Development and Significance of Cysteamine and Propionitrile Models of Duodenal Ulcer

Cysteamine is widely used in rodents to induce duodenal ulcer. Herein, the pathogenesis of duodenal ulceration in its earliest stages was reviewed using findings from cysteamine-and propionitrile-induced duodenal ulcer in rodent models, especially taking into account changes in the secretion of gastric acid, duodenal and pancreatic bicarbonate as well asgastroduodenal motility. The effect of cysteamine-HCl in inducing ulcers in rats is circadian rhythm-dependent. The effect is greatest from just before the end of diurnal rest to just after the start of nocturnal activity. The chronobiologic effect may be in part due to the circadian rhythm-dependent increased gastric acid production from cysteamine. Titratable acidity was found to be twice as great in the gastric juice of rodents when cysteamine was given by injection at 2000 (just after the start of nocturnal activity) in comparison to when given at 0800 or 1200 (at the beginning or middle span of daily rest). Further studies have shown that adrenalectomy of rats 7 days before cysteamine administration obliterated the observed circadian susceptibility to ulcer formation. Duodenal ulceration, at least in the cysteamine model, appears to be under chronobiologic neuroendocrine control or influence, seemingly mediated by the adrenal glands.     

Tolerance induction by a poorly arthritogenic collagen II can prevent collagen-induced arthritis

Collagen type II (CII)-induced arthritis (CIA) can be induced in 78% of B10.RIII mice (H2r) by intradermal (id) immunization with CII of bovine origin in complete Freund's adjuvant (CFA), whereas immunization with CII of chick origin induces arthritis in less than 5% of these mice. Nevertheless, tolerization of B10.RIII mice with intravenously injected chick CII renders the animals resistant to induction of CIA by immunization with bovine CII. Such tolerization can be achieved either by intravenous injection of 500 micrograms chick CII 1 week prior to immunization with bovine CII in CFA or by such an intravenous injection of chick CII 2 weeks after immunization with bovine CII in CFA. Postimmunization treatment results in a significant decrease in the concentration of antibody to bovine CII. Preimmunization administration of chick CII causes a marked decrease in the antibody reactive with chick CII without a significant effect on the anti-bovine CII antibody concentration. In DBA/1 mice, a strain in which both bovine CII and chick CII can induce a high incidence of the disease, intravenous injection of bovine CII can also prevent arthritis induced by chick CII, even when given 7 or 14 days after immunization. The fact that chick CII as tolerogen is quite effective in preventing arthritis in B10.RIII mice, while as immunogen it is very ineffective in inducing arthritis in this strain, may be interpreted as evidence for interaction between different epitopes on CII in the pathogenesis of CIA.     

Evidence for chromosome instability in vivo in bloom syndrome: Increased numbers of micronuclei in exfoliated cells

Summary The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: (1) to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS) cells proliferating in vitro also occurs in vivo, and (2) as part of a broad survey of various cancer-prone populations, to determine whether estimating micronucleus frequencies in exfoliated cell samples might be useful for identifying individuals with genetically determined chromosome instability. Eight individuals homozygous (bl/bl) for the BS gene, i.e., persons with the clinical syndrome, were examined, along with 11 obligate heterozygotes (bl/+), parents of affected persons. Exfoliated cells were obtained from two sites, the oral cavity and the urinary tract. Striking and statistically highly significant elevations in the frequencies of cells with micronuclei were observed in cells from both sites in bl/bl individuals compared to that in bl/+ (P<0.001) and in a control population, indicating that chromosome instability occurs in vivo in BS. In contrast, micronucleus frequencies at either site did not differ significantly between bl/+ individuals and the control population. This survey, in combination with similar earlier ones of populations predisposed to cancer not on a genetic basis but because of exposure to some environmental carcinogen, suggests that the exfoliated cell micronucleus test identifies individuals whose somatic genetic material has, for either genetic or environmental reasons, been damaged in a way that produces chromosome breakage and rearrangement.     

Bloom's syndrome

Summary The biochemical defect in Bloom's syndrome (BS) remains unknown, but two characteristic features of BS cells point to a disturbance of DNA replication, namely, an excessive number of sister-chromatid exchanges (SCEs) in bromodeoxyuridine (BrdU)-substibuted cells and an abnormally slow rate of replicon elongation. The hypothesis of an abnormal DNA polymerase as the explanation for these observations was tested using an in situ assay system for DNA polymerase activity and to estimate molecular weights in cellular extracts of cultured BS cells. DNA polymerase subunits in cellular extracts from the BS cells when separated electrophoretically on polyacrylamide gels showed the same mobilities (i.e., molecular weights) as the controls and were equally effective at promoting the incorporation of isotopically labeled nucleosides. It is concluded that the genetic defect in BS has no direct effect on either DNA-polymerase activity or the amounts and molecular weights of the different forms of the enzyme.     

Bloom's syndrome. III. Analysis of the chromosome aberration characteristic of this disorder

The following hypothesis is put forward: X chromatin in man condenses around a center which is situated on Xq at a short distance from the centromere. The hypothesis is based on, and explains, two classes of observations. (1) Abnormal X chromosomes that have the assumed center in duplicate form bipartite Barr bodies in part of the cells. The frequency of bipartite bodies and the distance between the two parts seem to be determined by the distance between the postulated centers. (2) A large number of variously abnormal X chromosomes have been described. Almost all of them possess the postulated center and it seems possible that the very few apparent exceptions represent misidentifications of chromosome Xq — as isochromosome i(Xp). According to the hypothesis, chromosomes lacking the center would form no Barr body and therefore presumably would not be inactivated, thus leaving the cell severely unbalanced. Furthermore, absence of the center might interfere with the viability of the chromosome itself.     

Plant transformation by microinjection techniques

Several techniques have been developed for introducing cloned genes into plant cells. Vectorless delivery systems such as PEG-mediated direct DNA uptake (e.g. Pasz-kowski et al. 1984), electroporation (e.g. Shillito et al. 1985), and fusion of protoplasts with liposomes (Deshayes et al. 1985) are routinely used in many experiments (see several chapters of this issue). A wide range of plant species, dicotyledonous as well as monocotyledonous, has been transformed by these vectorless DNA transfer systems. However, the availability of an efficient protoplast regeneration system is a prerequisite for the application of these techniques. For cells with intact cell walls and tissue explants the biological delivery system of virulent Agrobacterium species has been routinely used (for review see Fraley et al. 1986). However, the host range of Agrobacterium restricts the plant species, which can be transformed using this vector system. In addition, all these methods depend on selection systems for recovery of transformants. Therefore a selection system has to be established first for plant species to be transformed. The microinjection technique is a direct physical approach, and therefore host-range independent, for introducing substances under microscopical control into defined cells without damaging them. These two facts differentiate this technique from other physical approaches, such as biolistic transformation and macroinjection (see chapters in this issue). In these other techniques, damaging of cells and random manipulation of cells without optical control cannot be avoided so far. In recent years microinjection technology found its application in plant sciences, whereas this technique has earlier been well established for transformation of animal tissue culture cells (Capecchi 1980) and the production of transgenic animals (Brin-ster et al. 1981, Rusconi and Schaffner 1981). Furthermore, different parameters affecting the DNA transfer via microinjection, such as the nature of microinjected DNA, and cell cycle stage, etc, have been investigated extensively in animal cells (Folger et al. 1982, Wong and Capecchi 1985), while analogous experiments on plant cells are still lacking.     

Statistical analysis for the spatial validity of a model to forecast the daily number of forest fires

In earlier papers a qualitative and quantitative model was developed for predicting the number of forest fires occurring per day. This model permits the forecast at 00.00 hours Universal Time Convention (UTC) of any day (d), the number of forest fires per day for a range of several days (d tod+5) over a particular region. Input data are the number of forest fires in the region during two preceding days (d–2 andd–1) and the type of day (real and evaluated from radiosonde ford–2,d–1,d and predicted from meteorological medium-range forecasts, i.e. of European Centre, ford+1,d+2,d+3,d+4 andd+5. As this model requires data obtained by radiosonde, particularly temperatures and geopotentials at 850 and 700 hPa and dew points (or specific humidity) at 850 hPa, this study investigates the spatial validity of the model in relation to the distance from the radiosonde station (RS). The highest quality forecast is obtained for the region immediately surrounding the RS, and diminishes with increasing distance from it, this being due to the data obtained from the RS not being representative of the atmospheric column over the region. Hence, the derivation of the critical distance for a particular quality level of measurement. Conversely, fixed quality level implies a specific separation between RS and the region for the prediction, with a higher predictive quality implying a shorter distance.     

Isolation of Propionibacterium acnes from central nervous system infections

Propionibacterium acnes is a common skin colonizer and its involvement in central nervous system (CNS) infections may be related with previous neurosurgical procedures. P. acnes was isolated in pure or mixed cultures from ten patients with CNS infections during a 5-year period. The clinical presentation, treatment and outcome were retrospectively reviewed. Nine out of 11 patients had CNS infections after a neurosurgical procedure. The clinical presentation was: brain abscess (five patients), subdural or epidural empyema (four patients) and shunt meningitis (one patient). Three patients had also secondary meningitis. All patients received antibiotic therapy and all abscesses and empyemas were drained. The patient with shunt meningitis cured without catheter removal. Only one patient with a brain abscess by P. acnes died, but several months thereafter and as a consequence of a Gram-negative superinfection. P. acnes is a pathogen for the CNS and infections must be surgically managed under adequate antibiotic treatment.     

Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice.

Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full-length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF-2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.