Structural polymorphism of glycophorins demonstrated by immunoblotting techniques

We have explored the polymorphism of the glycophorin system in the human erythrocyte membrane using the immunoblotting techniques and examining 52 individuals selected without prior bias as to their serologic state and ten documented serologic variants of M, N, S, s blood group system. Polyclonal antisera to alpha glycophorin and to alpha glycophorin CNBr carboxyl terminal fragment C (residues 82-131) and M and N specific monoclonal antibodies (MoAbs) were used. The first two reagents detect specific regions of the alpha glycophorin molecule and all electrophoretically resolved species of glycophorins immunologically related to alpha and delta glycophorins (delta glycophorin, [alpha-delta] hybrids and other glycophorins with an alteration in the carboxyl terminal segment); the M and N MoAbs identified the glycophorin species containing or lacking the M or N determinant in the amino terminal octapeptide structures. We find that immunoblotting confirmed in all cases the serologically determined phenotype; we also find that polymorphic forms of the glycophorin system are relatively infrequent; immunoblotting, independent from serologic testing, was capable of detecting five mutants, two most likely S-s-U-phenotypes; a new glycophorin species was detected in normal red cells with both antiglycophorin and antipeptide C sera, which is not evident with MoAbs; immunoblots of known glycophorin variants (En(a-), U-, Mg, Mi I, II, III, V, and Sta) confirmed but also extended our knowledge of the abnormal glycophorins involved; and the He+ and Wrb(-) cells showed normal patterns.     

Toxicity of some broad-spectrum antibacterials in normal rat liver: the role of mitochondrial membrane permeability transition pore

Ciprofloxacin (CIP) and Amoxycillin/Clavulanate (AC) are broad-spectrum antibiotics that are commonly administered for treatment of various bacterial infections. Studies have reported the antiproliferative and apoptotic activities of CIP in several cancer cell lines while AC has been implicated in drug–induced liver injury. We investigated the influence of CIP and AC on mitochondrial Permeability Transition (mPT) pore, ATPase activity, and cytochrome C release of normal Rat Liver Mitochondria (RLM) spectrophotometrically. In vitro, CIP and AC induced the opening of the mPT pore in a concentration-dependent manner with evidence of cytochrome C release maximally at 70?µg/ml by 13 and 10 folds, respectively. In vivo, CIP (100, 200?mg/kgbw) significantly induced mPT pore opening with induction folds of 2.4 and 2.6, respectively. However, low dose of AC (10?mg/kgbw) had no effect whatsoever on the mPT pore while higher dose (30?mg/kgbw) significantly induced pore opening by 3.4 folds. Similarly, CIP(100?mg/kgbw) and AC (30?mg/kgbw), significantly enhanced RLM ATPase activity, induced cytochrome C release and increased levels of RLM malondialdehyde generation and triggered the activation of caspases-9 and 3 in liver post-mitochondrial fraction. There were also significant (p<0.05) elevation in levels of serum aminotransferases and white blood cell count. Our results show that prolonged use of Ciprofloxacin and Amoxicillin Clavulanate could result in mitochondrial membrane breakdown via induction of opening of mPT pore leading to expulsion of cytochrome C, lipid peroxidation and decrease in energy content in healthy liver cells. These drugs should therefore be used with caution.     

An anti-EnaTS detected in the serum of an MiI homozygote

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.     

Antibiotic resistance in bacteria - an emerging public health problem

The discovery and eventual introduction of anti-microbial agents to clinical medicine was one of the greatest medical triumphs of the twentieth century that revolutionized the treatment of bacterial diseases. However, the gradual emergence of populations of antibiotic-resistant bacteria resulting from use, misuse and outright abuse of antibiotics has today become a major public health problem of global proportions. This review paper examines the origins and molecular epidemiology of resistance genes, global picture of antibacterial resistance, factors that favour its spread, strategies for its control, problems of control and the consequences of failure to contain antibiotic resistance in bacteria.     

The inhibitory effect of N-(phosphonomethyl)glycine in vivo on energy-dependent,phosphate-induced swelling of isolated rat liver mitochondria

Spectrophotometric measurement of the absorbance of mitochondria at 520 nm indicated that, 5 h after administration of a single intraperitoneal dose of N-(phosphonomethyl)glycine (PMG) to rats there was a significant inhibition of energy-dependent, phosphate-induced swelling of isolated liver mitochondria. Doses of 120 and 240 mg PMG/kg caused inhibitions of 40 and 65% respectively, when either succinate or β-hydroxybutyrate was used as the substrate.