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1.
Br J Surg ; 108(4): 359-372, 2021 04 30.
Article in English | MEDLINE | ID: mdl-33778848

ABSTRACT

BACKGROUND: Assessment of anastomotic blood perfusion with intraoperative indocyanine green fluorescence angiography (ICG-FA) may be effective in preventing anastomotic leak compared with standard intraoperative methods in colorectal surgery. METHODS: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for RCTs and observational studies on intraoperative ICG-FA to May 2020. Odds ratios (ORs), risk differences and mean differences (MDs) were calculated with 95 per cent c.i. based on intention-to-treat analysis. The number needed to treat for an additional beneficial outcome was also estimated. RESULTS: Twenty-five comparative studies included a total of 7735 patients. The use of intraoperative ICG fluorescence angiography was linked with a significant reduction in all grades anastomotic leak (OR 0.39 (95 per cent c.i. 0.31 to 0.49), P < 0.001; number needed to treat for an additional beneficial outcome (NNTB) 23) and length of hospital stay (MD -0.72 (95 per cent c.i. -1.22 to -0.21) days, P = 0.006). A significantly lower incidence of grade A (OR 0.33 (0.18 to 0.60), P < 0.001), grade B (OR 0.58 (0.35 to 0.97), P = 0.04) and grade C (OR 0.59 (0.38 to 0.92), P = 0.02) anastomotic leak was demonstrated in favour of ICG-FA. For low or ultra-low rectal resection, the odds of developing anastomotic leakage was 0.32 (0.23 to 0.45) (P < 0.001; NNTB 14). There were no differences in duration of surgery, and no adverse events related to ICG fluorescent injection. CONCLUSION: The use of ICG-FA instead of standard intraoperative methods to assess anastomosis blood perfusion in colorectal surgery leads to a significant reduction in anastomotic leakage and in the need for surgical reintervention for anastomotic leak, especially in patients with low or ultra-low rectal resections.


Subject(s)
Anastomotic Leak/prevention & control , Colon/surgery , Fluorescein Angiography , Fluorescent Dyes , Indocyanine Green , Rectum/surgery , Fluorescein Angiography/methods , Humans
2.
Br J Surg ; 106(9): 1187-1196, 2019 08.
Article in English | MEDLINE | ID: mdl-31197829

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy. METHODS: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment. RESULTS: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS. CONCLUSION: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.


Subject(s)
Adenocarcinoma/pathology , Antineoplastic Agents/therapeutic use , Gastrectomy , Lymph Node Excision , Neoadjuvant Therapy , Neoplasm Staging/methods , Stomach Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Antineoplastic Agents/administration & dosage , Combined Modality Therapy , Female , Gastrectomy/methods , Humans , Kaplan-Meier Estimate , Lymph Node Excision/methods , Male , Middle Aged , Reproducibility of Results , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Survival Analysis
3.
G Chir ; 37(4): 158-161, 2016.
Article in English | MEDLINE | ID: mdl-27938532

ABSTRACT

Foreign body ingestion is not an uncommon problem in clinical practice. While most ingested foreign bodies pass uneventfully through the gastrointestinal tract, sharp foreign bodies such as toothpicks should cause intestinal perforation. We reported the case of a perforation of the appendix caused by a toothpick, which also pierced the liver without hepatic damages, in a male with an intestinal malrotation and subhepatic appendix. The patient was admitted to our hospital for abdominal pain in the right upper quadrant. An abdominal computed tomography scan revealed the anomalous position of the first portion of the large intestine with inflamed appendix. A laparoscopic appendicectomy and the exploration of the abdominal cavity was performed using minimally invasive technique.


Subject(s)
Appendectomy , Appendicitis/etiology , Appendix/abnormalities , Appendix/injuries , Digestive System Abnormalities/complications , Foreign-Body Migration/complications , Intestinal Volvulus/complications , Laparoscopy , Aged , Appendectomy/methods , Appendicitis/diagnosis , Appendicitis/surgery , Foreign-Body Migration/diagnosis , Foreign-Body Migration/surgery , Humans , Laparoscopy/methods , Male , Tomography, X-Ray Computed , Treatment Outcome
4.
Genet Mol Res ; 13(3): 6272-86, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-25158254

ABSTRACT

Abscisic acid-responsive element binding protein (AREB1) is a basic domain/leucine zipper transcription factor that binds to the abscisic acid (ABA)-responsive element motif in the promoter region of ABA-inducible genes. Because AREB1 is not sufficient to direct the expression of downstream genes under non-stress conditions, an activated form of AREB1 (AREB1ΔQT) was created. Several reports claim that plants overexpressing AREB1 or AREB1ΔQT show improved drought tolerance. In our studies, soybean plants overexpressing AREB1ΔQT were characterized molecularly, and the phenotype and drought response of three lines were accessed under greenhouse conditions. Under conditions of water deficit, the transformed plants presented a higher survival rate (100%) than those of their isoline, cultivar BR 16 (40%). Moreover, the transformed plants displayed better water use efficiency and had a higher number of leaves than their isoline. Because the transgenic plants had higher stomatal conductance than its isoline under well-watered conditions, it was suggested that the enhanced drought response of AREB1ΔQT soybean plants might not be associated with altered transpiration rates mediated by ABA-dependent stomatal closure. However, it is possible that the smaller leaf area of the transgenic plants reduced their transpiration and water use, causing delayed stress onset. The difference in the degree of wilting and percentage of survival between the 35S-AREB1ΔQT and wildtype plants may also be related to the regulation of genes that protect against dehydration because metabolic impairment of photosynthesis, deduced by an increasing internal CO2 concentration, was not observed in the transgenic plants.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Basic-Leucine Zipper Transcription Factors/genetics , Gene Expression Regulation, Plant , Glycine max/genetics , Plant Leaves/genetics , Water/metabolism , Abscisic Acid/metabolism , Arabidopsis/chemistry , Arabidopsis Proteins/metabolism , Basic-Leucine Zipper Transcription Factors/metabolism , Droughts , Plant Leaves/metabolism , Plants, Genetically Modified , Response Elements , Glycine max/metabolism , Transgenes
5.
Br J Surg ; 100(2): 191-208, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23161281

ABSTRACT

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) may offer advantages over conventional laparoscopic cholecystectomy (LC). METHODS: MEDLINE, Embase, PubMed, CINAHL, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for randomized clinical trials on SILC versus LC until May 2012. Odds ratio (OR) and weight mean difference (WMD) were calculated with 95 per cent confidence intervals (c.i.) based on intention-to-treat analysis. RESULTS: Thirteen randomized clinical trials included a total of 923 procedures. SILC had a higher procedure failure rate than LC (OR 8·16, 95 per cent c.i. 3·42 to 19·45; P < 0·001), required a longer operating time (WMD 16·55, 95 per cent c.i. 9·95 to 23·15 min; P < 0·001) and was associated with greater intraoperative blood loss (WMD 1·58, 95% of c.i. 0·44 to 2·71 ml; P = 0·007). There were no differences between the two approaches in rate of conversion to open surgery, length of hospital stay, postoperative pain, adverse events, wound infections or port-site hernias. Better cosmetic outcomes were demonstrated in favour of SILC as measured by Body Image Scale questionnaire (WMD -0·97, 95% of c.i. -1·51 to -0·43; P < 0·001) and Cosmesis score (WMD -2·46, 95% of c.i. -2·95 to -1·97; P < 0·001), but this was based on comparison with procedures in which multiple and often large ports (10 mm) were used. CONCLUSION: SILC has a higher procedure failure rate with more blood loss and takes longer than LC. No trial was adequately powered to assess safety.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Gallbladder Diseases/surgery , Abdominal Pain/etiology , Bias , Blood Loss, Surgical/statistics & numerical data , Body Image , Cholecystectomy, Laparoscopic/adverse effects , Conversion to Open Surgery/statistics & numerical data , Hernia, Abdominal/etiology , Humans , Length of Stay , Operative Time , Pain, Postoperative/etiology , Patient Satisfaction , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , Surgical Wound Infection/etiology , Treatment Failure
6.
J Invertebr Pathol ; 112(2): 152-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23220241

ABSTRACT

The polyphagous pests belonging to the genus Spodoptera are considered to be among the most important causes of damage and are widely distributed throughout the Americas'. Due to the extensive use of genetically modified plants containing Bacillus thuringiensis genes that code for insecticidal proteins, resistant insects may arise. To prevent the development of resistance, pyramided plants, which express multiple insecticidal proteins that act through distinct mode of actions, can be used. This study analyzed the mechanisms of action for the proteins Cry1Ia10 and Vip3Aa on neonatal Spodoptera frugiperda, Spodoptera albula, Spodoptera eridania and Spodoptera cosmioides larvae. The interactions of these toxins with receptors on the intestinal epithelial membrane were also analyzed by binding biotinylated toxins to brush border membrane vesicles (BBMVs) from the intestines of these insects. A putative receptor of approximately 65 kDa was found by ligand blotting in all of these species. In vitro competition assays using biotinylated proteins have indicated that Vip3Aa and Cry1Ia10 do not compete for the same receptor for S. frugiperda, S. albula and S. cosmioides and that Vip3Aa was more efficient than Cry1Ia10 when tested individually, by bioassays. A synergistic effect of the toxins in S. frugiperda, S. albula and S. cosmioides was observed when they were combined. However, in S. eridania, Cry1Ia10 and Vip3Aa might compete for the same receptor and through bioassays Cry1Ia10 was more efficient than Vip3Aa and showed an antagonistic effect when the proteins were combined. These results suggest that using these genes to develop pyramided plants may not prove effective in preventing the development of resistance in S. eridiana.


Subject(s)
Bacterial Proteins/toxicity , Endotoxins/toxicity , Hemolysin Proteins/toxicity , Host-Pathogen Interactions , Insecticides/toxicity , Pest Control, Biological , Spodoptera/drug effects , Animals , Bacillus thuringiensis Toxins , Bacterial Proteins/metabolism , Cloning, Organism , Endotoxins/metabolism , Hemolysin Proteins/metabolism , Insect Proteins/metabolism , Insecticides/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Larva , Life Cycle Stages , Receptors, Cell Surface/metabolism , Spodoptera/metabolism
7.
Colorectal Dis ; 14(9): e521-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22632654

ABSTRACT

AIM: A meta-analysis was conducted to compare preservation with ligation of the inferior mesenteric artery (IMA) during sigmoidectomy for diverticular disease. METHOD: Randomized and non-randomized clinical trials were identified using the following electronic databases: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central, Science Citation Index, Greynet, SIGLE, National Technological Information Service, British Library Integrated Catalogue. The analysed end-points were the anastomotic leakage rate, overall morbidity and 30-day postoperative mortality. RESULTS: Four studies were included involving 400 patients. The anastomotic leakage rate was 7.3% in the preservation group and 11.3% in the ligation group. There was no statistically significant difference between the groups (OR 0.72, 95% CI 0.11-4.76; P=0.73). Overall morbidity and 30-day postoperative mortality were not compared since these data were reported in only one study. CONCLUSION: The meta-analysis did not show any advantage for preservation of the IMA during sigmoid colectomy for diverticular disease in terms of anastomotic leakage.


Subject(s)
Anastomotic Leak/etiology , Colectomy/methods , Diverticulitis, Colonic/surgery , Mesenteric Artery, Inferior/surgery , Sigmoid Diseases/surgery , Colectomy/adverse effects , Humans , Ligation/adverse effects , Ligation/methods
8.
Genet Mol Res ; 11(3): 1990-6, 2012 Aug 06.
Article in English | MEDLINE | ID: mdl-22911583

ABSTRACT

The fig (Ficus carica L.) is a fruit tree of great world importance and, therefore, the genetic improvement becomes an important field of research for better crops, being necessary to gather information on this species, mainly regarding its genetic variability so that appropriate propagation projects and management are made. The improvement programs of fig trees using conventional procedures in order to obtain new cultivars are rare in many countries, such as Brazil, especially due to the little genetic variability and to the difficulties in obtaining plants from gamete fusion once the wasp Blastophaga psenes, responsible for the natural pollinating, is not found in Brazil. In this way, the mutagenic genetic improvement becomes a solution of it. For this reason, in an experiment conducted earlier, fig plants formed by cuttings treated with gamma ray were selected based on their agronomic characteristics of interest. We determined the genetic variability in these fig tree selections, using RAPD and AFLP molecular markers, comparing them to each other and to the Roxo-de-Valinhos, used as the standard. For the reactions of DNA amplification, 140 RAPD primers and 12 primer combinations for AFLP analysis were used. The selections did not differ genetically between themselves and between them and the Roxo-de-Valinhos cultivar. Techniques that can detect polymorphism between treatments, such as DNA sequencing, must be tested. The phenotypic variation of plants may be due to epigenetic variation, necessitating the use of techniques with methylation-sensitive restriction enzymes.


Subject(s)
Ficus/genetics , Mutation/genetics , Trees/genetics , Amplified Fragment Length Polymorphism Analysis , Brazil , Flowers/genetics , Genetic Markers , Random Amplified Polymorphic DNA Technique
9.
Braz J Biol ; 84: e256933, 2022.
Article in English | MEDLINE | ID: mdl-35293546

ABSTRACT

Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The female's weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.


Subject(s)
Bacillus thuringiensis , Moths , Adaptation, Physiological , Animals , Female , Hemolysin Proteins/pharmacology , Male , Glycine max
11.
Braz. j. biol ; 84: e256933, 2024. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1364505

ABSTRACT

Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The female's weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.


Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.


Subject(s)
Animals , Phenotype , Glycine max , Bacillus thuringiensis , Pest Control, Biological
12.
Braz. j. biol ; 842024.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469404

ABSTRACT

Abstract Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The females weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.


Resumo Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.

13.
J Med Chem ; 31(6): 1190-6, 1988 Jun.
Article in English | MEDLINE | ID: mdl-3373488

ABSTRACT

The synthesis and structure-activity relationships of a series of orally absorbed O-2-isocephems are described. These compounds possessed a D-[(p-hydroxyphenyl)glycyl]amino substituent at the 7-position while the substituent at the 3-position was varied. Relative to the analogous cephems, the O-2-isocephems exhibited comparable to better activity against Gram-positive organisms. Against Gram-negative organisms, their activity was variable but did indicate a lower beta-lactamase stability. Following oral administration, the O-2-isocephems generally exhibited longer half-lives but lower Cmax's and urinary recoveries.


Subject(s)
Cephalosporins/chemical synthesis , Administration, Oral , Cephalosporins/pharmacokinetics , Cephalosporins/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
14.
J Med Chem ; 35(22): 4205-13, 1992 Oct 30.
Article in English | MEDLINE | ID: mdl-1433222

ABSTRACT

A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3- carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Naphthyridines/chemical synthesis , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Dogs , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Mice , Microbial Sensitivity Tests , Naphthyridines/pharmacokinetics , Naphthyridines/pharmacology , Stereoisomerism , Structure-Activity Relationship
15.
Toxicol Sci ; 63(1): 107-14, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11509750

ABSTRACT

Lung tumors frequently exhibit altered expression of oncogenes and/or tumor suppressor genes. Although some of these alterations are believed to arise from chemical exposure, the ability of specific chemicals to cause distinct changes in gene expression is not well characterized. We previously reported the development of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene expression is significantly increased in small-cell lung carcinoma cells. In the present study, quantitative RT/PCR was used to assess the effect of model toxins cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells. Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared to the cytotoxic response as measured by the neutral red assay. Cycloheximide elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells, but did not alter expression of the housekeeping gene beta-actin. A maximum increase for c-myc expression (200% of control) was observed 5 h after treatment with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent decrease in c-myc expression in A549 cells, but no significant change in c-myc was observed in NHBE cells. The results from this study suggest that the quantitative RT/PCR method may be an appropriate technique for monitoring gene expression changes following chemical exposure. Hence, these types of studies may assist in the identification of specific chemicals which may induce the genetic alterations involved in the development of lung cancer as well as provide information relevant to the interactive effects of chemicals within complex mixtures.


Subject(s)
Bronchi/drug effects , Cycloheximide/toxicity , Gene Expression Regulation, Neoplastic/drug effects , Genes, myc , Methylnitronitrosoguanidine/toxicity , RNA, Messenger/drug effects , Respiratory Mucosa/drug effects , Actins/genetics , Actins/metabolism , Adenocarcinoma , Adult , Bronchi/metabolism , Carcinogens/toxicity , Child , Dose-Response Relationship, Drug , Humans , Lung Neoplasms , Male , Proto-Oncogene Mas , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA, Messenger/metabolism , Respiratory Mucosa/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism
16.
J Antibiot (Tokyo) ; 46(1): 167-76, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8436550

ABSTRACT

Mono- and dipeptide derivatives of C4-beta-aminoalkyl carbapenems were synthesized by the use of amino acid N-carboxy anhydride for the peptide bond formation. They were shown to act as prodrugs in vivo while imparting the much desired chemical stability. The beta-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial.


Subject(s)
Amino Acids/chemical synthesis , Anti-Bacterial Agents/pharmacology , Carbapenems/chemical synthesis , Carbapenems/pharmacology , Oligopeptides/chemical synthesis , Prodrugs/chemical synthesis , beta-Alanine/analogs & derivatives , Bacteria/drug effects , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , beta-Alanine/chemical synthesis
17.
Am J Vet Res ; 40(3): 400-2, 1979 Mar.
Article in English | MEDLINE | ID: mdl-475093

ABSTRACT

Values for total serum proteins and relative percentages of albumin, alpha 1-globulin, alpha 2-globulin, beta-globulin, and gamma-globulin were determined for the goat. These normal values were compared with those obtained for goats infected with Corynebacterium pseudotuberculosis. Goats chronically infected with C pseudotuberculosis show significantly higher total serum protein values than normal goats, apparently due to increased gamma-globulins. This higher protein value is also associated with a decrease in serum alpha 2- and beta-globulins.


Subject(s)
Blood Proteins/analysis , Corynebacterium Infections/veterinary , Goats/blood , Lymphadenitis/veterinary , Animals , Corynebacterium Infections/blood , Female , Lymphadenitis/blood
19.
Infect Immun ; 48(3): 658-63, 1985 Jun.
Article in English | MEDLINE | ID: mdl-2581898

ABSTRACT

Partially delipidated Salmonella typhimurium (O-1,4,5,12) lipopolysaccharide was incorporated into small multilamellar liposomes composed of either naturally occurring or synthetic phospholipids. Vaccination of mice with the liposome-lipopolysaccharide complexes induced a cellular response specific for O-1,4,5,12 determinants, as determined by the development of a delayed-type hypersensitivity reaction. The liposome-lipopolysaccharide vaccines were significantly more effective, compared with other nonviable vaccines tested, in protecting mice against a lethal intravenous challenge infection with virulent S. typhimurium. Protection afforded by the liposome-lipopolysaccharide vaccines was comparable to that conferred by a live S. typhimurium vaccine. Results suggest that liposome-induced modulation of the host immune response in favor of cell-mediated immunity may be more efficacious in preventing diseases in which cell-mediated immunity is of prime importance.


Subject(s)
Antigens, Bacterial/administration & dosage , Immunization , Liposomes/administration & dosage , Salmonella Infections/prevention & control , Animals , Antibodies, Bacterial/analysis , Hypersensitivity, Delayed , Immunity, Cellular , Lipopolysaccharides/administration & dosage , Mice , O Antigens , Salmonella Infections/immunology
20.
J Infect Dis ; 148(3): 563-70, 1983 Sep.
Article in English | MEDLINE | ID: mdl-6352828

ABSTRACT

Multilamellar liposomes (lipid bilayer vesicles) composed of phosphatidylcholine, cholesterol, and phosphatidylserine (molar ratio, 6:3:1) were produced and then made to entrap an aqueous solution of cephalothin. Resident murine peritoneal macrophages were shown to be capable of interiorizing the liposome-antibiotic complex; this event resulted in a relatively high intracellular concentration of cephalothin. In macrophages infected in vitro with Salmonella typhimurium, intracellular killing of the bacteria was maximal at 60 min of incubation; at this time, 60% of the interiorized organisms had been killed. Treatment of infected macrophages with liposome-encapsulated cephalothin enhanced the intraphagocytic killing of S typhimurium over that by macrophages treated with free cephalothin. These results demonstrate the superiority of liposome-encapsulated antibiotics to free antibiotics in effecting the elimination of a facultative intracellular bacterium from its intracellular site. This type of complex may find application in the treatment of diseases caused by this group of microorganisms.


Subject(s)
Cephalothin/pharmacology , Liposomes/administration & dosage , Macrophages/microbiology , Salmonella typhimurium/drug effects , Animals , Endocytosis , Mice , Salmonella typhimurium/physiology
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