Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis

Human C-reactive protein (CRP), as a mediator of innate immunity, removed damaged cells by activating the classical complement pathway. Previous studies have successfully demonstrated that CRPs are differentially induced as glycosylated molecular variants in certain pathological conditions. Affinity-purified CRPs from two most prevalent diseases in India viz. tuberculosis (TB) and visceral leishmaniasis (VL) have differential glycosylation in their sugar composition and linkages. As anemia is a common manifestation in TB and VL, we assessed the contributory role of glycosylated CRPs to influence hemolysis via CRP-complement-pathway as compared to healthy control subjects. Accordingly, the specific binding of glycosylated CRPs with erythrocytes was established by flow-cytometry and ELISA. Significantly, deglycosylated CRPs showed a 7–8-fold reduced binding with erythrocytes confirming the role of glycosylated moieties. Scatchard analysis revealed striking differences in the apparent binding constants (10⁴–10⁵ M⁻¹) and number of binding sites (10⁶–10⁷sites/erythrocyte) for CRP on patients’ erythrocytes as compared to normal. Western blotting along with immunoprecipitation analysis revealed the presence of distinct molecular determinants on TB and VL erythrocytes specific to disease-associated CRP. Increased fragility, hydrophobicity and decreased rigidity of diseased-erythrocytes upon binding with glycosylated CRP suggested membrane damage. Finally, the erythrocyte-CRP binding was shown to activate the CRP-complement-cascade causing hemolysis, even at physiological concentration of CRP (10 μg/ml). Thus, it may be postulated that CRP have a protective role towards the clearance of damaged-erythrocytes in these two diseases.     

The use of invertebrate functional groups to characterize ecosystem attributes in selected streams and rivers in south Brazil

An analysis conducted at nine stream/river sites in the Atlantic Forest region in the State of Paraná, Brazil used macroinvertebrate functional feeding group (FFG) assessments to evaluate ecological condition of the sites. The FFG approach categorizes qualitative macroinvertebrate collections according to their morphological-behavioral adaptations for food acquisition (e.g. scrapers that harvest non-filamentous, attached algae from stable surfaces in flowing water). FFG ratios were employed as surrogates for stream/river ecosystem attributes: balance between autotrophy and heterotrophy; linkage between riparian inputs of coarse particulate organic matter and in-stream food webs; relative dominance of fine particulate organic matter in transport (suspended load) compared to that deposited in the sediments; and geomorphic stability of the channel. The analyses indicated that all nine sites were heterotrophic, six of the nine carried expected levels of suspended organic load and showed below expected linkage with riparian inputs, and in only two were stable substrates limiting. The implications of the findings and recommendations for further analysis and modifications of the protocol are discussed.     

Brugada-type Electrocardiographic Pattern Induced by Electrocution

Heart is one of the most frequently affected organs in electrocution. Electrical injury can cause life-threatening cardiac complications such as asystole, ventricular fibrillation, and myocardial rupture. In this case report, we describe a 22-yr-old male patient who sustained electric burn injury and presented with electrocardiogram showing transient Brugada type pattern.     

Structural studies of the capsular polysaccharide from streptococcus pneumoniae type 37

The structure of the capsular polysaccharide elaborated by Streptococcus pneumonia type 37 has been investigated; methylation analysis, Smith degradation, and n.m.r. spectroscopy were the principal methods used. It is concluded that the polysaccharide is composed of disaccharide repeating-units having the following structure.

This comb-like structure is very crowded, which influences the n.m.r. spectra of the polysaccharide.     

Can asthma control be improved by understanding the patient's perspective?

Background

Clinical trials show that asthma can be controlled in the majority of patients, but poorly controlled asthma still imposes a considerable burden. The level of asthma control achieved reflects the behaviour of both healthcare professionals and patients. A key challenge for healthcare professionals is to help patients to engage in self-management behaviours with optimal adherence to appropriate treatment. These issues are particularly relevant in primary care, where most asthma is managed. An international panel of experts invited by the International Primary Care Respiratory Group considered the evidence and discussed the implications for primary care practice.

Discussion

Causes of poor control Clinical factors such as exposure to triggers and concomitant rhinitis are important but so are patient behavioural factors. Behaviours such as smoking and nonadherence may reduce the efficacy of treatment and patients' perceptions influence these behaviours. Perceptual barriers to adherence include doubting the need for treatment when symptoms are absent and concerns about potential adverse effects. Under-treatment may also be related to patients' underestimation of the significance of symptoms, and lack of awareness of achievable control. Implications Three key implications for healthcare professionals emerged from the debate. First, the need for simple tools to assess asthma control. Two approaches considered were the monitoring of biometric markers of control and questionnaires to record patient-reported outcomes. Second, to understand the reasons for poor control for individual patients, identifying both clinical (e.g. rhinitis) and behavioural factors (e.g. smoking and nonadherence to treatment). Third was the need to incorporate, within asthma review, an assessment of patient perspectives including their goals and aspirations and to elicit their beliefs and concerns about asthma and its treatment. This can be used as a basis for agreement between the healthcare professional and patient on a predefined target regarding asthma control and a treatment plan to achieve this.

Summary

Optimum review of asthma is essential to improve control. A key priority is the development of simple and effective tools for identifying poor control for individual patients coupled with a tailored approach to treatment to enable patients to set and achieve realistic goals for asthma control.     

Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes

Genomic imbalance is a common cause of phenotypic abnormalities. We measured the relative expression level of genes that map within the microdeletion that causes Williams-Beuren syndrome and within its flanking regions. We found, unexpectedly, that not only hemizygous genes but also normal-copy neighboring genes show decreased relative levels of expression. Our results suggest that not only the aneuploid genes but also the flanking genes that map several megabases away from a genomic rearrangement should be considered possible contributors to the phenotypic variation in genomic disorders.     

Lectin histochemistry for detecting cadmium-induced changes in the glycosylation pattern of rat placenta

Cadmium (Cd) is an industrial and environmental pollutant that produces toxic effects on gametogenesis, pre- and post-implantation embryos, and the placenta. Because the effects of acute Cd intoxication on the placenta are not well understood, we investigated changes in its glycosylated components in Cd treated dams at days 4, 7, 10 and 15 of gestation using lectin histochemistry. CdCl₂ was administered to pregnant rats; control animals received sterile normal saline. Placentas were processed for DBA, Con A, SBA, PNA, UEA-I, RCA-I and WGA lectin histochemistry to evaluate changes in the carbohydrate pattern of the placenta that might modify cell interactions and contribute to embryonic alterations. Lectin binding was analyzed in the yolk sac; trophoblast giant cells; trophoblast I, II and III; spongiotrophoblast cells and endovascular trophoblast cells in the chorioallantoic placenta. Our lectin binding patterns showed that Cd caused alteration of SBA and DBA labeling of trophoblast-derived cells, which suggested increased expressions of α and β GalNAc. Cd also caused decreased UEA-1 binding affinity, which indicated fewer α-L-Fuc residues in placentas of Cd treated dams. The nonreactivity in trophoblast I of the control placentas incubated with Con-A contrasted with the labeling in placentas of experimental dams, which indicated increased expression of terminal α-D-Man, and α-D-Glc residues. We found that Cd altered the reactivity of placenta to several lectins, which indicated modification of the glycotype presented by the fetal component of the placenta. We report that Cd exerts a deleterious effect on the glycosylation pattern of the placenta.     

Streptococcus Suis Isolated from Pigs in Finland

A total of 58 Streptococcus suis strains were isolated from deceased pigs submitted to the National Veterinary Institute, Regional Laboratory in Kuopio, Finland, over a 3 1/2 year period, most frequently from cases of pneumonia. The bacteria were isolated from cases of meningitis, sepsis, rhinitis, endocarditis and abortion. S. suis was also isolated from nasal cavity, lung and brain of some sick piglets without signs of inflammation. Further S. suis was detected in 12 out of 107 tonsils of healthy fatteners tested. S. suis strains were identified by biochemical methods followed by typing. The most common capsular types were 7, 3 and 2, respectively. Only one type 1 strain and no types 6 and 9 strains were found. All S. suis strains tested were sensitive to penicillin and ampicillin. S. suis is not uncommon in Finnish pig herds. S. suis may be regarded as a potentially pathogenic organism which under certain predisposing conditions may cause serious disease.