Highly resolving two-dimensional gels for protein sequencing.

Two-dimensional (2D) PAGE, using carrier ampholytes for the first-dimension separation, has provided a tool for the simultaneous analysis of cellular proteins. To extend the utility of 2D PAGE to the preparative level, we have investigated the use of immobilized pH gradients (IPG) for the first-dimension separation. The results we have obtained indicate that as much as 1 mg of cellular protein can be loaded onto a single IPG gel without loss of resolution. Mutant polypeptides previously detected in carrier ampholyte-based 2D gels were equally detectable in IPG-based 2D gels. With IPG gels several hundred cellular polypeptides can be isolated, from as few as 10 gels, in sufficient amount for sequencing with current sequencing technology. We therefore conclude that IPG greatly enhances the prospects for the large-scale sequencing of cellular proteins for the development of 2D gel-related protein data bases and for the identification of new polypeptide gene products, with the attendant implications for a genome sequencing effort.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Partial abnormal pulmonary venous return. An underestimated and unknown association in Turner-Ullrich syndrome. Presentation of an original case]

The authors report the case of a 59-year-old woman with a complex cardiac lesion consisting of degenerative major mitral insufficiency masking partial abnormal pulmonary venous return. These cardiac abnormalities fell within a context of genetic disease since the patient had Turner's syndrome, confirmed at the age of 58 by a 45 x 0 karyotype. They detail the originality of the clinical manifestations of partial abnormal pulmonary venous return and review the literature concerning cardiac malformations in Turner's syndrome.     

TANDEM URETEROCYSTOPLASTY

Background : Bladder augmentation may be undertaken by using various gastrointestinal segments but their use is associated with a multitude of well-recognized complications. The mega-ureter has proven to be a satisfactory alternative; in patients with bilateral mega-ureters, both ureters may be used for this purpose. Methods : Seventeen patients had augmentation ureterocystoplasty, including three in whom both distal ureters were used in tandem. The latter included two patients with neurogenic bladder and one with bladder exstrophy. Results : Satisfactory augmentation was achieved in all patients undergoing tandem ureterocystoplasty. The neurogenic bladder patients are managed by urethral clean intermittent catheterization (CIC) and the exstrophy patient is managed by CIC of an appendico-vesicostomy (Mitrofanoff). All are continent. Conclusions : The mega-ureter provides an excellent source of augmentation material in patients with small non-compliant bladders. In those with bilateral mega-ureters, consideration should be given to using both ureters in tandem to achieve the maximum possible bladder capacity.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Prognostic and immunohistochemical validation of the capella classification of pancreatic neuroendocrine tumours: an analysis of 82 sporadic cases

AIMS: To study the clinical outcome of 82 cases of pancreatic neuroendocrine tumours classified according to the recent histological and prognostic classification of Capella. METHODS AND RESULTS: Eighty-two surgical cases of pancreatic neuroendocrine tumours were examined histologically with immunohistochemical staining of paraffin sections using streptavidin-biotin complex and application of antibodies against chromogranin A and 10 hormonal peptides. Classification in four groups correlated with long follow-up and outcome of these cases. Histological examination showed 30 group I, four group II, 41 group III and seven group IV tumours. Twenty-one (70%) of group I tumours were insulinomas, whereas 25% of group III tumours were glucagonomas and 25% were unclassified. Most group IV tumours were unclassified, showing no immunohistochemical staining with any of the 10 hormonal peptides tested. Outcome was clearly correlated with tumour group. Among the 14 patients who died of the disease, four had group IV and 10 group III tumours. Thus, unclassified asymptomatic tumours without immunohistochemical staining had a poorer prognosis than asymptomatic tumours with staining. CONCLUSION: This study validates the Capella classification as easy to apply and useful in predicting clinical outcome.     

Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis.

Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients.