Hemoglobins Aida (alpha 64 Asp leads to Asn) and D-Los Angeles (beta 121 Glu leads to Gln) in an Asian-Indian family

Hemoglobins D-Los Angeles (beta 121 Gln) and Aida (alpha 64 Asn) were encountered in an Asian Indian, unassociated with any clinical manifestations. These hemoglobins had normal oxygen affinities and were stable to heat and isopropanol. The ratio of alpha chain synthesis to beta chain synthesis was close to unity. The identical change in isoelectric points of the two variants produced an interesting electrophoretic pattern.     

Immunohistochemical localization of SKALP/elafin in psoriatic epidermis

Recently we have reported the purification and biochemical characterization of a new, inducible elastase inhibitor [skin-derived antileukoproteinase (SKALP)], which could be extracted in high amounts from psoriatic skin but not from normal human skin. Here we demonstrate the immunohistochemical localization of SKALP in psoriatic epidermis. SKALP was found exclusively in the upper layers of the suprabasal compartment and stratum corneum of lesional psoriatic epidermis. Basal keratinocytes were always negative. No immunoreactive SKALP was found in normal epidermis and non-lesional psoriatic epidermis, in accordance with findings in functional assays. Western blots of skin extracts from psoriatic and normal skin confirmed the immunohistochemical findings and revealed two major bands with apparent molecular weights of 10.5 and 11.5 kDa. We would hypothesize that SKALP could act as a modulator of epidermal inflammation by interfering with polymorphonuclear leukocyte trafficking, and that it could protect structural proteins against elastase-mediated damage.     

Structural organization and chromosomal localization of the human ribosomal protein L9 gene

Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microsomal fraction (Mc) and cross-reactive with mammalian tissues were used to evaluate the ability of cross-reactive T. cruzi antigens to induce an immune response in Chagas' disease. Thus, we studied the ability of sera from Chagas' disease patients (CDP) with different degrees of cardiac dysfunction to block the immune recognition of these MoAb to the target antigen determining for each serum an inhibition index (II). By means of this approach we inferred that blocking of monoclonal antibody binding to T. cruzi microsomes by subjects' serum represents antibodies with the same reactivity. After serological and medical examinations, individuals were separated into the following groups: Chagas' disease patients without manifest cardiac involvement (CDP-0), CDP with suspected or borderline cardiac disease (CDP-1), CDP with moderate myocardial dysfunction (CDP-2), CDP with overt cardiac dysfunction (CDP-3) and controls including healthy subjects (HS) and patients with idiopathic myocarditis (IMP). The reactivity between MoAb 5F2 and its target antigen was significantly (p < 0.05) inhibited by sera from CDP irrespective of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD: control: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p < 0.05) sera from CDP with mild disease (CDP clinical grade 0/1: n = 26, 34 +/- 18) from that of CDP with severe disease (CDP clinical grade 2/3: n = 20, 67 +/- 7). Moreover, the inhibitory capacity of sera from asymptomatic CDP (CDP-0) correlated with patients age (r = 0.66, p < 0.05). CDP-0 below or equal 40 years of age had results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean inhibition of CDP-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable (p > 0.05) from that of patients with severe disease. Competitive assay with MoAb 5A9B11 also showed significant differences (p < 0.05) between sera from CDP (n = 46, 46 +/- 24) and controls (n = 13, 5 +/- 5). On the contrary, the differences observed between CDP with different cardiac involvement was not significant (mild: n = 26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of data from asymptomatic sera revealed the existence of two levels of reactivity, with low and high capacity to inhibit the reaction of 5A9B11 against Mc. On the contrary, CDP sera showed a blocking activity for 1A10C11 comparable to that of controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). Some cross-reactive MoAbs recognized epitopes partially composed of carbohydrates. Interestingly, 5F2 and 5A9B11 epitopes did not appear to have carbohydrates moieties. In summary, immunoinhibition assays revealed differences in the immune response of chronic chagasic patients against parasite epitopes. These results have opened the possibility to identify a prognosis marker of the disease suggesting the clinical utility of monitoring levels of these anti-Mc antibodies in patients with chronic Chagas' disease.     

New ideas on the pathophysiology and treatment of lung disease

In the present study, the effects of compounds extracted from Tanacetum microphyllum, four flavonoids and one sesquiterpene lactone, on arachidonic acid metabolism in cellular systems were examined. In the PGE2- and LTC4-release assay, most compounds did not exhibit any significant effect. Only hydroxyachillin, and the flavonoids centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol showed a significant effect, although with less potency than the reference drugs, indomethacin and NDGA. However, all compounds inhibited the release of TXB2 from ionophore-stimulated human platelets. The action is more marked with the flavonoids santin and ermanin.     

An endogenous sialoprotein and a bacterial B cell superantigen compete in their VH family-specific binding interactions with human Igs

Staphylococcal protein A (SpA), a bacterial membrane protein, and protein Fv (Fv binding protein (pFv)), a human sialoprotein involved in gut-associated immunity, have both recently been shown to have unconventional V(H) family-restricted binding interactions with Igs. To determine whether these Ig binding proteins interact with related structures, we performed a series of comparative binding studies. The results confirmed that both molecules are bound by most V(H)3 IgM, but pFv is also recognized by V(H)3 and V(H)6 Ig that do not interact with SpA. We discovered that pFv and SpA (or a single domain of SpA) can compete for binding to a V(H)3 Ab, which suggests that they can recognize the same (or adjacent) V(H) sites. For both SpA and pFv, binding is less frequent among IgG than IgM. However, V(H)3 IgG more commonly possess Fab-mediated binding activity for pFv than for SpA. Binding studies of denatured Ig suggested that both pFv and SpA interact with conformationally dependent V(H) sites, although in certain cases pFv binding is more permissive than SpA binding. Taken together, these results indicate that the superantigen properties of SpA, a microbial protein, and those of pFv, an endogenous sialoprotein, involve binding interactions with overlapping and at times functionally equivalent sites in the V(H) domain, indicating that self and foreign proteins can employ highly conserved strategies to create superantigens for the Ag receptors of B lymphocytes.     

Posts and cores: state of the art

The primary way of preventing HIV infections is to change behaviors that enable transmission of the virus, specifically those behaviors relating to sex and drug injection. Realistic public health workers have focused on encouraging adoption of safer sexual practices, primarily condom use. The fundamental way to persuade people to engage in preventive practices is through targeted education aimed at particularly at-risk communities. Other effective behavioral interventions against HIV infections are: testing and follow-up counseling; comprehensive sex education; peer influence and community action; advertising and marketing; easing access to condoms; physician-patient dialogue; drug treatment; access to clean needles; and direct outreach. On the contrary, interventions that do not work are the following: one-time exposure to information; delivering a single message; abstinence-only programs; and coercive measures to identify people with HIV or their sexual partners.     

Nasal airflow after septorhinoplasty

The changes in nasal function which occur after septorhinoplasty for obstruction were investigated by anterior rhinomanometry in 15 subjects. Objective and subjective measures of outcome were compared. Anterior rhinomanometry was performed after nasal decongestion. These data were mathematically transformed to determine the amount of airflow asymmetry through the nostrils and the stiffness of the nasal valve. The results suggested that the presence of gross airflow asymmetry (> +/- 80%) in patients prior to surgery was a bad prognostic indicator for post-operative satisfaction with the airway. Patient satisfaction with function and cosmetic appearance post-operatively was correlated with the presence of symmetrical nasal airflow. Nasal valve stiffness did not seem to be affected by septorhinoplasty.