Biomedical subjects

R E Moore

Publications and source records attributed to R E Moore.

At least 55 records · Page 3Linked to original sources

PubMed1996

Dendroamides, new cyclic hexapeptides from a blue-green alga. Multidrug-resistance reversing activity of dendroamide A.

Dendroamide A (1), one of three new bistratamide-type cyclic hexapeptides from the terrestrial blue-green alga (cyanobacterium) Stigonema dendroideum Fremy, exhibits multidrug-resistance reversing activity. The gross structures of the three compounds, dendroamides A-C, were determined by NMR and mass spectral analyses. Their absolute stereochemistries were determined by Marfey and chiral GC/MS analyses of derivatives formed from acid hydrolysis of the intact and ozonized peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Overview of the Fernald Dosimetry Reconstruction Project and source term estimates for 1951-1988.

The Feed Materials Production Center, northwest of Cincinnati, processed uranium concentrates and uranium compounds recycled from other stages of nuclear weapons production, as well as some uranium ore and thorium. Particulate releases were primarily uranium (natural, depleted, and slightly enriched. In addition, two large silos containing radium-bearing residues were emission sources of radon and its decay products. The Fernald Dosimetry Reconstruction Project was undertaken to help the Centers for Disease Control and Prevention to evaluate the impact of the Feed Materials Production Center on the public from radionuclides released to the environment from 1951 through 1988. At this point in the study, the project has estimated the quantities of radioactive materials released to air, surface water, and in groundwater; developed the methodology to describe the environmental transport of the materials; developed mathematical models to calculate the resulting radiation doses; and evaluated environmental monitoring data to verify that the estimates of releases and transport are reasonable. Thorough review of historical records and extensive interaction with former and current employees and residents have been the foundation for reconstructing routine operations, documenting accidents, and evaluating unmonitored emission sources. The largest releases of uranium to air and water occurred in the 1950's and 1960's. Radon releases from the silos remained elevated through most of the 1970's. The quantity of uranium released to surface water was much less than that released to air. Best estimates of releases are reported as median values, with associated uncertainties calculated as an integral part of the estimates. Screening calculations showed that atmospheric pathways dominate the total dose from Feed Materials Production Center releases. Accordingly, the local meteorology, effluent particle size and chemical form, and wet and dry deposition, were particularly important in this study. The final goal of the project is the calculation of radiation doses to people living in the study domain, which is represented by a circle with radius of 10 km centered on the Feed Materials Production Center production area.

Air Pollutants, Radioactive↗

PubMed1996

Effect of Metal Cations on the Viscosity of a Pectin-Like Capsular Polysaccharide from the Cyanobacterium Microcystis flos-aquae C3-40.

The properties of purified capsular polysaccharide from the cyanobacterium Microcystis flos-aquae C3-40 were examined by capillary viscometry. Capsule suspensions exhibited similar viscosities between pH 6 and 10 but were more viscous at pH <=4 than at pH 6 to 11. At pH 7, a biphasic effect of metal ion concentration on capsule viscosity was observed: (i) capsule viscosity increased with increasing metal ion concentration until a maximal viscosity occurred at a specific concentration that was a reproducible characteristic of each metal ion, and (ii) the viscosity decreased with further addition of that ion. Because the latter part of the biphasic curve was complicated by additional factors (especially the precipitation or gelation of capsule by divalent metal ions), the effects of various metal chlorides were compared for the former phase in which capsule viscosity increased in the presence of metal ions. Equivalent increases in capsule viscosity were observed with micromolar concentrations of divalent metal ions but only with 10 to 20 times greater concentrations of Na(sup+). The relative abilities of various metal salts to increase capsule viscosity were as follows: CdCl(inf2), Pb(NO(inf3))(inf2), FeCl(inf2) > MnCl(inf2) > CuCl(inf2), CaCl(inf2) >> NaCl. This pattern of metal efficacy resembles known cation influences on the structural integrity of capsule in naturally occurring and cultured M. flos-aquae colonies. The data are the first direct demonstration of an interaction between metal ions and purified M. flos-aquae capsule, which has previously been proposed to play a role in the environmental cycling of certain multivalent metals, especially manganese. The M. flos-aquae capsule and the plant polysaccharide pectin have similar sugar compositions but differ in their relative responses to various metals, suggesting that capsular polysaccharide could be a preferable alternative to pectin for certain biotechnological applications.

Journal Article↗

PubMed1996

Infectious keratoconjunctivitis in free-ranging mule deer (Odocoileus hemionus) from Zion National Park, Utah.

An epizootic of infectious keratoconjunctivitis (IK) was studied opportunistically in free-ranging mule deer (Odocoileus hemionus) from Zion National Park, Utah (USA), from November 1992 to March 1994. Moraxella sp. and Chlamydia sp. were isolated from the conjunctiva of two of seven deer. In addition, Thelazia californiensis occurred on the conjunctivas of six of seven deer. Based on field observations, adults appeared to be affected clinically at a higher incidence during both years as opposed to juveniles. Corneal opacity was the most apparent clinical sign from 1992 to 1993. However, in the following year, blepharospasm and epiphora were noted more often. We were also able to document the clinical recovery of three affected deer. In addition, Moraxella sp. was recovered from the eyes of a clinically unaffected deer 1 year after the epizootic occurred.

Animals↗

PubMed1996

Preclinical anticancer activity of cryptophycin-8.

Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.

Animals↗

PubMed1995

Tubercidin stabilizes microtubules against vinblastine-induced depolymerization, a taxol-like effect.

A sensitive assay for the detection of microtubule-stabilizing agents [1] was used to screen an extensive collection of cyanobacterial and microalgal extracts. The hydrophilic extract of the cyanobacterium, Plectonema radiosum (UH isolate IC-70-1), exhibited microtubule-stabilizing activity. Bioassay-directed purification of the active compound yielded tubercidin (7-deazaadenosine), a potent cytotoxic nucleoside analog. Further studies revealed that tubercidin protected a population of cellular microtubules against vinblastine-induced depolymerization, a microtubule-stabilizing, taxol-like effect. The microtubule-stabilizing effect of tubercidin is dose dependent and limited by the cytotoxicity of the agent. Tubercidin represents another natural product that interacts with microtubules and is one of the few to cause microtubule stabilization.

Animals↗

PubMed1995

Gossypol toxicity in preruminant calves.

Twenty-four of 57 calves fed a diet containing 33% cotton seed meal (CSM) died between 7 and 15 weeks of age. Initial deaths were not accompanied by premonitory signs, but after CSM withdrawal most calves developed rough coats, anorexia, weakness, ascites and subcutaneous oedema. Those that died had large volumes of serous fluid in the body cavities, hard livers of 'nutmeg' appearance, and pulmonary congestion. Histopathologically the livers showed periacinar necrosis in acute cases and periacinar fibrosis in chronic cases. Lungs from several calves had oedema, haemosiderosis and fibrosis in some pulmonary vessels. Atrophy of myocardial fibres was present in most cases. The concentration of free gossypol in the diet was 100 to 220 mg/kg. Ante-mortem and post-mortem findings supported a diagnosis of gossypol poisoning. The deaths continued for 4 weeks after withdrawal of CSM from the diet.

Age Factors↗

PubMed1995

Gastrointestinal problems in patients who have type-III osteogenesis imperfecta.

We performed a study of forty-three patients who had type-III osteogenesis imperfecta. Our purpose was to determine the frequency and severity of abdominal problems and the relationship between these problems and pelvic deformity. Twelve patients had had recurrent episodes of abdominal pain. Eleven of them had a history of chronic constipation, and five had been treated for fecal impaction. Radiographs had been made for ten of these patients, and eight of them had radiographic evidence of pelvic deformity with severe acetabular protrusion. Chronic constipation and recurrent abdominal pain are more frequent in patients who have osteogenesis imperfecta and acetabular protrusion than in those who do not have protrusion. These patients may benefit from early attention to a bowel program and referral to a gastrointestinal specialist.

Abdominal Pain↗

PubMed1995

Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance.

Welwitindolinones are a family of novel alkaloids recently isolated from the blue-green alga Hapalosiphon welwitschii as a part of our effort to identify new compounds that overcome multiple drug resistance. The abilities of three structurally similar members of this family to interact with P-glycoprotein have been compared. Similarly to the effects of verapamil, N-methylwelwitindolinone C isothiocyanate (compound 1) attenuated the resistance of MCF-7/ADR cells to natural product anticancer drugs, including vinblastine, taxol, actinomycin D, daunomycin, and colchicine, without affecting the cytotoxicity of cisplatin. These effects of compound 1 were apparent at doses as low as 0.1 microM, indicating that it is considerably more potent than verapamil for reversal of resistance. Welwitindolinone C isothiocyanate (compound 3) demonstrated weaker reversing activity, whereas an analogue of compound 1 in which the isothiocyanate group is replaced by an isonitrile group (compound 2) was inactive. The accumulation of [3H]vinblastine in SK-VLB-1 cells was increased by compound 1 > compound 3 > verapamil >> compound 2. Interestingly, only compound 1 and verapamil enhanced [3H]taxol accumulation by these cells. Photoaffinity labeling of P-glycoprotein with [3H]azidopine in membranes from SK-VLB-1 cells was inhibited by compounds 1 and 3, but not by compound 2. Therefore, the differences in the size and/or the electronegativity of the isothiocyanate and isonitrile moieties appear to dramatically affect the abilities of the compounds to interact with P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Cryptophycin: a new antimicrotubule agent active against drug-resistant cells.

Cryptophycin is a cytotoxic dioxadiazacyclohexadecenetetrone isolated from cyanobacteria of the genus Nostoc. Incubation of L1210 leukemia cells with cryptophycin resulted in dose-dependent inhibition of cell proliferation in parallel with increases in the percentage of cells in mitosis (half-maximal effects at < 10 pM). Indirect immunofluorescence studies demonstrated that treatment of A-10 vascular smooth muscle cells with cryptophycin results in marked depletion of cellular microtubules and reorganization of vimentin intermediate filaments, similar to the effects of vinblastine. Cytochalasin B caused the depolymerization of microfilaments in these cells, while neither vinblastine nor cryptophycin affected this cytoskeletal component. Pretreatment of cells with taxol prevented microtubule depolymerization in response to either vinblastine or cryptophycin. While microtubule depolymerization in response to vinblastine was rapidly reversed by removal of the drug, cells treated with cryptophycin remained microtubule depleted for at least 24 h after removal of the compound. Combinational treatments with vinblastine and cryptophycin resulted in additive cytotoxicity. Ovarian carcinoma and breast carcinoma cells which are multiply drug resistant due to overexpression of P-glycoprotein are markedly less resistant to cryptophycin than they are to vinblastine, colchicine, and taxol. Therefore, cryptophycin is a new antimicrotubule compound which appears to be a poorer substrate for P-glycoprotein than are the Vinca alkaloids. This property may confer an advantage to cryptophycin in the chemotherapy of drug-resistant tumors.

Animals↗

PubMed1994

beta-Carbolines from the blue-green alga Dichothrix baueriana.

Three new chlorine-containing beta-carbolines, bauerines A-C (1-3), have been isolted from the terrestrial blue-green alga Dichothrix baueriana GO-25-2, and identifying mass and nmr spectral analysis. The alkaloids show activity against herpes simplex virus type 2.

Animals↗

PubMed1994

Lifetime and five-year prevalence of homelessness in the United States.

OBJECTIVE: Intense debate exists concerning the number of homeless people in the United States. Previous studies, counting currently homeless people, have provided point-prevalence estimates of homelessness but have been criticized on methodological grounds. This study reports lifetime and 5-year prevalence estimates of homelessness using a different methodological approach. METHODS: Random-digit dialing was used to interview 1507 adults living in households with telephones in the 48 contiguous states in the fall of 1990. Respondents were asked whether they had ever been homeless and if so, where they had slept while homeless. RESULTS: Lifetime and 5-year prevalence of all types of homelessness combined were 14.0% (26 million people) and 4.6% (8.5 million people), respectively. Lifetime "literal homelessness" (sleeping in shelters, abandoned buildings, bus and train stations, etc.) was 7.4% (13.5 million people). Five-year (1985 through 1990) prevalence of self-reported homelessness among those who had ever been literally homeless was 3.1% (5.7 million people). CONCLUSIONS: The magnitude of the problem of homelessness is much greater than most previous attempts to enumerate homeless people have led us to believe. This finding requires reconsideration of inferences about the causes of homelessness that were derived from point-prevalence studies of currently homeless people.

Adolescent↗

PubMed1994

Reversal of multiple drug resistance by tolyporphin, a novel cyanobacterial natural product.

The effects of a novel porphyrin, tolyporphin, on P-glycoprotein-mediated multiple drug resistance in human ovarian and breast cell lines were characterized. Compared with parental SKOV3 and MCF-7 cells, the P-glycoprotein-overexpressing sublines SKVLB1 and MCF-7/ADR were 5- and 1.3-fold less sensitive to the cytotoxic effects of tolyporphin. Subtoxic doses of tolyporphin increased the sensitivity of the SKVLB1 and MCF-7/ADR cells to P-glycoprotein-transported drugs, but did not increase the antiproliferative effects of nontransported drugs. Tolyporphin also enhanced the accumulation of [3H]-vinblastine in SKVLB1 and MCF-7/ADR cells at doses approximately 10-fold lower than those required for similar responses to verapamil. In contrast, tolyporphin did not affect drug accumulation in SKOV3 or MCF-7 cells. Tolyporphin reduced [3H]-vinblastine efflux from SKVLB1 cells, reduced [3H]-vinblastine binding to membranes from SKVLB1 cells, and blocked the ability of [3H]-azidopine to photoaffinity-label P-glycoprotein in these membranes. These results indicate that tolyporphin binds to P-glycoprotein and inhibits the transport of cytotoxic natural product drugs. This novel natural product, and related compounds, may be useful for the reversal of multiple drug resistance and for further definition of the drug binding site(s) of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Scytophycins, novel microfilament-depolymerizing agents which circumvent P-glycoprotein-mediated multidrug resistance.

Cells demonstrating the multidrug resistance phenotype because of overexpression of P-glycoprotein, a drug efflux pump, are resistant to the cytotoxic effects of most natural product drugs. To determine if P-glycoprotein confers resistance to the syctophycins, a family of natural cytotoxic macrolides recently isolated from cyanobacteria of the family Syctone-mataceae, we have characterized the effects of these compounds on drug-sensitive (SKOV3) and drug-resistant (SKVLB1) human ovarian carcinoma cells. While SKVLB1 cells demonstrated > 150- and 10,000-fold decreases in sensitivity to Adriamycin and vinblastine, respectively, they were equally sensitive as SKOV3 cells to the antiproliferative effects of tolytoxin and certain related scytophycins. The SKVKB1 cells were 4- to 11-fold resistant to other scytophycins and were 14-fold resistant to cytochalasin B. Microfilaments in SKOV3 and SKVLB1 cells were depolymerized by similar concentrations of tolytoxin, while cytochalasin B was less potent toward SKVLB1 cells than SKOV3 cells. Both tolytoxin and cytochalasin B enhanced the cytotoxicity of vinblastine toward SKVLB1 cells; however, neither compound affected the sensitivity to Adriamycin or cisplatin. Verapamil markedly increased the accumulation of [3H]vinblastine by SKLVB1 cells, while cytochalasin B caused only modest increase, and tolytoxin had no effect on [3H]vinblastine accumulation. These results suggest that some of the scytophycins, including tolytoxin, are not subject to P-glycoprotein-mediated efflux from cells exhibiting multidrug resistance due to overexpression of this transport protein. These compounds may therefore be useful for killing drug-resistant tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

The development and characterization of Vinca alkaloid-resistant Caco-2 human colorectal cell lines expressing mdr-1.

Several novel cell lines with variable resistance to Vinca alkaloids have been derived from the Caco-2 human colorectal carcinoma cell line. Parental Caco-2 cells were found by PCR analysis and immunofluorescence studies to produce a low amount of the mdr-1 gene product (P-glycoprotein) that may well be clinically significant. These cells, which were initially highly sensitive to desacetylvinblastine sulfate (DAVLB sulfate) were selected, without mutagenesis, through continuous culture with increasing concentrations of DAVLB sulfate over a 335-day period. This selection resulted in cell lines that displayed an mdr (multiple-drug-resistance) cross-resistance profile that could be reversed with agents such as verapamil and vindoline. During the selection process the amount of mdr-1 mRNA present, the extent of gene amplification and the amount of gp170 expressed all correlated well with the level of drug resistance. However, this correlation does not hold in the absence of selective pressure for the more resistant cell lines where gene amplification and the amount of P-glycoprotein present remained constant while the level of drug resistance and the amount of mdr-1 mRNA present declined. These cell lines are potential models for studying mdr-I gene expression and drug resistance in human epithelial malignancies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Characterization of beta-adrenergic receptors on rat and human osteoblast-like cells and demonstration that beta-receptor agonists can stimulate bone resorption in organ culture.

We have shown by receptor-binding analyses that the beta-2 adrenergic receptor is present on rat ROS 17/2.8 osteoblast-like cells. This was confirmed by PCR amplification of cDNA copied from the mRNA. The beta-1 adrenoreceptor subtype was absent and its mRNA was not detectable, even at the level of sensitivity afforded by PCR analysis. The beta-adrenergic receptors present on ROS 17/2.8 cells were functional as measured by ligand-induced enhancement of cAMP production. We investigated whether adrenergic agonists could mimic the action of PTH to stimulate bone resorption in neonatal mouse calvariae in organ culture. PTH induced a large increase in cAMP while norepinephrine and isoproterenol induced a small but significant increase. In the presence of a phosphodiesterase inhibitor and an antioxidant, norepinephrine consistently stimulated bone resorption. In order to determine whether functional beta-adrenergic receptors were unique to ROS 17/2.8 cells, human SaOS-2 osteoblast-like cells were also examined for enhancement of cAMP production by norepinephrine, and essentially the same results were obtained. Thus, adrenergic agonists efficiently activate beta-receptors on two osteoblast-like cells and can stimulate bone resorption in intact mouse calvariae.

Adrenergic beta-Agonists↗

PubMed1993

Inhibition of reverse transcriptase activity by extracts of cultured blue-green algae (cyanophyta).

Lipophilic and hydrophilic extracts of over 900 strains of cultured blue-green algae (cyanophyta) were examined in vitro for their ability to inhibit the reverse transcriptases (RT) of avian myeloblastosis virus (AMV) and human immunodeficiency virus, type 1 (HIV-1). Eighteen (2.0%) aqueous extracts showed activity against AMV and HIV RTs. The maximal level of RT inhibition achieved by some of the active extracts was equivalent to that measured for 3'-azido-2',3'-di-deoxythymidine (AZT) at 668 ng/ml. Examination of partially purified fractions prepared by C18 column chromatography demonstrated that the RT inhibition observed could not be attributed entirely to the degradation of transcript DNA, template RNA, or enzyme protein in the reaction mixture. Thus, these results indicate that cultured blue-green algae may represent a novel source of compounds that inhibit RT activity, including that of HIV-1.

Antiviral Agents↗

PubMed1993

Nemesis revisited: tuberculosis infection in a New York City men's shelter.

In November 1990, a screening was conducted to determine the point prevalence of tuberculosis infection in a volunteer sample of homeless men (n = 161) living in a congregate shelter in New York City. Of those for whom we have results (n = 134), 79% were positive for tuberculosis. The mean length of shelter stay from date of shelter entry was 31.8 months and was significantly associated with the tuberculosis infection rate. The findings suggest that crowded living conditions and the presence of a stable resident pool in crowded congregate shelters may be associated with transmission of tuberculosis infection.

Adult↗