Syntheses and Antibacterial Activity of N-Acylated Ciprofloxacin Derivatives Based on the Trimethyl Lock

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Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

The swelling of secretory vesicles has been implicated in exocytosis, but the underlying mechanism of vesicle swelling remains largely unknown. Zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas, swell in response to GTP mediated by a G(alpha)i3 protein. Evidence is presented here that the water channel aquaporin-1 (AQP1) is present in the ZG membrane and participates in rapid GTP-induced vesicular water gating and swelling. Isolated ZGs exhibit low basal water permeability. However, exposure of granules to GTP results in a marked potentiation of water entry. Treatment of ZGs with the known water channel inhibitor Hg2+ is accompanied by a reversible loss in both the basal and GTP-stimulatable water entry and vesicle swelling. Introduction of AQP1-specific antibody raised against the carboxyl-terminal domain of AQP1 blocks GTP-stimulable swelling of vesicles. Our results demonstrate that AQP1 associated at the ZG membrane is involved in basal as well as GTP-induced rapid gating of water in ZGs of the exocrine pancreas.     

Long-term results of open and closed sphincterotomy for anal fissure

Three hundred fifty patients who underwent open or closed lateral internal anal sphincterotomy for acute or chronic anal fissure between January 1981 and June 1985 were reviewed. Minimum follow-up was 14 months (mean, 37 months). No patient underwent an additional procedure at the time of sphincterotomy. Twenty-one failed to heal or developed a recurrence in the interval (6 percent). Five of these individuals were found subsequently to have Crohn's disease. Excluding these patients, the incidence of nonhealing was 4.6 percent. Eight patients (2.3 percent) developed postoperative infections requiring drainage, one half of which were associated with fistulas. Sixty patients (17 percent) complained of incontinence for flatus or feces. For two thirds, this was transient. There was no statistically significant difference in rate of healing or morbidity when comparing the open with the closed method.     

Maximum-entropy calculation of the electron density at 4 A resolution of Pf1 filamentous bacteriophage.

A 4 A electron-density map of Pf1 filamentous bacterial virus has been calculated from x-ray fiber diffraction data by using the maximum-entropy method. This method produces a map that is free of features due to noise in the data and enables incomplete isomorphous-derivative phase information to be supplemented by information about the nature of the solution. The map shows gently curved (banana-shaped) rods of density about 70 A long, oriented roughly parallel to the virion axis but slewing by about 1/6th turn while running from a radius of 28 A to one of 13 A. Within these rods, there is a helical periodicity with a pitch of 5 to 6 A. We interpret these rods to be the helical subunits of the virion. The position of strongly diffracted intensity on the x-ray fiber pattern shows that the basic helix of the virion is right handed and that neighboring nearly parallel protein helices cross one another in an unusual negative sense.     

Sympathetic innervation improves the contractile performance of neonatal cardiac ventricular myocytes in culture

We propose that sympathetic innervation could contribute to the improvement in cardiac contractility that normally occurs during neonatal life because these processes are developmentally coincident. Effects of sympathetic innervation were studied in primary cultures of isolated, not previously innervated ventricular cardiomyocytes from neonatal rats. Innervation was produced by addition of autologous neurons from the thoracolumbar sympathetic ganglia, and amplitude and frequency of myocyte contraction were measured by on-line video motion analysis. Sympathetic innervation significantly (P less than 0.0001) increased amplitude of contraction (by 34 +/- 8%) and decreased contraction frequency (by 36 +/- 3%). The effect of innervation on myocyte contractility was not attenuated by adrenoceptor blockade (10(-6) M propranolol and 10(-6) M phentolamine), but could be reproduced using medium conditioned by cocultures of neurons and myocytes. Sympathetic innervation improves the contractility of isolated cardiomyocytes, indicating that autonomic innervation contributes to maturation of cardiac function.     

Ventricular arrhythmias and cardiac hemodynamics in patients with myocardial infarction. Comparison of the acute and post-hospitalization phases

Sixty-six patients with myocardial infarction (MI) were studied during the acute hospital phase and during the six months after hospital discharge. The clinical characteristics, location of infarction, and data from right heart catheterization were studied in an attempt to determine what factors were associated with ventricular rhythm disturbance.Those patients with serious ventricular arrhythmias (SVA) in the acute phase of infarction were found to have a significantly greater degree of myocardial dysfunction as measured by pulmonary artery and pulmonary wedge pressure than patients with more normal rhythm (p<.05). Clinical classification of patients and location of infarction were not helpful in predicting SVA during the acute infarction period.Knowledge of hemodynamic data, presence of SVA and clinical characteristics in the acute infarction period were of no value in predicting the occurrence of SVA after hospital discharge. Patients having had an acute diaphragmatic infarction were found to have a higher incidence of SVA after hospital discharge.     

Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging

The standard approach to assess hematopoietic stem cell (HSC) engraftment in experimental bone marrow transplantation models relies on detection of donor hematopoietic cells in host bone marrow following death; this approach provides data from only a single time point after transplantation for each animal. In vivo bioluminescence imaging was therefore explored as a method to gain a dynamic, longitudinal profile of human HSC engraftment in a living xenogeneic model. Luciferase expression using a lentiviral vector allowed detection of distinctly different patterns of engraftment kinetics from human CD34+ and CD34+CD38- populations in the marrow NOD/SCID/beta 2mnull mice. Imaging showed an early peak (day 13) of engraftment from CD34+ cells followed by a rapid decline in signal. Engraftment from the more primitive CD34+CD38- population was relatively delayed but by day 36 increased to significantly higher levels than those from CD34+ cells (P <.05). Signal intensity from CD34+CD38-engrafted mice continued to increase during more than 100 days of analysis. Flow cytometry analysis of bone marrow from mice after death demonstrated that levels of 1% donor cell engraftment could be readily detected by bioluminescence imaging; higher engraftment levels corresponded to higher image signal intensity. In vivo bioluminescence imaging provides a novel method to track the dynamics of engraftment of human HSC and progenitors in vivo.