Birth Weight and Its Relationship to Size Attained and Relative Fat Distribution at 7 to 12 Years of Age

The relationship between birth weight and relative subcutaneous fat distribution at school age was considered in 131 boys and 106 girls 7 to 12 years of age. Relative fat distribution at school age was estimated with the ratio of the subscapular to triceps skinfolds (S/T) for the total sample, and with the ratio of the sum of two trunk (subscapular, midaxillary) to the sum of two extremity (triceps, medial calf) skinfolds (T/E) for subsamples of 102 boys and 63 girls. There were no sex differences in the S/T ratio (mm/mm), boys 0.62 ± 0.15, girls 0.63 ± 0.18; T/E ratio (mm/mm), boys 0.58 ± 0.13, girls 0.59 ± 0.16; and BMI (kg/m²), boys 17.1 ± 2.4, girls 16.9 ± 2.2. Second order partial correlations, controlling for age and the BMI or age and sum of skinfolds, between birth weight and the skinfold ratios are, respectively, ?0.22 and ?0.20 (p<0.01) for S/T and ?0.29 and ?032 (p<0.01) for T/E in girls, and ?0.18 and ?0.17 (p<0.05) for S/T and ?0.06 and ?0.6 for T/E in boys. Though low, the correlations suggest that as birth weight decreases proportionally more subcutaneous fat is accumulated on the trunk than on the extremities, more so in females than in males. Results of stepwise multiple regression analyses indicate that birth weight accounts for from 2% to 8% of the variance in relative subcutaneous fat distribution at school age.     

Image analysis, neural networks, and the taxonomic impediment to biodiversity studies

The taxonomic impediment to biodiversity studies may be influenced radically by the application of new technology, in particular, desktop image analysers and neural networks. The former offer an opportunity to automate objective feature measurement processes, and the latter provide powerful pattern recognition and data analysis tools which are able to 'learn' patterns in multivariate data. The coupling of these technologies may provide a realistic opportunity for the automation of routine species identifications. The potential benefits and limitations of these technologies, along with the development of automated identification systems are reviewed.     

Of mice and wrens: the relation between abundance and geographic range size in British mammals and birds

We examine the relation between population size and geographic range size for British breeding birds and mammals. As for most other assemblages studied, a strong positive interspecific correlation is found in both taxa. The relation is also recovered once the phylogenetic relatedness of species has been controlled for using an evolutionary comparative method. The slope of the relation is steeper for birds than for mammals, but this is due in large part to two species of mammals that have much higher population sizes than expected from their small geographic ranges. These outlying mammal species are the only ones in Britain to be found only on small offshore islands, and so may be exhibiting density compensation effects. With them excluded, the slope of the abundance–range size relation for mammals is not significantly different to that for birds. However, the elevation of the relation is higher for mammals than for birds, indicating that mammals are approximately 30 times more abundant than birds of equivalent geographic range size. An earlier study of these assemblages showed that, for a given body mass, bats had abundances more similar to birds than to non-volant mammals, suggesting that the difference in abundance between mammals and birds might be due to constraints of flight. Our analyses show that the abundance–range size relation for bats is not different for that from other mammals, and that the anomalously low abundance of bats for their body mass may result because they have smaller than expected geographic extents for their size. Other reasons why birds and mammals might have different elevations for the relation between population size and geographic range size are discussed, together with possible reasons for why the slopes of these relations might be similar.     

Mutant HLA-A2 antigens as restricting elements for virus-specific cytotoxic T cells

Mutants of the EB virus-transformed cell line T5-1 (HLA-Al, 2; B8, 27), bearing well-characterized alterations in HLA-A2 antigen expression and unable to bind the HLA-A2-specific monoclonal antibody 13137.2, have been tested for their susceptibility to EB virus-specific cytolysis using effector T-cell preparations functionally restricted through relevant HLA antigens. Initial experiments first confirmed that the parent line T5-1 was susceptible to cytolysis by both common A2-restricted and 1327-restricted effector cells. While those T5-1 mutants with little or no surface A2 expression were not lysed by A2-restricted effectors, those targets with quantitatively normal expression of mutant A2 molecules were as susceptible to A2-restricted lysis as the parent line itself. In contrast, all the T5-1 mutant lines were susceptible to B27-restricted cytolysis. The results demonstrate that experimentally induced mutations of HLA-A2 antigen structure, affecting a serologically defined site on the molecule, can occur without altering that same molecule's expression of the T cell-restricting determinant(s). Such experimentally induced mutations are quite different from the naturally occurring variant A2 antigens which are present within the serologically defined A2 antigen group and which show changes at the T cell-restricting site.     

Composition of O-antigenic lipopolysaccharides from Enterobacter cloacae

Analyses have been carried out on lipopolysaccharides (LPS) from 14 strains of Enterobacter cloacae representing different O serotypes. All of the products appeared to have a composition and architecture typical of enterobacterial LPS, but points of interest include the absence of phosphate residues from the core oligosaccharide, the presence of both L-glycero-D-mannoheptose and D-glycero-D-mannoheptose (ratio usually about 4:1), and the presence in lipid A of small amounts of fatty acids with odd numbers of carbon atoms (mainly C13) in addition to tetradecanoic acid and 3-hydroxytetradecanoic acid. Monosaccharides identified as components of polymeric fractions from the LPS were glucose, galactose, mannose, rhamnose, glucosamine, galactosamine, fucosamine, and galacturonic acid. Most polymeric fractions also probably contained an O-acetyl substituent. Closely similar chemotypes found for the polymeric fractions from the LPS of cross-reacting serotypes support the view that these fractions contain the O-antigenic determinants and represent the side chains of the LPS.     

Protection of mice and nude rats against toxoplasmosis by a multiple antigenic peptide construction derived from Toxoplasma gondii P30 antigen.

The first part of this work presents the sequence of the first 20 NH2 terminus residues obtained from P30, the major surface Ag of Toxoplasma gondii, purified by HPLC. A synthetic peptide (P30 48-67) has been prepared both in linear form and as a multiple antigenic peptide (MAP) construct. Immunization of mice and rats with the P30 48-67 MAP in the presence of IFA induces high levels of IgG antibodies that recognize both the linear peptide and the MAP construct in ELISA, and P30 in Western blots of NP-40-extracted tachyzoite Ag. Because these sera are negative in immunofluorescence assays with whole tachyzoites, it seems that IgG antibodies induced by P30 48-67 MAP, although recognizing the denatured structure, are unable to recognize the native protein. However, the protective effect of both constructs has then been studied in mice and nude rats. Whereas immunization of mice with the monomeric peptide does not confer any protection against oral infection with 1200 cysts of T. gondii 76K strain (mortality within 11 days), 40% of mice immunized with the MAP construct survived up to 75 days after infection. Nude rats were passively transferred with 5 x 10(4) T lymphocytes from P30 48-67 MAP-immunized Fischer rats before infection with 5 x 10(4) RH strain tachyzoites. They survived up to 40 days after infection and raised an intense IgG antibody response against P30, whereas nude rats transferred with control lymphocytes died within 21 days. This shows that immunization with P30 48-67 MAP also induces an efficient T cell immune response. The present work confirms the recently demonstrated role of P30 in protective immunity and shows the interest of peptide octameric constructions as inducers of partially protective immune responses in toxoplasmosis, as already demonstrated in schistosomiasis.     

Brain Ligatin: A Membrane Lectin That Binds Acetylcholinesterase

Ligatin, a lectin that recognizes phosphorylated sugars, has been demonstrated in mammalian tissues to bind specific hydrolases to cell surfaces. Ligatin exists as a filament that can be released from membranes still complexed with its bound hydrolases by treatment of membrane preparations with CaCl₂ and/or pH 8.0. The ligatin-hydrolase complexes subsequently can be dissociated with ethyleneglycol-bis(β-amino-ethyl ether) N, N′-tetraacetic acid, resulting in a concurrent depolymerization of the ligatin filament. From membrane preparations of cerebrum, this procedure solubilized ligatin and a membrane-bound acetylcholinesterase (EC 3.1.1.7). Binding of the cosolubilized acetylcholinesterase to ligatin could be demonstrated in vitro by affinity chromatography using the immobilized lectin. Ligatin-hydrolase complexes have been shown to be dissociated by specific phosphorylated sugars (mannose 6-phosphate and glucose 1-phosphate). These sugars were also effective in eluting bound brain acetylcholinesterase from ligatin affinity columns. Analysis of labeled glycitols produced by tritiated borohydride reduction confirmed the presence of phosphorylated sugars on the ligatin-cosolubilized material from brain.     

2,5-Dihydroxymethyl 3,4-dihydroxypyrrolidine dans les feuilles de Derris elliptica

A new natural imino-alcohol, 2,5-dihydroxymethyl 3,4-dihydroxypyrrolidine has been isolated from the leaves of Derris elliptica. Its structure was determined by chemical and physical methods.     

Effect of concanavalin A on membrane-bound enzymes from mouse lymphocytes

The ionic influence and ouabain sensitivity of lymphocyte Mg²⁺-ATPase and Mg²⁺-(Na⁺ + K⁺)-activated ATPase were studied in intact cells, microsomal fraction and isolated plasma membranes. The active site of 5′-nucleotidase and Mg²⁺-ATPase seemed to be localized on the external side of the plasma membrane whereas the ATP binding site of (Na⁺ + K⁺)-ATPase was located inside the membrane.Concanavalin A induced an early stimulation of Mg²⁺-ATPase and (Na⁺ + K⁺)-ATPase both on intact cells and purified plasma membranes. In contrast, 5′-nucleotidase activity was not affected by the mitogen. Although the thymocyte Mg²⁺-ATPase activity was 3–5 times lower than in spleen lymphocytes, it was much more stimulated in the former cells (about 40 versus 20 %). (Na⁺ + K⁺)-ATPase activity was undetectable in thymocytes. However, in spleen lymphocytes (Na⁺ + K⁺)-ATPase activity can be detected and was 30 % increased by concanavalin A. Several aspects of this enzymic stimulation had also characteristic features of blast transformation induced by concanavalin A, suggesting a possible role of these enzymes, especially Mg²⁺-ATPase, in lymphocyte stimulation.     

Pyronaridine–artesunate real-world safety,tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm,open-label,cohort event monitoring study

BackgroundIn Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine–artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.Methods and findingsThis single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine–artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine–artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine–artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.ConclusionsPyronaridine–artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine–artesunate as an operationally useful addition to the management of acute uncomplicated malaria.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03201770","term_id":"NCT03201770"}}NCT03201770.

Gaston Tona Lutete and co-workers report on safety and effectiveness of the antimalarial drug pyronaridine-artesunate in African countries.