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Biomedical subjects

A Grabowska

Publications and source records attributed to A Grabowska.

At least 19 recordsLinked to original sources

Is there a role for nitric oxide in regulation of T cell secretion of IL-2?

Nitric oxide (NO) can have both effector (cytotoxic) and regulatory roles in immune function. In this study, we have re-examined the potential role of nitric oxide in mediating the macrophage-dependent suppression of IL-2 synthesis. In our model, TNP-specific CD4+ T cells are cocultured with Ag and either peritoneal or alveolar macrophages. Both populations of macrophages after in vitro stimulation with IFN-gamma can inhibit IL-2 release. In vitro stimulation also induces substantial levels of NO release by these macrophages, as well as high levels of prostaglandin E2 (PGE2). However, there was no correlation between NO levels and inhibitory activity. Furthermore, NG-monomethyl-L-arginine monoacetate, a specific inhibitor of NO release had no effect on IL-2 release, while indomethacin, which blocked prostaglandin synthesis, largely abrogated the suppressor activity of both macrophage populations. Although the addition of exogenous NO donors at high concentrations could inhibit IL-2 release by T cells, our data does not support the hypothesis that NO is a major macrophage mediator of suppression in this model.

Animals

Interhemispheric transmission of information and functional asymmetry of the human brain.

The study investigated directional differences in interhemispheric transmission time using the VEPs method. Specifically we were interested in whether there exists an asymmetry in the transmission of information to and from the hemisphere specialized in its processing. Two type of stimuli, specific for the left and right hemisphere, were presented in the left and right visual fields. The latency differences between visual evoked potential components registered in the hemispheres ipsilateral and contralateral to the stimulated hemifield were compared. Interhemispheric transmission time was shorter when the information was transferred from the hemisphere non-specialized for its processing to the specialized one than in the opposite direction. The results suggest the existence of a physiological mechanism that ensures fast transmission of information to that hemisphere which is more efficient in its processing.

Brain

Visual-spatial-frequency model of cerebral asymmetry: a critical survey of behavioral and electrophysiological studies.

In this article, the authors present a review of research on the role of the 2 hemispheres in processing spatial frequencies. J. Sergent (1982a) postulated that the hemispheres differ in their sensitivity to frequency characteristics of the sensory outputs on which cognitive processes are performed. Specifically, she proposed that the right hemisphere displays greater efficiency than the left hemisphere in processing low-spatial-frequency content of a visual image, whereas the left hemisphere is better equipped than the right to deal with high frequencies. The authors present an extensive review of behavioral and electrophysiological studies whose researchers tried to verify Sergent's hypothesis and offer its reformulation, taking into account the findings that have accumulated in the last 10 years.

Brain

Disturbances in time limited storage sensory information after right temporal lobectomy.

Our previous study performed on subjects with no brain damage suggested that processes involved in the storage of sensory information are lateralized to the right hemisphere. The present research aimed at verifying this hypothesis by studying the effect of unilateral temporal lobe lesion on performance in a sensory information storage test. Seventeen patients who had undergone a unilateral temporal lobectomy for the relief of intractable epilepsy (8 subjects--left hemisphere damage, 9 subjects--right hemisphere damage) and 11 normal control subjects with no brain damage were tested. The subjects were presented with geometrical Vanderplas type figures exposed in pairs, each for 100 ms, one after another, with short (50 ms and 500 ms) and long (3,000 ms) interstimulus intervals (ISI). The task of the subjects was to judge whether the second stimulus was the same as, smaller or bigger than the first one. The first stimulus in each pair was exposed unilaterally, randomly in the left (LVF) or right (RVF) visual field, and the second one in the centre of the screen. In short ISI conditions the RH-damaged group performed worse than both the control group and the LH-damaged group. In long ISI conditions the RH-damaged group did not differ from the controls. On the contrary the LH-damaged group did not differ significantly from the controls in any ISI condition. The results show that temporal lobe structures are involved in time limited storage of sensory information. Moreover, they provide further evidence for the right-hemispheric locus of this storage.

Adult

Sex differences in the processing of odd and even numbers.

Previous research has shown that decisions about odd numbers take longer than decision about even numbers (the "odd effect"). It has also been shown that females are better at processing linguistic stimuli and males are better at processing spatial stimuli. In the present experiment, male and female subjects made odd versus even classification judgments on numbers presented visually in three different formats: digits, number words, and dot patterns. Males showed longer decision times for odd numbers only when the numbers were presented in the dot pattern format. Females showed this effect only when the stimuli were presented in the word format. These results suggest that a differential speed of response to odd and even numbers is found most strongly when the stimuli are presented in a format which is processed more efficiently by the subjects. This finding may imply that the effect is being produced by some higher order cognitive process, based on higher order representations that do not necessarily involve linguistic or verbal coding.

Adult

Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages.

Nitric oxide (NO) plays a key role in mediating macrophage cytotoxicity towards different targets, including tumoral cells and intracellular pathogens. However, its role in macrophage immunoregulation is less well defined. In this study, we have investigated the effect of altering NO levels on the production by mouse macrophages of cytokines, and reactive oxygen intermediates as measured by luminol-dependent chemiluminescence. Our results demonstrate that NO can enhance the release of both tumor necrosis factor-alpha and interleukin-1 alpha, and chemiluminescence. Thus, in addition to acting as a powerful effector molecule in mediating cytotoxic activities of mouse macrophages, NO can play a role in enhancing the production of a variety of other inflammatory mediators, and thus can contribute both directly and indirectly to the immunopathology of macrophage-dependent inflammation.

Animals

Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators.

Taurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self-destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long-lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor alpha, and interleukin-6, but TauCl slightly enhanced the release of IL-1 alpha. The formation of nitrites by interferon-gamma-activated macrophages was inhibited by TauCl in a dose-dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration-dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.

Animals

The modulation of IL-2 dependent proliferation of CTLL-2 cells by 2-methyl-thiazolidine-2,4-dicarboxylic acid.

It is known that cysteine and other thiol compounds are able to modulate the immune response. The extracellular concentration of cysteine was shown to determine the intracellular level of glutathione (GSH). Thus cysteine, by enhancing GSH production, is able to affect some T-cell functions like IL-2 dependent cell proliferation and the generation of cytotoxic T cells. However, physiologically blood plasma cysteine is maintained at a very low concentration. The use of cysteine as a therapeutic compound in vivo is strongly limited due to its cytotoxicity. Recent studies demonstrate that N-acetyl-cysteine (NAC) as well as a variety of thiazolidine derivatives (TDs), which are the products of the reaction of L-cysteine with carbonyl compounds, could serve as a 'delivery' system for cysteine into the cell. In the present study, we have shown that 2-methyl-thiazolidine-2,4,-dicarboxylic acid (CP), the product of condensation of L-cysteine and pyruvate, strongly increases the proliferation of one particular cell line, IL-2 dependent CTLL-2 cells. We have also shown that this compound significantly increases the intracellular level of non-protein sulfhydryls (NPSH), but we did not find any correlation between NPSH levels and cell viability and proliferation. In contrast to CP, free cysteine showed its toxic properties by affecting cell viability of different cell lines and also by cancelling the influence of CP on the proliferation of CTLL cells.

Adjuvants, Immunologic

Effect of pentoxifylline on nitric oxide released by murine macrophages.

The growing knowledge on the pathological role of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in septic shock stimulated efforts to control their generation pharmacologically in clinical situations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl-L-arginine (an inhibitor of NO synthase), PTXF influenced NO generation only during the induction phase. In conclusion, we suggest that a possible new therapeutic approach in septic shock may result from the inhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental investigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.

Amino Acid Oxidoreductases

An improved experimental model for the study of in vitro release of nitric oxide by murine peritoneal macrophages.

In the immune system macrophages are the cells responsible for nitric oxide (NO) production. The synthesis of NO by activated macrophages correlates with their cytotoxic effect on neoplastic cells as well as killing of intracellular parasites. In the present paper we test several parameters that may influence (in vitro) NO production by murine peritoneal macrophages previously stimulated in vivo by intraperitoneal injection of thioglycollate. In our system the maximum NO/NO2- release was obtained in the culture containing 10(6) M phi/ml after 24 h incubation. For macrophage activation we used lipopolysaccharide (LPS) and several recombinant cytokines (IFN-gamma, TNF-alpha, IL-2, IL-3, IL-6). We also tested the influence of latex phagocytosis on NO production by simultaneously activated macrophages.

Animals

Differential effects of chlorination of bacteria on their capacity to generate NO, TNF-alpha and IL-6 in macrophages.

Activated rodent macrophages produce high amounts of nitric oxide (NO). NO as a tumoricidal and defence molecule against intracellular parasites is commonly accepted. However, its role as an obligatory killing factor for extracellular bacteria is controversial. In the present study we stimulated murine peritoneal macrophages by heat-killed bacteria (Staphylococcus aureus, S. epidermidis and Escherichia coli). In some groups bacteria were pretreated with HOCl, to replace the chlorinating system in activated neutrophils that operates as a bactericidal system in vivo. High levels of NO, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected after stimulation by all non-chlorinated bacteria strains tested. However, after chlorination Gram-positive bacteria lost their ability to induce NO and TNF-alpha, whereas phagocytosis and IL-6 production were not affected by chlorination.

Animals

Memory impairment in patients with stereotaxic lesions to the hippocampus and amygdala.

The study aimed at testing: (1) whether stereotaxic damage to the hippocampus and amygdala results in a memory deficit, (2) whether the memory functions subserved by the hippocampus are lateralized and (3) whether time limited storage of sensory information is impaired after focal hippocampal and amygdalar lesions. Seven patients with unilateral stereotaxic damage to the anterior part of hippocampus and unilateral or bilateral damage to the medial part of amygdala and 11 control subjects with no brain damage participated in the research. They were presented with memory tests that required either remembering a spatial arrangement of simultaneously presented verbal vs nonverbal stimuli or a temporal order of sequentially presented items. Moreover, a sensory information storage test was used. The results indicate that even small damage limited to the anterior part of the hippocampus and medial part of the amygdala results in a mild memory deficit. Memory impairment was not related to the side of hippocampal lesion. This suggests that memory function subserved by the hippocampus is not lateralized. Differential effects of left and right lobectomies found in previous studies were, thus, probably due to the damage to temporal cortex. The results showed, however, that sensory information storage limited to 3 s is not impaired after focal damage to the hippocampus and amygdala. A clear lateralization effect showing right hemisphere advantage in that function was found.

Amygdala

Individual differences in the functional asymmetry of the human brain.

Standard models of hemispheric asymmetry assume the dychotomous division of functional competence between the two hemispheres. Individual subjects, however, often do not fit such prototypical patterns and show great variation with respect to the functional differentiation of their hemispheres. The present paper reviews the results of some of our investigations on the effect of various subject related factors on brain lateralization. Among these individual experience, gender and handedness seem to be of most significance.

Dominance, Cerebral

[Topical treatment of oral bleeding in children with clotting disturbances].

Owing to substitutive therapy an inhibition is possible of bleeding from oral mucosa as well as stomatological procedures in children with haemorrhagic diathesis. For elimination or limiting of substitutive therapy in 29 children with congenital haemorrhagic diathesis caused by plasma or platelet disorders, tissue glue was used. The preparation Tissucol, IMMUNO, was given during 37 stomatological procedures in which 44 tooth were extracted, and for post-traumatic bleeding from oral mucosa. Very good and good results were obtained in 95% of the performed stomatological procedures. That makes possible a statement that Tissucol is effective in maintaining of local haemostasis in children with haemorrhagic diathesis. This method is safer and less expensive than blood-derived preparations used for substitutive therapy, and is especially valuable in the treatment of children with haemophilia type A with antibodies against factor VIII.

Administration, Topical

Hemispheric asymmetry in stimulus size evaluation.

In the present study a possible hemispheric asymmetry in size evaluation was tested. Subjects were presented with geometrical Vanderplas type figures of various sizes and shapes. The stimuli were exposed in pairs, for 100 ms, one after another. The subject's task was to decide (by pressing one of three buttons) whether the second stimulus was the same as, smaller or bigger than the first one. The first stimulus in each pair was exposed unilaterally (randomly in the left or right visual field), and the second one in the centre of the screen. Three different interstimulus intervals (ISI) were used: 50 ms, 500 ms, and 2,000 ms. The results showed shorter reaction times for left visual field presentation than for right visual field presentation at the 50 ms and 500 ms interstimulus interval. No laterality effect occurred at the 2,000 ms ISI. The results indicate a right hemisphere predominance in stimulus size evaluation. Moreover, they suggest that hemispheric asymmetry is not a stable feature of the brain but is a dynamic process that may change in the course of information processing.

Adult

Transsexualism and sex-related differences in hemispheric asymmetry.

Sex differences in human brain lateralization are documented by studies on normal subjects, patients with the unilateral brain damage, and individuals with atypical level of hormones. However, there is no agreement as to the specific role of gender in the development of hemispheric asymmetry. This experiment was designed to examine whether gender identity plays an important role in the formation of brain lateralization, as some recent data seem to suggest. A group of subjects showing gender dysphoria (transsexuals) and two groups of control male and female subjects were presented with verbal and visual-spatial tasks. Results show that neither biological sex nor gender identity are sufficient factors to determine the pattern of hemispheric asymmetry.

Adolescent

The effect of unilateral brain lesions on perception of visual illusions.

The study tested the effect of the left and right hemisphere lesions on the susceptibility to visual illusions. Twenty-five patients with left hemisphere damage, 22 patients with right hemisphere damage and 23 control subjects inspected series of figures producing four different illusions: Ponzo, Ehrenstein-Orbison, Poggendorff and Zoellner. Series of stimuli configurations were constructed so that different degrees of distortion opposite to the illusory effect were introduced in each pattern. The amount of distortion was increased in steps so that at a certain point of the series the patterns produced percepts opposite to the illusory ones. That point indicated the strength of the illusion. Stimuli of a given series were presented to each subject 5 times in random order and subject's judgements of illusions were collected. The illusion strength was established using the Spearman distribution method for determining psychophysical thresholds. The results showed that the left and right hemisphere lesions either did not affect the subject's susceptibility to illusions (in Ponzo and Poggendorff) or their effects were similar, i.e. they reduced the strength of the perceived illusions (in Ehrenstein-Orbison and Zoellner). Our data contradict the hypothesis of hemisphere differences in the perception of visual illusions and support the view that those phenomena are multiple-caused.

Attention