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Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 253 records · Page 14Linked to original sources
PubMed1988

The adenovirus tripartite leader sequence can alter nuclear and cytoplasmic metabolism of a non-adenovirus mRNA within infected cells.

All mRNAs encoded by the adenovirus major late transcription unit share a common 5' noncoding region, 200 nucleotides in length, termed the tripartite leader sequence. To assess function of the tripartite leader, recombinant viruses were prepared which carried either a bona fide herpes simplex virus thymidine kinase gene or a modified thymidine kinase gene whose normal 5' noncoding domain was replaced with the adenovirus leader sequence. The tripartite leader simultaneously decreased the nuclear half-life and increased the cytoplasmic half-life of the thymidine kinase-specific mRNA. The tripartite leader stabilized the non-adenovirus mRNA only within the environment of an adenovirus-infected cell during the late phase of the infectious cycle.

Adenoviruses, Human↗
PubMed1988

Synergism among interleukin 1, interleukin 3, and interleukin 5 in the production of eosinophils from primitive hemopoietic stem cells.

The in vitro production of eosinophils from committed progenitor cells is influenced by interleukin (IL)-5 (eosinophil differentiation factor) and to a lesser extent by IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In primary suspension cultures of marrow cells taken from eosinophilic mice, IL-3 induced a modest stimulation of eosinophil production compared to IL-5. In contrast, IL-3 was sevenfold more effective than IL-5 in generating eosinophil progenitors (eosinophil colony-forming units (CFU-eo] from more primitive precursors present in the marrow of normal mice. Pre-incubation of marrow cells in suspension culture with IL-3, but not IL-5, increased the recovery of myeloid precursors responsive to G-CSF, GM-CSF, CSF-1, or IL-3 two- to fourfold while eosinophil progenitor cells responsive to IL-5 were increased by more than 70-fold. Similarly, pre-incubation of bone marrow cells under clonal conditions with IL-3, but not IL-5, resulted in a more than 50 fold increase in CFU-eo responsive to IL-5 over input values. Bone marrow from mice pre-treated with 5-fluorouracil is greatly depleted of progenitor cells directly responsive to IL-3 or IL-5. IL-1 which synergistically interacts with various CSF species to confer a clonogenic response by primitive stem cells present in 5-fluorouracil-treated marrow also failed to stimulate eosinophil production. A marked synergism was observed when IL-1 and IL-3 were combined in the suspension pre-culture phase with a more than sixfold recovery of CFU-eo than induced by either factor alone. Furthermore, pre-culture of 5-fluorouracil-treated marrow cells with a combination of IL-1 and IL-3 resulted in a more than 260-fold increase of CFU-eo over input numbers. These data suggest that the concatenate action of IL-1, IL-3, and IL-5 is an absolute requirement for the in vitro generation of eosinophils from primitive hemopoietic stem cells.

Animals↗
PubMed1988

Histochemical and microbiochemical demonstration of reduced pyruvate kinase activity in thioacetamide-induced neoplastic nodules of rat liver.

A new method for the histochemical demonstration of pyruvate kinase (PK) activity was developed using a semi-permeable membrane and ATP-dependent phosphorylation of glucose coupled with tetrazolium reduction via glucose-6-phosphate dehydrogenase (G6PD) in order to investigate normal liver tissue and neoplastic hepatic nodules induced by thioacetamide (TAA). A series of control reactions and comparison with microbiochemical analysis of microdissected lyophilised material were used to determine the specificity of the reaction. In agreement with earlier reports, an activity gradient in control liver decreasing from zone 3 to zone 1 was apparent both histochemically and after biochemical analysis. Liver neoplastic nodules induced by 25 weeks dietary thioacetamide administration and characterized by increased G6PD demonstrated a clear decrease in PK activity. In contrast, epithelial cells within areas of cholangiocellular tumour development were characterized by a strong increase. Comparison of the results with immunohistochemical and biochemical data from the literature indicate that the specific histochemical method described will be of great assistance in future assessment of disease and physiological alteration in activity of this key enzyme of glycolysis.

Acetamides↗
PubMed1988

Modulating influence of dehydroepiandrosterone administration on the morphology and enzyme phenotype of dimethylaminoazobenzene-induced hepatocellular foci and nodules.

The effect o 4 weeks dietary administration of the hormone dehydroepiandrosterone (DHEA) on enzyme and morphological phenotype of focal lesions previously induced by dimethylaminoazobenzene (DAB) treatment was investigated in Sprague-Dawley rats. In contrast to the DAB-alone livers where large numbers of glycogen-storing, mixed cell nodules homogeneously positive for glutathione S-transferase P form (GST-P) were apparent, DHEA treated animals were characterized by significantly fewer, more heterogeneous lesions, in some cases demonstrating increased amphophilia and structured basophilia. The enhanced heterogeneity, in some ways reminiscent of that reported earlier for 'reversibility' or 'remodelling' of rapidly induced nodular lesions, was associated with increased catalase (CAT), acid phosphatase (AP) and glucose-6- phosphatase (G6Pase) and decreased glycogen contents and phosphorylase (PHO) activity in both nodules and background parenchyma. Glucose-6-phosphatase (G6PD) activity was elevated irregularly focal lesions also demonstrating a heterogeneous reaction. The experimental data suggest two separate effects of the hormone treatment the first involving modulation of the usual altered phenotype of preneoplastic lesions with a shift towards 'tigroid' cell character and the second, similar to that reported earlier for rapidly induced nodules, involving enhanced phenotypic instability and leading to reduction in numbers.

Animals↗
PubMed1988

Proliferation of leukemic B cells in response to SAC and anti-mu. Evidence for different modes of action and comparison to proliferation and differentiation induced by conditioned medium.

We investigated the proliferative responses and immunoglobulin production of highly purified E-rosette negative largely leukemic B cells from patients with CLL to Staphylococcus aureus Cowan I (SAC) or to SAC in combination with anti-mu or conditioned medium (CM). The latter was derived by stimulating human peripheral blood mononuclear leukocytes with PHA. We observed: (1) that purified E-rosette negative largely leukemic B cells from 25% (five out of 20) of the patients exhibited proliferative responses to SAC; (2) inhibition of SAC-induced proliferation by anti-mu in certain patients, whereas synergism between SAC and anti-mu in inducing proliferative responses in others; (3) the lack of synergism between SAC and CM in inducing proliferative responses, which is in contrast to the strong synergism that was observed between anti-mu and CM in inducing proliferation; and (4) induction or enhancement by SAC alone of Ig production by largely leukemic B-cell populations from few patients with CLL and purified tonsillar B lymphocytes, but not peripheral blood B cells from normal donors. These results suggest that SAC and anti-mu induce proliferation of B cells by different mechanisms and that B-cell proliferation and differentiation is dependent not only on the mitogen but also on the activation state of the cells.

Adjuvants, Immunologic↗
PubMed1988

Production of a Shiga-like cytotoxin by Campylobacter.

Cell lysates and culture supernatants of 36 Campylobacter isolates from patients with enteritis were tested for cytotoxic activity on HeLa cells. Cytotoxic activity was considered Shiga-like if neutralized by monoclonal antibody to the B subunit of Shiga-like toxin I of Escherichia coli and rabbit anti-Shiga toxin. Fifteen of the Campylobacter isolates produced no detectable cytotoxin, 10 produced a non-neutralizable cytotoxin, and 11 produced low levels of a cell-associated SLT. However, under low stringency conditions no hybridization was observed between a DNA fragment containing cloned SLT-I genes and restriction enzyme-digested total DNA from a Campylobacter strain that produced low levels of a Shiga-like toxin I. The Shiga-like toxin neutralizing titers in sera from 15 patients with C. jejuni infections, 5 patients infected with S. sonnei, and 20 healthy persons were then determined. No rise in neutralizing titer between acute and convalescent sera of patients with C. jejuni infection or S. sonnei infection was observed, although 27% of C. jejuni-infected patients, 40% of S. sonnei-infected patients, and 30% of the healthy controls had neutralizing activity in their sera. These data indicate that low levels of Shiga-like toxin are produced by some Campylobacter isolates but that SLT is genetically distinct from the SLT-I toxin produced at high levels by certain E. coli. The findings also suggest that exposure to SLTs is common in the adult population but not as a consequence of infection with C. jejuni or S. sonnei.

Adult↗
PubMed1988

Dehydroepiandrosterone induced alterations in rat liver carbohydrate metabolism.

Long-term dietary administration of the adrenal hormone dehydroepiandrosterone (DHEA) to male Sprague-Dawley rats induced significant alterations in the activities of enzymes involved in liver carbohydrate metabolism. Although glycogen synthase activity was increased and phosphorylase decreased, glycogen stores were reduced. This was presumably related to lysosomal glycogen degradation, since alpha-glucosidase was increased. All rate-limiting enzymes of glucose metabolism which were studied (glucose-6-phosphate dehydrogenase, total hexokinases, pyruvate kinase, fructose-1,6-bisphosphatase) revealed markedly reduced activity, only glucose-6-phosphatase activity was increased. These enzymatic changes point to a far-reaching metabolic shift towards energy loss via decreased glucose consumption and increased glucose output. The enzyme pattern induced by DHEA is in many respects opposite to that induced in preneoplastic and neoplastic liver lesions by chemical hepatocarcinogens.

Animals↗
PubMed1988

Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions.

The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N-hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme-altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population. This indicates that BHA, EQ and AAP have the potential to inhibit the growth of the phenotypically stable lesions thought most likely to be the immediate precursors of hepatocellular carcinomas. The two anti-oxidants were associated with periportal increase of all enzymes investigated, whereas AAP induced GST species and mEHb in the perivenular zone. Irrespective of slightly elevated enzyme levels in surrounding parenchyma, mEHb antibody binding levels within lesions showed a reciprocal shift from positive to negative in rats treated with BHA, EQ and AAP.

Animals↗
PubMed1988

Enzyme histochemical and morphological phenotype of amphophilic foci and amphophilic/tigroid cell adenomas in rat liver after combined treatment with dehydroepiandrosterone and N-nitrosomorpholine.

Male Sprague-Dawley rats were investigated after N-nitrosomorpholine (NNM) treatment with concomitant and subsequent administration of dehydroepiandrosterone (DHEA) for development of pre-neoplastic and neoplastic liver lesions. In addition to clear, acidophilic, mixed cell and basophilic foci, a hitherto undescribed lesion type demonstrating a unique morphological and histochemical phenotype was observed in animals receiving both NNM and DHEA. The cells of the majority of these lesions for which we propose the designation amphophilic foci were characterized by increased granular acidophilia and randomly scattered cytoplasmic basophilia. Histochemically, reduced glycogen content and elevated activity of glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), acid phosphatase (AP), succinate dehydrogenase (SDH) and catalase (CAT) were evident. The lack of gamma-glutamyl transpeptidase (GGT) or glutathione S-transferase placental form (GST-P) in foci of this type allowed clear differentiation from other NNM-induced focal lesions while suggesting certain similarities to pre-neoplastic cells induced by hypolipidemic agents. Similar enzyme histochemical patterns were characteristic for foci and later appearing nodules (adenomas) composed of amphophilic/tigroid cells the basophilic material of which was increased and frequently arranged in long striped bands. DHEA treatment, while not itself inducing any preneoplastic foci, was thus associated with altered phenotypic expression of foci and adenomas generated by NNM.

Animals↗
PubMed1988

Enhancement of DHPN induced hepatocellular, cholangiocellular and pancreatic carcinogenesis by Opisthorchis viverrini infestation in Syrian golden hamsters.

Infection with 100 Opisthorchis viverrini (OP) metacercariae prior to two injections of dihydroxy-di-n-propyl nitrosamine (DHPN) (1000 mg/kg body weight) brought about significant enhancement of resultant preneoplastic lesion development in Syrian hamster liver and pancreas tissue. Thus combined treatment with carcinogen and parasite was associated with pancreatic atypical (dysplastic) foci, hepatocellular nodules, cholangiofibrosis and cholangiocarcinomas. No such lesions were observed in carcinogen alone, parasite alone or untreated control groups. In addition, parasite induced hyperplastic gall bladder epithelium was found to include areas of putative preneoplastic cells only in the DHPN-OP combined group. The results strongly suggest that pancreatitis and biliary cirrhosis associated with liver fluke infestation are responsible for the observed enhancement of carcinogenesis, and that the resultant increased proliferation plays a major role in tumorigenesis.

Adenoma, Bile Duct↗
PubMed1988

Early lesions induced by DHPN in Syrian golden hamsters: influence of concomitant Opisthorchis infestation, dehydroepiandrosterone or butylated hydroxyanisole administration.

The effects of concomitant Opisthorchis infestation and dehydroepiandrosterone (DHEA) or butylated hydroxyanisole (BHA) administration on dihydroxy-di-n-propylnitrosamine (DHPN) induction of preneoplastic lesions were investigated in Syrian golden hamsters. Whereas parasite infection was primarily associated with first-order ductular proliferation in the liver and a secondary appearance of cholangiofibrotic lesions, DHEA treatment brought about increased carcinogen toxicity and enhanced generation of glutathione-S-transferase P (GST-P)-positive hepatocellular foci, liver cysts and focal proliferative changes in the pancreas. BHA also exerted an enhancing influence on pancreatic but not liver carcinogenesis. The results suggest that whereas alteration of DHPN metabolism by DHEA and BHA treatment effected changes at the initiation level, opisthorchiasis principally exerted an enhancing influence subsequent to carcinogen withdrawal.

Animals↗
PubMed1988

Phenotypic modulation of hepatocarcinogenesis and reduction in N-nitrosomorpholine-induced hemangiosarcoma and adrenal lesion development in Sprague-Dawley rats by dehydroepiandrosterone.

Dietary administration of 0.25% dehydroepiandrosterone (DHEA) during and subsequent to 7 weeks treatment with N-nitrosomorpholine (NNM) resulted in significantly reduced development of adrenal cortical lesions and hemangiosarcomas in the liver. In addition, distinct phenotypic modulation of hepatocellular tumours was observed after combined hormone and carcinogen treatment. Thus the neoplasms were characterized by a higher degree of differentiation, lower mitotic rate and reduced potential for metastasis as compared to tumours observed after NNM alone. The data clearly indicate that DHEA exerts an inhibitory effect on both adrenal and hepatocarcinogenesis similar to that earlier reported for neoplasia in lung, thyroid, colon and skin.

Adenoma↗
PubMed1988

Sex-dependent, tissue-specific opposing effects of dehydroepiandrosterone on initiation and modulation stages of liver and lung carcinogenesis induced by dihydroxy-di-n-propylnitrosamine in F344 rats.

Administration of the hormone dehydroepiandrosterone (DHEA) (0.6% in the diet) during or subsequent to injections of the carcinogen dihydroxy-di-n-propylnitrosamine (DHPN) (2 X 1000 mg/kg body weight, i.p.) brought about alteration in the yield of preneoplastic lesions in liver and lung of both male and female F344 rats. Concomitant treatment with DHEA was associated with decrease in the numbers and size of glutathione S-transferase (GST-P)-positive hepatocellular foci while effecting a significant increase in development of lung lesions, especially in females. Long-term treatment with the hormone subsequent to carcinogen exposure brought about a reduction in numbers of liver foci in both sexes but in males was also associated with the development of large GST-P-negative foci and nodules of amphophilic/tigroid cell character. DHEA itself did not induce any focal lesions in the lungs or livers of either sex. Thus the hormone increased sensitivity to 'initiation' in the lung while decreasing that in the liver and exerted a sex-dependent pronounced modulation of the phenotype of a proportion of hepatocellular lesions.

Animals↗
PubMed1988

Generation of high yields of Syrian hamster cholangiocellular carcinomas and hepatocellular nodules by combined nitrite and aminopyrine administration and Opisthorchis viverrini infection.

Combined administration of 0.1% nitrite and 0.1% aminopyrine in the drinking water for eight to ten weeks resulted in subsequent development of both hepatocellular nodules and cholangiofibrotic lesions/cholangiocellular carcinomas in Syrian golden hamsters. Additional prior dosing with Opisthorchis viverrini metacercariae (100/animal) induced inflammatory and proliferative changes in the livers of infected hamsters and was associated with a significant increase in yields of hepatocellular and cholangiocellular preneoplastic and neoplastic lesions. Thus, environmental factors thought to be casually related to the high levels of human liver cancer observed in the Northeastern provinces of Thailand were sufficient to bring about development of equivalent tumors in experimental animals. The results indicate that parasite associated liver injury and non-specific compensatory regeneration may play an important role in generation of both hepatocellular and cholangiocellular carcinomas in man.

Adenoma, Bile Duct↗
PubMed1988

Selection pressure and altered hepatocellular islands after a single injection of aflatoxin B1.

Development of glutathione S-transferase placental form (GST-P)-positive focal populations was investigated subsequent to single injections of the hepatocarcinogens aflatoxin B1 (AfB1), dimethylnitrosamine (DMN) and diethylnitrosamine (DEN). While DEN proved far more potent at inducing putative initiated hepatocytes, the AfB1 treatment was associated with a very rapid (3 weeks) development of lesions approaching nodular proportions. Autoradiographic investigation revealed selective incorporation of label into GST-P-positive hepatocytes and oval cells at the day 7 time point following AfB1 treatment. Administration of butylated hydroxyanisole (BHA) subsequent to carcinogen injection was associated with a decrease in the final yield of lesions and increased tritiated thymidine incorporation in perivenular zone 3 background hepatocytes. The results suggest that 'selection pressure', resulting in rapid growth and development of putative preneoplastic lesions, is inherent in a single injection of the mycotoxin and indicate that variations of the present short-term model may be useful for elucidating the mechanisms underlying AfB1-induced hepatocarcinogenesis.

Aflatoxin B1↗
PubMed1988

In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin.

T-cell-mediated inhibition of granulomonopoietic progenitors (CFU-GM) was studied in vitro in 27 patients with severe aplastic anaemia (AA). In nine out of 13 responders to anti-thymocyte globulin (ATG), cultured T-cells obtained prior to therapy, as well as their conditioned medium strongly suppressed both normal allogeneic and autologous CFU-GM (the latter obtained after marrow recovery). Addition of anti-interferon-gamma to the cultures abolished the suppressive effect on CFU-GM. After ATG therapy, no similar inhibitory effect was detected. Employing the panning method with monoclonal antibodies (CD4+ for inducer/helper and CD8+ for cytotoxic/suppressor T-cells) we were able to show that the cells responsible for in vitro CFU-GM inhibition were included in the cytotoxic/suppressor T-cell subpopulation. Cultured T-cells and their conditioned medium obtained from 14 non-responders to ATG did not show CFU-GM suppression. The mean interferon (IFN) levels in the T-cell conditioned media of ATG-responders was 625 +/- 125 mu/ml while in non-responders the level was 45 +/- 15 mu/ml (normal control levels 43 +/- 24 mu/ml). Freshly isolated peripheral blood lymphocytes from either group did not show any in vitro inhibitory effect. The response rate to ATG was statistically significant when the generation in culture of high versus low IFN production was compared (P = 0.0001). Experiments with T-cells obtained from heavily transfused thalassaemia major, and myelodysplastic syndrome patients, as well as normal volunteers, also did not demonstrate any suppression of CFU-GM. Our results indicate that the response rate to ATG is significantly higher in patients with AA who have an abnormal regulation of interferon-gamma (g-IFN) production.

Adult↗
PubMed1988

Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor.

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14-day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.

Agranulocytosis↗