Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Raman spectroscopic study of glutaraldehyde-stabilized collagen and pericardium tissue

For the first time, Raman spectroscopy has been employed to investigate formation of cross-links in collagen and porcine pericardium tissue upon glutaraldehyde (GA) treatment. GA treatment causes a very high fluorescence background, which overlaps Raman bands. It has been found that short fixation time, i.e. 2 h, reduces background radiation significantly, providing new possibilities for studying changes in molecular structure of collagen upon GA modification. The observed changes in position and intensity of Raman bands allowed us to recognize different types of GA-collagen interactions. Strong spectral evidence has been found for the peptide contribution to the formation of the GA-collagen cross-links and for the formation of secondary amines via Schiff base intermediates, and pyridinium-type cross-links. The results also revealed that different hydration levels and a more complex structure of intact tissue in comparison to collagen preparation strongly influence the formation of a GA cross-linking network, e.g. ether-type bond is preferred to form in a less hydrated collagen preparation. Our results have shown that GA treatment causes an increase in water content of pericardium tissue and collagen.     

New evidence from magnetic resonance imaging of brain changes after climbs at extreme altitude

The aim of the present study was to look for anatomical changes in climbers' brains, using magnetic resonance imaging (MRI), after extremely high-altitude climbs and to relate them to possible associated risk factors. Clinical history, neurological examinations and MRI were carried out on a group of nine climbers before and after climbing to over 7500 m without the use of supplementary oxygen. None of the subjects showed any neurological dysfunctions. In five climbers MRI abnormalities (high signal areas, cortical atrophy) were observed before the expedition. After the descent, two of them showed new high intensity signal areas recorded by MRI. Both subjects suffered severe neurological symptoms during the climb. The present study suggested that the brain changes observed by MRI could be related to the severity of clinical events at high altitude. However, we do not know the exact meaning of such MRI findings or the reason for their location, predominantly in posterior regions of the brain. The new evidence that a high percentage of climbers show MRI brain abnormalities, and especially the appearance of changes after the ascent, reinforces the possibility of a potential neurological risk in high-altitude climbing.     

Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Macrophage antitumor activity in vitro. Comparative analysis of cytolytic, cytostatic, and cytotoxic activities of mouse macrophages and human monocytes

Mouse peritoneal M phi and human blood monocytes were assayed for their antitumor activity in vitro with a cytolysis, a cytostasis and a cytotoxicity test performed in parallel. Both natural and stimulus-induced M phi antitumor capacities were assessed. Results indicate that natural cytolytic activity of unstimulated M phi is generally unable to restrict final tumor cell growth, since it is not coupled with cytostatic capacity. In contrast, exposure of M phi in vitro to either MAF or IFN-beta, besides augmenting M phi cytolytic capacity, induced a very significant cytostatic activity and thus efficiently restricted the survival of tumor cells.     

Role of NK cells and gamma interferon in transplacental passage of Toxoplasma gondii in a mouse model of primary infection

Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and BALB/c mice decreased congenital Toxoplasma transmission, contrasting with an exacerbation of maternal infection. These data suggest that a partially protective immunity against congenital toxoplasmosis is achieved due to the increased number of NK cells in RAG-2(-/-) mice. However, it seems that IFN-gamma enhances, directly or indirectly, the transplacental transmission.     

Follicular cells of tonsils metabolise more deoxycytidine than other cell populations

Nine subpopulations of tonsillar lymphocytes and the unseparated cells were compared in their utilization of exogenous deoxycytidine ([5-3H]CdR) and thymidine ([3H]TdR). Uptake phosphorylation and incorporation of labeled precursors were determined in B and T lymphocytes, in low density (LD; enriched in S phase cells) and in high density (HD; enriched in G0/G1 phase cells) cell fractions as well as in LD and HD subfractions of B and T lymphocytes, and in cells isolated from follicles of tonsils. As expected, LD cells and B lymphocytes were more active in TdR incorporation than HD cells and T lymphocytes. However, the ratio of [5-3H]CdR to [3H]TdR in their total phosphorylation and incorporation into DNA was much lower than the expected value of 1: about 0.5 for total phosphorylation and about 0.3 for incorporation in all subpopulations, except for the follicular cells, where these ratios were 1.0 and 0.7, respectively. These results show that the relative utilization of the two pyrimidine deoxyribonucleoside precursors varies among different lymphocyte subpopulations. However, this variation is not due to the different rate of DNA synthesis; rather, it depends on the differentiation stage of lymphocytes occurring in the germinal center of the follicles.     

Exchange equilibria on anion resins, 2. Effect of chemical structure of functional groups in macroporous polystyrene resins

Anion exchange equilibria were studied by the batch technique on macroporous polystyrene resins with the following functional groups: \documentclass{article}\pagestyle{empty}\begin{document}$ - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm CH}_{\rm 3} ({\rm M),} - \mathop {\rm N}\limits^ + {\rm H(CH}_{\rm 3} )_2 ({\rm DE),} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 3} )_3 ({\rm TM),} - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH (E),} - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 2} ({\rm DE),} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 3} ({\rm TE),} - \mathop {\rm N}\limits^ + {\rm CH}_{\rm 3} {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 2} ({\rm MDE), and} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 3} {\rm )}_{\rm 2} {\rm CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH (DME)}$\end{document}. The selectivity order for these groups in slightly acidic, dilute solutions for the following anion systems: Br^?/Cl^?, I^?/Cl^?, and ClO₄^?/Cl^? was found to be TM > DME > MDE > TE > DM > M > DE > E, but it was entirely reversed in the case of F^?/Cl^? system. These results are discussed in view of some known theories of ion exchange selectivity. It seems that the experimental data can be best explained in terms of the Chu-Diamond-Whitney theory which takes into consideration mainly changes of the water structure caused by counter-ions, co-ions, and functional groups of the ion exchanger.     

Antipeptide monoclonal antibodies inhibit the binding of rabies virus glycoprotein and alpha-bungarotoxin to the nicotinic acetylcholine receptor

It has been reported that binding to muscle nicotinic acetylcholine receptor at the post-synaptic membrane is an important event of the rabies virus neurotropism. The binding site can be located within the 190-203 region of the virus glycoprotein sharing a high degree of homology with the "toxic loop" of the curare-mimetic snake neurotoxins. We have synthesized a tetradecapeptide corresponding to this glycoprotein region and used it, following conjugation with an immunogenic carrier to raise MAbs. We found that some MAbs raised against the peptide were able to recognize both the virus glycoprotein and the snake neurotoxin alpha-bungarotoxin; moreover, they can inhibit the binding of rabies virus glycoprotein and alpha-bungarotoxin to the nicotinic acetylcholine receptor extracted from the electric organs of Torpedo marmorata. On the basis of this cross-reactivity, we suggest that rabies virus glycoprotein and curare-mimetic snake neurotoxins share three-dimensionally similar structures in order to bind to the nicotinic cholinergic receptor. The potential use of the immunogenic properties of the peptide for the rational design of a synthetic vaccine against rabies is proposed.