The modular architecture of protein-protein binding interfaces.

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

Proof of the patent subcutaneous fibrous tract in children with V-P shunt malfunction.

A connective tissue sheath that forms around the peritoneal catheter of silicone ventriculo-peritoneal (V-P) shunt tubing is quite often observed in children with V-P shunts. However, proof of the passage of cerebrospinal fluid (CSF) through these sheaths has been reported in only one published study to date. We present four cases associated with chronic malfunction of the V-P shunt peritoneal catheter. In these cases, CSF passage through the subcutaneous fibrous tract, which had a pericatheter connective tissue sheath, was demonstrated around the V-P shunt peritoneal catheter. In the first case the patient suffered intermittent headache attacks over a long period of time; abdominal migration of the peritoneal catheter was detected. The second patient, who had been asymptomatic in the follow-up period with an outgrown peritoneal catheter, was admitted with acute hydrocephalus symptoms. A peritoneal catheter disconnection was detected in another patient, who had had multiple shunt revisions previously. In the last case, an obstruction of the peritoneal catheter was detected. The existence of the subcutaneous fibrous tract and its function were demonstrated by radio-opaque shuntogram in two cases and radionuclide shuntogram in the other two cases. In all four cases V-P shunt revision was performed. Within this study, the possible passage of CSF through a fibrous tract in cases of migration, outgrowth, disconnection or obstruction of the peritoneal shunt catheter was demonstrated. In conclusion, patients with shunt malfunction with a well-grown pericatheter fibrous sheath who are either asymptomatic or minimally symptomatic and show no evidence of active ventricular dilatation on their cranial CT scan should not be regarded as having arrested hydrocephalus until radio-opaque or radionuclide shuntogram studies have been done.

The effect of condylectomy on extreme lateral transcondylar approach to the anterior foramen magnum.

The dorsolateral, suboccipital, transcondylar technique was used in this cadaveric study. The angle and distance measurements in the corridors were taken intradurally both superior and inferior of the foramen magnum level. In the first stage of this study, the findings which were gained from the standard lateral suboccipital approach were compared with the findings after condyle and lateral atlantal mass removal. After condylectomy, the approach to anterior foramen magnum via both corridors was found to be shorter and the lateral angle of the exposure of the anterior foramen magnum was found to be wider. The considerable shortening of the distances to the anterior foramen magnum, especially in the superior corridor, emphasises the necessity of combining standard approaches with condylectomy. In addition, it was found that after condylectomy, considerable widening of both transverse and longitudinal planes in the inferior corridor allows the surgeon greater access to work on lesions. Furthermore, the freed space between the superior corridor and the interior corridor, which was gained by condylectomy, shows that condylectomy provides a combined approach to the inferior and superior parts of the foramen magnum anteriorly.

Post-traumatic bilateral diffuse cerebral swelling.

This study confirms that bilateral diffuse cerebral swelling with or without parenchymal haemorrhages (< 15 cc) is a more common occurrence in the paediatric patients with severe head injury as compared with adults, since the analysed sample represented 42.55% and 20.43% of all paediatric and adult patients with severe head injury recorded in our clinic at the time of the study, respectively. The incidence of patients with diffuse cerebral swelling without parenchymal haemorrhages was found to be 27.65% of paediatric patients and 5.37% of adult patients with severe head injury. Secondary neurological deterioration occurred only in 5 (12.5%) paediatric patients and in 4 (10.5%) adult patients with diffuse cerebral swelling and was not to be found associated with parenchymal haemorrhages. A better outcome was seen in paediatric patients. Mortality rates were 12.5% in paediatric patients and 34.21% in adult patients. Our data also suggest that the mortality rate between paediatric and adult patients with diffuse cerebral swelling without parenchymal haemorrhages was similar (15.38% and 20% in paediatric and adult group, respectively), while the adult patients with diffuse cerebral swelling associated with small intraparenchymal haemorrhages have a worse prognosis than paediatric patients.