Specificity of mutagenesis by 4-aminobiphenyl: mutations at G residues in bacteriophage M13 DNA and G-->C transversions at a unique dG(8-ABP) lesion in single-stranded DNA

Mutagenesis by the human bladder carcinogen 4-aminobiphenyl (ABP) was studied in single-stranded DNA from a bacteriophage M13 cloning vector. In comparison to ABP lesions in double-stranded DNA, lesions in single- stranded DNA were approximately 70-fold more mutagenic and 50-fold more genotoxic. Sequencing analysis of ABP-induced mutations in the lacZ gene revealed exclusively base-pair substitutions, with over 80% of the mutations occurring at G sites; the G at position 6310 accounted for 25% of the observed mutations. Among the sequence changes at G sites, G- ->T transversions predominated, followed by G-->C transversions and G-- >A transitions. In order to further elucidate the mutagenic mechanism of ABP, an oligonucleotide containing the major DNA adduct, N- (deoxyguanosin-8-yl)-4-aminobiphenyl (dG(8-ABP)), was situated within the PstI site of a single-stranded M13 genome. After in vivo replication of the adduct containing ABP-modified and control (unadducted) genomes, the mutational frequency and mutational specificity of the dG(8-ABP) lesion were determined. The targeted mutational efficiency was approximately 0.01%, and the primary mutation observed was the G-->C transversion. Thus dG(8-ABP), albeit weakly mutagenic at the PstI site, can contribute to the mutational spectrum of ABP lesions.      

Assessment of abnormal bowel perfusion using contrast‐enhanced ultrasonography after small bowel transplantation: A case report

A 59‐year‐old man with short‐bowel syndrome received a small bowel transplantation. Because the recipient complained of severe abdominal pain 40 hours after the surgery and was highly suspected of having mesenteric vascular thrombosis, contrast‐enhanced sonography (CEUS) was performed at his bedside. CEUS demonstrated that the superior mesenteric artery was patent, but the bowel graft showed hypoenhancement, indicating severely inadequate perfusion of the graft. Due to this complication, the patient underwent an exploratory laporatomy, and the bowel graft was removed. The pathologic findings support the diagnosis of acute vascular rejection after intestinal transplantation. This case suggests that CEUS can be used to assess perfusion and vascular complications after intestinal transplantation, as it is noninvasive and easily performed at bedside. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 41 :370–372, 2013     

Types of biochemical response to acute pharmacological indomethacin probe in healthy volunteers

By the type of biochemical response to acute pharmacological indomethacin probe, a group of both male and female healthy volunteers can be subdivided into two parts. The first part includes volunteers with a stability index reduced as a result of accumulation of the oxidized products and a decrease in the content of reduced glutathione (GSH). The second part includes volunteers with the stability index increased as a result of decrease in the amount of lipid peroxidation products and an increase in the GSH content. A difference between males and females with respect to the response type consisted in that females features changes in the gutathione buffer components, and males, in the activity of antioxidant enzymes (catalase and peroxidase).     

Therapeutic Efficiency of Dimephosphone and Xydiphone in Experimental Pulse Therapy with Prednisolone

Experiments on rats showed that pulse therapy with prednisolone (100 mg/kg intraperitoneally for 3 days) stimulated urinary excretion of hydroxyproline, increased the content of inorganic phosphorus, promoted the increase in the content of dienic conjugates and catalase activity, and decreased serum levels of MDA and ceruloplasmin. Ten-day treatment with dimephosphone (208 mg/kg) or xydiphone (45 mg/kg) after pulse therapy with prednisolone normalized urinary excretion of hydroxyproline and reduced the levels of dienic conjugates. Dimephosphone did not change, while xydiphone normalized the level of MDA decreased by prednisolone.     

The survival motor neuron protein in spinal muscular atrophy

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non- SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.      

Preimplantation hormonal differences between the conception and non- conception menstrual cycles of 32 normal women

We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non- conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism.