Mega-introns in the dynein gene DhDhc7(Y) on the heterochromatic Y chromosome give rise to the giant threads loops in primary spermatocytes of Drosophila hydei.

The heterochromatic Y chromosomes of several Drosophila species harbor a small number of male fertility genes (fertility factors) with several unusual features. Expression of their megabase-sized loci is restricted to primary spermatocytes and correlates with the unfolding of species-specific lampbrush loop-like structures resulting from huge transcripts mainly derived from clusters of loop-specific Y chromosomal satellites. Otherwise, there is evidence from genetic mapping and biochemical experiments that at least two of these loops, Threads in Drosophila hydei and kl-5 in D. melanogaster, colocalize with the genes for the axonemal dynein beta heavy chain proteins DhDhc7(Y) and Dhc-Yh3, respectively. Here, we make use of particular Threads mutants with megabase-sized deletions for direct mapping of DhDhc7(Y)-specific exons among the large clusters of satellite DNA within the 5.1-Mb Threads transcription unit. PCR experiments with exon-specific primer pairs, in combination with hybridization experiments with exon- and satellite-specific probes on filters with large PFGE-generated DNA fragments, offer a simple solution for the long-lasting paradox between megabase-sized loops and protein-encoding transcription units; the lampbrush loops Threads and the DhDhc7(Y) gene are one and the same transcription unit, and the giant size of the DhDhc7(Y) gene as well as its appearance as a giant lampbrush loop are merely the result of transcription of huge clusters of satellite DNA within some of its 20 introns.

Molecular aspects of intron evolution in dynein encoding mega-genes on the heterochromatic Y chromosome of Drosophila sp.

Fertility genes on the heterochromatic Y chromosome of various Drosophila species are unique for several reasons. Most of them are megabase-sized. Their expression is restricted to premeiotic spermatocytes and often associated with unfolding of huge species-specific lampbrush loops. Molecular analysis of the orthologous dynein genes Dhc-Yh3, DhDhc7(Y) and DeDhc7(Y) on the Y chromosome of the three species D. melanogaster, D. hydei and D. eohydei, respectively, revealed that the megabase gene size as well as the species-specific morphology of the corresponding lampbrush loops kl-5, Threads and diffuse loops result from huge introns and their specific sequence composition, whereas the majority of all 20 introns in each of the three genes is in a size of 45-72 bp. The loop-specifying introns are extreme exceptions due to extended assemblies of degenerated transposable elements and/or large clusters of satellite DNAs. Here we use sequence information from the complete intron sets of three orthologous Y chromosomal dynein genes to deduce a scenario for an evolutionary pathway leading to the megabase-sized genes on the heterochromatic Y chromosome of Drosophila. The obvious bias between very small and species-specific mega introns is explained as the result of an autocatalytic mode of intron growth. An initial coincidental hit by a single transposable element extends the size of a 50 bp intron for about two orders of magnitude and determines it for preferential extension by similar insertion events. This phase of continuous moderate growth is followed by rapid size enlargements by repeating amplifications generating extended clusters of satellite DNA. Size control by recombination, on the other hand, is suppressed in Drosophila males by achiasmatic meiosis.

Proteins with tandemly arranged repeats of a highly charged 16-amino-acid motif encoded by the Dhmst101 gene family are structural components of the outer sheath of the extremely elongated sperm tails of Drosophila hydei.

Fruit fly species of the genus Drosophila show a remarkable variation in sperm length. Some of them produce gigantic sperm several times the total male body length. Sperm of Drosophila hydei, for example, are more than 20 mm long. Little is known about the advantage of such elongated sperm or about the proteins that stabilize their thin flagellar tails. Recently, two members of a novel gene family Dhmst101(1) and Dhmst101(2), whose gene products are associated with the sperm tail, were isolated and characterized. Here a third member of this gene family, Dhmst101(3), is described. It was previously demonstrated that all three genes are located in a single small cluster on chromosome 5 of D. hydei. They are located within 15 kb of genomic DNA, oriented in the same direction and transcribed testis-specifically. The encoded sperm tail-specific proteins are mainly composed of tandemly arranged repeats of a highly charged, cysteine-containing motif of 16 amino acids with the consensus sequence KKKCA/EEAAKKEKEAAE. Experiments with synthetic repeat monomers and dimers have demonstrated a tendency for alpha-helical rod formation, which increased strongly with an increase in repeat number. Therefore, Dhmst101 proteins with 7-60 repeats with regularly spaced cystein-residues are thus expected to form long alpha-helical rods cross-linked by numerous Cys-Cys bridges. Here we apply immunoelectron microscopy and monospecific antibodies, alpha-mst101, raised against the KKKCAEAAKKEKEAAE-motif to investigate the distribution of Dhmst101 proteins within the sperm tail of D. hydei. We show that Dhmst101 proteins are part of the outer sheath of the sperm tail where they presumably help to provide a tight but elastic envelope for the extremely extended spermatozoa of D. hydei.

The Y chromosomal fertility factor Threads in Drosophila hydei harbors a functional gene encoding an axonemal dynein beta heavy chain protein.

To understand the contradiction between megabase-sized lampbrush loops and putative protein encoding genes both associated with the loci of Y chromosomal fertility genes of Drosophila on the molecular level, we used PCR-mediated cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes gratilla shows homology over the entire length of the protein chains. Therefore the proteins can be assumed to fulfill orthologous functions within the sperm tail axonemes of both species. Functional dynein beta heavy chain molecules, however, are necessary for the assembly and attachment of outer dynein arms within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA, results from an infertile Threads- mutant where large clusters of Threads specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are missing simultaneously. Consequently, the complete lack of the outer dynein arms in Threads- males most probably causes sperm immotility and hence infertility of the fly. Moreover, preliminary sequence analysis and several other features support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the heterochromatic Y chromosome of both species might indeed code for orthologous dynein beta heavy chain proteins.

High-dose radiation therapy alone for inoperable non-small cell lung cancer--experience with prolonged overall treatment times.

The purpose of this study as to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non-small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a restaging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n = 50), 12 weeks (n = 79) and > 12 weeks (n = 100), 5-year survival was 4%, 6%, and 8%, respectively (p = 0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment.

Is the time interval between surgery and radiotherapy important in operable nonsmall cell lung cancer? A retrospective analysis of 340 cases.

PURPOSE: To evaluate the influence of prognostic factors in postoperative radiotherapy of NSCLC with special emphasis on the time interval between surgery and start of radiotherapy. METHODS AND MATERIALS: Between January 1976 and December 1993, 340 cases were treated and retrospectively analyzed meeting the following criteria: complete follow-up; complete staging information including pathological confirmation of resection status; maximum interval between surgery (SX) and radiotherapy (RT) of 12 weeks (median 36 days, range 18 to 84 days); minimum dose of 50 Gy (R0), and maximum dose of 70 Gy (R2). Two hundred thirty patients (68%) had N2 disease; 228 patients were completely resected (R0). One hundred six (31%) had adenocarcinoma, 172 (51%) squamous cell carcinoma. RESULTS: In univariate analysis, Karnofsky performance status (90+ >60-80%; p = 0.019 log rank), resection status stratified for nodal disease (R+

[Combined breast-preserving surgery, chemotherapy and radiotherapy in the treatment of breast carcinoma. Effect of the interval between surgery and the beginning of radiotherapy]. / Kombinierte brusterhaltende Chirurgie, Chemotherapie und Strahlentherapie bei der Behandlung des Mammakarzinoms. Der Einfluss des Intervalls zwischen Operation und Bestrahlungsbeginn.

BACKGROUND: The timing of breast conserving surgery, chemotherapy, and radiotherapy in breast cancer treatment has become the subject of increasing interest over the last years. PATIENTS AND METHOD: Seventy-four patients who underwent postoperative radiotherapy at our institution between 1985 and 1992 form the basis of this study. Median follow-up time was 5 years. Seventy-three percent of patients were pre- or perimenopausal. Almost all patients (91%) were UICC-stage II. Axillary lymph nodes were positive in 95% of cases. Complete gross resection was achieved in all patients, and in 65% final pathological margins were free of invasive or intraductal carcinoma. Postoperatively, 70% of patients received 6 cycles of polychemotherapy (predominantly CMF) before onset of irradiation. The radiation dose was in almost all cases 60 Gy including 10 Gy boost. RESULTS: Five years after start of treatment overall survival, disease-free survival, and local recurrence rates were 86% (95%-confidence limits, 76 to 93%), 73% (61 to 83%), and 8% (3 to 16%), respectively. For disease-free survival, the only significant prognostic factor was the number of involved lymph nodes: 0 to 3 = 86%, > or = 4 = 40% (p < 0.0001). The interval between surgery and radiation (< or = versus > 20 weeks) had no significant influence on disease-free survival or local tumor control. In contrast, there was a trend of increased regional and distant failure with shortening of the interval due to the delivery of less than 6 cycles chemotherapy before the onset of radiotherapy. CONCLUSIONS: In our experience, there was no negative impact of a delay of radiotherapy in order to deliver full course chemotherapy before initiation of radiotherapy. However, the low statistical power of this analysis due to the small number of patients must be considered. it appears possible that a less intense chemotherapy before starting radiation treatment correlates with enhanced distant failure and subsequently decreased disease-free survival rates. Therefore, for patients at increased risk for distant metastasis, we prefer to give 6 cycles polychemotherapy before irradiation.

Strukturdifferenzierungen in Y-chromosom von Drosophila hydei: the unique morphology of the Y chromosomal lampbrush loops Threads results from 'coaxial shells' formed by different satellite-specific subregions within megabase-sized transcripts.

The results of pulsed-field gel electrophoresis (PFGE) analysis and two-colour transcript fluorescence in situ hybridization (FISH) for the three Threads-specific DNA satellites YLII, YLI and rally are in support of long-range clustering of these sequence families within the subterminal region on the long arm of the Y chromosome of Drosophila hydei. On the basis of the linear arrangement of at least four extended clusters of satellite-specific sequences, the loop morphology of wild-type and several mutant Threads can be explained by assumption of a single Threads-specific transcription unit comprising about 5.1 Mb of repetitive DNA located between the Pseudonucleolus and the Nucleolus organizer. Transcription is unidirectional from the Pseudonucleolus towards the terminally located Nucleolus organizer. Transcripts most likely start in front of or within the 3.2 Mb region of YLII-related sequences, pass through subsequent blocks of 1.2 and 0.3 Mb of YLI- and rally-related sequences, respectively, and cease within the region of a smaller block of YLI-related repeats. The megabase-sized transcripts remain physically linked to the DNA axis and their extended satellite-specific regions form coaxial clouds or shells around the central DNA axis. In this way each cluster of earlier-transcribed sequences generates a cloud or shell on top of the later-transcribed ones. According to this model of 'satellite-specific coaxial shells' the tube-like morphology and other peculiarities of the Y chromosomal lampbrush loops Threads can be explained as a result of satellite-specific RNA superstructures and/or formation of extended ribonucleoprotein (RNP) complexes between clusters of satellite-specific transcripts and specific proteins. On the basis of this model the specific morphology of several Threads mutants can be interpreted as the result of large interstitial or terminal deletions that alter the total length of the Threads-specific transcription unit without exerting other major effects on principal features of the transcription process along the Threads.

Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases.

PURPOSE: Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients with SCLC and SVCS as compared to SCLC without SVCS. METHODS AND MATERIALS: A retrospective analysis of 408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done. RESULTS: Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/- 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80-100%; p = 0.008) were of significant importance. CONCLUSIONS: SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended.

Prognostic factors in high-grade malignant glioma. A multivariate analysis of 76 cases with postoperative radiotherapy.

PURPOSE: Patients with malignant gliomas have a limited survival prognosis. We retrospectively analyzed data of malignant glioma patients with the aim of defining prognostic factors on which individualized treatment strategies might be built on. PATIENTS AND METHODS: Seventy-six patients with primary malignant glioma (51 glioblastoma multiforme, 20 anaplastic astrocytoma, 4 anaplastic oligo-astrocytoma, 1 anaplastic glioma) were postoperatively irradiated with 5 and 8 Me V photons, 2 Gy per fraction to a median total dose of 60 Gy (range 50 to 70 Gy). RESULTS: The youngest quartile of patients (up to 45 years) had the highest 3-year survival rates (mean +/- SE: 15 +/- 8%) and median survival time (17.9 months, 95% confidence interval: 9.2, 24.2 months) as compared to the oldest quartile (> 61 years) with no 3-year survivor and a median survival time of 9.7 months (7.2, 12.3 months). The middle quartiles (46 to 61 years) showed intermediate results. The difference between the youngest and oldest quartile (p = 0.01) and the middle quartile versus the oldest quartile (p = 0.04) was significant. In univariate analysis, tumor size (p = 0.04 for -30 mm vs > 50 mm) was of importance. In multivariate analysis only age of the patient reached statistical significance (p = 0.03). As compared to the youngest quartile of patients, the oldest quartile had a relative risk of 2.1 (95% confidence interval: 0.9, 5.1) of dying from the disease; the age group of 46 to 61 years had a relative risk of 2.0 (0.9, 4.3). CONCLUSIONS: Age of the patient is the most important factor for survival prognosis favouring younger age (< or = 45 years). The possible implications for radiation therapy are discussed.

Tandemly arranged repeats of a novel highly charged 16-amino-acid motif representing the major component of the sperm-tail-specific axoneme-associated protein family Dhmst101 form extended alpha-helical rods within the extremely elongated spermatozoa of Drosophila hydei.

We have previously reported that the sperm-tail-specific proteins in Drosophila hydei, encoded by the small Dhmst101 gene family, contained several tandem repeats of a novel highly charged, well-conserved cysteine-containing motif of 16 amino acids, KKKCAEAAKKEKEAAE [Neesen, J., Bünemann, H. & Heinlein, U. A. O. (1994) Dev. Biol. 162, 414-425] and suggested that this motif might be important in the structural and functional integrity of the sperm tail. We tested this suggestion by examining structure formation by model synthetic peptides containing the 16-residue sequence and corresponding peptides with one and two repeats of the sequence with Cys being replaced by Ala. We find that all these peptides form monomeric alpha-helices and that the helix content is considerably enhanced as the number of tandem repeats increases. These results are consistent with tandemly arranged 16-amino-acid repeats in Dhmst101 proteins forming extended alpha-helical rods, with the highly conserved Cys present in each 16-amino-acid motif being involved in regular interhelical cross-linking, thus providing a rigid, stable framework within the extremely elongated spermatozoa of Drosophila hydei.

Representative and efficient cloning of satellite DNAs based on PFGE pre-fractionation of restriction digests of genomic DNA.

Using DNA from Drosophila hydei KUN-DH-33 cells we describe an efficient method for selective and representative cloning of complex mixtures of satellite DNAs from eukaryotic genomes. Effective separation of satellite DNA from the bulk of all other sequences it obtained by fractionation of high molecular weight DNA by PFGE after treating it with '6 bp' restriction enzymes. Since extended clusters of tandemly arranged, so called simple sequence, repeats are inert to cleavage by most '6 bp' restriction enzymes the DNA fraction recovered from the gel region > 50 kb is mainly a mixture of satellites. Efficient and representative cloning of this DNA is performed by sonication to an average size of 50-500 bp and ligation of the blunt ended DNA fragments into the Bluescript vector pBS.

[The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases]. / Strahlentherapie des inoperablen nichtkleinzelligen Bronchialkarzinoms. Eine retrospektive Analyse von 427 Fällen.

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.

The Drosophila hydei gene Dhmst101(1) encodes a testis-specific, repetitive, axoneme-associated protein with differential abundance in Y chromosomal deletion mutant flies.

To understand the effect of the megabase-sized, Y chromosomal fertility genes on different stages of spermatogenesis in Drosophila hydei, an immunoscreening was performed to search for testis-specific protein-encoding cDNAs. The array of isolated clones contained cDNA sequences derived from a gene on chromosome 5 at 101BC. The gene, Dhmst101(1), is a member of a small gene family and is specifically expressed in adult testis tissue. The mRNA encodes a protein of 344 amino acids with a deduced apparent molecular weight of 37,793 Da. The main portion of the protein sequence comprises repetitive, highly charged amino acid units and shows repeat number variations among several D. hydei laboratory stocks. Immunocytochemistry with antibodies raised against synthetic peptides localized the protein product in elongated spermatids. This pattern of expression and the evaluation of biophysical considerations on the protein sequence data suggest that the Dhmst101(1) gene product may have some importance for the structural integrity of the sperm tail. Moreover, Y chromosomal deletions affecting correct spermiogenesis lead to degradation of the Dhmst101(1) gene product.

Inoperable non-small cell lung cancer: a retrospective analysis of 427 patients treated with high-dose radiotherapy.

PURPOSE: The influence of patient and treatment characteristics on survival as well as normal tissue toxicity were retrospectively analyzed. METHODS AND MATERIALS: Four hundred twenty seven patients with unresectable non-small cell lung cancer received at least 60 Gy and two-thirds were treated with 70 Gy. RESULTS: Five-year survival rates and median survival time (95% confidence interval) were 2 +/- 2% (mean +/- s.e.) and 11.1 months (9.1-14.5) after 60-66 Gy (median 60 Gy); 8 +/- 2% and 14.9 months (13.3-16.5) after > or = 70 Gy (p = 0.0013). Stage I-II patients had significantly higher survival rates as compared to Stage III patients (p = 0.0015). Within the subgroup of Stage III patients those with Stage IIIA had significantly higher survival rates than Stage IIIB (p = 0.0167). Female patients achieved 5-year survival rates after 70 Gy of 15 +/- 7% as compared to only 7 +/- 2% of their male counterparts. Chemotherapy, histology, Karnofsky status, and age had no influence on survival after univariate and multivariate analysis. Nine percent and 11% of the patients suffered from moderate to severe pneumonitis and esophagitis. CONCLUSION: High-dose radiotherapy of unresectable non-small cell lung cancer with total doses > 60 Gy conventionally fractionated is feasible. With doses of > or = 70 Gy significantly higher survival rates were achieved as compared to 60-66 Gy. Normal tissue toxicity was acceptable. For Stage IIIB patients, however, treatment results are disappointingly low even after 70 Gy with no 5-year survivor.

A telomere-like satellite (GGGTCAT)n comprises 4% of genomic DNA of Drosophila hydei and is located mainly in centromeric heterochromatin of all large acrocentric autosomes.

We describe the isolation and analysis of a G+C-rich telomere-like (GGGTCAT)n satellite of Drosophila hydei. GGGTCAT-specific clones were obtained by a combination of restriction enzyme digestion and fractionation of D. hydei DNA by pulsed-field gel electrophoresis (PFGE). High-molecular-weight DNA (> 50 kb) was recovered from gels, sheared by sonication and cloned into the pBS plasmid vector. The results of PFGE analysis, quantitative dot blot measurements and fluorescence in situ hybridization (FISH) on metaphase chromosomes show that the tandemly arranged GGGTCAT sequences comprise 4% of genomic DNA and are organized as megabase-sized clusters in the pericentric region of all large acrocentric autosomes. A telomere-related function is rather unlikely, because the chromosomal ends of D. hydei seem to be free of GGGTCAT repeats and several other species of Drosophila do not contain any cross-hybridizing sequences at all.

Towards a physical map of the fertility genes on the heterochromatic Y chromosome of Drosophila hydei: families of repetitive sequences transcribed on the lampbrush loops Nooses and Threads are organized in extended clusters of several hundred kilobases.

The understanding of structure and function of the so-called fertility genes of Drosophila is very limited due to their unusual size--several megabases--and their location on the heterochromatic Y chromosome. Since mapping of these genes has mainly been done by classical cytogenetic analyses using a small number of cytologically visible lampbrush loops as the sole markers for particular fertility genes, the resolution of the genetic map of the Y chromosome is restricted to 3-5 Mb. Here we demonstrate that a substantially finer subdivision of the megabase-sized fertility genes in the subtelomeric regions of the Y chromosome of Drosophila hydei can be achieved by a combination of digestion with restriction enzymes having 6 bp recognition sequences, and pulsed field gel electrophoresis. The physical subdivision is based upon large conserved fragments of repetitive DNA in the size range from 50 up to 1600 kb and refers to the long-range organization of several families of repetitive DNA involved in Y chromosomal transcription processes in primary spermatocytes. We conclude from our results that at least five different families of repetitive DNA specifically transcribed on the lampbrush loops nooses and threads are organized as extended clusters of several hundred kb, essentially free of interspersed non-repetitive sequences.

[Is short-term follow-up by skeletal scintigraphy of use in deciding on curative irradiation of inoperable non-small cell bronchial carcinoma? The experiences with 363 cases]. / Ist die kurzfristige Kontrolle des Skelettszintigramms von Nutzen bei der Entscheidung zur kurativen Bestrahlung des inoperablen nichtkleinzelligen Bronchuskarzinoms? Erfahrungen an 363 Fällen.

In a series of 363 patients, it was investigated if close-meshed bone scintigraphy is valuable for the decision whether or not to perform a high-dose curative radiotherapy of non-small cell bronchial carcinomas. The control of the bone scintigram made at the time of diagnosis, which was performed during the last phase of the treatment period before finally defining the treatment aim, was only helpful in some exceptional cases. Therefore a control of the first examination is not necessary if the latter has been performed not more than six months ago and if in the meantime no suspicious findings or other symptoms of a formation of skeletal metastases have been observed.