Shades of gray matter: Noninvasive optical images of human brain reponses during visual stimulation

Recent theories about human brain function emphasize the need for imaging methods that allow the study of dynamic interactions among different structures. In this paper, we report on a new technique, based on the measurement of parameters of migration of near-infrared photons, that yields functional images of the human occipital cortex, combining a spatial resolution of 0.5 cm and a temporal resolution of 50 ms. This technique appears to be suitable for studying the dynamics of cortical activation.     

Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus-insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris-buffer or homogenized H. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non-reducing but not under reducing conditions. The predominant IgG-sub-classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec-tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission-blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).     

Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages

Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients with myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.Key words: limb girdle muscle dystrophies, muscle fatigue, muscle exercise     

High-dose epirubicin in patients with advanced or recurrent uterine sarcoma

Twenty patients with advanced or recurrent uterine sarcoma who had not received prior chemotherapy, were treated with epirubicin 120 mg m⁻² intravenously every 3 weeks. Four patients (20%) achieved complete response (pathologically confirmed in three cases) and three (15%) achieved partial response. The overall response rate was 35% (95% CI: 15–59). no response was observed for pelvic lesions in previously irradiated areas. Three patients (15%) exhibited stable disease, while 10 (50%) had progressive disease. The median number of courses was six in responders and two in non-responders. The median survival was 48 months (range 19–50+ months) in responders and 6 months (range 2–18 months) in non-responders. Adverse effects consisted primarily of myelosuppression, nausea and vomiting. No patients experienced life-threatening toxicity. High-dose epirubicin appears to be active in patients with advanced or recurrent uterine sarcoma.     

Polymorphism at the 5'' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.     

FN14 Signaling Plays a Pathogenic Role in a Mouse Model of Experimental Autoimmune Myocarditis

BackgroundThe pathogenesis of inflammatory cardiomyopathy is affected by the activation of autoimmune-mediated cascades. To study these cascades, we developed an experimental model of troponin I (TnI)-induced autoimmune myocarditis (EAM). One factor playing a pivotal role in the context of autoimmune disorders is the receptor fibroblast growth factor-inducible 14 (FN14). Thus, the impact of FN14 in the development of autoimmune myocarditis was investigated.Methods and ResultsTnI-immunization led to a significantly increased myocardial FN14 mRNA and protein expression in wild-type (wt) mice. To investigate the precise role of FN14 in EAM, FN14 knockout (ko) and wt littermates were immunized with TnI or control buffer. The animals were evaluated for cardiac parameters and indicators of myocardial injury. FN14 deficiency resulted in better cardiac performance, less myocardial inflammation, fibrosis, and cardiac damage. A lower myocardial mRNA expression of inflammatory cytokines and chemokines as well as their receptors could be demonstrated in TnI-immunized FN14ko compared to wt mice also immunized with TnI. Western blot analysis revealed a contribution of nuclear factor kappa-light-chain-enhancer of activated B cells to FN14-induced signaling cascades.ConclusionsIn the pathogenesis of autoimmune myocarditis, the inflammatory response to cardiac injury is attenuated in FN14ko mice. Thus, inhibition of FN14 in patients might represent a novel therapeutic strategy in the treatment of inflammatory cardiomyopathy.