A rare metastatic region of cervical cancer; the brain: a case report

Cervical cancer metastasizes commonly to the bone, lungs, liver and the supraclavicular lymph nodes. Rare sites of metastasis the brain, breast, paraspinal muscles, duodenum and heart have been reported. Case report: A 53-year-old postmenopausal woman presented to our facility with a one-month history of vaginal bleeding. She was found to have an exophytic cervical mass on pelvic examination. She was managed as a case of stage IIIB cervical cancer. Histology revealed Squamous Cell Carcinoma type. She had radiotherapy and was symptoms free. She represented 3 months later with visual disturbance, headache and vomiting. She was found to have metastatic lesion to her brain. She survived for 3 months and 3weeks after first treatment. Conclusion: The prognosis of cervical cancer patients with brain metastases is frequently poor with median survival of only a few months such as in this case who survived 3 months and 3 weeks after first treatment. Only few reports have incidences of long-term, disease-free survival in these patients

Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile-onset cardiomyopathy

Recessively inherited variants in AARS2 (NM_020745.2) encoding mitochondrial alanyl-tRNA synthetase (mt-AlaRS) were first described in patients presenting with fatal infantile cardiomyopathy and multiple oxidative phosphorylation defects. To date, all described patients with AARS2-related fatal infantile cardiomyopathy are united by either a homozygous or compound heterozygous c.1774C>T (p.Arg592Trp) missense founder mutation that is absent in patients with other AARS2-related phenotypes. We describe the clinical, biochemical and molecular investigations of two unrelated boys presenting with fatal infantile cardiomyopathy, lactic acidosis and respiratory failure. Oxidative histochemistry showed cytochrome c oxidase-deficient fibres in skeletal and cardiac muscle. Biochemical studies showed markedly decreased activities of mitochondrial respiratory chain complexes I and IV with a mild decrease of complex III activity in skeletal and cardiac muscle. Using next-generation sequencing, we identified a c.1738C>T (p.Arg580Trp) AARS2 variant shared by both patients that was in trans with a loss-of-function heterozygous AARS2 variant; a c.1008dupT (p.Asp337*) nonsense variant or an intragenic deletion encompassing AARS2 exons 5-7. Interestingly, our patients did not harbour the p.Arg592Trp AARS2 founder mutation. In silico modelling of the p.Arg580Trp substitution suggested a deleterious impact on protein stability and folding. We confirmed markedly decreased mt-AlaRS protein levels in patient fibroblasts, skeletal and cardiac muscle, although mitochondrial protein synthesis defects were confined to skeletal and cardiac muscle. In vitro data showed that the p.Arg580Trp variant had a minimal effect on activation, aminoacylation or misaminoacylation activities relative to wild-type mt-AlaRS, demonstrating that instability of mt-AlaRS is the biological mechanism underlying the fatal cardiomyopathy phenotype in our patients.Peer reviewe

Combined Effect of Dietary Cadmium and Benzo(a)pyrene on Metallothionein Induction and Apoptosis in the Liver and Kidneys of Bank Voles

Bank voles free living in a contaminated environment have been shown to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions. The objective of this study was to find out whether benzo(a)pyrene (BaP), a common environmental co-contaminant, increases Cd toxicity through inhibition of metallothionein (MT) synthesis—a low molecular weight protein that is considered to be primary intracellular component of the protective mechanism. For 6 weeks, the female bank voles were provided with diet containing Cd [less than 0.1 μg/g (control) and 60 μg/g dry wt.] and BaP (0, 5, and 10 μg/g dry wt.) alone or in combination. At the end of exposure period, apoptosis and analyses of MT, Cd, and zinc (Zn) in the liver and kidneys were carried out. Dietary BaP 5 μg/g did not affect but BaP 10 μg/g potentiated rather than inhibited induction of hepatic and renal MT by Cd, and diminished Cd-induced apoptosis in both organs. The hepatic and renal Zn followed a pattern similar to that of MT, attaining the highest level in the Cd + BaP 10-μg/g group. These data indicate that dietary BaP attenuates rather than exacerbates Cd toxicity in bank voles, probably by potentiating MT synthesis and increasing Zn concentration in the liver and kidneys

Effects of a single intraperitoneal administration of cadmium on femoral bone structure in male rats

<p>Abstract</p> <p>Background</p> <p>Exposure to cadmium (Cd) is considered a risk factor for various bone diseases in humans and experimental animals. This study investigated the acute effects of Cd on femoral bone structure of adult male rats after a single intraperitoneal administration.</p> <p>Methods</p> <p>Ten 4-month-old male Wistar rats were injected intraperitoneally with a single dose of 2 mg CdCl₂/kg body weight and killed 36 h after the Cd had been injected. Ten 4-month-old males served as a control group. Differences in body weight, femoral weight, femoral length and histological structure of the femur were evaluated between the two groups of rats. The unpaired Student's t-test was used for establishment of statistical significance.</p> <p>Results</p> <p>A single intraperitoneal administration of Cd had no significant effect on the body weight, femoral weight or femoral length. On the other hand, histological changes were significant. Rats exposed to Cd had significantly higher values of area, perimeter, maximum and minimum diameters of the primary osteons' vascular canals and Haversian canals. In contrast, a significant decrease in all variables of the secondary osteons was observed in these rats.</p> <p>Conclusions</p> <p>The results indicate that, as expected, a single intraperitoneal administration of 2 mg CdCl₂/kg body weight had no impact on macroscopic structure of rat's femora; however, it affected the size of vascular canals of primary osteons, Haversian canals, and secondary osteons.</p

Participation of metallothionein and superoxide dismutase in the blood of smoking smelters

Objectives: Metallothionein (MT) and two forms of superoxide dismutase (SOD), which are dependent on zinc and copper ions, are involved in defense against the same superoxide anion radicals and are present in extra- and intracellular compartments. The aim of our study was to investigate MT concentration and Cu/Zn SOD activity in the plasma and erythrocyte lysate of the non-smoking and smoking smelters. Material and Methods: The investigations were performed in the blood of 300 male smelters and 100 non-exposed male subjects. We have measured zinc, copper, malondialdehyde (MDA) and MT concentrations as well as SOD activity. Results: We have observed an increase of Cu/Zn coefficient and decrease of Zn/Cu coefficient in the serum of smelters in comparison with the non-smoking control group. Concentration of MDA in the plasma of smelters was higher in comparison with its concentration in the non-smoking control group. The plasma and the erythrocyte lysate MT concentration increased significantly in the whole group of smelters as compared to the non-smoking control group. The mean value of MT concentration in plasma of the smoking smelters was above 2-fold higher than in the non-smoking control group. The activity of Cu/Zn SOD in plasma of the smoking and non-smoking smelters was decreased in comparison with the smoking and non-smoking control groups, respectively. The lowest activity of Cu/Zn SOD, about 2-3‑fold decreased in comparison with the smoking and non-smoking control groups, was detected in plasma of the smelters. An inverse relationship was observed in the erythrocyte lysate. The highest activity of Cu/Zn SOD was reported in the erythrocyte lysate of the smoking smelters and it was about 2-fold higher than in the non-smoking control group. Conclusions: In extracellular environment MT plays a crucial role in comparison with the SOD, while in the intracellular compartment Cu/Zn SOD and MT cooperate with each other

An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene.

We describe a new zinc finger gene sequence (CMPX1 or HGM symbol ZNF6; isolated by cross-hybridization of ZFY to clones in a testis cDNA library) which possesses a zinc finger domain closely related to the transcriptional activator gene ZFX. The putative acidic activation domain is only 11.5% homologous with ZFX, whereas the putative DNA binding domain shares 75% homology and shows the same organisation composed of a basic two fingered repeat unit. ZNF6 has an unusually large 5' untranslated region (UTR) of 1.2 Kb which contains 26 potential ATG initiation codons, only one of which is associated with a long open reading frame. Southern and Northern blot analysis has shown that this 5' UTR is shared with many other sequences in the genome and transcribed associated with a large range of mRNA species. In situ hybridisation, analysis of somatic cell hybrids and male individuals carrying deleted X chromosomes have mapped the gene to Xq21.1-q21.3. The gene is highly conserved amongst the primates, in the mouse and can be detected weakly in the genome of a metatherian mammal (possum). Dosage in male and female mice indicates that it is also X-linked in this species. Possible origins of ZFX, ZFY and CMPX1 from a common ancestral gene are discussed