Engineered assembly of intertwined oligomers of an immunoglobulin chain

Domain 1 of CD2 (CD2.D1) forms a conventional Ig fold stabilised by non-covalent antiparallel contacts between beta-strands. Removing two residues from the middle of the protein sequence, where the polypeptide chain normally folds back upon itself, stabilises an open conformation. In this modified molecule, the optimum evolved contacts between side-chains can only be satisfied through the antiparallel association of two chains to create a symmetrical pair of pseudo-domains. Here, we describe the dynamics of the switch between monomeric and dimeric states and demonstrate the extension of this novel underlying principle to trimer and tetramer formation. The ability of a protein molecule to form higher-order antiparallel structures is reminiscent of the behaviour of hairpins, duplexes, three-way and Holliday junctions in DNA.     

Rasmussen's encephalitis with concomitant cortical dysplasia: the role of GluR3

The role of the glutamate receptor GluR3 in Rasmussen's encephalitis is actively under investigation. Autoimmune processes with this receptor as the target are currently theorized. We provide an additional case of pathologically proved Rasmussen's encephalitis (with concomitant cortical dysplasia) in the presence of antibodies against the GluR3 receptor.     

Respiratory sinus dysrhythmia persists in transplanted human hearts following autonomic blockade

1. The present study was performed to test whether beat-to-beat cardiovascular control in cardiac allograft recipients resides in cholinergic and/or adrenergic nerves that are intrinsic to the heart. 2. Heart rate (HR) fluctuations synchronous with respiration during spontaneous, double tidal volume and metronome-synchronized breathing were quantified in 13 human heart transplant recipients. We also examined the effects of sequential cholinergic and beta-adrenoceptor (combined) autonomic blockade on respiratory sinus arrhythmia (RSA). We computed RSA amplitude and the correlation between respiration and changes in HR (cardiopulmonary synchronization; CPS). Group means were compared using repeated-measures analysis of variance. Transplant recipients served as their own controls. 3. In the basal state, moderate RSA amplitude and CPS were observed. During cholinergic and combined blockade, we observed no significant change in RSA amplitude, whereas CPS increased significantly during combined blockade (P < 0.05). The amplitude of RSA increased during respiration at double baseline tidal volume, but not at any of the other breathing manoeuvres (P < 0.01). In contrast, CPS increased significantly during both patterned breathing manoeuvres. No significant correlation was seen between mean right atrial pressure and RSA amplitude. In 23% of subjects with low CPS, HR oscillated with arterial pressure. These oscillations were independent of respiration. During all three patterns of respiration, a significant inverse correlation was observed between CPS and pulse pressure (r = -0.53 to -0.73). Thus, as the amplitude of pulse pressure increased, respiration accounted for a smaller percentage of HR variation. 4. In conclusion, RSA persists and the magnitude of CPS increases following combined autonomic blockade. These studies suggest that while RSA after cardiac transplantation is not cholinergically or adrenergically mediated, it may be related to mechanical stretch of the sinus node caused by changes in intrathoracic pressure and perfusion pressure.     

Conversion from phacoemulsification to extracapsular cataract extraction: incidence, risk factors, and visual outcome

PURPOSE: To evaluate the incidence, risk factors, and visual outcome in cases converted from phacoemulsification to routine extracapsular cataract extraction (ECCE). SETTING: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS: A retrospective study was performed in 540 eyes that had clear corneal phacoemulsification performed by an experienced phacoemulsification surgeon. The cases in which phacoemulsification was initiated and then converted to ECCE were studied. The main parameters evaluated were the factors responsible for the conversion, corneal endothelial cell loss, and visual outcome. RESULTS: Twenty eyes (3.7%) required conversion to ECCE during phacoemulsification. Pupillary miosis (6 cases), posterior capsule rupture (5 cases), prolonged phaco time (4 cases), posterior extension of the capsulorhexis (2 cases), corneal thermal burn (1 case), subluxation of the lens (1 case), and malfunctioning of the ultrasonic handpiece (1 case) were the reasons for the conversion. The mean percentage of endothelial cell loss was 11.06% +/- 2.3 (SD); 18 cases (90.0%) achieved a visual acuity of 20/40 or better at 6 weeks. CONCLUSIONS: Intraoperative pupillary miosis, posterior capsule rupture, and very hard nuclear cataract causing prolonged phacoemulsification were the major risk factors for conversion to ECCE. Optimal preoperative preparation and prompt recognition of complications during phacoemulsification can lead to timely conversion to ECCE to achieve a good visual outcome.     

Prospective evaluation of quality of life after conventional abdominal aortic aneurysm surgery

The authors report a case of paraplegia caused by a lumbar intraspinal paracoccidioidomycosis (PCM) granuloma. Clinical neurological diagnosis of a compressive spinal cord lesion was confirmed by spinal magnetic resonance imaging (MRI). Patient was submitted to surgery with total excision of the lesion. Histopathological analysis confirmed the diagnosis of PCM. Patient is on sulfamethoxazole/trimethoprim combined with fluconazole and is experiencing positive neurological recovery.     

Gastroenteritis in children: principles of diagnosis and treatment

Gastroenteritis in children is a common reason for visits to family physicians. Most cases of gastroenteritis have a viral etiology and are self-limited. However, more severe or prolonged cases of gastroenteritis can result in dehydration with significant morbidity and mortality. This is often the scenario in third-world countries, where gastroenteritis results in 3 million deaths annually. A proper clinical evaluation will allow the physician to estimate the percentage of dehydration and determine appropriate therapy. In some situations, laboratory studies such as determination of blood urea nitrogen and serum electrolytes may be helpful. Stool studies are indicated if a child is having bloody diarrhea or if an unusual etiology is suspected, such as Escherichia coli O157:H7 or Cryptosporidium. Most children with gastroenteritis can be treated with physiologically balanced oral rehydration solutions. In children who are hypovolemic, lethargic and estimated to be more than 5 percent dehydrated, initial treatment with intravenous boluses of isotonic saline or Ringer's lactate may be required. Children with severe diarrhea need nutrition to restore digestive function and, generally, food should not be withheld.     

Inhibition by the JAK/STAT pathway of IFNgamma- and LPS-stimulated nitric oxide synthase induction in vascular smooth muscle cells

Inducible nitric oxide synthase (iNOS) is induced in many cell types by cytokines and lipopolysaccharide (LPS). Cytokine signal transduction is believed to be mediated primarily through the JAK/STAT pathway. We therefore examined the effects of a JAK2-specific inhibitor, an antisense oligonucleotide to JAK2, and electroporation of neutralizing anti-STAT1 and anti-STAT3 antibodies on IFNgamma- and LPS-stimulated induction of iNOS in vascular smooth muscle cells. Unexpectedly, we found that the JAK/STAT pathway suppresses IFNgamma- and LPS-stimulated iNOS induction in these cells. In contrast, the JAK/STAT pathway appears to have a positive role in iNOS induction in RAW 264.7 macrophages.