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1.
Dis Esophagus ; 27(8): 751-6, 2014.
Article in English | MEDLINE | ID: mdl-24165297

ABSTRACT

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.


Subject(s)
Barrett Esophagus/complications , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/pathology , Goblet Cells/pathology , Intestines/pathology , Adenocarcinoma/complications , Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Aged , Barrett Esophagus/pathology , Esophageal Neoplasms/complications , Esophagus/pathology , Female , Humans , Male , Metaplasia , Middle Aged , Prevalence
2.
J Fish Dis ; 36(3): 209-20, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23347188

ABSTRACT

Emamectin benzoate has been used to treat sea lice, Lepeophtheirus salmonis, infestations on farmed Atlantic salmon, Salmo salar. Recent evidence suggests a reduction in effectiveness in some locations. A major challenge in the detection of tolerance emergence can be the typically low proportion of resistant individuals in a population during the early phases. The objectives of this study were to develop a method for determining differences in temporal development of tolerance between sea lice life stages and to explore how these differences might be used to improve the monitoring of treatment effectiveness in a clinical setting. This study examined two data sets based on records of sea lice abundance following emamectin benzoate treatments from the west coast of Scotland (2002-2006) and from New Brunswick, Canada (2004-2008). Life stages were categorized into two groups (adult females and the remaining mobile stages) to examine the trends in mean abundance and treatment effectiveness. Differences in emamectin benzoate effectiveness were found between the two groups by year and location, suggesting that an important part of monitoring drug resistance development in aquatic ectoparasites may be the need to focus on key life stages.


Subject(s)
Copepoda/drug effects , Drug Tolerance/physiology , Ivermectin/analogs & derivatives , Age Factors , Animals , Copepoda/physiology , Female , Fisheries , Ivermectin/pharmacology , Models, Statistical , Population Density , Salmo salar/parasitology
3.
Front Public Health ; 10: 912455, 2022.
Article in English | MEDLINE | ID: mdl-36062121

ABSTRACT

Background: The Holiday Activities and Food (HAF) Programme is a UK Government initiative created to alleviate food insecurity and promote health and well-being among children and their families, who are eligible for Free School Meals (FSM), during the school holidays. This process evaluation investigated factors that facilitated and acted as a barrier to the delivery of the HAF Programme from the perspectives of key stakeholders (Co-ordinators, Providers, and Parents) involved in the HAF Programme across an East Midlands county. Methods: This evaluation utilized a mixed-methods approach, incorporating focus groups and online surveys to gain rich, multifaceted data. The focus groups were analyzed using a hybrid inductive-deductive thematic analysis and the online surveys were analyzed using mixed-methods approach due to the variation in question type (i.e., quantitative, Likert scale and open response) to align themes to the Government Aims and Standards of the HAF Programme. Findings: The stakeholders highlighted several factors that facilitated and acted as a barrier to the delivery of the HAF Programme. Facilitating factors included existing and maintaining relationships between Co-ordinators, Providers, and facilities/schools/communities as this improved communication and attendance. Additionally, transport provision for those attending the Programme helped overcome barriers to attendance. The primary barrier of the Programme was the late awarding of the Programme contract as this limited the time available to prepare and organize the Programme. This in turn, had several "knock on" effects that created more barriers and resulted in some of the Government Aims and Standards not being met such as, nutrition education for children and parents. Despite the challenges faced, Co-ordinators and Providers were able to deliver the Programme and positively impact upon the children and their families that attended the Programme. Conclusion: Following the facilitators and barriers that were highlighted in this evaluation, several recommendations have been made to enhance the delivery of the HAF Programme and ensure Government Aims and Standards, to improve children and family's health and well-being, are attained.


Subject(s)
Health Promotion , Holidays , Child , Focus Groups , Humans , Parents , Schools
4.
J Vet Intern Med ; 23(5): 957-63, 2009.
Article in English | MEDLINE | ID: mdl-19627473

ABSTRACT

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic/veterinary , Copper/metabolism , Dog Diseases/diet therapy , Dog Diseases/metabolism , Gluconates/administration & dosage , Hepatitis, Animal/chemically induced , Animals , Biopsy/veterinary , Chemical and Drug Induced Liver Injury, Chronic/diet therapy , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Copper/administration & dosage , Dogs , Double-Blind Method , Female , Genetic Predisposition to Disease , Gluconates/pharmacokinetics , Hepatitis, Animal/diet therapy , Histocytochemistry , Liver/drug effects , Liver/metabolism , Male
5.
J Clin Invest ; 58(1): 61-70, 1976 Jul.
Article in English | MEDLINE | ID: mdl-1084355

ABSTRACT

A competitive protein binding assay for measurement of the plasma concentration of 1 alpha, 25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] has been extended to include the immediate precursor of this hormone, 25-hydroxyvitamin D3 (25-OHD3). In addition, the assay system is capable of measuring the two metabolic products of ergocalciferol, namely. 25-hydroxyvitamin D2 (25-OHD2) and 1alpha, 25-dihydroxyvitamin D2 [1alpha, 25-(OH)2D2]. The target tissue assay system consists of a high affinity cytosol receptor protein that binds the vitamin D metabolites and a limited number of acceptor sites on the nuclear chromatin. By utilizing a series of chromatographic purification steps, a single plasma sample can be assayed for any of the four vitamin D metabolites either individually or combined. Therefore, the assay procedure allows for both the quantitative and qualitative assessment of the total active vitamin D level in a given plasma sample. To show that the binding assay was capable of measuring 1alpha, 25-(OH)2D2 as well as 1alpha, 25 (OH)2D3, two groups of rats were raised. One group, supplemented with vitamin D3, produced assayable material that represented 1alpha, 25-(OH)2D3. The other group, fed only vitamin D2 in the diet, yielded plasma containing only 1alpha, 25-(OH)2D2 as the hormonal form of the vitamin. The circulating concentrations of the two active sterols were nearly identical (15 ng/100 ml) in both groups, indicating that the competitive binding assay can be used to measure both hormonal forms in plasma. In a separate experiment, 1alpha, 25-(OH)2D2 was generated in an in vitro kidney homogenate system using 25-OHD2 as substrate. Comparison of this sterol with 1alpha, 25-(OH)2D3 in the assay system showed very similar binding curves; the D2 form was slightly less efficient (77%). Comparison of the respective 25-hydroxy forms (25-OHD2 vs. 25-OHD3) at concentrations 500-fold that of 1alpha, 25-(OH)2D3, again suggested that the binding of the D2 metabolite was slightly less efficient (71%). Finally, the assay was employed to measure the total active vitamin D metabolite pools in the plasma of normal subjects and patients with varying degrees of hypervitaminosis D. The normal plasma levels of 25-OHD and 1alpha, 25-(OH)2D measured in Tucson adults were 25-40 ng/ml and 2.1-4.5 ng/100 ml, respectively. Both sterols were predominately (greater than 90%) in the form of vitamin D3 metabolites in this environment. Typical cases of hypervitaminosis D exhibited approximately a 15-fold increase in the plasma 25-OHD concentration, and a dramatic changeover to virtually all metabolites existing in the form of D2 vitamins. In contrast, the circulating concentration of 1alpha, 25-(OH)2D was not substantially enhanced in vitamin D-intoxicated patients. We therefore conclude that hypervitaminosis D is not a result of abnormal plasma levels of 1alpha, 25-(OH)2D but may be cuased by an excessive circulating concentration of 25-OHD.


Subject(s)
Dihydroxycholecalciferols/blood , Ergocalciferols/analogs & derivatives , Hydroxycholecalciferols/blood , Vitamin D/adverse effects , Animals , Binding, Competitive , Chickens , Chromatography , Dihydroxycholecalciferols/metabolism , Ergocalciferols/blood , Ergocalciferols/metabolism , Humans , Hydroxycholecalciferols/metabolism , Male , Protein Binding , Radioligand Assay , Rats
6.
Br J Pharmacol ; 151(7): 1061-70, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17549048

ABSTRACT

BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.


Subject(s)
Receptor, Cannabinoid, CB2/agonists , Analgesics/pharmacology , Animals , Benzoxazines/pharmacology , CHO Cells , Calcium Channel Blockers/pharmacology , Camphanes/pharmacology , Cannabinoids/chemistry , Cannabinoids/metabolism , Cannabinoids/pharmacology , Carrageenan/toxicity , Colforsin/pharmacology , Cricetinae , Cricetulus , Cyclic AMP/antagonists & inhibitors , Cyclic AMP/metabolism , Cyclohexanols/pharmacology , Dose-Response Relationship, Drug , Humans , Hyperalgesia/chemically induced , Hyperalgesia/physiopathology , Hyperalgesia/prevention & control , Indoles/pharmacology , Mice , Morpholines/pharmacology , Naphthalenes/pharmacology , Protein Binding/drug effects , Pyrazoles/pharmacology , Radioligand Assay , Rats , Receptor, Cannabinoid, CB2/genetics , Receptor, Cannabinoid, CB2/metabolism , Species Specificity , Stereoisomerism , Tritium
7.
Dev Biol (Basel) ; 130: 109-10, 2007.
Article in English | MEDLINE | ID: mdl-18411941

ABSTRACT

Avian influenza can be considered one of the greatest global challenges the animal health sector has ever had to face. It is primarily a disease of animals and must be effectively managed by the veterinary community. Infection of humans in contact with the H5N1 virus continues to occur, however, with the possibility of mutations or re-assortment and the ever-present threat of the emergence of a pandemic. Therefore, whatever measures can be taken when outbreaks of avian influenza occur to reduce the amount of virus in circulation and potential human exposure must be reviewed constantly. Conventional methods for controlling diseases of epizootic proportions, such as avian influenza, have tended to rely on bio-security and culling (stamping out) of enormous numbers of animals. Such approaches might not be adequate in areas of intensive animal husbandry, and society is questioning more and more the ethics of slaughtering millions of animals. The costs and economic impact of this strategy also has a considerable effect on the economy of the country or region in which the disease outbreak occurs.


Subject(s)
Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/supply & distribution , Influenza in Birds/prevention & control , Animals , Birds , Disease Outbreaks/prevention & control , Disease Outbreaks/veterinary , Drug Industry , Drug Stability , Drug Storage , International Cooperation , Vaccines, Synthetic/supply & distribution
8.
Rev Sci Tech ; 26(2): 379-93, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17892159

ABSTRACT

Vaccines are one of the most important tools available in the prevention and control of diseases in animals. It is therefore of the utmost importance that when vaccines are used, such use should meet with the requirements of the World Organisation for Animal Health Terrestrial Animal Health Code and must be authorised by the recognised licensing body in the country/region where the vaccines are to be used, in accordance with the three key criteria of quality, safety and efficacy. This article provides a comprehensive and comparative description of the regulatory requirements in place for veterinary vaccines in major regions of the world, highlighting the similarities and pointing out also where there are differences. Recent advances in harmonisation of such testing requirements achieved through the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) are also described. The contents will provide a valuable guide to those engaged in the research and development of vaccines globally, and reassure those involved in the prevention and control of animal diseases that veterinary vaccines, when fully authorised and used according to the label instructions, are safe and efficacious.


Subject(s)
Animal Diseases/prevention & control , Legislation, Veterinary , Vaccination/veterinary , Vaccines/standards , Veterinary Medicine/standards , Animals , International Cooperation , Quality Control , Safety , Vaccination/legislation & jurisprudence
9.
Pharmazie ; 62(1): 15-26, 2007 Jan.
Article in German | MEDLINE | ID: mdl-17294807

ABSTRACT

The chloroimine 1a reacted with the novaldiamine-base to yield the 5-(2-methylpyrrolidinyl)-derivative 3. The 5-chloro-benzonaphthyridines 1 and 9 reacted with secondary aliphatic amines to give the amidines 5-8 and 10, while the aromatic amidines 11-14 were obtained with primary aromatic amines. Mixtures of the phenol Mannich bases 15 and 16 of the isoquine type were isolated from the aminomethylation of 13b. The amodiaquine analogues 19 and 20 were obtained from the reaction of 1b and 9a with 4-amino-2-piperidinomethyl-phenol dihydrochloride. The structure of the compounds 5a (potassium salt), 6b, 10a, 11e and 18 was proven by X-ray crystal analysis. Compounds 3, 6a-e, 7, 10a, 11a, 16, 19 and 20 were tested for in vitro antimalarial activity using a chloroquine-sensitive and -resistant Plasmodium falciparum strain. The highest activity against the sensitive strain was shown by the amodiaquine analogoue 20 with an IC50 value of 160 nM. The mixture of the isoquine derivatives 15a and 16a possessed the highest activity against the resistant strain with an IC50 value of 1100 nM.


Subject(s)
Amines/chemical synthesis , Amines/pharmacology , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Naphthyridines/chemical synthesis , Naphthyridines/pharmacology , Animals , Crystallography, X-Ray , Indicators and Reagents , Mass Spectrometry , Models, Molecular , Plasmodium falciparum/drug effects , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet
10.
Pharmazie ; 62(2): 89-93, 2007 Feb.
Article in German | MEDLINE | ID: mdl-17341024

ABSTRACT

2,5-Dichloro-4-methyl-benzo[c][2,7]naphthyridine (1) reacted with aromatic amines selectively by substitution at the 5-position to yield the amidines 2. The 4-aminophenol 2c could also be synthesized by cleavage of the ether 2b. The structure of 2c was proved by X-ray crystal analysis. Aminomethylation of 2c yielded the amodiaquine analogue 3. The mono- and bisaminomethylated derivatives 4 and 5 were obtained by reaction of compound 1 with phenol Mannich base hydrochlorides. Compounds 3-5 were tested in vitro for antimalarial activity using chloroquine-sensitive and resistant Plasmodium-falciparum strains. The highest activities were shown by the pyronaridine-type compounds 5a and 5b with IC50 values of approximately 200 nM.


Subject(s)
Amodiaquine/chemistry , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Mannich Bases/chemical synthesis , Naphthyridines/chemistry , Quinones/chemistry , Animals , Crystallography, X-Ray , Plasmodium falciparum/drug effects , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet
11.
Pharmazie ; 61(1): 4-9, 2006 Jan.
Article in German | MEDLINE | ID: mdl-16454197

ABSTRACT

The pyridone 1a reacts with POCl3/DMF to yield the title compound 2a. After irradiation of 2a the enolether 3 is isolated, as shown by an X-ray structure determination. The pyridine 4 obtained by dehydrogenation of 2a leads under reductive conditions to the benzo[c][2,7]naphthyridines 5-7. The reaction of 4 with o-phenylenediamine gives the benzimidazole 8, while using 2-aminophenol or 2-aminothiophene respectively the pyrido[2,3-b[1,5]benzoxazepine 11 and the corresponding benzothiazepine 12 are obtained.


Subject(s)
Heterocyclic Compounds/chemical synthesis , Nitro Compounds/chemical synthesis , Pyridines/chemical synthesis , Indicators and Reagents , Models, Molecular , X-Ray Diffraction
12.
Pharmazie ; 61(3): 183-7, 2006 Mar.
Article in German | MEDLINE | ID: mdl-16599256

ABSTRACT

The 8,8'-biquinoline-5,5'-diones 2A are formed by the erythroquine and thalleioquine reaction from the 6-methoxyquinolines 1 as model compounds. The red substances 2A react with hydrochloric acid to yield the yellow biquinolinedihydrochlorides 3. The structure of 3b dihydrate is determined by X-ray crystal analysis. The redox properties of 2A are investigated by voltammetric methods.


Subject(s)
Quinolines/chemistry , Hydrochloric Acid , Indicators and Reagents , Magnetic Resonance Spectroscopy , Mass Spectrometry , Models, Molecular , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , X-Ray Diffraction
13.
Pharmazie ; 61(7): 575-81, 2006 Jul.
Article in German | MEDLINE | ID: mdl-16889062

ABSTRACT

The irreversible aromatase inhibitor exemestane (6) reacts with nitromethane and sodium ethanolate to yield the Michael adduct 9. The aldehyde 10 is obtained by Nef reaction of the nitro compound 9 and affords the 1,4-dihydropyridine (DHP) 11 by Hantzsch reaction using methyl beta-aminocrotonate in acetic acid. The new compounds showed a reduced inhibitory potency towards aromatase (IC50 values: 9, 0.91 microM; 10, 2.5 microM; 11, 10 microM) compared to 6 (IC50 = 0.23 microM). The 1,4-DHP 11 was dehydrogenated with CAN or electrochemically (E1/2 =1.18 V) to yield the corresponding pyridine 12.


Subject(s)
Androstadienes/chemical synthesis , Androstadienes/pharmacology , Aromatase Inhibitors/chemical synthesis , Aromatase Inhibitors/pharmacology , Crystallography, X-Ray , Humans , Indicators and Reagents , Magnetic Resonance Spectroscopy , Microsomes/drug effects , Microsomes/enzymology , Models, Molecular , Molecular Conformation , Oxidation-Reduction , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared
14.
Pharmazie ; 61(12): 975-80, 2006 Dec.
Article in German | MEDLINE | ID: mdl-17283651

ABSTRACT

The 2,5-dichlorobenzo[c][2,7]naphthyridine 6 was synthesized starting from the 2-pyridone 1 in four or five steps, respectively. The 5-yl amine 7 and the 2,5-diyl amines 8 and 9 were isolated by the reaction of compound 6 with the novaldiamine base. Starting with the reaction of the 6-chloropyridine 3 with the novaldiamine base to yield the 6-aminopyridine 11, the 2-yl amine 13, isomeric to 7, was obtained. Compounds 7-13 were tested for in vitro antimalarial activity using a chloroquine sensitive and resistant Plasmodium falciparum strain. The highest activity was shown by 8 with IC50 values of 90 nM and 190 nM, respectively.


Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Naphthyridines/chemical synthesis , Naphthyridines/pharmacology , Animals , Chloroquine/pharmacology , Crystallography, X-Ray , Indicators and Reagents , Molecular Conformation , Plasmodium falciparum/drug effects , Structure-Activity Relationship
15.
J Gen Appl Microbiol ; 62(4): 189-98, 2016 Sep 12.
Article in English | MEDLINE | ID: mdl-27477251

ABSTRACT

As similarly observed in nutrient-poor media at 37°C, Escherichia coli forms small rods in nutrient-rich media at temperatures near 8°C, the minimum temperature of growth. A study was initiated to identify proteins required to facilitate the small rod morphology at low temperature. E. coli contains three nonessential SPOR domain proteins (DamX, RlpA, and DedD) that have been demonstrated to bind to the septal ring. In contrast to the normal growth and small rod morphology of damX and rlpA null mutants at 10°C, the dedD null mutant exhibited reduced growth and formed filamentous cells. The presence of plasmid-encoded DedD restored growth and small rods. Plasmid-encoded FtsN, an essential SPOR domain protein that functions to stabilize the septal ring and to initiate septation, in the dedD null mutant resulted in increased growth and the formation of shorter chained cells. However, plasmid-encoded DedD failed to restore growth and cell division of cells lacking FtsN at 10°C. In contrast to cell division protein DedD, RodZ is a cell elongation protein particularly required for growth at 30°C. However, the rodZ null mutant grew similarly as the wild type strain and produced cocci in LB broth at 10°C. Moreover at 10°C, the concerted deletion of dedD and rodZ resulted in severe inhibition of growth accompanied with the formation of swollen prolate ellipsoids due to a block in septal ring assembly and cell elongation. The data indicate the cellular requirement of both FtsN and DedD for septation as well as RodZ for cell elongation to maintain the small rod morphology at temperatures near 8°C. In comparison to the growth and small rods of the wild type in M9-glucose minimal media at 37°C, the dedD null mutant grew at the same rate and produced elongated cells while the rodZ null mutant grew at a slightly slower rate and produced cocci. The data indicate that DedD and RodZ are also required to maintain the small rod morphology in nutrient-poor media, but there is a higher cellular requirement of DedD for growth and cell division in nutrient-rich media at low temperature.


Subject(s)
Cold Temperature , Cytoskeletal Proteins/metabolism , Escherichia coli Proteins/metabolism , Escherichia coli/cytology , Escherichia coli/metabolism , Membrane Proteins/metabolism , Cell Division/genetics , Cold Shock Proteins and Peptides/genetics , Cold Shock Proteins and Peptides/metabolism , Culture Media/chemistry , Cytoskeletal Proteins/genetics , Escherichia coli/genetics , Escherichia coli/growth & development , Escherichia coli Proteins/genetics , Membrane Proteins/genetics , Mutation , Plasmids
16.
Biochim Biophys Acta ; 1402(3): 288-91, 1998 Apr 24.
Article in English | MEDLINE | ID: mdl-9606987

ABSTRACT

Heterotrimeric G proteins integrate signals between receptors and effector proteins. We have cloned the human beta 5 subunit from a human brain cDNA library. The clone has a 1059 bp open reading frame and is highly homologous to the murine clone. In contrast to the brain specific mouse beta 5, northern analysis showed it to be expressed in multiple tissues.


Subject(s)
DNA, Complementary/isolation & purification , GTP-Binding Protein beta Subunits , GTP-Binding Proteins/genetics , Heterotrimeric GTP-Binding Proteins , Amino Acid Sequence , Animals , Base Sequence , Brain , Cloning, Molecular , GTP-Binding Proteins/chemistry , GTP-Binding Proteins/isolation & purification , Humans , Mice , Molecular Sequence Data , Organ Specificity/genetics , Sequence Homology, Amino Acid
17.
J Am Coll Cardiol ; 38(2): 409-14, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11499731

ABSTRACT

OBJECTIVES: The study compared procedural outcomes and long-term survival for patients undergoing percutaneous coronary intervention (PCI) of a chronic total coronary artery occlusion (CTO) with a matched non-CTO cohort to determine whether successful PCI of a CTO is associated with improved survival. BACKGROUND: Percutaneous coronary intervention of a CTO is a common occurrence, and the long-term survival for patients with successful PCI of a CTO has not been clearly defined. METHODS: Between June 1980 and December 1999, a total of 2,007 consecutive patients underwent PCI for a CTO. Utilizing propensity scoring methods, a matched non-CTO cohort of 2,007 patients was identified and compared to the CTO group. The cohorts were stratified into successful and failed procedures. RESULTS: The in-hospital major adverse cardiac event (MACE) rate was 3.8% in the CTO cohort. Technical success has improved over the last 10 years (overall 74.4%, slope 1.0%/yr, p = 0.02, R2 = 49.9%) as did procedural success (overall 69.9%, slope 1.2%/yr, p = 0.02, R2 = 51.5%) without a concomitant increase in in-hospital MACE rates (slope 0.1%/yr, p = 0.7). There was a distinct 10-year survival advantage for successful CTO treatment compared with failed CTO treatment (73.5% vs. 65.1%, p = 0.001). The CTO versus non-CTO 10-year survival was the same (71.2% vs. 71.4%, p = 0.9). Diabetics in the CTO cohort had a lower 10-year survival compared with nondiabetics (58.3% vs. 74.3%, p < 0.0001). CONCLUSIONS: These data represent follow-up of the largest reported series of patients undergoing PCI for a CTO. The 10-year survival rates for matched non-CTO and the CTO cohorts were similar. Success rates have continued to improve without an accompanying increase in MACE rates. A successfully revascularized CTO confers a significant 10-year survival advantage compared with failed revascularization.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Disease/mortality , Coronary Disease/therapy , Chronic Disease , Cohort Studies , Coronary Disease/complications , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome
18.
Arch Intern Med ; 146(7): 1397-9, 1986 Jul.
Article in English | MEDLINE | ID: mdl-3521526

ABSTRACT

Forty-one patients with cancer who were receiving cefoperazone sodium plus mezlocillin sodium were prospectively followed up for the development of abnormal bleeding or hypoprothrombinemia. Ten of 41 patients developed an increased prothrombin time, three with a hemorrhagic episode. Serum transport proteins and serum carotene were measured in 18 patients, six of whom developed hypoprothrombinemia. Low serum prealbumin and low serum carotene levels were associated with the development of hypoprothrombinemia. Patients with cancer are especially predisposed to the development of antibiotic-associated hypoprothrombinemia. This is probably a result of protein-calorie malnutrition and low vitamin K stores.


Subject(s)
Cefoperazone/adverse effects , Hypoprothrombinemias/chemically induced , Mezlocillin/adverse effects , Neoplasms/drug therapy , Carotenoids/blood , Cefoperazone/administration & dosage , Clinical Trials as Topic , Creatinine/blood , Drug Therapy, Combination , Factor VII/analysis , Humans , Mezlocillin/administration & dosage , Prealbumin/analysis , Prothrombin Time , Random Allocation , Time Factors
19.
Arch Intern Med ; 144(3): 549-51, 1984 Mar.
Article in English | MEDLINE | ID: mdl-6322710

ABSTRACT

A prospective randomized study was undertaken in neutropenic patients to evaluate the efficacy of prophylactic ketoconazole v nystatin in reducing yeast infections. Eighteen patients received 500,000 units of nystatin suspension four times daily, and 18 patients received 200 mg of ketoconazole daily. The nystatin group experienced nine local yeast infections (four thrush, three esophagitis, and two vaginitis); three patients receiving ketoconazole had thrush. No cases of disseminated candidiasis occurred in either group. Ketoconazole was better tolerated than nystatin and neither drug caused toxic effects. In addition to being nontoxic and better tolerated, ketoconazole appeared to be slightly more effective than nystatin in reducing locally severe yeast infections.


Subject(s)
Agranulocytosis/drug therapy , Ketoconazole/therapeutic use , Mycoses/prevention & control , Neutropenia/drug therapy , Nystatin/therapeutic use , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Random Allocation
20.
Arch Intern Med ; 159(19): 2273-8, 1999 Oct 25.
Article in English | MEDLINE | ID: mdl-10547166

ABSTRACT

CONTEXT: Intercessory prayer (praying for others) has been a common response to sickness for millennia, but it has received little scientific attention. The positive findings of a previous controlled trial of intercessory prayer have yet to be replicated. OBJECTIVE: To determine whether remote, intercessory prayer for hospitalized, cardiac patients will reduce overall adverse events and length of stay. DESIGN: Randomized, controlled, double-blind, prospective, parallel-group trial. SETTING: Private, university-associated hospital. PATIENTS: Nine hundred ninety consecutive patients who were newly admitted to the coronary care unit (CCU). INTERVENTION: At the time of admission, patients were randomized to receive remote, intercessory prayer (prayer group) or not (usual care group). The first names of patients in the prayer group were given to a team of outside intercessors who prayed for them daily for 4 weeks. Patients were unaware that they were being prayed for, and the intercessors did not know and never met the patients. MAIN OUTCOME MEASURES: The medical course from CCU admission to hospital discharge was summarized in a CCU course score derived from blinded, retrospective chart review. RESULTS: Compared with the usual care group (n = 524), the prayer group (n = 466) had lower mean +/- SEM weighted (6.35 +/- 0.26 vs 7.13 +/- 0.27; P=.04) and unweighted (2.7 +/- 0.1 vs 3.0 +/- 0.1; P=.04) CCU course scores. Lengths of CCU and hospital stays were not different. CONCLUSIONS: Remote, intercessory prayer was associated with lower CCU course scores. This result suggests that prayer may be an effective adjunct to standard medical care.


Subject(s)
Heart Diseases/complications , Religion , Aged , Coronary Care Units , Double-Blind Method , Female , Heart Diseases/therapy , Hospitals, University , Humans , Length of Stay , Male , Middle Aged , Missouri , Prospective Studies , Severity of Illness Index , Treatment Outcome
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