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PubMed2002

Primary epithelioid sarcoma of the dura: case report.

OBJECTIVE AND IMPORTANCE: Epithelioid sarcomas are rare mesenchymal neoplasms that occur most often in the extremities of young adults. Despite isolated reports of epithelioid sarcomas arising in the head and neck region, these lesions have not been described previously, to our knowledge, in the central nervous system. CLINICAL PRESENTATION: We present the case of an 18-year-old woman with a unique dural sarcoma that arose in the right frontotemporal region. As visualized on magnetic resonance imaging studies, the 4.5-cm tumor focally traversed the cranium to penetrate the galea, the temporal muscle, and subcutaneous tissue. No brain invasion was noted. INTERVENTION: Despite gross total removal and postoperative radiotherapy (59 Gy), a large recurrence was noted 5 months after surgery. Histologically, the partly necrotic tumor consisted of epithelioid and spindle cells showing widespread vimentin and variable cytokeratin as well as epithelial membrane antigen immunoreactivity. Ultrastructurally, the cohesive cells featured various organelles, intermediate filaments, junctions, and filopodia-containing intercellular spaces. CONCLUSION: With the inclusion of epithelioid sarcoma, the spectrum of central nervous system sarcomas continues to expand.

Adolescent↗
PubMed2001

Multiple-point and multiple-time correlation functions in a hard-sphere fluid.

A recent mode-coupling theory of higher-order correlation functions is tested on a simple hard-sphere fluid system at intermediate densities. Multiple-point and multiple-time correlation functions of the densities of conserved variables are calculated in the hydrodynamic limit and compared to results obtained from event-based molecular dynamics simulations. It is demonstrated that the mode-coupling theory results are in excellent agreement with the simulation results provided that dissipative couplings are included in the vertices appearing in the theory. In contrast, simplified mode-coupling theories in which the densities obey Gaussian statistics neglect important contributions to both the multiple point and multiple-time correlation functions on all time scales.

Journal Article↗
PubMed1983

Structural conservation in globular proteins.

Some well sequenced classes of homologous proteins have been analysed in the light of their representative tertiary structures to reveal the nature of structural conservation during protein evolution. Within 'the sphere of influence' around conserved residue sites preferential association of other conservative sites has been observed to be a feature of natural selection valid for all residue types. An information theory approach evolved to examine residue variability reveals that even some non-conservative sites scaffold clusters of high biochemical specificity and intermediate folding units.

Amino Acid Sequence↗
PubMed2004

Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus.

Steroid hormones are regulators of adult hippocampal neurogenesis and are central to hypotheses regarding adult neurogenesis in age-related and psychiatric disturbances associated with altered hippocampal plasticity--most notably dementias and major depression. Using immunohistochemistry, we examined the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors during adult hippocampal neurogenesis. In young mice only 27% of dividing cells in the subgranular zone expressed GR, whereas 4 weeks after division 87% had become positive for GR and MR. GR was expressed by 50% of the radial glia-like type-1 and type-2a progenitor cells, whereas MR was expressed only by mature calbindin-positive granule cells. Doublecortin-positive neuronal progenitor cells (type-2b) and early postmitotic calretinin-positive neurons were devoid of GR and MR expression. Fifty per cent of the intermediate type-3 cells showed GR expression, possibly reflecting cells terminating maturation. Thus, all subpopulations of dividing precursor cells showed an identical receptor profile (50% GR, no MR), except for type-2b cells, which expressed neither receptor. There was also no overlap between calretinin and GR early postnatally (P8) or after physical activity or exposure to an enriched environment, both of which are potent neurogenic stimuli. In contrast, in old age calretinin-positive young neurons became GR and MR positive, suggesting increased steroid sensitivity. Age also increased the expression of GR in type-1 and type-2a precursor cells. Other intermediates were so rare in old age that they could not be studied. This course and variability of receptor expression in aging might help to explain differential vulnerability of adult neural precursor cells to corticoid-mediated influences.

Animals↗
PubMed1996

Enumeration of viable bacteria in the marine pelagic environment.

The low percentage of living bacteria commonly obtained when comparing viable counts with total direct counts in seawater could be due more to inappropriate techniques for appreciating the growth ability of living cells than to unadapted culture conditions. The most-probable-number counts in filtered seawater cultures and the microscopic counts of 4(prm1),6-diamidino-2-phenylindole (DAPI)-stained aggregate-forming units grown on black polycarbonate filters appeared significantly correlated to the direct counts. Both these techniques show that in the superficial and intermediate water masses, the living cells may constitute an important (frequently higher than 20%) but highly variable part of the total populations. These viable counts appear more realistic than the conventional CFU counts, which provide only 0.001 to 0.2% of the total counts.

Journal Article↗
PubMed1989

The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein.

Interchromosomal translocations within lymphoid neoplasms frequently involve the antigen receptor genes. We cloned the breakpoints of the t(11;14)(p15;q11) in a CD3-negative T-cell acute lymphoblastic leukemia cell line (RPMI 8402) in order to identify new genes potentially involved in T-cell neoplasia. An extensive comparison of both breakpoints and their germ line counterparts indicated that an inadvertant recombinase-mediated break at chromosome segment 11p15 recombined with the delta T-cell receptor at 14q11. The derivative 11 breakpoint resembles a coding joint in which 11p15 rather than a variable region was introduced 5' to a D delta 1 D delta 2 J delta 1 intermediate rearrangement. Conversely, the derivative 14 breakpoint corresponds to a signal joint between the 5' heptamer-spacer-nonamer recombinational signal of D delta 1 and an isolated heptamer at 11p15. Multiple, apparently distinct transcripts were found flanking both breakpoints of 8402. RNAs of 3.5, 4.4, 1.4, and 8.0 kilobases originating from either side of the derivative 14 breakpoint were highly expressed in 8402 compared with other cells. This suggests that this translocation deregulated multiple genes and provides the opportunity to assess any multifactorial contribution they may have to malignancy. We cloned and sequenced several cDNAs representing the 1.4-kilobase transcript (termed Ttg-1 [T-cell translocation gene 1]) from an 8402 library. The predicted protein of 156 amino acids contained two internal repeats which could potentially form zinc fingers.

Amino Acid Sequence↗
PubMed1988

Effect of high fat consumption on cell proliferation activity of colorectal mucosa and on soluble faecal bile acids.

To assess the effect of fat consumption on the proliferation of the rectal mucosa, 30 normal volunteers (22 to 71 years) were randomly allocated to three groups: (a) basal low fat diet containing 30 g of fat per day; (b) the basal diet with doses of 30 g corn oil taken with each of the three meals: 120 g fat/day; (c) the basal diet with one dose of 90 g corn oil after the last meal: 120 g fat/day. Rectal biopsies were taken 15 cm from the anal verge after five days on the diets and mucosal cell proliferation was measured by labelling index (LI). The LI was significantly (p less than 0.01) higher in group (c) (9.2) than in group (a) (5.9), with group (b) intermediate (6.8). In multiple stepwise regression analysis, the data were best fitted with age and the variable indicating fat consumed as a bolus as predictors of LI (r2 = 0.39, p less than 0.001). In separate analyses the regression coefficient with age in the fat bolus group was 0.23, p less than 0.001. There was some tendency towards lower bile acids in the faecal water in group (a) than in groups (b) and (c) following the diets and between the bile acids and LI (for lithocholic acid r = 0.48, p = 0.01). These data show that dietary fat given as a bolus can lead to an increase in the proliferation of human colonic cells, possibly as a consequence of raised levels of cytotoxic acidic lipids in the faecal stream.

Adult↗
PubMed2004

Effects of continuous water flow on the swelling properties of polyelectrolyte hydrogels.

We report the swelling behavior of a polyelectrolyte copolymer gel in water, which consists of poly(N-isopropylacrylamide) and sodium acrylate. The diameter of the cylindrical gels was measured at room temperature under a continuous flow of solvent water (equivalent to an infinite amount of water; open system). After a sufficient water flow, the diameter of the gel in the limited amount of water (closed system) was measured as a function of the temperature. The gel in the open system was found to shrink as a result of the continuous flow of water, and the gel in the closed system began to swell again at the phase transition point by increasing the temperature. The effects of the degree of initial ion exchange by the water flow on the macroscopic swelling behavior were discussed in terms of the exchange of counterions (the ion dissociation of carboxyl groups) and of the creation and destruction of intermolecular forces (hydrogen bonding). It was concluded that the amount of solvent water determines the environmental variables, such as the pH and ion concentration, which affects the swelling properties of polyelectrolyte hydrogels; intermediate re-swollen states can be observed in a closed system.

Journal Article↗
PubMed1990

Differential localization of two glucose transporter isoforms in rat kidney.

The localization of two glucose transporter isoforms was mapped in the rat kidney: the high-Michaelis constant (Km; 15-20 mM) low-affinity "liver" transporter and the low-Km (1-2 mM) high-affinity "erythroid/brain" transporter. Both are basolateral membrane proteins, but the liver transporter was present exclusively in the S1 part of the proximal tubule, whereas the erythroid/brain transporter was expressed at variable levels in different nephron segments. Staining intensity was low in the straight proximal tubule (S3), intermediate in the medullary thin and thick ascending limbs, and highest in connecting segments and collecting ducts. In the collecting duct, the erythroid/brain glucose transporter was expressed at the highest level in intercalated cells; less was present in principal cells. In the papilla, only intercalated cells expressed this transporter isoform. These results suggest specific involvements of each transporter isoform in transepithelial glucose reabsorption by different segments of the proximal tubule. They also indicate that while the liver glucose transporter is present in gluconeogenic cells, there is a good correlation between the level of expression of the erythroid/brain glucose transporter and the glycolytic activity of the different nephron segments.

Animals↗
PubMed2002

Reconstructed skin kits: reproducibility of cutaneous irritancy testing.

The aim of this study was to determine the reproducibility of data obtained from in vitro irritation testing using three industrial reconstructed human epidermis models, EpiDerm, Episkin and SkinEthic, and one in-house model developed at Wella/Cosmital. A common protocol was established based on the measurement of cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and of extracellular release of proinflammatory mediators and cytosolic enzymes after a range of exposure times to sodium lauryl sulfate (SLS). This time course protocol was applied to 6 different batches of each skin model using triplicate tissue cultures per test condition. The parameters analyzed for intra- and inter-batch reproducibility were the cell viability determined as MTT reduction capacity and the ET-50 values in the 6 batches, as well as the release of the cytokine IL-1alpha and of the cellular enzymes LDH and GOT in 3 batches only. The MTT viability results showed that EpiDerm was the most resistant to the SLS treatment and at the same time the most reproducible model, SkinEthic was the most sensitive to SLS and the least reproducible, and Episkin and the Cosmital model were intermediate. Measurements of IL-1alpha release showed a relatively high intra- and inter-batch variability in all the skin models. It was not possible to detect the extracellular release of the enzymes LDH and GOT in the Episkin assay medium. With the 3 other models, the release of LDH and GOT varied in about the same range as that of IL-1alpha. For all the parameters in this study, the inter-batch variability was generally greater than the intra-batch variability. A possible reduction in the number of batches and replicates for future applications in routine irritancy testing is discussed on the basis of the results obtained using 6 batches in triplicate.

Humans↗
PubMed1994

Stages of change in adopting healthy diets: fat, fiber, and correlates of nutrient intake.

The stages of change construct, which addresses the readiness to change, has only recently been applied to dietary behavior, such as fat consumption. This article describes the application of the stages of change construct to dietary fat and fiber consumption and examines the association of dietary stages to eating practices and related demographic and psychosocial factors in a large, geographically diverse population of workers. We present results from the baseline survey of 17,121 employees in the Working Well Trial. We assessed stage from an algorithm based on seven items and measured dietary intake with an 88-item food frequency questionnaire. Findings indicated that a greater proportion of the population has actively tried to reduce fat intake than to consume more fiber. Stage of change was associated with fat, fiber, and fruit and vegetable intake in a stepwise manner, as predicted. In multivariate analyses that controlled for demographic characteristics, stage of change predicted between 8 and 13% of the variance in dietary intake, and more than demographic variables. These findings have implications for the design of nutrition interventions and for the evaluation of intermediate outcomes.

Adult↗
PubMed2003

Effects of willow hybridisation and simulated browsing on the development and survival of the leaf beetle Phratora vitellinae.

BACKGROUND: Interspecific hybridisation is common between many plant species and causes rapid changes in a variety of plant characters. This may pose problems for herbivores because changes in recognition characters may be poorly correlated with changes in quality characters. Many studies have examined different systems of hybrids and herbivores in attempts to understand the role of hybridisation in the evolution of plant resistance. The results from different systems are variable. Studies of hybrids between Salix caprea (L., Salicaceae) and S. repens show that they are intermediate between the two parental species in most resistance characters. However, a plants herbivore resistance depends also on its biotic and abiotic environment. Important biotic factors that may influence plant growth and plant chemistry include the interactions between different herbivores that occur through their exploitation of common host plants. Although the effects on plants of previous herbivory are likely to be strongly affected by environmental conditions, they are also species-specific. Damage may therefore have different effects on hybrids than on their parental species, and this could influence the performance of herbivores on pure and hybrid species of plants. To evaluate the effects of hybridisation on insect performance, the development and survival rates of Phratora vitellinae (L. 1758, Coleoptera: Chrysomelidae) larvae on pure S. repens, pure S. caprea and Fl hybrids of the two species was monitored. Further, to examine the effect of herbivorous mammals on the performance of the larvae, plants were damaged to simulate winter foraging by voles or spring leaf stripping by moose. RESULTS: The results show that development rates were highest on S. repens and equally low on S. caprea and the Fl hybrid. In addition, development of the plants treated to simulate mammalian herbivore damage was slower than that of corresponding controls. CONCLUSIONS: The results of this experiment suggest that P. vitellinae has a higher development rate, and thus probably higher performance, on species with high concentrations of phenolic glucosides. Therefore, it would be of adaptive benefit for P. vitellinae females to have an ovipositional preference for S. repens, compared to S. caprea and intermediate preference for Fl hybrids. The faster development observed on S. repens supports the hypothesis that P. vitellinae obtains additional adaptive benefits from phenolic glucosides beyond protection against predators. Therefore, it is important to consider further factors, such as damage caused by other herbivores, when studying this hybrid complex.

Adaptation, Physiological↗
PubMed2005

Ecomorphology of the external flight apparatus of blackcaps (Sylvia atricapilla) with different migration behavior.

An analysis of the external flight apparatus of 700 blackcaps from eight different populations (sedentary to long-distance migrators) is presented. With increasing migration distances of populations, (1) wing length, aspect ratio, and wing pointedness increase; (2) wing load decreases; (3) slots on the wing tips become relatively shorter; (4) the alula tends to be shorter in relation to wing length; and (5) the tail is shorter in relation to wing length. Although body mass increases from southern to northern populations, changes in wing length and wing area are two to three times larger than expected for simple isometric relationships. Regarding the aerodynamic background of these changes, it can be stated that traits for energy-effective flight are more strongly developed and traits for maneuverability are less developed in birds traveling longer distances, presumably as a consequence of trade-offs. Nonmigratory blackcaps from Madeira and the Cape Verde islands do not always show the traits we would expect in view of their sedentary behavior. This can be seen as a result of recent colonization of these islands by migrants or of selection by factors other than migration behavior. In migratory populations, changes between the first and the second set of primaries during first complete molt show almost the same pattern as the changes from nonmigratory to migratory populations. During molt of the primaries, blackcaps of nonmigratory populations do not show these changes. Hybrids between migrating and nonmigrating blackcap populations (Moscow and Madeira) showed intermediate values between parent populations in wing length, wing shape, and wing area; in the other variables they resembled either parent population.

Aging↗
PubMed1996

Significance of cytogenetic clonal evolution in chronic myelogenous leukemia.

PURPOSE: To describe the incidence and significance of clonal evolution patterns. PATIENTS AND METHODS: We analyzed 264 patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed clonal evolution between 1967 and 1993. RESULTS: The median survival time following clonal evolution was 19 months. Factors associated with worse survival (P < .01) were as follows: chromosome 17 abnormality or chromosomal translocations other than Ph, high percentage of abnormal metaphases, longer time to clonal evolution, and presence of other accelerated-phase features. A recursive partitioning technique (CART) identified different risk groups. The best group (37 patients; no chromosome 17 abnormality, abnormal metaphases < 16%, and interval to clonal evolution < or = 24 months) had an estimated median survival time of 54 months. The worst two groups included 27 patients with chromosome 17 abnormalities and > or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22 patients with other accelerated features and > or = 16% abnormal metaphases (estimated median survival time, 7 months). The intermediate group had an estimated median survival time that ranged from 13 to 24 months. Prior interferon therapy evaluated within risk groups showed a significant survival advantage only in the intermediate-risk group. A multivariate analysis showed similar results, and identified the following independent poor prognostic variables: chromosome 17 abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to clonal evolution (cutoff, 24 months), other accelerated-phase features, and no prior interferon therapy. Patients with none, one, two, three, or more of the first four features had median survivals times of 51, 24, 14, and 7 months, respectively. CONCLUSION: The prognostic significance of clonal evolution in CML is not uniform and is related to the specific abnormality, time to its development, its predominance in metaphases, and the presence of other accelerated features, and it may be modified by specific therapies.

Bone Marrow Transplantation↗
PubMed1996

The challenge of mechanism-based modeling in risk assessment for neurobehavioral end points.

The mathematical form for a dose-time-response model is ideally not just a convenience for summarizing or fitting a particular data set--it represents a hypothesis. The more this hypothesis reflects a mechanistically sophisticated view of the likely reality, the more it can lead to potentially informative validating or invalidating types of predictions about the results of real experiments and (in the long run) reasonably credible predictions outside the range of direct observations. This paper first reviews some distinctive features of the nervous system and neurotoxic responses and theoretically explores some basic quantitative implications of these features. Relationships are derived for how dose-response relationships for the inhibition of function should depend on the numbers of neurons in series or redundant parallel arrangements that are required or capable of performing the function. Previous work is reviewed in which some less nervous-system-specific features were the foci of quantitative risk-assessment modeling for specific neurotoxic end points. These include a) rates of repair of putatively reversible damage in the case of acrylamide; b) human interindividual variability in susceptibility to fetal/developmental effects in the case of methylmercury; and c) opportunities to use intermediate biomarkers to assist in integrated animal toxicological and epidemiologic investigations of the chronic cumulative risks posed by agents that contribute to neuronal loss with increasing age and pathology.

Behavior↗
PubMed2005

Molecular diagnosis of neurogenetic disorders involving trinucleotide repeat expansions.

There are more than 15 known neurogenetic disorders involving trinucleotide repeat expansion. Expanded repeats range from small expansions of 20-100 copies to larger expansions of up to several thousand units. These dynamic expansions result in variability in age of onset, degree of severity and clinical presentation. Individuals carrying alleles in the intermediate range, known as premutation alleles, are often asymptomatic, but can potentially transmit a further expanded allele to his/her offspring. For autosomal dominant adult-onset disorders, carriers are asymptomatic prior to disease onset. With current molecular tools, it is now possible to determine the presence and number of expanded repeats for accurate diagnosis, presymptomatic testing and carrier status screening. This review examines some of the current approaches for molecular diagnosis and discusses the issues unique to triplet repeat diseases.

Clinical Laboratory Techniques↗
PubMed2006

The pharmacogenetics of asthma therapy.

Asthma affects an estimated 300 million individuals worldwide, resulting in substantial morbidity, mortality, and health care utilization. The response to the three major classes of asthma therapy, beta-agonists, leukotriene antagonists, and inhaled corticosteroids, demonstrates wide inter-individual variability, with a significant number of non-responders. In addition, both asthma itself and the intermediate phenotypes of asthma that are measured in response to therapy, including the forced expiratory volume at one second (FEV1), are highly heritable. Both of these facts indicate that a significant portion of the therapeutic response to asthma may be determined by genetic factors. This review summarizes the asthma pharmacogenetics literature as it pertains to human studies, focusing on asthma pharmacogenetic phenotypes and human genetic association studies that have been published for response to each of the three major classes of asthma therapy. Of the four major classes of pharmacogenetic response, there is now evidence that genetic factors influencing the pharmacokinetics, the pharmacodynamics, and the disease modification of asthma therapies may form the basis of credible pharmacogenetic associations. Altogether, the available data indicate that an individual's likelihood of responding to a given therapy is influenced by genetics. Therefore, genetic testing may play a significant role in the care for individuals with asthma in the forseeable future.

Adrenal Cortex Hormones↗
PubMed1996

Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure. A possible link to increased cardiovascular mortality?

OBJECTIVE: Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin. RESEARCH DESIGN AND METHODS: We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin. RESULTS: Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction. CONCLUSIONS: Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.

Biomarkers↗