Breast cancer angiogenesis: therapy target and prognostic factor.
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Biomedical subjects
Publications and source records attributed to P Scott.
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The aim of this work was to investigate the role of fructose 2,6-bisphosphate (Fru 2,6-P2) during photosynthesis. The level of Fru 2,6-P2 in tobacco plants was elevated by the introduction of a modified mammalian gene encoding 6-phosphofructo-2-kinase (6-PF-2-K). Estimates of the metabolite control coefficient (C) for Fru 2,6-P2 levels in response to increased 6-PF-2-K activity, suggest that small increases in 6-PF-2-K activity have little effect upon steady-state Fru 2,6-P2 levels (C = +0.08 for a 0-58% increase in 6-PF-2-K activity). However, larger changes resulted in dramatic rises in Fru 2,6-P2 levels (C = +3.35 for 206-268% increase in 6-PF-2-K activity). Transgenic plants contained Fru 2,6-P2 levels in the dark that ranged from 104 to 230% of the level in wild-type tobacco. Plants with altered levels of Fru 2,6-P2 were used to determine the effects of this signal metabolite upon carbohydrate metabolism during the initial phase of the light period. Here we provide direct evidence that Fru 2,6-P2 contributes to the regulation of carbon partitioning in tobacco leaves by inhibiting sucrose synthesis.
We present the first case in literature of a chorionic carcinoma following in vitro fertilisation. Until now, only two case reports of hydatidiforme mole following IVF are published.
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A case of obstructive jaundice secondary to a neurofibroma in the common hepatic duct is presented. The histological appearance was that of a plexiform neurofibroma. The clinicopathological features are discussed.
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A significant reduction in challenge worm survival occurred when BALB/cBYJ mice were vaccinated against Onchocerca volvulus infective third stage larvae (L3) by using irradiated O. volvulus L3. Challenge infections consisted of L3 implanted in diffusion chambers, which were used as a means to contain, and thus efficiently recover, the larvae from the host. The goal of the present study was to describe the mechanism of immune-mediated killing of O. volvulus L3 in diffusion chambers in mice. Direct contact between host cells and parasites was required for killing of larvae in immunized hosts. To define the mechanism of immune-mediated killing in this system, the time of influx of cells and cytokines into the infection site was compared with the time challenge infections were killed. The only cell type that was found to increase in diffusion chambers in immunized mice was eosinophils; maximal levels of eosinophils were coincident with the time of parasite killing. IL-5 was found in diffusion chambers of immunized mice coincident with the time of parasite killing; IL-5 was not found in diffusion chambers recovered from control mice. Significant levels of IFN-gamma were absent in the diffusion chambers of both groups. Immunized mice were treated with mAb to eliminate IL-5 or IL-4 to assess the role these cytokines or their by-products play in larval killing. Elimination of either IL-5 or IL-4 significantly reduced the protective effects of vaccination against larval O. volvulus.
Protection induced by vaccination depends on the capacity of the vaccine to elicit an appropriate immune response. In leishmaniasis, protection requires leishmanial-specific CD4+ T helper (TH) cells. Vaccination of BALB/c mice with leishmanial antigens and interleukin-12 (IL-12) promoted the development of leishmanial-specific CD4+ TH1 cells. These mice were resistant to subsequent infection with Leishmania major. Thus, IL-12 is an effective adjuvant for the initiation of protective cell-mediated immunity against leishmaniasis and may be an important component in other vaccines that need to induce cell-mediated immunity.
Experimental infections of mice with the protozoan parasite Leishmania major provide an excellent model for defining the conditions required for generation of CD4+ Th1 and Th2 cells in vivo. Since interleukin-12 (IL-12) has been implicated in the development of Th1 cells, we investigated whether L. major stimulates IL-12 production in vitro or in vivo. Surprisingly, macrophages cultured in vitro failed to produce IL-12 following L. major infection. In contrast, lymph node cells from C3H mice infected for 2 days with L. major produced elevated levels of IL-12. In order to determine if the inability to stimulate IL-12 production was limited to in vitro infections, we infected macrophages in vivo by inoculating L. major into the peritoneal cavity. Peritoneal cells isolated 24 h later exhibited a significant increase in the number of cells producing IL-12. In addition, supernatants harvested from these cells following culture contained elevated levels of IL-12. These data indicate that L. major infection induces increased IL-12 production in mice.
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Although there has been nearly complete agreement in the scientific community that Monte Carlo techniques represent a significant improvement in the exposure assessment process, virtually all state and federal risk assessments still rely on the traditional point estimate approach. One of the rate-determining steps to a timely implementation of Monte Carlo techniques to regulatory decision making is the development of "standard" data distributions that are considered applicable to any setting. For many exposure variables, there is no need to wait any longer to adopt Monte Carlo techniques into regulatory policy since there is a wealth of data from which a robust distribution can be developed and ample evidence to indicate that the variable is not significantly influenced by site-specific conditions. In this paper, we propose several distributions that can be considered standard and customary for most settings. Age-specific distributions for soil ingestion rates, inhalation rates, body weights, skin surface area, tapwater and fish consumption, residential occupancy and occupational tenure, and soil-on-skin adherence were developed. For each distribution offered in this paper, we discuss the adequacy of the database, derivation of the distribution, and applicability of the distribution to various settings and conditions.
One hundred and two consecutive patients undergoing upper gastrointestinal endoscopy were tested for H. pylori by a rapid urease test, using antral biopsy specimens. There were 60 men (mean age 54 yrs) and 42 women (mean age 49 yrs). Fifty-six patients (55%) were positive for H. pylori. Of male patients, 36 (60%) and of female patients, 20 (48%) tested positive. Sixty-eight per cent of patients with antral gastritis, 65% with duodenal ulcer and 60% with gastric ulcer had H. pylori. Thirty-nine patients (70%) positive for H. pylori were from major urban areas, and 17 (30%) were from rural areas of Jamaica. In patients without H. pylori, 61% and 39% were from urban and rural areas, respectively. Forty-four patients (79%) with H. pylori and 40 (87%) without H. pylori had piped water in their homes. Ninety-three per cent of all patients had electricity and 88% had refrigeration. There was no difference between patients positive or negative for H. pylori with regard to the use of alcohol, marijuana or tobacco. There was also no difference between both groups in exposure to domestic animals in the home environment. H. pylori is associated with antral gastritis and peptic ulcer disease in Jamaican patients. There are no specific environmental or social factors that seem to predispose to infection.
Everyone involved in orthognathic surgery would like some means of identifying the so-called psychologically "bad risk" patient. This article reviews a number of techniques and concludes that, not only is this identification impossible to achieve, but it is probably unnecessary since most patients do well psychologically after orthognathic surgery regardless of their preoperative psychological profile. The few psychologically dissatisfied patients cannot be accurately identified preoperatively.
Infection of mice with the protozoan Leishmania major provides an excellent model to define the factors involved in T helper (Th) subset development, since Th1 cells confer protection in resistant strains of mice, whereas Th2 cells are associated with the fatal outcome of susceptible mice. We previously found that interferon gamma (IFN-gamma) was required for Th1 cell development after infection of mice with L. major. In this report, we evaluate the contribution of natural killer (NK) cells to IFN-gamma levels early in L. major infection. NK cell activity was higher in resistant C3H/HeN mice than in susceptible BALB/c mice during the first week of infection, and removal of NK cells significantly decreased IFN-gamma levels and promoted interleukin 4 (IL-4) production in both the draining lymph nodes and spleen. IFN-gamma production by NK cells required the presence of CD4+ T cells or IL-2, but not CD8+ T cells. Enhanced disease, as measured by parasite numbers and lesion development, was observed in NK cell-depleted mice. Furthermore, a comparison of the NK cell response and the subsequent parasite burden in several inbred strains of mice demonstrated that NK cells mediate early resistance to L. major. Together, these data indicate that the stimulation of NK cells, through the production of IFN-gamma, plays an important role in initiating Th1 cell differentiation in leishmaniasis and in controlling early resistance to L. major.
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The complexity and chronicity of parasitic infections have obscured the identification of biologically relevant antigens. Analysis of the T cell receptor repertoire used by mice infected with Leishmania major revealed the expansion of a restricted population of CD4+ cells. These cells expressed the V alpha 8-J alpha TA72, V beta 4 heterodimer in both progressive infection and protective immunity and across several major histocompatibility haplotypes. Thus, the same immunodominant parasite epitope drives the disparate outcomes of this infectious process, suggesting that candidate vaccine antigens selected by screening of immune individuals may be capable of exacerbating disease in genetically susceptible individuals.
Vitamin C is a key antioxidant in human blood plasma and hence could influence the outcome of conditions such as acute pancreatitis in which oxidative stress apparently plays a pivotal role. The concentrations of vitamin C and its immediately bioavailable form, ascorbic acid, in fasting plasma samples from 30 healthy volunteers were compared with those in admission samples from 29 consecutive patients with acute pancreatitis and 27 patients with other acute abdominal crises. Median (range) levels of vitamin C and ascorbic acid, respectively, were 15 (6.3-19) and 12 (4.5-18) micrograms/ml in the control group, 2.8 (0.3-10) and < 0.5 (< 0.5-6.0) micrograms/ml in patients with acute pancreatitis, and 3.7 (0.6-15) and 2.3 (< 0.5-15) micrograms/ml in those with other acute abdominal problems. Admission plasma samples showed equally low vitamin C levels in both groups of patients (P < 0.001 versus controls), but those from patients with acute pancreatitis were further characterized by a disproportionate reduction in ascorbic acid, such that the concentration of ascorbic acid and its ratio to vitamin C were both significantly lower than in samples from patients with an acute abdomen (P < 0.005 and P < 0.001 respectively). It is concluded that the stress of an acute intra-abdominal crisis is accompanied by a non-specific decrease in the plasma level of vitamin C. In acute pancreatitis early and profound oxidative stress compounds this problem by denaturing the available vitamin. There may be a case for the judicious parenteral administration of ascorbic acid to patients with acute pancreatitis to boost plasma antioxidant defence.