L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease

The effective action of endothelium-derived nitric oxide (EDNO) is impaired in patients with atherosclerosis. This impairment has been attributed in part to increased vascular oxidative stress. EDNO action is improved by administration of ascorbic acid, a water-soluble antioxidant. Ascorbic acid is a potent free-radical scavenger in plasma, and also regulates intracellular redox state in part by sparing cellular glutathione. We specifically investigated the role of intracellular redox state in EDNO action by examining the effect of L-2-oxo-4-thiazolidine carboxylate (OTC) on EDNO-dependent, flow-mediated dilation in a randomized double-blind placebo-controlled study of patients with angiographically proven coronary artery disease. OTC augments intracellular glutathione by providing substrate cysteine for glutathione synthesis. Brachial artery flow-mediated dilation was examined with high-resolution ultrasound before and after oral administration of 4.5 g of OTC or placebo in 48 subjects with angiographically documented coronary artery disease. Placebo treatment produced no change in flow-mediated dilation (7.0+/-3.9% vs. 7.2+/-3.7%), whereas OTC treatment was associated with a significant improvement in flow-mediated dilation (6.6+/-4.4% vs. 11.0+/-6.3%; P = 0.005). OTC had no effect on arterial dilation to nitroglycerin, systemic blood pressure, heart rate, or reactive hyperemia. These data suggest that augmenting cellular glutathione levels improves EDNO action in human atherosclerosis. Cellular redox state may be an important regulator of EDNO action, and is a potential target for therapy in patients with coronary artery disease.     

Interferon-gamma antagonizes transforming growth factor-beta2-mediated immunosuppression in murine Toxoplasma encephalitis

The in vivo modulating activity of recombinant transforming growth factor (TGF)-beta2 on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta2 lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta2 induced a profound dose-dependent increase of the intracerebral parasitic load as well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a coincident decrease of MHC class II antigen expression of macrophages, microglial cells, and B cells. Furthermore, TGF-beta2-treated C57BL/6 mice showed a reduced activation of CD4+ and CD8+ T cells and a diminished recruitment of immune cells to the brain. The TGF-beta2-mediated development of lethal toxoplasmosis in C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma.     

Accurate estimates of the generalization ability for symmetric set of predictors and randomized learning algorithms

The main issue of the combinatorial approach to overfitting is to obtain computationally efficient formulas for overfitting probabilities. A group-theoretical approach is proposed to simplify derivation of such formulas when the set of predictors has a certain group of symmetries. Examples of the sets are given. The general estimate of overfitting probability is proved for the randomized learning algorithm. It is applied to four model sets of predictors—a layer of the Boolean cube, the Boolean cube, the unimodal chain, and a bundle of monotonic chains.     

Projection of topographic maps from curved brain surfaces into a plane

The environment is represented in the brain by topographic maps. These maps and their interrelationship form a dominant feature in the brain, but unfortunately, they are often projected onto surfaces which are variously curved. It would be useful to be able to compare the topography on these surfaces quantitatively with the origin of the map. This comparison would be possible if the curved brain surfaces could be represented in planes. Therefore, it was necessary to develop a procedure for unfolding maps on convex structures like the retina and the optic tectum of the chick. For this purpose a unit sphere was constructed whose origin was close to the centre of gravity of the curved brain structure. The surface of this structure was then projected into the sphere. From its representation on the spherical surface it was unfolded into the plane using a polar azimuthal radially equidistant projection. Our method can safely be applied to convex structures only. However, it is not limited to the visual system. The mathematical procedure is formulated in such a way as to be easily implemented. It is exemplified by experiments on the optic tectum and the developing retina of the chick.     

Controlled multicenter trial of laparoscopic transabdominal preperitoneal hernioplasty vs Shouldice herniorrhaphy. Early results

BACKGROUND: In February 1993 a prospective randomized multicenter trial was initiated to compare laparoscopic transabdominal preperitoneal hernioplasty to Shouldice herniorrhaphy as performed by surgeons of nonspecialized clinics. METHODS: Until January 1994, 87 patients with 108 hernias took part in the trial (43 Shouldice and 44 laparoscopic repairs). RESULTS: The laparoscopic procedure took significantly longer than did the open operation but caused less pain as measured by pain analogue score and consumption of paracetamol and narcotics. The postoperative complication rate was 26% in the open and 16% in the laparoscopic group. The patients in the laparoscopic group were discharged earlier and their convalescence was shorter than after open hernia repair. There has been one early recurrence in the laparoscopic and two in the open group to date with a mean follow-up of 201 days. CONCLUSIONS: Laparoscopic hernia repair causes less pain than the conventional operation and enables the patient to return to full work and usual activities earlier. The recurrence rate will not be known for 5 years.     

Lower limb paralysis induced in mice by a temperature-sensitive mutant of Moloney leukemia virus

A temperature-sensitive mutant of Moloney murine leukemia virus defective in an early function and injected into newborn mice produced lower limb paralysis. Susceptible mice were inbred strains CFW/D, CBA/H, C3H/Bi/Ka, and outbred NIH Swiss stock. Inbred W/Fu rats and C57BL/Ka mice did not develop the paralysis, though the latter were infected with virus; the sera from these mice produced paralysis in susceptible CFW mice.