Showing papers by "University of Southern Denmark published in 1993"
Journal Article•
TL;DR: It is concluded that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis.
Abstract: Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa.
100 citations
TL;DR: Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements.
Abstract: Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours.
91 citations
TL;DR: The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band, and shows that recombinations between 6p21 and14q24 are common, and hence probably pathogenetically important.
Abstract: Cytogenetic analysis of short-term cultures from seven pulmonary hamartomas revealed an abnormal karyotype in six of them. The most characteristic aberration was an exchange of material between 6p21 and 14q24, found in three tumours. Abnormalities of either 6p or 14q were seen in another two hamartomas. Other regions that were rearranged more than once were 12q (three times) and 17p (twice), sometimes in exchange with 6p or 14q and giving rise to complex derivative chromosomes. Only one tumour had aberrations that did not involve 6p, 12q, 14q, or 17p. These results-together with the data on three previously reported pulmonary hamartomas, two of which also had t(6;14)-show that recombinations between 6p21 and 14q24 are common, and hence probably pathogenetically important. The data support the view that these tumours are genuine neoplasms rather than developmental anomalies. The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band.
79 citations
TL;DR: This work focuses on the karyotypes of colorectal carcinomas and how the cytogenetic findings correlate with clinicopathologic features.
Abstract: Background Little is known about the karyotypes of colorectal carcinomas and, in particular, about how the cytogenetic findings correlate with clinicopathologic features
Methods Short-term cultures from 49 colorectal adenocarcinomas were analyzed cytogenetically The karyotypes were correlated with grade, stage, lymphocytic infiltration, and site (using the chi-square test), with patient age and tumor size (using the Student t test), and with survival (using the log-rank or Mantel-Haenszel test)
Results Normal karyotypes were detected in 17, simple numeric changes in 22, and multiple structural and numeric abnormalities in 10 The most common numeric aberrations were +7, −Y, −18, and −22 The most common structural rearrangements were, in decreasing order of frequency, of chromosomes 1 (eight samples, leading to loss of 1p material in five), 3,11,17,6,8,13, and 20 Marked or moderate lymphocytic infiltration was seen significantly less often (P < 005) in tumors with complex chromosomal abnormalities than in those with simple anomalies or normal karyotypes The subset of patients who had tumors with multiple chromosomal abnormalities had a significantly shorter survival time (P < 0025) than those who had lesions with simple changes or normal karyotypes
Conclusions Loss of 1p material is the most consistent chromosomal change in colorectal carcinomas but probably represents a progressional rather than a primary event Structural changes of chromosomes 3 and 11 seem to be more common in tumors located in the distal part of the large intestine The significantly shorter survival time of patients with complex aberrations indicates that the karyotype could be used as a prognostic parameter in patients with colorectal cancer
79 citations
TL;DR: Standard measles vaccination before 9 months is not associated with higher childhood mortality than is the currently recommended strategy of immunising from 9 months, and it may reduce mortality, which has implications for measles immunisation strategy in developing countries.
Abstract: OBJECTIVE--To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age. DESIGN--Children vaccinated in 1980-3 at 4-5, 6-8, and 9-11 months of age were followed to migration, death, or the age of 5 years. SETTING--One urban district and nine villages in two rural areas of Guinea-Bissau. SUBJECT--307 children vaccinated at 4-8 months and 256 at 9-11 months. MAIN OUTCOME MEASURES--Mortality from 9 months to 5 years of age for children immunised at 4-5, 6-8, and 9-11 months. RESULTS--Mortality was significantly lower in children vaccinated at 6-8 months than at 9-11 months (mortality ratio = 0.63, (95% confidence interval 0.41 to 0.97), p = 0.047). As vaccination was provided in semiannual or annual campaigns it is unlikely that age at vaccination reflected a selection bias. The trend was the same in all three study areas. Improved survival after early immunisation was not related to better protection against measles infection. With a Cox multivariate regression model to adjust for age, sex, season at risk, season at birth, measles infection, and region, children vaccinated at 4-8 months had a mortality ratio of 0.61 (0.40 to 0.92, p = 0.020) compared with children vaccinated at 9-11 months. Reimmunised children tended to have lower mortality than children who received only one vaccine (0.59 (0.28 to 1.27, p = 0.176)). CONCLUSION--Standard measles vaccination before 9 months is not associated with higher childhood mortality than is the currently recommended strategy of immunising from 9 months, and it may reduce mortality. This has implications for measles immunisation strategy in developing countries.
68 citations
TL;DR: The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis.
Abstract: Interstitial deletions of the short arm of chromosome 3 were found in short-term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p– coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis. © 1993 Wiley-Liss, Inc.
67 citations
TL;DR: Gain of one chromosome 8 as a frequent primary karyotypic abnormality in embryonal rhabdomyosarcomas and additional gains of chromosome 8 material seem to be common secondary changes.
Abstract: An embryonal rhabdomyosarcoma was analyzed cytogenetically. In primary cultures fed a serum-containing medium, 11 clones with karyotypic abnormalities were found. One had trisomy 8 only. The other 10 clones had trisomy 8 as well as additional evolutionary changes that included trisomy for part or all of chromosome 2, isochromosomes for the short and long arms of chromosome 11, isochromosomes for the long arm of chromosome 8, and extra copies of chromosome 8, some of which had an interstitial deletion in 8q. In those primary cultures that had grown in a chemically defined, serum-free medium and in all passaged cultures, trisomy 8 was the only aberration. Our findings and a survey of published information point to gain of one chromosome 8 as a frequent primary karyotypic abnormality in embryonal rhabdomyosarcomas. Trisomy for part or all of chromosomes 2 and 11 and additional gains of chromosome 8 material seem to be common secondary changes. © 1993 Wiley-Liss, Inc.
31 citations
TL;DR: In this article, Monte Carlo simulations were performed on two lattice gas systems with Coulombic interactions and the effect of backward correlations on the particle diffusivity was found to be similar to that for the strictly repulsive system, however, backward correlations are much stronger due to the presence of immobile Coulomb traps.
Abstract: Monte Carlo simulations were performed on lattice gas systems with Coulombic interactions. Emphasis was placed on two lattice gases. The first consists of both mobile anions and cations while the second is composed of mobile anions and a random distribution of fixed cations. Comparisons are made to a strictly repulsive lattice gas. The addition of attractive forces is shown to significantly retard particle motion relative to the repulsive system. In the mobile‐anion, mobile‐cation system, at temperatures high enough to suppress ion clustering, the effect of backward correlations on the particle diffusivity is found to be similar to that for the strictly repulsive system. In the mobile‐anion, fixed‐cation system, however, backward correlations are much stronger due to the presence of immobile Coulomb traps. Both systems deviate from Nernst–Einstein behavior. The mobile‐anion, mobile‐cation system exhibits diminished conductivity (Haven ratio ≳1) due to the migration of neutral ion pairs, whereas the mobile...
24 citations
TL;DR: In this article, experimental time series of [O 2 ] generated by the peroxidase-oxidases reaction were analyzed using various methods from nonlinear dynamics and the following results were obtained: (1) aperiodic time series are chaotic as evidenced by (i) the observation of period doubling bifurcations in response to increasing the amount of 2,4-dichlorophenol in the reaction mixture, (ii) well-defined next amplitude maps, (iii) positive Lyapunov exponents corresponding to about 0.5 bits per
Abstract: Experimental time series of [O 2 ] generated by the peroxidase-oxidase reaction were analyzed using various methods from nonlinear dynamics. The following results were obtained: (1) Aperiodic time series are chaotic as evidenced by (i) the observation of period doubling bifurcations in response to increasing the amount of 2,4-dichlorophenol in the reaction mixture, (ii) well-defined next amplitude maps, (iii) positive Lyapunov exponents corresponding to about 0.5 bits per orbital excursion, and (iv) fractal dimensions ranging from 2.6 to 2.8. Prediction profiles obtained by subjecting the data to nonlinear forecasting give further evidence of deterministic chaos. (2) The chaotic data are nonuniform, since none of the above-mentioned methods work well when applied to the continuous data
20 citations
TL;DR: This study illustrates the potential use of chromosome painting in resolving karyotypic uncertainties in NHL, and it shows that new cytogenetic subgroups may emerge when classical banding analysis is supplemented with fluorescence in situ hybridization techniques.
Abstract: Chromosomal in situ suppression (CISS) hybridization with biotin labeled chromosome-specific libraries was performed on short-term cultures from five cases of non-Hodgkin's lymphoma (NHL). The painting analysis proceeded in three stages. First-stage CISS hybridization was done with libraries specific for chromosomes that seemed to be lost or rearranged as judged by banding analysis. Second-stage CISS included hybridization with probes specific for chromosomes that, because of banding pattern similarities, were considered to be likely candidates to have contributed unidentified chromatin blocks in the abnormal karyotype. The third and final stage was a confirmation hybridization with a library specific for the chromosome that, at the stage two analysis, was found to have donated the previously unknown chromosomal segment. The aberrant chromosomes were often more complex than the banding analysis had led us to believe. Among the rearrangements whose nature was determined by CISS hybridization were two add(1)(p36) which, in both cases, were shown to be a der(1)t(1;2)(p36;q31). This study illustrates the potential use of chromosome painting in resolving karyotypic uncertainties in NHL, and it shows that new cytogenetic subgroups may emerge when classical banding analysis is supplemented with fluorescence in situ hybridization techniques. © 1993 Wiley-Liss, Inc.
15 citations
Posted Content•
TL;DR: The equilibrium between Z and E isomers of Schiff bases derived from 3-formyl-4-thio(seleno)coumarin 1, 2 resulting from the hindered rotation around the exocyclic carbon-carbon bond in the stable ketoamine tautomeric form has been studied by means of IR and 1D and 2D (NOESY)1H NMR spectroscopy and ab initio and semi-empirical calculations as discussed by the authors.
Abstract: The equilibrium between Z and E isomers of Schiff bases derived from 3-formyl-4-thio(seleno)coumarin 1, 2 resulting from the hindered rotation around the exocyclic carbon–carbon bond in the stable ketoamine tautomeric form has been studied by means of IR and 1D and 2D (NOESY)1H NMR spectroscopy and ab initio and semiempirical calculations The ratio between the Z and E forms in solution was found to lie in the range 35:1–58:1 (XS) and 24:1–31:1 (XSe) The activation energy for Z⇌E interconversion was estimated for 1a and 2a using dynamic 1H NMR spectroscopy to be 457 and 353 kJ mol–1, respectively The process was found to be catalysed by trifluoroacetic acid The relative stability of both tautomeric and conformational isomers calculated theoretically at MP2/6–31G* level for the model molecules of 3-methylimino-4-hydroxy(thio, seleno)-2-pyrone is in good agreement with experimental data Estimated activation barriers for the rotational mechanism are higher than experimentally obtained which may indicate a contribution from acid-promoted reaction pathways
Journal Article•