Species-specific treatment effects of helminth/HIV-1 co-infection: a systematic review and meta-analysis

In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=-0·10; 95% Confidence interval (CI): -0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.     

Development of 2‐phenylethanol plus acetic acid lures to monitor obliquebanded leafroller (Lepidoptera: Tortricidae) under mating disruption

We evaluated the effectiveness of 2‐phenylethanol (PET) in combination with acetic acid (AA) as a binary lure for monitoring male and female obliquebanded leafroller, Choristoneura rosaceana (Harris). Studies were conducted in apple, Malus domestica Borkhausen, orchards treated with or without sex pheromone dispensers for mating disruption (MD). Open polypropylene vials, closed membrane cups, and rubber septa loaded with AA and/or PET in varying amounts were first evaluated in a series of trapping experiments. Membrane cups loaded with 800 mg of PET were as effective as 10‐mg septa, but longer lasting, and were comparable to the open vials. A membrane cup AA lure was effective in tests, but further work is needed to increase its release rate and extend its activity. Catches of codling moth, Cydia pomonella (L.), and C. rosaceana were unaffected by combining PET with (E,E)‐8,10‐dodecadien‐1‐ol, the sex pheromone of codling moth, pear ester, (E,Z)‐2,4‐ethyl‐decadienoate and AA lures. Adding (E)‐4,8‐dimethyl‐1,3,7‐nonatriene to this blend to enhance codling moth catch significantly reduced catches of C. rosaceana. PET + AA was a more attractive binary lure than AA plus phenylacetonitrile (PAN) for C. rosaceana. The addition of PET or PAN to traps already baited with the sex pheromone of C. rosaceana significantly reduced male catches. Traps baited with PET + AA placed in blocks not treated with MD caught significantly fewer C. rosaceana than traps baited with sex pheromone. In comparison, sex pheromone‐baited traps in MD blocks caught ≤1 male moth per season which was significantly lower than total moth (>10) or female moth (≥3) catch in these blocks with PET + AA. A high proportion (>70%) of trapped females were mated in both untreated and MD‐treated orchards. Further refinement of this binary, bisexual lure using membrane cup technology may allow the establishment of action thresholds and improve management timings for C. rosaceana.     

Role of membrane oxidation in controlling the activity of human group IIa secretory phospholipase A2 toward apoptotic lymphoma cells

The membranes of healthy lymphocytes normally resist hydrolysis by secretory phospholipase A₂. However, they become susceptible during the process of apoptosis. Previous experiments have demonstrated the importance of certain physical changes to the membrane during cell death such as a reduction in membrane lipid order and exposure of phosphatidylserine on the membrane surface. Nevertheless, those investigations also showed that at least one additional factor was required for rapid hydrolysis by the human group IIa phospholipase isozyme. This study was designed to test the possibility that oxidation of membrane lipids is the additional factor. Flow cytometry and confocal microscopy with a fluorescent probe of oxidative potential suggested that oxidation of the plasma membrane occurs during apoptosis stimulated by thapsigargin. When oxidative potential was high, the activity of human group IIa secretory phospholipase A₂ was enhanced 30- to 100-fold compared to that observed with conditions sufficient for maximal hydrolysis by other secretory phospholipase A₂ isoforms. Direct oxidation of cell membranes with either of two oxidizing agents also stimulated hydrolysis by secretory phospholipase A₂. Both oxidizers caused externalization of phosphatidylserine, but a change in lipid order did not always occur. These results demonstrated that membrane oxidation strongly stimulates human group IIa secretory phospholipase A₂ activity toward apoptotic cells. Interestingly, the change in membrane order, previously thought to be imperative for high rates of hydrolysis, was not required when membrane lipids were oxidized. Whether phosphatidylserine exposure is still necessary with oxidation remains unresolved since the two events could not be deconvoluted.     

New species and records of Laboulbeniales from the subantarctic islands of New Zealand

Until now Rhachomyces kenodactyli Balazuc & W. Rossi has been the only species of Laboulbeniales known to occur on Coleoptera in the Bounty, Antipodes, Auckland, Campbell and Snares Islands, which lie 48° to 35° S. Four new species (Diphymyces depressus, Diphymyces leschenii, Laboulbenia subantarctica and Laboulbenia loxomeri) and five new records for the subantarctic (Cucujomyces phycophilus, Diphymyces penicillifer, Laboulbenia sp. 1, Rhachomyces sp. 1 and Teratomyces sp. 1) are reported, increasing the known number of taxa tenfold. An expanded geographic range for Rhachomyces kenodactyli is reported. A relatively high percentage (12%) of known beetle species in the subantarctic serve as hosts for Laboulbeniales. This host utilization rate is higher than that in tropical and north temperate regions. The high proportion of intertidal coleopteran taxa in the subantarctic fauna probably accounts for the greater number of host species utilized. Fungi on intertidal beetles (Omaliinae [Staphylinidae], Oopterus [Carabidae] and Kenodactylus audouini [Carabidae]) are known from many host individuals and collections, while those on terrestrial species are known from few, and in some cases, a single collection or host. The sporadic occurrence of some species encountered increases the likelihood that a few species of Laboulbeniales on Coleoptera probably remain undiscovered in the region.     

Impaired renal NaCl absorption in mice lacking the ROMK potassium channel,a model for type II Bartter's syndrome

ROMK is an apical K(+) channel expressed in the thick ascending limb of Henle (TALH) and throughout the distal nephron of the kidney. Null mutations in the ROMK gene cause type II Bartter's syndrome, in which abnormalities of electrolyte, acid-base, and fluid-volume homeostasis occur because of defective NaCl reabsorption in the TALH. To understand better the pathogenesis of type II Bartter's syndrome, we developed a mouse lacking ROMK and examined its phenotype. Young null mutants had hydronephrosis, were severely dehydrated, and approximately 95% died before 3 weeks of age. ROMK-deficient mice that survived beyond weaning grew to adulthood; however, they had metabolic acidosis, elevated blood concentrations of Na(+) and Cl(-), reduced blood pressure, polydipsia, polyuria, and poor urinary concentrating ability. Whole kidney glomerular filtration rate was sharply reduced, apparently as a result of hydronephrosis, and fractional excretion of electrolytes was elevated. Micropuncture analysis revealed that the single nephron glomerular filtration rate was relatively normal, absorption of NaCl in the TALH was reduced but not eliminated, and tubuloglomerular feedback was severely impaired. These data show that the loss of ROMK in the mouse causes perturbations of electrolyte, acid-base, and fluid-volume homeostasis, reduced absorption of NaCl in the TALH, and impaired tubuloglomerular feedback.     

The Anatomy and Function of a Segment of the X Chromosome of DROSOPHILA MELANOGASTER

An average size chromomere of the polytene X chromosome of Drosophila melanogaster contains enough DNA in each haploid equivalent strand to code for 30 genes, each 1,000 nucleotides long. We have attempted to learn about the organization of chromosomes by asking how many functional units can be localized within a chromomere. This was done by 1) recovery of mutants representative of every cistron in the 3A2-3C2 region; 2) the characterization of the function of each mutant type and grouping by complementation tests; 3) the determination of the genetic and cytological position of each cistron by recombination and deletion mapping. The data clearly show one functional group per chromomere. It is postulated that a chromomere is one cistron within which much of the DNA is regulatory in function.     

Fracture patterns at the Medieval Leper Hospital in Chichester

Humans are constantly at risk of bone fractures, not only when threatened by personal violence, but also by the challenge of daily living. Because fractures are a cross-cultural phenomenon and are one of the more commonly observed skeletal lesions in archaeological collections, their presence provides a unique opportunity to compare living conditions, and thereby assess fracture risk in coexisting cultures. This study analyzed long bone fracture patterns of 212 sexed adults from the medieval leper hospital of St. James and St. Mary Magdalene in Chichester, England. The comparison of this hospital sample to other British medieval skeletal samples examined the level of health manifest in fracture etiology. The fracture frequency for this sample was 15.1%, with males accounting for 85.4% of the fractures. The fracture frequencies from the samples not affiliated with hospitals ranged from 3.3 to 5.6%. Because medieval urban lifestyle was notoriously difficult due to inadequate sanitation and living conditions, the overall health of the population at large was inferior, placing all at similar fracture risk. Therefore, more specific complications associated with the fractures were examined. Osseous modifications of the skeletons due to lepromatous leprosy were associated with 28% of individuals sustaining fractures. However, persons with the milder tuberculoid leprosy do not exhibit skeletal lesions, but are more prone to accident due to the earlier loss of sensory perception and visual impairment. It is argued that the presence of leprosy is underestimated in archaeological populations and may be a major contributing factor to the prevalence of fracture resulting from accidental falls. Am J Phys Anthropol 105:43–55, 1998. © 1998 Wiley-Liss, Inc.     

Lethality Patterns and Morphology of Selected Lethal and Semi-Lethal Mutations in the Zeste-White Region of DROSOPHILA MELANOGASTER

Aspects of the developmental genetics of lethal and semi-lethal mutants representing 13 complementation groups (cistrons) in the 3A-3C region of the X chromosome of Drosophila melanogaster are given. Each of these cistrons is associated with a particular chromomere in the salivary gland chromosome. Mutants within each cistron have similar lethality patterns and morphological attributes, and the characteristics of a given cistron are distinct with respect to other cistrons. These results provide additional evidence that only one function is associated with each chromomere.-The results of the lethality pattern analysis are also compared with previous studies of lethal mutants of Drosophila.     

N-terminal modifications leading to peptide ORL1 partial agonists and antagonists.

Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that is the endogenous ligand for the G protein-coupled receptor (opioid receptor like 1, ORL1), a member of the opioid receptor family. Although it is clear that this receptor system is involved in a variety of physiological functions, including analgesia, the precise actions of N/OFQ remain largely uncharacterized. One reason for this has been limited high affinity ligands to ORL1, and particularly the lack of availability of useful specific antagonists. Herein we describe the pharmacological activity of a series of N-terminally modified hexapeptides with high affinity for ORL1. These compounds were tested for binding affinity using [3H]N/OFQ binding to human ORL1 in CHO cells, and functional activity by measuring stimulation of [35S]GTPgammaS binding in CHO cell membranes. The N-terminal modifications have produced compounds that maintained very high receptor affinity, but led to significant changes in intrinsic activity. One compound, pentanoyl-RYYRWR-NH2, with barely measurable agonist activity was tested in vivo. It was found to possess modest analgesic activity, but it was unable to block the morphine modulatory activity of N/OFQ.