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Context:Gestational diabetes (GDM) influences the fetal phenotype.Objective:In the present study, our aim was to determine the effect of GDM specifically on fetal brain activity.Design:Pregnant participants underwent an oral glucose tolerance test (OGTT, 75 g). At 0, 60, and 120 minutes, maternal metabolism was determined, and fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device.Setting:All measurements were performed at the fMEG Center in Tübingen.Participants:Twelve women with GDM and 28 normal glucose-tolerant (NGT) pregnant women participated on a voluntary basis.Interventions:OGTT (75 g, 120 minutes) was used in this study.Main Outcomes and Measures:Fetal auditory evoked response latencies were determined for this study.Results:In the fetuses of NGT women, latencies decreased between 0 and 60 minutes from 260 ± 90 to 206 ± 74 ms (P= .008) and remained stable until 120 minutes (206 ± 74 vs 230 ± 79, P=.129). In fetuses of women with GDM, there was no change in response latencies during OGTT (P= .11). Sixty minutes after glucose ingestion, fetal latencies in the GDM group were longer than in the NGT group (296 ± 82 vs 206 ± 74 ms, P= .001). Linear regression revealed a significant effect of maternal glucose, insulin levels, and insulin sensitivity on response latencies after 60 minutes.Conclusions:Fetal postprandial brain responses were slower in the offspring of women with GDM. This might indicate that gestational diabetes directly affects fetal brain development and may lead to central nervous insulin resistance in the fetus.

The serine protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are known to be involved in the invasion and metastasis of many solid tumors. In this study, we analyzed the role of the uPAR/uPA system in both the development and progression of pancreatic cancer in invasive ductal adenocarcinomas of the pancreas (PDA) and their premalignant precursors (PanIN lesions) in 50 patients with long-term clinical follow-up. We found overexpression of the uPAR in 48 of 50 invasive carcinomas as well as in a large proportion of high-grade PanIN lesions by immunohistochemistry and in situhybridization. Fluorescence in situhybridization analysis showed both high- and low-level amplification of the uPARgene in ∼50% of cases with strictly identical patterns between invasive cancers and their accompanying precursor lesions. These results suggest that PDA may develop from PanIN lesions along an alternative rather than a sequential molecular pathway. The detection of the gene amplification of uPARwas a highly significant, adverse prognostic parameter (P< 0.001) because it likely renders the tumors more sensitive to uPA and its proproliferative and anti-apoptotic signals. We conclude that the activation of the uPAR/uPA system is an early event in the development of PDA and that uPARgene amplifications identify a subgroup of particularly aggressive tumors, making the uPAR/uPA system a critical and highly promising target for therapeutic interventions.

Measurements are described involving neutron spin echo and quasi-elastic light scattering in an end-linked polyfluorosilicone (PFS) gel swollen in acetone as well as in the equivalent solution. Small-angle elastic neutron scattering measurements were performed on the same system. For the PFS−acetone system, both dynamic light scattering and neutron spin echo yield similar results for the characteristic relaxation rates and for the intensity scattered by concentration fluctuations. It is shown that the relaxing part of the spin echo decay is described by the same thermodynamic concentration fluctuations that define the osmotic modulus of the system. Both the collective diffusion coefficient and the intensity of the dynamically scattered light are found to be greater in the gel than in the solution. This difference indicates that the polymer solvent friction coefficient in the cross-linked network is lower than in the un-cross-linked solution.

Despite the continuous progress in molecular methodology, the genetic events involved in the initiation and progression of ductal adenocarcinoma of the pancreas remain largely unknown. In this study, 33 pancreatic ductal adenocarcinomas were screened for genomic alterations by comparative genomic hybridization (CGH). To date, most CGH studies of pancreatic cancer have been based on cell lines. To emphasize genetic imbalances that are involved in the in vivo development and progression of pancreatic carcinoma only fresh-frozen or paraffin-embedded tumour samples were analysed in the present study. Twenty-two tumours (67%) showed genomic alterations involving up to three (12%) or more (55%) chromosomal regions. The number and nature of the genetic imbalances did not, however, correlate with tumour stage or grade. Chromosome 18 was preferentially altered in the tumours analysed. Frequent chromosomal losses were found at 18q, 10q, 8p, and 13q. Commonly gained regions were located on 8q and 3q. Moreover, high copy number amplifications of the chromosomal regions 5p, 8q22-ter, 12p12-cen, 19q12–13.2, and 20q were identified. These data provide evidence for the occurrence of characteristic genomic alterations which are of biological relevance for the genesis of pancreatic cancer. The identified altered chromosomal regions may harbour tumour genes which involved in the multistep process of pancreatic carcinogenesis. Copyright © 2000 John Wiley & Sons, Ltd.

The mithun (Bos frontalis) and its hybrids with Bos indicuswere studied to provide further cytogenetic information which might throw light on the mechanisms of male hybrid infertility and facilitate the establishment of a stable crossbreed. It was shown that compared with conventional cattle the mithun has a homozygous, species specific 2/27 centric fusion which reduced the diploid chromosome number from 60 to 58. This provided further proof that Robertson translocation-type rearrangements have been the major source of interspecies karyotype differences in the evolution of the Bovidae. In the mithun there was also significant polymorphism between centromeres of non-homologous chromosomes and there was heteromorphism between several homologous chromosomes which could possibly serve as useful genetic markers for breeding programmes. In F1 hybrids spermatogenesis progressed to a relatively advanced stage, without going so far as to produce spermatozoa. In back crosses to B indicusspermatogenesis progressed further so that spermotozoa could be seen, though not as numerous as in normal bulls. In most hybrids there were haemoglobin bands which corresponded either to Hb A or Hb B of cattle but were much wider. It was shown that these were a combination of Hb Mi derived from the mithun and Hb A or Hb B derived from B indicus.In a few hybrids there were only Hb Mi. In these cases Hb Mi had been present in both parents and proved that the dam was not a pure siri. The possible mechanism of hybrid male infertility is discussed including faults in the epistatic gene effect between chromosomes and changes in the degree of association of centromeric regions in interspecies hybrids. It is suggested that additional cytogenetic examination of blood lymphocytes and especially of testicles would help the understanding of the fertility barriers of hybrid males and would make a breeding programme for a stable crossbreed possible.

Pulsed NMR measurements of the nuclear magnetic susceptibility of liquid3He-4He solutions at saturated vapor pressure are presented. They extend over the whole temperature range between 50 mK and 825 mK, for both concentrations of the coexisting dilute and3He-rich phases. The results have been compared to those obtained with pure3He, and the temperature dependence of the ratio of molar susceptibilities of coexisting phases is derived. The consequences on the efficiency of fractional distillation as a method to enhance nuclear polarization are discussed.

In the present study the establishment and characterization of a nontumorigenic liver epithelial cell line (HACL-1) derived from a human hepatocellular adenoma is described. The HACL-1 cells have a finite life span (i.e., they proliferate for a period of 2 months and then senesce), show cell–cell contact inhibition, do not grow in soft agar, are not tumorigenic when injected in nude mice, and possess a normal diploid karyotype. The cultured cells resemble hepatocytes, but exhibit some features of dedifferentiation. At the ultrastructural level the cells are endowed with round or oval nuclei, abundant cytoplasmic organelles, and varying amounts of glycogen. The rough endoplasmic reticulum is disorganized, while peroxisomes and matrix granules within mitochondria are lacking. HACL-1 cells are cytokeratin 18-positive as well as (transiently) albumin- and α-fetoprotein-positive, but do not express cytokeratin 19. Furthermore, no mutations were observed in exons 5–8 of the tumor suppressor genep53.Taken together these results show that HACL-1 cells are nontumorigenic proliferating liver epithelial cells, which might prove to be of great value in future studies on diverse aspects of human liver cell biology and carcinogenesis.

Cytogenetic studies of the mithun (Bos frontalis), the siri (Bos indicus) and their hybrids, as well as histological examinations of testes and epididymis of siri and hybrids were undertaken to throw further light on male hybrid infertility and interspecies incompatibility, in order to facilitate the possible development of a stable interspecies crossbreed which would be similar to the highly profitable jatsum, the female mithun cross siri hybrid. In both species there are distinct centromeric heteromorphisms which should provide a rich source of genetic markers for tracing chromosomes in controlled hybrid programmes. The nucleolar organisers in the F1hybrids were derived from both parents, in contrast to other interspecies hybrids where the nucleolar organisers of one species tend to be suppressed by the other. This indicates a relatively close relationship between mithun and siri and supports the prospect of success for developing a stable crossbreed. Transferrins which may also be a useful source of genetic markers were identified and differences between siris and mithuns noted, especially in the D-bands. No A-bands were found in the siris and no E-bands in the mithuns. Whether this is a breed or species characteristic will have to be confirmed by examination of more animals. The findings on blood groups and haemoglobins, including differences between the two species, were similar to results obtained previously. In meiosis the sex vesicles were intact which indicates that infertility and incompatibility factors should be located in autosomes. In cytogenetic and histological examinations the testes of the siris were comparable to those of European cattle, while in all hybrids spermatogenetic activity was deficient although there were great differences between and within generations. While the exact mechanism of this diversity is not known at this stage, it should make it possible to select for increased male hybrid fertility which would be a prerequisite for developing a stable interspecies crossbreed. This selection would be facilitated by correlating infertility and incompatibility with genetic profiles and markers. A mithun cross siri crossbreed would also serve as a model for other interspecies breeding.

The karyotypes of three avian species--Meleagris gallopavo, Anser anser L., and Columba livia domestica--were investigated by means of counterstain-enhanced fluorescence techniques (chromomycin A3/distamycin A/DAPI followed by DAPI/actinomycin D staining). A heterochromatin characterization of macro- and microchromosomes was performed. CMA3-positive (GC-rich) regions in the turkey included the telomeres of chromosomes 1, 3, 4, and Z. In the goose, the chromosome 2 was also CMA3-bright at the telomeres. The W chromosome possessed large amounts of CMA3-bright material on the short arm in both the turkey and the goose. Two types of centromeric heterochromatin were distinguished on acro- to telocentric chromosomes 6 to 14 in the pigeon. The microchromosomal heterochromation of the turkey and goose was GC-rich but had a high degree of variation. In the pigeon, several microchromosomes possessed predominantly AT-rich heterochromatin.

Sequential staining with a counterstain-contrasted fluorescent R-banding technique (chromomycin A3/distamycin A-DAPI) followed by DAPI-actinomycin D-induced quinacrine-fluorescence-Hoechst 33258 (QFH)-type banding allowed the identification of quail chromosomes up to chromosome 19. The chromomycin A3-positive staining behavior of the W chromosome and of the heterochromatic areas of most microchromosomes indicated their GC-rich nature.

Chromomycin A3 (CMA3) banding in mitotic sets of the Equidae horse and donkey were used to demonstrate both constitutive heterochromatin and R-banding. Intra and Interindividual variation In the size of the heterochromatic blocks was observed In many cases. CMA3-posittve telomeric heterochromatin blocks appeared on several chromosomes of the horse and donkey. Some of them were especially spectacular in the donkey. A sequential silver NOR-chromomycin A3/distamycln A-DAPI (CDD) staining procedure led to the detection of the localization of active nucleolus-organizing regions (NORs) and to the identification of chromosomes. The data revealed individual specific NOR patterns in both species.

In this paper we show that the concentration dependence of the plateau shear elastic modulus and of the viscosity can be understood if two lengths, the correlation length of concentration fluctuations and the tube diameter, are considered. To interpret the temperature variation of the viscosity and of the self-diffusion coefficient with the solvent quality, one has to take into account the local viscosity to which monomers are sensitive. This concentration dependent local viscosity, deduced from neutron spin−echo measurements, is independent of the polymer molecular weights, solvent viscosities and &THETAV; temperatures. The local viscosity decreases to reach the solvent viscosity value at high temperature, that is, under good solvent conditions. The role of the macroscopic concentration on a local scale, seems to indicate that, in semidilute &THETAV; solutions, the polymers are transparent to each other, as far as dynamic properties are concerned.

Chicken chromosomes were identified up to No. 18 by a sequential counterstain-enhanced fluorescence technique. A heterochromatin characterization of macro- and microchromosomes was performed; in general, the microchromosomes were GC-rich, but with a high degree of variation. The NORs are localized on chromosome No. 17.

The mutagenicity and micronucleus induction by the furocoumarin hydroperoxides 1aand 2aand, for comparison, their corresponding alcohols 1band 2bwere investigated in L5178Y tk+/−mouse lymphoma cells and AS52 Chinese hamster ovary cells. The furocoumarin hydroperoxide 1aenhanced the micronucleus frequency in L5178Y tk+/−mouse lymphoma cells significantly, while its alcohol 1bexhibited a rather moderate effect. In contrast, both the furocoumarin hydroperoxide 2aand its alcohol 2binduced high frequencies of micronuclei. Only the furocoumarin hydroperoxide 1a, but not its alcohol 1b, was mutagenic in both L5178Y tk+/−and AS52 cells. On the other hand, the furocoumarin hydroperoxide 2aand its alcohol 2bwere mutagenic. For all furocoumarin derivatives 1a,band 2a,bno mutagenicity and genotoxicity was observed in the absence of UVA light. The multifunctional furocoumarin hydroperoxides may serve as potential photochemotherapeutic agents.