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Biomedical subjects

M Fluck

Publications and source records attributed to M Fluck.

12 recordsLinked to original sources
PubMed2002

Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM).

The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only), dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2), daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-alpha was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively.

Administration, Oral↗
PubMed2001

Kinetic analysis of the steps of the polyomavirus lytic cycle.

Kinetic studies of the accumulation of early and late transcripts, early and late proteins, genomes, and live virus, during the lytic cycle of murine polyomavirus wild-type A2, were carried out in synchronized NIH 3T3 cells released from G(0) by the addition of serum after infection. This first-time simultaneous analysis of all parameters of the virus life cycle led to new insights concerning the transcriptional control at the early-to-late transition. During the early phase, early transcripts were synthesized at very low levels, detectable only by reverse transcription-PCR, from 6 h postinfection (hpi). Large T protein could be detected by 8 hpi (while infected cells were in the G(1) phase). The level of expression of the middle T and small T proteins was lower than that of large T at all times, due, at least in part, to a splicing preference for the large-T 5' splice site at nucleotide 411. A large increase in the level of both early and late transcripts coincided closely with the detection in mid-S phase of viral genome amplification. Thereafter, both classes of transcripts continued to further accumulate up to the end of the experiments (48 hpi). In addition, during the late phase, "giant" multigenomic transcripts were synthesized from the early as well as the late promoter. Thus, a major type of transcriptional control appears to be applied similarly to the transcription of both early and late genes. This view differs from that in the literature, which highlights the enhancement of late transcription and the repression of early transcription. However, despite this parallel transcriptional control, additional regulations are applied which result in higher levels of late compared to early transcripts, as previously described. In the accompanying article, a key role for middle T and/or small T in this late-phase enhancement of early and late transcription is demonstrated (16). Other novel findings, e.g., the synthesis of a very abundant short early promoter proximal RNA, are also described.

3T3 Cells↗
PubMed2001

Counting and cardinal understanding in children with Down syndrome and typically developing children.

This study compares the procedural counting ability (independently and with parental support) and conceptual understanding of cardinality of a group of children with Down syndrome and a group of typically developing children, matched for non-verbal mental age. Participants were 23 children with Down syndrome (chronological age range: 3.5-7 years; mental age range: 2.5-4 years) and 20 typically developing children (chronological age range: 2-4 years; mental age range: 2.5-4 years), and their main caregiver. The children were asked to count sets of toys (assessing procedural counting skills) and to give sets of toys (assessing understanding of cardinality), with set sizes between 2 and 18 items. The counting task was performed in two conditions, with and without parental support. The children were also asked to say the count word sequence aloud, to assess sequence production independent from object counting. The typically developing children produced significantly more number words altogether, longer standard number sequences and could count larger sets than the children with Down syndrome. Support from an adult improved performance on the count task significantly for both groups of children, and there was no significant difference between the groups in the degree of improvement, i.e. the zone of proximal development. No significant differences were found between the frequency of children (approximately one third) in each group who used counting to solve the give task, indicating an understanding of cardinality.

Child↗
PubMed2000

Enantiomer separation by complexation SFC on immobilized Chirasil-nickel and Chirasil-zinc.

The use of complexation SFC for enantiomer separation of Lewis base selectands on chiral nickel(II)- and zinc(II)-bis[(3-heptafluorobutanoyl)-10-methylene-(1R)-camphora te] chemically bonded to poly(dimethylsiloxane) (Chirasil-nickel and Chirasil-zinc) and employed as Lewis acid selectors is described. The method is especially suited for less volatile and configurationally labile racemates. The variation of the experimental parameters temperature T, pressure p and density rho of the mobile phase carbon dioxide on the retention factor k, relative retention r and chiral separation factor alpha is studied, providing insights into the mechanisms of chiral recognition under supercritical conditions. For mecoprop methyl ester (methyl 2-(4-chloro-2-methylphenoxy)propanoate) an unusual increase of alpha at increased temperature is observed on Chirasil-nickel. Supercritical carbon dioxide does not inadvertently affect the complexation equilibria between Lewis donor selectands and the Lewis acid metal selectors during complexation SFC.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed2000

(Re-) constructing pre-linguistic interpersonal processes to promote language development in young children with deviant or delayed communication skills.

BACKGROUND: Approaches to intervention with young children with delayed or deviant communication skills have tended to focus directly on the production and comprehension of linguistic forms. Research in developmental psychology, however, has highlighted the role of joint attention and action within a mutually negotiated frame in early communicative development. AIMS: An approach to intervention was developed which uses graded participation in such 'formats' to promote language development in 3- to 5-year-olds with significant delays or deviance in communication skills. This study was designed to evaluate this in comparison with a more conventional approach. SAMPLE: The sample comprised twenty 3- to 5-year-olds attending a diagnostic nursery or a speech and language support centre attached to a mainstream primary school. METHOD: In the intervention, developmentally ordered sequences of exchange games provided predictable ruled-based and structured joint contexts of action, within which verbal and non-verbal exchanges between an adult and child could be meaningfully used. In the control condition, participants received more conventional intervention focusing more directly on language per se. Level of participation in dyadic play was assessed in terms both of role and cognitive complexity, and for the present study language development was assessed using the verbal subtests of the WPPSI. The study entailed both a between- and a within-subjects design. RESULTS: Cross-sectional and longitudinal comparisons confirmed that this form of intervention was significantly more effective than the control condition in increasing children's level of participation in social game formats and in promoting their language development; moreover, these were significantly correlated. CONCLUSIONS: The results indicate that the development of language skills can be promoted more effectively through (re-) constructing the interpersonal framework of pre-linguistic communicative development than through conventional intervention focusing directly upon language per se.

Adult↗
PubMed1998

Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.

The discovery, in vitro and in vivo studies of the highly potent ETA antagonist EMD 122946 are presented. This compound displayed high binding affinity and functional antagonism [IC50 = 3.2 x 10(-11) M, pA2 = 9.5 (ETA)] and inhibited the ET-1 induced pressor response in pithed rats with an ED50 of 0.3 mg/kg. In conscious spontaneously hypertensive rats and in DOCA-salt hypertensive rats the compound lowered mean blood pressure with an ED50 of 0.06 mg/kg. EMD 122946 exhibited high bioavailability in rats and monkeys.

Animals↗
PubMed1996

Counting and cardinality in English nursery pupils.

This study examines the development of counting and cardinality in a structured sample of 60 English 3 1/2-4 1/2 year-olds attending local education authority nursery classes in socially mixed areas of Portsmouth. Children were given two types of task: counting sets of animals, and giving specified numbers of items from a pile. Three measures of cardinal understanding were used: spontaneous repetition of the last word on completion of a counting trial, repetition of the last word in reply to a question, and use of counting vs. grabbing when asked to give a specific number of items from a heap. In line with research on other populations the results indicate a pronounced developmental discrepancy between procedural and conceptual knowledge of counting, but cardinality appears to develop six months later in this population than in other populations studied. There were marked individual differences, however. Proficiency with object counting was found to be necessary, but not sufficient, for cardinal understanding. Children rarely repeated final count words spontaneously. Last word repetition in response to a verbal prompt depended on the nature of the prompt. Contrary to previous research, the present results indicate that last word repetition elicited by the prompt 'how many?' is not merely a conventional reply but generally implies an understanding of cardinality. The findings also indicate that an understanding of cardinality emerges relatively suddenly, consistent with the discovery or construction of a principle. Whether nursery pupils treat counting simply as a conventional routine without cardinal significance appears to depend on the situation as well as on their understanding of cardinality. The findings are discussed in relation to Karmiloff-Smith's Representational Redescription model.

Analysis of Variance↗
PubMed1995

Unified enantioselective capillary chromatography on a Chirasil-DEX stationary phase. Advantages of column miniaturization.

Immobilized Chirasil-DEX (mono-6-O-octamethylenepermethyl-beta-cyclodextrin chemically linked to dimethylpolysiloxane) can be employed as a versatile chiral stationary phase in chromatography. The chiral polymer has a long lifetime and is configurationally and thermally stable. The concept of unified enantioselective chromatography has been demonstrated for the enantiomer separation of hexobarbital by gas chromatography, supercritical fluid chromatography, liquid chromatography and capillary electrochromatography on a single open-tubular column (1 m x 50 microns I.D.) coated with Chirasil-DEX. The advantages of miniaturization in contemporary chromatographic enantiomer separation are demonstrated. Chirasil-DEX coated on porous silica is also useful for enantiomer separation in high-performance liquid chromatography.

Carbohydrate Sequence↗
PubMed1985

Expression of proto-oncogenes in normal and papovavirus-transformed or -infected rat fibroblasts.

Dot blot hybridization was used to determine the transcript levels of 10 cellular oncogenes in Fischer rat fibroblasts transformed or infected in tissue culture by polyoma virus or SV40. The level of these messages was compared to that determined for nontransformed, noninfected control cells. The analysis includes the oncogenes myc, sis, mos, erbB, erbA, Ha-ras, Ki-ras, src, fps, and abl. For all the oncogenes tested, except for mos, detectable expression was observed in all cell lines studied including the normal control cells; when normal and transformed or infected cells were compared, no significant difference in transcript level was found for any of the oncogenes except one. A slight elevation of sis message was observed for some transformants. The results of this study apply to six polyoma and seven SV40 transformants which were chosen with the purpose of analyzing transformants displaying a variety of properties. Thus, the polyoma-transformed cell lines varied in their expression of the transformed phenotype as judged by anchorage-independent growth and cell morphology, in their coding capacity for and expression of early gene products, and included two classes of rat fibroblasts transformed by ts-a mutants: those with a temperature-insensitive transformed phenotype, and those with a temperature-sensitive phenotype, A-type and N-type, respectively. Concerning the latter two types, no differences in oncogene expression were observed between cells grown at low and those grown at high temperatures, or between the two groups of cells at either temperature.

Animals↗
PubMed1984

Intracellular morphogenesis of bacteriophage T4. I. Gene dosage effects on early functions and tail fiber assembly.

Mixed infection of nonpermissive bacteria by amber mutant and wild-type T4 phage reduces the burst size in a manner that depends on the nature of the gene product eliminated by the mutation. While the genotypic proportions produced by such mixedly infected cells were directly proportional to those in the starting mixtures, the fraction of the burst size compared to wild-type-infected cells was dependent on the kind of mutant used. For example, mutants in genes 56, 42, and 43, which control catalytic functions for DNA synthesis, produced normal burst sizes even at ratios of four mutant to one wild-type phage. The multiplicity of infection in these experiments was near 20, and most cells received one wild-type phage. By contrast, infection with mutants in tail fiber structural genes gave a normal burst size with 1:1 mixtures of wild-type phage, but showed a decrease in burst size below this ratio. The conclusions drawn are that enzymes of DNA replication are present in large excess over the amount needed for phage DNA synthesis, and that tail fiber structural proteins are made in a three- to fourfold excess over the amount needed for phage maturation under normal laboratory conditions.

DNA Replication↗
PubMed1976

Localization of gene functions in polyoma virus DNA.

Polyoma virus mutants of four functionally distinct groups have been mapped by the marker rescue technique using restriction enzyme fragments of wild-type viral DNA. Nontransforming host-range mutants map in the proximal part of the early region of the viral genome. The same DNA fragment that restores a normal host range also restores normal transforming ability to these mutants. ts-25D, a temperature-sensitive (ts)-a class mutant, maps in the distal part of the early region. ts-3 and ts-1260 map in the proximal and distal parts of the late region, respectively.

Chromosome Mapping↗