YC-1 potentiates the antiplatelet effect of hydrogen peroxide via sensitization of soluble guanylate cyclase.

In the present study, we showed that 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, could potentiate H2O2-induced inhibition of platelet aggregation and increase of platelet cGMP levels. The synergistic effect of YC-1 and H2O2 on platelet aggregation and increases of cGMP were almost completely prevented by catalase and a selective soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or partially attenuated by the hydroxyl radical scavenger mannitol. In contrast, superoxide dismutase failed to influence H2O2/YC-1-induced inhibition of aggregation. Furthermore, YC-1 could enhance the activation of soluble guanylate cyclase caused by FeSO4/H2O2 and, this effect was prevented markedly by mannitol. These results suggest that YC-1 may enhance the antiaggregatory effect of H2O2 via the sensitization of platelet soluble guanylate cyclase. In addition, this phenomenon is, at least in part, dependent on H2O2-derived hydroxyl radical.     

Helicobacter pylori clearance and serum gastrin and pepsinogen I concentrations in omeprazole treatment of duodenal ulcer patients

Objective: To determine which demographic factors may influence serum gastrin and pepsinogen I (PGI) levels in duodenal ulcer patients undergoing omeprazole treatment. Methods: We conducted an outpatient-based prospective study in the Veterans General Hospital, Taipei, to investigate the pharmacological effects on patients with duodenal ulcers receiving omeprazole treatment for 4 weeks. Sixty-eight patients (61 males/7 females, aged 25–73 years) with endoscopically confirmed duodenal ulcer were included. Gastrin and pepsinogen I levels were measured before and after treatment. Demographic factors including age, sex, smoking, ulcer healing and antral Helicobacter pylori colonization/clearance were analyzed, in order to measure their probable influences on serum gastrin and pepsinogen I levels. Results: Ulcer healing was seen in 92.6% of patients while 48 (70.6%) antral clearances were seen in 66 H. pylori colonized patients at the end of trial. Omeprazole monotherapy led to a marked elevation of serum gastrin (85.8 pg · ml⁻¹, SD 32.0 pg · ml⁻¹ vs 133.9 pg · ml⁻¹, SD 71.6 pg · ml⁻¹, P < 0.01), and pepsinogen I (111.0 ng · ml⁻¹, SD 36.7 ng · ml⁻¹ vs 253.6 ng · ml⁻¹, SD 64.8 ng · ml⁻¹, P < 0.01) levels when measured on day 29. Only patients showing antral H. pylori clearance exhibited an influence on the magnitude of pepsinogen I elevation following omeprazole monotherapy (143.9%, SD 67.3% vs 78.6%, SD 51.2%, P < 0.01). Moreover, the sensitivity and specificity of serum pepsinogen I variations were plotted on a receiving operating characteristic (ROC) curve. The 140% increased pepsinogen I level yielded a maximum accuracy of 80% specificity or 50% sensitivity to predict antral H. pylori clearance. Conclusion: Antral H. pylori clearance is at least partially responsible for the omeprzaole-induced hyperpepsinogenemia I. The magnitude of hyperpepsinogenemia I probably provides a non-invasive alternative for predicting H. pylori clearance. Received: 22 August 1996 / Accepted in revised form: 1 October 1998     

An N-linked high-mannose type oligosaccharide, expressed at the major outer membrane protein of Chlamydia trachomatis, mediates attachment and infectivity of the microorganism to HeLa cells.

The structure of the carbohydrate of the 40-kD major outer membrane component of Chlamydia trachomatis and its role in defining infectivity of the organism were investigated. The oligosaccharides were released from the glycoprotein by N-glycanase digestion, coupled to a 2-aminopyridyl residue, and subjected to two-dimensional sugar mapping technique. The major fractions consisted of "high-mannose type" oligosaccharides containing 8-9 mannose residues. Bi- and tri-antennary "complex type" oligosaccharides having terminal galactose were detected as minor components. These oligosaccharides were N-linked and contained no sialic acid. This structural profile is consistent with our previous characterization based on lectin-binding and glycosidase digestion. Functional specificity of identified chlamydial oligosaccharides was analyzed using glycopeptides fractionated from ovalbumin and structurally defined oligosaccharides from other sources. The glycopeptide fraction having high-mannose type oligosaccharide, as compared to those having complex or hybrid-type, showed a stronger inhibitory effect on attachment and infectivity of chlamydial organisms to HeLa cells. Among high-mannose type oligosaccharides, the strongest inhibition was observed with mannose 8 as compared with mannose 6, 7, or 9. These results indicate that a specific high-mannose type oligosaccharide linked to the major outer membrane protein of C. trachomatis mediates attachment and infectivity of the organism to HeLa cells.     

Effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease

Objective: The effect of ₂-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. Methods: To evaluate the effect of ₂-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV₁/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl^–1), FEV₁ or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl^–1 and it increased after salbutamol by 0.1 mEq·dl^–1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl^–1) compared to the saline control (3.7 mEq · dl^–1) and salbutamol (3.6 mEq · dl^–1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV₁, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.     

Demonstration of a software package for the reconstruction of the dynamically changing structure of the human heart from cone beam X-ray projections

The Dynamic Spatial Reconstructor (DSR) is a device constructed at the Biodynamics Research Unit of the Mayo Clinic for (among other things) the visualization of the beating heart inside the intact thorax. The device consists of 28 rotating X-ray sources arranged on a circular arc at 6° intervals (total span 162°) and a matching set of 28 imaging systems. The whole thorax of the patient is projected onto the two-dimensional screen of the imaging systems by cone beams of X rays from the sources. All of the X-ray sources are switched on and off within a total period of 10 milliseconds. The Medical Image Processing Group at the State University of New York at Buffalo has developed a software package for the design and evaluation of algorithms to be used by the DSR. In this paper we illustrate the operation of the package and a particular algorithm for the reconstruction of the dynamically changing structure of the heart from data collected by the DSR.     

Microbial O-carbamylation of novobiocin

Novobiocin was inactivated by Streptomyces niveus US 2094 in fermentation. The inactivation product was isolated and characterized by NMR and MS as 2"-O-carbamylnovobiocin. The MICs of novobiocin and 2"-O-carbamylnovobiocin were determined for S. niveus strains.     

Doppler velocimetry of intraplacental fetal arteries

Doppler velocimetry of the umbilical and intraplacental fetal arteries was studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream to the umbilical artery decreased significantly with advancing gestational age, and its S/Ds were persistently lower than those of the umbilical artery. The difference in the S/D between the umbilical artery and its intraplacental downstream branches decreased with advancing gestational age and approached zero as the pregnancy progressed to term. We conclude that intraplacental fetal arteries, possibly fetal arteries in main stem villi, can be imaged by color flow mapping and that there is a significant "resistance gradient" between the intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery velocimetry using color flow mapping may give further insights into the umbilical-placental circulation.     

Initial results of laser angioplasty under angioscopic guidance for salvage of an ischemic lower limb: preliminary report

From March to July 1989, nine patients at risk for peripheral artery disease underwent intraoperative Nd:YAG laser angioplasty using angioscopy at the Veterans General Hospital (Taipei, Taiwan, Republic of China). Following the laser angioplasty, balloon dilatation was performed in all cases. Eight men and one woman at an average age of 68 were included in the study (range: 58 to 78 years old). Ischemic symptoms included five patients with disabling claudication, four with pain at rest and one with gangrene on the toes. Eight of the nine patients had complete occlusions ranging from 2 to 19 cm in length. Two patients had high degree multiple segmental stenosis of the superficial femoral artery from 1 to 2 cm in length. Initial clinical success (indicated by relief of symptoms and increase in Doppler ankle pressure and index) and improvement in the angiographic luminal diameter was noted in 9 of 10 occluded vessels (90%) that underwent Nd:YAG laser treatment which was delivered at 10 to 12 watts through laser probes. Prelaser intraluminal diameter increased from 0.05 +/- 0.07 to 0.53 +/- 0.07 mm, Doppler ankle pressure index rose from 0.51 +/- 0.12 to 0.81 +/- 0.12, Doppler ankle pressure increased from 62.44 +/- 16.10 to 104 +/- 21.21 mmHg and the amplitude of pulse volume recorder at ankle level rose from 5.77 +/- 2.80 to 12.11 +/- 2.77 mm as compared with prelaser therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Observation of nervous tissue in a Wilms' tumor: its histogenetic significance.

A case of Wilms' tumor occurring in a horseshoe kidney is reported in which bona fide nervous tissue containing ganglion cells was observed. This finding cannot be reconciled with the currently held "metanephrogenic blastema" theory of the histogenesis of this tumor. Masson's concept of "neuroepithelial origin" of the Wilms' tumor should be re-evaluated.     

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.