Doris H. Wurster-Hill

Distribution of non-telomeric sites of the (TTAGGG)n telomeric sequence in vertebrate chromosomes

The intrachromosomal distribution of non-telomeric sites of the (TTAGGG)n telomeric repeat was determined for 100 vertebrate species. The most common non-telomeric location of this sequence was in the pericentric regions of chromosomes. A variety of species showed relatively large amounts of this sequence present within regions of constitutive heterochromatin. We discuss possible relationships between the non-telomeric distribution of the (TTAGGG)n sequence and the process of karyotype evolution, during which these sites may provide potential new telomeres.

Isolation and growth characteristics of continuous cell lines from small-cell carcinoma of the lung

Sixteen continuous tumor‐cell cultures have been isolated from 91 tissue specimens from patients with small‐cell carcinoma of the lung. Biopsy and autopsy specimens of primary and metastatic tumors have been utilized. The developing cell lines were recognized by proliferation of tumor cells in the culture from one to 14 weeks after explantation and have been maintained for up to four years. Primary lung tumor, bone marrow aspirations, pleural effusions and other metastases have all been productive explant material for the development of cell lines. Their human origin has been demonstrated by chromosome and/or isoenzyme analysis. Dense core vesicles, characteristically found in small‐cell tumor cells were observed by electron microscopic examination of cultured cells. Growth rates in vitro have been measured and the in vitro cycle time in tumors of one cell line (DMS 79) has been compared with in vivo cycle time in tumors arising from DMS 79 cells in nude athymic mice.

The interrelationships of chromosome banding patterns in canids, mustelids, hyena, and felids

The G-banding patterns of six canids, four mustelids, one hyena, and 12 felids have been studied, and data from the study of 30 felids are summarized. The canids are karyotypically very similar to one another, but minor differences have tentatively been identified. The mustelids show the greatest karyotypic diversity of all the carnivore families so far studied. They do display, however, considerable G-band conservatism, as is common throughout the Order, and appear karyotypically more closely related to the Feloidea than to the Canoidea. The hyena shares many autosomes with the felids, showing a close relationship to that family. The felids are for the first time divisible into small groups or individually identifiable on the basis of 16 different karyotypic patterns.

Cytogenetics of small cell carcinoma of the lung

Nineteen cell lines derived from various malignant tissues of 15 patients with small cell carcinoma of the lung (SCCL) have been studied. The results showed heterogeneity in all cell lines, with no one consistent abnormality among them. Cell lines from 11 of the patients had minute and double minute chromosomes, and cell lines from 2 patients had abnormally banding regions, designated as ABRs, as distinguished from homogeneously staining regions (HSRs). The latter 2 and several of the former cell lines were derived from specimens taken before the patients were placed on therapy. All but 2 of the cell lines had a constant marker load, consisting of 24%-35% of the complement. Some markers remained stable through months and years of culture life, while other markers came and went. Chromosomes #1, #6 and #11 were most frequently involved in marker formation in the cell lines, and these were compared to similar markers in direct bone marrow preparations. Chromosome #1 markers were of variable structure, whereas #6 and #11 most often took the form of 6q- and 11p+ markers, with breakpoints most frequently at 6q23-25 and 11p11-12. A 3p- marker was found in a minority of cell lines. All of these markers were also found in direct marrow preparations from some patients with SCCL. Nonmonoclonal tumors arose from inoculation of bimodal cell lines into nude mice, but population selection by undetermined mechanism was evident. Cytogenetic parameters showed no positive correlation with hormone production by these cell lines.

Fragile sites, telomeric DNA sequences, B chromosomes, and DNA content in raccoon dogs, Nyctereutes procyonoides, with comparative notes on foxes, coyote, wolf, and raccoon

Earlier studies of the genus Nyctereutes disclosed two subspecies of differing chromosome numbers accompanied by B chromosomes. To further define the relationship of these subspecies to each other, and to other carnivores, and to learn more about the structure and function of their chromosomes, we characterized and compared the genomes in terms of DNA content by flow cytometry, fragile sites induced by aphidicolin, and telomere sequences using biotinylated DNA probes detected with fluorescence. We also characterized the B chromosomes of these two subspecies.

Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: a Cancer and Leukemia Group B Study.

PURPOSE To determine the treatment outcome of standard acute myeloid leukemia (AML)-type chemotherapy in a subset of patients with newly diagnosed myelodysplastic syndromes (MDS) compared with that of patients with de novo AML as defined using French-American-British (FAB) criteria. In addition, to determine the pretreatment variables having prognostic significance for treatment outcome in patients with MDS. PATIENTS AND METHODS Nine hundred seven newly diagnosed patients with no history of cytopenias having a local institutional de novo AML successfully karyotyped and treated on Cancer and Leukemia Group B (CALGB) protocols for AML from 1984 to 1992. Thirty-three of the 907 patients were reclassified as having MDS on central pathology review using FAB criteria and form the basis of this analysis. RESULTS The treatment outcomes for patients with MDS and AML were similar; the complete remission (CR) rate was 79% and 68%, respectively (P = .37); median CR duration was 11 and 15 months, respectively (P = .28); and median survival was 13 and 16 months, respectively (P = .72). For the MDS patients, there were no prognostic variables for CR rate identified. For CR duration, only the Sanz classification had prognostic value. The prognostic factors for survival in a univariate analysis included age, WBC count, Sanz classification, and percent blood blasts. In a proportional hazards analysis of survival, age greater than 60 years and WBC less than 2.6 x 10(9)/L were adverse prognostic factors. CONCLUSION In patients with no known history of cytopenias who are treated intensively at diagnosis, the FAB distinctions between MDS (refractory anemia with excess blasts and refractory anemia with excess blasts in transformation) and AML appear to have little therapeutic relevance.

Distribution of constitutive heterochromatin in carnivores

The distribution of constitutive heterochromatin (C-banding) in the genomes of nine species of Felidae, one species of Mustelidae, two species of Procyonidae, one species of Viverridae, one species of Canidae, and one species of Ursidae has been studied. In the chromosomes of several felid species the C-band is apparently absent. A few chromosomes show only telomeric staining in one arm or sometimes in both arms. Centromeric and interstitial distribution of heterochromatin has also been demonstrated in other species of Carnivors, but, in general, the C-banded material in felids is comparatively less in amount, and more weakly staining, than in other mammals. Induction of C-banding patterns in certain carnivore species is rather difficult, probably because of the minimal amount of heterochromatin present.

Comparative cytogenetics of Chinese and Japanese raccoon dogs, Nyctereutes procyonoides

We investigated the relationships between subspecies of Nyctereutes procyonoides from China (2n = 54 + B chromosomes) and Japan (2n = 38 + B chromosomes). The chromosomes of Chinese and Japanese raccoon dogs were compared by means of conventional staining, G- and C-banding, and silver nitrate staining of NORs. Extensive G-banding homologies revealed karyotype evolution through chromosomal fusion. We believe the reduced diploid number in the Japanese raccoon dogs was achieved by fusion of 16 acrocentrics to form eight metacentric and submetacentric elements. Ten pairs of autosomes appeared to be identical in these subspecies and were presumed to have occurred as such in a common ancestor. G-band patterns of the sex chromosomes were similar in the two subspecies, but differences were noted with other banding and staining techniques. B chromosomes were present in varying numbers and sizes in all animals examined, but the morphology of the B chromosomes differed in the two subspecies. It was concluded from chromosomal and paleontological evidence that the two subspecies were derived from a common mainland ancestor and that the Japanese raccoon dogs is a relatively recent form.

The interrelationship of chromosome banding patterns in the giant panda (Ailuropoda melanoleuca) hybrid bear (Ursus middendorfi × Thalarctos maritimus), and other carnivores

The banded chromosomes of the giant panda (Ailuropoda melanoleuca) and a hybrid bear (Ursus middendorfi X Thalarctos maritimus) have been studied and compared to those of other carnivores. The giant panda shares only a few apparently homologous chromosome arms with the bear (Ursidae) and equally few with the lesser panda, Ailurus fulgens (Procyonidae). Chromosomal evidence suggests appropriate placement of the giant panda in a family separate from the Uridae and the Procyonidae.

Chromosomal aberrations and neoplasm—a family study

A family is described in which four out of five siblings have chromosomal aberrations both in the myeloid and lymphoid cells. One of these died in the blastic phase of chronic myelogenous leukemia, another had myelofibrosis and carcinoma of the breast, a third had squamous cell carcinoma of the lip, and the other two siblings are normal. The mother had carcinoma or the breast. Two of the siblings have had occupational exposure to organic solvents. The relationship of genetic pre‐disposition to malignancy, chromosomal instability, and environmental stresses is discussed.