Herd immunity to filarial infection is a function of vector biting rate

Despite the existence of an impressive body of work on human immune responses against filarial infections, the occurrence of a protective response to infection remains unclear. Here, we use a combined modelling and comparative data analysis framework to address this issue for human infections with the filarial parasite, Wuchereria bancrofti. By analogy with previous work, the analysis involves the comparison of observed field patterns of infection with epidemiological patterns predicted by a mathematical model of parasite immunity. Unlike most other human helminths, which are transmitted by ingestion or dermal penetration, exposure to infection with lymphatic filariasis can be measured explicitly in terms of vector mosquito biting rates, thereby also allowing, probably for the first time, examination of the suggested role of exposure in generating herd immunity to macroparasites. Observed field patterns in this study were derived from 19 different published studies, which gave parallel estimates of community exposure rates and the corresponding age--prevalence patterns of infection, while predictions of the epidemiological impact of herd immunity were obtained using a catalytic model framework. The results provide the first conclusive evidence to date that variations in the observed age--prevalence patterns of infection in filariasis can be effectively explained by the occurrence of an exposure-driven acquisition of herd immunity. We discuss this result in terms of implications for the new World Health Organization-led initiative for the global control of this parasitic disease.     

The MUC2 gene product: a human intestinal mucin

Sera from 82 cases of leptospirosis (confirmed by micro-agglutination tests or IFAT) and 108 patients with other diseases were investigated using the microcapsule agglutination test (MCAT) for leptospirosis. The overall sensitivity (90.2%), specificity (96.3%), positive predictive value (94.9%), negative predictive value (92.9%), and accuracy of the MCAT (93.7%) were encouraging. MCAT is simple, can be performed by unskilled personnel with minimum laboratory facilities, and produces results in 3 h. MCAT would be a reliable serodiagnostic test for rapidly screening individuals for leptospirosis, in various geographical areas of Thailand.     

Phonosurgery

Phonosurgery is composed of procedures that are intended to maintain or improve the quality of the voice by correcting defects in laryngeal sound production. These procedures are rooted in a rich medical history that dates back to the early 19th century. There has been a recent convergence of physiologic principles of voice production with surgical technique theory. Recognition of this interdependence has provided a catalyst for collaboration among surgeons, scientists, speech pathologists, vocal pedagogists, and performing artists. We live in a society that is linked to effective communication, and there is a growing population of individuals who have professional voice responsibilities as part of everyday life. This has created a need for the recent developments in phonosurgery and its emergence as a subspecialty of otolaryngology.     

Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation

The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.     

Pulmonary function test outcomes in healthy Navajo Native American adolescents

Prediction equations for estimating lung volumes have been determined for Caucasians, African-Americans, and Mexican-Americans. These separate equations were determined because of differences in thoracic morphology between people of various racial groups, making it impossible to use one prediction formula to accurately estimate lung volumes for all individuals. One hundred ninety-one adolescent Navajo children (males, n = 110; females, n = 81) between 11 and 18 yr of age volunteered for the study and underwent a series of pulmonary function tests (PFT). New pulmonary function prediction equations for Navajo youth were generated for estimating pulmonary volumes and capacities that more accurately predict expected PFT outcomes than formulas in common use for Caucasian, Mexican-American, or African-American youth.     

The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma-mediated cartilage degradation

Angiogenesis is an important component of the development of chronic inflammatory diseases such as rheumatoid arthritis. It is known that clinically used anti-rheumatic drugs exert, in part, effects on the angiogenic response. Little work, however, has investigated the potential of experimental angiostatic therapies in chronic inflammatory disease models. The effect of one such angiostatic treatment, cortisone combined with heparin, was tested in an in vivo model of granuloma-mediated cartilage degradation. Angiostatic treatment significantly retarded the growth of granulomatous tissue, mononuclear cell influx into the granuloma, and the degradation of juxtaposed cartilage. This correlated with a decrease in the vascularity of the granulomatous tissue. Modulation of this component of pathogenesis of "angiogenesis-dependent disease" may be useful as a new therapeutic approach.     

Restrained and nonrestrained eaters'' orienting responses to food and nonfood odors

This study attempted to induce a major shift in the utilization of endogenous substrates during exercise in men by the use of a potent inhibitor of adipose tissue lipolysis, Acipimox, and to see to what extent this affects the 13C/12C ratio in expired air CO2. Six healthy volunteers exercised for 3 h on a treadmill at approximately 45% of their maximum O2 uptake, 75 min after having ingested either a placebo or 250 mg Acipimox. The rise in plasma free fatty acids and glycerol was almost totally prevented by Acipimox, and no significant rise in the utilization of lipids, evaluated by indirect calorimetry, was observed. Total carbohydrate oxidation averaged 128 +/- 17 (placebo) and 182 +/- 21 g/3 h (Acipimox). Conversely, total lipid oxidation was 84 +/- 5 (placebo) and 57 +/- 6 g/3 h (Acipimox; P < 0.01). Under placebo, changes in expired air CO2 delta 13C were minimal, with only a 0.49/1000 significant rise at 30 min. In contrast, under Acipimox, the rise in expired air CO2 delta 13C averaged 1/1000 and was significant throughout the 3-h exercise bout; in these conditions calculation of a "pseudooxidation" of an exogenous sugar naturally or artificially enriched in 13C, but not ingested, would have given an erroneous value of 19.8 +/- 2.6 g/3 h. Thus under conditions of extreme changes in endogenous substrate utilization, an appropriate control experiment is mandatory when studying exogenous substrate oxidation by 13C-labeled substrates and isotope-ratio mass spectrometry measurements on expired air CO2.     

Problems with India ink skin markings

India ink skin markings allow consistently reproducible radiation field setups. The authors report a case in which a facial tattoo was applied with an injection, resulting in permanent "black eyes." The vaccination technique has not been associated with this complication.     

The cortisol response to psychological stress in temporomandibular dysfunction

Recombinant antibody fragments can be produced in large quantities using bacterial expression systems and could potentially be useful for the generation of biofilters for the selective removal of viral particles from fluids. A human single chain-Fv antibody library, derived from synthetic repertoires of germ line VH-gene segments rearranged in vitro and paired to a single light chain (Nissim et al., 1994, EMBO J., 13, 692-698), has recently been used to isolate hundreds of different binding specificities by panning with antigen. Antibodies from this library typically have affinities in the 10(6)-10(7) M-1 range. Occasionally, better binders are isolated but at other times the affinities recovered are poor. In the latter situation binding cannot be detected with soluble antibodies, but only by high-avidity display of multiple copies of antibodies on phage. By panning with human cytomegalovirus (HCMV)-coated immunotubes, we have isolated a number of antibody clones from this library that bound to the antigen only if displayed on the filamentous phage, but not in soluble form. One of these clones was selected for an affinity maturation procedure, achieved by combinatorial mutagenesis of the complementarity determining region 3 (CDR3) of the antibody light chain, followed by selection of the resulting library for HCMV binding. By this means, we were able to isolate a number of binders, some of which exhibited specific HCMV binding in soluble form. The clone that gave the strongest ELISA signal was expressed in bacteria, purified in solution, characterised using a novel capture methodology with surface plasmon resonance detection on a BIAcore instrument and used for the production of an immunofilter for the removal of HCMV form human serum. The filter removed more than 99% of applied HCMV in 10 min circulation time, while the amount of HCMV retained non-specifically in a cartridge derivatised with a non-specific antibody was less than 10% under similar conditions.