Current trends in surgical intervention favour a minimally invasive approach, in which complex procedures are performed through very small incisions. Specifically, in neurosurgery there is a need for minimally invasive keyhole access, which conflicts with the lack of manoeuvrability of conventional rigid instruments. In an attempt to address this shortcoming, the current state of progress is reported on a soft-tissue intervention and neurosurgical guide (STING) to access deep brain lesions through curved trajectories. The underlying mechanism of motion, based on the reciprocal movement of interlocked probe segments, is biologically inspired and was designed around the unique features of the ovipositor of certain parasitic wasps. Work to date has focused on probe development, low- and high-level control, and trajectory planning. These aspects are described, together with results on each aspect of the work, including biomimetic microtexturing of the probe surface. Progress is very encouraging and demonstrates that forward motion into soft tissue through a reciprocating mechanism is indeed viable and can be achieved through a suitable combination of microtexturing and microfabrication techniques.

This paper describes some properties of glutamine oxidation and glutaminase isoform expression in cell lines derived from human colorectal adenomas and carcinomas. The slow-growing adenoma-derived cell line AA/C1, and the rapidly proliferating carcinoma cell line HT29, both required glutamine for growth. The rate of (14)CO(2) production from [U-(14)C]glutamine was faster in AA/C1 cells than in HT29 cells. Conversely HT29 cells showed faster rates of glucose oxidation and lactate production. The activity of glutaminase was 3 times higher in AA/C1 cell extracts than in extracts of HT29 cells. Glutaminase activity in the two cell lines had similar K(m) values for glutamine, but the activity in AA/C1 cells had a higher K(0.5) for activation by phosphate. Glutaminase activity in extracts of both cells was inhibited by glutamate. Western blotting showed the presence, in both cell lines, of isoform(s) of glutaminase with an molecular mass of 63 kDa, intermediate between that of kidney glutaminase and liver glutaminase. PCR-based analysis showed that an mRNA species identical to the kidney-type isoform glutaminase C was present in both cell types as was an additional mRNA species identical to the liver-type glutaminase isoform from human breast tumour cells. Northern blotting using isoform-specific cDNA probes demonstrated that mRNA for both glutaminase isoforms was expressed at significant levels in both cell types. Similar results to those in AA/C1 cells and HT29 cells were obtained in two further adenoma and carcinoma cell lines respectively. These results contrast with those reported previously in hepatocyte/hepatoma model systems with respect to fuel selection, glutaminase activity and isoform expression. They also constitute the first demonstration of simultaneous expression of two glutaminase isoforms in a single cell type.

To determine whether latent Epstein-Barr virus (EBV) modifies DNA damage responses in B lymphocytes, cells were treated with agents either producing DNA cross-links and adducts or generating double-strand breaks. The cyclin-dependent kinase inhibitor p21 WAF1 accumulated in mitogen-stimulated primary B cells following exposure to all genotoxins tested. In contrast, when proliferation was EBV driven, p21 WAF1 failed to accumulate after treatment with the DNA adduct-producing agents. The tumor suppressor p53 was stabilized and phosphorylated after all treatments, irrespective of whether latent EBV was present. This suggests that regulatory pathways upstream of p53 are unaffected by latent EBV but downstream effectors are altered if DNA adducts or distortions are involved.

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The bottom and the middle fluoroscopic images of Fig. 2 are swapped around.The correct figure appears below.