Detection and recognition of radial frequency patterns

Detection thresholds for radial deformations of circular contours were measured using a range of radii and contour peak spatial frequencies. For radial frequencies above two cycles, thresholds were found to be a constant fraction of the mean radius across a four-octave range of pattern radii and peak spatial frequencies (mean Weber fraction: 0.003-0.004). At low radial frequencies, thresholds were unaffected by contrast reduction. In 167 ms presentations, subjects were able to identify radial frequencies of six cycles and below with an accuracy of over 90% correct even when phase was randomized. The extreme sensitivity of subjects to these radial deformations (as low as 2-4 s of arc) cannot be explained by local orientation or curvature analysis, and points instead to the global pooling of contour information at intermediate levels of form vision.     

Absolute conservation of residue 6 of immunoglobulin heavy chain variable regions of class IIA is required for correct folding

While studying the expression of single-chain antibodies (scFv) derived from several murine monoclonal antibodies, we found that residue 6 in Framework region 1 of the heavy chain variable domain plays a crucial role in antibody folding. Binding activity of three murine antibodies with a heavy chain variable region (VH) subgroup IIA was completely lost when at this position the wild-type residue glutamine (Q) was substituted by glutamate (E). Increased sensitivity towards trypsin digestion of soluble scFv suggested that the lack of binding activity was caused by incorrect folding of Q6E mutants. Grafting of the three additional class IA derived FR1 residues, based upon the comparison between both classes of VH sequences, on to the 'defect' subgroup IIA sequence, partially restored the antigen binding activity of the Q6E-containing scFv. Our results suggest that residue 6 of the heavy chain may be part of a folding nucleus, involving the first two beta-strands of Framework region 1. The evolutionary conservation of either glutamine or glutamate at position 6 in different antibody families may well indicate that within immunoglobulin VH domains, different family specific folding nuclei have evolved.     

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.     

Stressful life events and personality styles: relation to impairment and treatment outcome in patients with social phobia

Forty-five patients with social phobia and 15 individuals with no mental disorder were compared on number and type of life events experienced. Social phobia patients were further examined to evaluate the effect of negative life events and of the interaction between personality style and life events on severity of impairment and reactions to cognitive-behavioral group therapy. Patients with social phobia reported more negative life events than participants with no mental disorder. Among patients with social phobia, more frequent negative life events were associated with higher scores on measures of depression and general anxiety. Patients high on autonomy who reported more negative autonomous (i.e., achievement-oriented) life events also scored higher on measures of social anxiety and general anxiety. There were no significant interactions between sociotropy and the frequency of reported socially oriented negative life events. However, patients high on sociotropy scored higher on measures of social anxiety, depression, and general anxiety. Patients who had experienced more negative life events improved more after treatment on measures of social anxiety than did those who had experienced fewer negative life events. Implications of these findings and recommendations for future research are discussed.     

Unusual immunocytochemical and ultrastructural features of synovial fluid cells in multicentric reticulohistiocytosis. A case report

We present the first report in which cells in synovial fluid from a patient with multicentric reticulohistiocytosis (MRH) were studied by immunocytochemistry for correlation with routine light and electron microscopy. MRH cells stained predominantly for lymphocyte-related surface antigens and not for the monocyte marker LEU M3 (CD14). These findings suggest a lymphocytic origin of MRH cells and not a histiocytic origin, as previously suggested. In addition, large numbers of membrane-bound, electron-dense, secretory-type granules were found ultrastructurally in the cytoplasm of these cells.     

Reversed-flow affinity elution applied to the purification of carboxypeptidase Y

BACKGROUND: Despite curative resection for colorectal cancer, many patients develop recurrence at the primary site or distant organs. These patients are candidates for (neo)-adjuvant chemotherapy. Very little is known about the effect of preoperative 5-fluorouracil (FU) on the healing of colonic anastomoses. The aim of this study was to assess this in a rat model. METHODS: Eighty male Wistar rats, weighing 160-215 g, were divided into three groups; (1) a control group underwent left colon resection and primary anastomosis (n = 20); (2) a sham group received 1 ml saline intraperitoneally (n = 30); (3) a study group received 5-FU intraperitoneally (20 mg kg-1). Both saline and 5-FU injections were given intraperitoneally for 5 days before operation. RESULTS: There was no difference in the rate of wound complications, intraperitoneal adhesions and anastomotic complications among the groups. Three and seven days after operation, mean bursting pressure of the anastomosis was 36.5 and 198 mmHg in group 1, 34 and 200 mmHg in group 2, and 39 and 190 mmHg in group 3 respectively (P not significant). Although the myeloperoxidase and hydroxyproline content were significantly lower after 5-FU therapy (P < 0.01, compared with others), the clinical outcome was similar. CONCLUSION: Preoperative 5-FU consecutive days before operation had no effect on the healing of colonic anastomoses.     

Laryngeal Kaposi's sarcoma in patients with AIDS

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.     

The recombinant dehydrin-like desiccation stress protein from the resurrection plant Craterostigma plantagineum displays no defined three-dimensional structure in its native state

Dehydration stress in the drought-tolerant resurrection plant Craterostigma plantagineum is accompanied by the accumulation of a large number of desiccation stress proteins (Dsp). One abundant class of these is represented by the dehydrin-related Dsp16 protein which contains 15 amino acid conserved lysine-rich repeats and a stretch of eight serine residues providing extremely hydrophilic characteristics. Recombinant Dsp16 from Craterostigma plantagineum has been cloned and expressed in Escherichia coli. The protein was purified and characterized regarding its physicochemical properties. Irrespective of successful crystallization experiments, dilute aqueous buffer solutions do not display a well-defined three-dimensional structure in terms of the canonical secondary structural elements. 1H-NMR (nuclear magnetic resonance) spectra in aqueous solution are characterized by a small chemical shift dispersion typical for an unfolded protein; however, the observed line-widths are not typical for a highly mobile random coil structure. Instead they indicate an equilibrium between conformational states with preferentially extended substructures. As a consequence of its loose structure, Dsp16 is extremely sensitive towards proteolysis unless its structure is stabilized by structure-making additives such as trifluoroethanol. Denaturants such as guanidinium chloride do not induce cooperative structural transitions. pH-dependent fluorescence changes reflect protonation/deprotonation rather than conformational changes. Sedimentation/diffusion experiments confirm the predicted molecular mass of 16 kDa. Due to the high serine/threonine content and its loose structure, Dsp16 is accessible to phosphorylation, supporting the idea that in situ the structurally relatively undefined protein may be involved in both water binding and phosphorylation.