Showing papers by "Horst Feldmann published in 1996"

Life with 6000 Genes

Abstract: The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.

Yeast Retrotransposon Ty4: The Majority of the Rare Transcripts Lack a U3-R Sequence

Abstract: The retrotransposon Ty4 is found in different yeast strains at only one to three copies per haploid genome. In the present study, we aimed at relating the apparent low transpositional activity of Ty4 to transcriptional features of this element. RT-PCR revealed that Ty4 is transcribed at a very low level, being comparable with that of GAL4. Contrary to other Ty elements, the transcriptional rate of Ty4 is not affected in a sin4 background nor by treatment of cells with alpha factor. From experiments measuring the expression levels in 1acZ fusion constructs, we conclude that Ty4 transcription is repressed by a negative regulating element residing within the LTR, whereas positive cis-acting elements, like those that have been found to mediate expression of Ty1/2 and Ty3, are absent from Ty4. Analysing Ty4 transcript termini by the RACE-PCR method, we found several distinct transcriptional initiation sites. But surprisingly, the majority of the polyadenylated Ty4 transcripts terminate shortly upstream from the 3' LTR boundary, so that these transcripts do not contain a U3-R sequence, which is normally required for obligate strand transfer during DNA synthesis. Thus, the extremely low transcription rate of Ty4 and imperfect Ty4 transcripts are the reason for the low transpositional activity of this element.

[Water-filtered infrared-A-hyperthermia combined with radiotherapy in advanced and recurrent tumors. Initial results of a multicenter phase I-II study].

Abstract: BACKGROUND Water-filtered infrared-A-radiation (IR/A-HT) can be used to heat superficial malignant tumors. A prospective multicenter phase I-II study was conducted to evaluate toxicity and efficacy of IR/A-HT combined with external beam radiotherapy (RT). PATIENTS, MATERIAL AND METHODS From December 1991 to June 1994, a total of 53 patients with 58 malignant lesions were entered in the study. There were 14 primary, 36 recurrent and 8 metastatic tumors which were located in the head and neck region (14), chest wall (31), abdominal wall (2) and the extremities (11). The mean tumor volume was 100 cm3. IR/A-HT was applied 1 to 2 times per week with up to 3 IR/A-HT-radiators directly before or after external RT for 1 hour at 40.5 to 44 degrees C. Temperatures were controlled at various locations at the skin surface and invasively at depth. RESULTS IR/A-HT was well tolerated: in 31 (53%) lesions acute (pain, pulse or blood pressure changes, increased skin reaction etc.) and in 25 (43%) chronic side-effects (atrophy, telangiectasis, fibrosis etc.) were noted; usually the toxicity was minor and temporary. At 3 months FU, 32 (55%) lesions achieved a local CR and 19 (35%) a PR; at 12 months FU, 25 (43%) had persistent CR; 16 patients (18 lesions) were deceased and 3 (4 lesions) not yet in FU. In univariate analysis the following prognostic factors for CR at 3 or 12 months FU were found: Karnofsky, metastatic status, tumor size, total RT-dose, thermal parameters T min(av) and T mean. For acute toxicity maximum temperature Tmax(av) was prognostically decisive. Significant differences were also found when considering the "quality of the HT-application". The microwave technique was superior to the infrared-A-HT-technique with regard to the penetration depth of energy deposition. CONCLUSIONS Water-filtered infrared-A-radiation can be safely and effectively applied to heat localized superficial tumors (up to 1 cm depth). To increase the area of HT application multiple infrared-A-radiators have to be combined. A multi-element-system is in progress.

Clinical Rationale for Thermoradiotherapy

Abstract: Oncological research has advanced in many areas, including surgery, chemotherapy (CT), radiotherapy (RT), and immunotherapy, but only in a few cancers has long-term control of locally advanced and disseminated disease been routinely attained. For most cancers, local tumor control is still the primary treatment goal, and determines long-term outcome.

Analysis of a 26 kb region on the left arm of yeast chromosome XV.

Abstract: In the framework of the EC programme for sequencing yeast chromosome XV, we have determined the nucleotide sequence of a 26 kb region. Subsequent analysis revealed 13 non-overlapping open reading frames, three of which correspond to known yeast genes. A pair of tRNA genes associated with remnant Ty elements were localized in this region. From structural parameters and/or similarity searches with entries in the current data libraries, a preliminary functional assessment of several of the putative novel gene products can be made. The gene density in this region amounts to one gene in 2 kb. Protein coding regions occupy 61% of the total DNA sequence. Within the intergenic regions, potential regulatory elements can be predicted. The data obtained here may serve as a basis for a more detailed biochemical analysis of the novel genes. The complete nucleotide sequence of the 26 kb segment as depicted in Figure 1 has been deposited at the EBI data library under Accession Number X91067.