in 34. Nine carcinomas of ductal origin were combined with lobular carcinoma in situ, all cases proved to have carcinomatous changes in the nipple. It is concluded that apart from the well-known influence of advanced tumor stages and tumor localization, nipple involvement correlates with multicentricity and multifocality of breast cancer as a disease of the whole organ.

Journal ArticleDOI
01 Jul 1987-Virology
TL;DR: Results indicate that (i) Neu5,9Ac2 is the primary receptor determinant required for influenza C virus to attach to tissue culture cells and to initiate infection and (ii) gangliosides containing this type of sialic acid are potential receptors for influenzaC virus.

Journal ArticleDOI
TL;DR: The inhibitory effect on exogenous cholecystokinin injection significantly decreased after SMS administration for seven days, indicating desensitization of the end organ by somatostatin.

Journal ArticleDOI
TL;DR: It is suggested that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.
Abstract: A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

Journal ArticleDOI
TL;DR: In this paper, the ennes with various hydroborating agents followed by refunctionalization at boron furnished 1,3-dienylboronates which undergo clean Diels-Alder addition to typical dienophiles.

Journal ArticleDOI
TL;DR: These cell lines are currently under intensive biochemical, molecular biological, and cytogenetical investigation in different laboratories and thus provide a tool for studying the biology of lung cancer.
Abstract: Cell lines from SCLC were established with a success rate of 43% from different metastatic sites of treated and untreated patients. All 6 SCLC cell lines grew as floating cell aggregates without substrate adherence. The degree of aggregation ranged from very tight spheroids to very loose sheets and chains. This gross morphological property showed a striking correlation to the PDT, with short PDTs in loose growing cell lines and long PDTs in tight growing cell lines. Cell size and nuclear features, i.e., chromatin pattern and nucleolar prominence, also seemed to correlate with the PDT and gross morphology. All SCLC cell lines had dense core granules by electron microscopical examination. Several different serum-free and serum-supplemented growth media were tested for their feasibility in establishing and permanently growing SCLC. Serum-free SIT medium and SIT2.5 medium provided the best results in liquid culture. For semisolid SCLC cultivation, R 10 medium was superior to all other media tested. These cell lines are currently under intensive biochemical, molecular biological, and cytogenetical investigation in different laboratories and thus provide a tool for studying the biology of lung cancer.

Journal ArticleDOI
TL;DR: Low cell yields obtained with ethanol as substrate indicate that P. propionicus does not conserve energy by electron transport-linked fumarate reduction, and the enzymes of the succinate-methylmalonyl CoA pathway all were detected at activities sufficient to be involved in ethanol fermentation.
Abstract: Whole cells of Pelobacter propionicus fermented (1-13C) ethanol and CO2 to nearly equal amounts of (2-13C) and (3-13C) propionate and to (1-13C) acetate indicating a randomizing pathway of propionate formation. Enzymes involved in the fermentation were assayed in cell-free extracts and cetyltrimethylammonium bromide-permeabilized cells grown with ethanol as sole substrate. Alcohol dehydrogenase, aldehyde dehydrogenase (benzylviologen-reducing), phosphate acetyl transferase, acetate kinase, pyruvate synthase, methylmalonyl CoA: pyruvate transcarboxylase, propionyl CoA: succinate CoA transferase, and the enzymes of the succinate-methylmalonyl CoA pathway all were detected at activities sufficient to be involved in ethanol fermentation. Very low amounts of a b-type cytochrome were detected in ethanol-grown cells (46 nmol δ g protein−1). Low cell yields obtained with ethanol as substrate indicate that P. propionicus does not conserve energy by electron transport-linked fumarate reduction. Despite the presence of a hydrogenase and a shift in the fermentation of lactate towards the formation of more propionate in the presence of hydrogen, P. propionicus was unable, to catalyze, the reduction of acetate and CO2 to propionate, unlike Desulfobulbus propionicus.

Book ChapterDOI
TL;DR: The research team of Coccagna and Lugaresi used direct measurements to document the blood pressure behavior during individual apnea episodes to study the effects on the hemodynamics during sleep as well as during the day.
Abstract: Sleep apnea, a nocturnal disturbance of the respiratory regulation, has effects on the hemodynamics during sleep as well as during the day. The first systematic inquiries into these relationships were conducted as early as 1965 by Jung and Kuhlo [1]. In 1972, the research team of Coccagna and Lugaresi used direct measurements to document the blood pressure behavior during individual apnea episodes [2].

Journal ArticleDOI
TL;DR: It is concluded that cAMP in anaerobic growth like in aerobic growth acts as the effector of CRP and that catabolite repression plays an important regulatory role in anerobic catabolism.
Abstract: The role of adenosine 3′,5′-monophosphate (cAMP) and of the Fnr protein, a transcriptional regulator of anearobic electron transport, in the expression of anaerobic respiration of Escherichia coli was investigated.

Journal ArticleDOI
15 Mar 1987-Cancer
TL;DR: It is suggested that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV and progression‐free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied.
Abstract: A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.