Prognostic significance of tumour markers in endometrial cancer

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.     

Compartment-ablation studies of GLUT4 distribution in adipocytes: evidence for multiple intracellular pools

The available data suggest that GLUT4 does populate the recycling endosomal system to some extent, but that a large proportion of the intracellular GLUT4 resides in a compartment that is devoid of transferrin receptors and may have properties more akin to specialized secretory vesicles. The study of the nature and biogenesis of this compartment will provide important insight into the mechanism by which insulin stimulates glucose transport. Further study of the role of the synaptobrevins in these distinct subcellular compartments will probably shed further light on the mechanism by which insulin stimulates GLUT4 translocation.     

Relationship between expression of epidermal growth factor and simian virus 40 T antigen in a line of transgenic mice

The pattern of expression of the simian virus 40 (SV40) T antigen gene and resultant dysplasia were re-examined in a line of transgenic mice in which the T antigen gene was under the control of the SV40 early promoter. We found that T antigen expression in the kidney, and resulting dysplastic lesions, occurred exclusively in the distal convoluted tubules and the ascending limbs of Henle. Epidermal growth factor (EGF) expression in the kidney of normal mice was similarly immunolocalized. The correlation between high EGF immunoreactivity in normal mouse tissues and T antigen expression in the transgenic counterpart was also seen in the choroid plexus epithelium and in the submandibular glands of male mice. T antigen was not found in the submandibular gland of transgenic females. Similarly, EGF was only rarely detected in the normal female submandibular gland. In contrast to the correlation between T antigen expression in the transgenic mice and EGF expression in the corresponding tissues of the normal mice, within the dysplastic lesions of the transgenic mice EGF expression was severely diminished. Adenocarcinomas of the male submandibular gland from another line of transgenic mice that expresses the Int-1 transgene, showed similarly reduced levels of immunostaining for EGF. Thus, reduced expression of EGF might be a general feature of dysplasia and tumorigenesis in those tissues that normally express EGF.     

Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia

IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability.     

Calcium Fluoride Precipitation and Deposition From 12 mmol/L Fluoride Solutions With Different Calcium Addition Rates

The effects of different Ca-addition rates on calcium fluoride (CaF₂) precipitation and deposition were investigated in 12 mmol/L sodium fluoride solutions to which 0.1 mol/L calcium chloride solution was continuously added at average rates of (5, 7.5, 10, 12.5, 15 or 20) mmol L⁻¹ min⁻¹. The changes in ionic fluoride and calcium concentrations, as well as turbidity, were continuously recorded by F and Ca electrodes, and a fiber optic based spectrophotometer, respectively. The F⁻ concentration decreased and turbidity increased with time indicating precipitation of CaF₂. For the systems with Ca-addition rates of (5, 7.5, 10, 12.5, 15, and 20) mmol L⁻¹ min⁻¹, the 1 min CaF₂ depositions in the model substrate (cellulose filter paper, pores 0.2 µm) expressed as mean ± SD of deposited F per substrate surface area were (3.78 ± 0.31, 11.45 ± 0.89, 9.31 ± 0.68, 8.20 ± 0.56, 6.63 ± 0.43, and 2.09 ± 0.28) µg/cm², respectively (n = 10 for each group). The 1-min F depositions did not show positive correlation to Ca-addition rates. The lowest 1-min F deposition was obtained in the systems with the highest Ca-addition rate of 20 mmol L⁻¹ min⁻¹ for which CaF₂ precipitation rate reached the maximum value of 0.31 mmol L⁻¹ s⁻¹ almost immediately after beginning of reaction (6 s). The largest 1-min F depositions were obtained from the systems with Ca addition rates of (7.5 to 12.5) mmol L⁻¹ min⁻¹ in which CaF₂ precipitation rates continuously increased reaching the maximum values of (0.13 to 0.20) mmol L⁻¹ s⁻¹ after (18 to 29) s, respectively. The 1-min F depositions were greatly enhanced in comparison with the control F solutions that did not have continuous Ca-addition. This indicates that continuous Ca addition that controls the rate of CaF₂ formation could be a critical factor for larger F depositions from F solutions. The efficacy of conventional F mouthrinses could be improved with addition of a substance that continuously releases Ca.     

APIC position paper: hepatitis C exposure in the health care setting. Association for Professionals in Infection Control and Epidemiology, Inc

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.     

Dental microwear of Griphopithecus alpani

The examination of microscopic dental wear allows inferences to be made about diet in extinct species. This study reconstructs the diet of Griphopithecus alpani, a 15 Ma fossil hominoid from the Miocene site of Pa?alar in north-western Turkey, using scanning electron microscopy (SEM) to examine the microscopic wear on its molar teeth. The microwear patterns of Griphopithecus are compared with those of three extant hominoid taxa-Gorilla gorilla gorilla, Pan troglodytes verus, and Pongo pygmaeus pygmaeus. The microwear on three occlusal wear surfaces is examined in this study, and sex and age differences are also included. Analysis of variance is performed on the following microwear variables-feature density, pit density, striation density, the ratio of pits relative to striations, pit widths, and striation widths. Griphopithecus has significantly higher microwear feature densities and higher percentages of pits than Gorilla. It also has larger pit frequencies and narrower striations than both Pan and Gorilla. There are no significant differences between the microwear patterns of Griphopithecus and Pongo. This suggests that the diet of Gripho-pithecus was more similar to that of Pongo, which consumes mainly fruit, and occasionally hard and unripe fruits and nuts, than to that of Pan and Gorilla. In addition, the high percentage of pits displayed by Griphopithecus may indicate that it was ingesting harder fruits and/or objects than the extant hominoids, although this is not a significant difference. There also are consistent variations in the microwear present on the three different wear facets examined in the study-Phase II facets display more microwear and pitting than the Phase I surface examined. The results of this study do not indicate variation in dental microwear according to sex or age.