scholarly journals First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Nürnberger ◽  
Simon F. Müller ◽  
Melanie Hamann ◽  
Joachim Geyer
Keyword(s):  
Drug Sensitivity ◽  
Translation Efficiency ◽  
Mrna Transcript ◽  
Suspected Drug ◽  
Multidrug Resistance Gene ◽  
Glycoprotein P ◽  
Mdr1 Mrna ◽  
Mrna And Protein Expression ◽  
Brain Material ◽  
Current Report

The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp). In the canine Mdr1 gene, a nonsense mutation was identified in certain dog breeds causing increased drug sensitivity to various P-gp substrates such as antiparasitic macrocyclic lactones. Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis. In the current report, a Thuringian goat developed similar neurological signs after treatment with doramectin, a compound from the macrocyclic lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected drug-sensitive goat. The only position where the Mdr1 sequence from the suspected drug-sensitive goat differed was in the 3′-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C>A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1 mRNA transcript and therefore might be associated with the suspected drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1 mRNA and protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1 mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses.

Study on the effect of superparamagnetic γ-Fe2O3 combined with carmustine on cervical cancer

2020 ◽  
Vol 10 (8) ◽  
pp. 1213-1217
Author(s):  
Jinghua Xiao ◽  
Yani Li ◽  
Yanxia Wang ◽  
Xinru Wang ◽  
Wanwan Zhang ◽  
...  
Keyword(s):  
Cervical Carcinoma ◽  
Drug Sensitivity ◽  
Combined Treatment ◽  
Scientific Basis ◽  
Carcinoma Cells ◽  
Sensitivity Test ◽  
Control Group ◽  
Multidrug Resistance Gene ◽  
Drug Sensitivity Test

This study aims to investigate the killing effect of γ-Fe2O3 combined with carmustine on cervical carcinoma cells, as well as the mechanism of drug resistance of this combined treatment. RT-PCR was used to detect the expression of Multidrug Resistance Gene (MDR-l) gene in all the samples. Results showed that the combination of γ-Fe2O3 and carmustine drugs was significantly better than the control group (P < 0.05), and the tumor showed different degrees of tolerance in combination with the drug. The results of an in vitro drug sensitivity test were consistent with those of mRNA expression of MDR-l gene (P < 0.04). The combination of superparamagnetic γ-Fe2O3 and carmustine derivatives has a better therapeutic effect on cervical carcinoma than either treatment alone. The drug sensitivity test and MDR-l mRNA detection in vitro can improve the accuracy and predictability of cervical carcinoma chemotherapy, providing a scientific basis for individual tumor chemotherapy.

scholarly journals Socio-demographic Profile and Drug Sensitivity Pattern of Suspected Drug Resistant Tuberculosis among Patients in Regional Tuberculosis Reference Laboratory (R.T.R.L) of a Tertiary Hospital

2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Suspected Drug ◽  
Drug Resistant Tuberculosis ◽  
Demographic Profile ◽  
Resistant Tuberculosis ◽  
Sensitivity Pattern ◽  
Mdr Tb

Background: Drug resistant tuberculosis has been reported in all regions of the world. In this study we address the socio-demographic profile and drug sensitivity pattern as well as prevalence of drug resistance tuberculosis in a tertiary center (regional TB reference laboratory) in Bangladesh.Method: This Study was carried out in R.T.R.L. (Regional TB Reference Laboratory) in 250 bedded Chittagong General Hospital. Patients who were referred to R.T.R.L during the period July 2012 to July 2013 were included in the study. Total 100 patients with suspected drug resistant tuberculosis (TB) who had any one of 9 criteria of NTP (National Tuberculosis Control Programme) were selected consecutively. Gene xpert MTB/RIF (Rifampicin resistance) test for all sputum positive cases were performed. Sputum sample of Patients with positive microscopy for AFB or positive Xpert/MTB was sent for culture. The samples with positive sputum culture were sent for drug sensitivity test for 1st line anti- tubercular drug.Result: Among 100 patients 78 were male and 22 were female, majority of the patients (64) were between 15-45 years with poor socio economic condition (73%) and primarily educated. Analysis of our Study result showed that 18% of patients were mono-drug resistant. Among them 13% showed resistance to isoniazid (INH), 4% to streptomycin and only 2% to rifampicin. No patient was found resistant to pyrazinamide (PNZ) and 38% of patient with suspected drug – resistant TB was found to have no drug resistance. 18% of patient had multidrug resistant tuberculosis (MDR-TB) among which 56% were relapse cases (48% after cat -I, 8% after cat II), 24% were non – converter of cat –I, 12% belonged to failure of cat –I, 3% failure of cat –II, 2% return after default and others. 1% of patient had history of contact with MDR –TB patient.Conclusion: Drug-resistance tuberculosis especially MDR-TB, was higher in patients with previously incomplete anti-tuberculosis treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. For this reason proper counseling of patients and attention towards the completion of the anti-TB treatment are needed.J MEDICINE July 2017; 18 (2) : 62-67

Expression of multidrug resistance gene mdr1 mRNA in a subset of normal bone marrow cells

1992 ◽  
Vol 81 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Jean-Pierre Marie ◽  
Nathalie A. Brophy ◽  
Mohamed N. Ehsan ◽  
Yukoh Aihara ◽  
Named A. Mohamed ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Bone Marrow Cells ◽  
Normal Bone Marrow ◽  
Multidrug Resistance Gene ◽  
Normal Bone ◽  
Mdr1 Mrna ◽  
Marrow Cells

scholarly journals Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia.

1989 ◽  
Vol 9 (10) ◽  
pp. 4357-4363 ◽  
Author(s):  
H Galski ◽  
M Sullivan ◽  
M C Willingham ◽  
K V Chin ◽  
M M Gottesman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Transgenic Mice ◽  
Bone Marrow Cells ◽  
Efflux Pump ◽  
Multidrug Resistance Gene ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Leukocyte Counts ◽  
Actin Promoter

The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers.

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-Related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4418-4418
Author(s):  
Hee Jin Huh ◽  
Chan-Jeoung Park ◽  
Seongsoo Jang ◽  
Eul-Ju Seo ◽  
Hyun-Sook Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Acute Leukemia ◽  
Mrna Expression ◽  
Prognostic Significance ◽  
Multidrug Resistance Gene ◽  
Lung Resistance Protein ◽  
Mdr1 Mrna ◽  
Resistance Protein ◽  
Multidrug Resistance Related Protein

Abstract The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (AML 39, ALL 32) using nested reverse transcription polymerase chain reaction (RT-PCR). The expression of each of these genes was then expressed as a ratio in relation to ß-actin gene expression, and the three genes were categorized as being either not expressed (0), weakly expressed (1+), moderately expressed (2+) or strongly expressed (3+). MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1%, respectively, of acute leukemia patients. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion of these patients, compared to LRP-negative patients (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-year survival (P=0.049 and p=0.04, respectively) compared to MRP-negative and non-high MDR1 mRNA-expressing patients, respectively. Patients expressing both MRP and LRP mRNA had poorer outcomes in response to induction chemotherapy and had worse 2-year survival compared to patients not expressing both genes. The present data suggest that MDR gene expression affects CR and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

scholarly journals SUSPECTED DRUG SENSITIVITY REACTION

1964 ◽  
Vol 36 (8) ◽  
pp. 516-518
Author(s):  
J.G. FRANCIS ◽  
M.S.B. VAILE
Keyword(s):  
Drug Sensitivity ◽  
Suspected Drug ◽  
Sensitivity Reaction

scholarly journals Expression of P-glycoprotein in adult T-cell leukemia cells

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2065-2071 ◽  
Author(s):  
Y Kuwazuru ◽  
S Hanada ◽  
T Furukawa ◽  
A Yoshimura ◽  
T Sumizawa ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Multidrug Resistant ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Glycoprotein P ◽  
Adult T Cell Leukemia ◽  
P Glycoprotein ◽  
Mdr1 Mrna

We have examined the expression of P-glycoprotein (P-gp) in adult T- cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

scholarly journals Expression of P-glycoprotein in adult T-cell leukemia cells

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2065-2071 ◽  
Author(s):  
Y Kuwazuru ◽  
S Hanada ◽  
T Furukawa ◽  
A Yoshimura ◽  
T Sumizawa ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Multidrug Resistant ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Glycoprotein P ◽  
Adult T Cell Leukemia ◽  
P Glycoprotein ◽  
Mdr1 Mrna

Abstract We have examined the expression of P-glycoprotein (P-gp) in adult T- cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

scholarly journals Characterization of Bicistronic Transcription in Budding Yeast

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Baojun Wu ◽  
Murray P. Cox
Keyword(s):  
Secondary Structure ◽  
Gc Content ◽  
Ribosome Profiling ◽  
Translation Efficiency ◽  
Mrna Transcript ◽  
Stable Secondary Structure ◽  
Intergenic Spacers ◽  
Eukaryotic Group ◽  
Basic Features

ABSTRACT Bicistronic transcripts (operon-like transcripts) have occasionally been reported in eukaryotes, including unicellular yeasts, plants, and humans, despite the fact that they lack trans-splice mechanisms. However, the characteristics of eukaryotic bicistronic transcripts are poorly understood, except for those in nematodes. Here, we describe the genomic, transcriptomic, and ribosome profiling features of bicistronic transcripts in unicellular yeasts. By comparing the expression level of bicistronic transcripts with their monocistronic equivalents, we identify two main categories of bicistronic transcripts: highly and lowly expressed. These two categories exhibit quite different features. First, highly expressed bicistronic transcripts have higher conservation within and between strains and shorter intergenic spacers with higher GC content and less stable secondary structure. Second, genes in highly expressed bicistronic transcripts have lower translation efficiency, with the second gene showing statistically significant lower translation efficiency than the first. Finally, the genes found in these highly expressed bicistronic transcripts tend to be younger, with more recent origins. Together, these results suggest that bicistronic transcripts in yeast are heterogeneous. We further propose that at least some highly expressed bicistronic transcripts appear to play a role in modulating monocistronic translation. IMPORTANCE Operons, where a single mRNA transcript encodes multiple adjacent proteins, are a widespread feature of bacteria and archaea. In contrast, the genes of eukaryotes are generally considered monocistronic. However, a number of studies have revealed the presence of bicistronic transcripts in eukaryotes, including humans. The basic features of these transcripts are largely unknown in eukaryotes, especially in organisms lacking trans-splice mechanisms. Our analyses characterize bicistronic transcripts in one such eukaryotic group, yeasts. We show that highly expressed bicistronic transcripts have unusual features compared to lowly expressed bicistronic transcripts, with several features influencing translational modulation.

Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia

1989 ◽  
Vol 9 (10) ◽  
pp. 4357-4363
Author(s):  
H Galski ◽  
M Sullivan ◽  
M C Willingham ◽  
K V Chin ◽  
M M Gottesman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Transgenic Mice ◽  
Bone Marrow Cells ◽  
Efflux Pump ◽  
Multidrug Resistance Gene ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Leukocyte Counts ◽  
Actin Promoter

The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers.

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