Bone Allograft in Revision Total Knee Replacement

Revision total knee replacement (TKR) is often associated with the necessity to reconstruct a certain amount of bone loss. In a retrospective study we reviewed the records of 137 patients who had undergone revision TKR in our department between 1990 and 1996, due to loosening or inflection. Bone allografts were used in 91 patients (67%) to accomplish stable, new prostheses. Three types of bone loss were identified in this group: Type I - minor, Type II – moderate, and Type III – large bone defects, located on either side of the knee joint – A, or both sides – B.The treatment results of these 91 patients, according to the type of bone loss, are presented, showing good functional outcome when utilizing bone allografts in revision TKR. However, careful preoperative planning, identification of bone loss type, and a well-equipped bone bank are mandatory to the success of the operation.     

Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR

PKR, an interferon (IFN)-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2alpha chain. We show that human IFN-gamma mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-gamma mRNA activates PKR through a pseudoknot in its 5' untranslated region. Mutations that impair pseudoknot stability reduce the ability to activate PKR and strongly increase the translation efficiency of IFN-gamma mRNA. Nonphosphorylatable mutant eIF2alpha, knockout of PKR and PKR inhibitors 2-aminopurine, transdominant-negative PKR, or vaccinia E3L correspondingly enhances translation of IFN-gamma mRNA. The potential to form the pseudoknot is phylogenetically conserved. We propose that the RNA pseudoknot acts to adjust translation of IFN-gamma mRNA to the PKR level expressed in the cell.     

Clearance of senescent erythrocytes: wheat germ agglutinin distribution on young and old human erythrocytes

To add an additional aspect to the process of recognition and removal of senescent human erythrocytes from the circulation, the binding of wheat germ agglutinin (WGA) to separated young, old and sialidase-treated human erythrocytes is evaluated with the immune-electron microscopical method. WGA/gold conjugate binding to old erythrocytes was lower (27%) than to young erythrocytes and even lower following treatment with sialidase (82%), exhibiting a clustered, non-continuous labeling pattern in all three erythrocyte populations, thus showing a possible redistribution of WGA binding sites. The decrease in bound WGA/gold particles correlates well with the previously reported decrease in surface sialic acid on old erythrocytes. The binding of WGA/gold are indicative of the changes occurring on erythrocyte membrane surfaces when interacting with different agglutinins.     

Dermatitis in humans associated with the mites Pyemotes tritici,Dermanyssus gallinae,Ornithonyssus bacoti and Androlaelaps casalis in Israel

Multiple erythematous papules accompanied by severe pruritus were observed in humans bitten by the mites (Acari) Pyemotes tritici (Newport) (Pyemotidae), Dermanyssus gallinae (De Geer) (Dermanyssidae), Ornithonyssus bacoti Hirst (Macronyssidae) and Androlaelaps casalis (Berlese) (Laelapidae). Eight case histories are presented and the impact of these species on human health is discussed.     

Evidence for mutualism between a plant growing in a phosphate-limited desert environment and a mineral phosphate solubilizing (MPS) rhizobacterium

Alkaline desert soils are high in insoluble calcium phosphates but deficient in soluble orthophosphate (Pi) essential for plant growth. In this extreme environment, one adaptive strategy could involve specific associations between plant roots and mineral phosphate solubilizing (MPS) bacteria. The most efficient MPS phenotype in Gram-negative bacteria results from extracellular oxidation of glucose to gluconic acid via the quinoprotein glucose dehydrogenase. A unique bacterial population isolated from the roots of Helianthus annus jaegeri growing at the edge of an alkaline dry lake in the Mojave Desert showed no MPS activity and no gluconic acid production. Addition of a concentrated solution containing material washed from the roots to these bacteria in culture resulted in production of high levels of gluconic acid. This effect was mimicked by addition of the essential glucose dehydrogenase redox cofactor 2,7,9-tricarboxyl-1H-pyrrolo[2,3]-quinoline-4,5-dione (PQQ) but the bioactive component was not PQQ. DNA hybridization data confirmed that this soil bacterium carried a gene with homology to the Escherichia coli quinoprotein glucose dehydrogenase. These data suggest that expression of the direct oxidation pathway in this bacterium may be regulated by signaling between the bacteria and the plant root. The resultant acidification of the rhizosphere may play a role in nutrient availability and/or other ecophysiological parameters essential for the survival of this desert plant.     

RNA secondary structure and compensatory evolution

The classic concept of epistatic fitness interactions between genes has been extended to study interactions within gene regions, especially between nucleotides that are important in maintaining pre-mRNA/mRNA secondary structures. It is shown that the majority of linkage disequilibria found within the Drosophila Adh gene are likely to be caused by epistatic selection operating on RNA secondary structures. A recently proposed method of RNA secondary structure prediction based on DNA sequence comparisons is reviewed and applied to several types of RNAs, including tRNA, rRNA, and mRNA. The patterns of covariation in these RNAs are analyzed based on Kimura's compensatory evolution model. The results suggest that this model describes the substitution process in the pairing regions (helices) of RNA secondary structures well when the helices are evolutionarily conserved and thermodynamically stable, but fails in some other cases. Epistatic selection maintaining pre-mRNA/mRNA secondary structures is compared to weak selective forces that determine features such as base composition and synonymous codon usage. The relationships among these forces and their relative strengths are addressed. Finally, our mutagenesis experiments using the Drosophila Adh locus are reviewed. These experiments analyze long-range compensatory interactions between the 5' and 3' ends of Adh mRNA, the different constraints on secondary structures in introns and exons, and the possible role of secondary structures in RNA splicing.     

Enhanced Brain Cell Proliferation Following Early Adrenalectomy in Rats

We have previously demonstrated an increase in adult brain DNA content in rats adrenalectomized on postnatal day 11. The present studies examined cell proliferation in cerebral cortex, cerebellum, hippocampus, and midbrain-diencephalon following adrenalectomy at this age. Compared to sham-operated controls, adrenalectomized animals showed increased [3H]thymidine incorporation into DNA (measured at 1 h following a pulse injection) in all brain regions at 7 and 14 days postsurgery. In some areas, the effect was already present as early as 2 days following adrenalectomy. Chronic replacement with corticosterone prevented this increase in DNA labelling in a dose-dependent manner. When cell proliferation in the cerebral cortex and cerebellum was independently assessed by measuring changes in thymidine kinase activity, enzyme activity was significantly elevated in both areas at 7 and 14 days postsurgery. Finally, histological examination of the cerebellar cortex suggested a delayed disappearance of the external granular layer in several cerebellar lobules of adrenalectomized animals. Overall, these findings indicate that day-11 adrenalectomy leads to a prolonged stimulation of mitotic activity in areas where cell formation at this time is exclusively glial (i.e., cerebral cortex and mid-brain-diencephalon) as well as in areas where postnatal neurogenesis is also occurring (cerebellum and hippocampus). It is hypothesized that this stimulation results from the removal of a tonic inhibitory effect exerted by circulating glucocorticoids in the normal intact animal.     

Iron deficiency induces reversal of dopamine dependent circadian cycles: differential response to d-amphetamine and TRH

Rats made nutritionally iron-deficient (ID) have significantly diminished haemoglobin, serum iron and hypothermic response to d-amphetamine (15 mg/kg). The reduction of d-amphetamine induced hypothermia is comparatively greater in the dark than in the light period. Neither TRH (1 mg/kg) nor CG 3703, a peptidase resistant TRH analogue (1 mg/kg), induced hypothermia in control of ID animals. However, in combination with d-amphetamine, TRH and CG 3703 did not alter the hypothermic effect observed initially with d-amphetamine. In contrast to control animals, ID rats treated with saline or d-amphetamine (15 mg/kg) exhibited a greater degree of motor activity in the light as compared to the dark period. However, the overall activity (light plus dark) was unchanged in the ID group. The motor activity in response to TRH or CG 3703 was not changed as a result of iron-deficiency. These differential responses may be due to a more pronounced action of d-amphetamine on dopaminergic system, which is known to be changed in iron-deficiency, and of TRH and CG 3703 on the noradrenergic neurones.