Greatest Proportionate Increase Research Articles

Abstract B144: Morphologic consequences for noncapsular lymphoid tissue in the case of malignancy of GERD (Barrett's esophagus)

Abstract In this case, the process of development of the Barrett's esophagus and the development of adenocarcinoma as a complication of this disease with involvement of lymphoid tissue with the formation of follicles of different types was studied. Barrett's esophagus (BE) is a precursor of adenocarcinoma of the esophagus, a disease with a growing burden in the Western world. The incidence of BE increased dramatically during the late 20th century and increased morbidity of this disease. Prevalence is between 0.5 and 2.0%. There are risk factors for BE, including obesity and tobacco smoking, but gastroesophageal reflux disease (GERD) is the strongest risk factor. Adenocarcinoma of the esophagus (ACE) is the most common form of esophageal cancer. However, the data from United Kingdom and the Netherlands show that the incidence of BE increased even after monitoring the increase in endoscopy indices. These estimates indicate an increase in the incidence of BE in approximately 65% between 1997 and 2002 and 159% between 1993 and 2005. It is disturbing that the greatest proportionate increase in the diagnosis of BE was in people younger than 60 years, which is consistent with other works from Europe. In analyzing the literature relating to the intrinsic glands of the esophagus and Barrett esophagus, concerned the esophagus's own glands and the presence of a large number of endocrine cells in them. N.I. Kolycheva, R.R. Bektayeva studied at ultramicroscopic level. When studying the work on the lymphoid formations of the esophagus, we can cite, concerning the lymphoid component of the esophagus. At present, the source of lymphocyte infiltration into its proper mucous plate, types of lymphoid formations, has not been studied. To study the lymphoid noncapsular formations of the mucous membrane of Barrett's esophagus, biopsy specimens of Barrett's esophagus were taken. Early only the epithelium of the esophagus was studied, but there was no evidence of a propria of the mucous membrane and lymphoid tissue. Citation Format: Bakhtiyar Talgatuly Azhken. Morphologic consequences for noncapsular lymphoid tissue in the case of malignancy of GERD (Barrett's esophagus) [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B144.

Hepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome.

While several molecular targets are under consideration, mechanistic underpinnings of the transition from uncomplicated nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) remain unresolved. Here we apply multiscale chemical profiling technologies to mouse models of deranged hepatic ketogenesis to uncover potential NAFLD driver signatures. Use of stable-isotope tracers, quantitatively tracked by nuclear magnetic resonance (NMR) spectroscopy, supported previous observations that livers of wild-type mice maintained long term on a high-fat diet (HFD) exhibit a marked increase in hepatic energy charge. Fed-state ketogenesis rates increased nearly 3-fold in livers of HFD-fed mice, a greater proportionate increase than that observed for tricarboxylic acid (TCA) cycle flux, but both of these contributors to overall hepatic energy homeostasis fueled markedly increased hepatic glucose production (HGP). Thus, to selectively determine the role of the ketogenic conduit on HGP and oxidative hepatic fluxes, we studied a ketogenesis-insufficient mouse model generated by knockdown of the mitochondrial isoform of 3-hydroxymethylglutaryl-CoA synthase (HMGCS2). In response to ketogenic insufficiency, TCA cycle flux in the fed state doubled and HGP increased more than 60%, sourced by a 3-fold increase in glycogenolysis. Finally, high-resolution untargeted metabolomics and shotgun lipidomics performed using ketogenesis-insufficient livers in the fed state revealed accumulation of bis(monoacylglycero)phosphates, which also accumulated in livers of other models commonly used to study NAFLD. In summary, natural and interventional variations in ketogenesis in the fed state strongly influence hepatic energy homeostasis, glucose metabolism, and the lipidome. Importantly, HGP remains tightly linked to overall hepatic energy charge, which includes both terminal fat oxidation through the TCA cycle and partial oxidation via ketogenesis.

Erythropoietin Receptor Expression: A Role for the Tal1/SCL and GATA-1 Complex

Tal1/SCL is required for hematopoietic stem cell development and is essential for normal erythropoiesis. Although Tal1-DNA binding is not required for hematopoietic development, Tal1 participates in a complex with other binding partners GATA-1, LMO2, Ldb1 and possibly Sp1. During erythropoiesis, Tal1 can activate expression via direct association with E-box-GATA DNA sequence motifs for lineage specific genes such as Protein 4.2. In mice, loss of Tal1 in adult erythropoiesis also affects TER119 expression and BFU-E growth resulting in anemia. We found that knock down of Tal1 expression in primary erythropoietin (EPO) stimulated hematopoietic progenitor cells in culture inhibited EPO receptor (EPOR) expression and erythroid differentiation, consistent with the anemia observed in mice with targeted deletion of adult Tal1 expression. In contrast, overexpression of Tal1 in erythroid cells increased both EPOR expression and erythroid differentiation. In fact, overexpression of EPOR was sufficient to increase differentiation in erythroid progenitor cell cultures. Increased EPOR expression by Tal1 was mediated by 3 conserved E-boxes in the 5′ UTR. In reporter gene assays in K562 erythroid cells, EPOR promoter activity was lost with the mutation of these E-boxes, which are located 75 bp downstream of the required GATA-1 binding motif in the human EPOR proximal promoter. Tal1/E2A dimer binding to the E-box region was demonstrated by gel mobility shift assay. Tal1 transactivated EPOR mRNA and chromatin immunoprecipitation (ChIP) analysis confirmed that Tal1 bound directly to the E-box region in intact erythroid cells. We previously showed that GATA-1 also transactivates EPOR gene expression and is required for high level of EPOR transcription activity. In ChIP assays, an antibody to Tal1 also pulled down chromatin containing the GATA-1 binding site as well as the E-box region and conversely, antibodies to GATA-1 pulled down chromatin corresponding to the GATA-1 binding site and the E-box region. These data show that the complex containing Tal1 and GATA-1 bound to the E-box region and to the GATA-1 site in the EPOR proximal promoter and that the complex has greater occupancy at the GATA-1 site in the proximal promoter. High-level Tal1 expression increased chromatin containing Tal1 or GATA-1 associated with the GATA-1 binding site as well as the down stream E-box region, with a greater proportionate increase in the E-box region. Hence, in addition to the GATA-1 binding site, the downstream E-box region is necessary for high-level EPOR expression. These data suggest that transactivation of the EPOR promoter via these sites is mediated by a Tal1 and GATA-1 containing complex and that during erythropoiesis EPO induction of both Tal1 and GATA-1 regulates the high expression of its own receptor. We hypothesize that the high binding of GATA-1 and Tal1 at the GATA site opens the upstream chromatin structure. The over-expression of Tal1 promotes the open status and facilitates the spreading of open chromatin along the chromatin to the downstream E-box region. Subsequent E-box binding by Tal1 and its interaction with GATA-1 maintains the open chromatin and activates transcription.

Induction of NAD(P)H:quinone Reductase by Probucol: A Possible Mechanism for Protection against Chemical Carcinogenesis and Toxicity

Dietary antioxidants protect laboratory animals against induction of tumours by a variety of chemical carcinogens. Among possible mechanism, protection against chemical carcinogenesis could be mediated via antioxidant-dependent induction of detoxifying enzymes, including quinone reductase and glutathione S-transferase (GSH transferase). Probucol is used cholesterol-lowering drug used in the clinic, with pronounced antioxidant effect that protect against chemical carcinogenesis and toxicity. In the present study we therefore examined the ability of probucol to induce activities of quinone reductase in the cytosolic fractions of various tissues of mice. Quinone reductase activity was increased significantly in 6 of 8 tissues examined from probucol-fed mice. The greatest proportionate increase, to 1.8 times control levels, was observed in liver. Probucol also increased quinone reductase activities of forestomach, heart, kidney, lungs and spleen. Quinone reductase is a major enzyme of xenobiotic metabolism that carries out obligatory two-electron reductions and thereby protects cells against toxicity of quinones. It is induced in many tissues coordinately with other enzymes that protect against electrophilic toxicity. The protective effects of probucol appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the non-oxidative metabolism of a wide variety of xenobiotics. The induction of such enzyme, quinone reductase by probucol suggests the potential value of this compound as a protective agent against chemical carcinogenesis and other forms of electrophilic toxicity. The significance of these results can be implicated in relation to cancer chemopreventive effects of probucol in various target organs.

Women's Self-Reported Condom Use: Intra and Interpersonal Factors

ABSTRACT In the past several years, the greatest proportionate increase in AIDS diagnoses has occurred among women. Yet, while the risk of HIV infection increases, female college students continue to report inconsistent HIV prevention behaviors. Past research on condom use among college women has focused on intrapersonal aspects of the behavior, and little is known about the influence of interpersonal factors on women's condom use. In this study we examined the relative salience of both intra and interpersonal factors on African American and white women's use of condoms. We found that interpersonal variables were particularly salient predictors of condom use. There were no ethnic differences in the effects of interpersonal variables; however, there were differences in the effects of self-efficacy on condom use.

Impact of laboratory-initiated reporting of CD4+ T lymphocytes on U.S. AIDS surveillance.

This study was conducted to measure the impact of laboratory-initiated reporting of CD4+ results on reporting of AIDS in the United States. States were categorized by whether CD4+ reporting was required; we compared the number and percentage of AIDS cases reported based on immunologic criteria, controlling for whether states also required HIV infection reporting. We observed cases reported in 1994 with CD4+ values and the delay between diagnosis and report by CD4+ and HIV-reporting status. From 1992 to 1994, states with CD4+ reporting had a greater proportionate increase in reported AIDS cases (98%) than states without CD4+ reporting (55%; p < 0.0001). From 1993 to 1994, the eight states with both CD4+ and HIV reporting had a higher increase in cases meeting immunologic criteria (7%) than the 13 states with only HIV reporting (< 1%), the three states with only CD4+ reporting (< 1%), and the 16 states with neither form of laboratory reporting (4%). Of 1987 definition cases reported in 1994, the percentage reported with CD4+ values was lower in states without either CD4+ or HIV reporting (79%) than in states with both CD4+ and HIV reporting (83%), only HIV reporting (84%), or only CD4+ reporting (88%). The percentage of AIDS cases reported within 3 months of diagnosis was lower in states without laboratory reporting (40%) than in states with CD4+ reporting (45%, p = 0.001). CD4+ reporting may enable states to report AIDS cases earlier in the course of HIV disease, permitting early targeting of health care and social services.

Cost analysis of medical care.

Information about medical and health care costs in Shanghai County are presented along with some comparisons of expenditures over time and between systems. In Shanghai County there are 4 primary sources of funds for medical and health services: direct government appropriation; contributions from factories and enterprises to the labor insurance system; commune and brigade contributions to the collective health systems; and individual contributions to the cooperative health system. The total identified amount of funds for medical and health services in Shanghai County in 1980 was 9350000 yuan (at the time this paper was written 1 yuan was approximately equivalent to US $0.60) of which 35% came directly from the government. The level of funding in 1980 was 2.6 times that in 1972. The greatest proportionate increase was in the category of administration yet expenditures for administration amounted to only 1-2% of total health expenditures both in 1972 and in 1980. The largest single category of expenditures in 1980 was for support of the County Central Hospital. Over the 1972-1980 period there was a 400% increase for the County Central Hospital expenditures. An analysis was made of the direct costs of care for patients hospitalized at the County Central Hospital for 14 selected conditions in 1980. The average length of stay for all admissions was 17.7 days with a range for the conditions studied from 5.8 days for infantile diarrhea to 52.2 days for radical surgery associated with gastric cancer. The identified direct costs/day of admission ranged from a low of 1.10 yuan for herniorrhaphy to a high of 10.00 yuan for ulcer surgery. The proportion of total direct costs which was spent for drugs used in management ranged from a low of 29.2% for herniorrhaphy to a high of 70.8% for bronchial asthma admissions. The drug costs accounted for 51.0% of direct costs for hospital care. Of the costs for hospitalization in the county hospital for residents of 162 brigades (68.1%) reimbursement was 50% or greater of the total cost. For hospitalization in the commune or town hospital level 99.2% of the brigades reimburse at least 50% of the cost (72.7% reimbursed 100% of cost). If prolonged hospitalization occurs with costs to the patient exceeding his/her ability to pay a high proportion of the cost is reduced or borne by the collective welfare fund.

Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity.

2(3)-tert-Butyl-4-hydroxyanisole (BHA) is one of several widely used antioxidant food additives that protect against chemical carcinogenesis and toxicity. The present report concerns the enhancement of dicoumarol-inhibited NAD(P)H:quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2] activity in mouse tissues in response to dietary administration of BHA. Cytosolic quinone reductase specific activity was increased significantly in 10 of 15 tissues examined from BHA-fed mice. The greatest proportionate increase, to 10 times control levels, was observed in liver. BHA also increased the quinone reductase activities of kidney, lung, and the mucosa of the upper small intestine severalfold. The increases of quinone reductase activities in liver and digestive tissues in response to BHA were comparable to the increases previously observed in glutathione S-transferase (EC 2.5.1.18) and epoxide hydratase (EC 3.3.2.3) activities. Quinones are among the toxic products of oxidative metabolism of aromatic hydrocarbons. NAD(P)H:quinone reductase exhibits broad specificity for structurally diverse hydrophobic quinones and may facilitate the microsomal metabolism of quinones to readily excreted conjugates. The protective effects of BHA appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the nonoxidative metabolism of a wide variety of xenobiotics.

Interaction in the cerebral metabolism of the biogenic amines: effect of intravenous infusion of L-tryptophan on the metabolism of dopamine and 5-hydroxyindoles in brain and cerebrospinal fluid.

1. In dogs, an intravenous injection of L-tryptophan followed by intravenous infusion of L-tryptophan, although unable to maintain stable concentrations of tryptophan in the plasma or cerebrospinal fluid, produced stable, raised concentrations of 5-hydroxyindol-3-ylacetic acid (5-HIAA) in the cerebrospinal fluid (c.s.f.). This indicated that it was possible to raise the concentrations of the 5-hydroxyindoles in brain and to maintain the cerebral metabolism in a new steady state.2. The regional distribution of the total molal concentration of the 5-hydroxyindoles in brain after the administration of tryptophan was similar to the distribution found in control animals, thus suggesting the normal rate limiting step of metabolism, the activity of the enzyme tryptophan 5-hydroxylase, was still the controlling factor.3. Tryptophan administration caused a greater proportionate increase in the concentration of 5-HIAA than in that of 5-hydroxytryptamine (5-HT) in all regions of brain, perhaps indicating that the ;storage' capacity for 5-HT becomes filled under these conditions.4. Administration of tryptophan caused a large rise in the concentration of homovanillic acid in c.s.f. demonstrating that there was an interaction between the cerebral metabolism of tryptophan and dopamine.

SALT NUCLEI IN MARINE AIR AS A FUNCTION OF ALTITUDE AND WIND FORCE

Abstract Large differences are shown to occur in the numbers and sizes of sea-salt particles in marine air over the sea as the altitude, position, and the time of sampling are varied. Increases in the amount of air-borne salt near cloud base are related to increases in wind force at the sea surface. The greatest proportionate increase in particle number occurs at the large end of the weight range. Most of the samples reported here were taken near the Hawaiian Islands. The differences in nuclei number and size with increasing altitude in the lower atmosphere are similar in pattern in Hawaii, Florida and South Australia. It is suggested that bursting air bubbles in “white caps” on the open sea are a major source of the salt nuclei, and that a greater portion of the sea surface may act as a source of these particles during average winds than might be judged from the relatively small area usually covered by white caps.

International Federation of University Women

THE International Federation of University Women is holding its twenty-sixth Council meeting—the first sinc the War—at Crosby Hall, Chelsea, by invitation of the British Federation of University Women, during July 27–August 1. Crosby Hall, which was requisitioned during the War, is re-opening as an international hall of residence and club for university women on August 6, immediately after the Council meeting. A large number of countries will be represented at the Council, including the Argentine, Australia, Belgium, Brazil, Denmark, Finland, France, India, Ireland, Luxemburg, the Netherlands, Norway, Palestine, Poland, Sweden, Switzerland and the United States. At a discussion meeting: “Bridging the Gap—1940 to 1945” on Sunday, July 28, three speakers will describe the experiences of university women during the War in the occupied, non-occupied and neutral countries respectively; and on July 30, Prof. Lise Meitner will give a public lecture on “Atoms and Atomic Energy” at Chatham House. The International Federation of University Women, which was founded in 1919 to promote understanding and friendship between university women of different nationalities, and thus to develop co-operation between their countries, had in 1939 a membership through its affiliated associations of nearly 80,000; there has been a considerable growth in membership during the war years, the estimated total being now about 94,000. The greatest proportionate increase has been recorded in the associations of the liberated countries. Since the liberation, several schemes have been launched by different national associations, including the British Federation, to help university women in the liberated countries to recuperate after the strain of enemy occupation, and to resume their professional careers and intellectual life.