Showing papers by "Uppsala University published in 1993"

Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects

Abstract: From 1980 to 1985, 471 patients with resectable rectal and rectosigmoid cancer were randomly allocated to receive either preoperative short-term high-dose irradiation (25.5 Gy in one week) for all patients or prolonged postoperative radiotherapy (60 Gy in seven to eight weeks) only for patients with a Dukes B or C lesion. After a minimum follow-up of five years, the local recurrence rate was statistically significantly lower after preoperative than after postoperative radiotherapy (13 percent vs. 22 percent; P = 0.02). No difference in overall survival was noted (P = 0.5). To evaluate possible late side effects on the bowel, urinary bladder, or skin after surgery and additional preoperative or postoperative radiotherapy, all patients included in the randomized trial, together with 58 patients from a preceding pilot study with the same preoperative regimen, were studied in a prolonged follow-up program. The hospital files of all patients were re-examined. Of the patients who were carefully examined, 176 had a survival exceeding five years and 19 had a survival exceeding 10 years. Overall, 7 percent (33/464) either were operated upon or have had a radiologic diagnosis of small bowel obstruction: 14/255 (5 percent) after preoperative irradiation, 14/127 (11 percent) after postoperative irradiation, and 5/82 (6 percent) after surgery alone. The cumulative risk of developing a bowel obstruction was significantly increased after postoperative radiotherapy. Among the 98 patients alive after preoperative irradiation, significant morbidity from the bowel was noted in 11 patients, from the urinary bladder in two, and from the skin in six. In the postoperatively treated group of 34 patients, the bowel, urinary bladder, and skin morbidity were significant in five, two, and five patients, respectively. Corresponding morbidity in 44 nonirradiated patients was seen in five, one, and two patients, respectively. It is concluded that preoperative, short-term, high-dose radiotherapy decreases the local recurrence rate relative to postoperative radiotherapy, with no indications of increased late morbidity after a follow-up of 5 to 10 years.

Evolution of the Zfx and Zfy genes: rates and interdependence between the genes.

Abstract: A phylogenetic analysis of sex-chromosomal zinc-finger genes (Zfx and Zfy) indicates that the genes have not evolved completely independently since their initial separation. The sequence similarities suggest gene conversion in the last exon between the duplicated Y-chromosomal genes Zfy-1 and Zfy-2 in the mouse. There are also indications of conversion (or recombination) between the X- and Y-chromosomal genes in the crab-eating fox and in the mouse. The method for estimating synonymous and nonsynonymous substitutions is modified by incorporating the substitutions in the twofold-degenerate sites in a novel way. The estimates of synonymous substitutions support the generation-time hypothesis in that the obtained rates are higher in mice (by a factor of 4.7) than in humans and higher in the Y-chromosomal genes (by a factor of 1.9) than in the X-chromosomal genes.

Small-scale plant species turnover in a limestone grassland: the carousel model and some comments on the niche concept.

Abstract: This study reports on small-scale changes in the distribution of plant species in a 2.5 m2 plot of grazed, species- rich Veronica spicata - Avenula pratensis grassland on shal- low, dry, nutrient-poor soil in the Great Alvar area (Stora Alvaret) of southern Oland, southeastern Sweden. Multivari- ate analysis of 0.001 m2 and 0.25 m2 quadrats within the plot showed that there is little floristic variation without any trend in the plot. Average species richness varied little throughout the study period from 1986 to 1991 with 1986 averages of 7.0 on 0.001m2, 16.3 on 0.01 m2, and 26.1 on 0.25 m2. On 0.001 m2 the highest species number found was 12, on 0.01 m2, 27. However, cumulative species richness, i.e. species number in the first year plus new species appearing in later years (aver- aged over 40 quadrats) increased over the same period, on 0.001 m2 from 7.0 in 1986 to 14.9 in 1991, and on 0.01 m2

Glycosaminoglycans and the regulation of blood coagulation.

Abstract: Blood coagulation involves the sequential activation of a series of serine proteinases, which culminates in the generation of thrombin and subsequent thrombin-catalysed conversion of fibrinogen into insoluble fibrin (Furie and Furie, 1988). Inhibitory modulation of this process, of paramount physiological importance, is primarily achieved by two principally different mechanisms (Figure 1). The enzymes may be inactivated by serine proteinase inhibitors (known as 'serpins'), which act by formation ofstable 1 :1 molar complexes with their target enzymes (Travis and Salvesen, 1983). Alternatively, the so-called protein C pathway leads to inactivation of auxiliary coagulation proteins (factors V. and VIII.) by cleavage at distinct sites (Esmon, 1989; Dahlbaick, 1991). The prime site of regulation is the surface of vascular endothelial cells, which have been known to possess anticoagulant properties (Colburn and Buonassisi, 1982). These properties are particularly conspicuous in the microcirculation, with its high wall surface to blood volume ratio (Busch, 1984). The ability of certain sulphated polysaccharides, glycosaminoglycans, to interfere with blood coagulation has a long-standing record, as illustrated by the extensive clinical use of heparin as an antithrombotic agent (see Roden, 1989). The main effect of heparin (and of its relative, heparan sulphate) is to accelerate the inactivation of coagulation enzymes by the serpin antithrombin (Rosenberg, 1977; Bjork and Lindahl, 1982). A more complex picture emerged with the finding of an additional serpin, heparin cofactor II, which is 'activated' not only by heparin, but also by another glycosaminoglycan, dermatan sulphate, and which selectively inactivates thrombin (Tollefsen et al., 1982; Tollefsen, 1989). Remarkably, also the other major regulatory mechanism, the protein C pathway, involves a glycosaminoglycan-containing molecular species, since the protein C activation cofactor, thrombomodulin, turned out to be a proteoglycan with a functionally important, covalently bound glycosaminoglycan chain (Bourin and Lindahl, 1990; Bourin et al., 1990). In this Review we attempt to summarize our current understanding of glycosaminoglycan involvement in the regulation of blood coagulation.

Applied factor analysis in the natural sciences

Abstract: This graduate-level text aims to introduce students of the natural sciences to the powerful technique of factor analysis and to provide them with the background necessary to be able to undertake analyses on their own. A thoroughly updated and expanded version of the authors' successful textbook on geological factor analysis, this book draws on examples from botany, zoology, ecology, and oceanography, as well as geology. Applied multivariate statistics has grown into a research area of almost unlimited potential in the natural sciences. The methods introduced in this book, such as classical principal components, principal component factor analysis, principal coordinate analysis, and correspondence analysis, can reduce masses of data to manageable and interpretable form. Q-mode and Q-R-mode methods are also presented. Special attention is given to methods of robust estimation and the identification of atypical and influential observations. Throughout the book, the emphasis is on application rather than theory.

The birth of the giant component

Abstract: Limiting distributions are derived for the sparse connected components that are present when a random graph on n vertices has approximately 1/2n edges. In particular, we show that such a graph consists entirely of trees, unicyclic components, and bicyclic components with probability approaching √2/3 cosh √5/18 ≈ 0.9325 as n∞. The limiting probability that it is consists of trees, unicyclic components, and at most one another component is approximately 0.9957; the limiting probability that it is planar lies between 0.987 and 0.9998. When a random graph evolves and the number of edges passes 1/2n, its components grow in cyclic complexity according to an interesting Markov process whose asymptotic structure is derived. The probability that there never is more than a single component with more edges than vertices, throughout the veolution, approaches 5 π/18 ≈ 0.8727. A “uniform” model of random graphs, which allows self-loops and multiple edges, is shown to lead to formulas that are substanitially simpler than the analogous formulas for the classical random graphs of Erdos and Renyi. The notions of “excess” and “deficiency,” which are significant characteristics of the generating function as well as of the graphs themselves, lead to a mathematically attractive structural theory for the uniform model. A general approach to the study of stopping configurations makes it possible to sharpen previously obtained estimates in a uniform manner and often to obtain closed forms for the constants of interest. Empirical results are presented to complement the analysis, indicating the typical behavior when n is near 2oooO. © 1993 John Wiley & Sons, Inc.

Verifying programs with unreliable channels

Abstract: The verification of a particular class of infinite-state systems, namely, systems consisting of finite-state processes that communicate via unbounded lossy FIFO channels, is considered. This class is able to model, e.g., link protocols such as the Alternating Bit Protocol and HDLC. For this class of systems, it is shown that several interesting verification problems are decidable by giving algorithms for verifying: the reachability problem (whether a finite set of global states is reachable from some other global state of the system); the safety property over traces, formulated as regular sets of allowed finite traces; and eventuality properties (whether all computations of a system eventually reach a given set of states). The algorithms are used to verify some idealized sliding-window protocols with reasonable time and space resources. >

The birth of the giant component

Abstract: Limiting distributions are derived for the sparse connected components that are present when a random graph on $n$ vertices has approximately $\half n$ edges. In particular, we show that such a graph consists entirely of trees, unicyclic components, and bicyclic components with probability approaching $\sqrt{2\over 3} \cosh\sqrt{5\over 18}\approx0.9325$ as $n\to\infty$. The limiting probability that it consists of trees, unicyclic components, and at most one other component is approximately 0.9957; the limiting probability that it is planar lies between 0.987 and 0.9998. When a random graph evolves and the number of edges passes $\half n$, its components grow in cyclic complexity according to an interesting Markov process whose asymptotic structure is derived. The probability that there never is more than a single component with more edges than vertices, throughout the evolution, approaches $5\pi/18\approx0.8727$. A ``uniform'' model of random graphs, which allows self-loops and multiple edges, is shown to lead to formulas that are substantially simpler than the analogous formulas for the classical random graphs of Erd\H{o}s and R\'enyi. The notions of ``excess'' and ``deficiency,'' which are significant characteristics of the generating function as well as of the graphs themselves, lead to a mathematically attractive structural theory for the uniform model. A general approach to the study of stopping configurations makes it possible to sharpen previously obtained estimates in a uniform manner and often to obtain closed forms for the constants of interest. Empirical results are presented to complement the analysis, indicating the typical behavior when $n$ is near 20000.

Sexual selection and the temporal separation of reproductive events: sperm storage data from reptiles, birds and mammals

Abstract: The duration of sperm storage by females differs markedly between reptiles (maximum: 2555 d [7 years] and birds (maximum: 117 d), with mammals showing both very short (

Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments.

Abstract: New data on the permeabilities of hydrophilic markers in two commonly used in vitro models, i.e., excised intestinal segments from the rat and monolayers of Caco-2 cells, are presented. The results are compared to human in vivo data. Two groups of hydrophilic marker molecules were tested: (1) monodisperse polyethylene glycols of molecular weights ranging from 194 to 502 g/mol and (2) a heterogeneous group of molecules consisting of urea, creatinine, erythritol, and mannitol (60–182 g/mol). The permeabilities of the marker molecules showed a nonlinear dependence on the molecular weight and decreased in the order rat ileum > rat colon > Caco-2 cells. Surprisingly, the polyethylene glycols permeated more easily than the other marker molecules, indicating that characteristics other than molecular weight, e.g., the flexibility of the structure, may also be important for permeation through the membrane. Comparisons with the published permeability profiles of polyethylene glycols in human intestinal segments in vivo (i.e., calculated permeability coefficients as a function of molecular weight) indicate that the human intestine is more permeable than the in vitro models. However, the permeability profiles of the corresponding segments in the human intestine and the in vitro models were comparable. Thus, good correlations were established between permeabilities of the human ileum and rat ileum and between those of human colon, rat colon, and the Caco-2 cells. We conclude that the paracellular absorption in humans can be studied mechanistically in these in vitro models.

On the automatic nature of phobic fear: conditioned electrodermal responses to masked fear-relevant stimuli.

Abstract: Normal subjects (n = 64) were exposed either to pictures of snakes and spiders or to pictures of flowers and mushrooms in a differential conditioning paradigm in which one of the pictures signaled an electric shock. In a subsequent extinction series, these stimuli were presented backwardly masked by another stimulus for half of the subjects, whereas the other half received non-masked extinction. In support of a hypothesis that suggests that nonconscious information-processing mechanisms are sufficient to activate responses to fear-relevant stimuli, differential skin conductance response to masked conditioning and control stimuli was obvious only for subjects conditioned to fear-relevant stimuli. These results were replicated in a second experiment (n = 32), which also demonstrated that the effect was unaffected by which visual half-field was used for stimulus presentation.

Interaction Between Chemicals and Melanin

Abstract: Various drugs and other chemicals, such as organic amines, metals, polycyclic aromatic hydrocarbons, etc., are bound to melanin and retained in pigmented tissues for long periods. The physiological significance of the binding is not evident, but it has been suggested that the melanin protects the pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which then are slowly released in nontoxic concentrations. Long-term exposure, on the other hand, may build up high levels of noxious chemicals, stored on the melanin, which ultimately may cause degeneration in the melanin-containing cells, and secondary lesions in surrounding tissues. In the eye, e.g., and in the inner ear, the pigmented cells are located close to the receptor cells, and melanin binding may be an important factor in the development of some ocular and inner ear lesions. In the brain, neuromelanin is present in nerve cells in the extrapyramidal system, and the melanin affinity of certain neurotoxic agents may be involved in the development of parkinsonism, and possibly tardive dyskinesia. In recent years, various carcinogenic compounds have been found to accumulate selectively in the pigment cells of experimental animals, and there are many indications of a connection between the melanin affinity of these agents and the induction of malignant melanoma.

Masking the face: Recognition of emotional facial expressions as a function of the parameters of backward masking

Abstract: Four experiments are reported investigating recognition of emotional expressions in very briefly presented facial stimulus. The faces were backwardly masked by neutral facial displays and recognition of facial expressions was analyzed as a function of the manipulation of different parameters in the masking procedure. The main conclusion was that stimulus onset asynchrony between target and mask proved to be the principal factor influencing recognition of the masked expressions. In general, confident recognitions of facial expressions required about 100-150 msec, with shorter time for happy than for angry expressions. The manipulation of the duration of both the target and the mask, by itself, had only minimal effects.

Fracture of the distal forearm as a forecaster of subsequent hip fracture: A population-based cohort study with 24 years of follow-up

Abstract: Objective: To determine the long-term risk of hip fracture following fracture of the distal forearm.

Female control of paternity.

Abstract: Of the two components of sexual selection, female choice is much less obvious than male—male competition, and hence has always been considered to be of secondary importance. However, recent field observations and new theory have brought about a radical change of emphasis. It now appears that although a female's choice of who fathers her offspring often occurs in a subtle manner, it may be widespread and take place through a variety of behavioural and physiological mechanisms, including the manipulation of male behaviour and the selection of sperm within the female reproductive tract.

The Swedish Wage Stucture: The Rise and Fall of Solidarity Wage Policy?

Abstract: Wage inequality in Sweden declined precipitously during the 1960s and the 1970s. There was a sharp reduction in overall wage dispersion and in the relative earnings advantage of highly-educated workers, a marked narrowing of wage differences between men and women, and a trend increase in youth relative wages. There was also a substantial narrowing of wage differentials among workers within broad occupational and educational groups. The trend decline in wage inequality was broken in the 1980s. Wage differentials along several dimensions have widened modestly from the rnid-1980s to the early 1990s. Much of the Swedish discussion has taken it for granted that the pay compression has been driven by the egalitarian ambitions of strong and coordinated trade unions. Our analysis of the Swedish wage structure suggests that institutions are only part of the story. We show that conventional demand and supply factors can go a substantial way towards explaining some key relative wage movements in Sweden.

Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route.

Abstract: The effects of the absorption enhancer sodium caprate on human intestinal epithelial cells were investigated using Caco-2 cell monolayers. The effects on epithelial integrity and drug transport are dependent on time and concentration and are decreased by Ca2+, most likely through the formation of Ca22+ soaps. Morphological data indicate that exposure to sodium caprate results in cytoskeletal changes and in structural alterations of the tight junctions in the form of dilatations, while the effects on the apical cell membranes are limited. We conclude that sodium caprate increases the absorption of drugs mainly by the paracellular route.

Diabetes and Embryonic Malformations: Role of Substrate-Induced Free-Oxygen Radical Production for Dysmorphogenesis in Cultured Rat Embryos

Abstract: The aim of this study was to evaluate the role of free-oxygen radicals in the embryonic maldevelopment of diabetic pregnancy. Rat embryos cultured in vitro during early organogenesis showed growth retardation and severe malformations after exposure to 50 mM glucose, 3 mM PYR, 10 mM HBT, or 3 mM KIC. Combinations of 25 mM glucose, 2.5 mM HBT, and 1 mM KIC also elicited embryonic growth retardation and malformations. The deleterious effects on embryonic development by all agents were alleviated by addition of SOD to the culture media, which yielded increased enzyme activity in the embryos and their membranes. The endogenous SOD activity also increased in embryos subjected to a high concentration of glucose or PYR in the culture medium. Addition of the mitochondrial PYR transport inhibitor CHC to the culture media blocked the dysmorphogenesis caused by glucose and PYR, but was without effect on the teratogenic actions of HBT and KIC. These findings implicate the embryonic mitochondria as a likely site for enhanced substrate-induced production of free-oxygen radicals mediating the teratogenic effect of a diabetic environment. In particular, the teratogenic process in diabetic pregnancy may depend on an increased production of free-oxygen radicals in immature embryonic mitochondria in response to a metabolic overload. This notion implies that every oxidative substrate entering the mitochondrial metabolism in excess may induce embryonic malformations and emphasizes the need for an extended metabolic surveillance of pregnant diabetic women. Consequently, optimal metabolic control should aim at normalizing the maternal serum concentrations of all possible oxidative substrates.